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Objective: To characterize the variability of hormonal profiles during the luteal phase in normal cycles., Design: Observational study., Setting: Not applicable., Patient(s): Ninety-nine women contributing 266 menstrual cycles., Intervention(s): The women collected first morning urine samples that were analyzed for estrone-3-glucuronide, pregnanediol-3-alpha-glucuronide (PDG), FSH, and LH. The women had serum P tests (twice per cycle) and underwent ultrasonography to identify the day of ovulation., Main Outcome Measure(s): The luteal phase was divided into three parts: the early luteal phase with increasing PDG (luteinization), the midluteal phase with PDG ≥10 μg/mg Cr (progestation), and the late luteal phase (luteolysis) when PDG fell below 10 μg/mg Cr., Result(s): Long luteal phases begin with long luteinization processes. The early luteal phase is marked by low PDG and high LH levels. Long luteinization phases were correlated with low E1G and low PDG levels at day 3. The length of the early luteal phase is highly variable between cycles of the same woman. The duration and hormonal levels during the rest of the luteal phase were less correlated with other characteristics of the cycle., Conclusion(s): The study showed the presence of a prolonged pituitary activity during the luteinization process, which seems to be modulated by an interaction between P and LH. This supports a luteal phase model with three distinct processes: the first is a modulated luteinization process, whereas the second and the third are relatively less modulated processes of progestation and luteolysis., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To study the pathologic findings among men evaluated for infertility., Design: A retrospective, single-center, cross-sectional study., Setting: University hospital-based research center., Participant(s): We included data from 1,213 medical records from infertile men referred for diagnostic work-up from 2005 to 2009., Interventions(s): None., Main Outcome Measure(s): Health history, clinical findings, chromosome/genetic aberrations, semen quality, reproductive hormones., Result(s): In total, 64.4% of the infertile men had one or more reproductive disorders or factors influencing fertility, leaving 35.6% diagnosed as idiopathic infertile. In 244 patients (20%), including seven cases of testicular cancer and/or germ cell neoplasia in situ, a pathologic finding was first detected during diagnostic work-up. Two hundred four patients (16.8%) had a history of cryptorchidism and 154 (12.7%) of varicocele (grade 2 and 3). Thirty-three patients had chromosomal abnormalities, including 16 with sex chromosome abnormalities (11 with 47,XXY). Y-chromosome microdeletions were detected in 65 patients (5.4%). One hundred thirty-three had azoospermia, of which 58 had testicular biopsy findings (Sertoli cell-only syndrome: n = 23; spermatogenic arrest: n = 7; impaired spermatogenesis and atrophy: n = 28). Additionally, in idiopathic infertile men and infertile men with additional symptoms of testicular dysgenesis syndrome, 22.5% presented with a degree of Leydig cell insufficiency, with the highest frequency (33.1%) among patients with sperm concentration <5 million/mL., Conclusion(s): We report pathologic findings that could explain the male-factor infertility in two-thirds of infertile men referred to our center. Thus, male infertility may be a sign of an underlying disease that warrants attention., (Copyright © 2016. Published by Elsevier Inc.)

Objective: To determine whether obesity affects serum and seminal measures of male reproductive potential among a multi-institutional cohort., Design: Retrospective multi-institutional cohort study., Setting: Infertility clinics., Patient(s): All men referred for male infertility evaluation from 2002 to 2014 (n = 4,440)., Intervention(s): None., Main Outcome Measure(s): Collected reproductive parameters included hormonal (gonadotropins, T, E 2 , PRL) and semen analysis (ejaculate volume, sperm concentration, motility, normal morphology) data. Body mass index (BMI) was calculated for all patients with comparisons to reproductive parameters using univariate and multiparametric models., Result(s): Based on World Health Organization definitions, 30.9% of the cohort was normal weight (BMI 18.5-24.9), 45.1% overweight (25-29.9), and 23.3% obese (>30). Neither FSH nor LH demonstrated significant correlations with BMI on multivariate analysis. Total T (r = -0.27) and the T:E 2 ratio (r = -0.29) inversely varied with BMI, whereas E 2 (r = 0.13) had a direct correlation. On univariate analyses, BMI had weak but significant negative correlations with ejaculate volume (r = -0.04), sperm concentration (r = -0.08), motility (r = -0.07), and morphology (r = -0.04). All parameters remained significant on multivariate modeling with the exception of sperm motility. Rates of azoospermia and oligospermia were also more prevalent among obese (12.7% and 31.7%, respectively) compared with normal weight men (9.8% and 24.5%)., Conclusion(s): In one of the largest cohorts of male fertility and obesity, serum hormone and semen parameters demonstrated mild but significant relationships with BMI, possibly contributing to subfertility in this population., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze the phenotypic and clinical aspects of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome., Design: Cross-sectional study., Setting: University hospital., Patient(s): Five hundred and ninety-four patients with MRKH syndrome., Intervention(s): Clinical examination, abdominal or perineal/rectal ultrasound, magnetic resonance imaging, hormonal profile, karyotype, and laparoscopy., Main Outcome Measure(s): Clinicopathologic data, VCUAM (vagina cervix uterus adnex-associated malformation) classification, types with cycle phase, and karyotype., Result(s): We identified associated malformations in 43 out of 594 (7.2%) cases of MRKH. The 594 patients could be grouped into hormone phases: 53.7% follicular, 35.2% luteal, and 11.1% ovulatory. The major karyotype of MRKH patients was 46,XX; abnormal karyotypes were found in two cases., Conclusion(s): A lower proportion of associated malformations were found when compared with those provided in the current literature. Renal anomalies were the most frequent associated malformations, and most of the patients presented with a normal karyotype. Given the large cohort of this study, the lower malformation rates might be related to geographic or referral patterns, so further investigation is warranted., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess whether the quality of early childhood environments among different groups of Bangladeshi women, including migrants to the United Kingdom (UK), contributes to variation in ovarian reserve and the rate of reproductive aging in later life., Design: Cross-sectional study., Setting: Not applicable., Patient(s): A total of 179 healthy women volunteers aged 35-59 years were divided into four groups: [1] 36 Bangladeshis living in Sylhet, Bangladesh; [2] 53 Bangladeshis who migrated to the UK as adults; [3] 40 Bangladeshis who migrated to the UK as children aged 0-16 years; and [4] a reference group of 50 women of European origin living in London., Intervention(s): None., Main Outcome Measure(s): Levels of serum antimüllerian hormone, inhibin B, FSH, and E2, and anthropometrics derived from biomarkers; reproductive, demographic, and health variables from structured questionnaires., Result(s): Bangladeshi migrants who moved to the UK as children and European women had a highly significantly larger, age-related ovarian reserve compared with migrant Bangladeshis who had moved to the UK as adults or Bangladeshi women still living in Bangladesh. There were no other significant covariates in the model aside from age and menopausal status., Conclusion(s): The study points to the importance of childhood development in considering variation in ovarian reserve across different ethnic groups. Clinical studies and research in assisted reproductive technology have emphasized the role of genes or race in determining inter-population variation in ovarian reserve. Early life developmental factors should be given due consideration when evaluating inter-group differences in response to assisted reproductive technology., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To test the hypothesis that the c-Jun NH2-terminal kinase (JNK) inhibitor (JNKI) bentamapimod (AS602801/PGL5001) can reduce induced endometriosis in baboons., Design: Prospective randomized placebo-controlled study., Setting: Nonhuman primate research center., Animal(s): Twenty baboons each underwent four laparoscopies. Initial screening laparoscopy (L1) was followed after one rest cycle by an endometriosis-induction laparoscopy (L2). Fifty days after L2, the baboons were randomized just before staging laparoscopy (L3). Treatment lasted for 60 days, followed by a post-treatment staging laparoscopy (L4)., Intervention(s): Randomization before a 60-day treatment in four groups: daily placebo (n = 5), daily oral administration of 20 mg/kg JNKI (n = 5), concomitant daily oral administration of 20 mg/kg JNKI and 10 mg medroxyprogesterone acetate (MPA; n = 5), or subcutaneous administration of 3 mg cetrorelix every 3 days (n = 5)., Main Outcome Measure(s): Type, surface area and volume of endometriotic lesions, and revised American Society for Reproductive Medicine score and stage were recorded during L3 and L4. Menstrual cycle length and serum hormonal concentration were recorded before and after treatment., Result(s): Compared with placebo, treatment with JNKI, JNKI + PMA, or cetrorelix resulted in lower total surface area and volume of endometriotic lesions. Remodeling of red active lesions into white lesions was observed more frequently in baboons treated with JNKI + MPA than in baboons treated with JNKI only. Menstrual cycle length and serum hormonal concentration were similar between placebo and JNKI groups., Conclusion(s): JNKI alone was as effective as JNKI + MPA or cetrorelix in reducing induced endometriosis in baboons, but without severe side effects or effect on cycle length or serum reproductive hormones., (Copyright © 2016. Published by Elsevier Inc.)

