Association of severity of menstrual dysfunction with cardiometabolic risk markers among women with polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is associated with a wide range of unfavorable cardiometabolic risk factors, including obesity, hypertension, insulin resistance, impaired glucose metabolism, dyslipidemia, and metabolic syndrome. Compared with women with regular menstrual cycles, women with a history of irregular menstrual periods have an increased unfavorable cardiometabolic risk. Recently, the association between the severity of oligomenorrhea and hyperinsulinemia and insulin resistance has been demonstrated. However, evidence linking the severity of menstrual cyclicity with cardiometabolic risk in PCOS women is scarce. MATERIAL AND METHODS: This work was a prospective cross-sectional study. A total of 154 women diagnosed with PCOS by the Rotterdam criteria were recruited from July 2021 to September 2022. PCOS women with eumenorrheic (eumeno group), oligomenorrhea (oligo group), and amenorrhea (ameno group) underwent history and physical examination, gonadal steroid hormone measurement, lipid profile, oral glucose tolerance test, and homeostasis model assessment of insulin resistance. RESULTS: A trend toward an increase in unfavorable cardiometabolic risk markers including obesity, hypertension, prevalence of insulin resistance, prediabetes, dyslipidemia, and metabolic syndrome was observed in the ameno group (n = 57) as compared with the eumeno (n = 24) or oligo group (n = 73). A higher prevalence of insulin resistance (odds ratio [OR]: 3.02; 95% confidence interval [CI]: 1.03-8.81) and prediabetes (OR: 3.94; 95% CI: 1.01-15.40) was observed in the ameno group than in the eumeno group, and a higher proportion of dyslipidemia (OR: 2.44; 95% CI: 1.16-5.15) was observed in the ameno group than in the oligo group in the binary logistic regression analysis after adjusting for confounding factors. CONCLUSIONS: PCOS women with amenorrhea show a higher prevalence of insulin resistance, prediabetes, and dyslipidemia compared with those with oligomenorrhea or eumenorrhea. The severity of menstrual dysfunction could be used as a readily obtainable marker for the identification of PCOS women at greatest risk of cardiometabolic diseases.

Prevalence of endocrine disorders in 304 premenopausal women referred with oligomenorrhoea.

INTRODUCTION: We aimed to evaluate 304 premenopausal women admitted to our clinic for oligomenorrhoea, and to screen for Cushing's syndrome (CS) in this population. MATERIAL AND METHODS: The study included 304 premenopausal women referred to our clinic for oligomenorrhoea. Anthropometric measurements and Ferriman-Gallwey score were evaluated, and thyroid hormone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone, prolactin, dehydroepiandrosterone sulphate (DHEA-S), and 17-hydroxyprogesterone (17-OHP) levels were measured in all patients. If basal 17-OHP was > 2 ng/mL, we evaluated adrenocorticotropic hormone (ACTH)-stimulated 17-OHP levels. CS was screened by 1 mg-dexamethasone suppression test, and if the cortisol value was > 1.8 µg/dL, we performed additional confirmatory tests, and if necessary, pituitary magnetic resonance imaging (MRI) and inferior petrosal sinus sampling (IPSS) were performed. RESULTS: The most common cause of oligomenorrhoea was polycystic ovary syndrome (PCOS) that was detected in 81.57% of cases, followed by hyperprolactinemia at 7.23% and hypothalamic anovulation at 5.26%. The prevalence of premature ovarian failure (POF) was 1.6%, and non-classical congenital adrenal hyperplasia (NCAH) was 1.97%. CS was detected in 7 (2.30%) patients. All the patients with CS were found to have Cushing's disease (CD). Although 3 patients with CD had classical signs and symptoms, 4 had none. Patients with CD had similar total testosterone values to those in the PCOS and NCAH groups, but they had significantly higher DHEA-S compared to both groups (CD vs. PCOS, p = 0.001 and CD vs. NCAH, p = 0.030). CONCLUSIONS: We found higher prevalence of CS in patients with oligomenorrhoea even in the absence of clinical signs. Therefore, we suggest routine screening for CS during the evaluation of patients with oligomenorrhoea and/or PCOS. The likelihood of CS is greater in patients with high androgen, especially DHEA-S levels.

