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Objective: To determine the frequency of phenotypes of polycystic ovarian syndrome (PCOS) in patients presenting with sub-fertility, and to compare the clinical and hormonal characteristics among them., Study Design: Descriptive cross-sectional study. Place and Duration of the Study: Department of Obstetrics and Gynaecology, Forest View Specialist Clinic, Peshawar, Pakistan, from August 2022 to January 2023., Methodology: The study included 662 female patients presenting with menstrual irregularities, hyperandrogenism, and infertility to the clinic. PCOS was diagnosed on the basis of the Rotterdam criterion and clinical features and classified into different phenotypes on the basis of the National Institute of Health (NIH) panel criteria. Data were entered and analysed by IBM SPSS VERSION 23.0. The frequency of four phenotypes was calculated and phenotypes were compared for age, weight, hormonal profiles, and history of miscarriages. A p <0.05 was considered statistically significant., Results: Frequency of PCOS in patients with infertility was 59.76%. Phenotype A was seen in 58.2%, phenotype D in 23.3%, phenotype C in 16.9%, and phenotype B in 1.7% of cases. The LH/FSH ratio was statistically significant in phenotype A as compared to other phenotypes, while other parameters were non-significant., Conclusion: The frequency of PCOS is high in patients with infertility. Phenotype A is the most common variant and is associated with significant impairment of the LH/FSH ratio., Key Words: Polycystic ovarian syndrome, Subfertility, Phenotypes of PCOS, Hyperandrogenism, Anovulation, R-C1.

Objective: To examine the relation of menstrual cyclicity abnormalities to hyperandrogenism (HA) and dynamic state insulin resistance (IR) in oligo-ovulatory women with polycystic ovary syndrome (PCOS)., Design: Prospective cross-sectional study., Setting: Tertiary-care academic center., Patient(s): Fifty-seven women with PCOS (1990 National Institutes of Health criteria) and 57 healthy control women matched by body mass index (BMI)., Intervention(s): Short insulin tolerance test (ITT)., Main Outcome Measure(s): Menstrual cyclicity, sex hormone-binding globulin (SHBG), measures of HA (i.e., modified Ferriman-Gallwey score, total and free testosterone, dehydroepiandrosterone sulfate), and the rate constant for plasma glucose disappearance (kITT) derived from the short ITT., Result(s): Adjusting for age, BMI, and ethnicity, the mean androgen measures were higher and SHBG trended lower, kITT was lower, and the prevalence of IR was higher in PCOS than in controls, independent of menstrual cyclicity. The optimal cutoff point for IR was set at kITT value of 3.57%/minute or lower. Overall, 79% of the women with PCOS had IR. To control further for the effect of ethnicity, a subgroup of 46 non-Hispanic white PCOS participants were studied; those who exhibited amenorrhea (n = 15) or oligomenorrhea (n = 19) had or tended toward having a lower kITT and a higher prevalence of IR than the women with PCOS and oligo-ovulatory eumenorrhea (n = 12). The kITT trended lower and the prevalence of IR trended higher in women with PCOS and amenorrhea than those with oligomenorrhea. The measures of SHBG and HA were similar across the three menstrual groups., Conclusion(s): Oligo-ovulatory women with PCOS and overt oligo/amenorrhea have greater degrees of IR but not HA when compared with oligo-ovulatory eumenorrheic women with PCOS, suggesting that IR and hyperinsulinemia but not HA play a role in determining the degree of menstrual dysfunction, which can be used as a clinical marker for the degree of IR in oligo-ovulatory PCOS., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Context: Anti-Müllerian hormone (AMH) measured in adolescence as biomarker for prediction of adult polycystic ovary syndrome (PCOS) is doubtful but not substantiated., Objective: To investigate whether serum AMH levels and other PCOS-associated features in adolescence can predict the presence of PCOS in adulthood., Design and Setting: A long-term follow-up study based on a unique adolescent study on menstrual irregularities performed between 1990 and 1997., Participants and Interventions: AMH was assayed in 271 adolescent girls. Data on PCOS features were combined with AMH levels. In 160 of the 271 (59%) participants, we collected information in adulthood about their menstrual cycle pattern and presence of PCOS (features) by questionnaire 2 decades after the initial study., Results: AMH was higher in adolescent girls with oligomenorrhea compared with girls with regular cycles, median (interquartile range): 4.6 (3.1-7.5) versus 2.6 (1.7-3.8) μg/L (P < 0.001). Women with PCOS in adulthood had a higher median adolescent AMH of 6.0 compared with 2.5 μg/L in the non-PCOS group (P < 0.001). AMH at adolescence showed an area under the receiver operating characteristic curve for PCOS in adulthood of 0.78. In adolescent girls with oligomenorrhea the proportion developing PCOS in adulthood was 22.5% (95% CI, 12.4-37.4) against 5.1% (95% CI, 2.1-12.0) in girls with a regular cycle (P = 0.005). Given adolescent oligomenorrhea, adding high AMH as factor to predict adult PCOS or adult oligomenorrhea was of no value., Conclusions: Adolescent AMH either alone or adjuvant to adolescent oligomenorrhea does not contribute as prognostic marker for PCOS in adulthood. Therefore, we do not recommend routine its use in clinical practice., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: Epidemiologic studies of polycystic ovary syndrome (PCOS) are limited, especially in populations where diagnostic resources are less available. In these settings, an accurate, low-cost screening tool would be invaluable., Objective: To test the use of a simple questionnaire to identify women at increased risk for PCOS and androgen excess (AE) disorders., Study Design: Prospective cohort study from 2006-2010., Setting: Community-based., Participants: Women aged 14 to 45 years., Intervention: A screening telephone questionnaire consisting of 3 questions was tested, where participants were asked to self-assess the presence/absence of male-like hair and menstrual irregularity. Participants were then invited to undergo a direct examination, including completing a medical history and undergoing a modified Ferriman-Gallwey (mFG) hirsutism score, ovarian ultrasound, and measurement of circulating total and free testosterone, DHEAS, TSH, prolactin and 17-hydroxyprogesterone levels., Main Outcome Measure: Accuracy of questionnaire in predicting PCOS, AE, and irregular menses., Results: Participants with self-assessed irregular menses and/or excess hair were labeled "Possible Androgen Excess (Poss-AE)" and those self-assessed with regular menses and no excess hair were labeled "Probable Non-Androgen Excess (Non-AE)." The study was completed in 206/298 (69%) of the Poss-AE and in 139/192 (73%) of the Non-AE. Of Poss-AE and Non-AE subjects, 82.5% and 15.8%, respextively, presented with PCOS. The calculated sensitivity, specificity, positive predictive value, and negative predictive value of the 3-question telephone survey to predict PCOS was 89%, 78%, 85%, and 83%, respectively., Conclusions: A simple telephone questionnaire, based on self-assessment of body hair and menstrual status, can be used with a high predictive value to identify women at risk for AE disorders, including PCOS, and to detect healthy controls. This approach could be an important tool for needed epidemiologic studies., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Different phenotypical features of women with hypothalamic hypogonadism (HH), also known as World Health Organization-1 anovulation, including ovarian morphology, have been scarcely described in large cohorts. Some studies have reported increased levels of anti-Müllerian hormone (AMH) in women with HH., Objective: To assess whether women with HH, compared with healthy controls, have increased serum levels of AMH and what proportion of these women erroneously meet the Rotterdam Criteria for Polycystic Ovarian Syndrome (PCOS)., Design, Setting and Participants: Retrospective cohort study in a Dutch academic medical center including 83 women with neither anovulation nor menstrual cycle disorders (healthy controls), 159 women with HH and 3640 women with PCOS. Age matching was used between the HH and PCOS group (1:2 ratio) to create a second group consisting of 318 age-matched women with PCOS., Intervention: None., Main Outcome Measures: AMH levels and ovarian morphology., Results: Median AMH serum levels for the HH group were 3.8 (<0.1-19.8), compared with 7.5 (<0.1-81.0) in the PCOS group and 1.9 (<0.1-21.5) in the control group (P < 0.001). In the HH group, 58 (36%) erroneously met the Rotterdam Criteria for PCOS (meeting 2 of 3 criteria)., Conclusions: AMH levels are increased in women with HH. We hypothesize that this increase, although there was no increase in follicle count, may be explained by the presence of a relatively large pool of antral follicles smaller than 2 mm in diameter, that are undetectable by transvaginal ultrasound. This study highlights the importance of measuring gonadotropins and estradiol before diagnosing a patient with PCOS., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder, clinically characterized by oligo-ovulation/chronic anovulation, menstrual irregularities, hyperandrogenism (such as hirsutism, acne), hyperinsulinemia, and obesity. Prostatic-specific antigen (PSA) has been identified as a potential new marker in PCOS women. Although the precise role of PSA in PCOS patients still remains undetermined, PSA might serve as a useful clinical marker and might even represent a new diagnostic criterion of hyperandrogenemia in females of PCOS., Methods: A meta-analysis was performed in the study to identify the association between the polycystic ovary syndrome and prostatic-specific antigen. To identify eligible original articles, we searched a range of computerized databases, including Medline via PubMed, EMBASE, CNKI and Web of Science with a systematic searching strategy. The characteristics of each study and standard mean differences (SMD) with corresponding confidence intervals (CIs) were calculated and subgroup analysis was performed to analyze heterogeneity., Results: A total of 532 patients from seven articles were included in the meta-analysis. We identified a significant relationship between polycystic ovary syndrome and prostatic-specific antigen, with a pooled SMD of 0.81 (95% CI: 0.58 to 1.04; P < 0.01). The pooled data were calculated with the random-effects model as a moderate significant heterogeneity was found among the studies., Conclusions: The meta-analysis suggested that there was a significant association between the polycystic ovary syndrome and prostatic-specific antigen and we should not ignore the role of PSA in the PCOS patients in clinical.

