Article

Systemic effects of transdermal testosterone for the treatment of microphallus in children

Authors:
If you want to read the PDF, try requesting it from the authors.

Abstract

To elucidate the metabolic effects of topical testosterone for the treatment of microphallus in children. We administered 5% testosterone ointment to 50 prepubertal boys for the treatment of microphallus, allowing us to observe its metabolic effect on plasma concentrations of testosterone as a marker of transdermally absorbed testosterone, insulin-like growth factor (IGF)-I as a marker of growth hormone secretion status, and osteocalcin as a marker of bone metabolic turnover. Transdermal application of testosterone for 30 days at a dose that affects penile growth increased mean (+/-SD) plasma testosterone concentrations from 7.5+/-5.1 to 31.0+/-8.2 ng/dL (pre- vs. post-treatment, respectively; P<0.01). This was associated with a slight but statistically significant elevation of IGF-I concentrations (117.2+/-76.9 vs. 154.4+/-81.5 ng/mL; P<0.05). No significant change in osteocalcin levels was found. When using testosterone ointment as a treatment for microphallus, it should be borne in mind that this application has systemic effects.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... It has been documented that the development, growth, and maintenance of penile-tissue function is an androgen-dependent process [10]. Clinical and preclinical studies have suggested that abnormalities in the AR, deficiency in 5α-reductase activity, or reduced plasma androgen levels due to the impairment of synthesis of testicular or adrenal androgens, leads to the development of a microphallus [55][56][57][58][59][60][61][62][63]. Grino et al. [64] postulated that children with impaired AR function develop micropenises. ...
... Gad et al. [60] showed that 5α-reductase activity correlates with penile length in intersex cases and suggested that 5α-reductase deficiencies may lead to the development of a micropenis. Androgen therapy of children with microphalli resulted in penile growth and marked enlargement of an abnormally small penis, achieved either by local application or systemic administration of testosterone [55][56][57][58][61][62][63][64][65]. It is worth noting that, in the early part of the steroid biosynthetic chain, deficiency of the enzyme 17,20-lyase in both gonads and adrenal glands resulted in the development of a microphallus. ...
Article
Androgens are deemed critical for penile‐tissue development, growth, and maintenance of erectile function, however, their role in erection, especially in humans, remains controversial. In this review, we summarize information from clinical and animal model studies to provide a comprehensive and rational argument for the role of androgens, or lack thereof, on penile erection ability in humans. The goal of this review is to present the clinical and preclinical evidence available in the literature with regard to testosterone and erectile physiology and engage the reader in this discussion. Ultimately, each reader will have to form his or her own conclusions based on the existing evidence. Traish AM, and Guay AT. Are androgens critical for penile erections in humans? Examining the clinical and preclinical evidence. J Sex Med 2006;3:382–407 In humans, androgen‐deficiency manifestations are noted in clinical situations such as: (i) inadequate development of the penis; and (ii) loss of erectile function in prostate cancer and benign prostatic hyperplasia patients managed with medical or surgical castration or antiandrogen therapy. Androgen treatment causes: (i) improvement in sexual function in hypogonadal patients treated with androgen supplementation; (ii) improvement in nocturnal penile tumescence in hypogonadal patients treated with androgens; (iii) improvement in erectile function with androgen supplementation in patients who did not respond to phosphodiesterase type 5 inhibitor therapy initially; and (iv) improvement in the well‐being, mood, energy, and sexual function in aging men who have testosterone deficiency treated with androgen therapy. In contrast to animals, especially rodents in which the adrenal cortex does not synthesize androgens, the human adrenal is a source of peripherally circulating androgen precursors, thus, complete androgen insufficiency may not be observed in men at a younger age. Furthermore, in light of the concept that a threshold of androgen levels exists in animals and humans below which sexual function is diminished, further contributes to the complexity of understanding androgens role in erections, especially in humans. Nevertheless, based on the preclinical and clinical data available in the literature, to date, we infer that androgens play a critical role in maintaining erectile physiology in humans.
... Topical testosterone application is effective during infancy. Arisaka et al (34) demonstrated increases in penile lengths in 50 infants and children aged between 5 months and 8 years, by administering 5% testosterone cream for a duration of 30 days. Testosterone that is absorbed transdermally was shown to stimulate growth hormone (GH) secretion from the pituitary gland and promote bone growth by increasing insulin-like growth factor-1 production. ...
