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Research question: The study aimed to evaluate the associations of endocrine and ultrasound characteristics with metabolic syndrome in women with polycystic ovary syndrome (PCOS), and whether these associations were modified by body mass index (BMI). Design(s): The study was a secondary analysis of baseline data from a randomized controlled trial of induction of ovulation in women with PCOS. Result(s): Among 947 Chinese women with PCOS, 153 (16.2%) were diagnosed with metabolic syndrome. The prevalence of metabolic syndrome in women with normal (<24 kg/m2) and high (>=24 kg/m2) BMI was 3.6% and 30.5%, respectively. In all women, a high free androgen index (FAI >=5%) was positively associated with metabolic syndrome (adjusted odds ratio [OR] 2.06, 95% confidence interval [CI] 1.11-3.82). High FAI was positively associated with metabolic syndrome among women with high BMI (adjusted OR 3.37, 95% CI 1.78-6.37), but the association was not significant in women with normal BMI (adjusted OR 1.27, 95% CI 0.34-4.70). The presence of polycystic ovary morphology was negatively associated with metabolic syndrome (adjusted OR 0.52, 95% CI 0.26-1.03) in all women (normal BMI adjusted OR 0.42, 95% CI 0.11-1.67; high BMI adjusted OR 0.54, 95% CI 0.23-1.28). LH, sex hormone-binding globulin (SHBG) and anti-Mullerian hormone (AMH) were negatively associated with metabolic syndrome. The associations of FAI, SHBG and AMH in relation to metabolic syndrome were significantly modified by BMI. Conclusion(s): The associations of endocrine characteristic with metabolic syndrome were modified by BMI in women with PCOS. Women with PCOS and normal BMI did not have an increased risk of metabolic syndrome.Copyright © 2019

Research question: The study aimed to evaluate the associations of endocrine and ultrasound characteristics with metabolic syndrome in women with polycystic ovary syndrome (PCOS), and whether these associations were modified by body mass index (BMI). Design(s): The study was a secondary analysis of baseline data from a randomized controlled trial of induction of ovulation in women with PCOS. Result(s): Among 947 Chinese women with PCOS, 153 (16.2%) were diagnosed with metabolic syndrome. The prevalence of metabolic syndrome in women with normal (<24 kg/m2) and high (>=24 kg/m2) BMI was 3.6% and 30.5%, respectively. In all women, a high free androgen index (FAI >=5%) was positively associated with metabolic syndrome (adjusted odds ratio [OR] 2.06, 95% confidence interval [CI] 1.11-3.82). High FAI was positively associated with metabolic syndrome among women with high BMI (adjusted OR 3.37, 95% CI 1.78-6.37), but the association was not significant in women with normal BMI (adjusted OR 1.27, 95% CI 0.34-4.70). The presence of polycystic ovary morphology was negatively associated with metabolic syndrome (adjusted OR 0.52, 95% CI 0.26-1.03) in all women (normal BMI adjusted OR 0.42, 95% CI 0.11-1.67; high BMI adjusted OR 0.54, 95% CI 0.23-1.28). LH, sex hormone-binding globulin (SHBG) and anti-Mullerian hormone (AMH) were negatively associated with metabolic syndrome. The associations of FAI, SHBG and AMH in relation to metabolic syndrome were significantly modified by BMI. Conclusion(s): The associations of endocrine characteristic with metabolic syndrome were modified by BMI in women with PCOS. Women with PCOS and normal BMI did not have an increased risk of metabolic syndrome.Copyright © 2019

Study question: In a population of men within a birth cohort, are features of an adverse cardiometabolic profile in late adolecence associated with impaired testicular function at 20 years of age? Summary answer: Despite the majority of men being only 20 years old, with a normal BMI, features of cardiometabolic disorder were associated with signs of testicular impairment. What is known already: An adverse cardiometabolic profile in adulthood has been reported to be associated with impaired testicular function; however no data exists from younger men. Hence it is unclear whether the metabolic disorder predates the adverse testicular function, or whether it is the lower serum testosterone concentration that predisposes the man to metabolic disorder in later life. Study design, size, duration: The Raine Study recruited 2900 women in pregnancy and retained the 2868 children born to form the Raine Study cohort. At 17 years of age males underwent a liver ultrasound for fatty liver (n = 490), and serum cytokines were measured (n = 520). At 20 years, measures included blood biochemistry (n = 618), a DEXA scan (n = 634), and a testicular assessment performed; semen sample (n = 365), testicular ultrasound (n = 404) and serum testosterone, LH, FSH and inhibin B concentrations were assayed (n = 620). Participants/materials, setting, methods: Fasting bloods were analysed for serum IL-18 by ELISA, tumor necrosis factor receptors (TNFR1 & 2) by cytometric bead array, and liver enzymes, insulin, glucose, lipids, high sensitivity CRP (hsCRP) and uric acid. Homeostasis model assessment (HOMA) was calculated and insulin resistance (IR) was defined by a HOMA>4. DEXA measurement was performed for lean and total fat mass. A cluster analysis was used to derive high-risk groups with features consistent with the metabolic syndrome. Main results and the role of chance: Participants that had testicular assess-ment were similar clinically to those that declined participation. The prevalence of

STUDY DESIGN, SIZE, DURATION: This study was a secondary analysis of the Polycystic Ovary Syndrome Acupuncture and Clomiphene Trial (PCOSAct), a large randomized controlled trial conducted at 27 hospitals from 2012 to 2015 in mainland China. PARTICIPANTS/MATERIALS, SETTING, METHODS: Out of 1000 women with PCOS, SHS exposure status were available in 500 women, of whom 271 women were non-exposed and 229 exposed to cigarette smoke (170 women ?10 cigarettes per day as low-SHS exposed and 59 women >10 cigarettes per day as high-SHS exposed). We compared circulating sex steroids, glucose and lipid metabolism, metabolic syndrome and phenotypes, fertility and obstetric outcomes between non-exposed and exposed women. MAIN RESULTS AND THE ROLE OF CHANCE: Women exposed to SHS, compared to non-exposed women, had a higher serum total testosterone (1.7 vs 1.5 nmol/L, P = 0.01), free androgen index (5.7 vs 4.0, P = 0.001) and lower sex hormone binding globulin (30.1 vs 35.6 nmol/L, P = 0.03). Metabolic syndrome, but not other phenotypes, was more frequent in exposed women as compared to nonexposed women (21.8 vs 13.3%, adjusted odds ratio (OR)=1.66; 95% CI, 1.022.71, P = 0.04). Ovulation rates between exposed and nonexposed groups were not significantly different (76.9 vs 82.9%, adjusted OR=0.72; 95% CI, 0.451.15, P = 0.17). Conception rates were significant lower in the exposed group (26.6 vs 36.9%; adjusted OR=0.61; 95% CI, 0.410.91; P = 0.01), while clinical pregnancy and live birth rates showed a similar trend that was not statistically significant. Gestational age, birth weight and other obstetric outcomes were not affected by SHS exposure. LIMITATIONS, REASONS FOR CAUTION: Data on SHS exposure were missing in 50% of the women. We did not assay serum nicotine or cotinine levels to quantify the SHS exposure status. WIDER IMPLICATIONS OF THE FINDINGS: These data suggest that smoking partners of infertile women with PCOS who seek treatment should be advised to quit smoking.Copyr