Background: The aim of this study was to evaluate serum vitamin D levels and to compare these with the menstrual cycle in young women with different body weights., Methods: Eighty-four students were recruited into the study of which 77 remained at the study's completion. Women were assigned to one of two subgroups, according to their 25-hydroxy vitamin D test level [25(OH)D] in which 60 women had low 25(OH)D levels (LD < 30 ng/mL) and 17 had normal levels (ND > 30 ng/mL ≤ 80 ng/mL)., Results: In the LD group, 40% of participants reported having long cycles, 27% were classified as having oligomenorrhoea, and 13% as having amenorrhoea. In the ND group, only 12% reported menstrual cycle disorders, 6% had oligomenorrhoea, and 6% had amenorrhoea. Women who did not meet the recommended level of 30 ng/mL of 25(OH)D had almost five times the odds of having menstrual cycle disorders as women who were above the recommended vitamin D level., Conclusion: A relationship was demonstrated between the frequency of menstrual disorders and low levels of vitamin D. Supplementation is necessary in women with low levels of vitamin D in order to compensate for this deficiency and to assess its effect in regulating menstrual disorders.

Context: Little is known about reproductive function in girls with youth-onset type 2 diabetes., Objectives: To characterize girls with irregular menses and effects of glycemic treatments on menses and sex steroids in the Treatment Options for Type 2 Diabetes in Youth (TODAY) study., Design: Differences in demographic, metabolic, and hormonal characteristics between regular- vs irregular-menses groups were tested; treatment group (metformin with or without rosiglitazone, metformin plus lifestyle) effect on menses and sex steroids over time in the study was assessed. This is a secondary analysis of TODAY data., Setting: Multicenter study in an academic setting., Patients: TODAY girls not receiving hormonal contraception and those at least 1-year postmenarche were included. Irregular menses was defined as three or fewer periods in the prior 6 months., Results: Of eligible participants with serum measurement of sex steroids (n = 190; mean age, 14 years), 21% had irregular menses. Those with irregular vs regular menses had higher body mass index (BMI) (P = 0.001), aspartate aminotransferase (AST) (P = 0.001), free androgen index (P = 0.0003), and total testosterone (P = 0.01) and lower sex hormone-binding globulin (SHBG) (P = 0.004) and estradiol (P = 0.01). Differences remained after adjustment for BMI. There was no treatment group effect on menses or sex steroids at 12 or 24 months, and no association of sex steroids was seen with measures of insulin sensitivity or secretion., Conclusions: Menstrual dysfunction is common in girls with recently diagnosed type 2 diabetes and associated with alterations in sex steroids, SHBG, and AST but not with alteration in insulin sensitivity or β-cell function and did not improve with 2 years of antihyperglycemic treatment.

The aim of this study was to assess the effects of intensive training on menstrual function and related serum hormones and peptides.Forty female participants who attended a training course for an officer at the Korea Third Military Academy, and had regular menstrual periods were enrolled. Menstrual questionnaires and fasting blood samples were collected before entry and at 4-week intervals for 8 weeks. The levels of corticotropin-releasing hormone (CRH), cortisol, prolactin, endorphin-β, neuropeptide Y (NPY), leptin, orexin-A, ghrelin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), thyrotropin (TSH), and thyroxine (T4) were determined.Body mass index and waist circumference decreased during the training course. Intensive training of military cadets resulted in changes of menstruation and related biomarkers. The levels of CRH, endorphin-β, NPY, orexin-A, ghrelin, E2, and T4 decreased substantially, and cortisol, prolactin, and TSH increased. Seventy percent of participants with regular menstrual periods before developed irregular during the training course. Participants were then categorized into 2 groups: those with regular menstruation (n = 12) and those with irregular menstruation (n = 28). The levels of hormones and peptides were not different between the 2 groups.In conclusion, cortisol, prolactin, and TSH level increased but levels of CRH, endorphin-β, NPY, orexin-A, ghrelin, E2, and T4 decreased throughout the training. Moreover, the levels were not different between participants with normal menstruation and those with irregular menstruation. Further research should extend these findings by investigating the exact mechanism by which high exercise levels, including intensive training, interfere with regular menstruation.

Treatment with antipsychotic drugs has been associated with hyperprolactinemia. The same antipsychotic drugs have also been associated with side effects such as menstruation disorders. The aim of this study was to evaluate the prevalence of hyperprolactinemia and menstruation disorders in women undergoing antipsychotic treatment. We performed a retrospective chart review study of psychiatric patients who underwent laboratory testing for serum prolactin (PRL) level between March 2011 and March 2015 in Ehime University Hospital. Patients presenting with and without menstruation disorders were evaluated to determine if they presented concomitant hyperprolactinemia. Patients with menstrual disorders had a significant increase in serum PRL level with a mean of approximately 90 ng/mL. Those with menstrual disorders presented increased PRL levels by 2-fold that of patients without menstrual disorder. However, there was no significant difference in the equivalent dose of chlorpromazine between these two groups. Additionally, about 70% of patients with menstrual disorders received risperidone treatment. The receiver operating characteristic curve showed that the optimal cutoff point of serum PRL level associated with the development of menstrual disorders was 60 ng/mL. Based on these results, we concluded that patients with menstrual disorders presented increased serum PRL, and that most of them underwent treatment with risperidone.

Objective: To examine the association between serum 25-hydroxyvitamin D [25(OH)D] and menstrual cycle length and regularity., Design: Community-based, cross-sectional study of serum 25(OH)D (adjusted for seasonal differences in timing of blood draw) and menstrual cycle length. Women aged 23-34 years reported their gynecologic history. Menstrual cycles were described with four independent categories (normal, short, long, irregular). We used polytomous logistic regression to estimate the association between a doubling of seasonally adjusted 25(OH)D and the odds of each cycle category., Setting: Not applicable., Patient(s): A total of 1,102 African American women., Intervention(s): Not applicable., Main Outcome Measure(s): Self-reported menstrual cycle length over the previous 12 months, excluding women who were using cycle-regulating medications over the entire year. Women who reported that their cycles were "too irregular to estimate" were classified as having irregular cycles. A typical cycle length of <27 days was considered "short," >34 days was "long," and 27-34 days was "normal.", Result(s): The median 25(OH)D level was 14.7 ng/mL (interquartile range, 10.9-19.6 ng/mL). A doubling of 25(OH)D was associated with half the odds of having long menstrual cycles: adjusted odds ratio (aOR) 0.54, 95% confidence interval (CI) 0.32-0.89. 25-Hydroxyvitamin D was not associated with the occurrence of short (aOR 1.03, 95% CI 0.82-1.29) or irregular (aOR 1.46, 95% CI 0.88-2.41) menstrual cycles. Results were robust to several sensitivity analyses., Conclusion(s): These findings suggest that vitamin D status may influence the menstrual cycle and play a role in ovarian function. Further investigation of 25(OH)D and ovarian hormones, and prospective studies of 25(OH)D and cycle length, are needed., (Copyright © 2016 American Society for Reproductive Medicine. All rights reserved.)