... Testosterone that is absorbed transdermally was shown to stimulate growth hormone (GH) secretion from the pituitary gland and promote bone growth by increasing insulin-like growth factor-1 production. Therefore, it can be said that longterm dermal application of testosterone promotes skeletal growth, as well as penile growth (34). ...
Article
Full-text available
Micropenis is a medical diagnosis based on correct measurement of length. If stretched penile length is below the value corresponding to - 2.5 standard deviation of the mean in a patient with normal internal and external male genitalia, a diagnosis of micropenis is considered. Micropenis can be caused by a variety of factors including structural or hormonal defects of the hypothalamic-pituitary-gonadal axis. It can also be a component of a number of congenital syndromes. For the etiological evaluation, endocrinologic tests are important. This article reviews the etiology, diagnosis, treatment and management of micropenis. Conflict of interest:None declared.
... Transdermally absorbed testosterone also has been shown to stimulate the secretion of growth hormone from the pituitary gland, which increases the production of insulin like growth factor-I, a factor that promotes bone growth. Longterm administration has the potential to enhance penile length as well as skeletal growth [20]. If the micropenis does not achieve adequate length through medical intervention one may turn to surgical options after all other treatments have been exhausted. ...
... 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 insulinlike growth factor-I, a factor that promotes bone growth. ...
Article
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.
... It has been proposed that endogenous sex-steroid hormones stimulate GH and IGF-I synthesis, as supported by observations of minimal or no pubertal growth spurt in patients with hypogonadism, and that patients with both true precocious puberty and GH deficiency can exhibit a growth spurt indistinguishable from that of children with true precocious puberty and normal GH secretion 457 . Additionally, both oral and trans-dermal exogenous androgens 458,459 or androgenic progestins 460,461 cause elevations in circulating IGF-I. The effect of exogenous estrogens depends on the route of administration. ...
... Treatment is based on testosterone supplementation administered for a short period to evaluate penile response. There is no consensus on the dose, method of administration or duration of testosterone therapy for micropenis 13 . Hatipoglu et al. 12 suggested that administration could be by intramuscular injection or topical application. ...
Article
Micropênis refere-se a um pênis normalmente formado, anormalmente pequeno, com um comprimento inferior a 2,5 desvios-padrão (DP) abaixo da média da idade ou do estágio de desenvolvimento sexual. Pacientes com micropênis verdadeiro geralmente apresentam cariótipo 46, XY, associado a gônadas masculinas normalmente localizadas, sem qualquer sinal de outras malformações penianas. O comprimento do pênis é medido a partir do ponto onde o pênis encontra o osso púbico até a ponta distal da glande no alongamento máximo, comprimindo qualquer gordura sobre a área suprapúbica. O diagnóstico diferencial inclui buried penis - penis embutido (incapacidade de expor adequadamente o pênis, devido a uma severa estomia associada à diminuição do comprimento da pele do pênis, que retém o eixo dentro da cavidade prepucial) e obesidade com excesso de gordura na região supra púbica. As causas do micropênis congênito ou verdadeiro podem ser divididas em três grandes grupos: hipogonadismo hipogonadotrófico (falência hipofisária / hipotalâmica), hipogonadismo hipergonadotrófico (insuficiência testicular primária) e idiopático (associado a um eixo hipotálamo-hipófise-testicular funcional). O tratamento clínico é baseado na terapia com testosterona. As opções de tratamento cirúrgico são usadas após falha do aumento do pênis com terapia de testosterona e incluem alongamento do pênis, aspiração de gordura suprapúbica e, eventualmente, neofaloplastia.
... In some countries, testosterone is available for percutaneous treatment: 0.2 g of 5% testosterone cream (i.e. 10 mg of testosterone) applied onto the phallus daily for 1 month showed efficacy (9-mm increase in penile length) and safe (no significant advancement in bone age). 86,87 DHT gels, which are available in certain countries, may be even more efficacious in patients with DSD, and especially in those with 5α-reductase deficiency. 64,88-91 Treatment consists of gel application onto the penis twice a day at a daily dose of 0.1-0.3 ...
