Review

Horm Res 2001;56:311

Received: April 11, 2001 Accepted after revision: October 9, 2001

Congenital Micropenis: Long-Term Medical, Surgical and Psychosexual Follow-Up of Individuals Raised Male or Female
Amy B. Wisniewski a Claude J. Migeon a John P. Gearhart b John A. Rock c Gary D. Berkovitz d Leslie P. Plotnick a Heino F.L. Meyer-Bahlburg e John Money f
of Pediatrics, Division of Pediatric Endocrinology, and b Department of Urology and Chief, Pediatric Urology, James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Md.; c Department of Gynecology and Obstetrics and Chief, Emory University School of Medicine, Atlanta, Ga.; d Department of Pediatrics, Division of Pediatric Endocrinology, University of Miami School of Medicine, Miami, Fla.; e Department of Psychiatry, Division of Child Psychiatry and Program of Developmental Psychoendocrinology, Columbia University College of Physicians and Surgeons and NYSPI, New York, N.Y.; f Medical Psychology and Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Md., USA
a Department

Key Words Micropenis W Psychosexual W Gender W Sexuality W Vaginoplasty W Intersex W Testosterone W Estrogen W Sexual function

Abstract Objectives: to document long-term medical, surgical and psychosexual outcome of individuals with congenital micropenis (13 males, 5 females). Methods: Physical measurements from childhood were collected retrospectively from medical records and at adulthood by physical examination. An adult psychosexual assessment was conducted with a written questionnaire and oral discussion. Results: Adult penile length was below the normal mean in all men. Three women had vaginoplasty resulting in normal length. All men reported good or fair erections but 50% were dissatisfied with their genitalia. Dissatisfaction with body image resulted from having a small penis (66%), inadequate body hair (50%), gynecomastia (33%) and youthful appearance (33%). Ten men

were heterosexual, 1 homosexual and 2 bisexual. Among women, 4 (80%) were dissatisfied with their genitalia. Three women reported average libido with orgasm and were also heterosexual. Two women had no sexual interest or experience. Finally, males were masculine and females feminine in their gender-role identity, and both groups were satisfied with their sex of rearing. Conclusions: Regarding choice of gender, male sex of rearing can result in satisfactory genito-sexual function. Female gender can also result in success, however it requires extensive feminizing surgery.
Copyright 2002 S. Karger AG, Basel

Portions of this work were presented by A.W. at the Lawson Wilkins Pediatric Endocrine Society meeting in Boston (May, 2000). This work was supported by a grant from the Genentech Foundation for Growth and Development (98-33C to C.M.), NIH National Research Service Award F32HD08544 (to A.W.), and by NIH, NCRR, General Clinical Research Center Grant RR-00052.

ABC
Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com

2002 S. Karger AG, Basel 03010163/01/05620003$17.50/0 Accessible online at: www.karger.com/journals/hre

Amy Wisniewski, PhD 600 N. Wolfe Street/Park 211 Baltimore, MD 21287 (USA) Tel. +1 410 614 5576, E-Mail amy@jhu.edu

During fetal sex differentiation, the genital tubercle and cloacal folds of an embryo emerge by the fourth week of gestation. By the sixth week, the cloacal folds divide to form urogenital and anal folds. At the same time, genital swellings form on each side of the genital folds, that later develop into either scrotal swellings or labia majora. In embryos that produce and respond to androgens sufficiently, the genital tubercle elongates to form a phallus, while the urogenital folds form the urethral groove. A penile urethra exists by the end of the first trimester of gestation, and the glans of the penis forms by the fourth month. Under further effects of androgens, elongation of the penis occurs during the second and third trimesters of gestation [1]. Androgen secretion by the fetal testes is controlled by human chorionic gonadotropins (HCG) during the first trimester, and by fetal pituitary hormones later in development. Mean stretched penile length for a full-term male is 3.5 cm [2]. Micropenis refers to a penis that formed normally during the first trimester, but then failed to lengthen [35]. Micropenis differs from microphallus in that microphallus is associated with hypospadias whereas micropenis is not. Stretched length of a micropenis is 2.5 SDs below the mean for age or less than 1.9 cm at birth [4]. Etiology of micropenis includes hypogonadotropic hypogonadism, hypergonadotropic hypogonadism, partial androgen insensitivity or idiopathic [4]. A study of nine patients with micropenis by Money et al. [6] revealed a final penile length less than 2.5 SDs below the mean for all participants. Seven of these men were dissatisfied with the appearance of their genitalia, and five reported a history of being teased about the size of their penis. Six men were heterosexual and three were homosexual [7]. In another study of seven patients with micropenis (the original group of twelve included five men with hypospadias and thus do not qualify as micropenis), Reilly and Woodhouse [8] reported penile length below the 10th percentile for all subjects. Many experienced teasing about their genital appearance. All had a male gender identity, although one lacked confidence in his male role. Participants unanimously reported heterosexual interests, erections and orgasms. Finally, a recent study by Bin-Abbas et al. [9] of 8 men with micropenis revealed that penile length increased three SDs following one or more courses of testosterone treatment in childhood, followed by adult replacement. Regardless of timing of treatment, penile length fell within two SDs of the normal range. All of the men experienced erections, ejaculation and reported a male gender