Bisphenol A (BPA) is a ubiquitous chemical suspected to possess oestrogenic hormonal activities. Male population studies suggest a negative impact on testicular function. As Sertoli cell proliferation occurs during fetal or early postnatal life, it is speculated that oestrogenic environmental exposures may influence mature testicular function. Among 705 Western Australian Pregnancy Cohort (Raine) Study men aged 20-22 years, 404 underwent testicular ultrasound examination (149 had maternal serum available), and/or 365 provided semen (136 had maternal serum) and/or 609 serum samples for sex steroids, gonadotrophins and inhibin B analysis (244 had maternal serum). Maternal serum collected at 18 and 34 weeks' gestation was pooled and assayed for concentrations of total BPA (free plus conjugated) as an estimate of antenatal exposure. Testicular volume was calculated by ultrasonography, and semen analysis performed. Serum LH, FSH and inhibin B were measured by immunoassay; testosterone, oestradiol, oestrone andBPA were measured by liquid chromatography-mass spectrometry. BPA levels were detectable in most (89%) maternal serum samples. After adjustment for maternal smoking, abstinence and varicocele, sperm concentration and motility were significantly correlated to maternal serum BPA (r = 0.18; P = 0.04 for both). No other associations of maternal serum BPA with testicular function were observed.Copyright © 2017

STUDY DESIGN, SIZE, DURATION: This study was a secondary analysis of the Polycystic Ovary Syndrome Acupuncture and Clomiphene Trial (PCOSAct), a large randomized controlled trial conducted at 27 hospitals from 2012 to 2015 in mainland China. PARTICIPANTS/MATERIALS, SETTING, METHODS: Out of 1000 women with PCOS, SHS exposure status were available in 500 women, of whom 271 women were non-exposed and 229 exposed to cigarette smoke (170 women ?10 cigarettes per day as low-SHS exposed and 59 women >10 cigarettes per day as high-SHS exposed). We compared circulating sex steroids, glucose and lipid metabolism, metabolic syndrome and phenotypes, fertility and obstetric outcomes between non-exposed and exposed women. MAIN RESULTS AND THE ROLE OF CHANCE: Women exposed to SHS, compared to non-exposed women, had a higher serum total testosterone (1.7 vs 1.5 nmol/L, P = 0.01), free androgen index (5.7 vs 4.0, P = 0.001) and lower sex hormone binding globulin (30.1 vs 35.6 nmol/L, P = 0.03). Metabolic syndrome, but not other phenotypes, was more frequent in exposed women as compared to nonexposed women (21.8 vs 13.3%, adjusted odds ratio (OR)=1.66; 95% CI, 1.022.71, P = 0.04). Ovulation rates between exposed and nonexposed groups were not significantly different (76.9 vs 82.9%, adjusted OR=0.72; 95% CI, 0.451.15, P = 0.17). Conception rates were significant lower in the exposed group (26.6 vs 36.9%; adjusted OR=0.61; 95% CI, 0.410.91; P = 0.01), while clinical pregnancy and live birth rates showed a similar trend that was not statistically significant. Gestational age, birth weight and other obstetric outcomes were not affected by SHS exposure. LIMITATIONS, REASONS FOR CAUTION: Data on SHS exposure were missing in 50% of the women. We did not assay serum nicotine or cotinine levels to quantify the SHS exposure status. WIDER IMPLICATIONS OF THE FINDINGS: These data suggest that smoking partners of infertile women with PCOS who seek treatment should be advised to quit smoking.Copyr

Bisphenol A (BPA) is a ubiquitous chemical suspected to possess oestrogenic hormonal activities. Male population studies suggest a negative impact on testicular function. As Sertoli cell proliferation occurs during fetal or early postnatal life, it is speculated that oestrogenic environmental exposures may influence mature testicular function. Among 705 Western Australian Pregnancy Cohort (Raine) Study men aged 20-22 years, 404 underwent testicular ultrasound examination (149 had maternal serum available), and/or 365 provided semen (136 had maternal serum) and/or 609 serum samples for sex steroids, gonadotrophins and inhibin B analysis (244 had maternal serum). Maternal serum collected at 18 and 34 weeks' gestation was pooled and assayed for concentrations of total BPA (free plus conjugated) as an estimate of antenatal exposure. Testicular volume was calculated by ultrasonography, and semen analysis performed. Serum LH, FSH and inhibin B were measured by immunoassay; testosterone, oestradiol, oestrone andBPA were measured by liquid chromatography-mass spectrometry. BPA levels were detectable in most (89%) maternal serum samples. After adjustment for maternal smoking, abstinence and varicocele, sperm concentration and motility were significantly correlated to maternal serum BPA (r = 0.18; P = 0.04 for both). No other associations of maternal serum BPA with testicular function were observed.Copyright © 2017

