Oxandrolone Treatment Results in an Increased Risk of Gonadarche in Prepubertal Boys With Klinefelter Syndrome.

Context: Klinefelter syndrome (KS) is a common genetic condition in which males have an extra X chromosome. KS is associated with testosterone deficiency, neurodevelopmental delays, and cardiometabolic disorders. There has been recent interest in prepubertal androgen treatment; however, the effects on puberty and gonadal function are unknown. Objective: To compare onset of puberty and testicular function in prepubertal boys treated with 2 years of oxandrolone (Ox) vs placebo (Pl). Design: Double-blind, randomized, controlled trial. Setting: Single tertiary care referral center. Participants: Eighty prepubertal boys with KS; mean age: 8.0 ± 2.2 years (range: 4 to 12). Interventions: Ox 0.05 mg/kg vs identical-appearing Pl capsule given for 2 years. Outcome Measures: Onset of gonadarche (testicular volume ≥4 mL) and onset of pubarche (Tanner 2 pubic hair); change in testicular hormone concentrations. Results: Ox-treated group had 20.5 times higher odds of reaching gonadarche (OR 95% CI: 6.5, 77.8) and 28.1 times higher odds of reaching pubarche (OR 95% CI: 8.8, 110.4) during the 2-year study period after adjusting for baseline age. Gonadarche and pubarche both occurred at a younger age in the Ox group (gonadarche: 9.8 ± 1.5 vs 12.1 ± 1.0 years, P < 0.001; pubarche: 10.2 ± 1.1 vs 11.6 ± 1.3 years, P = 0.02). Serum concentrations of testicular hormones and gonadotropins were not different between groups. Conclusions: Two years of Ox treatment in prepubertal boys with KS results in an increased risk of early gonadarche, on average 2 years earlier than in Pl-treated boys. Ox did not affect serum concentrations of testicular hormones.

Importance of Serum Testicular Protein Hormone Measurement in the Assessment of Disorders of Sex Development.

Commonly known for testosterone secretion, the testes also produce the protein hormones anti-müllerian hormone (AMH), inhibin B, and insulin-like factor 3 (INSL3). AMH and inhibin B are secreted by Sertoli cells, whereas INSL3 is a Leydig cell product. AMH is involved in fetal sex differentiation and induces the regression of the anlagen of the uterus and fallopian tubes. INSL3 participates in fetal testicular descent. Serum testicular protein hormone assessment can be very useful and complementary to testosterone measurements in patients with DSD. AMH and inhibin B determination is extremely helpful during childhood, when basal testosterone is normally low. Serum AMH and inhibin B above the female range are indicative of the presence of testicular tissue, and their circulating levels reflect the amount of functional Sertoli cells. In DSD patients with normal male levels of AMH and inhibin B, the diagnosis of gonadal dysgenesis can be ruled out, and isolated androgen secretion deficiency or androgen insensitivity should be suspected. In externally virilized XY patients with persistent müllerian ducts, serum AMH levels determine the diagnosis to AMH deficiency or resistance. At pubertal age, inhibin B levels serve to predict spermatogenic development.

The Testicular Hormones AMH, InhB, INSL3, and Testosterone Can Be Independently Deficient in Older Men.

BACKGROUND: Late-onset hypogonadism is symptomatically diverse and not fully explained by circulating testosterone level. The adult testes secrete four distinct hormones (testosterone, AMH, INSL3, and InhB) into the circulation. Testosterone and InhB have proven dynamic regulation, with limited information available for AMH and INSL3. During aging, there is cellular senescence, which may underlie the diversity of hypogonadism. This leads to the postulate that the relative levels (profile) of the four testicular hormones in older men are variable and cannot be evaluated by the measurement of one hormone. METHODS: 111 men aged 19-50 years and 98 men aged 70-90 years were examined. The circulating levels of the testicular hormones were measured using ELISAs, and the variation in the levels of hormones was analyzed by various correlative analyses. RESULTS: All four hormones were largely or totally independent. Some men were deficient in multiple hormones, but no man had multiple elevated hormones. The average hormonal levels were lower in older men, with diverse profiles of the four testicular hormones. Hence, some men had one or more hormones below the reference range, with testosterone the most conserved. Consequently, testosterone levels were not indicative of the complete state of the endocrine testes. CONCLUSIONS: The four hormones vary independently of each other, in younger and older men. This indicates that they are regulated dynamically rather than influenced by endocrine cell number. Older men exhibited diverse profiles of low levels of testicular hormones, suggesting that the testes age differently between men. Testosterone alone inadequately describes gonadal states.