identity. Six reported satisfactory heterosexual relationships. In light of some discrepancies regarding outcome of males with congenital micropenis, additional follow-up is needed. Furthermore, little information exists regarding outcome of patients sex-reassigned to female [1012]. Finally, follow-up of patients with congenital micropenis allows for the investigation of the influence of prenatal androgen exposure, sufficient for a penile urethra to form but insufficient for penile elongation, on long-term psychosexual development. The present study focuses on long-term medical, surgical and psychosexual outcome for 46,XY individuals with congenital micropenis, 13 reared male and 5 reared female. (For the remainder of this paper, participants reared as female will be referred to as females or women.)

Subjects and Methods

This research was approved by the Joint Committee of Clinical Investigations of Johns Hopkins University School of Medicine. Written, informed consent was obtained from all subjects prior to participation. Participants completed a questionnaire and a physical examination. Subjects The recruited population consisted of patients with a chromosomal complement of 46,XY and congenital micropenis seen at the Pediatric Endocrine Clinic of Johns Hopkins Hospital, 21 years of age or older. The total number of 46,XY congenital micropenis patients seen at Johns Hopkins who were over 21 years of age included 45 subjects, 33 males and 12 females. Charts could not be located for 2 patients reared male as a result of changes in archiving of patient information at Johns Hopkins Hospital. Eleven individuals were not included because they exhibited severe cognitive impairment as indicated by medical history. Ten individuals were not located, and an additional person died due to cardiac disease. Of the remaining possible participants, 3 refused to participate (table 1). Mean age for male participants was 38 years (range 2154 years), and for male non-participants was 38 years (3150 years). Mean age for female participants was 26 years (2329 years), and for female non-participants was 30 years (2440 years). Four men who participated had been included in a previous psychological study [6]. Etiology of micropenis for the 13 male participants was attributed to Kallmanns syndrome (No. 16), panhypopituitarism (No. 79), hypergonadotropic hypogonadism (No. 10, 11) and idiopathic (No. 12, 13). Etiology for the five female participants included panhypopituitarism (No. 14, 15), hypogonadotropic hypogonadism (No. 16), hypergonadotropic hypogonadism (No. 17) and undetermined (No. 18). Although participants did not differ from non-participants by age or endocrinopathy, they did differ by level of cognitive function. Those individuals who were unable to complete the questionnaire due to cognitive impairment consisted of subjects with CHARGE

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Table 1. Micropenis patients categorized as participants and non-

participants Males Participants Total Nonparticipants Chart not found Unable to locate individual Died Severe cognitive impairment Refused to participate Total Females Total