Study question: In a population of men within a birth cohort, are features of an adverse cardiometabolic profile in late adolecence associated with impaired testicular function at 20 years of age? Summary answer: Despite the majority of men being only 20 years old, with a normal BMI, features of cardiometabolic disorder were associated with signs of testicular impairment. What is known already: An adverse cardiometabolic profile in adulthood has been reported to be associated with impaired testicular function; however no data exists from younger men. Hence it is unclear whether the metabolic disorder predates the adverse testicular function, or whether it is the lower serum testosterone concentration that predisposes the man to metabolic disorder in later life. Study design, size, duration: The Raine Study recruited 2900 women in pregnancy and retained the 2868 children born to form the Raine Study cohort. At 17 years of age males underwent a liver ultrasound for fatty liver (n = 490), and serum cytokines were measured (n = 520). At 20 years, measures included blood biochemistry (n = 618), a DEXA scan (n = 634), and a testicular assessment performed; semen sample (n = 365), testicular ultrasound (n = 404) and serum testosterone, LH, FSH and inhibin B concentrations were assayed (n = 620). Participants/materials, setting, methods: Fasting bloods were analysed for serum IL-18 by ELISA, tumor necrosis factor receptors (TNFR1 & 2) by cytometric bead array, and liver enzymes, insulin, glucose, lipids, high sensitivity CRP (hsCRP) and uric acid. Homeostasis model assessment (HOMA) was calculated and insulin resistance (IR) was defined by a HOMA>4. DEXA measurement was performed for lean and total fat mass. A cluster analysis was used to derive high-risk groups with features consistent with the metabolic syndrome. Main results and the role of chance: Participants that had testicular assess-ment were similar clinically to those that declined participation. The prevalence of

Activin production and signaling must be strictly regulated for normal testis development and function. Inhibins are potent activin inhibitors; mice lacking the inhibin-alpha gene (Inha-/- mice) cannot make inhibin and consequently have highly elevated activin and FSH serum concentrations and excessive activin signaling, resulting in somatic gonadal tumors and infertility. Dose-dependent effects of activin in testicular biology have been widely reported; hence, we hypothesized that male mice lacking one copy of the Inha gene would produce less inhibin and have an abnormal reproductive phenotype. To test this, we compared hormone concentrations, testis development, and sperm production in Inha+/+ and Inha+/- mice. Serum and testicular inhibin-alpha concentrations in adult Inha+/- mice were approximately 33% lower than wild type, whereas activin A, activin B, FSH, LH, and T were normal. Sixteen-day-old Inha+/- mice had a mixed phenotype, with tubules containing extensive germ cell depletion juxtaposed to tubules with advanced Sertoli and germ cell development. This abnormal phenotype resolved by day 28. By 8 weeks, Inha+/- testes were 11% larger than wild type and supported 44% greater daily sperm production. By 26 weeks of age, Inha+/- testes had distinct abnormalities. Although still fertile, Inha+/- mice had a 27% reduction in spermatogenic efficiency, a greater proportion of S-phase Sertoli cells and lower Leydig cell CYP11A1 expression. This study is the first to identify an intratesticular role for inhibin/inhibin-alpha subunit, demonstrating that a threshold level of this protein is required for normal testis development and to sustain adult somatic testicular cell function.Copyright © 2015 by the Endocrine Society.

Activin production and signaling must be strictly regulated for normal testis development and function. Inhibins are potent activin inhibitors; mice lacking the inhibin-alpha gene (Inha-/- mice) cannot make inhibin and consequently have highly elevated activin and FSH serum concentrations and excessive activin signaling, resulting in somatic gonadal tumors and infertility. Dose-dependent effects of activin in testicular biology have been widely reported; hence, we hypothesized that male mice lacking one copy of the Inha gene would produce less inhibin and have an abnormal reproductive phenotype. To test this, we compared hormone concentrations, testis development, and sperm production in Inha+/+ and Inha+/- mice. Serum and testicular inhibin-alpha concentrations in adult Inha+/- mice were approximately 33% lower than wild type, whereas activin A, activin B, FSH, LH, and T were normal. Sixteen-day-old Inha+/- mice had a mixed phenotype, with tubules containing extensive germ cell depletion juxtaposed to tubules with advanced Sertoli and germ cell development. This abnormal phenotype resolved by day 28. By 8 weeks, Inha+/- testes were 11% larger than wild type and supported 44% greater daily sperm production. By 26 weeks of age, Inha+/- testes had distinct abnormalities. Although still fertile, Inha+/- mice had a 27% reduction in spermatogenic efficiency, a greater proportion of S-phase Sertoli cells and lower Leydig cell CYP11A1 expression. This study is the first to identify an intratesticular role for inhibin/inhibin-alpha subunit, demonstrating that a threshold level of this protein is required for normal testis development and to sustain adult somatic testicular cell function.Copyright © 2015 by the Endocrine Society.

To test the efficacy and safety of leuprolide acetate (Lupron Depot®) in the treatment of Alzheimer's disease (AD), we conducted a 48-week, double-blind, placebo-controlled, dose-ranging study in women aged 65 years or older with mild to moderate AD. A total of 109 women with mild to moderate AD and a Mini-Mental State Examination score between 12 and 24 inclusive were randomized to low dose Lupron Depot® (11.25 mg leuprolide acetate), high dose Lupron Depot® (22.5 mg leuprolide acetate), or placebo injections every 12 weeks. There were no statistically significant differences in primary efficacy parameters (ADAS-Cog and ADCS-CGIC), although there was a non-statistically significant trend in favor of the high dose Lupron group on the ADAS-Cog. There were no statistically significant differences in secondary efficacy parameters (NPI, ADCS-ADL, BI, and ADCS-Severity Rating). However, in the a priori designated subgroup analysis of patients taking an acetylcholinesterase inhibitor (AChEI), there was a statistically significant benefit in the high dose group compared to both the low dose and placebo groups as determined by ADAS-Cog (mean decline: 0.18, 4.21, and 3.30), ADCS-CGIC (% subjects experiencing decline: 38, 82, and 63), and ADCS-ADL (mean decline: -0.54, -8.00, and -6.85), respectively. No differences between treatment groups were seen on the NPI, ADCS-CGI Severity Rating, or the BI in the subgroup analysis. These data indicate that cognitive function is preserved in patients treated with high dose Lupron who were already using AChEIs. The positive interaction between Lupron and AChEIs warrants further investigation for the treatment of AD.