Objective: To determine whether sonographic markers of ovarian morphology or male pattern hair growth scores predict androgen levels in women with regular or irregular menstrual cycles., Design: Cross-sectional observational study., Setting: Clinical research unit., Patient(s): Seventy-six women of reproductive age (18-39 years) were evaluated for male-pattern hair growth (using a modified Ferriman-Gallwey scoring system), ovarian morphology (by transvaginal ultrasonography), and total serum testosterone (T) (by liquid chromatography tandem mass spectrometry)., Intervention(s): Not applicable., Main Outcome Measure(s): Regional and total modified Ferriman-Gallwey scores, number of follicles per follicle size category, follicle number per ovary, ovarian volume, ovarian area, stromal to ovarian area ratio, stromal echogenicity index, total testosterone (total T), and menstrual cycle length., Result(s): Neither regional nor total modified Ferriman-Gallwey scores correlated with total T concentrations in women with regular or irregular menstrual cycles, as judged by the Least Absolute Shrinkage and Selection Operator technique. By contrast, a sonographic marker (follicle number per ovary 6-9 mm) significantly predicted total T concentrations in women with regular menstrual cycles but not in women with irregular menstrual cycles., Conclusion(s): Sonographic markers of ovarian morphology, but not hirsutism scores, predicted total T levels. However, the predictive value of ovarian morphology for total T differed by menstrual cycle status. That sonographic markers did not predict androgen levels in a diverse cohort of women with cycle irregularity suggests the potential for distinct variations in ovarian morphology for androgenic and nonandrogenic types of cycle irregularity. Overall, our findings support that an assessment of ovarian morphology may be helpful in reflecting total T levels., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Menstrual irregularity and above-average testosterone levels in adolescence may presage polycystic ovary syndrome (PCOS) in adulthood but persist in only a minority. Prolonged anovulatory cycles in normal adolescents are associated with increased testosterone levels. Thus, questions have been raised about the accuracy of PCOS diagnosed in adolescents., Objective: The purpose of this study was to follow-up hyperandrogenic adolescents with features of PCOS to test the hypothesis that adolescent functional ovarian hyperandrogenism (FOH) persists into adulthood., Study Subjects: A series of adults previously reported to have adolescent PCOS, with most documented to have FOH by GnRH agonist or dexamethasone androgen-suppression test criteria, were recalled., Methods: Recall occurred >3 years after the initial diagnosis and at the age of >18.0 years. Respondents underwent examination, baseline androgen evaluation, and an oral glucose tolerance test after discontinuing oral contraceptive therapy., Results: Of the adolescent hyperandrogenic patients, 68% (15 of 22) were traceable, and 60% of those traced returned for follow-up, including half (n = 8) of the original FOH group. The baseline characteristics of respondents and nonrespondents were not significantly different. Patients with FOH were reevaluated when their mean age was 23.0 years (range, 18.4-29.4 years), gynecologic age was 10.7 years (range, 5.5-18.4 years), and body mass index was 42.3 kg/m(2) (range, 28.3-52.1 kg/m(2); P = .02 vs adolescence). Serum free testosterone was 24 pg/mL (range, 10-38 pg/mL, normal, 3-9 pg/mL; not significant vs adolescence); all were oligomenorrheic. Whereas 3 of 8 had impaired glucose tolerance as adolescents, at follow-up 6 of 8 had developed abnormal glucose tolerance (2 with type 2 diabetes mellitus)., Conclusions: Adolescents with FOH, which underlies most PCOS, uniformly have persistent hyperandrogenism, and glucose tolerance tends to deteriorate. Testing ovarian androgenic function in hyperandrogenic adolescents may be of prognostic value.

Background: Antipsychotic medications, particularly second-generation antipsychotics, are increasingly being used to alleviate the symptoms of schizophrenia and other severe mental disorders in the pediatric population. While evidence-based approaches examining efficacy and safety outcomes have been reported, no review has evaluated prolactin-based adverse events for antipsychotic treatments in schizophrenia and schizophrenia spectrum disorders., Methods/design: Searches involving MEDLINE, EMBASE, CENTRAL, PsycINFO, and clinical trial registries (ClinicalTrials.gov, Drug Industry Document Archive [DIDA], International Clinical Trials Registry Platform [ICTRP]) will be used to identify relevant studies. Two reviewers will independently screen abstracts and relevant full-text articles of the papers identified by the initial search according to the prospectively defined eligibility criteria. Data extraction will be conducted in duplicate independently. Pairwise random effects meta-analyses and network meta-analyses will be conducted on individual drug and class effects where appropriate., Discussion: This systematic review will evaluate prolactin-based adverse events of first- and second-generation antipsychotics in the pediatric population with schizophrenia and schizophrenia spectrum disorders. It will also seek to strengthen the evidence base of the safety of antipsychotics by incorporating both randomized controlled trials and observational studies., Systematic Review Registration: PROSPERO CRD42014009506.

Context: Although adequate luteal hormone production is essential for establishing pregnancy, luteal phase deficiency (LPD) is poorly characterized among eumenorrheic women., Objective: We assessed the prevalence and overlap of two established LPD diagnostic criteria: short luteal phase duration less than10 days (clinical LPD) and suboptimal luteal progesterone of 5 ng/mL or less (biochemical LPD) and their relationship with reproductive hormone concentrations., Design, Setting, and Participants: We conducted a prospective study in western New York (2005-2007) following 259 women, aged 18-44 years, for up to two menstrual cycles., Results: Among ovulatory cycles with recorded cycle lengths (n = 463), there were 41 cycles (8.9%) with clinical LPD, 39 cycles (8.4%) with biochemical LPD, and 20 cycles (4.3%) meeting both criteria. Recurrent clinical and biochemical LPD was observed in eight (3.4%) and five (2.1%) women, respectively. Clinical and biochemical LPD were each associated with lower follicular estradiol (both P ≤ .001) and luteal estradiol (P = .03 and P = .02, respectively) after adjusting for age, race, and percentage body fat. Clinical, but not biochemical, LPD was associated with lower LH and FSH across all phases of the cycle (P ≤ .001)., Conclusions: Clinical and biochemical LPD were evident among regularly menstruating women. Estradiol was lower in LPD cycles under either criterion, but LH and FSH were lower only in association with shortened luteal phase (ie, clinical LPD), indicating that clinical and biochemical LPD may reflect different underlying mechanisms. Identifying ovulation in combination with a well-timed luteal progesterone measurement may serve as a cost-effective and specific tool for LPD assessment by clinicians and researchers.

Background: In this study, the characteristics of menstrual cycle in shift workers employed in the pharmaceutical industry are investigated., Method: This study was conducted in a pharmaceutical industrial complex in Tehran in 2012. 406 female workers in packaging units were studied on the menstrual cycle characteristics. The studied workers were divided into two groups of shift workers and non-shift workers and were compared in terms of the frequency of menstrual disorder (short-term cycle, long-term cycle, irregular cycle and bleeding during menstrual cycle) as well as hormonal values (FSH, LH, TSH, and Prolactin)., Results: The odds ratio (OR) for menstrual disorder in the shift workers was 5.54 (95% CI=2.78-11.02) compared to the non-shift workers. The mean difference of hormonal values (except prolactin) between shift workers and non-shift workers was not significant (P>0.05)., Conclusion: This study suggests that shift work may disrupt the menstrual cycle.