13 2 8 1 7 2 20

5 0 2 0 4 1 7

18 2 10 1 11 3 27

naire. Three men (ID 4, 5, 13) received testosterone therapy during their first year of life as 6 weeks of HCG, testosterone cream applied to the genitalia and/or 4 i.m. injections of testosterone enanthate (50 mg monthly). Later testosterone therapy was given as i.m. injection of testosterone enanthate in males starting at 1213 years of age (50100 mg monthly) for 1218 months, and then increased to 200 300 mg every 34 weeks. In females, estrogen therapy was initiated at 1213 years of age as 0.3 mg of premarin for 1824 months, followed by a contraceptive pill (days 121 of each month). Psychosexual Assessment Genito-sexual function: Participants were asked about the adequacy of their genitalia for sexual functioning, self-estimated strength of libido, and experience of orgasms. Body image: Participants were asked about satisfaction with their appearance, and to indicate which physical characteristics contributed to dissatisfaction. Femininity and masculinity: Participants were asked how masculine and feminine they considered themselves throughout development. Sexual orientation: Participants were asked if they were sexually attracted to, fantasized about, or participated in sexual activity with males, females, both or neither [15]. Marriage and parenthood: Frequency of marriage and parenthood was asked for all participants. Satisfaction with sex of rearing: Participants were asked about satisfaction with their sex of rearing, and if at any point they had considered changing their sex of rearing. Opinions concerning treatment: Females were asked their opinion regarding timing of gonadectomy, feminization of external genitalia and vaginoplasty. All participants were asked their opinion about categorizing intersex children as a third gender. Long-term counseling: Participants reported whether they had received psychological or psychiatric counseling. Knowledge of medical/surgical history: Participants were evaluated by a pediatric endocrinologist (C.J.M.) and psychologist (A.B.W.) to determine their level of understanding of micropenis. Documented for males was knowledge of the appearance of their genitalia et birth, etiology of their condition and importance of endocrine treatment in adulthood, if indicated. Documented for females was knowledge of the appearance of their genitalia at birth and corresponding female sex-assignment, etiology of their condition and importance of endocrine treatment in adulthood. Statistical Analysis A one-tailed t test (in favor of early treatment) was used to detect a difference in final penile length between men whose testosterone treatment was initiated in infancy compared to those whose treatment was initiated later. Two-tailed t tests were used to detect differences between males and females for stretched penile length (in SDs) at first presentation, participants satisfaction with their genitalia, participants satisfaction with their appearance and participants satisfaction with their sex of rearing. Masculinity and femininity scores were analyzed with a 2-factor, repeated-measures analysis of variance (ANOVA). The between subjects factor was male or female, and the within subjects factor was childhood, adolescence or adulthood. Least squares regression analysis was used to examine the relationship between penile length at initial presentation and final penile length for males. All mean differences were considered statistically significant if p ! 0.05.

syndrome (n = 1), septo-optic dysplasia with variable but major brain abnormalities (n = 6), Prader-Willi syndrome (n = 1), Rudd syndrome (n = 1) or occipital encephalocele (n = 2). Cognitive impairment has previously been reported to occur in conjunction with micropenis [4, 5]. However, IQ was not negatively affected among patients with micropenis who did not have these syndromes [13]. None of the individuals with cognitive impairment (4 reared female, 7 reared male) underwent a change of sex of rearing. Physical Measurements Physical Measures in Infancy or Childhood. Appearance of external genitalia was noted from medical records and consisted of stretched penile length as described by Lee et al. [4] and size of testes when palpable. Physical Measures in Adulthood. For males, stretched penile length, quality of corporal bodies and size of testes were evaluated independently by two physicians (C.J.M. and J.P.G.) and then agreed upon. If all three genital measures were within the normal range cosmetic appearance of the genitalia was rated as good. If one of the three measures was abnormal a rating of fair was given, and if two or more measures were abnormal the cosmetic appearance of the genitalia was rated to be poor. Breast size was measured and reported in cm, horizontally and vertically for each breast. Measurement did not differentiate between glandular or adipose tissue. The existence and size of the prostate was noted. Pubic hair distribution was recorded as male-typical Tanner stage ratings [14]. For females, cosmetic appearance of the external genitalia was evaluated and included vaginal depth measured with graduated vaginal dilators and reported in cm. The proper placement of the vaginal introitus on the perineum was noted. Clitoral length was also measured and reported in cm. Similar to the males, cosmetic appearance of the genitalia was rated as good if all three measures were normal, fair if any one measure was abnormal, and poor if two or more measures were abnormal. Age at gonadectomy, amount of feminization of the external genitalia, and type and timing of vaginoplasty were obtained from surgical records, and then verified during physical examination. Breast size was measured as described for males. Pubic hair distribution was recorded as female-typical Tanner stage ratings [14]. Participants were asked about their endocrine treatment from childhood to the time of participation. Responses were compared to information obtained from medical charts and from the question-

