Treatment of persistent pubertal gynecomastia with dihydrotestosterone heptanoate

Four boys with persistent pubertal gynecomastia were given intramuscular dihydrotestosterone heptanoate (DHT-hp) at 2 to 4-week intervals for 16 weeks. By the end of treatment, breast size in all four boys had decreased 67% to 78%. Initial plasma levels of gonadotropins, estradiol, testosterone, and dihydrotestosterone (DHT) were normal. Mean plasma DHT concentration rose with the injections of DHT-hp, and remained elevated throughout the treatment period. Estradiol, LH, FSH, and testosterone decreased during treatment, as did 24-hour urinary LH and FSH. No regrowth of breast tissue was observed 6 to 15 months after treatment, although hormone concentrations had returned to near pretreatment values by 2 months after the last injection. DHT-hp has potential to be an effective medical therapy for persistent pubertal gynecomastia.     

Evaluation of human chorionic gonadotropin stimulation tests in prepubertal and early pubertal boys

We evaluated the diagnostic significance of single versus repeated human chorionic gonadotropin (hCG) stimulation of testicular steroidogenesis in 25 boys (10 prepubertal group A; 15 early pubertal, group B) with suspected hypogonadism. All subjects received a single injection of hCG (5000 U/1.7 m²) and 1 month later, three repeated injections of 1500 U, one each on alternate days. In 19 out of the 25 boys, testosterone increased normally in both tests: from 20±6 to 156±82 ng/dl and from 107±105 to 615±293 ng/dl, following a single hCG injection, and from 30±19 to 439±298 ng/dl and from 94±55 to 826±272 ng/dl, following repeated injections in groups A and B, respectively. The difference between the tests was significant (P<0.01).Conclusion Single hCG injection used as a screening test in the evaluation of hypogonadism is conclusive when positive. Only when the initial test is negative may a repeated test help establish the diagnosis.     

Developmental processes in early adolescence: relationships between adolescent adjustment problems and chronologic age, pubertal stage, and puberty-related serum hormone levels

Relations between adolescent psychosocial adjustment problems and markers of biologic development, including chronologic age, pubertal status, and serum hormone levels, were examined in 56 normal boys and 52 normal girls, ages 9 to 14 years. Adolescent psychosocial adjustment was assessed by adolescent self-ratings of various aspects of self-image (Offer Self-Image Questionnaire for Adolescents) and parent ratings of adolescent behavior problems (Child Behavior Checklist). The pubertal status measure used in the analyses was Tanner genital stage for boys and Tanner breast stage for girls. The hormone measures, determined by radioimmunoassay, were serum levels of gonadotropins (luteinizing hormone and follicle stimulating hormone), sex steroids (testosterone and estradiol), and adrenal androgens (dehydroepiandrosterone and its sulfate, and androstenedione). The testosterone/estradiol ratio also was computed. Overall, findings were stronger, more consistent, and more generalized for boys than for girls. For boys, adjustment problems typically were associated with a multivariate profile that may be characteristic for later maturers: relatively low sex steroid levels, or lower pubertal stage, and relatively high adrenal androgen (androstenedione) levels, frequently in conjunction with higher chronologic age. Univariate relations predominated for girls; that is, associated with adjustment problems for girls were relatively high levels of gonadotropins, relatively low levels of dehydroepiandrosterone sulfate, and relatively high levels of androstenedione on their own or in conjunction with lower pubertal stage. Higher levels of androstenedione, a steroid particularly responsive to stress, were associated with adjustment problems in both boys and girls. This relation may reflect the stress of later maturation, which could result from environmental factors, such as adolescent self-comparisons with same-age peers, or endogenous effects of hormones.     

Pituitary-gonadal function in Klinefelter syndrome before and during puberty

Serum concentrations of follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol were determined at intervals before and during puberty in 40 individuals with Klinefelter syndrome (47,XXY karyotype), of whom 27 had been detected in neonatal cytogenetic screening programs. Prior to the appearance of secondary sexual changes, basal serum hormone concentrations and acute responses to stimulation with gonadotropin-releasing hormone and human chorionic gonadotropin were normal. The timing of the onset of clinical puberty was normal. Early pubertal boys showed initial testicular growth and normal serum testosterone levels, while serum follicle-stimulating hormone and estradiol concentrations were significantly elevated. By midpuberty, the Klinefelter subjects were uniformly hypergonadotropic and their testicular growth had ceased. Serum testosterone concentrations after age 15 remained in the low-normal adult range. Serum estradiol levels remained high, irrespective of the presence or absence of gynecomastia. Exaggerated responses to gonadotropin-releasing hormone are seen in pubertal subjects with elevated basal gonadotropin values.     