Study Question: Are self-reported menstrual disorders associated with hyperandrogenaemia and metabolic disturbances as early as in adolescence?, Summary Answer: Menstrual disorders at the age 16 are a good marker of hyperandrogenaemia, and an adverse lipid profile was associated with higher androgen levels., What Is Known and What This Paper Adds: Hyperandrogenism per se has been suggested to be a significant metabolic risk factor in women and a cause of physical and psychological morbidity in adolescent girls. A weak positive correlation has been described between hyperandrogenaemia and obesity in adolescent girls, but the clinical consequences are still poorly understood. Hyperandrogenism and insulin resistance are also key features of polycystic ovary syndrome (PCOS), and women with PCOS are consequently at an increased risk of developing type 2 diabetes mellitus and/or metabolic syndrome, and may have increased cardiovascular morbidity. Our findings confirm that the association between menstrual disorders, hyperandrogenism, obesity and metabolic risks is already evident in adolescence., Study Design: This population-based, cross-sectional study used postal questionnaires to targeting 15-16-year-old girls in the Northern Finland Birth Cohort 1986 (n= 4567)., Participants and Setting: There were 3669 girls who answered the postal questionnaire and out of 3373 girls who also underwent clinical examinations and blood tests, 2448 were included in the analyses. The questionnaire included one question about the regularity and length of the menstrual cycle: 'Is your menstrual cycle (the interval from the beginning of one menstrual period to the beginning of the next period) often (more than twice a year) longer than 35 days?' The girls who answered 'yes' to this question were considered to be suffering from menstrual disorders and were classified as 'symptomatic'. The girls who answered 'no' were defined as 'non-symptomatic'., Main Results and the Role of Chance: There were 709 (29%) girls who reported menstrual disorders (symptomatic girls) and 1739 who had regular periods (non-symptomatic girls). In the whole population and in both study groups, there were significant correlations between body mass index (BMI) (and waist-to-hip ratio), hyperandrogenaemia and metabolic parameters. Symptomatic girls exhibited significantly higher serum concentrations of testosterone (P= 0.010), lower levels of sex hormone-binding globulin (P =0.042) and higher free androgen indices [FAIs; geometric mean 3.38 (interquartile range (IQR): 2.27, 5.18) versus 3.08 (IQR: 2.15, 4.74), P= 0.002]. The two groups had comparable BMI and insulin sensitivity, and serum levels of glucose, insulin and lipids. There was a significant linear trend towards higher FAI values in the higher BMI quartiles in both symptomatic and non-symptomatic girls. In the whole population, there was a statistically significant linear decrease in high-density lipoprotein concentrations (P < 0.001) and higher triglyceride concentrations (P =0.004) in the upper FAI quartile., Implications: Information regarding menstrual disorders in adolescence is a good marker of hyperandrogenaemia and may be an early risk factor for the development of PCOS in adulthood. The association between obesity, hyperandrogenism and metabolic risks is already evident in adolescence, which strengthens the importance of noting menstrual disorders at an early stage. BIAS, LIMITATIONS, GENERALIZABILITY: The cross-sectional nature of the study does not allow us to draw conclusions concerning the metabolic risks of this population in later life. The diagnosis of menstrual disorders was based on a questionnaire, suggesting a risk of information bias in reporting the symptoms. This study was not designed to diagnose PCOS, as ultrasonography was not available and there was no clinical evaluation of hyperandrogenism (i.e. hirsutism). However, we were able to take into account potential confounding factors in the analyses., Study Funding/competing Interests: This work was supported by grants from the Finnish Medical Society Duodecim, the North Ostrobothnia Regional Fund, the Academy of Finland (project grants 104781, 120315, 129269, 1114194, SALVE), University Hospital Oulu, Biocenter, University of Oulu, Finland (75617), the European Commission (EURO-BLCS, Framework 5 award QLG1-CT-2000-01643) and the Medical Research Council, UK (PrevMetSyn/SALVE). None of the authors have any conflict of interest to declare.

Earlier menarche and irregular periods, among other markers of sex-hormone levels, have been associated with a higher risk of asthma and allergic diseases. This has suggested an etiologic role of sex hormones in the development of these conditions. The authors investigated the association of age at menarche, irregular periods, duration of menstruation, and acne with reported medical history of asthma and/or atopy (hay fever and/or eczema/urticaria) in a historical cohort of students born before the rise in asthma prevalence in the United Kingdom and attending university in 1948-1968. Finding consistent associations in a cohort that has experienced different life-course exposures and has different confounding structure can help to identify causal associations. In the Glasgow Alumni Cohort, irregular periods were associated with atopic asthma (multinomial odds ratio (MOR) = 2.79, 95% confidence interval (CI): 1.33, 5.83) and atopy alone (MOR = 1.40, 95% CI: 1.06, 1.84) but not with nonatopic asthma (MOR = 1.02, 95% CI: 0.45, 2.30), compared with students reporting no asthma and no atopy. The authors found no association with acne, a marker of high testosterone levels, that they hypothesized could point to polycystic ovary syndrome underpinning these associations. In summary, the authors found evidence for a potentially etiologic role of irregular menstruations with some specific asthma phenotypes, namely, atopic asthma and atopy, but not with nonatopic asthma.

Background: There have been few studies examining the associations between menstrual irregularity, androgens and bone mass in population-based samples of premenopausal women. This study aimed to describe the associations between menstrual pattern, testosterone, sex hormone binding globulin (SHBG) and bone mass in a population-based sample of premenopausal women., Methods: Cross-sectional study (N = 382, mean age 31.5 years). Menstrual pattern was assessed by questionnaire, bone mass measured by quantitative ultrasound (QUS) and androgen status was assessed by levels of serum testosterone, SHBG and the free androgen index (FAI)., Results: Women with irregular cycles (n = 41, 11%) had higher free androgen index (FAI, P = 0.01) and higher QUS measurements including speed of sound (SOS, 1%, P < 0.05), quantitative ultrasound index (QUI, 7%, p < 0.05), and broadband ultrasound attenuation (BUA, 7%, p = 0.10). These associations persisted after adjustment for age and body mass index (BMI). After further adjustment for hormonal factors (either testosterone, SHBG or FAI), the strength of the associations was moderately attenuated, however, women with irregular cycles still had a 6% increase in mean QUS. Total testosterone, FAI and SHBG were also associated with QUS measures (testosterone and FAI, r +0.11 to +0.21, all p < 0.05; SHBG r -0.14 to -0.16, all p < 0.05) and the associations remained significant after adjustment., Conclusion: Irregular menstrual cycles were associated with higher bone mass in this population-based sample of premenopausal women suggesting menstrual disturbance should continue to be evaluated but may be less harmful for bone mass. The association between menstrual irregularity and bone mass was partially mediated by markers of androgen status especially free testosterone.

Background: Alterations in circulating steroids are believed to be important mediators of the impact that diet and exercise have on breast cancer risk and changes in bone density. This study aimed to test the hypothesis that moderate exercise training combined with caloric restriction would produce significant menstrual disturbances and alterations in ovarian steroids in premenopausal women., Methods: Sedentary premenopausal women (25-40 years; body mass index: 23.6 +/- 0.6 kg/m(2)) assigned to either a light conditioning (LC, n = 9) or an exercise combined with caloric restriction group (EX + CR, n = 24) were studied for one screening, one baseline and four intervention periods equivalent to the length of subjects' menstrual cycles. Exercise consisted of supervised training sessions, i.e. two LC or four EX + CR times per week, 30-60 min at a moderate intensity. The EX + CR group was prescribed a diet representing a caloric restriction of 20-35% below baseline energy requirements, whereas the LC group remained eucaloric. Ovarian steroid exposure was determined with daily urinary estrone-1- and pregnanediol glucuronides (E1G and PdG, respectively) and mid-cycle urinary LH measures. Fitness, body composition, and serum sex hormone binding globulin (SHBG) and serum estradiol (E2) were assessed repeatedly., Results: The intervention produced significant increases in VO(2) max and decreases in both body weight (-3.7 +/- 0.5 kg; ranged from -8.8 to +1.8 kg) and percent body fat (-4.5 +/- 0.7%; ranged from -12 to +0.3%), which were attributable primarily to changes in the EX + CR subjects (time x group; P < 0.05). Serum E2 and urinary E1G and PdG concentrations declined significantly across the intervention period (time; P < 0.05), whereas SHBG increased transiently (time; P < 0.05) in the EX + CR subjects, with no significant changes observed in the LC group. The decrease in E1G area under the curve was significantly related to the daily energy deficit (R =0.61; P = 0.003), not the amount of weight lost. There was no significant impact of the intervention on menstrual cyclicity or the incidence of menstrual disturbances in either group., Conclusions: A moderate aerobic exercise training program combined with modest weight loss in accordance with recommended guidelines produces significant reductions in ovarian steroid exposure without disrupting menstrual cyclicity in premenopausal women aged 25-40 years. Exposure to a daily energy deficit is a stronger predictor of the decline in estrogen exposure than decreases in body weight.