Article
Full-text available
Clinical manifestations and the need for treatment varies according to age in males with hypogonadism. Early foetal-onset hypogonadism results in disorders of sex development (DSD) presenting with undervirilised genitalia whereas hypogonadism established later in foetal life presents with micropenis, cryptorchidism and/or micro-orchidism. After the period of neonatal activation of the gonadal axis has waned, the diagnosis of hypogonadism is challenging because androgen deficiency is not apparent until the age of puberty. Then, the differential diagnosis between constitutional delay of puberty and central hypogonadism may be difficult. During infancy and childhood, treatment is usually sought because of micropenis and/or cryptorchidism, whereas lack of pubertal development and relative short stature are the main complaints in teenagers. Testosterone therapy has been the standard, although off-label, in the vast majority of cases. However, more recently alternative therapies have been tested: aromatase inhibitors to induce the hypothalamic-pituitary-testicular axis in boys with constitutional delay of puberty and replacement with GnRH or gonadotrophins in those with central hypogonadism. Furthermore, follicle-stimulating hormone (FSH) priming prior to hCG or luteinizing hormone (LH) treatment seems effective to induce an enhanced testicular enlargement. Although the rationale for gonadotrophin or GnRH treatment is based on mimicking normal physiology, long-term results are still needed to assess their impact on adult fertility.
Article
Full-text available
Testosterone replacement therapy (TRT) is routinely prescribed in adolescent males with constitutional delay of growth and puberty (CDGP) or hypogonadism. With many new testosterone (T) formulations entering the market targeted for adults, we review current evidence and TRT options for adolescents and identify areas of unmet needs. We searched PubMed for articles (in English) on testosterone therapy, androgens, adolescence, and puberty in humans. The results indicate that short-term use of T enanthate (TE) or oral T undecanoate is safe and effective in inducing puberty and increasing growth in males with CDGP. Reassuring evidence is emerging on the use of transdermal T to induce and maintain puberty. Long-term safety and efficacy of TRT for puberty completion and maintenance have not been established. Current TRT regimens are based on consensus and expert opinion, while evidence-based guidelines are lacking. Limited guidance exists on when and how T should be administered and optimal strategies for monitoring therapy once it is initiated. Only TE and T pellets are FDA approved for use in adolescent males in the US. Despite the introduction of a wide variety of new T formulations, they are designed for adults, and their metered doses are difficult to titrate in adolescents. In conclusion, TRT in adolescent males is hindered by lack of long-term safety and efficacy data and limited options approved for use in this population. Additional research is needed to identify the route, dose, duration, and optimal timing for TRT in adolescents requiring androgen therapy.
Article
Full-text available
During adolescence, androgens are responsible for the development of secondary sexual characteristics, pubertal growth, and the anabolic effects on bone and muscle mass. Testosterone is the most abundant testicular androgen, but some effects are mediated by its conversion to the more potent androgen dihydrotestosterone (DHT) or to estradiol. Androgen deficiency, requiring replacement therapy, may occur due to a primary testicular failure or secondary to a hypothalamic–pituitary disorder. A very frequent condition characterized by a late activation of the gonadal axis that may also need androgen treatment is constitutional delay of puberty. Of the several testosterone or DHT formulations commercially available, very few are employed, and none is marketed for its use in adolescents. The most frequently used androgen therapy is based on the intramuscular administration of testosterone enanthate or cypionate every 3 to 4 weeks, with initially low doses. These are progressively increased during several months or years, in order to mimic the physiology of puberty, until adult doses are attained. Scarce experience exists with oral or transdermal formulations. Preparations containing DHT, which are not widely available, are preferred in specific conditions. Oxandrolone, a non-aromatizable drug with higher anabolic than androgenic effects, has been used in adolescents with preserved testosterone production, like Klinefelter syndrome, with positive effects on cardiometabolic health and visual, motor, and psychosocial functions. The usual protocols applied for androgen therapy in boys and adolescents are discussed.