Inverse relationship between serum inhibin B and FSH levels in prepubertal boys with cryptorchidism.

To investigate the gonadal control of FSH secretion in prepuberty, we studied the relationship between circulating inhibin B and FSH levels in 16 prepubertal boys with cryptorchidism (age range, 1-8 y). The effect of Leydig cell stimulation on the secretion of inhibin B, sex steroids, and FSH was investigated in nine boys who were given human chorionic gonadotropin (hCG) treatment. In these boys, serum inhibin B, testosterone, estradiol, and gonadotropin levels were measured before and on the fourth day of the last (third) hCG injection, given at 1-wk intervals. Except for one boy with both high inhibin B and FSH concentrations, basal serum levels of these hormones correlated negatively (r(s) = -0.79, n = 15, p < 0.005). This inverse relationship remained significant in the subgroup of boys younger than 2 y of age (r(s) = -0.84, n = 11, p = 0.008) who also had greater variance of serum FSH concentrations than 14 control boys of similar age with normally located testes (p < 0.01). hCG stimulation increased serum testosterone and suppressed serum FSH concentrations in each boy (n = 9, p < 0.005). In the four oldest subjects, the serum inhibin B level increased from the mean of 91 to 135 pg/mL (p < 0.05). These findings suggest that inhibin B regulates FSH secretion in early childhood. Moreover, the hCG-induced suppression of FSH secretion was probably mediated by sex steroids rather than by inhibin B. Finally, the increase in serum inhibin B concentration during the hCG treatment was likely to be indirect via Leydig cell-Sertoli cell or Sertoli cell-germ cell interaction(s).     

MALE PSEUDOHERMAPHRODITISM DUE TO DEFICIENCY OF TESTICULAR 17-KETOSTEROID REDUCTASE

ABSTRACT. A 12.9 year-old girl, genotypically 46, XY, and considered to have a testicular feminization syndrome, developed signs of virilization and gynaecomastia. Very high androstenedione concentrations (10-fold the mean of the reference interval in boys) in relation to low normal testosterone in peripheral serum indicated a 17-ketosteroid reductase deficiency. In addition to androstenedione, the basal peripheral levels of 17-hydroxyprogesterone and estrone were increased, being 5- and 3-fold the mean of the reference interval, respectively, whereas pregnenolone, progesterone, dehydroepiandrosterone, 5α-dihydrotestosterone and estradiol concentrations were within pubertal stage-appropriate reference intervals. The total spermatic vein serum steroid concentrations were about 5-fold the mean in old men, and androstenedione, estrone and dehydroepiandrosterone were particularly elevated, whereas estradiol was normal and testosterone subnormal by a factor of 1/8. In the testis tissue, the concentration of androstenedione was extremely high, whereas that of testosterone tended to be relatively low. Our patient was obviously producing testicular steroids at her maximal rate, because no response to hCG administration was observed. This state was assiociated with a high-normal circulating LH concentration. The concentration of testicular LH/hCG receptors was only one-fifth of that seen in old men, which may have resulted from receptor down-regulation associated with a high degree of stimulation.     

Kinetics of the HCG-induced steroidogenic response of the human testis. III. Studies in children of the plasma levels of testosterone and HCG: rationale for testicular stimulation test

Little information is available regarding the time, rhythm, number, and appropriate dosage of human chorionic gonadotropin (HCG) for adequate testing of testicular function in human. The time course of the effect of two, three, or seven HCG injections at intervals of one, five, and two days, respectively, on the plasma levels of testosterone was studied in 11 boys. The first injection induced a progressive and modest rise of T. The second given one day later had little additive effect, maximal values being seen 72 to 120 hr later. In the prepubertal boys to whom several HCG injections were given, testosterone levels reached comparable levels after four injections every five days or seven injections every other day. Although the number of subjects studied was relatively small, these results give some rational basis for the following HCG test: two or four injections at four-day intervals.     

