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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. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a reproductive, endocrine, and metabolic disorder affecting millions of women worldwide. Women with PCOS are often identified in adolescence or early adulthood with symptoms of oligomenorrhea or hirsutism or when presenting for infertility care. The health risks associated out of PCOS, however, go far beyond management of these common presenting symptoms or fertility treatment and likely extend past the reproductive years through and beyond menopause. International surveys suggest that most patients are dissatisfied with long-term counseling related to medical and psychologic issues. We performed a review of comorbidities, including diabetes mellitus, dyslipidemia, obesity, hypertension, metabolic syndrome, depression, anxiety, obstructive sleep apnea, nonalcoholic fatty liver disease, endometrial cancer, and cardiovascular disease, in both reproductive-age and older women with PCOS. Most meta-analyses in reproductive-age women demonstrate increased risks independent from obesity. Longitudinal and cross-sectional studies including women with PCOS >40 years of age are limited in number and design, but many demonstrate that some of these comorbidities persist. All providers involved in the multidimensional care of women with PCOS should be aware of these long-term health risks to provide appropriate counseling, screening, and management options. We identify limitations that should be the focus of future studies designed to study health outcomes in postmenopausal women with PCOS. [ABSTRACT FROM AUTHOR]

Objective To estimate the prevalence of uterine müllerian duct anomalies in a general population. Design Cross-sectional study. Setting University hospital in collaboration with the Danish Civil Registry. Patient(s) A total of 1,654 women randomly recruited from a general population; 686 women were eligible and accepted inclusion (429 pre- and 257 postmenopausal). Saline contrast sonohysterography (SCSH) was finally performed in 622 women (aged 20-74 years) (the procedure was impossible owing to cervical stenosis in 58, contraindicated in 2, other patient-related factors in 4). Intervention(s) The shape of the uterus was dynamically evaluated in the transversal and longitudinal planes during SCSH and classified in accordance with American Fertility Society as normal, arcuate, septate (partial, complete), bicorn (partial, complete), or unicorn. History of previous miscarriage and menstrual cycle was obtained by a questionnaire. Main Outcome Measure(s) Prevalence of müllerian anomalies, miscarriage, and oligomenorrhea. Result(s) The overall prevalence of müllerian anomalies was 9.8% (61 of 622) (95% confidence interval [CI] 7.5-12.1). The majority had arcuate uteri (n = 42, 6.8%), 17 partial septate (2.7%), 1 complete septate (1.6%), and 1 unicorn uterus (1.6%). Müllerian anomalies were significantly more frequently diagnosed in nulliparous (20% [26 of 128]) compared with parous women (7% [35 of 494]). Müllerian anomalies were more frequent in women with oligomenorrhea compared with women with normal menstrual periods (19% [15 of 79] vs. 10% [34 of 339]). One first-trimester miscarriage or multiple miscarriages (more than one) were not significantly more frequent in premenopausal women with müllerian anomalies compared with women with normal-shaped uteri (24% [6 of 25] vs. 22% [57 of 265]). Conclusion(s) In a general population examined by SCSH the prevalence of Müllerian anomalies is estimated at 9.8%. Müllerian anomalies were more frequent in nulliparous women. Both impaired fertility and a pregnancy-associated modulation of the uterine corpus are among explanations. Müllerian anomalies were associated with oligomenorrhea in premenopausal women. In this general population there was no association between miscarriage and müllerian anomalies; however, the number of cases was limited. [ABSTRACT FROM AUTHOR]