Article
Full-text available
We provide an in-depth review of the role of androgens in male maturation and development from the fetal stage through adolescence into emerging adulthood and discuss the treatment of disorders of androgen production throughout these time periods. Testosterone, the primary androgen produced by males, has both anabolic and androgenic effects. Androgen exposure induces virilization and anabolic body composition changes during fetal development, influences growth and virilization during infancy and stimulates development of secondary sexual characteristics, growth acceleration, bone mass accrual, and alterations of body composition during puberty. Disorders of androgen production may be subdivided into hypo- or hypergonadotropic hypogonadism. Hypogonadotropic hypogonadism may be congenital or acquired, resulting from cranial radiation or trauma, although there are many less common causes. Hypergonadotropic hypogonadism occurs in males with Klinefelter syndrome and may occur in response to pelvic radiation, certain chemotherapeutic agents, and other less common causes. These disorders all require testosterone replacement therapy during pubertal maturation and many require life-long replacement. Androgen (or gonadotropin) therapy is clearly beneficial in those with persistent hypogonadism and self-limited delayed puberty and is now widely used in transgender male adolescents. With more widespread use and newer formulations approved for adults, data from long-term randomized placebo-controlled trials are needed to enable pediatricians to identify the optimal age of initiation, route of administration and dosing frequency to address the unique needs of their patients.
Chapter
One of the most commonly encountered problems in the practice of sexual medicine has been the serious concern men frequently have about penis size starting from puberty to adulthood. Men are extremely anxious about their penile length [1]. The penis is credited with the dual function of coitus and micturition. In biology, the ability to transfer sperms denotes maleness of an organism. To a man, no matter what his socioeconomic status is, the size of the penis always matters [2].
Article
Male production of testosterone is crucial for the development of a wide range of functions. External and internal genitalia formation, secondary sexual characteristics, spermatogenesis, growth velocity, bone mass density, psychosocial maturation, and metabolic and cardiovascular profiles are closely dependent on testosterone exposure. Disorders in androgen production can present during all life-stages, including childhood and adolescence, and testosterone therapy (TT) is in many cases the only treatment that can correct the underlying deficit. TT is controversial in the pediatric population as hypoandrogenism is difficult to classify and diagnose in these age groups, and standardized protocols of treatment and monitorization are still lacking. In pediatric patients, hypogonadism can be central, primary, or a combination of both. Testosterone preparations are typically designed for adults’ TT, and providers need to be aware of the advantages and disadvantages of these formulations, especially cognizant of supratherapeutic dosing. Monitoring of testosterone levels in boys on TT should be tailored to the individual patient and based on the anticipated duration of therapy. Although clinical consensus is lacking, an approximation of the current challenges and common practices in pediatric hypoandrogenism could help elucidate the broad spectrum of pathologies that lie behind this single hormone deficiency with wide-ranging implications.
Chapter
An inconspicuous penis refers to a group of conditions that the penis appears to be small but the shaft can be normal or abnormal in size. It could be a source of constant concern for both parents and children. The term “inconspicuous penis” was first used in the literature by Bergeson et al. [1] in 1993. This could be secondary to short penile shaft often termed as micropenis. But more commonly, this inconspicuous appearance is secondary to other causes ranging from congenital conditions such as penoscrotal webbing or megaprepuce, developmental conditions like prepubic adiposity that overhangs the penis, and iatrogenic causes like trapped penis after adhesions secondary to circumcision [2]. However up to now there is still confusion by defining of inconspicuous penis in the literature review and in the clinical practice [3–15].
Article
Aim. Hypospadias is one of the most common malformation in childhood. Testosterone (TT) ointment before surgery seems to be useful to enlarge penile size to facilitate urethroplasty. The aim of this study was to evaluate and to report the useful of TT treatment. Methods. We retrospectively reviewed the medical charts of patients who underwent hypospadias repair between June 1999 and June 2009. Patients were divided into two groups: patients which received testosterone oinment before surgery and patients that underwent surgery without testosterone treatment. Inclusion criteria were created. We evaluated the complication rate between groups (cosmetic and functional aspects) and the secondary effect of treatment. Results. During the study period 53 patients were considered for the study (20 patients received TT ointment). After surgery cosmetic and functional results between groups were similar without statistical differences; patients with testosterone treatment before surgery had a similar complication respect to the others. (p<0.05). Conclusion. Testosterone treatment seems to be useful to enlarge the penile size to facilitate surgeon during urethroplasy; this treatment is not associated with surgical complications.