Objective: To answer the questions: Are perinatal reproductive hormone profiles different in case of a twin compared with a singleton pregnancy? Are reproductive endocrine profiles of twin girls influenced by their male co-twin and vice versa?, Design: Prospective cohort study from January 2004 to October 2009., Setting: Not applicable., Patient(s): A total of 204 mothers of twins and 248 singleton control subjects, aged >18 years, pregnant with a twin or singleton and no endocrine disease or malignancy., Intervention(s): Blood samples were collected at mid-gestation from the mother and at delivery from the mothers and the umbilical cords. Estrogens, androgens, sex hormone-binding globulin, progesterone, and gonadotropins were measured., Main Outcome Measure(s): Hormonal profiles were compared between singletons and twins, different types of twins, and opposite-sex and same-sex twins., Result(s): Estrogen and progesterone concentrations were higher in mothers of twins compared with singletons, but twin babies had lower estrogen and progesterone concentrations at birth. Opposite-sex twin girls did not have higher androgens in cord blood compared with same-sex twin girls. Boys of an opposite-sex twin had lower luteinizing hormone concentrations compared with dizygotic twin boys with a brother as a co-twin., Conclusion(s): Children from a twin are not overexposed to sex steroids at the time of birth, despite higher concentrations in their mothers, and girls from opposite sex twins do not show androgenic influences from their male co-twin. The female co-twin may influence the hypothalamic-pituitary-testicular axis of her brother via central inhibition., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the effects of an antioxidant cocktail (AC) on bleomycin, etoposide, and cisplatin (BEP)-induced testicular dysfunction., Design: In vivo study., Setting: Research laboratory., Animal(s): Adult male and female Sprague-Dawley rats., Intervention(s): The rats were treated with three cycles of 21 days each of therapeutically relevant dose levels of BEP (0.75, 7.5, and 1.5 mg/kg) with or without the AC (a mixture of α-tocopherol, L-ascorbic acid, Zn, and Se)., Main Outcome Measure(s): Sperm parameters, fertility, serum hormone levels (ELISA), testicular histopathology, and expression of proliferating cell nuclear antigen (PCNA), and transferrin (Western blotting and immunohistochemistry) were evaluated at the end of treatment and a 63-day recovery period., Result(s): At the end of treatment, the AC improved BEP-induced decrease in sperm motility and increase in abnormality but had no effect on reduced sperm count, fertility, and tubular atrophy, although it up-regulated germ cell proliferation. The AC normalized reduced inhibin B levels, but had no effect on decreased transferrin and testosterone and elevated LH levels. At the end of the recovery period, the AC enhanced the expression of PCNA and transferrin, repopulation of germ cells, LH-testosterone axis, and fertility, but had no effect on reduced FSH and elevated inhibin B levels., Conclusion(s): The antioxidants protect and then enhance the recovery of testicular and reproductive endocrine functions when administered concomitantly with BEP therapy. The AC may be beneficial to regain testicular functions after chemotherapy., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To demonstrate that adequate pubertal history, physical examination, and a basal hormone profile is sufficient to exclude disorders of sexual development (DSD) in adult transsexuals and that chromosomal analysis could be omitted in cases of unremarkable hormonal profile and pubertal history., Design: Retrospective chart analysis., Setting: Endocrine outpatient clinic of a psychiatric research institute., Patient(s): A total of 475 subjects (302 male-to-female transsexuals [MtF], 173 female-to-male transsexuals [FtM]). Data from 323 (192 MtF/131 FtM) were collected for hormonal and pubertal abnormalities. Information regarding chromosomal analysis was available for 270 patients (165 MtF/105 FtM)., Intervention(s): None., Main Outcome Measure(s): Pubertal abnormalities, menstrual cycle, and hormonal irregularities in relation to chromosomal analysis conducted by karyotype or hair root analysis., Result(s): In the MtF group, 5.2% of the patients reported pubertal irregularities and 5.7% hormonal abnormalities, and in the FtM group 3.8% and 19.1%, respectively. Overall chromosomal abnormality in both groups was 1.5% (2.9% in the FtM and 0.6% in the MtF group). The aneuploidies found included one gonosomal aneuploidy (45,X[10]/47,XXX[6]/46,XX[98]), two Robertsonian translocations (45,XXder(14;22)(q10;q10)), and one Klinefelter syndrome (47,XXY) that had already been diagnosed in puberty., Conclusion(s): Our data show a low incidence of chromosomal abnormalities and thus question routine chromosomal analysis at the baseline evaluation of transsexualism, and suggest that it be considered only in cases of abnormal history or hormonal examination., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the effects of different hormonal levels on endometrial biochemical development during ovulation induction for assisted reproduction technology (ART) cycles., Design: Prospective controlled study., Setting: University center., Patient(s): Nine women during a natural cycle (control) and 9 oocyte donors (treated) during an ART cycle., Intervention(s): At the time consistent with day 3 embryo transfer (LH+5 in control, hCG+5 in treated), transvaginal ultrasound, endometrial biopsy, and blood sampling were performed. Real-time reverse-transcription polymerase chain reaction was used to measure mRNA levels for insulin receptor (InsR), type I IGF receptor (IGFRI), prolactin receptor (PRL-R), androgen receptor (AR), TSH receptor (TSHR), nuclear receptors for T3 and T4 (TRα1, TRα2, and TRβ1), iodothyronine deiodinase (DIO2), and 1,25-dihydroxyvitamin D3 receptor (VDR) in the endometrial tissue., Main Outcome Measure(s): Biochemical endometrial development., Result(s): IGFRI mRNA levels were 69% lower in treated patients than in control subjects, 0.12 ± 0.005 pg/μg RNA versus 0.39 ± 0.01 pg/μg RNA. TSHR mRNA was 57% lower, 2.6 ± 0.1 fg/μg RNA versus 6.0 ± 0.2 fg/μg RNA. TRα1 and TRα2 mRNA did not change, but TRβ1 mRNA levels were 63% higher. DIO2 mRNA was 63% lower, 1.2 ± 0.07 pg/μg RNA versus 3.2 ± 0.2 pg/μg RNA. InsR mRNA levels, despite being 68% lower in treated patients, did not reach significance, and PRL-R, AR, and VDR did not significantly change., Conclusion(s): Exposure of the endometrium to ovarian stimulation appears to influence insulin and thyroid hormone signaling pathways in the decidua at day 3 embryo transfer, whereas prolactin, androgen, and vitamin D pathways are uninfluenced. These findings echo the known delayed endometrial maturation during ovarian stimulation., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To test relationships between adipokines, adiposity, and vasomotor symptoms (VMS), including how these associations vary by menopause stage., Design: A subcohort of the longitudinal cohort Study of Women's Health Across the Nation completed questionnaires, physical measures, and a fasting blood draw annually for 8 years. Associations between a poorer adipokine profile (lower adiponectin, lower high-molecular-weight [HMW] adiponectin, higher leptin, lower soluble leptin receptor, higher monocyte chemoattractant protein 1 [MCP-1]) and VMS were tested with the use of generalized estimating equations adjusting for potential confounders. Interactions by menopause stage (pre-/early perimenopause, late peri-/postmenopause) were tested., Setting: Community., Patient(s): A total of 536 women ages 42-52 at baseline., Intervention(s): None., Main Outcome Measure(s) Vms Result(s): Associations between adipokines and hot flashes varied by menopause stage, with a poorer adipokine profile associated with higher odds of hot flashes early in the transition (adiponectin(log): odds ratio [OR] 0.68, 95% confidence interval [CI] 0.51-0.90; HMW adiponectin(log): OR 0.70, 95% CI 0.58-0.85; leptin(log): OR 1.23, 95% CI 0.99-1.54; multivariable models including body mass index [BMI]), but not later in the transition. The direction of associations between BMI and VMS also varied by menopausal stage. Higher MCP-1 was associated with more night sweats (OR 1.37, 95% CI 1.06-1.76) across menopausal stages., Conclusion(s): An adverse adipokine profile was associated with more VMS, particularly early in the menopause transition., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate whether zona pellucida thickness (ZPT) of human embryos is correlated with maternal age, patient's hormonal status, embryo quality, and IVF outcomes., Design: Prospective study., Setting: University-affiliated IVF clinic., Patient(s): Couples undergoing IVF-ET cycles., Intervention(s): Zona measurements, clinical data collection., Main Outcome Measure(s): Correlation between the ZPT and maternal age, basal FSH and E(2) levels, stimulation protocols, cause of infertility, embryo quality, and implantation/pregnancy rates., Result(s): The measurements of ZPT were collected from 5,184 day 3 human embryos originated from 744 IVF patients. The overall mean ZPT was 16.18 ± 2.00 μm. No significant