Are ABO/Rh blood groups A risk factor for polycystic ovary syndrome?

This study goaled to evaluate the ABO/Rh blood group distribution and its relationship with clinical and biochemical factors in polycystic ovary syndrome (PCOS) patients. ABO/Rh blood group distribution of the patients and the healthy individuals were compared. In addition, the features of clinical and biochemical factors were compared according to the ABO/Rh blood groups. Two hundred and sixty-five patients were involved in the study. At the time of diagnosis, hirsutism (86%) and oligomenorrhea (80.9%) were the most prevalent symptoms. There were 166 (62.6%) patients with baseline ultrasonography results consistent with PCOS. In 111 (41.9%) patients, insulin resistance was found. ABO blood group distributions in the patient (42.6% A, 17% B, 9.4% AB, 30.9% O) and control (42% A, 16% B, 8% AB, 34% O) groups were found to be similar (P = .9). There was no difference between oligomenorrhea, hirsutism, hair loss, acne, obesity, high androgen level, insulin resistance, and ultrasound characteristics according to ABO/Rh blood groups. In this study, ABO/Rh blood group distribution in individuals with PCOS was found to be similar to healthy individuals, and it was determined that ABO/Rh blood group was not a risk factor for PCOS. In addition, no correlation was found between the clinical and biochemical characteristics of the patients at the time of diagnosis and the ABO/Rh blood group.

The prospective association of hyperandrogenism, oligomenorrhea and polycystic ovary syndrome with incident gestational diabetes: The coronary artery risk development in young adults women's study.

In this 28-year prospective study of 455 women (mean age: 26 years), polycystic ovary syndrome (PCOS) was associated with a 2.6-fold elevated risk of gestational diabetes (GDM). However, hyperandrogenism or oligomenorrhea in the absence of PCOS was not associated with GDM.

Evaluation of Hormonal Profile and Ovarian Morphology among Adolescent Girls with Menstrual Irregularities in a Tertiary Care Centre at Central India.

Menstrual disturbances are common among adolescents with a prevalence rate of 11.3-26.7%. The most frequent menstrual irregularities are oligomenorrhea, menorrhagia, polymenorrhoea, and hypomenorrhea. PCOS (polycystic ovarian syndrome) is now recognized as the most prevalent endocrine disorder among the women of reproductive age. The current study was planned to evaluate socio-demographic factors, endocrine profiles, and ovarian morphology among adolescent girls with menstrual irregularities and compare these parameters in different phenotypes of adolescent PCOS cases. It is a hospital-based cross-sectional study among 248 adolescent girls (10-19 years) with menstrual irregularities. After obtaining informed consent, history and clinical examination findings were recorded on preform proforma. All girls were assessed on day 2/3 of the menstrual cycle for hormonal profile (serum TSH, FSH, LH, prolactin, and serum testosterone) and ovarian morphology (by transabdominal ultrasonography). All participating girls were divided into three groups (groups 1, 2, and 3) corresponding to phenotypes A, B, & D as per the Rotterdam criteria. In the study, oligomenorrhea was the most common menstrual disorder (70.97%). Biochemical hyperandrogenism and thyroid dysfunction were reported in 14.91% and 8.46% of girls, respectively. Our study noted that phenotype D ,i.e., group 3 (MI + PCOM-HA; 49.43%) was the most common phenotype in the study. In a comparative analysis of different groups, significant differences (p < 0.05) in hormonal and metabolic parameters showed highest in group 2, which represents phenotype B of PCOS (hyperandrogenic anovulation). This analysis revealed that adolescent hyperandrogenism (phenotypes A and B) is associated with a more deranged hormonal and metabolic profile than nonandrogenic PCOS (phenotype D). To prevent long-term sequelae, lifestyle changes, early treatment, and close follow-up are recommended in this subset of girls.