Micropenis Follow-Up

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Fig. 1. Adult stretched penile length (cm) for patients with congenital

micropenis reared male. Darkened circles represent men not receiving testosterone replacement at time of participation. The men who did not receive testosterone, but who had a penile length in the normal range produced sufficient testosterone endogenously. Shaded area represents the mean B 2 SDs for stretched penile length based on Schonfeld and Beebe [16].

Fig. 2. Stretched penile length at first presentation (SD) in relation to final stretched penile length in adulthood (cm). There was no significant association between penile length at first presentation and penile length in adulthood.

Results

Males Physical Measures. In all of the men, penile length was less than the mean (13.3 B 1.6 cm) established by Schonfeld [16]. In 5 men, penile length was between the mean and 2 SDs, in 3 men length was at 2 SDs and in 5 others length was below 2 SDs (fig. 1). Among the 5 men with

penile length below 2 SDs, 3 were noncompliant with testosterone treatment in adulthood (treatment was discontinued at ages 19 0/12, 19 4/12 and 14 5/12 for ID 6, 9 and 10, respectively). Penile length at first presentation was not related to final length for the men receiving adult testosterone therapy at the time of study participation (R2 = 0.195, p = 0.23) (fig. 2). A larger sample size may be necessary to identify an association if one exists. Men treated with testosterone improved their penile length compared to their initial presentation. Absence of testosterone treatment in adulthood results in a shorter adult penile length whatever the etiology of micropenis, as indicated by ID 6, 9 and 10 (table 2). Of the 9 men treated with testosterone from adolescence to the time of study participation, 3 were also treated in infancy (ID 4, 5 and 13). One (ID 12) produced his own testosterone endogenously during infancy. The adult penile lengths of these 4 men showed a trend toward longer final length compared to those men whose treatment was initiated later in development (p = 0.166). Finally, the 3 participants affected by panhypopituitarism (ID 79) received growth hormone, thyroid hormone and cortisol replacement in addition to androgen therapy throughout their treatment history. In addition to having a small penis, 6 participants (46%) had small testes (3 had prostheses) and poor quality of their corpora, both of which contributed to fair or poor cosmetic appearance of the external genitalia in these men (table 2). Seven men had gynecomastia and one a mastectomy. Gynecomastia occurs in males who present with abnormally high concentrations of estrogen, or when testosterone concentrations do not reach adult values. None of the men in this study had an elevated estradiol concentration at the time of participation. It is likely that an adult history of inadequate testosterone replacement contributed to the gynecomastia observed in these men, however we could not confirm this based on the medical records available to us. Tanner rating for pubic hair growth was 3.6 (range 15). Presence of the prostate gland was demonstrated for all men who completed this portion of the physical examination (table 3). Genito-Sexual Function. One man refused to answer questions about sexual function and body image. Six men (50%) were satisfied with their genitalia regarding sexual functioning. The remaining 6 reported dissatisfaction with their genitalia. Seven men (58%) rated their erections to be good, and 5 (42%) to be fair. All respondents reported the ability to ejaculate. Libido was reported as

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Table 2. Stretched penile length and SD for age of males during their first JHU Pediatric Endocrine visit, during adulthood and physician-rated cosmetic appearance of the genitalia in adulthood

Subject No.

Childhood age years 6 15 14 0 5/12 0 9/12 14 2 3 0 1/12 3 0 11/12 3 0 6/12 penile length SD cm 3.5 4.0 3.5 1.0 1.5 2.5 2.0 2.0 1.5 2.0 1.0 1.0 2.0 2.7 2.3 2.8 3.6 3.5 3.7 3.3 3.4 3.0 3.5 4.1 4.5 2.9

Adulthood penile length cm 12.0 11.0 10.0 10.0 13.0 2.4 12.2 8.0 6.5 5.5 7.0 12.2 10.0 SD genital appearance good good good good good poor good fair fair fair poor good poor

1 2 3 4 5 6* 7 8 9* 10* 11 12 13

0.8 1.4 2.0 2.0 0.2 6.8 0.7 3.3 4.2 4.9 3.9 0.7 2.0

* Indicates subject was not producing or receiving testosterone at the time of study participation.