Chapter
Full-text available
Article
Full-text available
In the newborn, penile length is determined by a number of androgen dependent and independent factors. The current literature suggests that there are inter-racial differences in stretched penile length in the newborn and although congenital micropenis should be defined as a stretched penile length of less than 2.5SDS of the mean for the corresponding population and gestation, a pragmatic approach would be to evaluate all boys with a stretched penile length below 2 cm, as congenital micropenis can be a marker for a wide range of endocrine conditions. However, it remains unclear as to whether the state of micropenis, itself, is associated with any long-term consequences. There is a lack of systematic studies comparing the impact of different therapeutic options on long-term outcomes, in terms of genital appearance, quality of life and sexual satisfaction. To date, research has been hampered by a small sample size and inclusion of a wide range of heterogeneous diagnoses; for these reasons, condition specific outcomes have been difficult to compare between studies. Lastly, there is a need for a greater collaborative effort in collecting standardized data so that all real-world or experimental interventions performed at an early age can be studied systematically into adulthood.
Article
Full-text available
The risk of some cancers is positively associated with body weight, which may influence circulating levels of sex-steroid hormones, insulin and IGF-I. Interrelationships between these hormones and the associations with adiposity were evaluated in healthy women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). A cross-sectional analysis was performed on anthropometric and hormonal data from 743 pre- and 1217 postmenopausal women. Body mass index (BMI) and waist circumference were used as indicators of adiposity. C-peptide, Insulin Growth Factor (IGF)-I, Insulin Growth Factor binding protein (IGFBP)-3, androgens, estrogens and sex hormone binding globulin (SHBG) were measured by immunoassays; free sex steroid concentrations were calculated. BMI and waist circumference were positively correlated with estrogens in postmenopausal women and with C-peptide, free testosterone and inversely with SHBG in all women. C-peptide and IGF-I were inversely correlated with SHBG, and positively with free sex steroids in postmenopausal women. IGF-I was positively associated with postmenopausal estrogens and androgen concentrations in all women. Sex-steroid concentrations appear to be regulated along several axes. Adiposity correlated directly with estrogens in postmenopausal women and with insulin, resulting in lower SHBG and increased levels of free sex steroids. Independent of adiposity and insulin, IGF-I was associated with decreased SHBG levels, and increased concentrations of androgens and postmenopausal estrogens.
Article
Full-text available
Excess weight has been associated with increased risk of cancer at several organ sites. In part, this effect may be modulated through alterations in the metabolism of sex steroids and IGF-I related peptides. The objectives of the study were to examine the association of body mass index (BMI) with circulating androgens (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)), estrogens (estrone and estradiol), sex hormone-binding globulin (SHBG), IGF-I and IGF-binding protein (IGFBP)-3, and the relationship between sex steroids, IGF-I and IGFBP-3. A cross-sectional analysis was performed using hormonal and questionnaire data of 620 healthy women (177 pre- and 443 post-menopausal). The laboratory measurements of the hormones of interest were available from two previous case-control studies on endogenous hormones and cancer risk. In the pre-menopausal group, BMI was not related to androgens and IGF-I. In the post-menopausal group, estrogens, testosterone and androstenedione increased with increasing BMI. The association with IGF-I was non-linear, with the highest mean concentrations observed in women with BMI between 24 and 25. In both pre- and post-menopausal subjects, IGFBP-3 did not vary across BMI categories and SHBG decreased with increasing BMI. As for the correlations between peptide and steroid hormones, in the post-menopausal group, IGF-I was positively related to androgens, inversely correlated with SHBG, and not correlated with estrogens. In the pre-menopausal group, similar but weaker correlations between IGF-I and androgens were observed. These observations offer evidence that obesity may influence the levels of endogenous sex-steroid and IGF-related hormones in the circulation, especially after menopause. Circulating IGF-I, androgens and SHBG appear to be related to each other in post-menopausal women.
