http://www.hindawi.com/journals/ijpe/2009/567430.html

Journal of Pediatric EndocrinologyVolume 2009 (2009), Article ID 567430, 7
pagesdoi:10.1155/2009/567430

Review Article

46,XY DSD with Female or Ambiguous External Genitalia at Birth due to Androgen
Insensitivity Syndrome, 5α-Reductase-2 Deficiency, or
17β-Hydroxysteroid Dehydrogenase Deficiency: A Review of Quality of Life
Outcomes

Amy B. Wisniewski1 and Tom Mazur2
1Section of Pediatric Diabetes and Endocrinology, Department of Pediatrics,
University of Oklahoma Health Sciences Center, 940 NE 13th Street, Room 2B2426,
Oklahoma City, OK 73117, USA
2Department of Pediatrics, State University of New York, Buffalo, NY 14222, USA

Received 3 June 2009; Accepted 29 July 2009

Academic Editor: Peter Lee

Copyright © 2009 Amy B. Wisniewski and Tom Mazur. This is an open access article
distributed under the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the
original work is properly cited.

Abstract
Disorders of sex development refer to a collection of congenital conditions in
which atypical development of chromosomal, gonadal, or anatomic sex occurs.
Studies of 46,XY DSD have focused largely on gender identity, gender role, and
sexual orientation. Few studies have focused on other domains, such as physical
and mental health, that may contribute to a person's quality of life. The
current review focuses on information published since 1955 pertaining to
psychological well-being, cognition, general health, fertility, and sexual
function in people affected by androgen insensitivity syndromes, 5-α
reductase-2 deficiency, or 17β-hydroxysteroid dehydrogenase-3
deficiency—reared male or female. The complete form of androgen insensitivity
syndrome has been the focus of the largest number of investigations in domains
other than gender. Despite this, all of the conditions included in the current
review are under-studied. Realms identified for further study include
psychological well-being, cognitive abilities, general health, fertility, and
sexual function. Such investigations would not only improve the quality of life
for those affected by DSD but may also provide information for improving
physical and mental health in the general population.

1. Introduction
Disorders of sex development (DSD) refer to a collection of congenital
conditions in which atypical development of sex occurs at one or more levels
(chromosomal, gonadal, anatomic). Genetic males with DSD (i.e., 46,XY DSD) can
present with an external genital phenotype that is female, ambiguous, or male
including a micropenis (stretched penile length 2.5 SD for age). Studies of
46,XY DSD have focused largely on aspects of gender development such as
satisfaction with gender of rearing, sexual orientation, gender identity, and
gender role (GI/R) [1]. Very few studies have reported on additional aspects of
physical or mental health despite the fact that patients and families often
inquire about such topics. Furthermore, few studies have addressed the question
of if, or how, a DSD diagnosis and related treatment impact quality of life
(QoL) for affected individuals. For the purpose of this review, QoL can be
operationally defined as the amount of enjoyment a person experiences in the
physical, psychological, social, and spiritual dimensions of their life [2].

Although much remains to be learned concerning psychosexual development as it
relates to DSD, the purpose of this paper is to review what is known about
aspects of physical and mental health that contribute to overall QoL beyond GI/R
and sexual orientation. Topics reviewed include QoL and psychological
well-being, cognition, general health, fertility, and sexual function.
Additionally, the focus of this review is on individuals affected by 46,XY DSD
due to androgen insensitivity syndromes (AIS), 5- reductase-2 deficiency
(5-RD-2), or 17-hydroxysteroid dehydrogenase-3 deficiency (17-HSD-3)—reared male
or female. These conditions were chosen because while much has been written
about gender development in affected individuals, less emphasis has been placed
on other outcomes that may contribute to QoL such as genital surgery or hormone
therapy to induce and maintain pubertal development. Congenital micropenis was
not included in the current review because too little information exists on
outcomes aside from gender development in this DSD for meaningful interpretation
of the data. Data on individuals with micropenis is further confused by the
incorrect practice of some authors of describing individuals with a small
phallus including hypospadias as having a micropenis.

2. Methods
A search of the databases Medline and Psyc INFO was performed using the terms
disorders of sex development, DSD, intersex, hermaphrodite, male
pseudohermaphrodite, ambiguous genitalia, androgen insensitivity, 5- reductase-2
deficiency, and 17-hydroxysteroid dehydrogenase-3 deficiency. Peer-reviewed
articles published in English since 1955 were considered if they referred to
adults with DSD grouped and analyzed according to the above-mentioned
etiologies. The year 1955 was chosen because this was when John Money started to
publish extensively on DSD in peer-reviewed scientific journals [3, 4].

To be considered for inclusion in the current review, articles must report on
mental or physical health outcomes other than, or in addition to, GI/R and
sexual orientation. Articles were excluded if they provided outcome information
about GI/R or sexual orientation only, or when data from study participants
could not be attributed to one of the specific DSD diagnoses referred to
earlier. A total of 35 articles were located and reviewed according to these
criteria.

3. Androgen Insensitivity Syndromes (AISs)
AISs in either the complete (CAIS) or partial (PAIS) form represent a relatively
common presentation of 46,XY DSD [5–7]. CAIS and PAIS result in complete or
partial end organ insensitivity to androgens, respectively. The majority of
mutations of the human androgen receptor gene are base substitutions, although
base and gene deletions, base insertions, and premature terminations occur.
While it is well established that androgens bind to intracellular androgen
receptors to alter gene expression in target tissues, evidence for nongenomic
actions of androgens is accumulating [8]. The degree of androgen insensitivity
of target tissues is usually inferred by the extent of under-masculinization of
the external genitalia at birth coupled with the degree of under-virilization at
puberty.

The clinical presentation of CAIS in adulthood is typically that of a tall woman
with a female distribution of adipose tissue, female breasts and external
genital development, and little or no sexual hair. Infants can present with
testes that descend into the inguinal canals or labia, and adolescents can
present with absent menses and sexual hair in conjunction with normal breast
development. Due to the female external genital phenotype associated with CAIS,
affected individuals are always assigned and reared as girls despite their
possession of a 46,XY chromosomal complement and testes. Individuals with PAIS
typically present as newborns with varying degrees of genital ambiguity. Thus,
male or female sex of rearing occurs, depending on the degree of
under-masculinization of the genitalia.

3.1. Health-Related Quality of Life, Psychological Well-Being, and Affective
Disorders in CAIS
While psychosexual evaluations of girls and women affected by CAIS unequivocally
reveal female GI/R [9–11], outcomes of other aspects of mental health vary
greatly across studies. For example, psychological distress as assessed by the
Brief Symptom Inventory (BSI), self-harming behavior, and suicidal tendencies
are prevalent in some samples of women with CAIS recruited from physicians or
support groups [12–14]. In a study of women with CAIS recruited from
subspecialty clinics at a University Hospital, participants affected by CAIS
reported better QoL scores and fewer depressive symptoms than women with other
types of DSD or unaffected control women when assessed with the Danish version
of the Quality of Life-Assessment of Growth Hormone Deficiency in Adults
(QoL-AGHDA) questionnaire [15]. In yet another study of women with CAIS
recruited from both a clinic sample and a support group, affected individuals
did not differ from controls on measures of self-esteem, assessed by the
Self-Esteem Scale, or psychological well-being, measured by responses to the
Psychological General Well-Being Scale (PGWBS) [12]. While it is surprising that
some studies of women with CAIS report equal or better QoL than unaffected
women, this may be due to small sample sizes and participation bias. Additional
QoL studies including larger sample sizes and greater participant diversity are
needed in this population to better understand the impact of having a 46,XY
chromosomal complement and being born with testes on overall psychological
well-being in this group of women. Recently, the German Network of Disorders of
Sex Development published clinical evaluation data on 439 individuals with DSD
[16]. QoL information from this study sample will prove extremely valuable when
published. Furthermore, a study that assesses potential differences in long-term
QoL among women with CAIS whose testes were removed during infancy, compared to
those who consented to gonadectomy later in their development, would provide
very useful information for optimizing medical and surgical treatment for this
group.

3.2. Cognition in CAIS
Mice with androgen receptor gene mutations (testicular feminization mutant or
tfm) exhibit a more pronounced impairment on spatial recognition and memory
retention tasks when considered in conjunction with the epsilon4 allele of the
apolipoprotein E gene (apoE4) [17]. This subclass of apolipoprotein plays an
important role in cholesterol metabolism and is associated with Alzheimer's
disease, impaired cognition, and reduced neurite growth [18]. The implication is
that androgen insensitivity may impact cognition in women affected by AIS who
also express the epsilon 4 allele of the APOE gene.

Only two studies of cognitive performance in girls and women affected by CAIS
exist in the peer-reviewed literature. The first employed standardized,
age-appropriate intelligence testing for participants ranging in age from 5 to
28 years and observed normal scores for all of the girls and women who
participated [19]. A second intelligence assessment was performed in women with
CAIS and revealed no group differences in overall IQ between CAIS participants,
unaffected men, and unaffected women [20]. However, unaffected women and those
with CAIS performed worse than men on visuospatial components of the IQ measure.
Taken together, these data reveal that girls and women with CAIS exhibit similar
IQ scores and cognitive performance patterns as unaffected women who possess a
46,XX chromosomal complement and end organ responsiveness to androgens. Whether
or not cognitive differences would be detected on measures of spatial
recognition and memory for women affected by CAIS when apoE4 is considered is
not known at this time. Future studies should consider the potential interaction
of end organ unresponsiveness to androgens with apoE4 in this population.
Additionally, more refined neuropsychological testing, regardless of apoE4
status, might reveal important cognitive differences in girls and women affected
by this type of DSD.

3.3. General Health in CAIS
Few long-term outcome studies of general health have been conducted in women
with CAIS. Obesity is commonly reported, however, at rates that mimic the
general population of women [10, 21]. Decreased bone mineral densities in the
lumbar spine and hip regions occur both prior to gonadectomy in women with CAIS
as well as in gonadectomized women receiving daily estrogen therapy [10, 21,
22]. These data suggest that women affected by CAIS are at an increased risk for
osteoporosis despite exposure to endogenous or exogenous estrogen. Whether women
with CAIS require higher doses of estrogen than their unaffected counterparts to
protect their bones, or whether androgens play a direct role in bone health for
this group, is unknown at this time.

Concerning cancer occurrence and risk, both germ cell tumor formation and risk
factors for developing prostate cancer have been investigated in women with
CAIS. Prepubertal girls with CAIS are considered to be at low risk (2%) for germ
cell tumor formation, as determined by review of 55 patients [23]. However, a
seminoma has been reported in a 14-year-old with CAIS [24], and a malignant
teratoma has been reported in a second affected child (also 14-years-old) [25].
In general, the risk for developing testicular tumors—including sertoli cell
tumors, seminomas, and leydig cell tumors—is thought to increase with age in
affected women [26, 27]. Additionally, women with CAIS appear to be at low risk
for developing prostate cancer as determined by prostate specific antigen (PSA)
testing and digital rectal exam, despite their possession of some prostate
tissue [28]. No studies were located that investigated other types of cancer
occurrence or risk in women with CAIS.

3.4. Fertility and Sexual Function in CAIS
As women with CAIS possess neither ovaries nor a uterus, fertility is not
possible in this group at the present time. While vaginal lengthening is needed
for penile penetration in some women with CAIS [29, 30], others have a normal
vaginal length and report satisfactory intercourse despite never having received
dilatation or surgery [10, 31]. Three studies of orgasmic function report that
women with CAIS can reach sexual climax [10, 32, 33], indicating that androgens
are not necessary for this aspect of sexuality in this group. Low libido, or
hyposexual function, is reported by some women with CAIS [33, 34].
Interestingly, even when women report sexual dysfunction, they also report
sexual satisfaction at levels that equal unaffected women [34]. Perhaps
hyposexual function associated with CAIS is secondary to vaginal hypoplasia, the
need for androgens to support libido (but not orgasm), or sexual avoidance by
women who feel stigmatized by their medical condition. Further research that
includes unaffected women as control subjects is needed to understand the
extent, and underlying causes, of hyposexual function in women affected by this
46,XY DSD. Additionally, future studies would benefit from considering the
impact of the type and timing of vaginoplasty on sexual satisfaction—an
important component of QoL.

3.5. Health-Related Quality of Life, Psychological Well-Being, and Affective
Disorders in PAIS
Self-reported psychological distress as determined by responses to the BSI,
self-harming behavior, suicidal tendencies, and suicidal attempts is observed in
people affected by PAIS—whether reared male or female [12–14]. In a long-term
followup study of adults with PAIS, psychological counseling for problems such
as difficulty with family members, depression, and substance abuse was commonly
reported during interviews—once again regardless of male or female rearing [35].
However, some studies of men and women affected by PAIS fail to observe
significant problems with mental health [36, 37]. Furthermore, QoL as determined
by responses to the SF-36 Health Survey exceeded normative data in one case
series of 3 women affected by PAIS [38]. While it is clear that some individuals
with PAIS experience mental health obstacles, both the extent and type of these
obstacles in this patient population remain to be elucidated. The potential
impact of clinical decisions such as the type and timing of genital surgeries on
QoL in affected people, regardless of their gender assignment, is important
information that is missing from our knowledge base at this time.

3.6. General Health and Cognition in PAIS
Based on studies of 24 patients, people with PAIS are thought to be at high risk
(50%) for developing germ cell tumors if the testes are not located in the
scrotum. For this group, gonadectomy is recommended at the time of diagnosis
[23]. 46,XY women affected by PAIS do not appear to be at risk for developing
prostate cancer, despite their possession of prostate tissue, as determined by
PSA levels and digital rectal exam. Presumably this is due to the fact that
these women are gonadectomized, and thus protected from androgenic actions on
the prostate. In contrast, men with PAIS have PSA levels comparable to
unaffected men matched for age and race [28]. Therefore, when individuals with
PAIS are reared male, screening for prostate disease is recommended in a manner
that is similar to the general male population. No other published reports on
general health outcome in 46,XY individuals with PAIS, reared male or female,
were located. Additionally, no studies on cognition in this group were found.

3.7. Fertility and Sexual Function in PAIS
At the present time fertility is challenging, but not impossible, for
individuals with PAIS raised male [39, 40]. In contrast, fertility is not
possible for individuals raised female. A study of 15 adults reared male found
that none had ever engaged in penile-vaginal intercourse and all experienced
severe sexual dysfunction [41]. In a second study of 21 men and 18 women with
46,XY DSD due to PAIS, most had participated in sexual relationships.
Dissatisfaction with sexual function was common but not universal, and this
dissatisfaction was similar for those reared male or female [35]. Smaller
investigations of sexual function in women with PAIS reveal that, for those who
participated in sexual relations with a partner, those experiences were rated as
both satisfactory [37] and unsatisfactory [29, 37]. The great variability in
outcome measures across studies indicates the need to study larger sample sizes
[16] as well as employ standardized, validated measures of sexual function when
examining men and women with PAIS.

4.  5-Reductase-2 Deficiency
5-reductase-2 (5-RD-2) deficiency can result in female external genitalia (with
a normal sized or enlarged clitoris) and male internal sex ducts in people with
a 46,XY chromosomal complement. This occurs because the enzyme 5-RD-2 is needed
to convert testosterone to dihydrotestosterone (DHT). DHT has a greater affinity
for the androgen receptor than testosterone and is required to masculinize the
external genitalia, but not the internal male sex ducts, during fetal
development. Testosterone alone is sufficient to support somatic virilization
postnatally [42, 43].

4.1. Health-Related Quality of Life, Psychological Well-Being, and General
Health in 5-RD-2 Deficiency
Clinical distress, determined by responses to the BSI and suicidal ideation, is
observed in 46,XY women affected by 5-RD-2 deficiency, although studies of
larger sample sizes are needed to determine the generalizability of this finding
[14]. Whether this distress is due to female assignment, feminizing surgeries,
or both is unknown at this time. A bone health investigation of affected adults
(none of whom had been gonadectomized nor given exogenous hormone replacement)
revealed that bone mineral density did not differ from unaffected men [22]. A
second bone density study concluded that DHT is not needed to maintain normal
bone health [44]. No other studies on general health outcomes were located for
review for this particular group of DSD. Of particular concern is the lack of
knowledge pertaining to germ cell tumor [23] or prostate cancer [28] risk for
this group. Additionally, no studies of cognitive performance were located.

4.2. Fertility and Sexual Function in 5-RD-2 Deficiency
Both sperm production and paternity have been documented in men affected by
5-RD-2 deficiency [43, 45–48]. High-dose androgen therapy improves virilization,
erectile response and ejaculatory volume in individuals reared male [45]. For
those who identify as women, sexual activity is reported to be satisfactory
following vaginal dilatation [44]. Similar to AIS, it is not clear how sexual
function in people with 5-RD-2 deficiency, reared male or female, contributes to
QoL.

5.  17-Hydroxysteroid Dehydrogenase-3 Deficiency
17-HSD-3 deficiency results in impaired testicular conversion of androstenedione
to testosterone [49]. The clinical presentation of 17-HSD-3 deficiency can be
confused with CAIS as affected individuals often present with female external
genitalia prior to puberty [50, 51]. If the testes remain in situ, virilization
at puberty occurs in a manner that is similar to what is observed in 5-RD-2
deficiency [50, 52].

5.1. Health-Related Quality of Life, Psychological Well-Being, and General
Health in 17-HSD-3 Deficiency
Clinical distress as determined by the BSI and suicidal ideation is observed in
46,XY women affected by 17-HSD-3 deficiency, but interpretation of these data is
limited by the small sample size studied [14]. Once again, how gender assignment
and the medical and surgical treatment that accompanies such assignment impact
QoL for this group is unknown. Germ cell tumor risk is estimated to be
intermediate (28%) [23, 50]. No other studies of general health or cognition
conducted in this category of 46,XY DSD were located for review.

5.2. Sexual Function and Fertility in 17-HSD-3 Deficiency
Case reports of 46,XY women with 17-HSD-3 deficiency indicate satisfactory
sexual function [44, 53], but available information is too incomplete to draw
conclusions with confidence. Case reports of affected individuals living as men
also indicate satisfactory sexual function [50, 53], although dissatisfaction
attributed to having a small phallus appears in the literature [51].

6. Summary and Conclusions
Of the 35 studies reviewed that included outcomes information apart from gender,
24 included information about CAIS, 9 about PAIS, 11 about 5-RD-2 deficiency,
and 5 about 17-HSD-3 deficiency. Possibly, greater emphasis has been placed on
studying CAIS apart from gender because female rearing in this particular DSD is
undisputed. In contrast, male or female rearing occurs in people affected by
PAIS, 5-RD-2, and 17-HSD-3 deficiencies. Perhaps GI/R and sexual orientation
have been the focus of studies in these conditions in response to the clinical
challenges of assigning gender in affected individuals. Finally, because CAIS
has an animal model (tfm) associated with it, this condition may lend itself
more easily to scientific investigation.

Results from studies of psychological well-being in the specific 46,XY DSD
categories considered here vary greatly across investigations. This is likely
due to the fact that these include only a handful of participants, interviewed
only once, in no particular relation to developmental stage or medical/surgical
event. Future studies should include larger samples and take into account
developmental stages as well as the potential impact of corresponding medical
and surgical procedures associated with these stages [16]. Additionally, for
those who have access to mental health services, it is critical to determine the
effectiveness of these services on psychological well-being within specific
categories of DSD.

No systematic studies of IQ or cognition have been conducted in people affected
by 46,XY DSD due PAIS or androgen biosynthetic defects due to 5-RD-2 or 17-HSD-3
deficiencies. Unlike tfm rodent models, it is unknown if women with CAIS are
more likely to develop spatial memory problems if they also express the epsilon
4 allele of the APOE gene. As individuals with 46,XY DSD are generally expected
to live a full lifespan, a more complete understanding of the potential for
their DSD to impact neuropsychological development, particularly later in
development, is needed.

General health outcome studies in people affected by AIS, 5-RD-2 deficiency, and
17-HSD-3 deficiency are few and have been limited to gonadal tumors, and bone
and prostate health. Further health outcome studies, particularly in conditions
that exhibit clear sex differences or influences of sex steroid action, are
needed. For example, whether or not possession of a Y chromosome places 46,XY
women at risk for developing a male-typical presentation and course of
cardiovascular disease, independent of androgen action, is not known.
Alternatively, it is currently unknown if under-masculinized genetic males have
an elevated risk for developing female-typical medical conditions such as
autoimmune diseases or depression. As our understanding of DSD broadens to
include physical and mental health outcomes apart from gender development, it is
anticipated that QoL will improve for affected individuals.