The blood-testis barrier (BTB) sequesters meiotic spermatocytes and differentiating spermatids away from the vascular environment. We aimed to assess whether meiosis and postmeiotic differentiation could occur when the BTB is permeable. Using a model of meiotic suppression and reinitiation, BTB function was assessed using permeability tracers of small, medium, and large (0.6-, 70-, and 150-kDa) sizes to emulate blood- and lymphatic-borne factors that could cross the BTB. Adult rats (n = 9/group) received the GnRH antagonist acyline (10 wk) to suppress gonadotropins, followed by testosterone (24cm Silastic implant), for 2, 4, 7, 10, 15, and 35 days. In acyline-suppressed testes, all tracers permeated the seminiferous epithelium. As spermatocytes up to diplotene stage XIII reappeared, both the 0.6- and 70-kDa tracers, but not 150 kDa, permeated around these cells. Intriguingly, the 0.6- and 70-kDa tracers were excluded from pachytene spermatocytes at stages VII and VIII but not in subsequent stages. The BTB became progressively impermeable to the 0.6- and 70-kDa tracers as stages IV-VII round spermatids reappeared in the epithelium. This coincided with the appearance of the tight junction protein, claudin-12, in Sertoli cells and at the BTB. We conclude that meiosis can occur when the BTB is permeable to factors up to 70 kDa during the reinitiation of spermatogenesis. Moreover, BTB closure corresponds with the presence of particular pachytene spermatocytes and round spermatids. This research has implications for understanding the effects of BTB dynamics in normal spermatogenesis and also potentially in states where spermatogenesis is suppressed, such as male hormonal contraception or infertility. Copyright © 2014 by the Endocrine Society.

The blood-testis barrier (BTB) sequesters meiotic spermatocytes and differentiating spermatids away from the vascular environment. We aimed to assess whether meiosis and postmeiotic differentiation could occur when the BTB is permeable. Using a model of meiotic suppression and reinitiation, BTB function was assessed using permeability tracers of small, medium, and large (0.6-, 70-, and 150-kDa) sizes to emulate blood- and lymphatic-borne factors that could cross the BTB. Adult rats (n = 9/group) received the GnRH antagonist acyline (10 wk) to suppress gonadotropins, followed by testosterone (24cm Silastic implant), for 2, 4, 7, 10, 15, and 35 days. In acyline-suppressed testes, all tracers permeated the seminiferous epithelium. As spermatocytes up to diplotene stage XIII reappeared, both the 0.6- and 70-kDa tracers, but not 150 kDa, permeated around these cells. Intriguingly, the 0.6- and 70-kDa tracers were excluded from pachytene spermatocytes at stages VII and VIII but not in subsequent stages. The BTB became progressively impermeable to the 0.6- and 70-kDa tracers as stages IV-VII round spermatids reappeared in the epithelium. This coincided with the appearance of the tight junction protein, claudin-12, in Sertoli cells and at the BTB. We conclude that meiosis can occur when the BTB is permeable to factors up to 70 kDa during the reinitiation of spermatogenesis. Moreover, BTB closure corresponds with the presence of particular pachytene spermatocytes and round spermatids. This research has implications for understanding the effects of BTB dynamics in normal spermatogenesis and also potentially in states where spermatogenesis is suppressed, such as male hormonal contraception or infertility. Copyright © 2014 by the Endocrine Society.

Study question: To prospectively study early life influences, in-utero, childhood and adolescence, that may impact on markers of testicular function: testicular volume (TV), sperm production (total motile sperm [TMS], sperm chromatin structural assay [SCSA], and hormone production (serum FSH, LH, testosterone [T], and inhibin B [InhB]), in men aged 20-22 years. Summary answer: 26.3% of men had an initial semen sample with abnormal morphology 18.9% had low total sperm number according to the WHO minimal criteria; there was a significant correlation between the total motile sperm count and testicular volume. In-utero growth restraint and maternal smoking were associated with reduced TMS in adulthood. What is known already: It is alleged that sperm counts are decreasing, with evidence for adverse effects of chronic smoking and in-utero exposure, although there is conflicting evidence for the effect of intrauterine growth restraint upon sperm production. Adult adiposity is associated with adverse effects on sperm counts, SCSA and hormonal markers of testicular function. Such studies are prone to selection bias as the cohorts have very low recruitment rates and compromise individuals with biased fertility status. Study design, size, duration: Prospective cohort study, using theWestern Australian Pregnancy (Raine) Cohort, who underwent regular assessment since birth in 1990-1991, including fetal measurements for half the cohort. Part of the 20 year follow-up involved testicular assessment. Of available 911 men; 696 attended general assessment and 423 took part in the testicular study. Participants/materials, setting, methods: 404 men underwent testicular ultrasound examination 365 underwent >=1 semen assessments (recruitment was 40% overall 46.1% of available cohort 60.3% of attendees of the 20 year assessments). General health assessment and DEXA scanning for adiposity was performed at a teaching hospital, and ultrasound examination and semen assessments at separate loca

Study question: To prospectively study early life influences, in-utero, childhood and adolescence, that may impact on markers of testicular function: testicular volume (TV), sperm production (total motile sperm [TMS], sperm chromatin structural assay [SCSA], and hormone production (serum FSH, LH, testosterone [T], and inhibin B [InhB]), in men aged 20-22 years. Summary answer: 26.3% of men had an initial semen sample with abnormal morphology 18.9% had low total sperm number according to the WHO minimal criteria; there was a significant correlation between the total motile sperm count and testicular volume. In-utero growth restraint and maternal smoking were associated with reduced TMS in adulthood. What is known already: It is alleged that sperm counts are decreasing, with evidence for adverse effects of chronic smoking and in-utero exposure, although there is conflicting evidence for the effect of intrauterine growth restraint upon sperm production. Adult adiposity is associated with adverse effects on sperm counts, SCSA and hormonal markers of testicular function. Such studies are prone to selection bias as the cohorts have very low recruitment rates and compromise individuals with biased fertility status. Study design, size, duration: Prospective cohort study, using theWestern Australian Pregnancy (Raine) Cohort, who underwent regular assessment since birth in 1990-1991, including fetal measurements for half the cohort. Part of the 20 year follow-up involved testicular assessment. Of available 911 men; 696 attended general assessment and 423 took part in the testicular study. Participants/materials, setting, methods: 404 men underwent testicular ultrasound examination 365 underwent >=1 semen assessments (recruitment was 40% overall 46.1% of available cohort 60.3% of attendees of the 20 year assessments). General health assessment and DEXA scanning for adiposity was performed at a teaching hospital, and ultrasound examination and semen assessments at separate loca