Objective: To determine the features of polycystic ovary syndrome (PCOS) that are implicated in the associated reproductive and metabolic morbidities. Design: Cross-sectional case–control study. Setting: Academic medical setting. Patient(s): A total of 1,062 women with PCOS and 1,887 women without PCOS. Intervention(s): None. Main Outcome Measure(s): Physical examination including hirsutism scoring, biochemical and hormone measurements, ovarian ultrasound, and a 75-g oral glucose tolerance test to measure glucose and insulin levels. Result(s): A factor analysis identified four dominant factors in women with PCOS. These factors were interpreted as follows: [1] metabolic and hyperandrogenemia factor, [2] oligomenorrhea and hyperandrogenemia factor, [3] blood pressure factor, and [4] ovarian morphology factor. In women with PCOS, hyperandrogenemia was a significant predictor of metabolic syndrome after adjusting for age, body mass index, and insulin resistance in the regression analysis. Conclusion(s): A factor analysis identified multiple factors that are responsible for the abnormalities associated with PCOS. Hyperandrogenemia was a common underlying feature of the metabolic and reproductive abnormalities in women with PCOS but not in women without PCOS. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the performance of antimullerian hormone (AMH) and inhibin B as ovarian function markers for differentiating common causes of secondary oligoamenorrhea, namely hypogonadotrophic hypogonadism (HH), polycystic ovary syndrome (PCOS), premature ovarian failure (POF), and hyperprolactinemia (HPRL).Design: Retrospective analysis.Setting: Two university hospitals.Patient(s): A total of 124 women with secondary oligoamenorrhea and 26 women with normal ovulation.Intervention(s): Serum samples from the subjects were analyzed for AMH and inhibin B.Main Outcome Measure(s): Serum AMH and inhibin B concentrations.Result(s): Serum AMH concentration was significantly raised in women having World Health Organization group 2 anovulation, either with or without PCOS, and was significantly decreased to very low levels in POF; the diagnostic accuracy in both conditions was excellent, with areas under the receiver operating characteristic curve (AUC) of 0.913 and 0.977, respectively. The discriminatory performance between HH and PCOS was also good, with AUC 0.861. AMH remained unchanged in HH and HPRL compared with ovulatory control subjects. There were large overlap of serum inhibin B levels in the different conditions, and a significant difference from control subjects existed only in the POF group.Conclusion(s): Serum AMH, but not inhibin B concentration, serves as a useful diagnostic tool in the differential diagnosis of secondary oligoamenorrhea. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prevalence and risk factors of menstrual cycle irregularities in adolescents with type 1 diabetes mellitus. Design: Prospective diary of menstrual cycle. Setting: Pediatric diabetes clinics and nearby schools. Patient(s): Adolescents with type 1 diabetes mellitus treated with multiple daily insulin doses (n = 56) and 56 healthy adolescents. Main Outcome Measure(s): Duration and variability of menstrual cycle. Result(s): Duration of the menstrual cycle was 48 ± 39 and 32 ± 7 days in girls with type 1 diabetes mellitus and controls, respectively. Oligomenorrhea (58.9% vs. 19.6%) and amenorrhea (10.7% vs. 1.8%) were more prevalent in girls with type 1 diabetes mellitus than in controls. Oligomenorrhea was observed in 53.3% of the girls with type 1 diabetes mellitus with optimal metabolic control. Girls with an HbA1c level of 7.6% to 8.9% exhibited increased cycle duration, menstrual cycle variability, and prevalence of oligomenorrhea compared with controls. Regression analysis showed that, for each point of increase in HbA1c, the menstrual cycle duration increased by 5.1 days. Cycle variability was associated with a higher daily insulin dose. Conclusion(s): Despite optimal metabolic control, a higher prevalence of oligomenorrhea was observed in girls with type 1 diabetes mellitus compared with controls. This is the first report to describe the high variability of the menstrual cycle in type 1 diabetes mellitus. HbA1c and insulin dose are important factors related to menstrual irregularities in type 1 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that women with polycystic ovary syndrome (PCOS) are distinguishable from those with 21-hydroxylase-deficient nonclassic adrenal hyperplasia on the basis of having polycystic ovaries and metabolic dysfunction.Design: Prospective observational.Setting: Tertiary care center.Patient(s): Fifty-two lean and 54 obese women with PCOS according to the 1990 National Institutes of Health criteria, 23 women with nonclassic adrenal hyperplasia, and 27 controls.Intervention(s): History and physical examination, blood sampling, ovarian sonography, oral glucose tolerance, and acute adrenocorticotropin stimulation testing.Main Outcome Measure(s): The frequency of clinical, biochemical, and metabolic features.Result(s): Women with PCOS had a higher frequency of oligomenorrhea or amenorrhea than those with nonclassic adrenal hyperplasia. Mean androstenedione and DHEAS levels were highest in nonclassic adrenal hyperplasia. The degree of metabolic dysfunction was greatest in obese women with PCOS; women with nonclassic adrenal hyperplasia and lean women with PCOS did not differ in degree of metabolic dysfunction. Women with nonclassic adrenal hyperplasia had a lower prevalence of polycystic ovaries than those with PCOS. The proportion of patients with an LH/FSH ratio >2 was greater in women with PCOS, compared with those with nonclassic adrenal hyperplasia. Basal 17-hydroxyprogesterone levels >2 ng/mL were found in 87%, 25%, 20%, and 7% of women with nonclassic adrenal hyperplasia, lean women with PCOS, obese women with PCOS, and controls, respectively.Conclusion(s): Nonclassic adrenal hyperplasia should be excluded in all women presenting with hirsutism, with use of a basal follicular phase 17-hydroxyprogesterone level, regardless of the presence of polycystic ovaries or metabolic dysfunction; however, women with nonclassic adrenal hyperplasia have a higher prevalence of normal ovulation and lower likelihood of having an LH/FSH ratio >2 or polycystic ovaries. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the metabolic profiles of adolescents with different phenotypes of polycystic ovary syndrome (PCOS). Design: Observational study. Setting: University outpatient clinic. Patient(s): Adolescents with PCOS (n = 120) were divided into four groups: oligomenorrhea and hirsutism (O-H, n = 50), oligomenorrhea, hirsutism, and polycystic ovaries (PCO-O-H, n = 22), oligomenorrhea, hirsutism, and hyperandrogenemia (A-O-H, n = 28), oligomenorrhea, and hirsutism, hyperandrogenemia, and polycystic ovaries (PCO-A-O-H, n = 20). A control group of age-matched adolescents (n = 30) was included. Intervention(s): Subjects underwent physical and ultrasound evaluations; fasting blood samples were taken for the measurement of endocrine and metabolic parameters. Main Outcome Measure(s): The endocrine and metabolic profiles were evaluated. Result(s): Adolescents with PCOS showed reduced insulin sensitivity and dyslipidemia. Triglycerides, and total and low-density lipoprotein cholesterol were higher in the phenotypes with hyperandrogenemia. Insulin resistance and body mass index were not significantly different between PCOS phenotypes. Triglyceride positively and high-density lipoportein cholesterol levels negatively correlated with free testosterone and free androgen index. Conclusion(s): The risk of metabolic alterations may vary in adolescent PCOS patients with different phenotypes. Hyperandrogenemia is a risk factor for dyslipidemia. This information may be of relevance in counseling adolescents with PCOS. [Copyright &y& Elsevier]