Clomiphene in the treatment of adolescent gynecomastia. Clinical and endocrine studies

Twelve boys, aged 12 to 19 years, with persistent gynecomastia were treated with the antiestrogen, clomiphene citrate, at a dose of 50 mg/day by mouth for one to three months. The mean breast size decreased by 0% to 36%, with only five boys experiencing a reduction of greater than 20%. Five boys subsequently required reduction mammoplasty. Levels of urinary gonadotropins, serum testosterone, and estradiol increased significantly during therapy. Since the ratio of testosterone to estradiol remained unchanged during treatment, the antiestrogen effects were achieved primarily at the level of breast tissue. Clomiphene citrate in a dose of 50 mg/day resulted in only small decreases in persistent pubertal gynecomastia and was not a satisfactory medical therapy for the condition.     

Monthly urinary LH and FSH secretory patterns in normal children and patients with sexual disorders

Urinary gonadotropin concentrations were determined by polyclonal double antibody RIA after ammonium sulfate extraction. Good correlation was observed between urinary gonadotropin/creatinine ratios in first morning voided and full 24-h urine collections. Using consecutive 30-d first morning voided urine specimens from normal children and from patients with sexual disorders, we have studied the monthly patterns of nighttime gonadotropin secretion. In normal prepubertal girls, the levels of urinary LH were low with few variations and those of urinary FSH were higher with episodic fluctuations. In early pubertal girls, the levels of urinary LH increased with striking, rhythmic fluctuations. The same changes were seen in urinary FSH. A single big surge of urinary gonadotropins was observed in postmenarcheal girls. In normal boys, the secretory patterns of urinary gonadotropins were similar to those of normal girls, but varied less. In patients with idiopathic precocious puberty, the patterns of urinary gonadotropins were similar to those of normal subjects matched for sexual stage. The measurement of 30-d first morning voided urinary gonadotropins can provide a simple and physiologic test of gonadotropin function in children.     

Diagnostic value of testosterone therapy in boys with delayed puberty

A brief course of testosterone injections is known to be an effective treatment for boys with constitutional delayed puberty. In this study, data from seven boys at least 14 years old who received testosterone enanthate (100 mg intramuscularly monthly for four months) were analyzed to see if linear and testicular growth responses could be useful diagnostically in excluding growth hormone deficiency (GHD) and isolated gonadotropin deficiency, two conditions that are often difficult to distinguish from constitutional delayed puberty. During four months of testosterone therapy, growth rate increased from 4.0 +/- 1.0 cm/y to 10.7 +/- 2.3 cm/y, and was greater than 8 cm/y in all patients. Since testosterone-induced stimulation of linear growth is largely GH-mediated, the large increase in growth rate in all boys is considered indicative of GH sufficiency. Testis length, which did not increase during testosterone therapy, increased by 0.6 to 0.8 cm in every patient (from 2.7 +/- 0.3 cm to 3.4 +/- 0.4 cm) over the following four months, indicating normal gonadotropin secretion and normal pubertal progression; in contrast, the increase in serum testosterone concentrations after discontinuation of testosterone treatment was more variable. It is concluded that the growth response to a four-month course of testosterone is helpful in excluding GHD in boys with delayed puberty, and an additional four months of follow-up is sufficient to document the onset of puberty, thereby eliminating the possibility of isolated gonadotropin deficiency.     

Pubertal gynecomastia and transient elevation of serum estradiol level.

Serum levels of testosterone, estradiol, progesterone, 17alpha-hydroxyprogesterone, follicle-stimulating hormone, and luteinizing hormone were measured in 16 boys with pubertal gynecomastia. Six patients had elevated serum estradiol concentrations, and four of these six also had elevated progesterone levels. Serum estradiol/testosterone ratios were high for the stage of puberty in 11 of the 16 patients. In five patients who had two or more determinations, the steroid concentrations returned toward or into the normal range. Transient increases in serum estradiol concentration or an abnormally high estradiol/testosterone ratio may be causally related to the development of gynecomastia in adolescent boys.     

Gonadotropin and testosterone measurements after estrogen administration to adult men, prepubertal and pubertal boys, and men with hypogonadotropism: evidence for maturation of positive feedback in the male.

Nineteen male subjects were fiven five daily injections of 17beta-estradiol and circulating levels of estradiol (E2), testerone (T), and gonadotropins were determined by radioimmunoassay before, during, and after the steroid course. Peak levels of E2 attained during the 5 days of treatment ranged from 173-577 pg/ml. Four of seven normal adult men and one castrate man demonstrated suppression of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) with a subsequent rise in LH (positive feedback) while E2 levels remained elevated. A rise in T was associated with the LH increment in the four normal men. Nine pre-, early, or midpubertal boys and two men with hypogonadotropic hypogonadism displayed only gonadotropin suppression after E2 administration. The difference in LH response to estrogen (i.e., positive feedback) between the adult men with normal or elevated gonadotropin levels as compared with the endocrinologically normal boys is significant (P less than 0.01).     