Context: Serum anti-Müllerian hormone (AMH) levels are significantly elevated in adolescents with polycystic ovary syndrome (PCOS) compared to normal controls. Whether adolescents with oligomenorrhea have elevated AMH levels is unknown., Objective: This study was performed to assess serum AMH levels in oligomenorrheic (OLIGO) girls without evidence of hyperandrogenism., Design: This was a prospective study comparing AMH levels in OLIGO, PCOS, and normal control adolescents., Setting: The study was conducted through four tertiary academic medical centers., Participants: The study groups were comprised of OLIGO (n = 24), PCOS (n = 153), and normal adolescent girls (n = 39), as well as PCOS (n = 73) and normal adult women (n = 36)., Interventions: In each subject, serum AMH levels were assessed in the early to midfollicular phases for regularly menstruating subjects and on an arbitrary day for OLIGO or PCOS subjects., Main Outcome Measure(s): Basal serum AMH levels were assessed among OLIGO, PCOS, and normal girls, in addition to PCOS and normal women., Results: OLIGO girls had serum AMH levels (5.33 +/- 0.47 ng/ml) that were significantly greater than the normal adolescents (3.05 +/- 0.31 ng/ml) and adults (2.33 +/- 0.22 ng/ml), but similar to values seen in the PCOS adolescents (5.28 +/- 0.26 ng/ml) and adults (6.36 +/- 0.47 ng/ml). Obese adolescents and PCOS women had significantly lower AMH levels compared to lean controls (P < 0.02)., Conclusion: In OLIGO adolescents, elevated serum AMH levels suggest increased antral follicle number similar to that observed in girls with PCOS.

Background: Menstrual disturbances in female athletes are often explained as a consequence of energy deficiency. Oral contraceptive (OC) treatment may have favorable metabolic effects. We evaluated effects of OCs on diurnal secretions of insulin, insulin-like growth factor binding protein 1 (IGFBP-1), growth hormone (GH) and cortisol in relation to changes in body composition in athletes with menstrual disturbance compared with regularly menstruating athletes and controls., Methods: Age- and BMI-matched groups of endurance athletes with menstrual disturbance (OAM, n = 9) and regularly cycling athletes (RM, n = 8) and sedentary controls (CTRL, n = 8) were examined, and hormone levels measured, before and after 8 months of treatment with a low-dose combined OC (30 microg ethinyl estradiol + 150 microg levonorgestrel)., Results: Before OC treatment, the diurnal profile of insulin was lower (P < 0.01) and levels of IGFBP-1 (P < 0.05) and cortisol (P < 0.05) were higher in OAM athletes than in CTRL, whereas GH secretion was higher than in RM athletes (P < 0.05). After treatment, diurnal secretions of these hormones were similar between groups with an increase of IGFBP-1 in the regularly menstruating subjects only (P < 0.001). OC treatment increased body fat mass in OAM athletes (P < 0.01 versus baseline). The change in total fat mass correlated positively with pretreatment diurnal levels of GH (r(s) = 0.67, P < 0.01) and cortisol (r(s) = 0.64, P < 0.01)., Conclusions: OC treatment in endurance athletes with menstrual disturbance increases body fat mass and results in diurnal levels of insulin, IGFBP-1, GH and cortisol that are comparable to those in regularly menstruating subjects. These results suggest that OCs improve metabolic balance in OAM athletes.

Multiple sclerosis is a chronic inflammatory disease of central nervous system.Women are more susceptible to this disease. One of the obvious clinical complaints in women with multiple sclerosis specially treated with Beta Interferones is menstrual cycle irregularity. The aim of this study was to determine the prevalence of menstrual irregularities and probable changes in blood levels of related hormones (FSH, LH, PRL, TSH, T4, T3) in 58 females with definite MS treated with beta interferones versus 58 healthy women. In comparison to the control group, the patients had higher prevalence of irregular menstruation (P=0.001), oligomenorrhea (p=0.03), abnormal amount of menstrual blood flow (P=0.001), abnormal duration of menstrual flow (P=0.01) and missed period (P=0.04). Mean LH level in patients group was higher than control group (P=0.04). Hyperprolactinemia (>25.5 ng/ml) was more prevalent in patients group. There were not a significant difference in plasma levels of FSH and thyroid hormones between two groups. There were some relations between the type of Beta interferones and the subtype of menstrual irregularities in the patients. In conclusion, the results of this study emphasized the high rate of menstrual problem and changes of related plasma hormone levels in MS patients.

Background: The purpose of this study was to test the hypothesis that menstruation is associated with a higher concentration of endometrial cells in peritoneal fluid(PF) and with increased white and red blood cell concentration in PF when compared to nonmenstrual phases of the cycle., Methods: PF was obtained at laparoscopy from 107 women with endometriosis (n = 59) and controls with a normal pelvis (n = 48) during the luteal (n = 46), follicular (n = 38) or menstrual (n = 23) phase of the cycle. Endometriosis was classified according to the classification of the American Society for Reproductive Medicine (rAFS into minimal (n = 25), mild(n = 20), moderate(n = 6) and severe(n = 8) disease. Cell counts (leucocytes, erythrocytes, thrombocytes) were determined on a cell counter. In a subset of 32 patients (13 controls and 19 women with endometriosis), PF was fixed, processed and thinlayers were prepared and stained with Papanicolaou method and with immunocytochemistry using monoclonal antibodies against cytokeratin 7(CK 7), CK 8/18, Ber-Ep4, vimentin, calretinin and CD68. Ber-Ep4 is a marker for cells with epithelial origin (in some cases for mesothelial cells as well). CD68 is specific for cells from monocyte/macrophage lineage; CK7 and CK8/18 are markers for both endometrial epithelial and mesothelial cells, whereas calretinin and vimentin are markers for both endometrial stromal and mesothelial cells., Results: In comparison with the nonmenstrual phase of the cycle, analysis of PF during menstruation showed an increased concentration of leucocytes (3.3 x 109/L vs 0.8 x 109/L, P = 0.03), erythrocytes (0.3 x 1012/L vs 0.02 x 1012/L, P = 0.006), hematocrit (0.03 L/L vs 0.003 L/L, P = 0.01) and hemoglobin (0.8 g/dL vs 0.1 g/dL, P = 0.01). Mesothelial cells stained positively with CK7, CK8/18, vimentin, and calretinin. Cells positive for Ber-Ep4 were not observed, except in 2 patients with endometriosis investigated during menses. In all patients 50-98% of single cells were strongly positive for both vimentin and CD68., Conclusion: When compared to nonmenstrual phases of the cycle, menstruation is associated with an increased concentration of red and white blood cells in PF. However, the presence of EM cells that are detectable by immunohistochemistry in PF is low during all phases of the cycle, including menstruation.

Background: Anti-Müllerian hormone (AMH) has been proposed as a clinical predictor of improvements in reproductive function following weight loss in overweight and obese women with polycystic ovary syndrome (PCOS). This study aimed to assess whether baseline and/or change in AMH levels with weight loss predict improvements in reproductive function in overweight and obese women with PCOS., Methods: Fifty-two overweight and obese women with PCOS and reproductive impairment (age 29.8 +/- 0.8 years, BMI 36.5 +/- 0.7 kg/m(2)) followed a 20-week weight loss programme. AMH, weight, menstrual cyclicity and ovulatory function were assessed at baseline and post-intervention., Results: Participants who responded with improvements in reproductive function (n = 26) had lower baseline AMH levels (23.5 +/- 3.7 versus 32.5 +/- 2.9 pmol/l; P = 0.03) and experienced greater weight loss (-11.7 +/- 1.2 versus -6.4 +/- 0.9 kg; P = 0.001) compared with those who did not respond (n = 26). Logistic regression analysis showed that weight loss and baseline AMH were independently related to improvements in reproductive function (P = 0.002 and P = 0.013, respectively). AMH levels did not change with weight loss in both responders and non-responders., Conclusions: In overweight and obese women with PCOS and reproductive dysfunction, a 20-week weight loss intervention resulted in improvements in reproductive function but no change in AMH levels., Clinical Trials Registration Number: ACTRN12606000198527.

This cross-sectional study aimed to examine the association between different body composition measures, menstrual cycle characteristics, and hormonal factors in a population-based sample of young women. The study sample included 726 Australian women aged 26-36 years who were not currently taking hormonal contraceptives and were not currently pregnant or breast feeding. Anthropometric measures included BMI, waist circumference (WC), and waist-hip ratio (WHR). Menstrual cycle characteristics were self-reported and usual cycles defined as short (or=35 days). Cycles were defined as irregular if there were >or=15 days between the longest and shortest cycle in the past 12 months. Fasting serum levels of sex hormone-binding globulin (SHBG), testosterone, insulin, and glucose were measured and the free androgen index (FAI) derived. Compared with those of normal weight, obese women had at least a twofold greater odds of having an irregular cycle, whether defined by BMI (odds ratio (OR) = 2.61; 95% CI = 1.28-5.35), WC (OR 2.28; 95% CI = 1.16-4.49), or WHR (OR = 2.27; 95% CI = 1.09-4.72). Body composition measures were significantly positively associated with fasting insulin, testosterone, and FAI, and negatively associated with SHBG (P < 0.01). Fasting insulin, SHBG, and FAI had the strongest influence on the associations between obesity and irregular cycles, with statistically significant ORs of having an irregular cycle being attenuated to near null values following adjustment. In conclusion, both overall and central obesity were significantly associated with having an irregular menstrual cycle. This association was substantially influenced by hormonal factors, particularly insulin and SHBG.