correlation was observed between the ZPT and the patient's age, E(2) values on the day of hCG administration, basal concentration of serum FSH, stimulation protocol, infertility diagnosis, and implantation/pregnancy rates. The ZPT was strongly influenced only by the embryo quality: Embryos with good morphology exhibited considerably thinner ZP compared with those of less favorable morphology (mean 15.87 ± 2.48 μm vs. 16.36 ± 2.57 μm, respectively). The ZPT had no significant impact on the implantation and pregnancy rates., Conclusion(s): The thickness of the human ZP of day 3 embryos is not influenced by women's age and hormonal levels. The strong correlation between ZPT and embryo quality suggests that thickness of ZP depends on inherent embryo properties. The overall ZPT is not a good predictive indicator for IVF clinical outcomes., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the effects of 2.5 mg letrozole with those of 1 mg anastrazole daily on the hormonal and semen profiles of a subset of infertile men with low T/E(2) ratios., Design: Prospective, nonrandomized study., Setting: Reproductive medicine clinic., Patient(s): The study group consisted of 29 infertile men with a low serum T/E(2) ratio (<10)., Intervention(s): Patients were divided into two groups. Group A included 15 patients treated with 2.5 mg letrozole orally once daily for 6 months, and Group B consisted of 14 patients treated with 1 mg anastrazole orally every day for 6 months., Main Outcome Measure(s): Hormonal evaluation included measurement of serum FSH, LH, PRL, T, and E(2). In all sperm analyses pretreatment and posttreatment total motile sperm counts (ejaculate volume × concentration × motile fraction) were evaluated., Result(s): The use of aromatase inhibitors (either letrozole or anastrazole) in cases of infertile men with low T/E(2) ratios improved both hormonal and semen parameters., Conclusion(s): This study suggests that some men with severe oligospermia, low T levels, and normal gonadotropin concentration may have a treatable endocrinopathy., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether nonobese adolescents with polycystic ovary syndrome (PCOS) have higher levels of retinol-binding protein 4 (RBP4) and ectopic fat than controls and whether RBP4 and ectopic fat correlate with comorbidities of metabolic disease., Design: Cross-sectional case-control study., Setting: Pediatric clinical research center based in a quaternary care medical center., Patient(s): Twenty-four nonobese adolescents between the ages of 13 and 21 years, 13 with PCOS and 11 controls., Intervention(s): Measurement of RBP4, insulin resistance, lipids, and body composition., Main Outcome Measure(s): Retinol-binding protein 4, reproductive and adrenal hormones, insulin resistance, intrahepatic and intramyocellular lipid levels, and visceral adipose tissue., Result(s): Adolescents with PCOS had higher intrahepatic lipid content and a statistical trend for higher RBP4 compared with controls. Retinol-binding protein 4 correlated with body fat, triglycerides, insulin resistance, and androgens but not intrahepatic lipid content; however, when adjusted for body fat, the correlation between RBP4 and triglycerides weakened to a statistical trend and was no longer statistically significant for the other measures., Conclusion(s): This small preliminary study of nonobese adolescent girls suggests that RBP4 may be involved in the dyslipidemia associated with PCOS and that there may be an independent relationship between RBP4 and triglycerides but not between RBP4 and insulin resistance. Although intrahepatic lipid content was higher in PCOS, it did not correlate with RBP4, triglycerides, or insulin resistance., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the effects of age on the hormonal, metabolic, and ultrasonographic features of polycystic ovary syndrome (PCOS)., Design: Observational study., Setting: University department of obstetrics and gynecology., Patient(s): Patients with PCOS (n = 1,212) and healthy women (n = 254)., Intervention(s): None., Main Outcome Measure(s): Differences in the hormonal, metabolic, and ultrasonographic features of PCOS between age groups., Result(s): A progressive decline in circulating androgens was observed with advancing age. Patients 21-30 years old had lower plasma glucose and insulin levels, lower area under the oral glucose tolerance test curve and lower homeostasis model assessment of insulin resistance index, and higher glucose/insulin and quantitative insulin sensitivity check index than patients 31-39 years old. The prevalence of PCOS phenotypes changed with age. More specifically, the distribution of the phenotypes did not differ substantially between patients ≤ 20 years old and patients 21-30 years old. However, a decline in the prevalence of phenotype 1 (characterized by anovulation, hyperandrogenemia, and polycystic ovaries) and an increase in the prevalence of phenotype 4 (characterized by anovulation and polycystic ovaries without hyperandrogenemia) were observed in patients 31-39 years old., Conclusion(s): In women with PCOS, hyperandrogenemia appears to diminish during reproductive life whereas insulin resistance worsens., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Male patients with chronic hepatitis C virus (HCV) infection (n = 57) demonstrated a statistically significant decrease in semen volume, sperm count, and progressive sperm motility and a statistically significant increase in abnormal sperm morphology compared with healthy controls (n = 40). The duration of the HCV infection was negatively correlated with semen volume and sperm motility where the HCV RNA viral load was negatively correlated with sperm count and sperm motility. Chronic HCV patients had statistically significantly lower total serum testosterone and higher serum E(2) and prolactin levels compared with healthy controls., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate endothelial function via serum asymmetric dimethylarginine (ADMA) levels, paraoxonase 1 (PON1) activity, and brachial artery flow-mediated dilatation (FMD) in women with polycystic ovary syndrome (PCOS)., Design: Prospective case-control study., Setting: University hospital., Patient(s): Thirty patients with PCOS with a mean age of 24.33 ± 4.50 years and 30 healthy controls matched for body mass index (BMI) and age., Intervention(s): Endothelial function was assessed biochemically with serum ADMA levels and serum PON1 activity and functionally with brachial artery FMD by ultrasonography., Main Outcome Measure(s): Serum ADMA levels, serum PON1 activity, brachial artery FMD, hormonal and biochemical parameters., Result(s): Patients with PCOS had higher levels of free testosterone and insulin, and higher waist-hip ratio and Ferriman Gallwey scores when compared with the controls. Fasting glucose and homeostasis model assessment of insulin resistance were not different between the groups. There was no statistically significant difference in ADMA levels between two groups. Serum PON1 activity and brachial artery FMD were statistically significantly lower in women with PCOS. There was negative correlation between ADMA and PON1 in patients with PCOS., Conclusion(s): Serum PON1 activity and brachial artery FMD, as markers of endothelial dysfunction and cardiovascular risk, were statistically significantly lower in women with PCOS compared with healthy controls matched for age and BMI. Endothelial dysfunction may be seen at earlier ages in patients with PCOS., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate a potential association among the hormonal profile, PROGINS polymorphism, and erectile dysfunction (ED) complaints in a large population-based sample in Sao Paulo, Brazil., Design: Population-based questionnaire study., Setting: Interviews, sleep recording, and blood sample were conducted in a sleep institute., Patient(s): The total study participants included 467 men., Intervention(s): General information was obtained through interviews, and a blood sample was collected for hormone levels, DNA extraction, and PROGINS genotyping., Main Outcome Measure(s): The effect of progesterone and the PROGINS polymorphism on the risk of developing ED were measured by questionnaire and blood sample., Result(s): Progesterone, prolactin, testosterone, and estradiol levels did not differ between the genotype groups (T1/T1 and T1/T2+T2/T2). No significant genotypic or allelic differences were found between individuals with ED complaints and controls. Multivariate logistic regression analyses including age, body mass index, hypertension, diabetes, apnea-hypopnea index, and genetic ancestry estimation, as well as the PROGINS polymorphism, confirmed the lack of association between the T2 allele carriers and the risk of ED (odds ratio = 0.80; 95% confidence interval = 0.40-1.62)., Conclusion(s): This is the first study to demonstrate the genotypic and allelic frequencies of the PROGINS polymorphism in a large population-based sample of men. The results do not support a direct role for the PROGINS polymorphism in the risk of developing ED; however, further examination of other variants within PR gene will be necessary to completely rule out an effect., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