Ovarian tissue cryopreservation and transplantation is a form of fertility preservation offered to young women at high risk of losing ovarian function after cancer treatment. While there have been successful births resulting from orthotopic site grafts, we report the first case of an ongoing pregnancy from a heterotopic graft in a patient who had previously undergone bilateral oopherectomy for a granulosa cell tumour. Frozen-thawed ovarian tissue was transplanted to the anterior abdominal wall. Subsequent ovarian stimulation and transabdominal ultrasound-guided oocyte retrieval from the grafts resulted in two oocytes. These were fertilized with ICSI and two embryos were transferred. Serial ultrasounds have confirmed an ongoing 26-week intrauterine twin pregnancy. Thus, this first demonstration of a pregnancy from a heterotopic graft site provides unequivocal evidence that cryopreservation preserves complete follicle development and that normal ovarian function can occur at a non-ovarian site. This provides optimism for further efforts to assist women who have had oophorectomy and pelvic surgery or radiotherapy, without an appropriate orthotopic site for grafting. © 2013 © The Author 2013. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Objective Investigation of clinicians' understanding of early menopause diagnosis/management in women with breast cancer. Methods A cross-sectional study of 176 randomly recruited Australian clinicians (35 gynecologists, 35 endocrinologists, 36 oncologists, 35 breast surgeons and 35 general practitioners (GPs)) involved in the care of women with breast cancer. This questionnaire study utilized an index case to assess understanding of early menopause diagnosis and management. Analysis involved descriptive statistics, chi2 tests and Student's t-test. Results Significant differences between clinician groups regarding diagnostic criteria for early menopause were observed; gynecologists, endocrinologists and GPs selected amenorrhea > 12 months, whereas oncologists and breast surgeons selected elevated serum follicle stimulating hormone level (p < 0.05). Non-hormonal treatment was preferred by most clinician groups. Complementary/alternative medicines were more commonly prescribed by breast surgeons (57%), gynecologists (54%) and endocrinologists (49%) compared to oncologists (28%) or GPs (9%) (p = 0.0001). Exercise (63%) and nutrition (66%) were selected by most gynecologists for treatment of hot flushes, whereas endocrinologists (91%), oncologists (94%), breast surgeons (69%) and GPs (63%) prescribed venlafaxine. Hormone therapy was mainly prescribed by breast surgeons (43%) compared to other groups (p = 0.001). Most clinicians reported that the main problem with menopausal therapies was failure to resolve hot flushes. Exercise, lifestyle and stress management were recommended by all clinician groups for treatment of anxiety/depression. Conclusion This exploratory study demonstrated a lack of consensus between clinician groups in their investigation, diagnosis and management of early menopause in women with breast cancer, with implications for both diagnosis and treatment. © 2013 International Menopause Society.

Ovarian tissue cryopreservation and transplantation is a form of fertility preservation offered to young women at high risk of losing ovarian function after cancer treatment. While there have been successful births resulting from orthotopic site grafts, we report the first case of an ongoing pregnancy from a heterotopic graft in a patient who had previously undergone bilateral oopherectomy for a granulosa cell tumour. Frozen-thawed ovarian tissue was transplanted to the anterior abdominal wall. Subsequent ovarian stimulation and transabdominal ultrasound-guided oocyte retrieval from the grafts resulted in two oocytes. These were fertilized with ICSI and two embryos were transferred. Serial ultrasounds have confirmed an ongoing 26-week intrauterine twin pregnancy. Thus, this first demonstration of a pregnancy from a heterotopic graft site provides unequivocal evidence that cryopreservation preserves complete follicle development and that normal ovarian function can occur at a non-ovarian site. This provides optimism for further efforts to assist women who have had oophorectomy and pelvic surgery or radiotherapy, without an appropriate orthotopic site for grafting. © 2013 © The Author 2013. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Objective Investigation of clinicians' understanding of early menopause diagnosis/management in women with breast cancer. Methods A cross-sectional study of 176 randomly recruited Australian clinicians (35 gynecologists, 35 endocrinologists, 36 oncologists, 35 breast surgeons and 35 general practitioners (GPs)) involved in the care of women with breast cancer. This questionnaire study utilized an index case to assess understanding of early menopause diagnosis and management. Analysis involved descriptive statistics, chi2 tests and Student's t-test. Results Significant differences between clinician groups regarding diagnostic criteria for early menopause were observed; gynecologists, endocrinologists and GPs selected amenorrhea > 12 months, whereas oncologists and breast surgeons selected elevated serum follicle stimulating hormone level (p < 0.05). Non-hormonal treatment was preferred by most clinician groups. Complementary/alternative medicines were more commonly prescribed by breast surgeons (57%), gynecologists (54%) and endocrinologists (49%) compared to oncologists (28%) or GPs (9%) (p = 0.0001). Exercise (63%) and nutrition (66%) were selected by most gynecologists for treatment of hot flushes, whereas endocrinologists (91%), oncologists (94%), breast surgeons (69%) and GPs (63%) prescribed venlafaxine. Hormone therapy was mainly prescribed by breast surgeons (43%) compared to other groups (p = 0.001). Most clinicians reported that the main problem with menopausal therapies was failure to resolve hot flushes. Exercise, lifestyle and stress management were recommended by all clinician groups for treatment of anxiety/depression. Conclusion This exploratory study demonstrated a lack of consensus between clinician groups in their investigation, diagnosis and management of early menopause in women with breast cancer, with implications for both diagnosis and treatment. © 2013 International Menopause Society.

Estrogen (17beta-estradiol, E2)-deficient aromatase knockout (ArKO) mice develop Sertoli and Leydig cells at puberty. We hypothesized that estrogen, directly or indirectly, regulates genes responsible for somatic cell differentiation and steroidogenesis. ArKO ovaries expressed estrogen receptors alpha and beta, and LH receptor, indices of estrogen responsiveness in the ovary. Wild-type (Wt) and ArKO mice received either E2 or placebo for 3 wk, from 7-10 wk of age. E2 decreased serum FSH and LH and increased uterine weights of 10-wk-old ArKO mice. We measured mRNA expression of Sertoli cell, Sry-like HMG box protein 9 (Sox9); three upstream transcription factors, liver receptor homolog-1 (Lrh-1), steroidogenic factor 1, and dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on the X chromosome gene 1; and one downstream factor, MUllerian-inhibiting substance. Placebo-treated ArKO ovaries have increased Sox9 (15-fold; P < 0.001), Mullerian-inhibiting substance (2.9-foLd), Lrh-1 (7.7-fold), and dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on the X chromosome gene 1 (12-fold) expression compared with Wt at 10 wk. Steroidogenic factor 1 was similar to Wt. Consistent with increased serum T levels and Leydig cells in their ovaries, placebo-treated ArKO ovaries had increased 17alpha-hydroxylase, 17beta-hydroxysteroid dehydrogenase type-3, and 17beta-hydroxysteroid dehydrogenase type-1 expression compared with Wt at 10 wk. E2 treatment for 3 wk improved the ovarian phenotype, decreased development of Sertoli cells, decreased the expression of Sox9, Lrh-1, and the steroidogenic enzymes in ArKO ovaries, and induced ovulation in some cases. In conclusion, the expression of the genes regulating somatic cell differentiation is directly or indirectly responsive to estrogen.