Fertility and sexual function can be important components to living a fulfilled
life and maintaining relationships; yet we know very little about such topics.
We do know from patient populations affected by conditions other than DSD that
infertility [54] sexual dysfunction [55] and surgeries to the reproductive
organs [56] negatively impact health-related QoL. Such information, as it
pertains specifically to DSD, is crucial in optimizing treatment and supporting
affected individuals.

Knowledge about the physical and mental health outcomes in DSD throughout the
life cycle is important for improving or maintaining health in affected
individuals and the population overall. For example, the few studies of bone
health that have been conducted in AIS and 5-RD-2 deficiency imply that
testosterone, but not DHT, is necessary for optimizing bone density. Such
information may be useful for developing treatments for conditions such as
osteopenia and osteoporosis.

It is important to focus on QoL factors for persons with a DSD diagnosis because
parents ask questions such as How will my child perform in school? Will my child
establish friendships? Will my child have a career? Will my child fall in love?
Parents also want to know how their children will feel about their DSD
diagnosis. In short, parents want information about their affected child's
future QoL. Only through systematic investigation of such questions will answers
be obtained, and appropriate interventions developed.

We could find no data pertaining to individual adjustment to the categories of
DSD discussed in the current review. Additionally, very little is known about
how family members respond to a child's diagnosis of DSD. While we know that
parents of children affected by CAIS or PAIS report feelings of shock, grief,
anger, and shame when they learn of their child's condition [57], more studies
of parents are needed as their attitudes surely exert a significant impact on
subsequent child health and well-being [58]. Finally, the definition for QoL
presented earlier includes social and spiritual components—neither of which were
investigated systematically in any of the papers reviewed.

In conditions in which GI/R does not always develop in concordance with sex of
rearing—such as PAIS, 5-RD-2 deficiency, and 17-HSD-3 deficiency—a better
understanding of factors that influence QoL may help to explain the
developmental trajectory of GI/R in people for whom GI/R development does not
match their initial gender assignment [11]. We still have a long way to go in
understanding why some people with these conditions change gender while others
do not. Importantly, approximately a third of people with DSD other than AIS,
5-RD-2 deficiency, or 17-HSD-3 deficiency are born with malformations that
likely affect QoL [59]. Future studies must consider those individuals as well.
This review has attempted to show that we also have a long way to go before we
have a full appreciation of the mental, physical, social, and spiritual domains
that contribute to QoL of people affected by 46,XY DSD who are born with either
female or ambiguous external genitalia.

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Perlmutter, "Functional, social and psychosexual adjustment after vaginal
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tamoxifen in a man with the incomplete androgen insensitivity syndrome," The
Journal of Clinical Endocrinology & Metabolism, vol. 68, no. 6, pp. 1207–1210,
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deficiency," Endocrine Reviews, vol. 14, no. 5, pp. 577–593, 1993.
M. D. Katz, I. Kligman, L.-Q. Cai, et al., "Paternity by intrauterine
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"Dihydrotestosterone regulation of semen in male pseudohermaphrodites with
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J. Imperato-McGinley, R. E. Peterson, R. Stoller, and W. E. Goodwin, "Male
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Copyright © 2009 Hindawi Publishing Corporation. All rights reserved.

Nick,

We have both had similar intersex conditions and i had 4 ovarian cysts removed
as well...Would hope we can be long term friends and your in my prayers with
your situation of the pregnancy..I am on facebook as well on there much more if
you like to friends list me   under      tduncan164330mi@...

talk soon,
tony




________________________________
From: Nick Doty <fighting_eternaly@...>
To: intersexsupport@yahoogroups.com
Sent: Thursday, August 13, 2009 4:22:39 PM
Subject: RE: [Intersex support] Re: Hi, new member and question

 

Yea, that does seem really similar to my situation. For me though, my
development seems a bit less. I was born and designated female at birth. Within
two weeks I was sent to Children's Hospital because of a "mass" in my pelvic
region. What the doctor determined, based on my outward appearance of a not
abnormally large clitoris and uterus, is that the mass was my ovaries that had
not seperated. They cut and seperated them. I never ovulated, but have had
menstrual cycles. In 2005, at age 17, I was diagnosed with a large ovarian cyst
that had grown so much that they had to remove one ovary. Right before this time
I started to look into transgendered issues because I had been living as male
for most of my life under the guise of being a masculine lesbian. I began taking
hormones three and a half years ago and just earlier this year started having
sex where fluids would intermingle. My fiance got pregnant in December and then
again in February, both
  pregnancies resulted in a miscarriage after a month. Just these last two months
we have begun noticing more signs of pregnancy. The issue we face now is that I
am still assigned a female gender and have outward female genitalia. I have
always been masculine, but never questioned by the medical community as anything
but female. To have three pregnancies raises a red flag since scientifically
speaking women can't get other women pregnant. I have never been tested for
chromosome abnormalities or anything, and telling a doctor that I want a sperm
count done when I am "female" doesn't go over so well. I appreciate you sharing
with me Tony. Thanks.

Bright Blessings,
Nickolas Morgaan

EMAILING FOR THE GREATER GOOD
Join me

To: intersexsupport@ yahoogroups. com
From: tonyiroc2@yahoo. com
Date: Thu, 13 Aug 2009 18:29:54 +0000
Subject: [Intersex support] Re: Hi, new member and question

Nick,

Welcome. was born with both a small vaginal opening and discendant testicals and
penis. My female parts were not reproductive and my testicals and penis
functional so was asigned as a male. They got is right in that fact though i
looked like a little tomboyish girl till puberty , I developed as a male after
puberty and was able to have children. My cervix,phillopian structure was all
removed after birth and my vaginal area was closed. My upper vaginal cavity is
still in tact and I have ovarial tissue throught my upper vaginal cavity,vaginal
path and scrodum which ultimately cause ovarian cysts that I had removed.

I was born with an intersex condition called PMSD(Persistent Mullerian duct
syndrome w/ ovairian tissue)...The doctors made the right disition in my mind
due to the fact my male organs were fully funtional and my vaginal opening was
only simi developed..I just have a situation where I have female inside of me
and have alwasys felt it and it took me going in for a visectomy procedure at
age 39 to find out..I had another surgery when i was age 4 because I was peeing
in 2 or 3 streems all over toilet,my mom told me it was to be able to pee like
the big boys and I thought nothing of it ...now i find out it was because of
ovarian tissue build up causing problems with my penis functions..

This made sense now that i know I was born with a vaginal opening ,cervix,
uterus and ovarian tissue at that location..I had total functional male organs
but female organs were not complete..Though now i know i still have female
ovarian like tissue in my body that was found when i had a vesectomy
procedure..My vaginal opening was closed at birth and uterus /fallopian tube
structure removed but still have vaginal path and upper vaginal cavity..My
vaginal cavity and scrodum is filled with ovarian tissue and had to have cysts

removed after they found them during the vesectomy procedure..what a shock to
find out at age 39,,,.I had 2 sons and very happy for that but the loss of part
of my body the way it was upsets me...

We seem quit similar from our birth. As for finding a doctor , I would think any
urologest can check on your sperm count that is quit a common check for couples
trying to conceave... fill free to write..

tony

.com, "Nick D" <fighting_eternaly@ ...> wrote:

>

> Hi, my name is nick. I was born and assigned female at birth, but had to have
surgery only a few weeks later due to an abnormality in my reproductive organs.
My "ovaries" did not split, or at least that what they said then. Twenty-two
years later I am with my current fiance and living as male and identify as
"transgendered" BUT my fiance has had two miscarriages and may be currently
pregnant. This is a rare annomoly, and I know that it seems implausable and the
first conclusion people jump to is that he has been sleeping around. This
assumption has been proven wrong. I have been having a hard time finding a
doctor willing to work with me to verify that I am producing sperm and thus
actually male. Does anyone know how one would go about talking to a doctor about
it?

>

> thanks for any answers,

> nick

>











[Non-text portions of this message have been removed]







[Non-text portions of this message have been removed]

Yea, that does seem really similar to my situation. For me though, my
development seems a bit less. I was born and designated female at birth. Within
two weeks I was sent to Children's Hospital because of a "mass" in my pelvic
region. What the doctor determined, based on my outward appearance of a not
abnormally large clitoris and uterus, is that the mass was my ovaries that had
not seperated. They cut and seperated them. I never ovulated, but have had
menstrual cycles. In 2005, at age 17, I was diagnosed with a large ovarian cyst
that had grown so much that they had to remove one ovary. Right before this time
I started to look into transgendered issues because I had been living as male
for most of my life under the guise of being a masculine lesbian. I began taking
hormones three and a half years ago and just earlier this year started having
sex where fluids would intermingle. My fiance got pregnant in December and then
again in February, both pregnancies resulted in a miscarriage after a month.
Just these last two months we have begun noticing more signs of pregnancy. The
issue we face now is that I am still assigned a female gender and have outward
female genitalia. I have always been masculine, but never questioned by the
medical community as anything but female. To have three pregnancies raises a red
flag since scientifically speaking women can't get other women pregnant. I have
never been tested for chromosome abnormalities or anything, and telling a doctor
that I want a sperm count done when I am "female" doesn't go over so well. I
appreciate you sharing with me Tony. Thanks.


Bright Blessings,
Nickolas Morgaan





  EMAILING FOR THE GREATER GOOD
Join me

To: intersexsupport@yahoogroups.com
From: tonyiroc2@...
Date: Thu, 13 Aug 2009 18:29:54 +0000
Subject: [Intersex support] Re: Hi, new member and question





















                   Nick,



Welcome.  was born with both a small vaginal opening and discendant testicals
and penis. My female parts were not reproductive and my testicals and penis
functional so was asigned as a male. They got is right in that fact though i
looked like a little tomboyish girl till puberty , I developed as a male after
puberty and was able to have children. My cervix,phillopian structure was all
removed after birth and my vaginal area was closed. My upper vaginal cavity is
still in tact and I have ovarial tissue throught my upper vaginal cavity,vaginal
path and scrodum which ultimately cause ovarian cysts that I had removed.



I was born with an intersex condition called PMSD(Persistent Mullerian duct
syndrome w/ ovairian tissue)...The doctors made the right disition in my mind
due to the fact my male organs were fully funtional and my vaginal opening was
only simi developed..I just have a situation where I have female inside of me
and have alwasys felt it and it took me going in for a visectomy procedure at
age 39 to find out..I had another surgery when i was age 4 because I was peeing
in 2 or 3 streems all over toilet,my mom told me it was to be able to pee like
the big boys and I thought nothing of it ...now i find out it was because of
ovarian tissue build up causing problems with my penis functions..

This made sense now that i know I was born with a vaginal opening ,cervix,
uterus and ovarian tissue at that location..I had total functional male organs
but female organs were not complete..Though now i know i still have female
ovarian like tissue in my body that was found when i had a vesectomy
procedure..My vaginal opening was closed at birth and uterus /fallopian tube
structure removed but still have vaginal path and upper vaginal cavity..My
vaginal cavity and scrodum is filled with ovarian tissue and had to have cysts

removed after they found them during the vesectomy procedure..what a shock to
find out at age 39,,,.I had 2 sons and very happy for that but the loss of part
of my body the way it was upsets me...



We seem quit similar from our birth. As for finding a doctor , I would think any
urologest can check on your sperm count that is quit a common check for couples
trying to conceave... fill free to write..



tony



.com, "Nick D" <fighting_eternaly@...> wrote:

>

> Hi, my name is nick. I was born and assigned female at birth, but had to have
surgery only a few weeks later due to an abnormality in my reproductive organs.
My "ovaries" did not split, or at least that what they said then. Twenty-two
years later I am with my current fiance and living as male and identify as
"transgendered" BUT my fiance has had two miscarriages and may be currently
pregnant. This is a rare annomoly, and I know that it seems implausable and the
first conclusion people jump to is that he has been sleeping around. This
assumption has been proven wrong. I have been having a hard time finding a
doctor willing to work with me to verify that I am producing sperm and thus
actually male. Does anyone know how one would go about talking to a doctor about
it?

>

> thanks for any answers,

> nick

>























[Non-text portions of this message have been removed]

Nick,

Welcome.  was born with both a small vaginal opening and discendant testicals
and penis. My female parts were not reproductive and my testicals and penis
functional so was asigned as a male. They got is right in that fact though i
looked like a little tomboyish girl till puberty , I developed as a male after
puberty and was able to have children. My cervix,phillopian structure was all
removed after birth and my vaginal area was closed. My upper vaginal cavity is
still in tact and I have ovarial tissue throught my upper vaginal cavity,vaginal
path and scrodum which ultimately cause ovarian cysts that I had removed.

I was born with an intersex condition called PMSD(Persistent Mullerian duct
syndrome w/ ovairian tissue)...The doctors made the right disition in my mind
due to the fact my male organs were fully funtional and my vaginal opening was
only simi developed..I just have a situation where I have female inside of me
and have alwasys felt it and it took me going in for a visectomy procedure at
age 39 to find out..I had another surgery when i was age 4 because I was peeing
in 2 or 3 streems all over toilet,my mom told me it was to be able to pee like
the big boys and I thought nothing of it ...now i find out it was because of
ovarian tissue build up causing problems with my penis functions..
This made sense now that i know I was born with a vaginal opening ,cervix,
uterus and ovarian tissue at that location..I had total functional male organs
but female organs were not complete..Though now i know i still have female
ovarian like tissue in my body that was found when i had a vesectomy
procedure..My vaginal opening was closed at birth and uterus /fallopian tube
structure removed but still have vaginal path and upper vaginal cavity..My
vaginal cavity and scrodum is filled with ovarian tissue and had to have cysts
removed after they found them during the vesectomy procedure..what a shock to
find out at age 39,,,.I had 2 sons and very happy for that but the loss of part
of my body the way it was upsets me...

We seem quit similar from our birth. As for finding a doctor , I would think any
urologest can check on your sperm count that is quit a common check for couples
trying to conceave... fill free to write..

tony







.com, "Nick D" <fighting_eternaly@...> wrote:
>
> Hi, my name is nick. I was born and assigned female at birth, but had to have
surgery only a few weeks later due to an abnormality in my reproductive organs.
My "ovaries" did not split, or at least that what they said then. Twenty-two
years later I am with my current fiance and living as male and identify as
"transgendered" BUT my fiance has had two miscarriages and may be currently
pregnant. This is a rare annomoly, and I know that it seems implausable and the
first conclusion people jump to is that he has been sleeping around. This
assumption has been proven wrong. I have been having a hard time finding a
doctor willing to work with me to verify that I am producing sperm and thus
actually male. Does anyone know how one would go about talking to a doctor about
it?
>
> thanks for any answers,
> nick
>

Hi Nick. I want to welcome you to this group. Unfortunately it isn't the most
active one around. I really wish I knew something to suggest. I am having
extremely difficult problems with Kaiser which is my HMO.

--- On Thu, 8/13/09, Nick D <fighting_eternaly@...> wrote:
> Hi. my name is Nick. I was born and assigned female at birth, but had to >
have surgery only a few weeks later due to an abnormality in my
> reproductive organs.
> My "ovaries" did not split, or at least that's what they said then.
> Twenty-two years later I am with my current fiance and living as male
> and identify as "transgendered." But my fiance has had two miscarriages > and
may be currently pregnant. This is a rare annomoly, and I know that > it seems
implausable and the first conclusion people jump to is that he > has been
sleeping around. This assumption has been proven wrong. I have > been having a
hard time finding a doctor willing to work with me to
> verify that I am producing sperm and thus actually male. Does anyone know
> how one would go about talking to a doctor about it?
> thanks for any answers,
> Nick

Hi, my name is nick. I was born and assigned female at birth, but had to have
surgery only a few weeks later due to an abnormality in my reproductive organs.
My "ovaries" did not split, or at least that what they said then. Twenty-two
years later I am with my current fiance and living as male and identify as
"transgendered" BUT my fiance has had two miscarriages and may be currently
pregnant. This is a rare annomoly, and I know that it seems implausable and the
first conclusion people jump to is that he has been sleeping around. This
assumption has been proven wrong. I have been having a hard time finding a
doctor willing to work with me to verify that I am producing sperm and thus
actually male. Does anyone know how one would go about talking to a doctor about
it?

thanks for any answers,
nick

Year : 2009  |  Volume : 6  |  Issue : 2  |  Page : 82-84

Transfer of surgical competences in the treatment of intersex disorders in Togo

K Gnassingbe1, S da Silva-Anoma2, GK Akakpo-Numado1, AH Tekou1, B Kouame2, C
Aguehounde3, L Coupris4, RB Galifer5, D Aubert6, Y Revillon7
1 Department of Pediatric Surgery, Lome Teaching Hospital (Lomé- Togo),
2 Department of Pediatric Surgery, Yopougon Teaching Hospital (Abidjan - Ivory
Coast),
3 Department of Pediatric Surgery, Cocody Teaching Hospital (Abidjan - Ivory
Coast),
4 Department of Pediatric Surgery, Angers Teaching Hospital (Angers-France),
5 Department of Pediatric Surgery, LAPEYRONIE Hospital (Montpelliers - France),
6 Department of Pediatric Surgery, St Jacques Hospital (Besançon- France),
7 Department of Pediatric Surgery, Necker Enfants Malades Hospital
(Paris-France),

Click here for correspondence address and email Date of Web Publication
29-Jul-2009


Abstract
Background: To evaluate the impact of scientific seminar on the sexual ambiguity
on patients and paediatric surgeons in French-speaking African countries.
Materials and Methods: This was a report of the proceeding of a teaching seminar
on intersex management, which was held from December 4 th to 8 th , 2006, in the
Paediatric Surgery Department of Tokoin Teaching Hospital and the Surgery
Department of "Saint Jean de Dieu" Hospital of Afagnan, Togo.
Results: There were 107 participants [five professors of paediatric surgery, 62
African paediatric surgeons (including 15 from African French- speaking
countries), and 40 general surgeons]. The workshop involved a two-day
theoretical teaching session (aimed at understanding, recognising, and treating
the sexual ambiguities), and practical session; during these sessions different
intersexes (one case of mixed gonadal dysgenesis, two of female
pseudohermaphroditism, and two of male pseudohermaphroditism), were operated
free of charge. Participants expressed satisfaction and confidence with regard
to the management of intersex after the seminar. Conclusion: This scientific
forum allowed possible exchange of competence among the paediatric surgeons with
regard to efficient treatment of sexual ambiguities.

Keywords: Paediatric surgeons, sexual ambiguities, transfer of competence

How to cite this article:
Gnassingbe K, da Silva-Anoma S, Akakpo-Numado GK, Tekou AH, Kouame B, Aguehounde
C, Coupris L, Galifer RB, Aubert D, Revillon Y. Transfer of surgical competences
in the treatment of intersex disorders in Togo. Afr J Paediatr Surg 2009;6:82-4

How to cite this URL:
Gnassingbe K, da Silva-Anoma S, Akakpo-Numado GK, Tekou AH, Kouame B, Aguehounde
C, Coupris L, Galifer RB, Aubert D, Revillon Y. Transfer of surgical competences
in the treatment of intersex disorders in Togo. Afr J Paediatr Surg [serial
online] 2009 [cited 2009 Aug 11];6:82-4.
Available from:
http://www.afrjpaedsurg.org/text.asp?2009/6/2/82/54768

Introduction
The complexity of intersex, similar to many other congenital anomalies, poses
treatment challenges to the African pediatric surgeons. Technological
improvements during previous years have permitted a great amelioration in the
detection and treatment of some pediatric surgical pathologies in the developed
countries; whereas, most of these advances are lacking in many developing
(African) countries. [1],[2] As a result, the transfer of competence in various
forms between the developed countries and the developing countries is the most
desired.

One forum to transfer such surgical competence is through seminars. In November
2006, a precongress workshop on paediatric urology and intersex was held in
Mombasa, Kenya; as a part of the sixth biennial congress of the Pan-African
Paediatric Surgical Association (PAPSA). In December 2006, the French-speaking
African Pediatric Surgery Society, Togo, organised a teaching seminar to improve
and reinforce the paediatric surgeons from French-speaking Africa countries, on
intersex management. This seminar was focused at initiating them to the new
surgical techniques in treatment of intersex. The aim of this study was to
evaluate the impact of such scientific exchange of competences on patients and
paediatric surgeons from the African countries.


Materials and Methods
This was a study of the patients treated for intersex during a workshop, held in
the paediatric surgery department of Tokoin Teaching Hospital and the Surgery
Department of "Saint Jean de Dieu" Hospital of Afagnan, Togo, from December 4 th
to 8 th , 2006. This workshop took the form of theoretical and practical
surgical sessions.