Kolaviron protects against benzo[a]pyrene-induced functional alterations along the brain-pituitary-gonadal axis in male rats.

Exposure to benzo[a]pyrene (B[a]P) is well reported to be associated with neurological and reproductive dysfunctions. The present study investigated the influence of kolaviron, an isolated biflavonoid from the seed of Garcinia kola, on functional alterations along the brain-pituitary-gonadal axis in male rats exposed to B[a]P. Benzo[a]pyrene was orally administered at a dose of 10mg/kg alone or orally co-administered with kolaviron at 100 and 200mg/kg for 15 consecutive days. Administration of B[a]P significantly (p<0.05) decreased plasma levels of pituitary hormones namely follicle-stimulating hormone (FSH) and prolactin but increased luteinizing hormone (LH) by 47%, 55% and 20.9%, respectively, when compared with the control. The significant decrease in gonadosomatic index (GSI) was accompanied by significant decrease in testosterone production and sperm functional parameters in the B[a]P-treated rats. Moreover, B[a]P-treated rats showed significant elevation in the circulatory concentrations of pro-inflammatory cytokines and oxidative stress indices in the brain, testes and sperm of B[a]P-treated rats. Light microscopy revealed severe necrosis of the Purkinje cells in the cerebellum, neuronal degeneration of the cerebral cortex, neuronal necrosis of the hippocampus and testicular atrophy in B[a]P-treated rats. Kolaviron co-treatment significantly ameliorated B[a]P mediated damages by suppressing pro-inflammatory mediators and enhancing the antioxidant status, neuroendocrine function, sperm characteristics and improving the architecture of the brain and testes in B[a]P-treated rats. The findings in the present investigation highlight that kolaviron may be developed to novel therapeutic agent against toxicity resulting from B[a]P exposure.

[Study on the association between maternal urinary phthalate metabolites and testicular steroid hormones in the cord blood in a Chinese population].

OBJECTIVE: The purposes of our study were to investigate the association between maternal urinary phthalate metabolites and the levels of inhibin B (INHB) and insulin-like factor 3 (INSL3) in the cord blood in a Chinese pregnant population. METHODS: Maternal urine samples in the third trimester of pregnancy of 69 participants were collected and stored, and the samples of cord blood (10 ml) were collected at delivery between June 2011 and September 2012 in a comprehensive hospital of gynecology and obstetrics in Tianjin, China.Four phthalate metabolites, monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), and mono-2-ethylhexyl phthalate (MEHP) were measured in the urine samples using liquid chromatography-tandem mass spectrometry. The levels of INHB, INSL3 in the cord blood were tested by ELISA. Associations of phthalate exposure with INHB and INSL3 levels were determined by spearman correlation and multiple regression model analysis. RESULTS: The median concentrations of observed metabolites in descending order were 49.74 µg/L for MMP, 24.96 µg/L for MEHP, 19.52 µg/L for MEP and 17.73 µg/L for MBP. The median concentrations of INHB and INSL3 were 89.09 and 106.21 ng/L.Significant negative associations between INHB and MMP(ß' = -0.252), MEP(ß' = -0.363) or the sum value (∑PAEs) (ß' = -0.346) were found by the multiple regression model analysis. For INSL3, only the sum value (ß' = -0.313) was inversely significantly associated with the levels of INSL3 in the cord blood. CONCLUSIONS: Maternal urinary phthalate metabolites were associated with INHB and INSL3 in the cord blood in a Chinese population.

Impact of chromosomal translocations on male infertility, semen quality, testicular volume and reproductive hormone levels.