Purpose of the Work: To assess bone mineral density (BMD) in girls with menstruation disorders in the first years after menarche and to demonstrate that BMD value may be one of the indicators confirming an early diagnosis of hypothalamic hypogonadism or androgenisation complex., Material and Methods: The research included 155 girls at the ages of 16-17, observed due to rare menstruation or secondary amenorrhea. In case of 71 girls functional, hypothalamic disorders were found (Group A), in 35 girls increasing androgenisation features were diagnosed additionally (Group B), and 49 healthy girls represented Group C--control group. BMI was determined, as well as FSH, LH, T, E2, PRL concentrations and the BMD test of lumbar spine section was made in all of the cases. RESEARCH RESULTS: The average values of BMI and BMD in Group A were the lowest compared to Group B (p<0.001) and Group C (p<0.001). E2 concentrations in Group A was the lowest and in Group B--the highest (p<0.001). T concentrations in Group B girls was the highest and SHBG--the lowest compared to Groups A and C (p<0.001; p<0.01). FSH concentrations in Group A were the lowest compared to Groups B and C (p<0.01), while LH in Group B was the highest (p<0.001; p<0.01). Basic PRL concentrations were not essentially different. In groups (A + B + C) together, a statistically significant correlation between BMD and BMI values was found (r=0.67; p<0.001), E2 (r=0.38; p<0.01) and T (r=0.56; p<0.001)., Conclusions: Low bone mineral density value compared to the age value may signify long-term hypoestrogenism, and high value - a complex of metabolic disorders with high concentration of androgens. Therefore, bone mineral density may be a reliable and highly sensitive metabolic and hormonal indicator of menstruation disorders of hypothalamic, functional type or androgenisation complex.

Objective: To examine the efficacy of sibutramine together with brief lifestyle modification for weight reduction in obese women with polycystic ovary syndrome (PCOS)., Design: Investigator-initiated, multicenter, double-blind, randomized, parallel-group clinical trial., Setting: Departments of Obstetrics and Gynecology in primary care, referral centers, and private practice., Patient(s): Forty-two patients with confirmed PCOS were included in the study, and 34 patients completed the study., Intervention: Sibutramine 15 mg once daily together with brief lifestyle modification was compare with placebo together with brief lifestyle modification., Main Outcome Measure(s): The primary endpoint was to assess weight loss. Secondary endpoints included the efficacy of sibutramine for treatment of menstrual pattern and cardiovascular risk factors., Result(s): After 6 months the sibutramine group had lost 7.8 +/- 5.1 kg compared with a weight loss of 2.8 +/- 6.2 kg in the placebo group. Sibutramine treatment resulted in significant decreases in apolipoprotein B, apolipoprotein B/apolipoprotein A ratio, triglycerides, and cystatin C levels., Conclusion(s): Sibutramine in combination with lifestyle intervention results in significant weight reduction in obese patients with PCOS. In addition to the weight loss, sibutramine seems to have beneficial effects on metabolic and cardiovascular risk factors.

Aims: To assess the prevalence of hormonal dysfunction in women addicted to alcohol during first week following drinking cessation; to determine whether fluctuations of hormone levels in follicular, ovulation and luteal phases in addicted women are equal to those normally found in healthy women; to determine the association between hormonal imbalances with selected clinical features., Methods: Biochemical parameters of liver function and hormone levels were assessed in 30 women treated for 30 days in a Short Term Therapy and Detoxification Ward. The following hormones were measured: prolactin (PROL), folliculotropin (FSH), luteotropin (LH), estradiol (ES) and testosterone (TEST)--(i) after menstruation, at follicular phase, between 5th and 7th day of the cycle; (ii) around ovulation, 11-14th day of the cycle; and (iii) before menstruation, at luteal phase, between 19th and 22th day of the cycle., Results: Mean PROL levels in all three cycle phases and progesterone level in follicular phase were above, while mean TEST level was below, the reference values. Over 50% of women had abnormally increased PROL values in all phases of the cycle while decreased values of PROG or LH were found in approximately 50% and >30% of study women., Conclusions: The menstrual cycle disturbances in alcoholic women are most prominent around the middle part of the cycle and age influences the pattern of hormonal changes.

Aim: Evaluation of CCCT results and anti-Müllerian hormone (AMH) plasma levels in women with menstrual cycle irregularities and/or infertility., Patients and Methods: 70 patients with menstrual cycle disturbances were recruited to the study. Clomiphene citrate challenge test (CCCT) was carried out in each patient enrolled. At day 3 of the cycle plasma basic levels of FSH, estradiol, progesterone, IGFBP-1, TSH, prolactin, DHEAS and anti-Müllerian hormone were measured. At day 10 of the cycle plasma levels of FSH and estradiol were evaluated. Plasma levels of hormones were measured by commercially available ELISA kits., Results: 50 women with normal result of CCCT (group A) had higher mean plasma level of AMH compared to 20 women with abnormal result of CCCT (group B). Mean plasma FSH level at day 3 of the cycle was lower in group A compared to group B. There were no other statistically significant differences in mean values of assessed parameters between groups A and B. Taking into account all patients enrolled to the study AMH correlated significantly with patients' age and plasma levels of FSH at day 3 and day 10 of the cycle). Basic AMH plasma levels in group A correlated negatively with plasma levels of FSH at day 3 and day 10. In group B plasma levels of FSH at day 10 of the cycle also correlated with basic AMH plasma levels. Plasma levels of estradiol at day 10 of the cycle were related inversely with basic AMH plasma levels in group A, but directly in group B., Conclusion: It should be recommended to perform the CCCT before infertility treatment. Evaluation of the anti-Müllerian hormone plasma level reflects the results of the CCCT.

Purpose: The aim of the study was to compare the effects of carbamazepine (CBZ) and oxcarbazepine (OXC) on the reproductive endocrine function in women with epilepsy. OXC is a novel antiepileptic drug (AED), and the occurrence of reproductive dysfunction in women treated with OXC monotherapy for epilepsy has not been studied previously., Methods: Thirty-five women with epilepsy were examined in the Department of Neurology at Oulu University Hospital. Sixteen patients were treated with CBZ monotherapy, and nineteen patients were treated with OXC monotherapy. The subjects were clinically examined, vaginal ultrasonography was performed, and serum sex hormone concentrations were measured., Results: The women taking CBZ or OXC had lower serum testosterone (T) levels and lower free androgen indexes (FAIs) than the control subjects. CBZ medication was associated with increased concentrations of serum sex hormone-binding globulin (SHBG). The patients taking OXC had higher concentrations of dehydroepiandrosterone sulfate (DHEAS) and androstendione (A) than did the women taking CBZ. Moreover, the prevalence of polycystic ovaries (PCOs) was high in the OXC-treated women., Conclusions: CBZ and OXC have different effects on the reproductive endocrine function. Although both drugs were associated with low serum T concentrations and low FAIs, only OXC was associated with a high frequency of elevated levels of A and DHEAS and with an increased prevalence of PCOs. These findings suggest that OXC may be disadvantageous for women with epilepsy and hyperandrogenism, whereas CBZ may be beneficial for these women.

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.

The aim of this study was to evaluate the diurnal pattern of testosterone and pituitary hormones in endurance female athletes with different types of menstrual disorder. Age- and body mass index-matched groups of endurance athletes with amenorrhea (n = 10) and oligomenorrhea (n = 6), regularly cycling athletes (n = 8), and sedentary controls (n = 8) were compared with respect to 24-h hormonal profiles of testosterone, LH, prolactin (PRL), GH, insulin, IGF binding protein 1 (IGFBP-1), and cortisol. The 24-h hormone profiles in amenorrheic athletes were characterized by decreased LH pulsatility and peak amplitude of PRL and increased baseline levels of GH and cortisol. However, oligomenorrheic athletes displayed a significantly different pattern with higher diurnal testosterone secretion than all other groups. Furthermore, LH, PRL, GH, and cortisol secretions were comparable with regularly menstruating subjects. In the combined group of athletes with menstrual disturbances, diurnal secretions of testosterone, LH, and PRL were positively, whereas cortisol was negatively correlated with the number of menstruations the last year. Although this could be explained by a gradual inhibition of the hypothalamic-pituitary-gonadal axis, our results indicate that the symptoms of amenorrhea and oligomenorrhea may reflect two hormonally distinct conditions. Thus, amenorrheic athletes displayed a hormonal pattern in agreement with hypothalamic inhibition due to energy deficiency, whereas oligomenorrheic athletes demonstrated increased diurnal secretion of testosterone, suggesting a different mechanism, e.g. essential hyperandrogenism.