Table 3. History of testosterone replacement, presence of gynecomastia and size of prostate gland for male partici-

pants Subject No. 1 2 3 4 5 6 7 8 9 10 11 12* 13 Testosterone Rx infancy no no no yes yes no no no no no no yes yes adolescence yes yes yes yes yes no yes yes yes yes yes yes yes presently yes yes yes yes yes no yes yes no no yes yes yes Gynecomastia (L and R) 12 ! 10 cm 10 ! 10 cm surgical removal no 12 ! 10 cm 18 ! 18 cm 18 ! 15 cm no no 14 ! 12 cm no 11 ! 9 cm no Prostate weight, g 10 15 !5 10 not done !5 !5 !5 !5 10 !5 10 not done

* Indicates normal, endogenous production of testosterone without additional testosterone replacement.

average or better by 8 (67%) men, and no man reported having an absent libido. Body Image. Mean self-rated score (scale: 1 mainly satisfied ... 5 mainly dissatisfied) was 2.6 (range 15). Contributing to dissatisfaction was having a small penis (n = 8 or 66%), unusual appearing genitalia (n = 8 or 66%), inadequate body hair (n = 6 or 50%), gynecomastia (n = 4 or

33%), young appearance (n = 4 or 33%) and short stature (n = 1 or 8%). Sexual Orientation. Ten men (77%) reported a male heterosexual orientation, 1 (8%) a male homosexual orientation, and 2 (15%) a bisexual orientation. Marriage and Parenthood. Six men (46%) were married, one was a parent via adoption and one was dating.

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Table 4. History of childhood feminization, vaginoplasty and adult physical status for patients with congenital micropenis raised female

Subject No.

Childhood surgical feminization gender re-assignment years 1 3/12 penile length cm, SD 2.0, 2.9 type of external feminizing surgery bilateral gonadectomy clitoral recession bilateral gonadectomy clitoral amputation bilateral gonadectomy clitoral amputation bilateral gonadectomy clitoral recession bilateral gonadectomy clitoral recession

Adult physical status clitoral length cm 2 vaginal length cm 7 age at vaginoplasty (type) 17 years (skin graft) none

14

15

3 3/12

1.5, 4.0

16

1 10/12

1.5, 3.0

none

17

1 6/12

1.0, 4.6

1.5

18 years (skin graft) 19, 22 (skin graft, colonic)

18

1 6/12

1.5, 3.5

1.5

12

Satisfaction with Sex of Rearing. Twelve men (92%) were satisfied with their male gender, one was dissatisfied. When asked if they had ever doubted their gender, 12 men replied no and one replied yes. This response was from the same man who reported dissatisfaction with his sex of rearing. Contrary to expectation, the dissatisfied man was compliant with his testosterone treatment regimen throughout childhood and adulthood. Females Physical Measures. Three subjects were reported to have no corpora at their first clinic visit early in life. However, stretched penile lengths obtained at the age of sex reassignment prior to surgery for females did not differ from those of patients reared male (p = 0.5). Feminization of the external genitalia occurred between 1 3/12 and 3 3/12 years of age. In three cases, clitoral recession, and in 2 clitoral amputation was performed (table 4). Three women had a skin graft vaginoplasty. One required an additional colonic procedure. Vaginal lengths for these women were 7, 7 and 12 cm. Mean vaginal length for the general population of women ranges between 7 and 11 cm according to various reports [1719]. One woman who had not had vaginoplasty at the time of participation is now considering the procedure. The remaining woman is