Among 11 patients, five had karyotype and genitography, and the rest were
excluded for the following reasons: (1) isolated hypertrophied clitoris, (2)
micropenis with testicular agenesis toward an infantilism, (3) vaginal agenesis,
(4) failure of a masculinising gιnitoplasty in a male pseudo
hermaphroditism, (5) a 23-year old patient, having a congenital adrenal
hyperplasia, refused to be feminised, and (6) micropιnis associated to
hypospadias in whom the hormonal stimulation has not be conducted.


Results
There were 107 participants [5 French professors of paediatric surgery, 62
African paediatric surgeons (including 15 from African French-speaking
countries), and 40 general surgeons].

The different intersex disorders treated during the practical session included
one case of mixed gonadal dysgenesis, two of female pseudohermaphroditism, and
two of male pseudohermaphroditism. The epidemiological, diagnostic, and
therapeutical characteristics of the patients treated during the workshop are
represented in [Table 1].

Participant's satisfaction and confidence assessed at the end of the seminar
with regard to the management of intersex showed high level of confidence in all
the participants.


Discussion
The frequency of genital malformations seems on the increase; environmental
pollution by pesticides, used to destroy mosquito larvae, has been implicated.
[3]

Genital malformations, in particular intersex, are important topics in our
countries because of the strong psychological pressure they impose [4] such as
stigmatisation and social exclusion leading to suicide in some cases. It is
therefore important to recognise them and treat them well.

Although paediatric surgery practice is well established [5] the number of
paediatric surgeons varies from one country to another. In Europe, the ratio of
paediatric surgeon to the patients varies from 1:424 to 1:35714, per year. [5]
In Africa, where 50% of the population is less than the age of 15 years, the
ratio is weak with an average of four paediatric surgeons per country. Due to
this, the children in Africa with intersex are treated most of the time by
urologists, who are not competent in this regard. This situation is compounded
by the lack of modern facilities (laboratories, magnifying glasses, and
microscopes).

These difficulties often push African paediatric surgeons to refer the patients
to developed countries for management, with attendant exorbitant cost. Non
Governmental Organisations (NGOs) such as, "Terre des Hommes", "La chaξne
de l'Espoir", sometimes play some role in assisting these high costs. At times
NGOs also collaborate with their western partners to carry out benevolent health
expeditions for local treatment of patients suffering from congenital
abnormalities, including intersex in Africa. [6] It was in the light of these
challenges that the French-speaking African Paediatric Surgery Society recently
chose to improve the level of competence of paediatric surgeons concerning the
management of intersex by organising a workshop during which some patients with
intersex were operated free [Table 1].

The high number of participants in the workshop underscored the perceived
interest, in this arrangement. Every practitioner, whether a paediatric surgeon,
a general practitioner, a general surgeon, or a urologist, has to be confronted
with the difficulties of treating these affections in one's professional life.
This probably explained why the general surgeons participated in these teaching
seminars and workshops.

The experience from this workshop highlights few facts: (1) the value of
cooperation between paediatric surgeons in Africa and the global pediatric
surgical community, (2) the late presentation of patients with intersex in some
African countries, (3) the potential role of media in health education in
Africa, and (4) the need for conducting similar workshops in the future.

We like to conclude that collaborative scientific/surgical workshops appear to
facilitate transfer of surgical competence, although evaluation of the
aftermaths of this training in a short or midterm is necessary before a definite
recommendation.

References
1. Harouchi A. Les progrθs de la chirurgie pιdiatrique moderne ont-ils
atteint les enfants africains ? Chir Pιdiatr 1990;31:284-6.
2. Balde I, Doumbouya N, Agbo-Panzo D, Diallo AF, da Silva-Anoma S. Panorama de
la chirurgie pιdiatrique en Afrique. Mιd Afr Noire 1999;46:243.
3. Hosie S, Loff S, Witt K, Niessen K, Waag KL. Is there a correlation between
organochlorine compounds and undescended testes? Eur J Paediatr Surg
2000;10:304-9.
4. Lazarovici. Consιquences psychologiques de l'ectopie testiculaire. Chir
Pιdiatr 1989;30:150-2.
5. Driller C, Holschneider AM. Training in Paediatric Surgery. A Comparison of
24 countries in Europe and other countries around the World. Eur J Paediatr Surg
2003;13:73-80.
6. Gbenou AS, Biotchane I, Fiogbι M, Lokossou T, Biaou O, Adibabi W. Bilan
de 4 missions chirurgicales caritatives ιtrangθres au Bιnin.
Bιnin Mιd 2002;22:65-70.


Correspondence Address:
K Gnassingbe
Department of Pediatric Surgery, Lome Teaching Hospital (Prof. Hubert Tekou), PO
Box 57, Lomé Togo



Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0189-6725.54768

Tables
[Table 1]

doi:10.1016/j.pedhc.2009.05.001
Copyright © 2009 National Association of Pediatric Nurse Practitioners Published
by Mosby, Inc.
Original Article

When Size Matters: A Clinical Review of Pathological Micropenis

Shirley Tsang MS, RN, CPNP,

Available online 23 July 2009.

Abstract
Micropenis is a significantly small penis with normal internal male genitalia.
Micropenis is usually diagnosed shortly after birth, and the cause should be
established; in addition, it should be differentiated from other associated
syndromes. The role of the pediatric nurse practitioner is to diagnose the
micropenis, guide the parents through the options of management, and support all
involved through the selected treatment, whether hormonal or surgical. Patients
affected with micropenis will need long-term management from their pediatric
nurse practitioners, as well as follow-up by endocrinologists, urologists,
pediatric surgeons (if surgery is chosen as the treatment), psychologists, and
social workers. The need of more long-term research on patients with micropenis
also is discussed.

Key words: Micropenis; hypogonadotropic hypogonadism; androgen insensitivity; 5
alpha reductase deficiency; testosterone treatment

Article Outline
Criteria for review
Normal development
Diagnostic criteria
Measurement
Pathophysiology
Hypogonadotropic Hypogonadism
Androgen Insensitivity
5-Alpha Reductase Deficiency
Diagnostic work-up
Treatment
Testosterone Therapy
Topical 5α-dihydrotestosterone Gel
Luteinizing Hormone/Follicle-stimulating Hormone
Surgical Options
Gender reassignment
The role of the pediatric nurse practitioner
Future research
Conclusion
Acknowledgements
References
Vitae

The human body can vary greatly in both shape and size, but the size of certain
body parts may signal an underlying pathology, one example being an extremely
small penis. Micropenis refers to an abnormally small, normally structured penis
with a stretched penile length of less than 2.5 standard deviations (SD) below
the mean for age or stage of sexual development (Zenaty et al., 2006). Patients
who have micropenis have a 46 X,Y karyotyping with gonads that are exclusively
testicular without any signs of hypospadias (Vogt, 2006). Micropenis can be
considered a clinical sign of a larger syndrome or an independent anomaly. One
epidemiological study showed that 1.5 per 10,000 infant males were born with
micropenis between 1997 and 2000 in the United States (Nelson et al., 2005).
Another similar term is "microphallus," which refers to ambiguous-looking
genitalia, but for the purpose of this article we will solely discuss the
subject of micropenis.

The purpose of this article is to familiarize the medical professional, more
specifically the pediatric nurse practitioner (PNP), with the phenomenon of
micropenis and to review normal penile development, as well as the diagnostic
criteria, causes, and treatments for micropenis. Long-term effects in terms of
treatment and gender role also are discussed, along with the important role of
the PNP in caring for affected patients. This article aims to provide PNPs with
insights on this condition and information on management, including necessary
referrals and treatments.

Criteria for review
The studies chosen for review were limited to recent articles and books from
1997 to 2008 and dealt with all aspects involving micropenis. The exception to
these criteria was the article "Micropenis. I. Criteria, Etiologies and
Classification" by Lee et al. (1980), which was published in 1970 and is
considered one of the "gold standards" on micropenis. The search was completed
using Ovid Medline 1950 to 2007 and PubMED, as well as the Augustus C. Long
Health Sciences Library at Columbia University and D. Samuel Gottesman Library
at Albert Einstein College of Medicine of Yeshiva University. Key words used in
the search were "micropenis," "5-alpha reductase deficiency," hypogonadism,"
"androgen insensitivity," and "ambiguous genitalia." The criteria focused on
classifications, causes, management, treatments, and future outcomes of patients
with micropenis.

Normal development
Human male sexual differentiation begins with the sex determination (testis
development) and is followed by sex differentiation (genital development)
(Sultan et al., 2001). Normal sexual differentiation begins the seventh week of
gestation when the fetus contains both the male and female genital ducts. In
normal male differentiation, the sex-determining region of the Y region (SRY)
directs the development of testes, and in the absence of the SRY gene, ovaries
will be formed.

Early in gestation, placental human chorionic gonadotropin stimulates the
developing testes to produce androgens, and by the fifteenth week, the
regulation of androgen secretion is taken over by gonadotropins (luteinizing
hormones and follicle-stimulating hormones) from the fetal pituitary, which is
regulated by the fetal hypothalamus to form the hypothalamic pituitary-gonadal
axis. The androgens produced are Müllerian inhibitory substance, which cause the
female internal genital structures to regress, and 5α-dihydrotestosterone
(DHT), which is required for the development of male internal genital structures
and the differentiation of male external genitalia (Byne, 2006).

Activation of androgen receptors by testosterone or DHT also appears to
contribute to the masculinization of brain structure and function in some
species. Fetal androgen levels in males are elevated between weeks 8 to 24 of
gestation, with peak levels occurring between weeks 14 to 16, while postnatal
male testosterone levels increase from birth to a peak at 1 to 3 months and then
decrease to prepubertal levels by 4 to 6 months (Byne, 2006). It has been found
that the highest penile growth velocity is associated with the increased levels
of testosterone during the 0- to 3-month period after birth. Thus the postnatal
surge in reproductive hormones appears to be important for genital growth (Boas
et al., 2006). Without satisfactory hypothalamic or pituitary function,
inadequate penile growth will occur despite a normally shaped penis. Similarly,
a primary testicular disorder that causes insufficient testosterone production
near the end of gestation also can result in minimal penile growth (Vogt, 2006).

Diagnostic criteria
The early diagnosis of "true micropenis" is essential and can give practitioners
and parents an early opportunity for various treatment options. The first step
to diagnosing micropenis is a physical examination of the external genitalia of
the patient. Micropenis is by definition a condition that solely affects XY
males, characterized by a small penis with a median raphe, foreskin, and glans
in which the urethral meatus is normally placed, that is, no hypospadias (Figure
1). It may be either retracted or pendulous depending upon the length of the
shaft and may or may not be erectile depending upon the presence or absence of
the corpora cavernosa and corpus spongiosum. The scrotum is present and normally
fused but may be underdeveloped, and the testes typically are descended and may
or may not be normal in function (Lee et al., 1980). In general, there should
not be any signs of feminization.

Full-size image (26K)
Figure 1. A, Micropenis in an infant. (From Morales, S., Guerra, G., Jr., &
Maciel-Cuerra, A. T. (2006). Female counterpart of shawl scrotum in
Aarskog-Scott syndrome. International Brazilian Journal of Urology, 32, 460.
Copyright 2006 by the International Brazilian Journal of Urology. Reprinted with
permission). B, Micropenis in an adult. (From Micropenis. Wikipedia the Free
Encyclopedia. Accessed July 14, 2009, from
http://en.wikipedia.org/wiki/Micropenis.) Figure 1B can be viewed in color
online at www.jpedhc.org.

View Within Article


Occasionally older boys are evaluated for small genitalia due to parental
concern. However, these boys usually are prepubertal and obese, and the minimal
size of their penis is a result of the penis being hidden in the prepubic fat.
The size of their penis is warranted as normal unless the size falls within the
micropenis criteria. An accurate penile length measurement and thorough physical
assessment can distinguish micropenis from other conditions (Vogt, 2006).
Misdiagnosing this condition may delay treatment and cause more frustration for
the parents.

Measurement
Getting the correct penile measurement is very important because a diagnosis of
micropenis really hinges on the size. An accurate measurement that correlates
with the requirement of 2.5 SD below the norm for age plus external and internal
organs of an XY karyotype can be sufficient evidence to support a diagnosis of
micropenis.

The conventional method for measuring the penis is using a ruler or calipers.
The penile length should be the fully stretched rather than flaccid and can be
achieved by grasping the glans between the thumb and forefinger and measuring
from the pubic ramus, along the dorsum, to the tip of the glans penis. The
suprapubic fat pad should be compressed in as completely as possible and the
foreskin, if present, is not included in the measurement (Lee et al., 1980).
Another option is using a 10-mL disposable syringe in a modified construction.
The needle-bearing end is removed and the piston is inserted in to the cut end
(Figure 2). The flanged end is then placed over the penis, firmly pressing in to
the fat pad while the piston is withdrawn, causing the penis to be suctioned
into the injector. Once the penis is stretched out within the syringe during
optimal suction, the penis length is read from the attached scale. Using this
method eliminates measurement variability caused by the suprapubic fat pad by
gently pressing the syringe on to the symphysis pubis (Ozbey, Temiz, & Salman,
1999).


Full-size image (12K)
Figure 2. Modified syringe used to measure the penis. This figure can be viewed
in color online at www.jpedhc.org.

View Within Article


After obtaining a correct measurement of the penis, the value is compared with
the normal size range for chronological age. The penis must measure less than
2.5 SD below the mean for age to qualify as micropenis. Table 1 contains the
average stretched penile length (in centimeters) of normal male subjects based
on age and the length 2.5 SD below. For premature newborns, the following
formula describes the expected penile length for infants born between 24 and 36
weeks gestation:

Table 1.
Stretched penile length in normal male subjects (cm)

Age Mean Mean –2.5 SD
Newborn: 30 wk 2.5 ± 0.4 1.5
Newborn: 34 wk 3.0 ± 0.4 2.0
Newborn: term 3.2 ± 0.4 2.5-2.4
0-5 mo 3.9 ± 0.8 1.9
6-12 mo 4.3 ± 0.8 2.3
1-2 y 4.7 ± 0.8 2.6
2-3 y 5.1 ± 0.9 2.9
3-4 y 5.5 ± 0.9 3.3
4-5 y 5.7 ± 0.9 3.5
5-6 y 6.0 ± 0.9 3.8
6-7 y 6.1 ± 0.9 3.9
7-8 y 6.2 ± 1.0 3.7
8-9 y 6.3 ± 1.0 3.8
9-10 y 6.3 ± 1.0 3.8
10-11 y 6.4 ± 1.1 3.7
Adult 13.3 ± 1.6 9.3

Full-size table
This table was published in Endocrinology, Volume, Custer, J., & Rau, R., The
Harriet Lane handbook, 18th ed., 269-300, Copyright Elsevier (2009).


View Within Article



Expected penile length (cm) = 2.27 + 0.16 X (gestational age in weeks)

In general, full-term newborns must achieve a measurement of less than 2.5 cm,
or 1 inch, to meet the definition of micropenis (Vogt, 2006). A penile length
that falls into the micropenis category warrants further evaluation of cause and
treatment (Table 1).

Other syndromes can also be mistaken for micropenis, such as concealed penises
(Figure 3) which are further categorized as buried penis, trapped penis, and
webbed penis. A buried penis is a typical-sized penis enclosed in the suprapubic
fat pad because of a lack of skin attachment to the shaft, while the trapped
penis results from excessive circumcision where adhesions form between the
scrotal and penile skin. A webbed penis is characterized by the skin of the
shaft being tethered to the ventral surface of the scrotum (Borsellino,
Spagnoli, Vallasciani, Martini, & Ferro, 2007). Additional differential
diagnoses are penile agenesis, where there is no penis at all, or penis with
marked chordee, when the head of the penis is curved downward (Menon & Khatwa,
2000).

Full-size image (33K)
Figure 3. Examples of concealed penises. (Reprinted from Urology, 69,
Borsellino, A., Spagnoli, A., Vallasciani, S., Martini, L., & Ferro, F, Surgical
approach to concealed penis: Technical refinements and outcome, 1196, Copyright
(2007) with permission from Elsevier.) This figure can be viewed in color online
at www.jpedhc.org.

View Within Article


Pathophysiology
Micropenis can occur as an isolated incident or in association with other
conditions, especially those involving hormone deficiencies. Some etiological
factors of micropenis due to hormone deficiencies are hypogonadotropic
hypogonadism resulting from an endocrine anomaly of the
hypothalamic-pituitary-gonadal axis and androgen insensitivity syndrome with
inadequate penile growth despite normal or excessive androgen secretion
([Ludwig, 1999] and [Menon and Khatwa, 2000]). Other possible causes of
gonadotropin deficiency are caused by hypothalamic dysfunction, such as
Kallmann's syndrome or Prader-Willi syndrome. There also can be decreased
synthesis of testosterone or conversion of testosterone to DHT, as is the case
of 5-alpha reductase deficiency (5αRD), decreased testosterone sensitivity,
and growth hormone deficiency. Table 2 describes in more detail the
pathophysiology, clinical findings, and diagnostic work-up results of
hypogonadotropic hypogonadism, androgen insensitivity, and 5αRD, while Box
1 lists other conditions associated with micropenis.

Table 2.
Hypogonadotropic hypogonadism, androgen insensitivity, and 5α reductase
deficiency

Differential Pathophysiology Clinical findings Diagnostic work-up
Hypogonadotropic hypogonadism (idiopathic or Kallman's syndrome) Failure of the
hypothalamus to secrete gonadotropin releasing hormones Idiopathic can present
with micropenis; Kallman's syndrome: micropenis or cryptorchidism, anosomia,
hyposomia, sensorineural deafness, visual abnormalities, cleft lip and palate,
congenital heart disease, renal agenesis, cerebellar ataxia, arm span greater
than height, short metatarsals 1. Demonstration of prepubertal serum
testosterone concentrations of less than 100 ng/dL in males

2. Low or normal serum LH and FSH concentrations (usually less than 4 to 5 IU/L)

3. Otherwise normal anterior pituitary function

4. Normal appearance of the hypothalamus and pituitary region on MRI

Androgen insensitivity (complete or partial) Defective mechanism of action of
the androgen on target cell or defective androgen receptor gene (loss-of-
function); caused by defects in gene coding, environmental chemicals that impair
DHT synthesis, and AR mediation Micropenis or ambiguous genitalia;CAIS: female
external genitalia with normal labia, clitoris, and vaginal canal; PAIS: wide
range, female with only clitoromegaly or male with micropenis and/or hypospadias
1. Karyotyping, chromosomally male or female

2. Normal or abnormal serum testosterone levels

3. Mutations on the coding region for AR seen upon sequencing

5α reductase deficiency Mutations in the steroid 5α-reductase type 2
gene causing a lack of enzyme production or defects in androgen receptor site
Isolated micropenis or hypospadias, severe ambiguity of external genitalia;
internal male genitalia are normally developed 1. Increased ratio of serum
testosterone to DHT

2. DHT level is low to undetectable

3. Testosterone level is normal to moderately elevated

4. Molecular analysis of 5αR type 2 gene (not commercially available)


Full-size table
From [Bertelloni et al., 2007], [Fechner et al., 2008], [Galani et al., 2008],
[Lee et al., 1980], [Ludwig, 1999], [Menon and Khatwa, 2000], [Sultan et al.,
2001], [Vogt, 2006] and [Wisniewski and Migeon, 2002].

AR, androgen receptor; CAIS, complete androgen insensitivity syndrome; DHT,
5α-dihydrotestosterone; FSH, follicle-stimulating hormone; LH, luteinizing
hormone; MRI, magnetic resonance imaging; PAIS, partial androgen insensitivity
syndrome.


View Within Article


Box 1. Conditions associated with micropenis

• Hypogonadotropic hypogonadism
Kallmann

Klinefelter

Prader-Willi

Bardet-Biedl

Rud

Septo-optic dysplasia

Robinow

• Partial androgen insensitivity

• Deficiency of 5α reductase

• Decreased testosterone production

Growth hormone deficiency

• Panhypopituitarism

• Other

CHARGE

Noonan

From Lee et al., 1980, and Ludwig, 1999.