Objective: To evaluate inappropriate gonadotropin secretion in women with polycystic ovary syndrome (PCOS). Design: Retrospective study. Setting: Academic tertiary center. Patient(s): A total of 373 women were classified into three groups: [1] healthy control women (n = 48); [2] women who were positive for PCOS risk factor; and [3] women with PCOS (n = 251). Intervention(s): None. Main Outcome Measure(s): Gonadotropin levels, LH-FSH ratio, body mass index, and clinical and/or biochemical presentations of PCOS. Result(s): The area under the receiver operating characteristic curve, used to predict PCOS for the LH-FSH ratio, showed similar diagnostic performance to total T and average ovarian volume. The LH-FSH ratio exhibits greater observed accuracy than total T and average ovarian volume for evaluation of women with oligomenorrhea or anovulation. An LH-FSH ratio of >1 presented the best combination of sensitivity and specificity. Body mass index was positively correlated with total T in non-PCOS and PCOS groups; however, body mass index was negatively correlated with LH in PCOS but showed no correlation in non-PCOS subjects. Conclusion(s): The LH-FSH ratio is a valuable diagnostic tool in evaluating women with PCOS and oligomenorrhea or anovulation, and an LH-FSH ratio of >1 may be used as a decision threshold. The link between body mass index and LH may provide clues for further understanding the pathological milieu of PCOS. [Copyright &y& Elsevier]