Purpose: Treatment with sodium valproate (VPA) may be associated with polycystic ovarian syndrome (PCOS) in some women with epilepsy. By comparing hormone profiles in young adults taking VPA or lamotrigine (LTG) as monotherapy, this study aimed to explore whether a pharmacologic effect of VPA could be responsible for this observation., Methods: Hormone profiles in men and women taking VPA (n = 40) or LTG (n = 36) monotherapy for epilepsy were compared. None of the women were receiving hormonal contraception or replacement. Patients gave details of seizure type and frequency, menstrual cycle, and medical and drug history. Body mass index was calculated, and fasting insulin, glucose, cholesterol, triglycerides (TG), high- and low-density lipoproteins, testosterone, dihydroepiandosterone (DHEA), androstenedione, sex hormone-binding globulin (SHBG), free androgen index (FAI), luteinising hormone (LH), follicle-stimulating hormone (FSH), and antiepileptic drug (AED) concentrations were measured., Results: There were no differences between treatment groups for both sexes in age and seizure control. Only four obese VPA-treated women were hyperinsulinaemic (p = 0.05); three with abnormal menstrual cycles; one with raised testosterone. Testosterone (p = 0.02), FAI (p = 0.03), and TG (p = 0.02) levels were higher, however, in women taking the drug. Obese patients of both sexes (p = 0.01) and VPA-treated men (p = 0.03) had higher insulin concentrations., Conclusions: VPA therapy may be associated with subclinical elevation in fasting insulin levels. Testosterone and TG levels were higher in VPA-treated women compared with the levels in those taking LTG. However, only a minority of obese females exhibited biochemical characteristics suggestive of PCOS. Biochemical screening may allow women at risk of developing PCOS to avoid VPA.

PRL exists in different forms in human serum. The predominant form is little PRL (molecular mass 23 kDa) with smaller amounts of big PRL (molecular mass 50--60 kDa) and at times big big or macroprolactin (molecular mass 150--170 kDa). The frequency and clinical consequences of macroprolactinemia have not been clearly established, mainly because of difficulty in identifying these patients biochemically. This previously required the use of gel filtration chromatography, which could not be used routinely. Recently, a screening test using polyethylene glycol (PEG) has been used to identify macroprolactin in serum. Consequently, this study was designed to examine the use of PEG precipitation in the identification of patients with a predominance of macroprolactin and to establish the clinical characteristics of such a cohort. Over 12 months, 18,258 requests for serum PRL were received and of these 1225 patients had a serum PRL more than 700 mU/L. A total of 322 of these patients (26%) had a percentage recovery after PEG precipitation of less than 40%, thus indicating the presence of a predominance of macroprolactin. Fifty-five of these patients were referred for detailed clinical assessment. Symptoms typical of hyperprolactinemia were not common in this cohort. None had sustained amenorrhea and eight have had oligomenorrhea at age less than 40 yr. One had galactorrhea. All had pituitary imaging, and four had a microadenoma with none having a macroadenoma. PEG precipitation allows easy identification of macroprolactin in routine clinical practice. As the clinical consequences of this entity at this stage seem relatively benign, referral and intensive investigation of these patients may not be necessary. However, follow-up of a large cohort is required to ensure that the long-term outlook is likewise benign. This would have important implications for both patients and healthcare systems.

Objective: To compare basal gonadotropin and estradiol levels between women using acetaminophen versus those using no or other types of analgesics., Design: Observational study., Setting: Three IVF clinics in greater Boston., Patient(s): Three hundred eighty-six women accepted for their first IVF treatment who completed questionnaires recording medical history, including analgesic use for menstrual pain, and who had blood drawn during the menstrual phase of a cycle before treatment., Main Outcome Measure(s): Basal FSH, LH, and estradiol., Result(s): Basal hormone levels, especially LH, were lower for women who regularly used acetaminophen compared with women who used no medication or other types of analgesics. Lower hormone levels in acetaminophen users were consistently observed when women were subdivided by age, body mass index, smoking history, and degree of menstrual pain-features that might have influenced analgesic use or hormone levels., Conclusion(s): This study provides preliminary evidence that acetaminophen may lower gonadotropin and estradiol levels and offers a biologic basis for the epidemiologic observation that acetaminophen use may reduce the risk of ovarian cancer.

Objective: To investigate whether the newly described G1502 to A1502 mutation in exon 3 of the LH beta-subunit gene, causing the amino acid substitution of Ser102 for Gly102, is related to female infertility., Design: Screening of fertile and infertile women for the G1502 to A1502 mutation in the LH beta-subunit gene., Setting: Clinics and laboratories of the National University Hospital obstetrics and gynecology department, Singapore., Patient(s): Two hundred twelve healthy fertile women; 40 infertile women with menstrual disorders, polycystic ovary syndrome, and endometriosis; and 12 women with idiopathic infertility., Intervention(s): Exon 3 of the LH beta-subunit gene was analyzed using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and PCR-mediated direct DNA sequencing., Main Outcome Measure(s): The PCR products of patients were analyzed by RFLP, and the results were compared with those of fertile controls. DNA sequencing radiographs were compared between two mutation-bearing patients and four controls., Result(s): The mutation was identified in only two infertile women with endometriosis; other women studied were found to be negative for this mutation., Conclusion(s): The missense mutation in the LH beta-subunit gene may be implicated in female infertility, possibly endometriosis-associated infertility in some women.

The present prospective clinical study was undertaken to determine the usefulness of midluteal phase serum immunoreactive alpha-inhibin concentrations as markers of luteal phase deficiency and whether they are better indicators of biopsy confirmed luteal phase defect than serum progesterone. Consecutive patients (n = 138) with regular menstrual cycles attending our Infertility Clinic (experimental group) and 15 fertile women who were requesting contraception and had regular menstrual patterns (control group) were included. In all women (patients and controls), basal body temperature, midluteal serum concentrations of oestradiol, prolactin, progesterone and immunoreactive alpha-inhibin, and premenstrual endometrial biopsy were used in the same cycle to assess luteal function. Out-of-phase secretory endometria were detected in 15 of the 138 patients. Thus, hormonal concentrations were compared between the following three groups of women: group 1 (n = 15), infertile patients with defective secretory endometria; group 2 (n = 123), infertile patients with normal secretory endometria; and controls (n = 15), fertile women with normal secretory endometria. Midluteal serum concentrations of progesterone, immunoreactive alpha-inhibin, oestradiol, and prolactin of the two groups studied were similar to those of the control group of fertile women. Our results indicate that midluteal serum inhibin determination does not accurately reflect histological maturation of the endometrium and it is not a better indicator of endometrial luteal phase deficiency than midluteal serum progesterone concentration.

Ovulatory dysfunction is common in patients with eating disorders. However, many women engage in pathologic dieting behaviors without meeting the current diagnostic criteria for anorexia or bulimia nervosa. Clinical eating disorders are only the most extreme form of pathologic eating attitudes and behaviors that are present in many young women. Specific food choices and nutrient intakes may be associated with altered gonadal hormone status of these dieters. This cross-sectional study was conducted to describe the nutritional characteristics of college-aged women defined by their eating attitudes and behaviors with a previously described questionnaire. We evaluated dietary intake, body composition, and selected biochemical indicators in 76 undergraduate women. Serum concentrations of estradiol, progesterone, lipids, and carotenoids were measured on days 6, 21, and 28 of one menstrual cycle. Dietary assessment was based on food records at two 3-d intervals during the cycle. Ovulatory status was definitively determined on the basis of biochemical data for 46 of the women. Increased degree of pathologic dieting was associated with a significantly lower intake of dietary fat (P < 0.02), despite similar mean body mass index and body composition across the eating pathology groups. Serum concentration of alpha-carotene was significantly greater (P < 0.005) in association with a greater degree of eating pathology. With ovulation as a between-group factor, serum lutein concentration and dietary intake of energy and fat differed significantly between groups (P < 0.003). Nutritional characteristics associated with pathologic dieting behavior may also be associated with menstrual irregularities in young women.