OBJECTIVE: To analyse the relationship between male infertility and chromosomal translocations, and the influence of different types of chromosomal translocations on semen quality, testicular volume and hormone levels. METHODS: A retrospective cohort of infertile men was recruited for chromosomal analysis using standard Giemsa stain banding. Physical examinations, semen analysis, hormonal analysis and the detection of azoospermia factor (AZF) microdeletions were carried out. Men with normal fertility were used as controls. RESULTS: Among the 1056 infertile men, 22 had chromosomal translocations (2.1%), including seven with Robertsonian translocations (0.7%), 11 with autosome-autosome reciprocal translocations (1.0%) and four with gonosome-autosome reciprocal translocations (0.4%). Left and right testicular volumes of patients with chromosomal translocations were significantly smaller than those in the fertile control group. There were no significant differences in hormone levels between patients with chromosomal translocations and fertile controls, except for significantly lower testosterone levels in patients with Robertsonian and gonosome-autosome reciprocal translocations compared with the controls. All AZF microdeletion analyses showed normal results. CONCLUSIONS: Chromosomal translocations may cause reductions in testicular volume and testosterone level, which may impact spermatogenesis, resulting in azoospermia or oligozoospermia and male infertility.

Antimüllerian hormone (AMH) not only a marker for prediction of ovarian reserve.

The main characteristics of the Antimüllerian hormone from the points of view of biochemistry, molecular genetics, physiological functions and importance for diagnostics in reproductive endocrinology and related biomedical fields are reviewed. The role of the hormone in male and female development, its participation in oocyte maturation including selection of a dominant follicle are summarized, as well as its changes under various pathological situations in both sexes. The physiological changes of serum AMH leves in the life span in both sexes and their alterations under various pathological conditions are provided, too.

Late hormonal function after testicular torsion.

INTRODUCTION: Testicular torsion may be an important cause of male infertility. We aimed to investigate the late hormonal function in patients with testicular ischemia/reperfusion injury of the testis after orchidectomy or detorsion. METHODS: Twenty patients (mean age, 13.6 years) were prospectively evaluated at a mean of 5 years after testicular torsion. The serum follicle-stimulating hormone, luteinizing hormone (before and after gonadotropin-releasing hormone stimulation), testosterone, and inhibin B were measured. Fifteen age-matched adolescents without evidence of endocrine disease were used as controls for inhibin B values. Data are quoted as mean +/- SEM. RESULTS: Twelve patients were treated with detorsion and orchidopexy, and 8 underwent orchidectomy. Serum follicle-stimulating hormone, luteinizing hormone, and testosterone were all within the reference range. Inhibin B levels were significantly reduced in the 2 groups compared with the controls (34.5 +/- 5.2 vs 63.9 +/- 12.8 pg/mL, P = .02), but were not significantly different between the orchidectomy group and the group that underwent detorsion (41.3 +/- 9.7 vs 30.4 +/- 5.9 pg/mL, P = .41). CONCLUSION: Hormonal testicular function can be compromised after testicular torsion, although the type of surgery (orchidectomy or orchidopexy) does not seem to change the effect of this ischemia/reperfusion injury.

Effects of maternal exposure to low doses of DES on testicular steroidogenesis and spermatogenesis in male rat offspring.

Our previous studies have demonstrated that prenatally administered diethylstilbestrol (DES) impairs testicular endocrine function in male offspring. The present study examined whether maternal DES treatment influences testicular steroidogenesis and spermatogenesis. DES was injected subcutaneously at 0.5 or 1.5 microg/kg/day (DES 0.5 and 1.5 groups, respectively) into pregnant SD rats on days 7-21 of gestation. Male offspring in the DES 0.5 and 1.5 groups were autopsied at 1, 3, 6 and 15 weeks after birth. At 1 week, DES treatment did not lead to a change in the volume of P450scc-positive cells (Leydig cells), suggesting that DES has no inhibitory effect on the development of Leydig cells. DES administration disrupted luteinizing hormone receptor (LHr) expression and exerted inhibitory effects on signal transduction from LHr to steroidogenic acute regulatory protein (StAR) in testicular steroidogenesis (P<0.05), although there were no changes in the mRNA expression levels of steroidogenic enzymes, such as P450scc, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and P450(17 alpha), which may have caused a decrease in the plasma testosterone level. DES treatment did not disrupt the cycle of spermatogenesis but did upregulate the expression levels of androgen receptor (AR) mRNA in both DES groups at 15 weeks (P<0.05). These results indicate that maternal DES treatment disrupts steroidogenesis but induces a high level of AR mRNA expression to counteract the low levels of testosterone during spermatogenesis.