We investigated the effect of letrozole, an aromatase inhibitor, on body mass index, serum hormones, and sperm parameters in infertile men with decreased T:E(2) ratios. All sperm parameters increased after letrozole treatment. Letrozole may be effectively used to improve sperm parameters in infertile men with a low serum T:E(2) ratio., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To present a case of a poor responder woman with a rare balanced autosomal translocation., Design: Case report., Setting: Infertility center in a university teaching hospital., Patient(s): A 34-year-old white woman with primary infertility., Intervention(s): Laboratory and ultrasound evaluation, karyotype analysis, ovarian stimulation with gonadotropins., Main Outcome Measure(s): Markers of ovarian reserve and ovarian response to gonadotropin stimulation., Result(s): The patient was a carrier of a balanced translocation (1;11) (q23;p11.2). The hormone ovarian reserve markers (FSH, anti-Mullerian hormone, inhibin B) were within the normal range. The antral follicle count (AFC) was measured twice and only in one occasion did it reach the lower limit of the normal range. Furthermore, the patient had regular menstrual cycles. However, ovarian response to the administration of a maximal dose FSH was extremely poor., Conclusion(s): Patients with balanced autosomal translocations should be counseled regarding their increased risk for poor response even if markers of ovarian reserve are in the range of normality., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To review the role of various factors influencing vascular nitric oxide (NO) and cyclic GMP, and consequently, erectile function and vascular health., Method(s): Pertinent publications are reviewed., Result(s): Daily moderate exercise stimulates vascular NO production. Maintenance of normal body weight and waist/hip ratio allows NO stimulation by insulin. Decreased intake of fat, sugar, and simple carbohydrates rapidly converted to sugar reduces the adverse effects of fatty acids and sugar on endothelial NO production. Omega-3 fatty acids stimulate endothelial NO release. Antioxidants boost NO production and prevent NO breakdown. Folic acid, calcium, vitamin C, and vitamin E support the biochemical pathways leading to NO release. Cessation of smoking and avoidance of excessive alcohol preserve normal endothelial function. Moderate use of alcohol and certain proprietary supplements may favorably influence erectile and vascular function. Treatment of any remaining testosterone deficit will both increase erectile function and reduce any associated metabolic syndrome. After production of NO and cyclic GMP are improved, use of phosphodiesterase-5 inhibitors should result in greater success in treating remaining erectile dysfunction. Recent studies have also suggested positive effects of phosphodiesterase-5 inhibitors on vascular function., Conclusion(s): A multifaceted approach will maximize both erectile function and vascular health., (Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To study the changes in semen parameters, gonadotropic and sex hormones, and serum leptin in obese fertile and infertile oligozoospermic men., Design: Prospective., Setting: University hospital., Patient(s): Forty-two obese fertile and 80 obese infertile oligozoospermic men (body mass index [BMI] >30)., Intervention(s): The BMI calculation, semen analysis, and serum FSH, LH, T, E(2), PRL, and leptin estimation., Main Outcome Measure(s): Semen and hormonal profiles., Result(s): Obese oligozoospermic patients had significant increase in mean BMI, serum FSH, LH, E(2), PRL, and leptin compared with obese fertile controls. The BMI had significant positive correlation with abnormal sperm morphology, LH, serum leptin and significant negative correlation with sperm concentration, sperm motility, serum T. Serum leptin demonstrated significant positive correlation with patients' age, abnormal sperm morphology, serum FSH, LH, PRL and significant negative correlation with sperm concentration, sperm motility, and serum T., Conclusion(s): Serum leptin mediates a link between obesity and male infertility., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To compare endocrine and follicular dynamics in ovulatory volunteer women in natural cycles and cycles stimulated with clomiphene (CC) and letrozole (LE)., Design: Prospective, randomized, double-blind, crossover study., Setting: A private tertiary fertility center., Patient(s): Thirty ovulatory volunteer women (<39 years)., Intervention(s): Randomized ovarian stimulation with CC and LE compared with no treatment., Main Outcome Measure(s): Hormone profiles, follicular development, and endometrial development through the cycles., Result(s): The LE-treated cycles had the shortest follicular phase (13.1 vs. 13.9 days with CC) with less multiple follicular development than CC. They showed higher midfollicular LH concentrations (7.5 IU/L vs. 6.0 IU/L), lower LH surge values (27.9 IU/L vs. 44.4 IU/L), and lower E(2) concentrations than natural cycles. The LE cycles showed significant increases in free androgen index in the midfollicular phase compared with the CC cycles. Endometrial thickness in LE cycles (8.3 mm) was similar to natural cycles, whereas in CC cycles it was reduced (7.6 mm vs. 8.5 mm) compared with natural cycles. Ovulation profiles were similar in all cycles., Conclusion(s): The LE treatment of normal women led to multiple follicular development, but less than CC. Estradiol concentrations were reduced, follicular phase length was shorter, whereas endometrial thickness and luteal P were normal. Follicular phase increased free androgen index is a novel finding and may explain the physiological observations., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To examine and compare the efficacy and safety of GnRH agonist (GnRHa) vs. aromatase inhibitor in premenopausal women with leiomyomas., Design: Multicenter, randomized, controlled clinical trial., Setting: University hospitals., Patient(s): A total of 70 subjects with a single uterine myoma measuring >or=5 cm. Subjects were randomized into two groups with use of a random table. They were treated with aromatase inhibitor (group A) or GnRHa (group B)., Intervention(s): Group A received letrozole (2.5 mg/d) for 12 weeks. Group B received triptorelin (3.75 mg/mo) for 12 weeks., Main Outcome Measure(s): Measurement of myoma volume and E(2), FSH, LH, and T levels., Result(s): Total myoma volume decreased by 45.6% in group A and 33.2% in group B. Reductions in myoma volume in the two groups were statistically significant. There was no significant change in hormonal milieu in group A. The serum level of hormones significantly decreased in group B by the 12th week of treatment., Conclusion(s): Uterine myoma volume was successfully reduced by use of an aromatase inhibitor. Rapid onset of action and avoidance of initial gonadotropin flare with an aromatase inhibitor may be advantageous for short-term management of women with myomas of any size who are to be managed transiently and who wish to avoid surgical intervention, specifically women with unexplained infertility having uterine myoma., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