adamant in her refusal of surgery. The 2 women who avoided vaginoplasty also received clitoral amputation. Factors contributing to a fair appearance of female external genitalia in 4 women (80%) included placement of the vaginal introitus too posteriorly, unusual appearance of the vaginal introitus and an absent clitoris or labia minora. One woman received a rating of good on the appearance of her genitalia. Average breast size for the women was (L) 14 ! 13 cm, (R) 14.5 ! 13.75 cm (range 9 ! 8 to 17 ! 16 cm). Pubic hair was rated at Tanner stage 45 for 4 of the women, and the 1 remaining woman had no axillary or pubic hair. This womans lack of sexual hair was attributed to untreated panhypopituitarism; as no androgen receptor gene mutation was identified when tested. At the time of participation, 4 of 5 women were receiving estrogen replacement. All 4 women reported compliance. The 2 women with panhypopituitarism (ID 14, 15) also received growth hormone, thyroid hormone and cortisol replacement. One woman had never been prescribed female hormone replacement as a result of her discontinuing any medical treatment. Genito-Sexual Function. One woman was satisfied with her genitalia, and the remaining 4 women were dissatisfied. Three women rated their libido as average, and

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the 2 who had a complete clitoral amputation and no vagina rated their libido as absent. The 3 with average libido reported the ability to experience orgasm; those who rated their libido as absent never experienced an orgasm. Body Image. Four of the 5 women were satisfied with their appearance, one was dissatisfied. However, even among the women who were satisfied, characteristics that were considered problematic included: scarring (n = 3), unusual appearing labia (n = 2), breasts too small (n = 1), breasts too large (n = 1), excessive or inadequate body hair (n = 2). Sexual Orientation. Three women reported a female heterosexual orientation, 1 reported bisexual attraction and fantasy and 1 no sexual attraction or fantasies. Of these 5 women, 3 reported female heterosexual experiences and 2 reported no experiences. Marriage and Parenthood. None of the women was married or a parent at the time of participation. Three women (60%) were dating. Satisfaction with Sex of Rearing. All were satisfied with their female rearing. Four women (80%) reported having questioned their sex of rearing in the past. Comparisons between Males and Females Satisfaction with body appearance did not differ between groups (p = 0.142), nor did satisfaction with genitalia (p = 0.111) or sex of rearing (p = 0.499). The number of participants was limited. Therefore, power to detect differences between groups is low. Femininity and Masculinity. A significant association with sex of rearing on masculinity and femininity was observed (fig. 3). Males were more masculine than females (F(1,39) = 15.033, p ! 0.0005), and females were more feminine than males (F(1,39) = 63.873, p ! 0.0001). Opinion of Treatment. For males, surgical procedures could include orchidopexy, implantation of prosthetic testes and reduction of gynecomastia, with the last two occurring post-pubertally. Males who favored patient consent for surgical procedures (45%) equaled those who did not (45%). One man responded that this is an issue to be decided case by case. Because surgical procedures experienced by men generally occur in late childhood or adolescence, opinions about surgical procedures in infancy were not considered. For females, surgical procedures include gonadectomy, feminization of the genitalia and vaginoplasty. Four women (80%) reported that patient consent for certain surgical procedures should not be required. These women believed that optimal timing for feminizing surgeries of

Fig. 3. Mean B SEM masculinity and fem-

ininity scores for male and female participants. Males rated themselves as significantly more masculine than females, and females as significantly more feminine than males.

the external genitalia and gonadectomy was during infancy with parental consent, but that vaginoplasty was best performed during adulthood with patient consent. One woman believed that optimal timing for all surgeries was during adolescence or later, and that patient consent should be required for all procedures. Opinion of Third Sex. Recommendations for several sexes, including but not limited to male, female and hermaphrodite have been published [20]. None of the participants believed that a third sex category was appropriate for individuals born with a micropenis. Psychological Treatment. The majority of men (n = 12) and women (n = 4) received counseling for their medical condition. Among men, genito-sexual difficulties (n = 4 or 33%) and severe teasing (n = 2 or 17%) were reasons for counseling. Two women (40%) reported sexual difficulties and 2 (40%) reported severe teasing as reasons for counseling. Knowledge of Medical History. Eight men (67%) and 4 women (80%) retained a good understanding of their medical condition.

Discussion

Eighteen patients, 13 raised male and 5 raised female, participated in the present study. In light of this small sample size, statistical power to detect differences between genders or associations between variables was low.