Anti-Müllerian Hormone Levels in Adolescence in Relation to Long-term Follow-up for Presence of Polycystic Ovary Syndrome.

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.

Prevalence of oligomenorrhea among women of childbearing age in China: A large community-based study.

OBJECTIVE: To investigate the prevalence and the related characteristics of oligomenorrhea among women within childbearing age in China. STUDY DESIGN: A large-scale community-based investigation was conducted from 2013 to 2015. A total of 12,964 women aged 18-49 years from 9 provinces/municipalities in China were recruited for healthcare screening in local community health centers. Outcome measures include clinical history, ultrasonographic exam, and hormonal and metabolic parameters. RESULTS: Among women within childbearing age in China, the prevalence of oligomenorrhea was 12.2% (1,579/12,964). Both sociodemographic factors and medical history were significantly associated with oligomenorrhea (P < 0.05). In such women, the prevalence of obesity, acne, seborrhea, acanthosis, larger ovarian size, and polycystic ovarian morphology was higher when compared with normal women; the prevalence of anti-Mullerian hormone, total testosterone, and androstenedione (P < 0.05) was higher as well. The infertility rates of all women were higher in the oligomenorrhea group (17.2%, 272/1,579) than in the non-oligomenorrhea group (9.0%, 1,024/11,385), and among women without contraception, for the oligomenorrhea group, the infertility rate was 32.5% (128/394), and for the non-oligomenorrhea group, 17.9% (400/2,240). In the oligomenorrhea group, 57.4% (156/272) of the women underwent treatments for infertility, which was higher than the non-oligomenorrhea group 36.1% (370/1,024). CONCLUSIONS: Obesity, acne, seborrhea, acanthosis, larger ovarian size, and polycystic ovarian morphology were significantly associated with oligomenorrhea. The increase of anti-Mullerian hormone, total testosterone, and androstenedione level was also demonstrated in the oligomenorrhea group. Higher prevalence of infertility and medical treatment rate was observed in women with oligomenorrhea.

How to Evaluate Acne in Reproductive-Age Women: An Epidemiological Study in Chinese Communities.

BACKGROUND: Acne is not only a skin condition but also a cardinal component of many systemic diseases or syndromes. This study was aimed to investigate the prevalence of acne in reproductive-age women in Sichuan province, China, and to evaluate acne as a skin problem alone or a symptom of gynecological/endocrinological disease. METHODS: From October 2008 to September 2009, 1043 reproductive-age women from 19 to 45 years of age from seven communities of three districts in Sichuan province completed a standardized questionnaire and a physical examination. Acne was classified using the Pillsbury scale, and hirsutism was assessed using a modified Ferriman-Gallwey method. Diagnosis of polycystic ovary syndrome (PCOS) was based on the 2003 Rotterdam criteria. Some endocrine and metabolic markers were detected for the women diagnosed with PCOS related to acne and the control group. RESULTS: The prevalence of acne was 32.5%, and the highest prevalence (9.6%) was seen in the 19-24-year-old age group. Prevalence among women eating dessert frequently, exercising seldom, or among sedentary workers was significantly higher in the acne group (14.1%, 55.6%, and 51.3%, respectively) than in the nonacne group (10.8%, 45.7%, and 35.5%; all P<0.05). The prevalence of oligomenorrhea and hirsutism in the acne group (17.6%, 24.7%) was significantly higher than in the nonacne group (8.6%, 15.1%; both P<0.05). Among the participants with acne, 64.3% had acne alone, 18.3% were diagnosed with hyperandrogenism, and 17.4% were diagnosed with PCOS. The level of serum androstendione in the group of PCOS (10.98±3.12 nmol/L) was significantly higher than that in the control group (8.85±3.09nmol/L) (P<0.05). CONCLUSION: When reproductive-age women with acne are encountered in gynecology-endocrinology or dermatology clinics, physicians should consider evaluating them from PCOS, hyperandrogenism, or acne alone.