Objective: To determine whether infertile oligomenorrheic women are insulin resistant, using an oral glucose tolerance test (OGTT). Design: Retrospective study. Setting: National Center for Child Health and Development. Patient(s): One hundred twenty-seven infertile women with oligomenorrhea (oligomenorrheal group) and 177 infertile eumenorrheic women (normal menstrual group) were recruited. Intervention(s): All women underwent an OGTT (75 g glucose). Main Outcome Measure(s): A homeostasis model assessment of insulin resistance (HOMA-IR), area under the curve (AUC) of insulin after the glucose load, and plasma insulin level at 120 minutes after glucose loading (IRI 120) were used as an index of insulin resistance. Result(s): The prevalence of insulin resistance (HOMA-IR ≥1.73) among oligomenorrheic women was 23.8%, which was significantly higher than that of eumenorrheic women, at 14.1%. The glucose AUCs (mean ± SE) in the oligomenorrheal group (13,609 ± 259 mg/min/dL) were similar to those for the normal menstrual groups (13,054 ± 196 mg/min/dL), but the insulin AUCs of the oligomenorrheal group (5333 ± 376 mU·min/L) were significantly higher than those of the normal menstrual groups (4517 ± 266 mU·min/L). Conclusion(s): The prevalence of insulin resistance assessed using an OGTT was significantly higher among infertile oligomenorrheic women with non-polycystic ovary syndrome than it was among women with normal menstrual cycles. [Copyright &y& Elsevier]

Objective: To determine the risk of metabolic complications, primarily metabolic syndrome, in all polycystic ovary syndrome (PCOS) phenotypes compared with control subjects. Design: Retrospective chart review. Setting: University practice. Patient(s): Women with PCOS (Rotterdam definition; n = 258) and women without PCOS seen during the same time period for an annual exam used as controls (n = 110). Intervention(s): None. Main Outcome Measure(s): Metabolic syndrome. Result(s): Three PCOS phenotypes had a significantly higher prevalence of metabolic syndrome compared with the control subjects: oligomenorrhea/oligo-ovulation (O) + hyperandrogenism (H) + polycystic ovaries (P), age-adjusted odds ratio [OR] 6.3 (95% confidence interval 2.1–18.9); O+H, OR 7.8 (2.2–27.5); and H+P, OR 8.2 (2.3–29.3). There was no significant difference in the prevalence of metabolic syndrome between women with O+P and control subjects, even in obese women. The prevalence of insulin resistance and glucose intolerance was not significantly different between POCS phenotypes Conclusion(s): The risk of metabolic syndrome may vary among the four phenotypes of PCOS based on the Rotterdam criteria. This new information may be of relevance in counseling women with PCOS although larger studies may be needed to validate our findings. [Copyright &y& Elsevier]

Objective: To determine which first-line medication is more effective in polycystic ovary syndrome (PCOS) patients for ovulation induction and pregnancy achievement and to verify whether any patient characteristic is associated with a better response to therapy. Design: Observational comparative study. Setting: Fertility clinic. Patient(s): One hundred fifty-four infertile women with oligomenorrhea and hyperandrogenism. Intervention(s): Group 1 (56 patients) received clomiphene citrate (CC) 50 mg from days 5–9 of the cycle. Group 2 (57 patients) received 500 mg of metformin 3 times a day. Group 3 (41 patients) received both medications. Main Outcome Measure(s): Ovulation and pregnancy. Result(s): Patients receiving metformin alone had an increased ovulation rate compared with those receiving CC alone (75.4% vs. 50%). Patients on metformin had similar ovulation rates compared with those in the combination group (75.4% vs. 63.4%). Pregnancy rates were equivalent in the 3 groups. Response to metformin was independent of body weight and dose. Finally, nonsmoking predicted better ovulatory response overall as well as lower fasting glucose for CC and lower androgens for metformin. Conclusion(s): Metformin is better for ovulation induction than CC alone and equivalent for pregnancy achievement. We suggest that metformin can be used first for ovulation induction in patients with PCOS regardless of their weight and insulin levels because of its efficacy and known safety profile. [Copyright &y& Elsevier]