Hypogonadotropic Hypogonadism
Hypogonadotropic hypogonadism can present initially with micropenis, which
allows it to be diagnosed shortly after birth (Main, Schmidt, Toppari, &
Skakkebaek, 2002). Hypogonadotropic hypogonadism is the failure of the
hypothalamus to secrete gonadotropin-releasing hormones (GnRH) that normally
stimulate the pituitary gland to secrete the gonadotropins luteinizing hormone
(LH) and follicle-stimulating hormone (FSH), which stimulate male testes to
secrete hormones that are responsible for normal pubertal maturation and
reproductive function (de Roux et al., 2003). The hypothalamic-pituitary
function is otherwise normal in most patients, and hypothalamic-pituitary
imaging reveals no space-occupying lesions. This condition can be idiopathic or
a result of Kallman's syndrome (Fechner, Fong, & McGovern, 2008). In Kallman's
syndrome, the failure of the hypothalamus to secrete GnRH leaves a deficiency in
sex hormones that presents with micropenis or cryptorchidism and anosmia (a lack
of smell) and hyposomia (inadequate development of the body). Kallman's syndrome
is an autosomal dominant, autosomal recessive or X-linked recessive disease and
can be distinguished from idiopathic hypogonadotropic hypogonadism with an
objective smell test to document anosmia (Fechner et al.). The syndrome is
diagnosed on the basis of clinical presentation, while the GnRH deficiency is
diagnosed biochemically.

Androgen Insensitivity
In complete androgen insensitivity syndrome (CAIS) and partial androgen
insensitivity syndrome (PAIS), the mechanism of the androgen action on the
target cell is defective, or in other words, there is a loss-of-function
mutation in the androgen receptor gene ([Menon and Khatwa, 2000] and [Wisniewski
and Migeon, 2002]). This x-linked recessive condition can result in micropenis
or genitalia that are more uncertain (Kohler et al., 2005). Individuals with
CAIS and PAIS are chromosomally and gonadally male; however, those with CAIS
have female external genitalia with a normal labia, clitoris, and vaginal canal,
while PAIS external genitalia can range from slightly virilized female to
slightly undervirilized male. For the purpose of this article, we will be
focusing on PAIS, although diagnostic screening would be the same for both. Male
subjects affected with PAIS have normal testes, most likely undistended, with
normal production of testosterone and normal conversion to DHT, and because they
produce normal amounts of Müllerian inhibitory substance, they do not have
fallopian tubes, a uterus, or a vagina. They also may or may not have normal
serum testosterone levels because they only have partial enzyme defects (Galani,
Kitsiou-Tzeli, Sofokleous, Kanavakis, & Kalpini-Mavrou, 2008).

5-Alpha Reductase Deficiency
Peripheral conversion of testosterone into DHT by enzyme 5αR is shown to
play a major role in the masculine differentiation of the external genitalia and
the subsequent phallic growth (Gad, Nasr, Mazen, Salah, & El-Ridi, 1997).
5αRD is primarily due to mutations leading to lack of enzyme production,
but it also can be caused by defects in the androgen receptor site. Patients
affected with 5αRD are genetically male, but some patients are mistakenly
assigned as female because of under-virilization and are raised as such.
However, during puberty a variable degree of virilization will occur because of
the increased surge of testosterone, and a change in gender may be needed
(Bertelloni et al., 2007). It has been questioned as to how much a role
5αRD plays in a male subject with congenital micropenis. In the study by
Gad and colleagues, it was found that 5αRD played a minimal role in
isolated micropenis and was more prevalent in cases of ambiguous genitalia with
micropenis; however, the study also found that 5αRD did correlate with
penile length in intersex cases. If 5αRD is not the main cause of
micropenis, it does seem to play a part in the growth of a penis.

Diagnostic work-up
The initial step of treatment of micropenis is to have a complete work-up
ordered by the primary care provider or endocrinologist, including chromosomal
analysis or karyotyping with Y fluorescence to determine the genetic sex and to
rule out other syndromes (Menon & Khatwa, 2000). Levels of serum gonadotropin
(LH and FSH), testosterone, DHT, and androstenedione (a precursor sex hormone)
also are measured (Table 3). The gonadotropin levels will be able to narrow down
the differential diagnoses, while testosterone and DHT levels can determine the
testes' responsiveness to gonadotropin stimulation. It also can be used to
diagnose 5αRD. A GnRH stimulation test will evaluate the pituitary gland's
ability to respond and produce LH and FSH. Levels of the growth hormone
cortisol, as well as total and free thyroxine levels, will determine
hypopituitarism, and a human chorionic gonadotropin stimulation test will
measure the body's ability to perform testosterone biosynthesis ([Custer and
Rau, 2009] and [Lee et al., 1980]). Imaging studies such as pelvic
ultrasonography can be helpful in cases of ambiguous genitalia to visualize the
internal reproductive organs, or a magnetic resonance imaging scan of the head
can be used to assess the pituitary and hypothalamic area (Vogt, 2006).

Table 3.
Normal serum levels of hormones

Gonadotropins
Age FSH (mIU/mL) LH (mIU/mL)
Prepubertal children 0.0-2.8 0.0-1.6
Men 1.4-14.4
Women, follicular phase 3.7-12.9
Testosterone
Age Testosterone (ng/dL)
Prepubertal children 10-20
Men 275-875
Women 23-75
Pregnancy 35-195
Dihydrotestosterone
Age Males (ng/dL) Females (ng/dL)
Cord blood <2-8 <2-5
1-6 mo 12-85 <5
Prepubertal <5 <5
Tanner stage II-III 3-33 5-19
Tanner stage IV-V 22-75 3-30
Androstenedione
Age Males (ng/dL) Females (ng/dL)
Pre-term infants
26-28 wk to day 4 of life 92-892 92-892
31-35 wk to day 4 of life 80-446 80-446
Full-term infants
1-7 day 20-290 20-290
1-12 mo 6-68 6-68
Prepubertal children 8-50 8-50
Tanner II 31-65 42-100
Tanner III 50-100 80-190
Tanner IV 48-140 77-225
Tanner V 65-210 80-240
Adults 78-205 85-275

Full-size table
This table was published in Endocrinology, Volume, Custer, J., & Rau, R., The
Harriet Lane handbook, 18th ed., 269-300, Copyright Elsevier (2009).

FSH, Follicle-stimulating hormone; LH, luteinizing hormone.


View Within Article


Treatment
Testosterone Therapy
Initial treatment is a short course of testosterone to assess the ability of the
penis to respond to the hormone. Treatment can be given via intramuscular
injections or applied topically. Testosterone cypionate or enanthate in oil, 25
mg, is given intramuscularly every 3 weeks for 4 months for the initial course.
The adverse effects are minimal and include temporary accelerated growth
velocity and bone age (Menon & Khatwa, 2000). Topical testosterone application
also has been shown to be effective in young children. Arisaka et al. (2001)
administered 5% testosterone ointment daily to 50 boys aged 5 months to 8 years
for 30 days, which resulted in increased penile length. Transdermally absorbed
testosterone also has been shown to stimulate the secretion of growth hormone
from the pituitary gland, which will increase the production of insulin-like
growth factor-I, a factor that promotes bone growth. Long-term administration
has the potential to enhance growth in penile length as well as skeletal growth
(Arisaka et al.).

Empirical evidence indicates that testosterone treatment has a positive impact
on penile growth during infancy, yet it is unclear whether the growth will
continue during adolescence and adulthood (Baskin et al., 1997). A lack of
response is likely to represent androgen resistance or androgen receptor
deficiency, and therefore failure to virilize at puberty is possible. An
important aspect of testosterone treatment is the recommendation to begin
treatment early in infancy and childhood. Patients with hypogonadotropic
hypogonadism show a decrease in penile androgen expression. There is a natural
decrease in androgen receptors in early adulthood, and so the early
administration of testosterone allows for increased penile androgen receptor
concentration and duration during the period before this decline (Menon &
Khatwa, 2000).

Topical 5&#945;-dihydrotestosterone Gel
In prepubertal patients with androgen insensitive syndrome, topical DHT gel
applied to the peri-scrotal region three times a day for 5 weeks raised serum
DHT. In a study by Ong, Wong, and Yong (1999), the aforementioned treatment
resulted in increased penile length and improved male genital development in a
46 X,Y infant. This treatment also has been shown to work with patients affected
with 5&#945;RD, although the large amount of testosterone produced at puberty
may be enough for complete virilization. In a research study by Bertelloni and
colleagues (2007), three Italian 46 X,Y newborns, two with 5&#945;RD, were given
a trial of DHT cream, which resulted in an increase of penile length of at least
120%. In a study by Charmandari, Dattania, Perry, Hindmarsha, and Brooka (2001),
percutaneous 2.5% DHT gel was used on six children (ages 1.9 to 8.3 years)
affected by micropenis of various etiologies. They found that administration of
DHT, 0.2 to 0.3 mg/kg once daily for 3 to 4 months, was able to increase phallic
growth. Adverse effects were minimal, with minor irritation to the skin, and
similar to adverse effects of testosterone treatment (Kaya et al., 2008).
Topical DHT can be a good alternative for patients who do not respond to
testosterone.

Luteinizing Hormone/Follicle-stimulating Hormone
In patients with hypogonadotropic hypogonadism, treatment with recombinant human
LH and FSH during the first year of life has been successful in inducing
testicular growth and a little increase in penile length. In a study by Main and
colleagues (2002), a patient with micropenis was given recombinant human LH and
FSH in doses of 20 and 21.3 IU as subcutaneous injections twice a week over a
period of 6 months and was able to achieve sufficient phallic growth when
testosterone was added to the treatment. Some adverse effects reported included
increased body hair and pigmentation as well as intermittent nausea. In general,
the treatment was well tolerated (Main et al.).

Although exogenous hormone treatments can result in increased penile growth in
the patient with micropenis, penile length still may be below average in
adulthood (Tietjen, Uramoto, Tindall, & Husmann, 1998).

Surgical Options
If the micropenis does not achieve adequate length through medical intervention,
surgical options are available, but these options should only be considered
after all other treatments have been exhausted. One option is surgical
construction of the penis, or elongation plastic surgery. These procedures are
highly complex and carry with them many risks, especially because the patient
most likely will undergo multiple treatments and the results may not produce
acceptable functional or cosmetic outcomes (Byne, 2006). Genitoplasty also can
have other complications such as increased scarring, pain, and decreased sexual
pleasure. These complex procedures requires a skilled team of physicians,
including plastic surgeons, microvascular surgeons, and urologists, and
currently they are being performed only in highly specialized centers that can
guarantee high standard outcomes (De Castro, Merlini, Rigamonti, & Macedo,
2006). However, social and psychological concerns justify early palliative
phalloplasty.

Gender reassignment
Gender reassignment was once a popular option because prompt surgical
normalization of external genital anomalies was viewed as necessary to establish
the perceived gender versus chromosomal gender (Byne, 2006). However, recent
reports in long-term follow-up have shown that the majority of male patients
with penile malformation who are raised as girls have demonstrated a marked
male-typical shift in psychosocial and psychosexual development, with most
declaring themselves to be male (De Castro et al., 2006). This information
provided by adults with micropenis who claim a male gender role, have a
heterosexual orientation, and indicate a steadfast male gender identity has led
to a change in attitude regarding gender reassignment. Furthermore, information
concerning the impact of androgen on the fetal brain suggests that sex steroid
exposure may have an organizing influence on gender, particularly in regard to
gender role (Lee & Houk, 2004). More recent reports suggest that biological
factors in the prenatal period also may have a significant role in gender
identification, especially due to brain imprinting from testosterone. On the
other hand, long-term psychosexual issues may occur in the presence of a small
sex organ (Gearhart, Rink, & Mouriquand, 2001). Although gender reassignment is
now discouraged, there are problems revolving around psychological concerns.
Some concerns include patients expressing that their quality of life had been
negatively affected by the presence of micropenis and seeking psychological
counseling because of concerns of sexual inadequacy and/or depression. A high
incidence of depression combined with the patients' perception that their
micropenis has negatively affected their quality of life indicates that
psychological counseling should be recommended routinely in the treatment of
these patients (Canning, 2006).

The role of the pediatric nurse practitioner
The first health care professional to discover the anomaly is most likely the
pediatrician or PNP during the newborn examination or a well-infant check-up
during the first year of life. The first step in diagnosing suspected micropenis
is to confirm that the length of the penis fits within the criteria of a
diagnosis of micropenis. Measuring should be done on the stretched penile length
using one of the two methods previously described, either the ruler or syringe.
The PNP making the diagnosis should be familiar with the genetic and
endocrinology principles that direct fetal sex differentiation as well as the
influence of fetal sex hormones on gender identity (Stein, Sandberg, Mazur,
Eugster, & Daaboul, 2004). This knowledge enables the PNP to explain to parents
how hormones affect penile growth and to provide basic information regarding
their child's condition. Next, the PNP should refer the patient to a pediatric
endocrinologist for consultation and more in-depth information on the condition.
The laboratory studies needed to confirm the diagnosis can be ordered either by
the PNP or the endocrinologist.

Once the work-up on the patient is complete and the endocrinologist involved in
the child's care has determined the cause of the micropenis, treatment and
management can begin. The person responsible for providing the parents with the
diagnostic and prognostic information must present all the information gathered
during the evaluation, as well as the pros and cons of each treatment option
(Lee et al., 1980). The initial treatment is testosterone therapy to increase
the size of the penis. This therapy can initiated by the endocrinologist and
followed up with the PNP, with a re-evaluation with the endocrinologist at the
end of the treatment. If the therapy is able to achieve adequate growth,
treatment is considered a success, although it is uncertain whether growth is
maintained into adulthood (Menon & Khatwa, 2000).

If the testosterone course fails in adding length, the other hormonal treatments
described in the treatment section can be administered. If all the hormonal
treatments fail, the PNP may provide the parents with information on surgical
options, such as penile reconstruction or sex reassignment, and a referral to a
pediatric surgeon or pediatric urology surgeon. The surgical options include the
technically difficult phalloplasty or the easier vaginoplasty, and each
procedure is associated with short- and long-term complications (Stein et al.,
2004 M. Stein, D. Sandberg, T. Mazur, E. Eugster and J. Daaboul, A newborn
infant with a disorder of sexual differentiation, Pediatrics 114 (2004), pp.
1473–1476.Stein et al., 2004).
If the parents decide to forgo surgery, and the PNP must devise a management
plan to help the patient adjust to life as a male with micropenis.

In all cases, psychological counseling and social services are helpful and most
likely necessary to both the patient and the parents and should be started early
because these patients seem to suffer emotionally (Husmann, 2004). Psychiatric
counseling may be needed as the child grows and deals with his condition. Common
issues among male subjects with micropenis include fear of sexual rejection,
sexual inadequacy, the size of their penis affecting their quality of life, and
poor body image (Husmann). On another note, long-term follow-up in some patients
has shown that there were no major alterations in male sexual activity comfort
or identity (Waldert et al., 2005).

The focus of management has remained fixed on determining which medical and/or
surgical interventions will yield an optimal outcome for the condition. The most
appropriate care has the medical team involving the parents in each step of
decision making along the way. Each set of parents, with their unique
sociocultural beliefs and backgrounds, would make different decisions based on
what their conception of their child's gender is and how they see their child's
future in the context of their family and society (Stein et al., 2004). Parents
must feel convinced that no medical information has been kept from them and that
the decision is done with full knowledge of alternatives with the support of the
PNP and the rest of the medical team.

Long-term follow-up is provided by the PNP within the context of the child'
primary health care setting. The PNP continues to monitor penile length,
maintains the hormone treatments or surgical outcomes, and screens for future
complications. She or he refers the patient as needed to specialty providers and
coordinates the care between the medical team and the patient and family. The
PNP also provides holistic care, which includes emotional support for the
parents during diagnosis and management and for the patient during long-term
follow-up.

Future research
Research into the field of micropenis is needed, because there are not many
long-term follow-up results. Long-term data are needed for patients with
micropenis who underwent hormone therapy or surgical procedures for penile
elongation or gender reassignment to see if the result remained permanent
throughout childhood, adolescence, and adulthood. A comparative study also is
needed to see which hormone treatment has yielded the most continuous results.
Appropriate phalloplasty should be explored as an option for younger children
because of the fact that some children experience significant psychological
disturbance and the current surgical procedures are aimed at the older child or
adult. Overall, more research is needed on which clinical practices are most
likely to achieve the best quality of life for people affected by micropenis.

Conclusion
A boy with a penis measuring 2.5 SD below the norm for age needs to be evaluated
for micropenis. Laboratory studies are done to determine the possible cause and
the best treatment to administer to get best possible outcome. Management of
these pediatric patients can be overseen by their PNP and will involve medical
or surgical treatment, appropriate referrals to an endocrinologist and possibly
a geneticist, psychological counseling, and follow-up throughout childhood. It
is important to counsel the parents of these children every step of the way to
ensure that the best quality of care is given.

I thank Dr. Rita Marie John, Director of the Pediatric Nurse Practitioner
Program at the Columbia University School of Nursing, for her help and advice
while I was writing this article.

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Conflicts of interest: None to report.

Correspondence: Shirley Tsang, MS, RN, CPNP
Vitae
Shirley Tsang, Pediatric Nurse Practitioner, Neighborhood and Family Health
Center, Bronx, NY.


Journal of Pediatric Health Caren Article in Press, Corrected Proof

doi:10.1016/j.jpedsurg.2008.10.111
Copyright © 2009 Elsevier Inc. All rights reserved.
Original article

Long-term physical, hormonal, and sexual outcome of males with disorders of sex
development

Yoshiyuki Kojima, a, , Kentaro Mizunoa, Akihiro Nakanea, Toshiki Katoa, Kenjiro
Kohria and Yutaro Hayashia
aDepartment of Nephro-urology, Nagoya City University Graduate School of Medical
Sciences, Nagoya 467-8601, Japan


Received 17 August 2008;  revised 28 October 2008;  accepted 29 October 2008. 
Available online 25 July 2009.

Abstract
Purpose
We investigated the long-term physical, hormonal, and sexual outcomes of males
with disorders of sex development (DSD) and discussed the necessity of long-term
follow-up for these patients after surgery.

Patients and Method
Twelve DSD patients (average age, 21.0 ± 3.6 years old) who had been designated
as male in childhood (3 ovotesticular DSD, four 45,XO/46,XY mixed gonadal
dysgenesis, four 46,XX testicular DSD, and one 46,XY DSD; androgen insensitivity
syndrome) were enrolled. For these patients, height, penile length, and
testicular volume were evaluated in adulthood. Serum levels of luteinizing
hormone, follicle-stimulating hormone, and testosterone were also measured
during follow-up. In addition, sexual function and romantic relationships were
evaluated.

Results
Development of the penis and testes was poor. According to the hormonal study,
these patients were diagnosed with hypergonadotropic hypogonadism or
normogonadism; 90% patients had experienced penile erection and masturbation at
the time of participation, and 70% and 40% patients had experienced ejaculation
and sexual intercourse with female partners, respectively. No patients preferred
to avoid sexual contact with women.

Conclusion
Although DSD males had an undeveloped penis and testis and had hypergonadotropic
hypogonadism or normogonadism, most had male sexual potential and male sex
identity as long as testicular tissues were preserved.

Key words: Sexual function; Disorders of sex development (DSD); Ovotesticular
DSD; XX testicular DSD; Mixed gonadal dysgenesis; Testis; Penis

Article Outline
1. Materials and methods
2. Results
3. Discussion
References
Disorders of sex development (DSD) are congenital conditions with atypical
development of chromosomal, gonadal, or anatomical sex [1]. The appearance of
the external genitalia is ambiguous, often with hypospadias or clitoromegaly,
with an undeveloped or ectopic testis or inadequate vagina.

Patients reared as males with ambiguous genitalia, especially proximal
hypospadias, are commonly referred to a urologic clinic to undergo hypospadias
repair, in which DSD patients are included. Generally, these patients need not
only reconstruction surgery for ambiguous external genitalia but also surgical
exploration of gonads and internal genitalia. The aim of reconstruction surgery
in DSD is to create "functional" external genitalia consistent with the sex
assigned to the patient; therefore, one of the most important issues is whether
they can achieve sexual potential as male or female in the future; however,
information about the long-term physical, hormonal, and sexual outcome of DSD
patients cannot be easily determined until decades after surgery because many
patients are lost to follow-up [2]. As a result, there are extremely few reports
of the outcome after surgery of DSD patients, especially those raised as males
[3], [4] and [5].

In our urologic clinic, we usually attempt to observe DSD males for as long as
possible. In this study, we investigated the long-term physical, hormonal, and
sexual outcomes of DSD patients raised as males, including ovotesticular DSD,
mixed gonadal dysgenesis (MGD), 46,XX testicular DSD, and 46,XY DSD, who had
undergone hypospadias repair previously at our institute and with whom we had
discussed the necessity of long-term follow-up after surgery.