Minimal difference in phenotype between adolescents and young adults with polycystic ovary syndrome.

OBJECTIVE: To test the hypothesis that the polycystic ovary syndrome (PCOS) phenotype, or its component features, is less severe in adolescents than in young adult patients, in a referred (clinical) population. DESIGN: Cross-sectional study. SETTING: Tertiary-care academic medical center. PATIENT(S): Two hundred seventy-four adolescents and young adults aged 13.0-24.9 years with PCOS according to the National Institute of Health 1990 criteria. Patients were categorized as adolescents (AD: 13.0-18.9 years; n = 91) and young adults (YA: 19.0-24.9 years; n = 183). Adolescents were further categorized as early adolescents (Early-AD: 13.0-15.9 years; n = 31) and late adolescents (Late-AD: 16.0-18.9 years; n = 60). INTERVENTION(S): History, physical examination, hormonal assays with the use of standardized protocols. MAIN OUTCOME MEASURE(S): Unadjusted and adjusted odds ratios (ORs; adjusted for body mass index [BMI] when applicable) were calculated for biochemical hyperandrogenism (HA), hirsutism (HIR), acne, and degree of oligo/amenorrhea (OA). PCOS phenotypes were classified as HIR+HA+OA, HA+OA, and HIR+OA. RESULT(S): Our analysis demonstrated minimal significant difference in the prevalence of the three PCOS phenotypes, or component features, between AD and YA patients. The risks for obesity were higher for YA versus AD, and the risk of acne was lower for YA versus AD. There was no significant difference between Early-AD and Late-AD. BMI-adjusted models did not significantly modify the main findings. CONCLUSION(S): The present study suggests that the PCOS phenotype is established in early adolescence, remains constant into adulthood, and is not related to BMI.

25(OH)D serum concentration in women with menstrual disorders -risk factors for Vitamin D deficiency.

INTRODUCTION: Vitamin D (VD) plays a crucial role in calcium metabolism as well as immunological and endocrine homeostasis. Previous studies revealed strong inverse correlation between VD levels and insulin resistance, parathyroid dysfunctions and autoimmune thyroid disease. Insufficient evidence concerns its dependency of ovarian hormones. Malfunctioning of the ovaries results in menstrual disorders that are one of the most common endocrine impairments in young women of reproductive age. MATERIAL AND METHODS: The study was aimed to evaluate the correlation between 25(OH)D serum concentration and estradiol, testosterone as well as body mass index (BMI) in women with oligomenorrhea. 134 women of reproductive age with oligomenorrhea were eligible for the study. 25-hydroxyvitamin D [25(OH)D], estradiol, testosterone and sex hormone-binding globulin (SHBG) were measured using chemiluminescence immunoassay. Free androgen index (FAI) and body mass index (BMI) were calculated. RESULTS: Critical 25(OH)D deficiency (<10 ng/ml) was found in 13.4% of women, the risk of deficiency (<30 mg/dl) was diagnosed in 69.4%, while sufficient level of VD (>30 mg/ml) in 17.2% of them. Significant negative correlation was detected between 25(OH)D and estradiol serum concentrations (r=-0.2; p=0.049), as well as BMI levels (r=-0.22; p=0.01). However, no significant correlation was found between 25(OH)D and testosterone (r=-017; p=0.055), SHBG (r=0.08; p=0.4) and FAI (r=-0.1; p=0.24). CONCLUSIONS: Thorough assessment of vitamin D deficiency/insufficiency is required among patients with menstrual disorders, especially those overweighed and obese. Early screening and VD supplementation in women with estrogen-dependent disorders may become a part of routine management in order to optimize endocrine health.

High Prevalence of Polycystic Ovary Syndrome in Type 1 Diabetes Mellitus Adolescents: Is There a Difference Depending on the NIH and Rotterdam Criteria?