Purpose: Diagnosis of dysgerminoma in the paediatric age group is uncommon, and most cases arise from dysgenetic gonads of 46, XY pure gonadal dysgenesis (PGD) patients. Bilateral gonadectomy is mandatory in these patients. So, the preoperative diagnosis of PGD is important in order to avoid multiple surgical procedures and delayed patient information in the case of a suspected 'ovarian' tumour. Our aim was to discuss preoperative clues that can lead to suspicion of dysgerminoma in the context of PGD. Material(s) and Method(s): We reviewed the charts of six patients treated for dysgerminoma associated with 46, XY PGD. We focused on particularities of clinical and biological evaluations. Result(s): Median age at diagnosis was 11 years. Pubertal development was absent or incomplete even at late ages. Dysgerminoma was associated with gonadoblastoma foci in all cases. Tumoral marker profile was a normal alfafetoprotein level, a high lactate dehydrogenase level and normal or moderate human chorionic gonadotropin (betaHCG) secretion, except for one patient who had a mixed tumour with notably a choriocarcinoma share (high betaHCG). Follicle-stimulating hormone (FSH) level was very high in all patients tested and, interestingly, also in one prepubertal patient. Conclusion(s): In the case of a suspected ovarian tumour, delayed pubertal development, moderate betaHCG level and elevated FSH level are clinical and biological clues to a diagnosis of dysgerminoma in the context of PGD and should prompt karyotype analysis before surgery. Because FSH is an efficient indirect marker of this condition, we suggest including this analysis in the management of gonadal tumours. © 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Background. Androgens acting via the androgen receptor bring about stimulation and maintenance of spermatogenesis. If mutations in the androgen-receptor gene interfere with the receptor's function, this effect may partly account for impaired spermatogenesis. We aimed to find out whether expansion of a trinucleotide repeat in the androgen-receptor gene is associated with male infertility. Methods. We analysed 67 coded semen and blood samples from a predominantly white group of male infertility patients and controls. Clinical analyses included cause of infertility, sperm count, and reproductive hormone concentrations. Analysis of trinucleotide (CAG) repeat length and point mutations in the androgen-receptor gene was done by PCR, single-stranded conformational polymorphism,and DNA sequencing. Findings. Screening and characterisation of the androgen-receptor gene in 35 patients and 32 controls showed no point mutations in the gene. 30 of the infertile patients had idiopathic azoospermia or oligozoospermia, and these men had significantly longer CAG repeat tracts than controls (mean 23.2 [SE 0.7] vs 20.5 [0.3], p = 0.0001). The odds of having CAG repeat lengths of 20 were six-fold higher for fertile men than for men with a spermatogenic disorder. Interpretation. Our results indicate a relation between CAG repeat length in the androgen-receptor gene and the risk of defective spermatogenesis. With the use of intracytoplasmic sperm injection, this mutation could be inherited, possibly leading to an increase in male infertility in future generations. Should further elongation of the CAG repeat occur in these future generations, there is an added risk of increased severity of male infertility, and potentially an increased incidence of neurodegenerative disease.

Objective: To determine that anti-Mullerian hormone (AMH) has been shown to inhibits E2 production in rodents and in luteinized granulosa cells (GC). We determined whether this occurs in human cells most highly expressing AMH (i.e., from small antral follicles) and whether this is an effect on aromatase promoter activity. We also investigated the effects of AMH on other factors determining FSH sensitivity. Design(s): Granulosa cells were exposed to AMH with and without gonadotropins for 48 hours. Setting(s): University laboratory. Patient(s): Not applicable. Intervention(s): None. Main Outcome Measure(s): Aromatase and FSH receptor messenger RNA expression measured using real time quantitative polymerase chain reaction (PCR). Aromatase promoter II activity measured using a luciferase assay. Estradiol, inhibin A and B, and vascular endothelial growth factor production were measured in the conditioned medium. Result(s): The AMH decreased gonadotropin-stimulated aromatase expression and decreased forskolin-stimulated aromatase in KGN cells and this effect was through a dose-dependent inhibition of promoter II. Surprisingly, AMH also reduced FSH receptor mRNA expression. High AMH doses had no effect on inhibin B, whereas a low dose stimulated production. There was no effect on inhibin A or vascular endothelial growth factor. Conclusion(s): The AMH inhibits factors affecting FSH sensitivity. As AMH levels decrease with follicle growth, this inhibition would be removed. The AMH overproduction in anovulatory polycystic ovaries (PCO) may therefore restrict folliculogenesis by an inhibitory effect on FSH sensitivity, thereby contributing to anovulation. © 2011 American Society for Reproductive Medicine.

The pituitary-ovarian axis describes a regulatory system in which pituitary gonadotrophins stimulate ovarian folliculogenesis and the production of both steroid and protein hormones, which in turn exercise feedback control on the pituitary and hypothalamus. The availability of a radioimmunoassay for serum inhibin has allowed exploration of inhibin's role in the regulation of follicle stimulating hormone (FSH). This gonadotrophin stimulates ovarian inhibin secretion within the physiological dose range, both after exogenous administration and during endogenous rises, as are seen during puberty and the mid-cycle FSH surge. No direct evidence of FSH suppression by inhibin administered to human subjects has been obtained. During periods of endogenously raised inhibin levels, however, FSH is suppressed, as seen during the luteal phase of the menstrual cycle (luteinizing hormone drives inhibin production at that time), during pregnancy and in patients with inhibin-secreting granulosa cell tumours of the ovary. In contrast, decreased inhibin levels in the presence of intact hypothalamo-pituitary function result in increased FSH concentrations - as in early childhood, during the luteal-follicular transition and during reproductive ageing. After the menopause inhibin levels are normally undetectable, with FSH being markedly elevated. These observations are compatible with a role for endogenous inhibin in the regulation of FSH, though the contribution of oestradiol is in most instances impossible to dissect out separately.