1. Materials and methods
We reviewed the medical records of DSD patients who had been designated as male
by both the medical team and family at our institution from 1975 to 1991 and
observed at least to 15 years old. Twelve patients raised as males (3
ovotesticular DSD, 4 MGD, four 46,XX testicular DSD, and one 46,XY DSD; androgen
insensitivity syndrome), who were 16 years or older at the time of the last
visit (average age, 21.0 ± 3.6 years old), were enrolled in this study. Clinical
record files of these patients detailed the initial clinical presentation,
diagnostic investigations, and therapeutic surgical intervention. The diagnostic
study between the first visit and operation had included a physical examination;
chromosomal analysis; hormonal evaluation, including human chorionic
gonadotropin (hCG) stimulation test (2400 IU/d for 3 days) and human menopausal
gonadotropin (hMG) stimulation (112.5 IU/d for 3 days); the presence of the
sex-determining region Y (SRY) sequence; magnetic resonance imaging; cystoscopy;
vaginoscopy; laparoscopy; and gonadal biopsy. After 1993, the presence of the
SRY sequence was examined by polymerase chain reaction method for most patients
during follow-up.

The clinical descriptions of 12 patients in childhood are presented in Table 1.
All patients presented with proximal hypospadias and had undergone hypospadias
repair in childhood. All patients had both Wolffian (epidydimis and/or vas
deferens) and Mullerian (fallopian tube and/or prostatic utricle) structures.
All patients had a prostatic utricle, which opened into the central area of the
verumontanum in the prostatic urethra.

Table 1.
Clinical characteristics of males with disorders of sexual development in
childhood



  Diagnosis

  Age at first visit

  External genitalia

  Internal genitalia

  Gonad Gonadectomy

  Chromosome

  HCG Stimulation test

  HMG Stimulation test

  SRY



Wolffian structure Mullerian structure

1 Ovotesticular DSD 3yo hypospadias (penoscrotal type) + + Rt) ovary Rt) abdomen
Rt) ovarectomy 46,XY + + +
       Lt) testis Lt) srotum
2 Ovotesticular DSD 1mo hypospadias (penoscrotal type) + + Rt) ovotestis Rt)
abdomen Bil) gonadectomy 46,XX + + -
       Lt) ovotestis Lt) inguinal region
3 Ovotesticular DSD 2mo hypospadias (penoscrotal type) + + Rt) testis Rt)
scrotum Lt) ovarectomy 46,XX/46,XY/47,XX10 + - +
       Lt) ovary Lt) abdomen
4 MGD 9mo hypospadias (scrotal type) + + Rt) streak gonad Rt) inguinal region
Rt) gonadectomy 45,XO/46,XY + - NA
       Lt) testis Lt) scrotum
5 MGD 0mo hypospadias (scrotal type) + + Rt) streak gonad Rt) abdomen Rt)
gonadectomy 45,XO/46,XY NA NA +
       Lt) testis Lt) scrotum
6 MGD 4yo hypospadias (scrotal type) + + Rt) testis Rt) scrotum Bil) gonadectomy
45,XO/46,XY NA NA +
       Lt) streak gonad Lt) abdomen
7 MGD 10yo hypospadias (penoscrotal type) + + Rt) testis Lt) streak gonad Rt)
inguinal region Lt) gonadectomy 45,XO/46,XY + - +
        Lt) abdomen
8 46,XX testicular DSD 2 mo hypospadias (scrotal type) + + Bil) testis Bil)
scrotum - 46,XX + - -
9 46,XX testicular DSD 8 mo hypospadias (scrotal type) + + Bil) testis Bil)
scrotum - 46,XX + - -
10 46,XX testicular DSD 9 mo hypospadias (scrotal type) + + Bil) testis Bil)
scrotum - 46,XX + - -
11 46,XX testicular DSD 5 mo hypospadias (scrotal type) + + Bil) testis Bil)
scrotum - 46,XX + - -
12 46,XY DSD 4 mo hypospadia (scrotal type) + + Bil) testis Rt) scrotum Lt)
inguinal region - 46,XY + - +


Full-size table
yo: years old.
mo: months old.
NA: not assessed.
Rt: right.
Lt: left.
Bil: bilateral.

HCG stimulation test +; response by serum testosterone after hCG stimulation, -;
response by serum testosterone after hCG stimulation.

HMG stimulation test +; response of urinary estradiol after hMG stimulation, -;
no response of urinary estradiol after hMG stimulation.


View Within Article



Three ovotesticular DSD had several complicated clinical characteristics.
Patient 1 with 46,XY had a right ovary with a fallopian tube and a uterus-like
structure in the abdomen and a left testis with an epididymis and vas deferens
in the scrotum. He had undergone right gonadectomy and resection of the
uterus-like structure. Patient 2 with 46,XX had a right ovotestis in the abdomen
and left ovotestis in the scrotum and had undergone bilateral gonadectomy.
Patient 3 with 46,XX/46,XY/47,XX10+ had a right testis with an epididymis and
vas deferens in the scrotum and a left ovary with an epididymis-like structure
in the abdomen. He had undergone left gonadectomy. The hCG response was normal
in all 3 patients, whereas the hMG response was present in 2 patients (patient
2). Patients 1 and 3 had an SRY sequence but patient 2 did not.

Four MGD patients had both a testis and streak gonad and underwent gonadectomy
for the streak gonad. Although two had undergone orchiopexy for undescended
testis in another clinic before the first visit, the other two (patients 4 and
6) had no testis in the scrotum at the first visit. All patients had a uterus
and an epididymis or fallopian tube. The hCG and hMG stimulation test was
performed for 2 patients (patients 4 and 7); the hCG response was normal,
whereas the hMG response was absent. Patients 5, 6, and 7 were confirmed as
having the SRY sequence.

Four 46,XX testicular DSD patients (patients 7-11) had not only an epididymis
and vas deferens but also a Mullerian remnant. One patient (patient 10) had
gynecomastia with age. All 46,XX testicular DSD patients had undergone open
bilateral gonad biopsy for their diagnoses, and histologic examination showed
bilateral testis. The left testis of one patient (patient 8) disappeared during
his follow-up period. The enlarged Mullerian structure (prostatic utricle) was
resected in one patient (patient 10) because of urinary tract infection. The hCG
response was normal, whereas the hMG response was absent in all patients,
showing that gonad tissues could potentially develop as testes without ovarian
tissue. All 46,XX testicular DSD patients had no SRY sequence. One patient
(patient 9) had a neurogenic bladder caused by myelomeningocele and underwent
cystectomy and neobladder replacement at the age of 25.

One 46,XY DSD patient (patient 12) had epididymis and vas deferens. He had
undergone open bilateral gonad biopsy, and histologic examination showed
bilateral testis.

For these patients, their height, penile length, and testicular volume in
adulthood were evaluated. Serum levels of luteinizing hormone (LH),
follicle-stimulating hormone (FSH), and testosterone were also measured by
radioimmunoassay (RIA) during follow-up. Radioimmunoassays for LH, FSH, and
testosterone were performed using RIA kits (LH and FSH, Japan DPC, Tokyo, Japan;
testosterone, Amersham Biosciences, Tokyo, Japan).

In addition, sexual function, such as their experiences with penile erection,
libido, orgasm, ejaculation, masturbation, and sexual intercourse, was
evaluated. Their romantic relationships and marriage were also detailed.

2. Results
Patients were observed for a median 19.8 ± 3.3 years (range, 16-28 years) after
diagnosis. Clinical features in adulthood are described in Table 2. The mean
final height of the 12 patients was 154.5 ± 3.8 cm, and most were under the 10th
percentile of the range of normal Japanese adult males. Development of the penis
and testes was poor. Average penile size was 4.1 ± 0.7 cm. No gonadal tumors
were detected during follow-up. They also had poor pubic hair.


Table 2.
Physical and sexual outcome of males with disorders of sexual development

  Diagnosis Present age height Testicular volume Penile size Erection
Masturbation Ejaculation Sexual intercourse Married
1 Ovotesticular DSD 18 yo 151 cm Rt) – 4.5 cm + + + - -
     Lt) 9.5 ml
2 Ovotesticular DSD 16 yo 156 cm Rt) – 3.5 cm NA NA NA NA NA
     Lt) -
3 Ovotesticular DSD 19 yo 161 cm Rt) 8.0 ml 5.2 cm + + + - -
     Lt) -
4 MGD 22 yo 153 cm Rt) – 3.0 cm NA NA NA NA -
     Lt) 2.9 ml
5 MGD 19 yo 150 cm Rt) – 5.0 cm + + + NA -
     Lt) 2.8 ml
6 MGD 21 yo 155 cm Rt) – 3.8 cm + + + - -
     Lt) -
7 MGD 27 yo 150 cm Rt) 3 ml 4.0 cm + + + + -
     Lt) -
8 46,XX testicular DSD 23 yo 157 cm NA 4.5 cm + + + + -
9 46,XX testicular DSD 28 yo 150 cm Rt) 5.1 ml 5.0 cm - - - - -
     Lt) -
10 46,XX testicular DSD 21 yo 156 cm Rt) 3.3 ml 3.6 cm + + + + -
     Lt) 3.2 ml
11 46,XX testicular DSD 20 yo 160 cm Rt) 4.2 ml 3.6 cm + + + + +
     Lt) 3.8 ml
12 46,XY DSD 18 yo 155 cm Rt) 4.5 ml 4.0 cm + + - - -
     Lt) 4.2 ml

Full-size table
yo: years old.
NA: not assessed.
Rt: right.
Lt: left.
Bil: bilateral.


View Within Article



Serum levels of LH, FSH, and testosterone were examined from infancy to
adulthood in 10 patients by RIA (Fig. 1). As in normal males, the concentrations
of these hormones in 10 of 12 patients, except patients 2 and 6, elevated
spontaneously during the pubertal period. Testosterone levels were low normal or
slightly decreased, and LH and FSH were elevated in these patients. These high
levels of LH and FSH began to be observed in the peripubertal stage.
Follicle-stimulating hormone was more frequently elevated than LH. According to
the concentrations of these hormones, these patients were diagnosed with
hypergonadotropic hypogonadism or normogonadism. Two patients (patients 2 and
6), who had undergone bilateral gonadectomy, received testosterone therapy
(intramuscular depot injections of testosterone esters) immediately before
puberty. One patient (patient 9), with mental retardation and neurogenic bladder
caused by myelomeningocele, also received testosterone therapy for deficiency of
sexual function at the age of 27, but he discontinued the therapy because of
adverse effects.






  Full-size image (72K)

Fig. 1. Hormonal evaluation of DSD patients from childhood to adulthood after
diagnosis and operation. Serum concentrations of LH, FSH, and testosterone of
DSD patients were determined by RIA at the ages indicated.

View Within Article



Of 10 DSD males, 9 (90%) had experienced penile erection and masturbation at the
time of participation. Of 10 patients, 7 (70%) had experienced ejaculation, and
5 of these 7 patients had ejaculation problems, including dribbling, retained,
or delayed ejaculation. No patient complained of problems with libido and
orgasms. Of 10 patients, 4 (40%) had experienced sexual intercourse with female
sex partners in the past year. Only one patient (patient 11), a 46,XX testicular
DSD, was married at the time of participation, and two 46,XX testicular DSD had
a stable female partner and expressed a desire for marriage in the future. No
patients preferred to avoid sexual contact with women. There were no cases of
fertility, and the only semen analysis showed azoospermia (patient 11).

3. Discussion
There are several previous reports about the long-term physical, hormonal, and
sexual outcomes of 46,XY DSD and 46,XX DSD, such as complete androgen
insensitivity syndrome (AIS) and congenital adrenal hyperplasia, which are
usually raised as female [6] and [7]; however, there are very few reports on the
long-term outcome of DSD males. In this study, we investigated the long-term
physical, hormonal, and sexual outcomes of 12 DSD males, including ovotesticular
DSD, MGD, 46,XX testicular DSD, and 46,XY DSD.

Consistent with previous reports, 46,XX testicular DSD and MGD were shorter than
normal males [8] and [9]. Although their reduced height might be attributed to
genes on the Y chromosome that control height [10], not only 46,XX testicular
DSD but also ovotesticular DSD and 46,XY testicular DSD with a complete Y
chromosome were also short.

Recent remarkable advances in hypospadias repair have provided satisfactory
penile reconstruction, not only cosmetically but also functionally; however,
female sex assignment has been considered optimal and common in severely
undermasculinized cases because feminization with surgical and endocrine
treatment was considered more successful than masculinization [11]. The size of
the penis and its potential to develop at puberty into a sexually functional
penis are one of the important concerns. There are several reports about penile
development in sporadic hypospadias patients [12] and [13]. Mureau et al [12]
reported that penile underdevelopment was noted about 2 times more often in
hypospadias patients than among age-matched normal boys. Bracka et al [13]
reported a clear correlation between the severity of hypospadias and penile
length. On the other hand, there are few reports about penile development in DSD
males. In 46,XX testicular DSD with genital abnormalities, penile size and
testicular volume, measured directly or after surgery in the case of cryptorchid
patients, were below the normal values obtained in controls [14]. The average
penile size of Japanese men is approximately 8 cm, and the critical testicular
volume indicating normal testicular function of Japanese men is approximately 30
mL [15]. In our study, all DSD males had proximal hypospadias and had an
underdeveloped penis after puberty. This insufficient virilization of the
external genitalia may result from hypogonadism. In the previous 46,XX
testicular DSD studied, hypogonadism started in the peripubertal stage, similar
to the pattern in Klinefelter's syndrome where high FSH levels are associated
with normal or low testosterone levels [16]. Conversely, in a study of
ovotesticular DSD, peripubertal testosterone levels were lower than in 46,XX
testicular DSD [16]. In our study, 10 patients were diagnosed with
hypergonadotropic hypogonadism or normogonadism, and the concentration of
testosterone in these patients was low or low normal in young adults,
concomitant with a rise in FSH, reflecting the degeneration of spermatogenesis
and Leydig cell function. The 46,XX testicular DSD is generally characterized by
azoospermia [8]. On the other hand, phenotypic males with normal spermatogenesis
and phenotypic females with normal conception and delivery have been reported in
ovotesticular DSD [17] and [18]. Although testicular functions of DSD in
adulthood are unclear, complete testicular function may not be expected.

In our study, most patients showed potential for erection, ejaculation, and
masturbation; however, they had some problems with ejaculation, such as
dribbling, retained, or delayed ejaculation or the absence of ejaculation, which
have been reported after hypospadias repair in patients even without DSD [19].
This may be secondary to dilation of the reconstructed urethra or the presence
of a Mullerian remnant [19]. On the other hand, no patient complained of
problems with libido and orgasms. Patients with DSD had been considered to have
an increased incidence of sexual dysfunction as a result of their condition and
psychologic factors that impact on sexual function [20]. Children with DSD,
their parents, and we always face the difficulty of dealing with the diagnosis
and accepting reconstructive surgery of the genitalia to avoid psychosexual
disturbance. Sex dissatisfaction may occur more frequently in individuals with
DSD [3]. Fortunately, however, no patient had serious psychosexual problems. All
patients were interested in women and desired to have contact and to fall in
love with women, and interestingly, three 46,XX testicular DSD patients and 2
MGD patients had experienced sexual intercourse with a female sex partner, and
one 46,XX testicular DSD patient was married. Both biologic and social factors
seem responsible for the development of sex identity [3]. Because the DSD males
in our study had received prenatal androgen exposure, although insufficient, and
had been raised as male, as a result, they may have had male sex identity;
however, more systemic psychologic assessments will be needed to conclude that
these patients had no psychologic problems.

The necessity for testosterone therapy for all DSD males is controversial.
Testosterone therapy may be expected to induce puberty, growth, sexual function,
and support for psychosexual maturation [1]; however, we performed testosterone
therapy for only 3 males—2 who underwent bilateral gonadectomy and 1 who
complained of deficiency of sexual function. However, most patients with testis
underwent no hormonal therapy because they did not desire additional therapy,
and puberty and the potential for sexual function developed without hormonal
therapy. Because routine hormonal therapy for a long period may affect the
quality of life, with a greater risk of developing prostate cancer in the future
[21], careful consideration may be required.

In conclusion, although DSD males usually have an undeveloped penis and testis
and have hypergonadotropic hypogonadism or normogonadism, most may have male
sexual potential and male sex identity without hormonal therapy, if testicular
tissues are preserved. This means that testicular function in DSD males may be
insufficient for masculinization of the fetal external genitalia but sufficient
to achieve male sexual function and develop male sex identity; however, our
study showed no difference in sexual potential and sex identity between DSD
males and age-matched normal males because a limitation of this study is the
small sample size. A large multicenter study is required to obtain more detailed
information on the long-term physical, hormonal, and sexual outcomes of DSD
males.

References

[1] P.A. Lee, C.P. Houk and S.F. Ahmed et al., International Consensus
Conference on Intersex organized by the Lawson Wilkins Pediatric Endocrine
Society and the European Society for Paediatric Endocrinology. Consensus
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[2] M. Diamond and H.G. Beh, Changes in the management of children with intersex
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[3] F.M. Slijper, S.L. Drop and J.C. Molenaar et al., Long-term psychological
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[4] C. Nihoul-Fékété, E. Thibaud and S. Lortat-Jacob et al., Long-term surgical
results and patient satisfaction with male pseudohermaphroditism or true
hermaphroditism: a cohort of 63 patients, J Urol 175 (2006), pp. 1878–1884.
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[5] G. Verkauskas, F. Jaubert and S. Lortat-Jacob et al., The long-term
follow-up of 33 cases of true hermaphroditism: a 40-year experience with
conservative gonadal surgery, J Urol 177 (2007), pp. 726–731. Abstract | Article
|  PDF (962 K) | View Record in Scopus | Cited By in Scopus (3)
[6] A.B. Wisniewski, C.J. Migeon and H.F. Meyer-Bahlburg et al., Complete
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outcome, J Clin Endocrinol Metab 85 (2000), pp. 2664–2669. Full Text via
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[7] N.S. Crouch, L.M. Liao and C.R. Woodhouse et al., Sexual function and
genital sensitivity following feminizing genitoplasty for congenital adrenal
hyperplasia, J Urol 179 (2008), pp. 634–638. Abstract | Article |  PDF (143 K) |
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[8] A. de la Chapelle, The etiology of maleness in XX men, Hum Genet 58 (1981),
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[9] J. Knudtzon and D. Aarskog, 45,X/46,XY mosaicism. A clinical review and
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[10] T. Ogata and N. Matsuo, Comparison of adult height between patients with XX
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29 (1992), pp. 539–541. Full Text via CrossRef | View Record in Scopus | Cited
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[11] C.J. Migeon, A.B. Wisniewski and J.P. Gearhart et al., Ambiguous genitalia
with perineoscrotal hypospadias in 46,XY individuals: long-term medical,
surgical, and psychosexual outcome, Pediatrics 110 (2002), p. e31. Full Text via
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[12] M.A. Mureau, F.M. Slijper and R.J. Nijman et al., Psychosexual adjustment
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norm-related study, J Urol 154 (1995), pp. 1902–1907. Abstract | Article |  PDF
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[14] J.E. Toublanc, C. Boucekkine and N. Abbas et al., Hormonal and molecular
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differentiation, Eur J Pediatr 152 (1993), pp. S70–S75. Full Text via CrossRef |
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hermaphroditism, Adolesc Pediatr Gynecol 1 (1988), pp. 55–56.
[19] R. Mieusset and M. Soulié, Hypospadias: psychosocial, sexual, and
reproductive consequences in adult life, J Androl 26 (2005), pp. 163–168. View
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1264–1265. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus
(39)
[21] E.L. Rhoden and A. Morgentaler, Testosterone replacement therapy in
hypogonadal men at high risk for prostate cancer: results of 1 year of treatment
in men with prostatic intraepithelial neoplasia, J Urol 170 (2003), pp.
2348–2351. Abstract | Article |  PDF (65 K) | Full Text via CrossRef | View
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Corresponding author. Tel.: +81 52 853 8266; fax: +81 52 852 3179.

Journal of Pediatric Surgery Volume 44, Issue 8, August 2009, Pages 1491-1496

http://www.biomedcentral.com/1471-2458/9/110

Hello, my name is Melissa and like to say hi to everyone. If I may say, I am a
luscious n curvy 38-28-43 5'7" MTF.  I am not sure where I fit in the category
of inner-sex but perhaps I am at the right place to find answers to some of my
anomalies.