Article
Hormonal therapy forms part of the treatment of every intersex condition. For some conditions, such as salt-wasting congenital adrenal hyperplasia, hormonal replacement therapy is life saving because hormones necessary for survival (cortisol and aldosterone) are replaced. In contrast, other hormones such as androgens or mineralocorticoids are secreted in excessive amounts in congenital adrenal hyperplasia due to an enzyme imbalance, and the role of hormonal therapy is to suppress the unwanted hormone excess by exerting negative feedback. For patients with one of the many causes of hypogonadism, sex hormone replacement therapy may be prescribed to stimulate sexual development: growth of a hypoplastic penis in a young boy, pubertal changes (male or female), psychosexual development, and adult sexual behavior. It has equally important and highly beneficial effects on bone mineral density. Hormonal therapy is also used to treat the unborn child. For the last 20 years, prenatal dexamethasone treatment administered to the pregnant woman has been used to prevent the development of ambiguous genitalia in females with 21-hydroxylase deficiency. Outcome studies show this treatment to be well tolerated and, in general, efficacious. Intersex conditions are, however, difficult to treat because they may intrinsically perturb complex aspects of the person’s gender identity, gender-role behavior, sexual orientation, sexual functioning, and psychologic adjustment. Furthermore, decisions made about the sex of an infant by doctors and parents do not always turn out to be correct; the person may grow up feeling uncertain about his or her gender identity, or worse still, harbor a sense of outrage about their life and treatment experiences. Such a person will have definite views about hormonal therapy when the time comes and skilful counseling will be needed. A vigorous debate about ethical aspects of current medical practices relating to intersex conditions has been waged for the last 7 years between certain patient advocacy organizations and the medical profession, and is expected to continue for some time. The quality of the debate will be improved by evidence. The results of a number of long-term follow-up studies have been published, and more are expected. The published studies show mixed, but mainly encouraging, results.
Article
• Topical application of 5% testosterone cream for 21 days resulted in enlargement of the penis to normal size for age in five boys with normal XY karyotype who had microphallus and hypopituitarism. In four patients, testosterone cream was applied locally to the penis and in one to an area of skin in the right axilla. Serum testosterone values rose from infantile levels before the start of therapy to normal adult male levels on the last day of treatment. All patients were receiving human growth hormone at the time of therapy with testosterone. No additional acceleration of linear growth and no advance in osseous maturation occurred during or after treatment. Application of testosterone locally for this brief period is a safe, effective, and simple means of stimulating phallic growth. Our findings suggest that topical testosterone causes penile growth predominantly through its systemic action. (Am J Dis Child 134:296-298, 1980)
Article
Japan has been experiencing ever more rapid socioeconomic development and changes in life style, especially for children, since the end of the Second World War. With these developments and changes the physical size of Japanese children has increased, but this secular trend has attained a plateau in the past 10 years.This phenomenon indicates that now Japanese children are growing in the nearly best conditions and their present physical conditions, for example, bone age, are thought to be specific and characteristic for the Japanese.The secular trend of linear growth since the end of the War is discussed, using the data of height in the annual reports of the school health program by the Ministry of Education, and the standardized TW2 bone age estimation method for Japanese children and adolescents is presented.
Article
We tested the efficacy of a thin flexible testosterone-impregnated membrane applied to the scrotum for the long term treatment of male hypogonadism. Ten men with primary hypogonadism were treated for 3 months (2 men) or 13 months (8 men). Serum testosterone concentrations increased in all 10 men, to within the normal range in 8. Serum dihydrotestosterone concentrations increased to supranormal values in all of the men, decreased to the normal range in 6, indicating the biological effectiveness of the testosterone in those subjects. Two men whose serum LH concentrations did not fall to normal had small or distorted scrotal surfaces. Seven of the 8 men whose serum testosterone concentrations became normal said that their hypogonadal symptoms were corrected by this treatment. We conclude that the transdermal administration of testosterone is an effective means of treating the majority of hypogonadal men who have a normal scrotum.
Article
Serum bone Gla-protein (BGP) was determined by RIA in 450 normal children (229 girls and 221 boys, aged 6-19 yr). Serum BGP concentrations changed in relation to age and sex with a pattern that resembles the height velocity curves for children. The increase in serum BGP occurred at the expected age of the growth spurt in both sexes, and the peak values occurred at the age of 12 yr in girls [mean, 49.2 +/- 5.6 (+/- SE) micrograms/L] and 14 yr in boys (64.0 +/- 6.3 micrograms/L). In the boys aged 10-14 yr and in the girls aged 9-12 yr, serum BGP correlated significantly with serum insulin-like growth factor I (IGF-I), serum testosterone, age and height. When the interrelationship was analyzed by means of partial correlation, with age held constant, serum BGP still correlated significantly with the other parameters, but when height was fixed there was only a correlation with serum IGF-I. In children with untreated central precocious puberty, the mean serum BGP concentration was significantly higher than in age-matched normal children [mean, 61.4 +/- 31.7 (+/- SD) vs. 29.0 +/- 10.3 micrograms/L; P less than 0.001]. Serum BGP values decreased significantly in these patients during 1 yr of treatment with a LHRH analog (buserelin) and cyproterone acetate. We conclude that serum BGP is a sensitive marker of bone growth in normal children and in children with increased growth velocity. Repeated measurements may provide useful information in the diagnosis and treatment of children with disturbances in bone turnover.