Plants contain compounds with oestrogen-like action called phytoestrogens. Soy contains daidzin, a potent phytoestrogen, and wheat flour contains less potent enterolactones. We aimed to show in 58 postmenopausal women (age 54, range 30-70 years) with at least 14 hot flushes per week, that their daily diet supplemented with soy flour (n = 28) could reduce flushes compared with wheat flour (n = 30) over 12 weeks when randomised and double blind. Hot flushes significantly decreased in the soy and wheat flour groups (40% and 25% reduction, respectively <0.001 for both) with a significant rapid response in the soy flour group in 6 weeks (P < 0.001) that continued. Menopausal symptom score decreased significantly in both groups (P < 0.05). Urinary daidzein excretion confirmed compliance. Vaginal cell maturation, plasma lipids and urinary calcium remained unchanged. Serum FSH decreased and urinary hydroxyproline increased in the wheat flour group.

Adjunctive use of estrogen therapy has been shown to be effective in enhancing the treatment of schizophrenia in women. In men, consideration of estrogen therapy has been impacted by concerns of feminising side effects, however, clinical trials of the use of estrogen in treating prostate cancer, bone density loss and even aggression and psychosis in dementia or traumatic brain injury, show this to be a safe and effective therapy. The current 14-day randomised placebo-controlled trial in 53 men with schizophrenia was conducted to evaluate the efficacy of 2. mg oral estradiol valerate as an adjunct to atypical antipsychotic treatment. Results demonstrated for estradiol participants a more rapid reduction in general psychopathology that occurred in the context of greater increases in serum estrogen levels and reductions in FSH and testosterone levels. Approximately 28% of estradiol participants did not achieve an increase (at least a 50% from baseline) in serum estrogen suggesting that further research is needed to refine the type, dose and administration route for estrogen therapy in men. Findings do, however, suggest further exploration of a therapeutic role for adjunctive estradiol treatment in men with schizophrenia is warranted. © 2010 Elsevier B.V.

Background. Inhibin is an ovarian hormone that inhibits the secretion of follicle-stimulating hormone (FSH) by the anterior pituitary gland. Women with granulosa-cell tumors of the ovary have elevated serum inhibin concentrations, but whether the concentrations are increased in women with other ovarian tumors is unknown. Methods. We measured serum inhibin and FSH concentrations before surgery in 212 postmenopausal women with suspected ovarian cancer and after surgery in 210 of them. Results. Eighteen of the 22 women (82 percent) with mucinous carcinomas (mucinous cystadenocarcinomas and mucinous borderline cystic tumors) of the ovary had elevated serum inhibin concentrations, whereas only 9 of the 53 women (17 percent) with serous carcinomas (serous cystadenocarcinomas and serous borderline cystic tumors) had elevated levels. Serum inhibin concentrations were also elevated in 2 of 12 women (17 percent) with clear-cell carcinomas, 4 of 26 women (15 percent) with undifferentiated carcinomas, 3 of 3 women (100 percent) with granulosa- cell tumors, and 5 of 27 women (19 percent) with other ovarian cancers. The serum concentrations of inhibin were increased in 2 of 28 women (7 percent) with nonovarian pelvic cancers and 11 of 41 women (27 percent) with benign ovarian diseases. All women but one with initially elevated serum inhibin concentrations had low values one week after surgery. Serum inhibin concentrations correlated negatively with serum FSH concentrations (P = 0.05) in women with granulosa-cell tumors but not in women with other tumors, suggesting that the inhibin secreted by tumors in the latter group has decreased biologic activity. Conclusions. Serum inhibin concentrations are elevated in most postmenopausal women with mucinous carcinomas of the ovary and in some women with other types of epithelial ovarian tumors. The concentrations fall after tumor removal.

Background: Pulsatile GH secretion from the anterior pituitary is a key mediator of human growth regulation and is affected by a number of genetic and environmental factors. Activation of neuronal nicotinic acetylcholine (nACh) receptors promotes GH release, but the role of these receptors in growth regulation is unknown. Aim(s): Our aim was to assess the effect of a mutation in the alpha4 subunit of the nACh receptor on cholinergic-mediated GH release. Method(s): Forty-one healthy volunteers (24 male, age 36.2 +/- 12.2 yr, mean +/- SD) and 13 subjects with the alpha4-Ser248Phe mutation (four male, age 43.2 +/- 16.8 yr) were studied. Serum levels of GH, LH, FSH, prolactin, TSH, free T4, and cortisol were measured at baseline and at regular intervals after infusion of physostigmine. Height and weight were recorded in all participants as well as from additional family members with (n = 11, four male) and without (n = 16, seven male) the mutation. Result(s): Subjects with the mutation were shorter (1.62 +/- 0.08 vs. 1.72 +/- 0.09 m, P < 0.05) and had a greater body mass index (31 +/- 6 vs. 24 +/- 3kg/m 2, P < 0.05) than healthy volunteers and unaffected members of the pedigree. In controls, physostigmine markedly increased the serum levels of GH (mean increase, +732%). In contrast, the response to physostigmine was markedly blunted in subjects with the mutation (+104%, P > 0.2 vs. control). Conclusion(s): These findings suggest a role of the nACh receptor in human growth regulation. Copyright © 2008 by The Endocrine Society.

To investigate the role of inhibin in the control of follicle- stimulating hormone (FSH) secretion, we have measured levels of immunereactive inhibin (ir-inhibin), inhibin B, Pro-alphaC containing inhibins, FSH, luteinizing hormone (LH), and testosterone in twelve men with hematological malignancies before, during, and after chemotherapy. Inhibin B levels fell significantly by i month from a mean +/- SE baseline level of 273.2 +/- 32.8 pg/mL, reaching a nadir of 52.6 +/- 15.3 pg/mL at 4 months (P < 0.0001). FSH levels increased within the first month from a baseline level of 3.9 +/- 0.6 IU/L, reaching a peak level of 22.4 +/- 3.3 IU/L at 4 months (P < 0.0001). FSH and inhibin B were significantly and inversely correlated (r = 0.69, P < 0.0001). Pro-alphaC containing inhibin levels increased significantly (P < 0.05) at 8 months and were significantly and positively correlated with FSH (r = 0.88, P = 0.002). LH levels increased significantly but to a much lesser extent than FSH, the increase becoming evident only 4 months after treatment commenced (P < 0.03). Levels of ir-inhibin and testosterone remained unchanged throughout the study. These data provide strong support to the hypothesis that inhibin B is the physiologically important form of inhibin in men, negatively regulating FSH secretion at the pituitary. Furthermore, they suggest that FSH stimulates inhibin alpha-subunit secretion by the testis.