This study investigated the forms of inhibin released into the circulation 1) in very early pregnancy, 2) after stimulation of the corpus luteum by exogenous hCG, and 3) in abnormal and failing human pregnancy. Samples were assayed by enzyme-linked immunosorbent assays for inhibin A, inhibin B, and inhibin pro-alphaC-related immunoreactivity (pro-alphaC-RI). The concentration of inhibin A rose steadily during the conception luteal phase to an initial peak 12 days after ovulation (104 +/- 23 pg/mL), then rose rapidly to a further peak 43 days after ovulation 424 +/- 6 pg/mL). The concentration of pro-alphaC-RI exhibited a much larger peak on day 15 after ovulation (1423 +/- 361 pg/mL), but fell thereafter. The concentration of inhibin B was low after ovulation and subsequently barely detectable in pregnancy. hCG treatment resulted in a significant rise in the concentrations of inhibin A and pro-alphaC-RI, but had no effect on the inhibin B concentration. The pro-alphaC-RI concentration was a better indicator of continuing pregnancy viability than either hCG or inhibin A. Early trophoblast secretes proportionately more bioactive inhibin than the corpus luteum. The corpus luteum and trophoblast do not secrete inhibin B into the circulation. These data support the concept of different physiological roles for different inhibin forms.

A patient with 17 alpha-hydroxylase deficiency (17OHD) who continued to menstruate is reported. A 24-year-old woman who presented with hypertension, hypokalemia and irregular menses had increased plasma ACTH and mineralocorticoids without any increase in glucocorticoids or sex steroids, and a bilateral adrenal enlargement on abdominal X-ray CT. ACTH stimulation test revealed hyperresponse of the metabolites of the mineralocorticoid pathway and blunted or absent response of those of the glucocorticoid and androgen pathway. Almost all of the abnormalities disappeared after dexamethasone administration. While 17OHD is usually known to accompany hypergonadotropic hypogonadism, the patient continued to menstruate, though irregularly. Although human chorionic gonadotropin administration failed to induce response, basal plasma levels of ovarian steroid (estradiol) and gonadotropins as well as response to LHRH stimulation test were all normal. Thus, the clinical and biochemical features of this case is compatible with the partial deficiency of both adrenals and ovaries, being less severe in the latter. A further analysis especially at molecular level is needed to elucidate the basis for the heterogeneity of this disorder.

Objective: To delineate the relationship between the pulsatile gonadotropin inputs in early follicular phase of the menstrual cycle and the P secretions by the corpus luteum in women., Design: For measuring pulsatile release of gonadotropin, blood samples were drawn every 15 minutes for 24 hours in the early follicular phase. Daily blood samples were drawn for LH, FSH, E2, and P., Setting: The reproductive endocrine unit of a university hospital., Patients: Fourteen patients with luteal phase defect (LPD) and 12 normally cycling women., Results: The length of follicular phase in LPD was significantly shorter than that of women with normal cycles. There were significant differences in LH pulsatile secretions and amplitudes in LPD patients when compared with those of women with normal cycles. Basal E2, PRL, and preovulatory E2 concentrations were not different between the two groups whereas the peak of P secretions in luteal phase was significantly decreased in LPD., Conclusions: These data suggest that LPD may result from the altered LH pulse frequency in early follicular phase of the menstrual cycle. Whether this increased LH pulse frequency results from an intrinsic disease of the pulse oscillator or to some event in the preceding cycle remains unknown. It is tempting to speculate that an increased LH pulsatile secretion in the early follicular phase of menstrual cycles in patients with LPD may down-regulate the LH secretion at midcycle, thereby lowering the LH surge, which in turn reduces the P secretion in luteal phase.

Objective: To investigate the clinical and endocrine effects of the antiandrogen flutamide in hirsute women., Design: Hirsutism was assessed before and after 3 months of treatment with flutamide 500 mg/d. Endocrine evaluations were performed before and during the 2nd month of treatment with flutamide 500 mg or 750 mg/d., Setting: Department of Obstetrics and Gynecology, Pisa, Italy., Participants: Eighteen hirsute women were studied: nine women were hyperandrogenic, and the other 9 had an idiopathic hirsutism., Interventions: Women were randomly treated with flutamide 500 mg/d (9 patients) or 750 mg/d (9 patients) for 3 and 2 months, respectively. Six received placebo 1 month before flutamide treatment., Main Outcome Measures: Hirsutism was assessed by measuring hair diameter. Follicle-stimulating hormone and LH responses to GnRH were evaluated. Basal plasma levels of T, androstenedione (A), 17-hydroxyprogesterone (17-OHP), DHEAS, cortisol (F), and sex hormone-binding globulin (SHBG) were evaluated. The same hormones were determined after a single dose of flutamide (250 or 500 mg) or placebo throughout a 12-hour period and in samples collected 60 and 120 minutes after ACTH intravenous injection., Results: Hair diameter was reduced by 30%. Both dosages of flutamide did not change basal and stimulated gonadotropin, T, A, 17-OHP, F, and SHBG levels. Both dosages reduced stimulated DHEAS levels., Conclusions: Flutamide may have a beneficial effect on hirsutism. This effectiveness is mainly due to its peripheral antiandrogen action. However, an effect on the adrenal gland seems to be present.

1. An epidemiological study of iron status in general practice has been undertaken. An age-sex register was established and a 10% stratified random sample (194 males and 220 females) of the patients above the age of 15 years was studied. A full blood count, serum Fe concentration, transferrin saturation and serum ferritin concentration were measured and correlated with clinical features associated with Fe deficiency. 2. The geometric mean for serum ferritin for males was 77 micrograms/l (20-196 micrograms/l) and for females 37 micrograms/l (8--177 micrograms/l). A low serum ferritin (male less than 30 micrograms/l, female less than 20 micrograms/l) in the absence of anaemia was found in fifteen males and thirty-five females. In this group forty patients had clinical features which are aetiologically associated with Fe deficiency. The incidence of similar features in a control group of thirty-three patients was seven. 3. It is suggested that this is indirect evidence that serum ferritin concentration is the most sensitive monitor of Fe status enabling the detection of pre-anaemic Fe deficiency.

Currently available measurements of beta-endorphin and beta-lipotropin in exercising women are in excellent agreement and indicate a 2-3 fold increase over basal levels. Possible effects of exercise upon the transfer of endorphins from the peripheral circulation to the brain are examined, and evidence is presented that suggests the occurrence of a concomitant exercise-related increase of endorphins in both humoral and central nervous system compartments. Steady-state measurements of circulating luteinizing hormone and follicle-stimulating hormone levels in oligo-amenorrheic athletes, on the other hand, do not agree. It is felt that the lack of consensus may be attributable partly to technical inadequacies and partly to lack of awareness of the need for frequent sampling. The bulk of the findings suggest a tendency for luteinizing hormone levels to be low and follicle-stimulating hormone levels to be normal or low, a pattern compatible with repeated activation of the CRH-ACTH-POMC system as a result of exercise.

Thirteen women with luteal phase defects (LPD) confirmed by endometrial biopsies and 14 with histologically normal endometria were studied for early follicular and midfollicular phase follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and for midluteal phase progesterone, estrogen, testosterone, and prolactin levels. The results showed that the women with LPD had significantly lower FSH levels and FSH/LH ratios in the early and midfollicular phases. LH levels, however, were similar in the LPD and normal women. During the midluteal phase, the LPD women showed significantly lower levels of progesterone and estrogen and normal levels of testosterone and prolactin. These findings reaffirm the prevailing concept that events surrounding follicular growth and development can indeed influence the quality of that cycle's corpus luteum. Furthermore, LPD as a result of hyperprolactinemia appears to be a different entity from that due to inadequate follicular phase FSH.

High serum follicle stimulating hormone (FSH) values are consistent with ovarian failure. We studied the progress of 67 women aged under 35 years with oligomenorrhoea or secondary amenorrhoea in whom the serum FSH value was greater than 20 U/1. Twenty-four patients remained amenorrhoeic, but 17 ovulated and six conceived, two on two occasions. Coincident mean serum luteinising hormone (LH) concentrations were significantly lower and mean total urinary oestrogen concentrations were significantly higher in patients who subsequently ovulated, but the degree of increase in FSH did not correlate well with later ovarian function. Treatment with oestrogens, clomiphene citrate, human pituitary gonadotrophin, and bromocriptine was of no benefit in inducing an ovarian response while FSH concentrations remained raised. Our results suggest that a considerable proportion of younger women with ovulatory disorders associated with FSH values in the menopausal range will spontaneously resume ovulation and some will conceive.