Protective effects of Digera muricata (L.) Mart. on testis against oxidative stress of carbon tetrachloride in rat.

Oxidative stress induced by carbon tetrachloride (2 ml/kg body weight i.p.) in rat substantially decreases the increase in body weight and relative testis weight. It also markedly increases the level of TBARS and nitrites along with corresponding decrease in reduced glutathione and various antioxidant enzymes in testis, i.e., catalase, peroxidase, superoxide dismutase and glutathione peroxidase. Serum level of testosterone, luteinizing hormone and follicle stimulating hormone was significantly decreased while estradiol and prolactin were increased with carbon tetrachloride treatment. Histopathology of CCl(4)-treated rats indicated the partial degeneration of germ and Leydig cells along with deformities in spermatogenesis. Supplementation of Digera muricata (100, 150, 200mg/kg body weight orally) once a week for 16 weeks results in decrease of TBARS and nitrite, while increase in antioxidant enzymes; catalase, peroxidase, superoxide dismutase, GSH-Px and GSH contents. Serum level of testosterone, luteinizing hormone, follicle stimulating hormone, estradiol, prolactin, histology, body weight and relative testis weight was also concomitantly restored to near normal level by D. muricata supplementation to carbon tetrachloride intoxicated rat. The results clearly demonstrate that D. muricata treatment augments the antioxidants defense mechanism against carbon tetrachloride induced toxicity and provides evidence that it may have a therapeutic role in free radical mediated diseases.

Food availability during migratory stopover affects testis growth and reproductive behaviour in a migratory passerine.

Long-distance migratory passerines initiate testicular recrudescence during spring migration to meet the demands of timely reproduction upon immediate arrival on the breeding grounds. The degree of testicular development is known to depend on environmental factors like stopover habitat quality; reproductive performance may be strongly impacted by testicular maturation upon arrival on the breeding grounds. We investigated the effect of stopover food availability on subsequent reproductive performance in garden warblers (Sylvia borin). Spring migration was simulated by repeated food deprivation and re-feeding to imitate the alternation of flight and stopover periods. During the two final stopover periods, males were either kept under ad libitum food (ad libitum males) or under limited food conditions (limited males). After simulated arrival in the breeding area, manipulation of previous stopover food availability resulted in significantly slower testicular recrudescence (p<0.001) and decreased plasma testosterone (p<0.01) in limited males compared to ad libitum males. Body mass change was not significantly different between the two groups (p=0.38). Limited males also exhibited reduced performance in reproductive behaviours employed in territorial and sexual contexts. Limited males had a longer 'freezing' interval (p<0.05) and decreased activity (p<0.01) when challenged with a live male decoy. In direct confrontation between limited and ad libitum males in the presence of a female, limited males exhibited significantly fewer behavioural traits in sexual context, i.e. directed to the female (p<0.001). Therefore, we suggest that conditions encountered during previous migratory stopover may affect subsequent annual reproductive success by influencing key reproductive behaviours.

Loss of ovarian reserve after uterine artery embolization: a randomized comparison with hysterectomy.