Pubertal development in male hypopituitarism

The spontaneous or therapeutically induced pubertal development of 65 male patients with idiopathic hypopituitarism was analysed. Spontaneous puberty occurred in 82% of the patients with prepubertal isolated growth hormone deficiency and in 32.5% of those with impairment in the secretion of more than one pituitary hormone.Out of this group, 36 patients could be studied longitudinally. In 15 patients, the onset of spontaneous puberty was delayed, on average, 3.2 years. It started at a bone age of 10.36±1.25 years and followed a pattern similar to that of normal boys. Testosterone levels at each pubertal stage were not different from those of normal boys. Mean peak height velocity reached 7.27±1.82 cm/year. In 21 patients with gonadotropin deficiency, hCG treatment was started at a chronological age of 19.04±2.17 years and a bone age of 12.94±0.80 years. Plasma testosterone attained normal adult levels in the majority of boys, while the development of sexual characteristics showed a wide variation. Mean growth velocity during the first year of hCG therapy reached 6.11±2.47 cm/year. Partial gonadotropin deficiency was diagnosed in two boys.Although testosterone seems today to be, for practical reasons, the replacement therapy of choice, hCG treatment is an alternative for hypopituitary patients with absent gonadotropin function.Abbreviations IGHD isolated growth hormone deficiency - MPHD multiple pituitary hormone deficiency - hCG human chorionic gonadotropin - hGH human growth hormone - PHV peak height velocity     

Sex hormones and the changes in adolescent male lipids: longitudinal studies in a biracial cohort

OBJECTIVE: To determine the role of increasing free testosterone and estradiol in pubertal changes in male lipids. METHODS: We conducted a 3-year, longitudinal, observation study with biannual visits of 251 black and 285 white boys who were 10 to 15 years of age at enrollment. Sex hormones, lipid parameters, and body composition measures were obtained according to a standard protocol. The body mass index (kg/m(2)) was used to characterize obesity. RESULTS: White boys had higher triglycerides, lower high-density lipoprotein cholesterol (HDL-C), lower apolipoprotein (apo)AI, and higher apoB than black boys. In boys of both races, increased body mass index was associated with increases in triglycerides, low-density lipoprotein cholesterol, apoB and decreases in HDL-C and apoAII. Within this framework, increased free testosterone was associated with increased apoB and decreased HDL-C and apoAI, whereas increased estradiol was associated with increased HDL-C and decreased triglycerides, low-density lipoprotein cholesterol, and apoB. CONCLUSION: Changes in sex steroid hormones have significant effects on changes in lipid parameters-increasing free testosterone levels has atherogenic effects and increasing estradiol has antiatherogenic effects.     

Differences of hexarelin-induced prolactin and cortisol responses between prepubertal and early pubertal short children and lack of correlation with gonadotropin-releasing hormone-induced gonadotropin response

Hexarelin (HEX), a synthetic hexapeptide with strong GH-stimulating activity, is known to induce the release of prolactin (PRL) and cortisol (F). The responses of GH and F vary according to age and pubertal development, correlating with serum levels of sex steroids, while the release of PRL does not. We evaluated GH, PRL and F responses to HEX (2 microg/kg i.v.) in 19 children with short stature, 12 prepubertal (Tanner stage I) and 7 early pubertal (stage II), and their correlation with those of FSH and LH to GnRH and with the serum levels of testosterone (T) or estradiol (E2). At baseline, the GH, PRL, F and sex steroid serum levels did not vary in the two groups of patients. HEX induced a strong GH and a slight PRL increase in prepubertal and early pubertal children, with no differences in the extent of the response, while F secretion was not affected in either group; these responses did not correlate with those of the gonadotropins to GnRH nor with basal T or E2.     

Does treatment with human chorionic gonadotropin induce reversible changes in undescended testes in boys?