This study compared serum and follicular anti-müllerian hormone, LH, FSH, E(2), and P concentrations in modified natural cycles and controlled ovarian hyperstimulation cycles to analyze their effect on oocyte and embryo quality and implantation. Follicular anti-müllerian hormone, FSH, E(2), and P concentrations had no effect on embryo quality, whereas high serum and follicular LH concentrations in natural cycles modified only with hCG did not compromise oocyte and embryo quality but might have a negative effect on implantation.

Objective: To determine the effect of meal composition on postprandial T levels in women with polycystic ovary syndrome (PCOS)., Design: Randomized, crossover design., Setting: Academic research center., Patient(s): Fifteen women with PCOS., Intervention(s): We evaluated changes in T, sex hormone binding globulin (SHBG), DHEAS, cortisol, glucose, and insulin for 6 hours after a high-fat, Western meal (HIFAT) (62% fat, 24% carbohydrate, 1 g fiber) and an isocaloric low-fat, high-fiber meal (HIFIB) (6% fat, 81% carbohydrate, 27 g fiber)., Main Outcome Measure(s): Change in T levels., Result(s): Testosterone decreased 27% within 2 hours after both meals. However, T remained below premeal values for 4 hours after the HIFIB meal and 6 hours after the HIFAT meal. Insulin was twofold higher for 2 hours after the HIFIB meal compared with the HIFAT meal. Glucose was higher for 1 hour after the HIFIB meal compared with the HIFAT meal. DHEAS decreased 8%-10% within 2-3 hours after both meals, then increased during the remainder of the study period. Cortisol decreased during the 6-hour period after both meals., Conclusions: Diet plays a role in the regulation of T levels in women with PCOS. Further studies are needed to determine the role of diet composition in the treatment of PCOS.

Objective: To determine the genetic cause of primary amenorrhea in a 46,XY woman., Design: Case report., Setting: Centre of Gynecological Endocrinology and Cytogenetics and Molecular Genetics Laboratory of university medical school., Patient(s): A 19-year-old woman referred for primary amenorrhea., Intervention(s): Clinical, endocrinologic, and ultrasonographic investigation and SRY mutation analysis., Main Outcome Measure(s): Hormone profile (LH, FSH, PRL, leptin, E(2), 17alpha-hydroxyprogesterone, 3alpha-androstanediol glucuronide), ultrasonographic evaluation, clinical follow-up., Result(s): A new SRY sporadic mutation due to a single nucleotide insertion at codon 13 position 38 (38-39insA) was found in a 46,XY woman with sex reversal. This mutation determined a frameshift of the reading frame sequence and a protein truncation at codon 16. Clinical and endocrinologic data are reported., Conclusion(s): This is a new rare case of a single nucleotide insertion affecting the SRY gene in 46,XY females with sex reversal. This new mutation should be considered in genetic counseling.

Objective: To explain the unexpected low response to GnRH antagonist protocol in reproductive women with normal baseline hormone profiles., Design: Retrospective study., Setting: University hospital., Patient(s): Twenty-five women undergoing their first IVF cycle., Intervention(s): Follicular fluid (FF) from large follicles (>15 mm) was obtained during oocyte retrieval from unexpected low responders (n = 13, group A) and 12 age-matched normal responders (n = 12, group B)., Main Outcome Measure(s): The FF markers known to reflect follicle environment (insulin-like growth factor [IGF] II, IGF-binding protein 4, müllerian-inhibiting substance, pregnancy-associated plasma protein A, soluble Fas, and vascular endothelial growth factor [VEGF]) were analyzed by ELISA., Result(s): The baseline characteristics (age, day 3 serum LH, FSH, E(2), duration and dose of r-FSH, GnRH antagonist) were not different between the two groups. The number of large follicles, oocytes retrieved, and serum E(2) levels on the day of hCG injection were significantly higher in group B. Whereas the other follicular markers did not differ between the two groups, VEGF was significantly higher in group A. In addition, the VEGF concentration showed an inverse correlation with the total number of oocytes retrieved., Conclusion(s): The unexpected low response in women with normal basal hormone profiles, during GnRH antagonist protocol, was associated with altered follicular VEGF expression.

Objective: To study serum and follicular fluid (FF) hormone levels after the administration of urinary or recombinant hCG to initiate the final stages of oocyte maturation during IVF., Design: Prospective randomized study between 250 microg of recombinant hCG and 7,500 IU of urinary hCG as the final trigger of ovulation during IVF., Setting: Private IVF center., Patient(s): Infertile women undergoing IVF/intracytoplasmic sperm injection (ICSI) using the long protocol and recombinant FSH., Intervention(s): IVF treatment. Serum and FF hormone measurements on the day of oocyte collection., Main Outcome Measure(s): Serum and FF E(2), P, hCG, and T levels., Result(s): Stimulation parameters, serum and follicular E(2), P, T, and hCG levels were similar in the recombinant and urinary hCG groups. The number of oocytes retrieved from follicles >14 mm, the proportion of mature oocytes, fertilization rate, and pregnancy rate (PR) were also comparable., Conclusion(s): Recombinant and urinary hCG provided similar serum and follicular hormonal environments during the final stages of oocyte maturation. The IVF outcome parameters were also comparable. The two medications appear to be equally effective.

This Committee Opinion outlines the stages of the menopausal transition, as defined by the July 2001 Stages of Reproductive Aging Workshop (STRAW).

Objective: To report a case of a 45,X man, a rare condition with a clinical course that has not been dealt with by any previous article in the literature., Design: Case report., Setting: University Genetic Center and Endocrine Clinic., Patient(s): A 41-year-old man, already known by our genetics center for a 45,X chromosome constitution and a normal male differentiation, came back with requests on his sexual and fertility potential. Twenty-one years ago, high-resolution analysis of prometaphase chromosomes revealed additional euchromatic material on a 15-p chromosome, and in situ hybridization with Y-specific probe pDP105 gave positive signal on 15p11.2, suggesting a t(Yp;15p) translocation., Intervention(s): Fluorescence in situ hybridization analyses on metaphase chromosomes, standard oral glucose tolerance test, dynamic hormone assays, semen analysis, and dual-energy x-ray absorptiometry., Main Outcome Measure(s): Reexamination at clinical, genetic, hormonal, and metabolic level., Result(s): The derivative chromosome 15 was characterized as der(15)(Ypter-->q11.21::15p11.2-->qter). The patient's findings satisfied the criteria of the metabolic syndrome. Hypergonadotropinemic hypotestosteronemia was diagnosed., Conclusion(s): Our study offers new insights into the natural history of this condition and suggests that hypogonadism could play a role in the development of metabolic syndrome.

Objective: To evaluate the effect of the soy isoflavone genistein on the metabolic and hormonal disturbances of polycystic ovary syndrome (PCOS), we studied a group of obese, hyperinsulinemic, and dyslipidemic women presenting this syndrome during 6 months of phytoestrogen administration., Design: Pilot prospective study., Setting: Operative division of endocrinological gynecology in a university hospital., Patient(s): Twelve Caucasian obese, hyperinsulinemic, and dyslipidemic women with PCOS., Intervention(s): Patients received 36 mg/d of genistein for 6 months. Ultrasonographic pelvic exams, hormonal and lipid features, oral glucose tolerance test, and euglycemic hyperinsulinemic clamp were performed at baseline and after 3 and 6 months of treatment., Main Outcome Measure(s): Basal hormonal assays, lipid profile, and glycoinsulinemic assessment., Result(s): Phytoestrogens supplementation significantly improved total cholesterol levels, reducing low-density lipoprotein (LDL) cholesterol and resulting in a significant decrease in the LDL-high-density lipoprotein ratio (LDL-HDL). Triglycerides showed a trend toward decrease, whereas no changes were detected in very low-density lipoprotein cholesterol plasma levels. Genistein treatment did not significantly affect anthropometric features, the hormonal milieu, and menstrual cyclicity. No significant changes occurred in glycoinsulinemic metabolism., Conclusion(s): The possible advantages derived from the therapeutic use of phytoestrogens in PCOS are limited to improvement of the lipidic assessment.

Objective: To determine trigger factors and neuropsychologic correlates of functional hypothalamic amenorrhea (FHA) in adolescence and to evaluate the correlations with the endocrine-metabolic profile., Design: Cross-sectional comparison of adolescents with FHA and eumenorrheic controls, Setting: Academic medical institution, Patient(s): Twenty adolescent girls with FHA (aged <18 years) and 20 normal cycling girls, Intervention(s): All subjects underwent endocrine-gynecologic (hormone) and neuropsychiatric (tests and interview) investigations. A separate semistructured interview was also used to investigate parents., Main Outcome Measure(s): Gonadotropins, leptin, prolactin, androgens, estrogens, cortisol, carrier proteins (SHBG, insulin-like growth factor-binding protein 1), and metabolic parameters (insulin, insulin-like growth factor 1, thyroid hormones) were assayed in FHA and control subjects. All girls were evaluated using a test for depression, a test for disordered eating, and a psychodynamic semistructured interview., Result(s): Adolescents with FHA showed a particular susceptibility to common life events, restrictive disordered eating, depressive traits, and psychosomatic disorders. The endocrine-metabolic profile was strictly correlated to the severity of the psychopathology., Conclusion(s): Functional hypothalamic amenorrhea in adolescence is due to a particular neuropsychologic vulnerability to stress, probably related to familial relationship styles, expressed by a proportional endocrine impairment.