BACKGROUND: Ovarian failure as a complication of uterine artery embolization (UAE) for symptomatic uterine fibroids has raised concerns about this new treatment modality. METHODS: We investigated the occurrence of ovarian reserve reduction in a randomized trial comparing UAE and hysterectomy by measuring follicle stimulating hormone (FSH) and anti-Mullerian hormone (AMH). A total of 177 pre-menopausal women with menorrhagia due to uterine fibroids were included (UAE:n=88; hysterectomy:n=89). FSH and AMH were measured at baseline and at several time-points during the 24 months follow-up period. Follow-up AMH levels were also compared to the expected decrease due to ovarian ageing during the observational period. RESULTS: FSH increased significantly compared to baseline in both groups after 24 months follow-up (within group analysis: UAE:+12.1; P=0.001; hysterectomy:+16.3; P<0.0001). No differences in FSH values between the groups were found (P=0.32). At 24 months after treatment the number of patients with FSH levels>40 IU/l was 14/80 in the UAE group and 17/73 in the hysterectomy group (relative risk=0.75; P=0.37). AMH was measured in 63 patients (UAE: n=30; hysterectomy: n=33). After treatment AMH levels remained significantly decreased during the entire follow-up period only in the UAE group compared to the expected AMH decrease due to ageing. No differences were observed between the groups. CONCLUSIONS: This study shows that both UAE and hysterectomy affect ovarian reserve. This results in older women becoming menopausal after the intervention. Therefore, the application of UAE in women who still wish to conceive should only be considered after appropriate counselling.

Endocrine features of menstrual cycles in middle and late reproductive age and the menopausal transition classified according to the Staging of Reproductive Aging Workshop (STRAW) staging system.

CONTEXT: Female reproductive aging based on changes in menstrual cycle length and frequency progresses through a number of stages as defined by the Stages of Reproductive Aging Workshop (STRAW) staging criteria. OBJECTIVE: This paper provides a comprehensive description of the endocrine features associated with the STRAW stages. DESIGN: Healthy women aged 21-35 and 45-55 yr submitted three blood samples a week over a single menstrual cycle. They were classified as mid-reproductive age (n = 21), late-reproductive age (n = 16), early menopause transition (n = 16), and late menopause transition (n = 23). RESULTS: There were nine, one, zero, and two anovulatory cycles identified in the late menopause transition, early menopause transition, late-reproductive age, and mid-reproductive age groups, respectively. Ovulatory cycle FSH, LH, and estradiol levels increased with progression of STRAW stage (P = 0.001, P < 0.01, and P < 0.05, respectively), and mean luteal phase serum progesterone decreased (P < 0.01). Early cycle (ovulatory and anovulatory) inhibin B decreased steadily across the STRAW stages (P < 0.01) and was largely undetectable during elongated ovulatory and anovulatory cycles in the menopause transition. Anti-Mullerian hormone decreased markedly (10- to 15-fold) and progressively across the STRAW stages (P < 0.01 and P < 0.001, respectively). CONCLUSIONS: Progression through the STRAW stages is associated with elevations in serum FSH, LH, and estradiol and decreases in luteal phase progesterone. The marked fall in inhibin B and particularly anti-Mullerian hormone indicate that they may be useful in predicting STRAW stage but future analyses of early cycle measurements on larger cohorts are needed to draw predictive conclusions.

Anti-Müllerian hormone as a predictor of IVF outcome.

Serum anti-Müllerian hormone (AMH) concentration and antral follicle count (AFC) are two increasingly popular static measures used to predict ovarian reserve prior to IVF treatment. While they have been shown to be good predictors of oocyte yield during ovarian stimulation, their status as indicators of oocyte quality and pregnancy rates is currently uncertain. The present study measured baseline concentrations of serum AMH and FSH, and AFC from 126 women undergoing IVF treatment. These data were then related to IVF outcomes. As expected, patients with lower serum AMH and AFC produced a significantly (P < 0.001) lower number of oocytes compared with patients with higher serum AMH/AFC. Fertilization rates in patients with lower serum AMH were significantly inferior compared with patients with higher serum AMH, irrespective of whether IVF (P = 0.043) or intracytoplasmic sperm injection (P = 0.006) was used to achieve fertilization. These low AMH patients yielded fewer oocytes, had lower fertilization rates, generated fewer embryos, and had a higher incidence of miscarriage during fresh transfers, ultimately culminating in a halving of the pregnancy rate per IVF cycle compared with the high AMH group.

Stable serum levels of anti-Müllerian hormone during the menstrual cycle: a prospective study in normo-ovulatory women.