BACKGROUND: Polycystic ovary syndrome (PCOS) is more frequently observed in type 1 diabetes mellitus (T1DM) adult women than in nondiabetic women. No such prevalence has yet been studied in adolescent girls with T1DM. AIM: The aim of this study was to evaluate the prevalence of PCOS in adolescent girls with T1DM and to determine the clinical and hormonal features associated with the disorder. METHODS: A cross-sectional study of 53 adolescent girls (gynecological age >2 years) referred for routine evaluation for T1DM was conducted. We diagnosed PCOS using the National Institutes of Health (NIH) and Rotterdam criteria. RESULTS: 26.4 and 47.9% of adolescents had PCOS according to NIH (NIH-PCOS) and Rotterdam (Rotterdam-PCOS) criteria. 66.7% of NIH-PCOS adolescents had a complete phenotype associated with hyperandrogenism, oligomenorrhea, and polycystic ovarian morphology, unlike only 33.3% of the Rotterdam-PCOS adolescents. A family history of type 2 diabetes mellitus (T2DM) was more frequent in PCOS than in non-PCOS girls, whichever criteria were used. Late pubertal development and a T1DM diagnosis close to puberty were factors associated with NIH-PCOS. CONCLUSION: Adolescents with T1DM had a high prevalence of PCOS. More differences between PCOS and non-PCOS patients were found using the NIH criteria, suggesting that clinical characteristics might be more accurate for diagnosing PCOS in girls with T1DM. A family history of T2DM is associated with a high risk of PCOS.

Psychological Distress Is More Prevalent in Fertile Age and Premenopausal Women With PCOS Symptoms: 15-Year Follow-Up.

Context: Polycystic ovary syndrome (PCOS) is associated with increased psychological distress, obesity and hyperandrogenism being suggested as key promoters. Objectives: To investigate the prevalence of anxiety/depression and their coexistence in women with PCOS/PCOS-related symptoms at ages 31 and 46. The roles of obesity, hyperandrogenism, and awareness of PCOS on psychological distress were also assessed. Design: Population-based follow-up. Setting: Northern Finland Birth Cohort 1966 with 15-year follow-up. Participants: At age 31, a questionnaire-based screening for oligoamenorrhea (OA) and hirsutism (H): 2188 asymptomatic (controls), 331 OA, 323 H, and 125 OA plus H (PCOS). Follow-up at age 46: 1576 controls, 239 OA, 231 H, and 85 PCOS. Interventions: Questionnaire-based screening for anxiety and depression symptoms (Hopkins Symptom Checklist-25) and previously diagnosed/treated depression at ages 31 and 46. Body mass index (BMI), serum testosterone/free androgen index, and awareness of polycystic ovaries/PCOS on psychological distress were also assessed. Main Outcomes: Population-based prevalence of anxiety and/or depression in women with PCOS/PCOS-related symptoms at ages 31 and 46. Results: Anxiety and/or depression symptoms, their coexistence, and rate of depression were increased at ages 31 and 46 in women with PCOS or isolated H compared with controls. High BMI or hyperandrogenism did not associate with increased anxiety or depression symptoms. The awareness of PCOS was associated with increased anxiety. Conclusions: Women with PCOS or isolated H present more often with anxiety and/or depression symptoms and their coexistence compared with controls. High BMI or hyperandrogenism did not provoke psychological distress in PCOS. The awareness of PCOS increased anxiety but did not associate with severe anxiety or depression.

Correlation of clinical and biochemical hyperandrogenism in Thai women with polycystic ovary syndrome.