  I am presently under a physicians care for HRT.  My lab results indicated my
estrogen levels were flagged extremely high at 1823 pg/mL (normal range 0-53)
and way out of whack so my doctor took me off hormones immediately. Six weeks
later she wanted to test my Estradiol levels and found they were just a bit
above normal 83pg/mL (normal range 0-53)  I am presently off of HRT and so I
would think that obviously my body may be producing estrogen somewhere on it's
own, wouldn't you agree?

A recent MRI preformed for a hip problem indicated that there is something
lodged up in right side of my pelvis that possibly could be an undesended
testical. Perchance this thing could be causing the problems? The doctor wants
to have it surgically remove but I am having my SRS this year so I will wait
till then to find out what it is.

I was recently medicated to dry up my milk production as I had lactated like a
cow steadily for the last 7 years. I was checked for the possibility of a
pituitary tumor and the results came back negative. Can all these things add up
to something?

Thank you,
Melissa

Year : 2009  |  Volume : 6  |  Issue : 1  |  Page : 14-18

Management of ambiguous genitalia in ile ife, Nigeria: Challenges and outcome

Oludayo A Sowande, Olusanya Adejuyigbe
Department of Surgery, Pediatric Surgery Unit, Obafemi, Awolowo University
Teaching Hospital, PMB 5538, Ile Ife, Osun State, Nigeria



Abstract
Background: Ambiguous genitalia are a major cause of parental anxiety and can
create social problems if not properly managed. Diagnosis and management can
however be challenging. The aim of this study is to highlight some of the
challenges in management of ambiguous genitalia in our environment.
Patients and Methods: All cases of ambiguous genitalia managed at the Paediatric
surgical unit of the Obafemi Awolowo University Teaching hospital, Ile Ife,
Nigeria, between January 1993 and October 2007 were analysed for age, sex at
presentation, investigation modality, and final sex of rearing and outcome of
surgery.
Result: Nine patients had surgical reconstruction for ambiguous genitalia during
the study period. Their age ranges from 5 weeks to 19 years at presentation. The
causes of genital ambiguity in the patients was congenital adrenal hyperplasia
(CAH) in 6, true hermaphroditism in 2 and male pseudo-hermaphroditism in 1.
Seven patients were reconstructed as females while 2 were raised as males.
Change of sex of raring was necessary in 2 patients.
Conclusion: The diagnosis and management of ambiguous genitalia is a challenging
problem in our environment. Early presentation and treatment is necessary to
avoid psychological and social embarrassment.

Keywords: Ambiguous genitalia, children, treatment

How to cite this article:
Sowande OA, Adejuyigbe O. Management of ambiguous genitalia in ile ife, Nigeria:
Challenges and outcome. Afr J Paediatr Surg 2009;6:14-8

How to cite this URL:
Sowande OA, Adejuyigbe O. Management of ambiguous genitalia in ile ife, Nigeria:
Challenges and outcome. Afr J Paediatr Surg [serial online] 2009 [cited 2009 Mar
26];6:14-8. Available from:
http://www.afrjpaedsurg.org/text.asp?2009/6/1/14/48569

Introduction
The first question that usually arises after the birth of any newborn is about
the gender of the child. This is easily answered in most cases by simple
examination of the external genitalia of the baby. Genitalia are ambiguous
whenever there is difficulty in attributing gender to a child based on the
appearance of the external genitalia. [1],[2] The appearance of the external
genitalia is a result of complex interaction between genetic and endocrine
processes during fetal development. Abnormalities of the external genitalia
sufficient to warrant genetic and endocrine studies is said to occur in 1 in
4,500-10,000 births. [3],[4] Ambiguous genitalia are a major cause of parental
anxiety and can create psychological and social problems if not properly
managed. Also life threatening conditions such as salt wasting crisis of
congenital adrenal hyperplasia (CAH) need to be detected and treated early. [5]
Diagnosis and management of this condition can be challenging requiring a
multidisciplinary approach. [6]

There has been considerable progress in diagnosis and management in recent
decades especially in CAH. [3] This is the commonest cause of ambiguous
genitalia of the newborn and can now be suspected and treated from in utero .

There is presently a paucity of information on the challenges and outcome of
management of ambiguous genitalia in our environment. The aim of this study is
to document and highlight the challenges in diagnosis and management of
ambiguous genitalia in a cohort of Nigerian children seen at a teaching hospital
in South Western Nigeria.

Patients and Methods
This is an analysis of cases of ambiguous genitalia managed at the Obafemi
Awolowo University Teaching hospital, Ile Ife, Nigeria between January 1993 and
October 2007. The patients were analysed for age, sex at presentation,
investigation modality, and final sex of rearing and outcome of surgery. Barr
body evaluation, sonogram, mini-laparotomy and cystoscopy were the main methods
of evaluation while hormonal assay was requested if patient can afford it.
Surgical reconstruction is embarked upon after dialogues with parents especially
in cases requiring change of sex of raring [Figure 1] and [Figure 2].

Result
Ten patients were seen with ambiguous genitalia during the study period but only
9 patients had surgical reconstruction for ambiguous genitalia. The median age
at presentation was 3 years. None of the patient presented in the neonatal
period. The earliest presentation was 5 weeks while the oldest was 19 years.
Presenting features were abnormal looking genitalia since birth in 7 patients.
Clitorimegaly was noticed at 2 and ½ years and 3 years in 2 patients who are
siblings and whose mother had been on fertility drugs prior to their conception.
There were 2 patients who are a set of twins. The oldest patient in this series
had gynaecomastia noticed since puberty.

All patients had routine haematological investigations done which were normal.
None of the patients had karyotyping done because it was not available; however,
Barr body examination was positive in three patients who ultimately turned out
to be female. Most of the patients were not able to afford biochemical hormonal
assay but 2 patients who had the investigation was inconclusive although the
patients were thought to have congenital adrenal hyperplasia. Diagnosis was
based mainly on demonstration of the internal genitalia. Ultrasound was done in
8 patients but the findings correlated with laparotomy findings in only three
while in 2, the presence of uterus and adnexiae was suggested but was absent at
laparotomy. In the other 3 patients the preliminary ultrasound was inconclusive.
In all, seven patients ultimately required laparotomy and another one
laparoscopy to define the internal genitalia [Table 1]. Two of the patients had
suspicious gonads on laparotomy and these were biopsied. Their histology
confirmed ovotestis. The gonadal biopsy result changed the diagnosis from CAH in
one of the patient to true hermaphroditism.

The final diagnosis of the causes of genital ambiguity in the patients was CAH
in 6, true hermaphroditism in 2 and male pseudo-hermaphroditism in 1. Seven
patients were reconstructed as females while 2 were raised as males. Change of
sex of raring was necessary in 2 patients. These two patients had change of name
while one of the parents had to relocate.

Discussion
Children born with the intersex problem comprise about 1.7% of all live births.
[7] The incidence of this condition in the African population is unknown.

Ambiguity of the external genitalia is easily recognised at birth and the
apparent sex of rearing will be obvious. [8] The general consensus is that the
diagnosis should be promptly established preferably before discharge so that an
early sex of raring can be assigned to the child as well as to plan treatment.
[1],[2] This aspect of the patient's management is important to facilitate
psychological development and good quality of life in the affected individuals.
Assigning a sex of raring to the child requires that elaborate investigation be
done to ascertain the genetic or endocrine causes of the anomaly. This early
part of the child's management should ideally be a multidisciplinary approach.
In many institutions in developed world, there are joint clinics established for
the management of these patients where collective decisions are made concerning
each patient. [6],[9] This type of clinic is not present in our own part of the
world therefore each patient does not have that benefit.

Investigating a child with ambiguous genitalia requires both genetic and
hormonal studies to establish the diagnosis and plan appropriate treatment. A
fast buccal smear for the presence of the extra X-chromosome will help in
establishing a suspicion of the chromosomal constitution of the individual. This
test has however been found to be unreliable and cannot be solely relied upon.
Karyotyping an important early test using cultured leucocytes is not available
in our hospitals and so cannot be used.

There are a myriad of hormonal assay that assist the clinician in establishing
diagnosis of ambiguous genitalia including serum testosterone, DHT,
gonadotropins and adrenal steroids such as
17-hydroxyprogesterone,17-hydroxypregnenalone, androstenedione and
dehydroepiandrosterone (DHEAS) and 11-hydroxycortisone, mullerian inhibiting
substance (MIS). These hormonal assays are very expensive and can barely be
afforded by the patients. Only 2 of our patients had enough money to go for
hormonal assay but the results were not helpful in the twins who are suspected
to have adrenogenital syndrome. Specific assay for enzymes such as 5 alpha
reductase, 21-hydroxylase are available in developed countries. All these are
not available in Nigeria.

In our environment, the incidence of these anomalies is unknown. It is obvious
that the cases of suspected CAH that we see in our setting are the non salt
wasting type as most of these ones may have succumbed at birth or in the
perinatal period. Nowadays cases of CAH are diagnosed in utero especially if
there is a previous or family history of the disease. Chorionic villous sampling
during the first trimester or amniotic fluid sampling will help to establish the
diagnosis. These patients are given dexamethasone in utero before the period of
sexual differentiation thereby reducing the chance of genital ambiguity. Two of
the patients we have managed are siblings and there is the possibility that
there is a genetic disorder in these patients although there was also a positive
history of maternal ingestion of fertility drugs which may be progestogens
during pregnancy with these children. It is also interesting that two of the
patients are also twins in which case a genetic predisposition or enzyme
deficiency was very likely. There are no facilities to determine the specific
enzyme deficiency in these patients.

In our setting, late presentation seems to be the case as only one of the
patient presented early. Late presentation can lead to a myriad of problem in
the subsequent management of these patients as wrong assignment of sex can lead
to serious consequences in the future. Even where correct sex of rearing has
been done, long-term psychopathologic disorders including gender identity
disorder and deviant gender role may develop. [10] Two of our patients require
that the sex of raring be changed because the final diagnosis dictated that the
appropriate genital reconstruction be done. A similar case of sex conversion in
a 21 year old patient has been reported from the eastern part of Nigeria. [11]
In general, the assignment of sex for rearing must be guided by the etiology of
the genital malformation, the anatomic condition, and family considerations. [6]
Recognition of parental acceptance is a fundamental determinant of success of
any management strategy in the case of intersex children is critical. [8]

In conclusion, the management of a child with ambiguous genitalia is a
challenging problem in our environment. Early presentation and treatment is
necessary to avoid psychological and social embarrassment. The ability to do
this is limited in most resource limited areas. Continue reliance on history,
physical examination, and limited investigative facilities available will
continue to be the only reliable mean of diagnosis and management.

References
1. Guerra-Júnior G, Maciel-Guerra AT. The role of the pediatrician in the
management of children with genital ambiguities. J Pediatr (Rio J)
2007;83:S184-91.
2. Byne W. Developmental endocrine influences on gender identity: Implications
for management of disorders of sex development. Mt Sinai J Med 2006;73:950-9.
3. Hughes IA. Early management and gender assignment in disorders of sexual
differentiation. Endocr Dev 2007;11:47-57.
4. Thyen U, Lanz K, Holterhus PM, Hiort O. Epidemiology and initial management
of ambiguous genitalia at birth in Germany. Horm Res 2006;66:195-203.
5. Al-Mutair A, Iqbal MA, Sakati N, Ashwal A. Cytogenetics and etiology of
ambiguous genitalia in 120 pediatric patients. Ann Saudi Med 2004;24:368-72.
6. Sultan C, Paris F, Jeandel C, Lumbroso S, Galifer RB. Ambiguous genitalia in
the newborn. Semin Reprod Med 2002;20:181-8.
7. Blackless M, Charuvastra A, Derryck A, fausto-Sterling A, Laizanne K, Lee E.
How sexually dimorphic are we? Review and synthesis. Am J Hum Biol
2000;12:151-6.
8. Houk CP, Lee PA. Intersex states: Diagnosis and management. Endocrinol Metab
Clin N Am 2005;34:791-810.
9. Gφllü G, Yildiz RV, Bingol-Kologlu M, Yagmurlu A, Senyücel MF, Aktug T,
et al . Ambiguous genitalia: An overview of 17 years' experience. J Pediatr Surg
2007;42:840-4.
10. Slijper FM, Drop SL, Molenaar JC, de Muinck Keizer-Schrama SM. Long-term
psychological evaluation of intersex children. Arch Sex Behav 1998;27: 125-44.
11. Aghaji MA, Chukwu CC. Anatomical sex conversion in a 21-year-old--case
report and review of literature. Cent Afr J Med 1992;38:82-5.


Correspondence Address:
Oludayo A Sowande
Department of Surgery, Paediatric Surgery Unit, Obafemi Awolowo University
Teaching Hospital, PMB 5538, Ile Ife, Osun State
Nigeria


Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0189-6725.48569


Figures
[Figure 1], [Figure 2]

Tables

[Table 1]

Her name is Naama Silva and her e-mail address is naama_silva@...
Thanks.

--- On Sat, 2/28/09, Karin Gonzales-McClellan <hotpinkmailbox@...> wrote:


From: Karin Gonzales-McClellan <hotpinkmailbox@...>
Subject: Trans/Giving Glamor Party Fundraiser for EVERY Gender!
To: transgiving@...
Date: Saturday, February 28, 2009, 5:28 PM









Cherry Bomb Transformation Studios Presents:

Saturday, March 21st 2009
Glamor Party Photo Fundraiser for Trans/giving

What: A fundraiser for LA's own transgender, gender queer and intersex art
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When: Appointments are on Saturday March 21 2009 beginning from 9 a.m. -4 pm
please allow a maximum of three hours for your makeover and photo session.
Appointments are on the hour and the half hour (9 a.m., 9:30, 10:00).
Please be on time.

Where: Five minutes from LAX

5966 Abernathy Drive
Westchester, CA 90045

Light snacks and refreshments will be served. Wine will be available for a small
donation.

How do I reserve my spot? You must prepay your $40 donation! Spots will fill
quickly! Email us at transgiving@... or call,  310.745.6661  or snail mail
us with the following information:

 


Your Name:
Contact Phone Number:
Email Address:
The name on your payment (if different from your name):
Your top three choices for an appointment time:


Method of Payment: check made out to Kalil Cohen, credit card via paypal to
transgiving@... or cash (send at your own risk!). To reserve your spot a
payment must be made! For those without Paypal ask about pay by phone.


FAQ's:

Q:Can guys do this to?
A: Yes! This can be as femme or as butch as you want it! It's about glamor for
EVERY gender!

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A: Something comfortable you can get in and out of easily. We will have
everything for you to wear. The wig, clothes and accessories go back at the end
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Q: How many different makeup/facial hair looks can I get for my $40 sitting fee?
A: Just one.

Q: Do I have to bring my own clothes?
A: Yes, can can if there is something really special you want to be photographed
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A: Yes, you can mail it to Trans/Giving attention Kalil at 818 Superba Avenue
Venice Ca 90291. Make checks out to Kalil Cohen.


Q: Can my friend or family member be in my pictures too?
A: Yes but the $40 only covers one make up makeover. For an additional makeover,
you may pay the makeup artist for an additional $20 and $10 for hair styling/wig
styling. The second person will have full access to the wardrobe and accessories
free of charge. If you are planning to do all "couples" pictures it may be or
economical to do it this way then purchasing two separate packages.

Q:Who can I call with my questions?
A: Call Karin at 310 745 6661


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A: Yes! Call our host Juhi at

310-910-0556 home
310-625-4386 cell

NOTE: CALL KARIN AT 310 745 6661 for ALL OTHER QUESTIONS







[Non-text portions of this message have been removed]

http://www.indianjurol.com/text.asp?2009/25/1/17/45532

doi:10.1016/j.jpedsurg.2008.10.101
Copyright © 2009 Published by Elsevier Inc.
BAPS papers

Results from a pediatric surgical centre justify early intervention
in disorders of sex development

Jennifer M. Crawforda, 1, , Garry Warneb, Sonia Grovera, b, c,
Bridget R. Southwellc and John M. Hutsona, b, c, ,
aSchool of Medicine, University of Melbourne, Parkville, Victoria
3052, Australia
bRoyal Children's Hospital, Parkville, Victoria 3052, Australia
cMurdoch Childrens Research Institute, Parkville, Victoria 3052,
Australia

Received 3 October 2008;  accepted 23 October 2008.  Available online
20 February 2009.

Abstract
Background

Controversy persists surrounding early management of disorders of sex
development. We assessed genital appearance, gender identity, and
quality of life in prepubertal children who have had early surgical
intervention.

Methods
Children treated for disorders of sex development who were 5 to 10
years of age were eligible (n = 54). Children were scored (modified
Creighton scale) for anatomical and cosmetic outcome, and both
patients and parents completed PedsQL quality-of-life and gender
identity questionnaires, with ethics approval.

Results
Of 54 patients, 41 presented for review. Treatment began at 13.2 (1.8-
250.1) months (median; range) and were reviewed at 7.5 ± 2.1 (mean ±
SD) years of age. Nineteen were raised as girls and 22 as boys. Girls
had good (85%) or satisfactory (15%) anatomical/cosmetic outcome,
whereas 52% boys had good, 38% satisfactory, and 10% poor cosmetic
outcomes. On gender identity questionnaire, boys scored 3.9 ± 0.4
(mean ± SD) and girls 3.6 ± 0.5; 1 of 19 boys and 3 of 19 girls had
lower scores, suggesting risk of gender identity disorder. Quality-of-
life scores were 80+ for physical and 65 to 80 for psychosocial
scores.

Conclusions
Early intervention is generally associated with positive outcomes for
patients and parents. Girls had better anatomical outcomes than boys,
and gender dysphoria risks were low in both sexes.

Key words: Disorders of sex development (DSD); Quality of life (QOL);
Gender identity; Health care satisfaction; PedsQL

Article Outline
1. Methods
2. Results
3. Discussion
References

Disorders of sex development (DSD) occur when an individual's
chromosomal, gonadal, or anatomical sex develops atypically [1].
Children affected by these disorders can present in a number of
different ways and at almost any age. However, most commonly,
children are noted to have a DSD at birth when their genitalia are
sufficiently ambiguous that immediate sex assignment is difficult.
This is a distressing situation and necessitates a multidisciplinary
team approach at a centre specialised in the management of these
patients [1].

Most tertiary centres specialising in DSD management advocate early
surgical intervention for patients with DSD. Biological reasons for
operating early include the maternal oestrogenic effect on infant
tissues, satisfactory results, and reduced risk of urinary tract
infections [1], [2] and [3]. Early surgery is also thought to be
psychologically beneficial to the child because normally appearing
genitalia allow for appropriate gender development and less stigma
associated with DSD while also minimising parental anxiety, allowing
for better bonding. Another assumed psychological benefit of early
surgery is the infant's inability to form long-term memories [2],
preventing the child from remembering traumatic hospital experiences.

Presently, there is controversy surrounding early intervention in
DSD, although at the Royal Children's Hospital (RCH), Melbourne, the
Australian and New Zealand referral centre for DSD management, its
multidisciplinary management team continues to offer early surgical
intervention as part of a holistic treatment plan. Some patient
advocacy groups, most notably, the Intersex Society of North America,
are calling for the practice to be abandoned. They claim that
performing such an operation that is not readily reversible and has
profound life-long effects without an individual's informed consent
is unethical. It is possible, however, that members of the Intersex
Society of North America only represent the end of the spectrum of
patients with DSD who experienced poor outcomes and are not
representative of all patients with DSD. Poor outcomes of feminising
genital surgery reported in the UK in 2001 [4] further contributed to
the argument against early intervention in DSD. As long as
controversy persists surrounding DSD management, evaluation of short-
and long-term outcomes is imperative for those centres who practise
early intervention to ensure that current practice is also best
practice.

This study aimed to determine the results of early intervention in
the RCH patient population aged 5 to 10 years. Outcomes measured
included anatomical and cosmetic result, quality of life, and gender
identity. Overall, we found that early intervention yielded
acceptable cosmetic results while producing minimal impairment in
quality of life and gender identity development.

1. Methods
The records of children born between 1997 and 2003 (aged 5-10 years
at time of study) who were treated for a DSD at the RCH were
retrospectively evaluated. Diagnoses, date of birth, and dates of
surgical intervention were noted. Those patients who had not
undergone surgery for ambiguous genitalia were excluded. At the time
of their review appointments, the study was explained to children and
their parents. After obtaining informed consent, children were
examined and genitalia scored on a modified scale by Creighton et al
[4] and completed the PedsQL Pediatric Quality of Life Inventory 4.0.
Parents also completed the Parent Report version of the quality of
life inventory as well as the Gender Identity Questionnaire for
Children (GIQC).