Objective: To thoroughly examine the mechanisms for insulin resistance in polycystic ovary syndrome (PCOS) and to evaluate the effects of pioglitazone treatment on insulin resistance, beta-cell function, LH secretion, and glucose metabolism., Design: Randomized, blinded, placebo-controlled study., Setting: Outpatient clinic, at a university hospital in Denmark., Patient(s): Thirty obese women with PCOS and 14 weight-matched healthy females., Intervention(s): Sixteen weeks of blinded treatment with pioglitazone (30 mg/d) or placebo., Main Outcome Measure(s): Fasting blood samples, 24-hour 20-minute integrated blood sampling (LH, insulin, and C-peptide), euglycemic hyperinsulinemic clamps including 3-(3)H glucose, and indirect calorimetry were performed before and after the intervention period., Result(s): Patients with PCOS had significantly lower insulin sensitivity compared with controls, including significantly decreased insulin-stimulated oxidative and nonoxidative glucose metabolism. Pioglitazone treatment resulted in significantly lower levels of fasting insulin and significantly higher insulin sensitivity, increased insulin-stimulated glucose oxidation, and increased insulin-stimulated inhibition of lipid oxidation. During 24-hour blood sampling, significantly lower area under-the-curve insulin and lower median insulin levels were observed. Secretion profiles of LH and E(2) and T levels did not change significantly., Conclusion(s): Insulin resistance in PCOS was characterized by hyperinsulinemia, impaired insulin-stimulated oxidative and nonoxidative glucose metabolism, which was partly reversed by pioglitazone treatment.

Objective: The study was designed to compare the follicular phase of women with recurrent pregnancy loss and a healthy control group. It is possible that a defective or aberrant follicular phase may be associated with poor oocyte quality leading to a production of an embryo with compromised quality and hence early pregnancy loss., Design: Prospective case-control study., Setting: A tertiary care hospital of Sheffield, UK., Patient(s): Thirty-four women with recurrent miscarriage and 10 women with no previous history of miscarriage and regular menstrual cycles (control group) were recruited., Intervention(s): The characteristics studied included Doppler assessment of blood flow to the follicle and the endometrium. Simultaneously, serum concentrations of biochemical markers such as anti-Müllerian hormone, inhibin B, FSH, LH, and P were compared in the two groups., Main Outcome Measure(s): Differences in the two groups., Result(s): We were unable to detect significant differences in various biochemical and ultrasound measurements in the follicular phase between women with recurrent miscarriage and a control group; however, the expected correlation between ovarian and pituitary hormones, which was observed in the control group, was absent in women with recurrent miscarriage., Conclusion(s): There may be subtle derangements of the feedback mechanism responsible for regulation of follicle development in this group of women. However, there were no obvious differences in the follicular phase of women with recurrent miscarriage and a healthy control group.

Objective: To compare the efficacy of rosiglitazone and clomiphene citrate (CC) with metformin and CC in women with CC-resistant polycystic ovary syndrome (PCOS)., Design: Randomized controlled trial (RCT)., Setting: A university teaching hospital in Jeddah, Saudi Arabia., Patient(s): Twenty-five women with CC-resistant PCOS., Intervention(s): Twelve women were assigned to the rosiglitazone and CC group, and 13 women were assigned to the metformin and CC group for three treatment cycles. The first cycle was started on the first day of the period with either rosiglitazone (4 mg twice daily) or metformin (500 mg three times daily) and continued for three cycles. Clomiphene citrate (100 mg) from the third day for 5 days was added to each cycle., Main Outcome Measure(s): Ovulation rate, number of follicles and estradiol (E2) on day 12 of the cycle, pregnancy rate, and changes in fasting glucose, serum insulin, HbA(1C), total testosterone (T), free T, luteinizing hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone sulfate (DHEAS), delta4-androstenedione (delta4-A), sex hormone-binding globulin (SHBG), insulin-like growth factor (IGF)-1, insulin-like growth factor binding protein (IGFBP)-1, and IGFBP-3., Result(s): No significant differences were found in the baseline characteristics of both groups. Ovulation rate was significantly higher in the rosiglitazone and CC group (18 out of 28 cycles [[64.3%]]) than the metformin and CC group (12 out of 33 cycles [[36.4%]]) (P=.035). Similarly, statistically significant differences were found in the number of follicles > or =14 mm in the rosiglitazone and CC group (2.2 +/- 1) compared with the metformin and CC group (1.1 +/- 0.9) (P=.02) and E2 on day 12 of the cycle in the rosiglitazone and CC group (1,991 +/- 1,389 pmol/L) compared with the metformin and CC group (548 +/- 327) (P<.001). The pregnancy rate was also higher in the rosiglitazone and CC group (6 out of 12 [[50%]] women) than the metformin and CC group (5 out of 13 [[38.5%]] women), but did not reach statistical significance (P=.58). Both groups showed no significant changes in fasting plasma glucose or HbA(1C) or IGFBP-3 values. However, in both groups, fasting serum insulin, total T, free T, LH, DHEA-S, delta4A, and IGF-1 levels decreased significantly, and SHBG and IGFBP-1 exhibited significant increases., Conclusion(s): These findings suggest that short-term use of rosiglitazone and CC is more efficacious than metformin and CC in ovulation induction in women with CC-resistant PCOS.

Objective: To investigate the relative effects of hormonal and relationship factors on female sexual function during the natural menopausal transition., Design: Prospective population-based questionnaire study., Setting: Interviews were conducted in the patients' homes., Patient(s): Four hundred thirty-eight Australian-born women aged 45-55 years who were still menstruating at baseline. Eight years of longitudinal data were available for 336 of these women, none of whom were hysterectomized., Intervention(s): Hormonal levels, age, menopausal status, partner status, and feelings for partner were measured and evaluated with longitudinal structural equation modeling., Main Outcome Measure(s): Short personal experiences questionnaire., Result(s): Sexual response was predicted by prior level of sexual function, change in partner status, feelings for partner, and E2 level (R2 = .65); dyspareunia was predicted by prior level of dyspareunia and E2 level (R2 = .53); and frequency of sexual activities was predicted by prior level of sexual function, change in partner status, feelings for partner, and level of sexual response (R2 = .52). The minimum effective dose needed to increase sexual response by 10% (700 pmol/L E2) is twice that needed to decrease dyspareunia., Conclusion(s): Prior function and relationship factors are more important than hormonal determinants of sexual function of women in midlife.

Objective: (1) Characterize the relationship between follicular phase hormone levels and menstrual bleeding patterns in the approach to menopause; (2) identify racial differences in hormone levels; (3) determine independent contributions of menstrual status, race, age, BMI, and smoking to hormone levels., Design: Randomly identified, population-based cohort, stratified to obtain equal numbers of African American and Caucasian women, prospectively followed for 5 years., Setting: Women in Philadelphia County, PA, identified by random-digit telephone dialing., Participant(s): Women aged 35 to 47 years with regular menstrual cycles at enrollment (N = 436)., Data Collection: Blood sampling twice in each of 7 assessment periods during days 1-6 of the cycle, menstrual dates identified through structured interview and daily symptom reports, anthropometric measures and standardized questionnaires at each assessment period., Main Outcome Measure(s): Serum levels of follicular E(2), FSH, inhibin B, and LH., Result(s): The mean levels of E(2), FSH, inhibin B, and LH were differentially associated with the 5 menstrual status groups defined by changes in bleeding patterns. Significant changes in hormone levels occurred prior to missed menstrual cycles for inhibin B, FSH, and LH. All hormones had a highly significant interaction between menstrual status and BMI. African American women had significantly lower levels of E(2) and LH compared to Caucasian women in univariate analyses. The interaction of race, menstrual status, and BMI was highly significant (P<.001) for E(2), with African American women having lower E(2) levels until postmenopause, when E(2) levels were higher in AA women with BMI > or =25 and BMI > or =30., Conclusion(s): Levels of E(2), FSH, LH, and inhibin B are significantly associated with menstrual bleeding patterns in late reproductive age women and differentiate the earliest stages of the menopausal transition. Racial differences in mean levels of E(2) appear strongly mediated by BMI.