AIM: The aim of this study was to determine the correlation of clinical hyperandrogenism and biochemical hyperandrogenism (hyperandrogenemia) in Thai women with polycystic ovary syndrome (PCOS). METHODS: This cross-sectional study was conducted at Siriraj Hospital, Thailand. Subjects were 145 women with PCOS who were diagnosed in accordance with the revised Rotterdam 2003 criteria and registered during January to July 2008. Clinical hyperandrogenism was assessed using the modified Ferriman-Gallwey score for hirsutism, the American Academy of Dermatology criteria for severity of acne, and the Ludwig scale for androgenic alopecia and virilization. Biochemical hyperandrogenism was determined from serum concentration of total testosterone (TT), dehydroepiandrosterone sulfate and free testosterone (FT). RESULTS: The participants had a mean age of 25.5 ± 6.5 years and a body mass index of 26.2 ± 6.9 kg/m(2) . The most common presenting symptom was oligomenorrhea or amenorrhea. The most common expression of clinical hyperandrogenism was acne (56.6%). Most of the participants (84.8%) had high serum-FT. There was a statistically significant correlation between clinical and biochemical hyperandrogenism in the following pairs: hirsutism and FT (r = 0.3, P < 0.001); hirsutism and TT (r = 0.26, P < 0.001); and acne and TT (r = 0.26, P = 0.002). The others had little or no correlations. CONCLUSION: Clinical hyperandrogenism is not a good predictor for biochemical hyperandrogenism in Thai women with PCOS. A modified Ferriman-Gallwey score cut-off point of 8 has low sensitivity but high specificity for hyperandrogenemia; therefore, it is useful for the diagnosis but not useful for the exclusion of hyperandrogenemia in Thai women with PCOS.

Associations between eating disorder diagnoses, behaviors, and menstrual dysfunction in a clinical sample.

We explored associations between lifetime eating disorder (ED) diagnoses and behaviors and menstrual dysfunction using logistic regression models. Body mass index (BMI) fully explained differences in the odds of secondary amenorrhea (SA) across diagnoses. Women with dieting behaviors had borderline significantly higher odds of SA than those without after accounting for BMI. We suggest the presence of a strong association between BMI and SA and that dieting might represent a risk factor for SA regardless of BMI and ED diagnosis.

Proposed criteria for the identification of polycystic ovary syndrome following menopause: An ancillary study of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

OBJECTIVES: To propose plausible criteria with which to identify menopausal women with PCOS. STUDY DESIGN: A cross-sectional study involving the baseline data of 713 menopausal women at admission to the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) in Salvador, Bahia, Brazil. MAIN OUTCOME MEASURES: PCOS was identified by the presence of two of three criteria. (1) A history of amenorrhea or oligomenorrhea (OL) (regular intermenstrual intervals ≥35 days during reproductive life); (2) clinical or biochemical hyperandrogenism (HA), identified by a score ≥5 points in a hirsutism questionnaire constructed and validated for women in this age group, or total or free testosterone ≥ the 95th percentile for women considered normal; (3) insulin resistance (IR) (a homeostatic model assessment [HOMA] index≥2.2). Validation was performed using probable epidemiological endpoints. RESULTS: According to these criteria, 7.6% of the women in the sample had PCOS. Of these, 7.4% had HA and OL, 72.2% had HA and IR, 14.8% had OL and IR and 5.6%, had HA, OL and IR. Women with PCOS were younger, had had fewer pregnancies and entered menopause earlier. Positive associations were found between PCOS and overweight (PR: 1.31; 95%CI: 1.18-1.46), obesity (1.44; 1.01-2.06), carbohydrate metabolism disorders (impaired glucose tolerance and diabetes mellitus) (1.30; 1.03-1.65), and with diabetes alone (1.41; 0.83-2.39), although this latter association failed to reach statistical significance. CONCLUSION: The women selected in accordance with these criteria had the characteristics of PCOS that are not only expected, but also widely associated with this disorder.

Adolescent oligomenorrhea (age 14-19) tracks into the third decade of life (age 20-28) and predicts increased cardiovascular risk factors and metabolic syndrome.