BACKGROUND: Anti-Müllerian hormone (AMH), secreted by the granulosa cells of preantral and small antral follicles, has been described as a potential marker of the ovarian reserve. The aim of this prospective study is to investigate the variations of AMH during the menstrual cycle in a young selected population of normo-ovulatory women and to analyse the correlation with other cyclic hormones. METHODS: Twenty healthy volunteers from 19 to 35 years old, with regular menstrual cycles (26-31 days), normal ovulation (day 10-16), normal hormonal profile and normal body mass index (18-26 kg/m2) were recruited. AMH, inhibin B, LH, FSH, estradiol and progesterone were measured on days 3, 7, 10, 11, 12, 13, 14, 15, 16, 18, 21 and 25 of a spontaneous cycle. RESULTS: AMH serum levels, either expressed by cycle day or aligned according to the ovulation day, did not show any significant variations during the menstrual cycle. CONCLUSIONS: No significant fluctuation of the AMH level during the menstrual cycle was observed. Therefore, this hormone is particularly interesting for clinical evaluation of the ovarian reserve as it may be used at any time during the cycle.

Anti-Müllerian hormone levels in peripubertal daughters of women with polycystic ovary syndrome.

CONTEXT: We have previously observed increased anti-Müllerian hormone (AMH) levels in prepubertal daughters of polycystic ovary syndrome (PCOS) women, suggesting that these girls may have an altered follicular development. However, it is not known whether AMH levels remain increased during puberty. OBJECTIVE: The aim was to establish whether the increased AMH levels observed in prepubertal daughters of PCOS women persist during the peripubertal period, a stage during which the gonadal axis is activated and PCOS may become clinically manifested. DESIGN: We studied 28 daughters (8-16 yr old) of PCOS women (PCOSd) and 33 daughters (8-16 yr old) of control women (Cd). In both groups, an oral glucose tolerance test was performed. Gonadotropins, sex hormones, and AMH were determined in a fasting sample. RESULTS: Both groups were comparable in age, body mass index, and breast Tanner stage. Free androgen index, testosterone, AMH (Cd 14.4 +/- 8.0 pM vs. PCOSd 24.0 +/- 19.0 pM; P = 0.012), and 2-h insulin levels were significantly higher in the PCOSd group compared with the control group. The average ovarian volume was significantly higher in the PCOSd group. In both groups a positive correlation between 2-h insulin and AMH concentrations was observed (PCOSd: r = 0.530, P = 0.007; Cd: r =0.561, P = 0.008). CONCLUSIONS: AMH concentrations are increased in peripubertal PCOSd. These findings, along with the results of our previous study, suggest that PCOSd appear to show an increased follicular mass that is established during early development, and persists during puberty.

Heterozygous mutation of steroidogenic factor-1 in 46,XY subjects may mimic partial androgen insensitivity syndrome.

CONTEXT: The clinical and biological features of Sertoli cell and Leydig cell dysfunction are usually investigated when characterizing disorders of sex development in 46,XY individuals: This allows gonadal dysgenesis, a defective development of the gonad, to be distinguished from defects restricted to androgen synthesis or sensitivity. In humans, mutations in steroidogenic factor-1 (SF-1), one of the critical factors involved in testis development, have been reported to cause gonadal dysgenesis with or without adrenal failure in 46,XY individuals. OBJECTIVE: We report a SF-1 mutation that caused ambiguous genitalia associated with strikingly different hormonal phenotypes in two affected 46,XY children from the same family. METHODS: Hormonal evaluation included testosterone (T), anti-Mullerian hormone (AMH), inhibin B, FSH, and LH measurements during the first weeks of life, a period when physiological activation of the gonadotropin-gonadal system occurs. Direct DNA sequencing of the coding sequence of the SF-1 and the androgen receptor (AR) genes was performed. RESULTS: Both 46,XY children had ambiguous genitalia with no Mullerian structures and no adrenal insufficiency. The older child showed normal elevation of T (up to 7.6 nmol/liter, 2.2 ng/ml), AMH (504 pmol/liter, 70.6 ng/ml), inhibin B (245 pg/ml), FSH, and LH during the first weeks, which led to a presumptive diagnosis of partial androgen insensitivity syndrome. The AR sequence was, however, normal. In the second child, T, AMH, and inhibin B were low, suggesting gonadal dysgenesis. In both children and their mother, a c.536delC frameshift mutation in the SF-1 gene was found. This mutation terminates translation at position 295, removing the ligand-binding domain and the activation function 2 (AF-2) domain, a critical domain for SF-1 transactivating activity. CONCLUSIONS: The usual markers of testis dysgenesis may be normal in 46,XY individuals with SF-1 mutation. Screening for SF-1 mutation should be performed in subjects with apparent partial androgen insensitivity syndrome and no mutation in the AR gene.