Article
Topical application of 5% testosterone cream for 21 days resulted in enlargement of the penis to normal size for age in five boys with normal XY karyotype who had microphallus and hypopituitarism. In four patients, testosterone cream was applied locally to the penis and in one to an area of skin in the right axilla. Serum testosterone values rose from infantile levels before the start of therapy to normal adult male levels on the last day of treatment. All patients were receiving human growth hormone at the time of therapy with testosterone. No additional acceleration of linear growth and no advance in osseous maturation occurred during or after treatment. Application of testosterone locally for this brief period is a safe, effective, and simple means of stimulating phallic growth. Our findings suggest that topical testosterone causes penile growth predominantly through its systemic action.
Article
To assess the influence of gonadal steroid testosterone (T) on bone mineral status in males during puberty, we observed the response of cortical bone density and serum biochemical parameters of bone metabolism to T treatment in 12 adolescent patients with hypogonadotropic hypogonadism (11 with both gonadotropin and growth hormone deficiency and one with isolated gonadotropin deficiency). The 12 patients aged 15 to 21 years (Tanner stage I to II) were divided into two groups: group 1 (n = 6) given T treatment for 2 consecutive years, and group 2 (n = 6) without T treatment for the first year and then with T treatment for the second year. Cortical bone density measured in the radius was less than the age-matched mean value for normal subjects in all 12 patients (groups 1 and 2) at the start of the study. Bone density in group 1 increased significantly during the 2-year T treatment period, but did not increase in group 2 during the first year without T treatment, although an increase was observed during the subsequent year with T treatment. Among circulating biochemical factors such as osteocalcin, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OHD), and 1,25-dihydroxyvitamin D [1,25-(OH)2D], only osteocalcin showed an increase in response to T treatment in both groups. Levels of insulin-like growth factor-I (IGF-I) remained consistently low and did not change in any patients except one with isolated gonadotropin deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Micropenis secondary to hypogonadotropic hypogonadism in the Sprague-Dawley rat was induced by either injection of supraphysiological doses of dihydrotestosterone to the timed pregnant dam on gestational days 16 and 17 or by long acting microspheres of the gonadotropic agonist, leuprolide acetate. Following the induction of micropenis the animals were treated with dihydrotestosterone beginning at either day 7, 28, 56 or 84 of life. Within the study populations all animals treated with dihydrotestosterone had phallic enlargement greater than untreated controls (p < 0.01). However, animals beginning treatment on day 7 or 28 had persistent microphallus (p < 0.01). In contrast, if hormonal therapy was initiated on day 56 or 84 the phallus became normal in length. Immunohistological studies for androgen receptor expression revealed that early androgen exposure accelerated the loss of androgen receptor protein from the penis during growth. These data suggest that prepubertal exposure of the penis to androgens may significantly reduce the eventual penile size of the hypogonadotropic hypogonadal micropenis.
Article
To investigate the efficacy of transdermal dihydrotestosterone therapy on 22 patients with microphallus, we applied dihydrotestosterone gel for 8 weeks to the external genitalia at daily doses of 12.5 mg. and 25 mg. for ages less than and older than 10 years, respectively. All patients were evaluated for penile and prostatic growth, pituitary-gonadal axis function, serum sex hormone binding globulin, lipid metabolism, hepatotoxicity, bone age and height velocity. All patients demonstrated growth of the penis during treatment. The mean increase rate (153%) in the first 4 weeks of treatment was higher than that (118%) of the second 4 weeks. Of importance is that responses were noted in 4 patients who had failed testosterone therapy for microphallus. The pituitary-gonadal axis was transiently suppressed during treatment, and serum sex hormone binding globulin and lipid metabolism were transiently affected during treatment. Serum alkaline phosphatase increased, mainly due to change of bone isoenzyme but bone ages and mean height velocity were not significantly affected. In conclusion, transdermal dihydrotestosterone therapy is an effective and relatively safe modality in the treatment of microphallus.