OBJECTIVE: Assess whether adolescent oligomenorrhea (age 14-19) tracks into young adulthood (age 20-28) and predicts increased cardiometabolic risk factors, metabolic syndrome (MetS), and impaired fasting glucose-type II diabetes mellitus (IFG+T2DM). MATERIALS AND METHODS: Prospective study of menstrual cyclicity and its metabolic effects in 865 black and white schoolgirls from age 9 to 19, and 605 of these 865 girls from age 20 to 28. MAIN FINDINGS: Patterns of menstrual delays (oligomenorrhea) during ages 14-19 and ages 20-28 were closely related (p<.0001). Adolescent menses delay (ages 14-19, p<.0001), mean insulin (ages 20-28, p=.0003), and self-identified polycystic ovary syndrome (PCOS, p=.049) predicted ages 20-28 menses delay. Menses delays during ages 14-19 and 20-28, and, their interaction product were correlated with IFG+T2DM and MetS at ages 20-28. Waist circumference (ages 20-28, p<.0001), mean triglyceride (ages 20-28, p=.005), and the number of average menstrual cycles≥42 days (ages 20-28, p=.04) predicted IFG+T2DM (ages 20-28). MetS (ages 9-19, p<.0001), mean insulin (ages 20-28, p=.0002), the number of ≥42 day gaps between menstrual periods (ages 20-28, p=.02), and cigarette smoking at age 18-19 (p=.04) were significant explanatory variables for MetS at ages 27-28. As MetS status category changed from age 14-19 to 27-28 from best to worst: (no → no), (yes → no), (yes → yes), (no → yes), the number of women with ≥2 menses delays during ages 20-28 rose from 3% to 4% to 15% to 17%, p=.0001. MetS status change from age 9-19 to 27-28 was positively associated with mean insulin (age 20-28, p<.0001), cigarette smoking (age 24-25, p=.01) and the number of menses delays during ages 20-28 (p=.04). PRINCIPAL CONCLUSIONS: Menstrual patterns track from adolescence to young adulthood, and oligomenorrhea predicts MetS and IFG+T2DM. Patterns of menses delays in adolescence should be considered as a significant risk factor for future development of young adult IFG+T2DM, MetS, oligomenorrhea, and polycystic ovary syndrome.

Obesity and menstrual disorders.

Obese women often present with oligomenorrhoea, amenorrhoea or irregular periods. The association between obesity and heavy menstrual bleeding is not well documented and data on its prevalence are limited. While the investigation protocols should be the same as for women of normal weight, particular focus is required to rule out endometrial hyperplasia in obese women. The treatment modalities of menstrual disorders for obese women will be, in principle, similar to those of normal weight. However, therapeutic outcomes in terms of effectiveness and adverse outcomes need special consideration when dealing with women with a high body mass index (BMI). Here, different treatment strategies are reviewed paying particular attention to the effect of weight on their efficacy and the challenges of providing each treatment option. This chapter aims to review the current literature and address areas where further evidence is needed, which will subsequently influence clinical practice.

Hyperandrogenic oligomenorrhea and metabolic risks across menopausal transition.

CONTEXT: Although there is evidence of metabolic risks in young women with irregular menses and androgen excess, persistence of risks after menopause is unclear. OBJECTIVE: The objective of the study was to determine the impact of menopause on the cardiometabolic profile in women with high androgens and a history of menstrual irregularity. METHODS: Study of Women's Health Across the Nation is a longitudinal cohort study. Data from 1929 women without metabolic syndrome (MetS) at baseline were analyzed for incidence of MetS, self-reported stroke, and myocardial infarction. Cox hazard ratios (HRs) were estimated, adjusting for age, ethnicity, body mass, smoking, menopausal status, and study site. RESULTS: Among MetS-free women at baseline, 497 new cases were identified during 20 249 woman-years of follow-up over 12 years. Women with hyperandrogenemia (HA) and oligomenorrhea (Oligo) developed incident cases of MetS at a comparable rate compared with their counterparts: eumenorrheic, normoandrogenic women [HR 1.4 (0.9-2.2)], oligomenorrheic, normoandrogenic women [HR 1.3 (0.8-2.2)], and eumenorrheic hyperandrogenic women [HR 1.2 (0.7-1.8)]. Smoking and obesity were the strongest predictors of incident MetS. There was no significant difference in incidence of self-reported stroke or MI by HA/Oligo status. CONCLUSIONS: Longitudinal evidence suggests that a history of androgen excess and menstrual irregularity is not associated with worsening of metabolic health after menopause. Our findings challenge the notion that a history of concurrent HA and Oligo reflects ongoing cardiometabolic risk in postmenopausal women.