Between May 1993 and November 1995, 71 cryptorchid boys were treated with human chorionic gonadotropin (hCG); 42 were operated upon following unsuccesful hCG treatment. A routine orchiopexy was performed in each case. In 10 cases a testicular biopsy was made during orchipexy within 3 days following hCG treatment; in another 10 biopsies were taken 6 to 9 months after treatment. Testicular biosies were taken at the time of orchiopexy in 5 cryptorchid boys who were not treated with hCG as a control group. A mild, inflammation-like reaction was found in the cryptorchid testes in the period immediately following the last hCG injections, but those studied 6 to 9 months after the last injection there were no apparent such reactions. In contrast to the inflammation-like reaction, the volume density of blood vessels, interstitial bleeding, and diameter of the seminiferous tubules had not regressed. The numbers of spermatogonia per tubular transverse section and the percentage of tubular transverse sections containing spermatogonia (the fertility index) were increased.     

Hypothalamic-pituitary-testicular function in prepubertal children with chronic liver disease

Adult patients with chronic liver disease (CLD) show clinical and biochemical signs of hypogonadism and estrogenization. However, no information is available on hypothalamo-pituitary-testicular function in prepubertal or early pubertal children with CLD. Eighteen prepubertal children with CLD, aged 5.8+/-5.5 years (mean +/- SD; range 0.32-12.8), were studied. Most of them had moderate liver function abnormality. Height was slightly decreased (SDS: -1.44-/+1.88) but weight for height was adequate. Serum gonadotropins were evaluated as a function of age. In the age group younger than 1 year (n = 7), serum LH was elevated (4.88+/-6.22 IU/l) when compared with a group of 39 control children (1.2+/-1.65), while serum FSH was normal. In this young group, serum testosterone was normal, but serum estradiol was significantly increased (24.1+/-19.7 pg/ml) when compared with the control group (6.5+/-3.54). In contrast, in the age group older than 2 years, no difference between patients with CLD and controls was observed, either in serum gonadotropins or in serum sex hormones. Taking the 18 patients with CLD together, serum SHBG (113.7+/-51 nmol/l; mean +/- SD) was significantly higher than in normal controls (76+/-38 nmol/l, n = 91, p <0.001). Moreover, and different from normal controls, no change with age was observed in serum SHBG, total testosterone or bioavailable testosterone (non-SHBG-bound). Normal testosterone response to hCG stimulation (>1 ng/ml) was found in a subgroup of 11 children with CLD. By contrast, eight of 11 patients with CLD had an inadequate decrease in SHBG after androgen stimulation. In conclusion, we observed that during the first year of life, a period which includes the postnatal activation of the hypothalamo-pituitary-testicular axis, there is an elevation of serum LH and serum estradiol that suggests the existence of a moderate deficiency of Leydig cell function. This disorder is no longer observed in older prepubertal children. Similar to reports in adults, children with CLD have elevation of serum SHBG levels. Furthermore, the lack of SHBG decrease and bioavailable testosterone increase with age, probably modulated by GH, suggests some degree of hepatic GH resistance in prepubertal patients with CLD.     

Spontaneous and GnRH-provoked gonadotropin secretion and testosterone response to human chorionic gonadotropin in adolescent boys with thalassaemia major and delayed puberty

To elucidate whether the cause of sexual maturation arrest in thalassaemia is of gonadal or pituitary etiology, 10 males with thalassaemia and delayed puberty and 10 with constitutional delay of growth and pubertal maturation (CSS) were extensively studied. Their spontaneous nocturnal gonadotropin secretion and gonadotropin response to intravenous 100 micrograms gonadotropin-releasing hormone (GnRH) were evaluated. Circulating testosterone concentration and clinical response were evaluated after 3 days, 4 weeks and 6 months of intramuscular administration of human chorionic gonadotropin (HCG) (2500 U/m2/dose). Thalassaemic boys had significantly lower circulating concentrations of testosterone compared to those with constitutional delay of growth and sexual maturation (CSS) at the same pubertal stage. Short- and long-term testosterone response to administrations of HCG was markedly decreased in thalassaemic boys. After 6 months of HCG administration 50 per cent (5/10) of the boys did not show significant testicular enlargement or genital changes. Despite the low circulating concentrations of testosterone, none of the patients had high basal or exaggerated gonadotropin response to gonadotropin releasing hormone (GnRH) stimulation. Luteinizing hormone (LH) peak responses to GnRH were significantly lower as compared to controls. Follicle-stimulating hormone (FSH) peak responses to GnRH did not differ among the two study groups. The mean nocturnal LH and FSH secretion was significantly decreased in all thalassaemic boys as compared to boys with CSS at the same pubertal stage (testicular volume). These data proved that hypogonadotropic hypogonadism is the main cause of delayed/failed puberty in adolescents with thalassaemia major. MRI studies revealed complete empty sella (n = 5), marked diminution of the pituitary size (n = 5), thinning of the pituitary stalk (n = 3) with its posterior displacement (n = 2), and evidence of iron deposition in the pituitary gland and midbrain (n = 8) in thalassaemic patients, denoting a high incidence of structural abnormalities (atrophy) of the pituitary gland. Moreover, in many of the thalassaemic boys, the defective testosterone response to long-term (6 months) HCG therapy denoted significant testicular atrophy and/or failure secondary to siderosis. It appears that testosterone replacement might be superior to HCG therapy in these patients. This therapy should be introduced at the proper time in these hypogonadal patients to induce their sexual development and to support their linear growth spurt and bone mineral accretion.     