Article
This article has no abstract; the first 100 words appear below. The female steroid hormones, estrogen and progesterone, are prescribed widely by physicians, and their risks and benefits have been studied extensively. Although androgen preparations have been available for many years, most clinicians are less familiar with these hormones, and their risks and benefits have received less attention. The most common indication for androgen therapy is hypogonadism in men, but other potential uses of androgens are being explored. In addition, androgen abuse has become common among athletes and bodybuilders. It is therefore important that physicians be aware of the physiology, pharmacology, clinical indications, and adverse effects of androgens. Physiology The hypothalamus . . . Source Information From the Veterans Affairs Medical Center and the Department of Medicine, University of Washington School of Medicine, Seattle. Address reprint requests to Dr. Bagatell at Endocrinology (111), VA Medical Center, 1660 S. Columbian Way, Seattle, WA 98108.
Article
Five girls with multiple pituitary insufficiency and atrichia pubis, aged 14 to 22 years, were instructed to apply 5% testosterone undecanoate cream on the pubic area twice daily. Pubic hair development became noticeable between days 15 and 20 of treatment; after 4 months the pubic hair density was at Tanner stage II to III. Testosterone blood levels did not increase. This treatment corrects an aesthetic problem, which is of great concern to adolescents with pituitary insufficiency. (J PEDIATR 1996;128:284-5)
Article
Recent studies in the rat suggest that early exposure to exogenous testosterone accelerates the loss of androgen receptors and compromises eventual penile length. To determine whether this is true in men we measured adult penile length of patients treated in childhood for sexual precocity. We examined 21 men with sexual precocity due to true precocious puberty (12) or congenital adrenal hyperplasia (9) who had been followed at our institution since childhood. Penile lengths were compared with data from normal men. Mean stretched penile length plus or minus standard deviation was 12.7 +/- 2.6 cm. in all patients, 12.1 +/- 2.6 cm. in those with true precocious puberty and 13.6 +/- 1.6 cm. in those with congenital adrenal hyperplasia. These lengths were not significantly different from those of normal men (12.4 +/- 2.7 cm.). In contrast to findings in rats, exposure to endogenous testosterone during gestation and/or childhood does not reduce adult penile length in men. Thus, the use of testosterone to treat childhood genitourinary anomalies would likely not compromise mature penile size.
Article
Micropenis is commonly due to fetal testosterone deficiency. The clinical management of this form of micropenis has been contentious, with disagreement about the capacity of testosterone treatment to induce a functionally adequate adult penis. As a consequence, some clinicians recommend sex reversal of affected male infants. We studied 8 male subjects with micropenis secondary to congenital pituitary gonadotropin deficiency from infancy or childhood to maturity (ages 18 to 27 years). Four patients were treated with testosterone before 2 years of age (group I) and four between age 6 and 13 years (group II). At presentation, the mean penile length in group I was 1.1 cm (-4 SD; range, 0.5 to 1.5 cm) and in group II it was 2.7 cm (-3.4 SD; range, 1.5 to 3.5 cm). All patients received one or more courses of 3 intramuscular injections of testosterone enanthate (25 or 50 mg) at 4-week intervals in infancy or childhood. At the age of puberty the dose was gradually increased to 200 mg monthly and later to an adult replacement regimen. As adults, both group I and II had attained a mean final penile length of 10.3 cm 2.7 cm with a range of 8 to 14 cm (mean adult stretched penile length for Caucasians is 12.4 2.7 cm). Six of 8 men were sexually active, and all reported normal male gender identity and psychosocial behavior. We conclude that 1 or 2 short courses of testosterone therapy in infancy and childhood augment penile size into the normal range for age in boys with micropenis secondary to fetal testosterone deficiency; replacement therapy at the age of puberty results in an adult size penis within 2 SD of the mean. We found no clinical, psychologic, or physiologic indications to support conversion of affected male infants to girls. Further, the results of this study do not support the notion, derived from data in the rat, that testosterone treatment in infancy or childhood impairs penile growth in adolescence and compromises adult penile length.