Prevalence, presentation and management of polycystic ovary syndrome in Enugu, south east Nigeria.

BACKGROUND: Polycystic ovary syndrome is the most common gynaecological endocrine disorder in women of reproductive age yet, its prevalence and management has not been documented in our area. OBJECTIVE: To determine the prevalence, presentation and management of polycystic ovary syndrome among women in Enugu, south east Nigerian. METHOD: A prospective descriptive study of women with polycystic ovaries seen in two major Infertility Clinics in Enugu, South East Nigeria over a 2 year period. RESULT: A total of 342 women presented with infertility in the centres within the two year period, out of whom 62 had PCOS. PCOS occurred in 18.1% of women in the infertility clinics of the two institutions. The common modes of presentation were: inability to conceive (infertility) in 52 (83.9%), oligomenorrhoea in 45 (72.6%), obesity in 32 (51.6%), LH/FSH ratio > 2 in 28 (45.2%), hyperprolactinaemia in 26 (41.9%) and hirsuitism in 19 (30.6%) women. Ovulation induction was carried out in 42 of the 50 women with anovulatory infertility only. For those 42 women, the mean number of induced cycles was 2.6 = 1.7 (range: 1-6) with 33 (78.6%) of the women being able to do only 3 induced cycles or less. The ovulation induction agents used were clomiphene citrate and human menopausal gonadotrophin either singly or in combination with tamoxifen or bromocryptine. Adjunctive treatments offered consisted of weight reduction in 20 (40.0%) women, metformin in 11 (22.0%) women and dexamethasone in 10 (20.0%) women. CONCLUSION: PCOS is fairly common occurring in approximately one in six infertile Nigerian women. Infertility, oligomenorrhoea, obesity, LH/FSH ratio > 2, hyperprolactinaemia and hirsutism are the commonest presenting features. On individualized management, about two-fifths of them conceive either spontaneously or following ovulation induction, despite poor compliance to recommended drug regimen.

Low-dose oral sirolimus and the risk of menstrual-cycle disturbances and ovarian cysts: analysis of the randomized controlled SUISSE ADPKD trial.

UNLABELLED: Sirolimus has been approved for clinical use in non proliferative and proliferative disorders. It inhibits the mammalian target of rapamycin (mTOR) signaling pathway which is also known to regulate ovarian morphology and function. Preliminary observational data suggest the potential for ovarian toxicity but this issue has not been studied in randomized controlled trials. We reviewed the self-reported occurrence of menstrual cycle disturbances and the appearance of ovarian cysts post hoc in an open label randomized controlled phase II trial conducted at the University Hospital Zürich between March 2006 and March 2010. Adult females with autosomal dominant polycystic kidney disease, an inherited kidney disease not known to affect ovarian morphology and function, were treated with 1.3 to 1.5 mg sirolimus per day for a median of 19 months (N = 21) or standard care (N = 18). Sirolimus increased the risk of both oligoamenorrhea (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.1 to 29) and ovarian cysts (HR 4.4, CI 1.1 to 26); one patient was cystectomized five months after starting treatment with sirolimus. We also studied mechanisms of sirolimus-associated ovarian toxicity in rats. Sirolimus amplified signaling in rat ovarian follicles through the pro-proliferative phosphatidylinositol 3-kinase pathway. Low dose oral sirolimus increases the risk of menstrual cycle disturbances and ovarian cysts and monitoring of sirolimus-associated ovarian toxicity is warranted and might guide clinical practice with mammalian target of rapamycin inhibitors. TRIAL REGISTRATION: ClinicalTrials.gov NCT00346918.