Hypergonadotropic Hypogonadism in Newborn Males with Primary Testicular Failure

ABSTRACT. Four infants with genital ambiguity but with apparent testes were given a gonadotropin-releasing hormone (GnRH) test and a human chorionic gonadotropin (hCG) test at age 3–12 days. The results were compared with those from 16 newborn males (aged 2 to 6 days) with minor genital anomalies; 9 with unilateral and 3 with bilateral incomplete testicular descent, 2 with surgically insignificant glandular hypospadias and 2 with penis length <(-2 SD) for gestational age. Treatment with testosterone resulted in clear phallus growth in all four patients. All four patients had elevated basal luteinizing hormone (LH) concentrations as well as an exaggerated LH response to GnRH; three of them also had an exaggerated follicle stimulating hormone (FSH) response. Thus in all patients the etiology of genital ambiguity was considered to be testicular. The testosterone response to hCG was normal in two of the patients but impaired in the other two. The steroidogenic response did not show any specific enzyme defect. We conclude that 1) newborn boys with Leydig cell failure are clearly hypergonadotropic, 2) the GnRH test is a more sensitive indicator of Leydig cell failure neonatally than the hCG test and 3) normal testes greatly inhibit the secretion of both LH and FSH during the first week of life.     

Leptin levels in boys with pubertal gynecomastia

BACKGROUND: It has been reported that there is a relationship between circulating leptin and sex steroid hormones and leptin is able to stimulate estrogen secretion by increasing aromatase activity in adipose stromal cells and breast tissue. Leptin receptors have been also shown in mammary epithelial cells and it has been suggested that leptin is involved in the control of the proliferation of both normal and malignant breast cells. AIM: To investigate circulating leptin levels in boys with pubertal gynecomastia. METHODS: Twenty boys with pubertal gynecomastia who were in early puberty and had no obesity, and 20 healthy individuals matched for age, pubertal stage and body mass index (BMI) with the study group, were enrolled in the study. Body weight, height and left midarm circumference (MAC) and left arm triceps skinfold thickness (TSF) were measured and BMI was calculated. A fasting blood sample was collected and routine hormonal parameters including prolactin, beta-human chorionic gonadotropin (betaHCG), total and free testosterone, estradiol, luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, androstenedione (AS) and dehydroepiandrosterone sulfate (DHEAS) levels were studied. Serum leptin levels were analyzed using radioimmunoassay. RESULTS: The mean ages of the study and control group were not different (13.9 +/- 0.89 and 14.2 +/- 0.66, respectively). No significant difference was found for BMI, MAC and TSF values between the two groups. There was no significant difference for hormonal parameters including FSH, LH, total and free testosterone, estradiol, AS, DHEAS and estradiol/total testosterone ratio between boys with pubertal gynecomastia and the controls. Serum leptin levels were found significantly higher in the study group compared with the healthy controls (5.58 +/- 0.81 and 2.39 +/- 0.29 ng/ml, respectively; p <0.001). No correlation could be determined between serum leptin levels and hormonal parameters. CONCLUSION: The presence of higher leptin levels in boys with pubertal gynecomastia indicates that leptin may be involved in the pathogenesis of pubertal gynecomastia. The role of circulating leptin in pubertal gynecomastia is probably related to increase in estrogen and/or estrogen/ androgen ratio by the stimulating effect of leptin on aromatase enzyme activity in both adipose and breast tissues, or a direct growth stimulating effect of leptin on mammary epithelial cells, or increase in sensitivity of breast epithelial cells to estrogen with inducing functional activation of estrogen receptors by leptin in breast tissue.