Objective: To determine whether cytokines implicated in uterine receptivity are detectable in cervicovaginal secretions and/or serum of fertile women, and whether their concentrations undergo hormonal regulation during the menstrual cycle., Design: Prospective, observational study., Setting: Academic medical center., Patient(s): Six fertile volunteers studied over two menstrual cycles., Intervention(s): Cervicovaginal lavages (CVLs) and peripheral blood specimens were obtained during the menstrual, proliferative, periovulatory, and midsecretory phases of the cycle. Endometrial biopsies were obtained during the midsecretory phase., Main Outcome Measure(s): Concentrations of leukemia inhibitory factor (LIF), macrophage-colony stimulating factor (M-CSF), interleukin-1beta (IL-1beta), transforming growth factor-beta1 (TGF-beta1), TGF-beta2, and epidermal growth factor (EGF) in CVL and peripheral blood of fertile women; endometrial cytokine messenger (m)RNA levels in midsecretory phase; and serum E(2) and P levels throughout the menstrual cycle., Result(s): Macrophage-colony stimulating factor and EGF were detectable in all CVL samples. Macrophage-colony stimulating factor concentrations were positively correlated with serum E2 levels and the E2/P ratio. Whereas EGF concentrations in serum and CVL samples remained constant throughout the menstrual cycle, individual concentrations during the secretory phase of the menstrual cycle were positively correlated with endometrial EGF mRNA levels. Interleukin-1beta, TGF-beta1, and TGF-beta2 were detected in most CVL samples. Interleukin-1beta concentrations in CVL were significantly higher at menses than at the periovulatory stage of the menstrual cycle; TGF-beta2 levels were higher at menses than at the periovulatory and secretory stages. Leukemia inhibitory factor was undetectable in CVL except at menses. In serum, TGF-beta1, TGF-beta2, M-CSF, and EGF were detectable, but there was no menstrual cycle effect. There were no correlations between cytokine levels in CVL and serum., Conclusion(s): This study demonstrates that several endometrial cytokines that have been implicated in uterine receptivity are detectable in cervicovaginal secretions and peripheral blood of reproductive-aged women, and it provides normal concentration ranges of these cytokines in CVL and serum of fertile women at four stages of the menstrual cycle. Macrophage-colony stimulating factor and EGF warrant further study in CVLs of fertile and infertile women to determine their predictive value as minimally invasive markers of uterine receptivity.

Objective: To examine the influence of hormone-related factors on the risk of invasive epithelial ovarian cancer (ovarian cancer)., Design: Population-based case-control study using in-person interviews., Setting: Academic department of preventive medicine., Patient(s): Four hundred seventy-seven ovarian cancer patients and 660 controls., Intervention(s): None., Main Outcome Measure(s): Numbers of and ages at births, oral contraceptive use, and use of menopausal hormone therapy., Result(s): Compared with nulliparous women, women whose only (last) birth was after age 35 years had an estimated 51% (95% confidence interval: 21%-70%) reduction in risk. If this birth occurred earlier, the reduction in risk was progressively less. Additional (earlier) births reduced the risk further. Oral contraceptive use also reduced risk. Increased body mass index increased risk, but this effect was confined to localized disease and is likely to be a diagnostic bias, as a consequence of other problems associated with being overweight and in itself having no etiological significance., Conclusion(s): If the major protective effect of a late birth can be confirmed, our most challenging task will be to understand the mechanism to develop a chemoprevention approach to exploit this finding.

Objective: To compare the value of basal follicle-stimulating hormone (FSH) measurement vs. the clomiphene citrate challenge test (CCCT) in predicting the ability to achieve a pregnancy in women who are undergoing infertility treatment., Design: Meta-analysis., Setting: All studies that evaluated either basal FSH or the CCCT for determining the likelihood of pregnancy., Patient(s): Infertility population undergoing treatment, which was defined as patients undergoing ovulation induction, IUI, or in vitro fertilization (IVF)., Intervention(s): None., Main Outcome Measure(s): Diagnostic test characteristics were calculated and pooled using standard methods. Inability to achieve a pregnancy with treatment was considered as the "disease.", Result(s): Twelve studies on basal FSH (with 6296 patients, mean age 33.8) and seven studies on the CCCT (with 1352 patients, mean age 34.5) fit our criteria and were analyzed. For basal FSH and the CCCT, the sensitivities were 6.6% (95% confidence interval [CI] 5.9, 7.3%) and 25.9% (95% CI 23.0, 29.0%), respectively, and specificities were 99.6% (95% CI 99.1, 99.9%) and 98.1% (95% CI 96.5, 99.1%), respectively. For "disease" prevalence ranging from 40%-100%, for basal FSH and the CCCT, the positive predictive values ranged from 91.7%-100% and 90.1%-100%, respectively, and negative predictive values ranged from 61.5%-0.0% and 66.5%-0.0%, respectively., Conclusion(s): Basal FSH and the CCCT are similar in predicting the ability to achieve a clinical pregnancy in women undergoing infertility treatment. With either test, a normal result is not useful, but an abnormal result virtually confirms that pregnancy will not occur with treatment.

Objective: To investigate whether premenstrual administration of a GnRH antagonist coordinates early antral follicle sizes during the subsequent follicular phase., Design: Prospective, longitudinal study., Setting: University Hospital in France, Patient(s): Twenty-five women, 50 cycles., Intervention(s): On cycle day 2 (control/day 2), women underwent measurements of early antral follicles by ultrasound and serum FSH and ovarian hormones. On day 25, they received a single cetrorelix acetate administration, 3 mg. On the subsequent day 2 (premenstrual GnRH antagonist/day 2), participants were re-evaluated as on control/day 2., Main Outcome Measure(s): Magnitude of follicular size discrepancies., Result(s): Follicular diameters (4.1 +/- 0.9 vs. 5.5 +/- 1.0 mm) and follicle-to-follicle size differences decreased on premenstrual GnRH antagonist/day 2 as compared with control/day 2. Consistently, FSH (4.5 +/- 1.9 vs. 6.7 +/- 2.4 mIU/mL), E(2) (23 +/- 13 vs. 46 +/- 26 pg/mL), and inhibin B (52 +/- 30 vs. 76 +/- 33 pg/mL) were lower on GnRH antagonist/day 2 than on control/day 2., Conclusion(s): Premenstrual GnRH antagonist administration reduces diameters and size disparities of early antral follicles on day 2, likely through the prevention of luteal FSH elevation and early follicular development. This simple, original approach may be used to coordinate multifollicular development in controlled ovarian hyperstimulation.

Objective: To evaluate the benefits of varicocelectomy in men with nonobstructive azoospermia., Design: Retrospective review of effect of prior varicocelectomy on sperm retrieval rates in men with nonobstructive azoospermia. Chart review of men with nonobstructive azoospermia who underwent microsurgical varicocelectomy to determine the effect of the procedure on the need for testicular sperm extraction (TESE)., Setting: Tertiary, university-based referral center., Patient(s): Men with clinical varicoceles and nonobstructive azoospermia., Intervention(s): Microsurgical varicocelectomy, TESE., Main Outcome Measure(s): Return of sperm to the ejaculate and need for TESE after varicocele repair, ability to find sperm using microdissection TESE., Result(s): Of 31 men who underwent varicocele repair at one institution for documented nonobstructive azoospermia, 7/31 (22%) had sperm reported on at least one semen analysis postoperatively. However, only 3/31 (9.6%) men after varicocele repair had adequate motile sperm in the ejaculate for ICSI, without TESE. Sperm retrieval rates for men with varicoceles were not affected by a history of prior varicocelectomy., Conclusion(s): Men with clinical varicoceles that are associated with nonobstructive azoospermia will rarely have adequate sperm in the ejaculate after varicocele repair to avoid TESE. A history of prior varicocele repair does not appear to affect the chance of sperm retrieval by TESE for men with clinical varicoceles and nonobstructive azoospermia. The benefits of varicocelectomy in men with nonobstructive azoospermia may be less than previously reported.