In the adult rat testis, macrophages belong to one of two subsets differentiated by expression or lack of expression of the resident macrophage surface antigen recognized by monoclonal antibody ED2. Local regulation of the testicular macrophage subsets was investigated in normal and 4-wk experimentally cryptorchid adult rats with and without s.c. testosterone implants (T-implants). Macrophage subsets ED2+ (resident-type) and ED2- (monocyte-like) were identified immunohistochemically and counted in perfusion-fixed frozen testis sections. Depletion of the spermatogenic cells by cryptorchidism had no effect on testicular macrophage numbers. Inhibition of Leydig cell and seminiferous tubule function by low-dose (3 cm) T-implants caused a 40% reduction in ED2+ resident macrophages in both scrotal and abdominal testes. High-dose (24 cm) T-implants, which inhibit Leydig cell function while maintaining normal seminiferous tubule function, also reduced the number of resident macrophages by approximately 40%, although this reduction was at least partially prevented in the abdominal testes. In the scrotal testis only, the ED2- monocyte/macrophage subset was significantly reduced in number by low-dose, but not highdose, T-implants. The concentration of the Leydig cell-secreted cytokine macrophage-migration inhibitory factor (MIF) in testicular fluid was reduced by cryptorchidism, but not by the T-implants. When data from all experimental groups were combined, ED2+ resident macrophage numbers showed a significant positive correlation with parameters of Leydig cell function (serum LH and testicular testosterone levels) but a negative correlation with MIF levels. This study indicates that Leydig cells regulate testicular macrophage numbers directly, rather than via an effect upon the seminiferous epithelium, in the adult rat testis. The data also suggest that testosterone and MIF play only a minor role, if any, in this regulation.

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(s): This paper provides a comprehensive description of the endocrine features associated with the STRAW stages. Design(s): 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). Result(s): 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). Conclusion(s): 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. Copyright © 2007 by The Endocrine Society.

The menopause, defined as the permanent cessation of menstruation resulting from the loss of ovarian follicular activity, marks the end of natural female reproductive life. It is preceded by a period of menstrual cycle irregularity, the menopausal transition, which usually begins in the mid-40s and is conventionally divided into early and late phases. The endocrine changes, which underlie the transition, are predominantly the consequence of a marked decline in ovarian follicle numbers. The most significant changes include a decrease in early cycle inhibin B and in anti-Mullerian hormone (AMH) levels. The decline in inhibin B results in an increase in FSH, which appears to be an important factor in the maintenance of estradiol (E2) concentrations until late in reproductive life. In the post-menopause, FSH levels are markedly raised, E2 levels are low, whereas inhibin B and AMH are undetectable. The menopausal transition is a time of marked hormonal instability. The Melbourne Women's Midlife Health Project has been an extremely productive study in which it has been possible to describe longitudinal changes in hormone levels throughout the menopause transition and to separate the effects of hormone change from the effects of ageing on a number of endpoints. This review provides the background for an accompanying manuscript in which a novel approach to modelling the hormonal changes during the transition is described. © The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

Purpose: Diagnosis of dysgerminoma in the paediatric age group is uncommon, and most cases arise from dysgenetic gonads of 46, XY pure gonadal dysgenesis (PGD) patients. Bilateral gonadectomy is mandatory in these patients. So, the preoperative diagnosis of PGD is important in order to avoid multiple surgical procedures and delayed patient information in the case of a suspected 'ovarian' tumour. Our aim was to discuss preoperative clues that can lead to suspicion of dysgerminoma in the context of PGD. Material(s) and Method(s): We reviewed the charts of six patients treated for dysgerminoma associated with 46, XY PGD. We focused on particularities of clinical and biological evaluations. Result(s): Median age at diagnosis was 11 years. Pubertal development was absent or incomplete even at late ages. Dysgerminoma was associated with gonadoblastoma foci in all cases. Tumoral marker profile was a normal alfafetoprotein level, a high lactate dehydrogenase level and normal or moderate human chorionic gonadotropin (betaHCG) secretion, except for one patient who had a mixed tumour with notably a choriocarcinoma share (high betaHCG). Follicle-stimulating hormone (FSH) level was very high in all patients tested and, interestingly, also in one prepubertal patient. Conclusion(s): In the case of a suspected ovarian tumour, delayed pubertal development, moderate betaHCG level and elevated FSH level are clinical and biological clues to a diagnosis of dysgerminoma in the context of PGD and should prompt karyotype analysis before surgery. Because FSH is an efficient indirect marker of this condition, we suggest including this analysis in the management of gonadal tumours. © 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

The aims of this study were: 1) to describe, in relation to the date of final menses, the average hormone levels of women in the years before and after this date and to determine the extent to which these average levels were dependent on age and body mass index (BMI); and 2) to determine the degree of tracking in residual hormone levels [i.e., the extent to which individuals above (below) the mean for their age or time relative to final menstrual period (FMP) and BMI remain above (below) the mean as time progresses]. Serial levels of serum FSH, circulating estradiol (E2), and the dimeric inhibins (INH) A and B were measured annually in 150 women who experienced a natural menopause during 6 years of follow-up. Means of the log-transformed hormonal levels were analyzed as a double-logistic function of time relative to FMP, as well as age and BMI and correlations between repeated hormonal levels, were measured. Mean FSH levels started to increase from about 2 years before the FMP, increased most rapidly about 10 months before the FMP, and had virtually plateaued by 2 years after the FMP. FSH levels were, on average, 3% greater for each year of age and 2% lower for each kg/m2 of BMI. After adjusting for time relative to the FMP, logFSH showed modest tracking. Age adjusted values of logFSH were moderately correlated across time, and much of this tracking was explained by the actual timing of a woman's FMP. Mean E2 levels started to decrease about 2 years before the FMP, decreased most rapidly around the time of the FMP, and had virtually plateaued by 2 years after the FMP. E2 levels were lower, on average, by about 9% per year of age, and residual values showed weak tracking. Levels of both INHA and INHB decreased, on average, in the years before the FMP and were undetectable (INHA, <10 pg/mL; INHB, < 25 pg/mL) in the majority of women by the time of the FMP and in almost all women by 4 years post-FMP. Significant negative correlations between log serum FSH and log E2 (r