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Additionally, participants may not represent the entire population of patients with congenital micropenis. Thus, statistical tests that failed to reach significance must be considered within these limitations. Subjects Reared Male For these subjects, expectations for adult, stretched penile length were of great concern. All men receiving testosterone therapy at the time of study participation had improved their number of SDs below the mean for penile length when compared to childhood. However, improvement was variable. The 5 testosterone-treated men with Kallmanns syndrome (table 2, ID 15) showed great amelioration in their penile length by adulthood, as they all attained final penile lengths within the normal range (range 1013 cm). This finding suggests that it is best to rear patients with Kallmanns syndrome as male if testosterone therapy is provided. For the 7 men with micropenis due to etiologies other than Kallmanns syndrome (table 2, ID 713), final penile lengths ranged from 5.5 to 12.2 cm, with 4 men failing to attain a stretched penile length within the normal range. However, 3 of these men were not receiving testosterone at the time of penile measurement, and subsequently had low levels of testosterone. Testosterone treatment initiated in infancy showed a trend toward better final penile length when compared to treatment initiated later in development, provided subjects were compliant with their life-long hormone therapy. In addition to micropenis, male participants presented additional features of major concern to them. Eight had gynecomastia (1 had plastic surgery for breast reduction). Many of the men were dissatisfied with their amount of sexual hair despite testosterone therapy; this was particularly true of facial hair. All of the men presented small testes as a combined result of their original syndrome and also exogenous androgen administration. Three men opted for testicular prostheses. Additionally, men had to deal with the problem of infertility, an important psychosocial problem for most participants. While fertility treatment may be theoretically possible for men with gonadotropin deficiency, the clinical application of such a therapy has yet to be applied. Finally, men with panhypopituitarism require pituitary hormone replacement therapy for life. Subjects Reared Female For these women, cosmetic outcome of feminizing genital reconstruction was of great concern. Two women

had no clitoris or vagina, the other 3 had a clitoris that was 1.52 cm in length, and a constructed vagina that measured 712 cm in length. Common features of concern for the women included genital scarring, unusual-appearing labia and a vaginal introitus that was placed too posteriorly. Similar to the patients reared male, patients reared female face the need for sex hormone replacement therapy and infertility. In addition, 2 women had to deal with additional medical treatment specific to panhypopituitarism. Adjustment to Micropenis and Its Treatment It is clear that whether reared male or female, all subjects had to adjust not only to problems related to their genitalia, but also to problems related to the underlying cause of their micropenis. Such adjustments have required patients to make compromises with their lives in terms of romance and sexual function. It is to the credit of these patients to have dealt with these compromises as well as they reportedly did. Overall, patients raised male or female were satisfied with their assigned gender in adulthood. However, dissatisfaction with sexual function, cosmetic appearance and stigmatization were reported by both genders. Additional problems are suggested by the fact that 3 men refused adult testosterone therapy, 1 man would not answer questions pertaining to his sex life, and 2 women had not agreed to vaginal construction. The majority of men (n = 12) and women (n = 4) received counseling for their medical condition. For men, genito-sexual difficulties (n = 4) and severe teasing (n = 2) were reasons for obtaining counseling. Two women reported genito-sexual difficulties and two reported severe teasing as reasons for counseling. Our experience with this study shows that patients reared as male or female require follow-up that includes psychological support and education about the condition of micropenis in addition to hormonal and surgical treatment by a medical team. Choice of Gender Our investigation has shown that: (1) Life-long problems were identified for both males and females. (2) Despite these problems, subjects reared male were masculine and those reared female were feminine. Importantly, the majority of subjects were satisfied with their sex of rearing, and none was interested in changing sex. These results support sex of rearing, as opposed to androgen exposure that is sufficient for the formation of a penile urethra, as a prime influence on human gender identity

10

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development. (3) The data on patients with Kallmanns syndrome supports rearing these subjects as males, confirming the observation of Bin-Abbas et al. [9]. For congenital micropenis associated with other endocrinopathy, female gender assignment has proven compatible with reasonable adjustment in adulthood in some cases. This is illustrated by satisfaction with sex of rearing and physical

appearance, and to a lesser extent sexual function, reported by the women in this study. That said, the success of male gender development and genito-sexual function observed in this study, as well as the difficulties associated with feminizing surgery, leads us to conclude that male gender assignment is preferable for most infants with congenital micropenis.

References
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