Objective: To quantify germ cell loss and the extent of testicular fibrosis in vasectomized patients of varying obstructive intervals., Design: Retrospective study., Setting: Specialized male reproductive surgery and endocrinology service., Patient(s): Thirty-four vasectomized patients 1-20 years after surgery and 10 normal subjects., Intervention(s): Thirty-four testicular biopsies taken at the time of vasectomy reversal (vasovasostomy). Control biopsies taken from 10 normal men at the time of vasectomy., Main Outcome Measure(s): Stereological assessment of testicular germ cell populations and testicular fibrosis., Result(s): Vasectomy caused a significant decrease in germ cells in the later stages of spermatogenesis, with significant reductions in pachytene spermatocytes (by 18%), round spermatids (by 40%), elongating spermatids (by 23%), and elongated spermatids (by 39%). The loss of spermatids showed a significant relationship with obstructive interval. A significant 2.7-fold increase in total (peritubular plus interstitial) fibrosis was observed, which showed a positive relationship with obstructive interval. Decreased germ cell populations and fibrosis did not seem to be related to sperm antibody levels nor to sperm counts obtained up to 2 years after vasovasostomy., Conclusion(s): Vasal obstruction results in significant reductions in germ cells in the later stages of spermatogenesis and increases in testicular fibrosis, both worsening with an increasing obstructive interval. Testicular damage after vasectomy might impact upon the prospects for reversal.

Objective: To study the effect on mammographic breast density of two different continuous combined regimens for hormone therapy., Design: Randomized clinical study., Setting: University hospital., Patient(s): Postmenopausal women without any previous history of breast disorder., Intervention(s): The women received either estradiol valerate/dienogest or estradiol/norethisterone acetate. Mammograms and venous blood samples were obtained at baseline and after 6 months., Main Outcome Measure(s): Change in mammographic breast density. Correlations with levels of hormones, growth factors, and binding proteins., Result(s): An increase in mammographic density was recorded in approximately 50% of the women, and there were no differences between treatments. Increased density showed a positive correlation with estradiol, estrone, and sex hormone-binding globulin and showed a negative association to free T. Among hormonal factors, levels of free T were the most important for predicting increased density., Conclusion(s): Continuous combined hormone therapy with different progestogens has a marked impact on the breast.

Objective: To document body composition and fat patterning characteristics in normal and underweight infertile women., Design: Status quo method., Setting: University clinics., Patient(s): Fifteen amenorrheic women with anorexia nervosa, 16 women with polycystic ovary syndrome (PCO2), 10 women with primary amenorrhea and 19 healthy controls., Intervention(s): None., Main Outcome Measure(s): Determination of body mass index, body composition parameters such as fat mass, lean body mass, bone mass using dual-energy x-ray absorptiometry (DEXA), fat distribution patterns, 17beta-estradiol, FSH, LH, prolactin, progesterone, testosterone, DHEA-S, and androstenedione levels., Result(s): A statistically significant difference was found comparing all proband groups with healthy controls for the majority of body fat and bone mineral content parameters but not for lean body mass. Infertile women of normal weight, with PCOS, and with primary amenorrhea exhibited an extraordinarily high amount of fat tissue and a tendency toward android fat patterning. In contrast, patients with anorexia nervosa and the healthy controls showed predominantly gynoid fat patterning. According to logistic regression analyses, anorexia nervosa was characterized by reduced fat tissue and PCOS was characterized by android fat patterning and an increased fat percentage. Patients with primary amenorrhea were characterized by reduced bone mass., Conclusion(s): Infertile young women showed characteristic differences in body composition and fat distribution patterns when compared with healthy, fertile, age-matched counterparts.

Objective: Using hyperstimulated rats, to elucidate the mechanisms of gonadotropin-releasing hormone agonist (GnRH-a) treatment to prevent early ovarian hyperstimulation syndrome (OHSS)., Design: Descriptive study of hyperstimulated rats as an early OHSS model with Western blot analysis, Northern blot hybridization, and vascular permeability assay., Setting: Experimental laboratory research., Animal(s): Sprague-Dawley female rats were used for collecting ovarian samples., Intervention(s): Hyperstimulated rats received consecutive GnRH-a treatment from the start of pregnant mare serum gonadotropin (PMSG) treatment through 2 days after hCG administration., Main Outcome Measure(s): Expressions of vascular endothelial growth factor (VEGF), VEGF receptor-1 (VEGFR-1: Flt-1), VEGF receptor-2 (VEGFR-2: KDR/Flk-1), and vascular permeability by Evans blue leakage., Result(s): GnRH-a treatment significantly reduced expressions of VEGF, VEGFR-1, and VEGFR-2 both in mRNA and protein levels in the ovaries of hyperstimulated rats. GnRH-a treatment also reduced vascular permeability in the ovaries of hyperstimulated rats., Conclusion(s): It is speculated that GnRH-a treatment may prevent early OHSS by reducing vascular permeability through the decrease in VEGF and its receptors.

Objective: To find the underlying defect in a case of primary FSH deficiency and to estimate the beneficial effect of FSH treatment., Design: Case report., Setting: University hospital fertility clinic., Patient(s): Normal, healthy, 37-year-old male patient with severe oligoteratozoospermia., Intervention(s): Levels of FSH, LH, LHRH provocation test, karyotyping, genomic analysis on the Y-chromosomal AZF region and sequencing of the FSHB gene, FSH treatment., Main Outcome Measure(s): We compiled detailed clinical and molecular data on four pregnancies. We compare this case with a similar case published recently., Result(s): There were detectable but very low FSH levels after LHRH provocation; the LH response was not entirely normal, and no genomic abnormalities were found in the FSHB gene. The FSH treatment resulted in four pregnancies, two of which ended in abortion; the other two resulted in the birth of two healthy children. Both our case and the published case had detectable but abnormally low FSH levels on some occasions, but normal or highly normal inhibin B levels that differed from the expected low levels. Both patients had a normal male phenotype and no detectable mutation in the FSHB gene. The published case differed from our patient in that the published case was azoospermic whereas ours was extremely oligoteratozoospermic. The beneficial effect of FSH treatment was only shown in our patient., Conclusion(s): The published case and ours may have a common, as yet unidentified, underlying defect. The dramatic and immediate effect of FSH treatment on our patient's fertility was clearly demonstrated.

Objective: To determine the clinical, hormonal, and biochemical effects of metformin therapy in obese and nonobese patients with polycystic ovary syndrome (PCOS)., Design: Controlled clinical study., Setting: Department of Gynecology of Federal University of São Paulo, São Paulo, Brazil., Patient(s): Twenty-nine patients with PCOS., Intervention(s): Patients were treated with 500 mg of p.o. metformin t.i.d. for 6 months., Main Outcome Measure(s): Clinical data as well as serum concentrations of sex steroids, sex hormone-binding globulin (SHBG), gonadotropins, leptin, GH, lipids, insulin, and glucose levels were assessed before and after treatment., Result(s): In the metformin group of nonobese patients, the mean fasting serum insulin concentration decreased from a pretreatment value of 12.1 +/- 2.4 to 6.3 +/- 0.6 microU/mL after treatment, and the area under the curve of insulin decreased from 5,189.1 +/- 517.4 to 3,035.6 +/- 208.9 microU/mL per minute. Also in the metformin group of nonobese patients, the mean basal serum total testosterone, free testosterone, and androstenedione concentrations decreased by 38%, 58%, and 30%, respectively. In the obese patients treated with metformin, only free testosterone showed a statistically significant decrease (1.7 +/- 0.2)., Conclusion(s): Our data suggest that nonobese patients respond better than obese patients to a 1.5 g/day metformin regimen.