Serum anti-Müllerian hormone and inhibin B in disorders of spermatogenesis.

This study investigates circulating concentrations of AMH and inhibin B in men with azoospermia. Serum AMH and inhibin B are significantly lower in the men with nonobstructive azoospermia compared to the controls and the men with obstructive azoospermia, suggesting that these hormones could be markers of nonobstructive azoospermia.

Gonadal function in low birth weight infants: a pilot study.

OBJECTIVE: To evaluate gonadal function and anti-Müllerian hormone (AMH) serum concentrations during the first 3 months of life in low birth weight (low-BW) and normal birth weight (normal-BW) infants. INFANTS: Twenty low-BW and 29 normal-BW infants were studied. METHODS: The pituitary-gonadal axis was evaluated by a GnRH agonist test (leuprolide acetate, 10 microg/kg s.c.). Circulating concentrations of gonadotropins, steroid hormones, sex hormone binding globulin, inhibin B and AMH were determined by specific assays. RESULTS: In both sexes, basal concentrations of gonadotropins, sex steroids, sex hormone binding globulin and inhibin B were similar between low-BW and normal-BW infants. However, AMH concentrations were significantly higher in low-BW compared to normal-BW females (p = 0.004). This was not observed in males. After leuprolide administration, estradiol concentrations were higher in low-BW compared to normal-BW females (p = 0.043). In males, post-stimulated sex steroid concentrations were similar in both groups except for 17-OHP, which was significantly higher after leuprolide in the low-BW group (p = 0.023). CONCLUSIONS: An increase in AMH and post-stimulated estradiol serum concentrations suggests altered follicular development in low-BW girls. In contrast, the normal circulating levels of AMH and inhibin B seem to indicate that Sertoli cell function is normal in low-BW boys. We suggest that ovarian function seems to be more vulnerable than testicular function in infants with intrauterine growth restriction.

Factors and markers of growth hormone secretion and gonadal function in Fanconi anemia.

UNLABELLED: Many factors may be involved in the growth and gonadal dysfunction of Fanconi anemia (FA). OBJECTIVE: To evaluate the (1) relationship between FA presentation, including genital abnormalities and pituitary stalk interruption syndrome (PSIS), (2) markers of growth hormone (GH) deficiency and gonadal function, and (3) factors influencing final height and gonadal function. PATIENTS: Twenty five patients with FA were included, 17 of them were given bone marrow transplantation. RESULTS: Six patients were diagnosed with GH deficiency and PSIS (group A), whereas 19 had no evidence of GH deficiency (group B). In group A, all patients had more than 3 FA malformations and all 5 boys had cryptorchidism associated with microphallus in 4. All patients had heights and plasma insulin-like growth factor I < -3SD. Final height was reached in 15 patients and was < or = -2SD in 12 of them, all but 3 were born small for gestational age and/or given norethandrolone and/or corticosteroids. Gonadal function was abnormal in 5/7 boys and 4/5 girls evaluated at pubertal age. The plasma concentrations were low in 4/9 for antimüllerian hormone and in 3/9 for inhibin B, 3 of them had been given bone marrow transplantation. CONCLUSIONS: PSIS can be part of a severe FA phenotype. It seems to occur mainly in boys, with more than 3 malformations, microphallus and cryptorchidism. This phenotype is associated with normal blood counts, defining a new clinical subgroup of patients.