The anatomical and cosmetic evaluation included the following
criteria for females: genital symmetry, clitoral size, clitoral
position, number of perineal openings, size of labia majora and
minora. Males were evaluated for stretched penile length (SPL),
testicular volume, genital symmetry, urethral position, presence of
chordee, scrotal fusion, scrotal position, and position of testes in
the scrotum. Both males and females were given an overall cosmetic
score of good (genitalia appear normal; no abnormal features),
satisfactory (up to 2 minor abnormalities; unlikely to be judged
abnormal by a nonmedically trained person), or poor (genitalia appear
abnormal; 3 or more abnormal features).

The PedsQL Generic Core Scales 4.0 for children and parents are
validated questionnaires, consisting of 23 items [5], [6] and [7].
Items are divided into physical (8 items) and psychosocial (15 items)
domains. Each question asks the child (or parent) to rate how often
an item has been a problem for them in the past 1 month. Possible
responses include the following: 0 = never a problem, 1 = almost
never a problem, 2 = sometimes a problem, 3 = often a problem, and 4
= almost always a problem. Each item was then reverse-scored and
linearly transformed to a scale of 0 to 100 so that 0 = 100, 1 = 75,
2 = 50, 3 = 25, and 4 = 0. The mean scores for each domain were then
calculated. Higher scores indicate better quality of life.

The GIQC is a validated parent-report questionnaire designed to
screen for gender identity disorder in the paediatric population [8].
This 16-item questionnaire encompasses a range of sex-typed
behaviours, and each is rated on a 5-point scale for frequency of
occurrence. Three items also include a response of not applicable.
The score of each item is averaged to obtain a score between 1 and 5
on the questionnaire. Higher scores indicate more same-gender
behaviour and lower scores indicate more cross-gender behaviour.

This project was approved by the institutional ethics committee.

For statistical analysis and descriptive statistics, GraphPad Prism
(Graph Pad, LaJolla, CA) was used.

2. Results
After review of medical records, 54 children were identified as being
eligible for participation in the study. Ten of these patients were
lost to follow-up. Of 44 patients, 41 participated in 1 or more
component of the study. Diagnoses of female participants included 16
congenital adrenal hyperplasia, 2 ovotesticular DSD, and 1 XX
virilisation of unclear cause, and diagnoses of males included 5
mixed gonadal dysgenesis, 3 partial androgen insensitivity syndrome,
3 ovotesticular DSD, 1 5á-reductase deficiency, 1 17â-hydroxysteroid
deficiency, 1 Klinefelter syndrome, 1 placental insufficiency, 1
vanishing testes syndrome, and 6 XY undervirilisation of unclear
cause. The median age of patients at their first surgical
intervention was 13.2 months (range, 1.8-250.1) and the mean age at
the time of study was 7.5 ± 2.1 (mean ± SD) years.

Thirteen females underwent anatomical evaluation. Eleven (85%)
received a cosmetic score of good and 2 (15%) scored satisfactory
(Fig. 1). Of the 21 males who were examined, 11 (52%) scored good, 8
(38%) satisfactory, and 2 (10%) poor. Short SPL was a commonly found
abnormal feature that contributed to the poorer outcomes in the male
population. Only 3 of 21 males had a SPL within 1 SD of normal and
only 10 of 21 were within 2 SD of normal [9].

Full-size image (30K)
Fig. 1. Cosmetic results of early surgery by sex in 5- to 10-year
olds.

View Within Article



Quality-of-life inventories were completed by both patients and
parents. Both parents and children rated physical quality of life as
being close to published values for healthy children [5], with the
exception of male children who rated their physical quality of life
lower (79.06), although this was not significantly lower than that
reported by female children or by parents of male children (Fig. 2
and Fig. 3). In terms of psychosocial quality of life, both parents
and children scored quality of life lower than healthy children [5].
Boys reported a lower psychosocial quality of life than girls as
reported by parents (66.85 vs 75.90, not significantly different) and
children (70.06 vs 78.96, not significantly different).

Full-size image (32K)
Fig. 2. Parent-reported PedsQL scores: healthy children (Varni et al
[5]) (solid black bar), male DSD group (striped bar), and female DSD
group (cross-hatched bar).

View Within Article

Full-size image (32K)

Fig. 3. Child-reported PedsQL scores: healthy children (Varni et al
[5]) (solid black bar), male DSD group (striped bar), and female DSD
group (cross-hatched bar).

View Within Article



Mean scores on the GIQC were significantly different for males and
females (3.95 vs 3.56; P = .0051). One of 19 males and 3 of 19
females had a score of 3 or less, suggesting that they may be at risk
of gender identity disorder or gender dysphoria (Fig. 4).

Full-size image (18K)

Fig. 4. Gender Identity Questionnaire for Children by sex. Data
points within circles represent those children at risk of gender
dysphoria or gender identity disorder.

View Within Article


3. Discussion
This study found that acceptable cosmetic results can be achieved by
early genital surgery, as 100% of females and 90% of males had
satisfactory or better outcomes. Also, when practised in concert with
appropriate psychological care as part of a holistic management plan,
early intervention results in minimal impairment in quality of life
or gender development.

The finding that most patients in our cohort at the RCH had
acceptable cosmetic results agrees with other reports in the
literature that rate cosmetic appearance after genitoplasty. In
addition, we have shown previously that long-term outcomes (at mean
age of 18 years) in our patients undergoing feminising genitoplasty
are excellent, with only 6% with poor cosmetic outcome and a very low
rate of redosurgery required in adolescence [3]. All patients in a
series evaluated by Bocciardi et al [10] were found to have good
cosmetic appearance, although the cosmetic criteria used were not
stated. Similarly, Roll et al [11] found that 13 of 19 patients had
excellent and 6 of 19 had good cosmetic appearance when scored on a
scale of excellent, good, satisfactory, or poor.

However, our results contrast sharply with those reported by
Creighton et al in 2001. They found that 41% of their patients had a
poor cosmetic result, which led to their conclusion that genital
surgery should be delayed until adolescence [4]. The subject
selection methods may explain the differing results of these studies.
In the Creighton study, patients were selected from an adult
gynaecology clinic based on having a history of feminising genital
surgery, whereas the RCH cohort consisted of all patients who
underwent genital surgery at our institution. The patients in
Creighton's cohort may represent the minority of patients with DSD
who are affected by worse outcomes that require adult gynaecological
treatment. Patients whose outcomes had been better may not see the
need for this type of specialised care and therefore may not be
included in their sample.

There is a paucity of information regarding quality of life in
paediatric patients with DSD. Physical quality of life, as reported
by both parents and children, was in the same range as those reported
by healthy children in other studies [5], [6] and [7], with the
exception of male children who rated their physical quality of life
lower (79.06). However, this was not statistically significantly
lower than the physical quality of life reported by female children
or by parents of male children. On the psychosocial quality of life
domain, female children and their parents reported that quality of
life was only slightly lower (78.96 and 75.90) than that reported by
healthy children (79.37) and their parents (80.58) [7]. Conversely,
both male children and their parents rated psychosocial quality of
life as being low at 70.06 and 66.85, respectively. This may be
because of the poorer cosmetic results related to micropenis in the
male patient group.

This study also found that children in the RCH cohort display more
cross-gender behaviour than normal children but that most were not at
serious risk of gender dysphoria or gender identity disorder. This is
not particularly surprising as similar cross-gender behaviour has
been found in boys with partial androgen insensitivity syndrome [12]
and in girls with congenital adrenal hyperplasia [13] and [14]
because of their aberrant prenatal hormone exposure. However, results
from a study by Zucker et al [14] suggest that although children with
congenital adrenal hyperplasia display more tomboyish behaviour, they
do not experience higher levels of gender dysphoria as adults.

The main limiting factor of this study was sample size and
participation rate, which were 41 (34 for anatomical/cosmetic
evaluation) and 76% (63%), respectively. Most nonparticipants were
lost to follow-up. This raises the concern of whether those lost to
follow-up experienced poorer outcomes than participants. However,
those lost to follow-up underwent fewer operations and were slightly
older than those studied, suggesting that nonparticipants actually
experienced better outcomes than those studied, and that they
subsequently lost contact with the hospital as they no longer
required specialised care.

In conclusion, results of this study support continuation of early
intervention in DSD. When practised in concert with a holistic
management plan, surgery yields positive outcomes in terms of
cosmesis, minimal impairment in quality of life, and appropriate
gender identity development.

References
[1] C.P. Houk, I.A. Hughes and S.F. Ahmed et al., Summary of
consensus statement on intersex disorders and their management.
International Intersex Consensus Conference, Pediatrics 118 (2)
(2006), pp. 753–757. Full Text via CrossRef | View Record in Scopus |
Cited By in Scopus (9)
[2]G. Gollu, R.V. Yildiz and M. Bingol-Kologlu et al., Ambiguous
genitalia: an overview of 17 years' experience, J Pediatr Surg 42 (5)
(2007), pp. 840–844. Article |  PDF (102 K) | View Record in Scopus |
Cited By in Scopus (1)
[3] W.L. Lean, A. Deshpande and J. Hutson et al., Cosmetic and
anatomic outcomes after feminizing surgery for ambiguous genitalia, J
Pediatr Surg 40 (12) (2005), pp. 1856–1860. Article |  PDF (325 K) |
View Record in Scopus | Cited By in Scopus (3)
[4] S.M. Creighton, C.L. Minto and S.J. Steele, Objective cosmetic
and anatomical outcomes at adolescence of feminising surgery for
ambiguous genitalia done in childhood, Lancet 358 (9276) (2001), pp.
124–125. Abstract | Article |  PDF (51 K) | View Record in Scopus |
Cited By in Scopus (74)
[5] J.W. Varni, T.M. Burwinkle and M. Seid et al., The PedsQL 4.0 as
a pediatric population health measure: feasibility, reliability, and
validity, Ambul Pediatr 3 (6) (2003), pp. 329–341. Abstract | Article
|  PDF (86 K) | Full Text via CrossRef | View Record in Scopus |
Cited By in Scopus (139)
[6] J.W. Varni, M. Seid and T.S. Knight et al., The PedsQL 4.0
Generic Core Scales: sensitivity, responsiveness, and impact on
clinical decision-making, J Behav Med 25 (2) (2002), pp. 175–193.
Full Text via CrossRef | View Record in Scopus | Cited By in Scopus
(82)
[7] J.W. Varni, M. Seid and P.S. Kurtin, PedsQL 4.0: reliability and
validity of the Pediatric Quality of Life Inventory version 4.0
generic core scales in healthy and patient populations, Med Care 39
(8) (2001), pp. 800–812. Full Text via CrossRef | View Record in
Scopus | Cited By in Scopus (258)
[8] L.L. Johnson, S.J. Bradley and A.S. Birkenfeld-Adams et al., A
parent-report gender identity questionnaire for children, Arch Sex
Behav 33 (2) (2004), pp. 105–116. Full Text via CrossRef | View
Record in Scopus | Cited By in Scopus (12)
[9] P.A. Lee, T. Mazur and R. Danish et al., Micropenis. I. Criteria,
etiologies and classification, Johns Hopkins Med J 146 (4) (1980),
pp. 156–163. View Record in Scopus | Cited By in Scopus (54)
[10] A. Bocciardi, A. Lesma and F. Montorsi et al., Passerini-Glazel
feminizing genitoplasty: a long-term followup study, J Urol 174 (1)
(2005), pp. 284–288 [discussion 8]. Abstract | Article |  PDF (533 K)
| Full Text via CrossRef | View Record in Scopus | Cited By in Scopus
(4)
[11] M.F. Roll, C. Kneppo and H. Roth et al., Feminising
genitoplasty: one-stage genital reconstruction in congenital adrenal
hyperplasia: 30 years' experience, Eur J Pediatr Surg 16 (5) (2006),
pp. 329–333. Full Text via CrossRef | View Record in Scopus | Cited
By in Scopus (0)
[12] M. Jurgensen, O. Hiort and P.M. Holterhus et al., Gender role
behavior in children with XY karyotype and disorders of sex
development, Horm Behav 51 (3) (2007), pp. 443–453. Article |  PDF
(201 K) | View Record in Scopus | Cited By in Scopus (4)
[13] S.A. Berenbaum and J.M. Bailey, Effects on gender identity of
prenatal androgens and genital appearance: evidence from girls with
congenital adrenal hyperplasia, J Clin Endocrinol Metab 88 (3)
(2003), pp. 1102–1106. Full Text via CrossRef | View Record in Scopus
| Cited By in Scopus (61)
[14] K.J. Zucker, S.J. Bradley and G. Oliver et al., Psychosexual
development of women with congenital adrenal hyperplasia, Horm Behav
30 (4) (1996), pp. 300–318. Abstract |  PDF (183 K) | View Record in
Scopus | Cited By in Scopus (118)

Presented at the 55th Annual Congress of the British Association of
Paediatric Surgeons, Salamanca, Spain, July 2-5, 2008.

Corresponding author. Department of Surgical Research, Royal
Children's Hospital, Parkville, VIC 3052, Australia. Tel.: +61 3 9345
5805; fax: +61 3 9345 7997.
1 Presenting author.


Journal of Pediatric Surgery Volume 44, Issue 2, February 2009, Pages
413-416

Michelle,

thanks so much for writing back..i have kids and have always knoow i was
diffferant but it took me get a visecimy to find out that i have female in
me..noot talking about being bisexual which i guss i always have been,,just the
wat i know my body..i was always the popolar so called pretty boy jock and goood
student but always knew i was differant from my friends,,I get off differantly
to not be blunt but know i feel floor and so confuse and rather pissed...i love
my mom so much and know my parents were talk into this and that time me being 40
i  guess doctors had the cards..I want that part of me but after talking to the
doctor it would not be safe for my heather and he was more than compasionant on
the matter...I have so manny amostions going on these day it sucks im down
/pissed and confused just need good understand friends and insit

tony




________________________________
From: Diane Michelle <dianemichellesinger@...>
To: intersexsupport@yahoogroups.com
Sent: Tuesday, February 24, 2009 12:44:30 AM
Subject: Re: [Intersex support] Hello from Michigan


Hello Tony,
I have had much the same sensations there and yet still seem to function like a
male when I need to masterbate. But I don't do so in the usual male way. Anyway
what I am getting to is that you aren't alone in any way here. So welcome.
Diane Michelle

--- On Mon, 2/23/09, tonyiroc2 <tonyiroc2@yahoo. com> wrote:
Hello,
My name is Tony. I'm a 40 year old male in Michigan with 2 young sons. Lived a
normal boy/male life but have recently found out I was born intersex during a
procedure from my doctor. I confronted my mother on the
issue and she explained my situation and that she had no control over
it in that day. I had a vaginal opening under my scrotum with a small
small vaginal path and ovarian like tissue that was removed and I was
sealed. I have always had stimulation from a young boy in that region
and learned to masturbate from rubbing that region instead of like most
boys stroking my penis so it explains a lot. I just feel robbed and upset that
this was taken from me. Have noone to talk to about it and looking for
answers/friends  with same situations. Sorry to run on but just mind is
twirling. Tony







[Non-text portions of this message have been removed]

Hello Tony,
I have had much the same sensations there and yet still seem to function like a
male when I need to masterbate. But I don't do so in the usual male way. Anyway
what I am getting to is that you aren't alone in any way here. So welcome.
Diane Michelle

--- On Mon, 2/23/09, tonyiroc2 <tonyiroc2@...> wrote:
Hello,
My name is Tony. I'm a 40 year old male in Michigan with 2 young sons. Lived a
normal boy/male life but have recently found out I was born intersex during a
procedure from my doctor. I confronted my mother on the
issue and she explained my situation and that she had no control over
it in that day. I had a vaginal opening under my scrotum with a small
small vaginal path and ovarian like tissue that was removed and I was
sealed. I have always had stimulation from a young boy in that region
and learned to masturbate from rubbing that region instead of like most
boys stroking my penis so it explains a lot. I just feel robbed and upset that
this was taken from me. Have noone to talk to about it and looking for
answers/friends with same situations. Sorry to run on but just mind is twirling.
Tony

Hello,

My name is Tony Im a 40 y/o male in michigan with 2 young sons..Lived a
normal boy/male life but have reciently found out i was born intersex
during and procedure  from my doctor..I confronted my mother on the
issue and she explained my situation and that she had no controll over
it in that day..I had a vaginal opening under my scodum with a small
small vaginal path and ovarian like tissue that was removed and i was
sealed...i have always had stimulation from a young boy in that region
and leared to masturbate from rubbing that region instead of like most
boys stroking my penis so it explains alot..I just feel robbed and
upset that this was taken from me..Have no one to talk to about it and
looking for answers/friends  with same situations...sorry to run on but
just mind is twerling....tony

http://www.bioline.org.br/request?js08009

Hi Terry and welcome.
Diane Michelle

--- On Tue, 12/16/08, puddydawg57 <puddydawg57@...> wrote:
> Hi Group. I am new to the group. My name is Terry and I am a 51 year
> old male that is not intersexed. I joined your group to make new
> friends and if a relationship developes later on, I will embrace it
> with open arms. I am looking to build a lasting friendship. To me a
> person's best feature is what is in their heart. Thank you, Terry

Hi Group , I am new to the group . My name is Terry and I am  a 51 year
old male that is not intersexed . I joined your group to make new
friends and if a relationship developes later on , I will embrace it
with open arms . I am looking to build a lasting friendship . To me a
persons best feature is what is in their heart .   Thank You  Terry

http://www.hindawi.com/GetArticle.aspx?doi=10.1155/2008/685897&e=html

http://www.springerlink.com/content/l0776r8734j717h4/fulltext.html

Pediatric Surgery International
© Springer-Verlag 2008
10.1007/s00383-008-2232-7
Original Article

Gender assignment and hormonal treatment for disorders of sexual
differentiation

Shilpa Sharma1 and D. K. Gupta1 Contact Information
(1) Department of Pediatric Surgery, All India Institute of Medical
Sciences, New Delhi, India

Contact Information  D. K. Gupta
Email: profdkgupta@...

Published online: 14 August 2008

Abstract
Purpose  To study the gender assignment and hormonal treatment
advocated for disorders of sexual differentiation (DSD).
Methods  A study was done on patients who were reviewed in the
Pediatric Intersex Clinic to evaluate the pattern of gender assignment
and hormonal treatment advocated.
Results and conclusion  The patients included male pseudohermaphrodite
(MPH) 169; congenital adrenal hyperplasia (CAH) 91; mixed gonadal
dysgenesis (MGD) 29; true hermaphrodite (TH) 25; pure gonadal
dysgenesis (PGD) 2; persistent mullerian duct syndrome (PMDS) 2 and
others (micropenis, severe hypospadias with cryptorchidism, 46XX male)
39. Out of 91 cases of CAH, 70 (76.9%) were on steroids (prednisolone,
hydrocortisone) and/or mineralocorticoids (fluoricortisone) for
adrenal suppression. Out of 146 cases of male pseudohermaphrodite and
21 cases of true hermaphrodite and 3 cases of mixed gonadal dysgenesis
reared as males, testosterone was given for local application for
phallic growth in 101 and/or as systemic injection for mental makeup
after puberty in 41 cases. Systemic testosterone injection was also
given for 7 cases of CAH reared as males. Out of 26, 15 cases with
mixed gonadal dysgenesis and one out of 2 cases of pure gonadal
dysgenesis that attained puberty after being reared as females, after
female genitoplasty, were given conjugated oestrogen (Premarin)
supplemented with progesterone, as the uterus was preserved. For 12
post-pubertal cases of complete androgen insensitivity syndrome (AIS),
only premarin was given as there was no uterus. Growth hormone and Gn
RH analogue was given in 2 patients with CAH to tide over the early
bone maturation induced by hormones with equivocal results. Thus
judicious hormonal supplementation based upon type of DSD and gender
assigned can provide a psychological and cosmetic benefit to patients
with DSD.

Keywords  Intersex disorders - DSD - Gender assignment - Hormones -
Genitoplasty

Introduction
The management of disorders of sexual differentiation (DSD) is complex
for those who do not have the exposure to a large number of cases [1,
2]. The management should have a multidisciplinary approach with
proper discussion at points of decision making giving due regard to
the patient and the family concerns. The success lies in timely
treatment and advice based on wisdom to prevent the psychological
stress associated with this disease imposed on the parents initially
and then transferred to the patients as they gain awareness. The
disease carries a social stigma that varies in different communities
and different countries.

In the most common five main groups of intersex disorders: female
pseudohermaphrodite (ovary only); male pseudohermaphrodite (MPH,
testis only); true hermaphrodite (TH, ovary + testis); mixed gonadal
dysgenesis (MGD, testis + streak gonad) and pure gonadal dysgenesis
(PGD, streak + streak gonad), the treatment involves surgery,
appropriate hormonal supplementation and psychological support. For
all practical purposes, the first four groups are the common main ones.

Purpose
The hormonal treatment given for cases with disorders of sexual
differentiation (DSD) depends upon the gender assigned. A study was
conducted to analyse the hormonal treatment advocated for DSD
depending upon the type of anomaly and the gender assigned.

Patients and method
This study is based on the treatment policy adopted at the Pediatric
Intersex Clinic at our institute, having a registry of 1,188 patients
till 2007. The study was approved by the Institutional review board
for clinical manuscripts. Patients who attended the clinic from
2005–2007 were reviewed to study the pattern of gender assignment and
hormonal treatment advocated in the different types of DSD. The
algorithm that was adopted for gender assignment is depicted in Fig.
1. The records of the hormonal treatment advocated according to the
gender assigned were studied.

MediaObjects/383_2008_2232_Fig1_HTML.gif
Fig. 1 Algorithm for gender assignment in disorders of sexual
differentiation (DSD). The four main types of DSD are MPH male
pseudohermaphrodite, CAH congenital adrenal hyperplasia, MGD mixed
gonadal dysgenesis, TH true hermaphrodite. The gender assigned was
mainly based on the phallic growth and the family desires

For male sex assignment, the required surgical procedures include male
genitoplasty, correction of penoscrotal transposition, insertion of
testicular prosthesis and the removal of all the undesired female
adenexa, if present, including seven cases of congenital adrenal
hyperplasia (CAH) with XX karyotype assigned male gender. For female
sex assignment, a female genitoplasty included clitoroplasty/clitoral
reduction, vaginoplasty and removal of the male gonad (if present).
Clitoroplasty for CAH was not done unless the hormonal status was well
under control. CAH cases reared as virilized males, received steroids
to suppress the adrenals and also testosterone supplementation.

For cases of TH, the abdominal testis was removed in all cases,
irrespective of the gender assigned. Female sex assignment was
preferred if there was ovary, fallopian tubes and uterus present.

For MGD, the streak gonad was removed irrespective of the sex
assigned. In the presence of the Y chromosome/cell line, not only the
streak but also the contra lateral testis, irrespective of its
location was removed.

For PGD, both the streak gonads were removed during surgery,
irrespective of age and chromosomal pattern.

For cases of complete androgen insensitivity syndrome (AIS) assigned a
female sex, the gonads were removed on one side and fixed high up on
the other side to avoid enlargement of the scrotal sacs. This group
formed part of the extreme spectrum of the MPH group that were totally
unvirilized or very partially virilized.

Results
During this period, 357 patients were reviewed in the Pediatric
Intersex Clinic. These included MPH 169; CAH 91: MGD 29; TH 25; PGD 2;
PMDS 2 and others (micropenis, severe hypospadias with cryptorchidism,
46XX male) 39.
The gender assigned for the various types of DSD are shown in Table 1.
The hormonal treatment advocated is given in Table 2.

Table 1 Gender assigned in the various DSDs in this series

DSD
Total
Male
Female
MPH
169
146
23

CAH
91
7
84

MGD
29
3
26

TH
25
21
4

PGD
2
–
2

PMDS
2
2
–

Others
39
39


–
MPH Male pseudohermaphrodite, CAH Congenital adrenal hyperplasia, MGD
mixed gonadal dysgenesis, TH true hermaphrodite, PGD pure gonadal
dysgenesis, PMDS persistent mullerian duct syndrome

Table 2 Hormonal treatment advocated in the various DSDs in this series

DSD
Total
Male
Received hormonal treatment
Female
Received hormonal treatment

MPH
169
146
LT–94,ST(ap)-36
23
E(ap)-12

CAH
91
7
ST-7,C-5
84
C ± M-65* GH-2

MGD
29
3
LT-3,ST(ap)-3
26
E + P(ap)-15

TH
25
21
LT-4,ST(ap)-2
4

PGD
2
–
2
E + P(ap)-1
*Noncompliant-4, Treatment stopped intermittently-15
MPH Male pseudohermaphrodite, CAH Congenital adrenal hyperplasia, MGD
mixed gonadal dysgenesis, TH true hermaphrodite, PGD pure gonadal
dysgenesis, PMDS persistent mullerian duct syndrome; LT local
testosterone, ST systemic testosterone, C corticosteroids, M
mineralocorticoids, E oestrogen (premarin), P progesterone, GH- Growth
hormone; ap after puberty

Out of 91 cases of CAH, 70 cases (76.9%) were on steroids
(prednisolone, hydrocortisone) and/or mineralocorticoids
(fluoricortisone) for adrenal suppression. Seven cases of CAH had been
reared as males and were receiving systemic testosterone injection.
Growth hormone and Gn RH analogue were given in 2 patients with CAH to
tide over the early bone maturation induced by hormones with equivocal
results.

The cases assigned a male gender included 146 cases of male
pseudohermaphrodite, 21 cases of true hermaphrodite and 3 cases of
mixed gonadal dysgenesis. Testosterone was given to them for local
application for phallic growth (101) after chordee correction had been
done and while they were awaiting urethroplasty. Twenty-one cases out
of these had also applied 5–10% testosterone before chordee
correction. There was a demonstrable increase in girth of the phallus
by more than 25% increase in the circumference in 49/101 (48.5%)
cases. There was no response in 52/101 cases.

The change in penile length was measured in 46 patients who were
applying testosterone locally at the time of the study. There was an
increase in length of the phallus by more than 1 cm in 6/46 cases less
than 8 years of age and assessed over a period of 6 months during the
time of the study.

Systemic testosterone injection was given in 41 cases for mental
makeup after puberty and for development of secondary sexual
characteristics.

Cases of DSD other than CAH assigned a female gender did not require
hormonal supplementation till they attained puberty. Most of them
developed breast tissue after the unwanted gonads with
testicular/dysgenetic components were removed even before puberty. Out
of 26, 15 children with MGD and 1 out of 2 cases of PGD had attained
puberty after being reared as females, after female genitoplasty. They
were given conjugated oestrogen (premarin) supplemented with
progesterone, as the uterus was preserved. In 12 cases of complete
androgen insensitivity syndrome reared as female who had reached
puberty, only premarin was given as there was no uterus. Ten of these
had the appearance of well-developed female sexual characteristics and
were leading a happy life.

Discussion
The management of DSD depends upon many factors and needs to be
individualised based on the type of the disorder, gonadal
differentiation, age at presentation, economical status, psychosocial
and cultural aspects [3–6]. Though the physical aspects of diagnosis
and management have become better understood, there are psychological
and social aspects that we have only begun to understand [7]. The
management is complex and constitutes many issues. Here, we will
discuss only the factors that affect the gender assignment and the
hormonal treatment.

The immediate problem when a child with DSD is brought is to take a
proper history, do a good clinical examination, reach a proper
diagnosis, consider the sex of rearing, assess the socioeconomic and
cultural background of the parents and then assign the sex of rearing,
preferably before the child is 6 months of age and before the baby is
exposed to the society. All this may take several visits and
counselling, giving the parents enough time to decide. If the child is
brought in newborn period or before 1 year, there is still a choice
that should be made taking all relevant aspects into consideration. If
the child presents late, sex of rearing is usually not changed except
if the parent desires so.

It is technically easier to construct a female genitalia rather than a
male. However, in a country with strong socio-cultural compulsions, a
considered decision is required before assigning the sex of the baby.
The chromosomal sex has no role to play in this respect. The pattern
of the internal gonads, internal and external genitalia and phallic
size mainly determine the sex to be assigned (Fig. 1).

Androgen responsiveness to a standard human chorionic gonadotropin
(hCG)-stimulation test (1,500 IU given intramuscularly for 3 days) in
neonates with ambiguous genitalia suggested by phallic growth may help
support a male sex assignment [8]. A positive hCG stimulation test in
the newborn or an LHRH stimulation test in mid-childhood might be
useful for evaluating cases of suspected AIS than the basal
gonadotrophin concentrations [9, 10]. The testosterone and
dihydrotestosterone (DHT) ratio following hCG stimulation is more
reliable than the basal testosterone:DHT ratio in identifying
5-reductase deficiency [10].

Gender assignment for patients with MGD is debatable. Some authors
feel that as no case has been reported of a tumour developing in a
fully descended testis in these patients, a male gender should be
assigned for those who are sufficiently virilized [11]. Others prefer
an elective feminine gender assignment for patients with MGD because a
uterus and vagina are always present and about half of the patients
are markedly short and have a high incidence of inadequate external
virilization [12]. The authors prefer male gender assignment only for
the most significantly virilized patients with a completely descended
testis. All the patients with bilateral dysgenetic gonads need to be
reared as females with excision of dysgenetic gonads. The authors have
seen a malignancy developing in a 17-year-old boy with MGD and a Y
cell line, and who had a scrotal testes retained.

Hormonal therapy forms part of the treatment of every intersex
condition [13]. The salt wasting type of CAH needs hormonal
replacement therapy (cortisol and aldosterone) as soon as diagnosed.
Prenatal cases with suspected CAH in families that have had an
affected baby in the past, are given dexamethasone soon after
confirmation of pregnancy even before the diagnosis of CAH is
established as by then it is too late to start treatment and
virilization would have already begun. The treatment is stopped if the
foetus is a male or an unaffected female after confirming with
amniocentesis and genetic mutation. This treatment is well tolerated
and, in general, and quite effective [13].

Almost all cases of CAH patients are reared as female, if the patient
is brought well in time. However, in this series, 7 patients were
brought late and were reared as males with a well developed phallus as
a result of uncorrected hormonal imbalance resulting in virilization
[8]. Of the seven, six have a male mental make up. There was only one
patient of CAH in this whole series who has a male mental makeup
though she is a well-developed female externally and has not yet
accepted a female gender mentally.

Out of 91 cases of CAH, 70 cases (76.9%) were on steroids
(prednisolone, hydrocortisone) and/or mineralocorticoids
(fluoricortisone) for adrenal suppression. The treatment for CAH was
stopped in one patient who got married, and developed amenorrhoea in 3
months duration and polycystic ovaries. The levels of 17 OHP were
normal but the levels of testosterone were high. The menstruation was
restored, though she is still under observation and has not conceived
as yet. Growth hormone and Gn RH analogue were given in two patients
with CAH to tide over the early bone maturation induced by hormones,
with equivocal results. These patients had stunted heights and high 17
OHP. The dose of the hormones, hydrocortisone and fluoricortisone had
to be reduced or stopped intermittently in nine patients with an
acceptable rise in 17 OHP so that bone growth could be achieved. Four
patients were non-compliant and stopped the medicines on their own.

Of the 101 patients with a small phallus who were treated with local
testosterone cream, only 48.5% showed response in the form of supple
penile skin. Most of these patients had a severe chordee. Though DHT
cream is reported to be effective in non-responders, yet the authors
did not have any experience with the use of DHT. The DHT cream in a
dose of 0.2–0.3 mg/kg per day for 3–4 months may be useful in the
management of patients with testosterone biosynthetic defects. Phallic
growth was reported, ranging from 0.5–2.0 cm, after 3–4 months in all
patients whose DHT concentrations were maintained within adult range
[14]. The testosterone/dehydrotestosterone (DHT) ratio was changed in
five patients who were diagnosed as 5-alfa reductase deficiency,
resulting in low levels of DHT.

Systemic testosterone injection was given in cases assigned a male
gender and who had attained puberty for the mental makeup and for
development of secondary sexual characteristics.

Anti-Mullerian hormone is used to facilitate the evaluation of
intersex disorders and as a marker of ovarian reserve assessment in
the infertility cases [15]. In prepubertal boys, AMH is involved in
testicular development and function [16]. When testes are non-palpable
a single measurement of serum AMH level can distinguish between
cryptorchidism and anorchia. AMH determination can help in the
diagnosis of intersex conditions [16]. AMH may be normally secreted in
intersex patients with defects restricted to androgen synthesis or
action, resulting in patients with female or ambiguous external
genitalia with no Müllerian derivatives [17].

In this series, one case of AIS that was assigned a female gender
failed to accept the same and had to be reassigned a male sex at the
age of 10 years. A phalloplasty was done using the vascularized
abdominal flap and he is now satisfied, though he still continues to
have a perineal meatus. He is still awaiting a penile implant.

Testosterone exposure during critical periods of early development
produces permanent behavioural changes including childhood play
behaviour, sexual orientation, core gender identity and other
characteristics that show sex differences [18]. There is also evidence
that testosterone works within the normal range to make some
individuals within each sex more sex-typical than others [18]. This
effect was significant in only two cases in this series, one patient
with AIS and the other with late diagnosed CAH. For decades, sex
assignment in children with intersex conditions has depended more on
surgical possibilities than on other criteria, since it was assumed
that children are psychosexually neutral at birth [19]. Adults with
intersex conditions and professionals in the field have increasingly
criticised this policy after reports suggesting that prenatal brain
exposure to sex hormones determines gender development and that the
patient may grow up feeling uncertain about his or her gender
identity, or worse still, harbour a sense of outrage about life and
treatment experiences [13, 19]. However, recent reviews on gender
dysphoria and gender change in patients with intersex conditions show
that initial gender assignment still seems to be the best predictor of
adult gender identity [19].

Three cases of MPH reared as boys and one case of CAH in this series
are married for last two years. All of them are sexually functional
and satisfied, though fertility has not yet been proved. The three
cases of MPH have oligospermia.

To conclude, the most crutial decision for management of DSD is gender
assignment. Appropriate surgical treatment should be done according to
the gender assigned [20]. The role of hormonal therapy in CAH is to
suppress the unwanted hormone excess of androgens or
mineralocorticoids by exerting negative feedback. For hypogonadism in
other disorders, sex hormone replacement therapy may be prescribed to
stimulate sexual development: growth of a hypoplastic penis, pubertal
changes, psychosexual development, adult sexual behaviour and bone
mineral density [13]. Thus, judicious hormonal supplementation based
upon type of DSD and gender assigned is the key to successful outcome
in patients with DSD.

References
1. Gupta DK, Menon PS (1997) Ambiguous genitalia—an Indian
perspective. Indian J Pediatr 64:189–194
PubMed SpringerLink ChemPort
2. Gupta DK (2005) Pediatric intersex dilemma. Clues to diagnosis and
management (Abstract). Asian J Surg 28(1):19
3. Gupta D K, Sharma Shilpa, Amini AC (2008). Hormonal treatment for
disorders of sexual differentiation. In: The proceedings of
international conference on molecular and clinical aspects of gonadal
and non-gonadal actions of gonadotrophins, New Delhi, 7–9 February
2008 (in press)
4. Gupta DK, Sharma S, Amini AC et al (2006) Congenital adrenal
hyperplasia: long-term evaluation of feminizing genitoplasty and
psychosocial aspects. Pediatr Surg Int 22:905–909
PubMed SpringerLink ChemPort
5. Gupta DK (1999) Preservation of testicular function in true
hermaphrodites: pediatric intersex clinic experience at AIIMS. In:
Gupta DK (ed) Ambiguous genitalia and hypospadias. Printext
Publishers, New Delhi, pp 73–74
6. Sharma S, Gupta D.K, Amini AC (2007) Followup after male
genitoplasty for patients with congenital adrenal hyperplasia (CAH).
Abstracted during the 2nd World Congress of International Society of
Hypospadias and Intersex Disorders, Rome Italy, 16–18 November 2007
7. Bomalaski MD (2005) A practical approach to intersex. Urol Nurs
25:11–18PubMed
8. Almaguer MC, Saenger P, Linder BL (1993) Phallic growth after hCG :
a clinical index of androgen responsiveness. Clin Pediatr 32:329–333
CrossRef ChemPort
9. Ahmed SF, Cheng A, Hughes IA (2000) Assessment of the
gonadotrophin-gonadal axis in androgen insensitivity syndrome. Arch
Dis Child 82:54–58PubMed CrossRef
10. Ng KL, Ahmed SF, Hughes IA (1999) Pituitary–gonadal axis in male
undermasculinisation. Arch Dis Child 80:324–329
11. Glassberg KI (1980) Gender assignment in newborn male
pseudohermaphrodites. Urol Clin North Am 7:409–421PubMed ChemPort
12. Raifer J, Walsh PC (1981) Mixed gonadal dysgenesis-dysgenetic male
pseudohermaphroditism. In: Josso N (ed) The intersex child, pediatric
and adolescent endocrinology. Karger, Basel, pp 105–111
13. Warne GL, Grover S, Zajac JD (2005) Hormonal therapies for
individuals with intersex conditions: protocol for use. Treat
Endocrinol 4:19–29PubMed CrossRef ChemPort
14. Charmandari E, Dattani MT, Perry LA et al (2001) Kinetics and
effect of percutaneous administration of dihydrotestosterone in
children. Horm Res 56:177–181PubMed CrossRef ChemPort
15. Vladimirov Ia, Tacheva D, Blagoeva V et al (2005) Anti-Mullerian
hormone: a gonadal hormone with multiple diagnostics resources. Akush
Ginekol (Sofiia) 44:37–40
16. Szarras-Czapnik M, Gajewska M, Ksiazyk J, Janas R,
Ginalska-Malinowska M (2006) Anti-Müllerian hormone (AMH) measurements
in the assessment of testicular function in prepubertal boys and in
sexual differentiation disorders. Endokrynol Diabetol Chor Przemiany
Materii Wieku Rozw 12:195–199PubMed
17. Rey R (2005) Anti-Müllerian hormone in disorders of sex
determination and differentiation. Arq Bras Endocrinol Metabol
49:26–36PubMed
18. Hines M (2006) Prenatal testosterone and gender-related behaviour.
Eur J Endocrinol 155(Suppl 1):S115–S121PubMed CrossRef ChemPort
19. Cohen-Kettenis P (2005) Psychological long-term outcome in
intersex conditions. Horm Res 64(Suppl 2):27–30PubMed CrossRef ChemPort
20. Gupta DK, Sharma S (2008) Male genitoplasty for intersex
disorders. Adv Urol (in press)

T04-O-06

Gender identity conflicts and psychological problems in adult subjects
with different forms of intersexuality (disorders of sex development,
dsd): the Hamburg Intersexnext term project

H. Richter-Appelta

aInstitute for Sex Research, Hamburg, Germany

Available online 27 June 2008.

Our knowledge of the treatment options and long-term outcomes with
different forms of intersexuality is insufficient. The demand for life
long follow-up studies asks for more than surgical outcomes data. The
objective of the Hamburg follow-up study is not only to gather
information about physical development and treatment experiences of
individuals with different forms of intersexuality but also about
their gender identity problems, social life and especially about their
psychological problems and well-being.

A comprehensive questionnaire was developed that comprises
standardized as well as self-constructed instruments. The instruments
assessed demographic aspects, physical and sexuel development,
diagnotic procedures hormonal and surgical treatment interventions,
gender identity, gender role, psychological impairments.

The sample includes 70 subjects with partial or complete androgen
insensitivity, disturbances of androgen biosynthesis, gonadal
dysgenesis (46, XY karyotype; co called XY women) and subjects with
CAH (46, XX karyotype.

Gender identity conflicts in intersex subjects living in the female
role will be described. Optimal treatment policy demands a stable
Gender identity in adulthood. This is the basic assumption for medical
treatment procedures. Encouraged by the public discussion and by
members of support groups many subjects ask for a more flexible view
of gender identity and sexual health.

From our data one can conclude that not all subjects finally want to
live in a clear male or female gender role as adults. Not all of them
want heterosexual relationships with the possibility of having
heterosexual intercourse with penetration. The option of medical
treatment procedures of sex assignment surgeries will be discussed.

Sexologies
Volume 17, Supplement 1, April 2008, Page S79
Abstracts of the 9th Congress of the European Federation of Sexology

Good night Kyle.
Diane Michelle

--- On Thu, 7/3/08, kyle <kokorokun@...> wrote:
> Well need to go sleep, night everybody.

Well need to go sleep, night everybody.

Any time.
Diane Michelle

--- On Thu, 7/3/08, kyle <kokorokun@...> wrote:
> Thanks.

thx

I will.
Diane Michelle

--- On Thu, 7/3/08, kyle <kokorokun@...> wrote:
> Well if there are any intersex people in Texas message me.