Objective: To determine whether obese, nonhirsute adolescents with oligomenorrhea exhibit similar increased LH pulse secretion patterns compared with obese girls with polycystic ovary syndrome (PCOS). Design: Prospective, observational study. Setting: Tertiary university hospital. Patient(s): Nine obese girls with oligomenorrhea, 15 with PCOS, and 10 controls. Intervention(s): Twenty-four-hour IV blood sampling for LH (every 10 minutes); measurement of steroid hormones (every 12 hours); and injection of leuprolide acetate (10 μgm/kg SC). Main Outcome Measure(s): Twenty-four-hour, wake, and sleep LH mean serum concentration, pulse frequency, amplitude; steroid hormones, including free androgen index (FAI); and pre- and post-leuprolide acetate 17-hydroxyprogesterone measurements. Result(s): Twenty-four-hour LH pulse frequency in oligomenorrheic girls (18.6 ± 1.2) (mean ± SE) was comparable to that in girls with PCOS (20.9 ± 0.7) and greater than in normal girls (13.4 ± 0.8). The pulse number during both sleep and wake was identical in oligomenorrheic and PCOS girls and significantly greater than that of normal girls. Mean 24-hour LH level, serum androgen levels, and FAI in oligomenorrheic girls were equivalent to those of normal controls and lower than those of PCOS girls. Conclusion(s): These preliminary results indicate that obese girls with oligomenorrhea exhibit increased LH pulse frequency in the absence of clinical and/or biochemical evidence of hyperandrogenism. [Copyright &y& Elsevier]

: ObjectiveTo investigate plasma viscosity, a hemorheologic variable, in oligomenorrheic and eumenorrheic hirsute women.: DesignDescriptive study.: SettingEndocrinology and metabolism clinic.: Patient(s)Twenty five hirsute women with oligomenorrhea and eumenorrhea and 30 age- and weight-matched healthy, eumenorrheic, nonhirsute women.: Main outcome measure(s)Plasma viscosity.: Result(s)Plasma viscosity was significantly elevated in hirsute women compared with eumenorrheic nonhirsute women. Significant correlations were observed between plasma viscosity and fasting insulin level, cholesterol level, and diastolic blood pressure.: Conclusion(s)Hirsute women with oligomenorrhea or eumenorrhea had a significantly elevated plasma viscosity compared with healthy controls. [Copyright &y& Elsevier]

: ObjectiveTo evaluate endocrine mechanisms underlying oligomenorrhea or amenorrhea in female athletes.: DesignCross-sectional study.: SettingWomen’s health clinical research unit at a university hospital.: Patient(s)Age- and BMI-matched groups of athletes active in endurance sports with and without menstrual disturbances and regularly cycling sedentary controls.: Intervention(s)Groups were compared with respect to endocrine status, body composition, and physical performance.: Main outcome measure(s)Identification of a subgroup of oligomenorrheic or amenorrheic athletes with increased androgen levels and anabolic body composition.: Result(s)A subgroup of 8 of 25 athletes with menstrual disturbances had significantly higher serum levels of free and total testosterone, androstenedione, LH-FSH ratio, and lower SHBG levels than did all other groups. Other oligomenorrheic or amenorrheic athletes had normal values comparable to those in regularly menstruating athletes and controls. The hyperandrogenic subgroup showed a more anabolic body composition, with higher total bone mineral density and upper-lower fat mass ratio than did oligomenorrheic or amenorrheic athletes with normal androgen levels. The hyperandrogenic subgroup had the highest VO2 max and the highest performance values in general.: Conclusion(s)Menstrual disturbances in female athletes are often explained as a consequence of hypothalamic inhibition and caloric deficiency. We suggest that essential hyperandrogenism is an alternative mechanism underlying oligomenorrhea or amenorrhea in some female athletes and may imply an advantage for physical performance. [Copyright &y& Elsevier]

Polycystic ovary syndrome (PCOS) is one of the major causes of adolescent hyperandrogenism and menstrual disorders. Because there is no universal definition for adolescent PCOS, we recommend four out of five criteria: clinical and biologic evidence of hyperandrogenism, hyperinsulinism, oligo-/amenorrhea, and polycystic ovaries on ultrasonography. [Copyright &y& Elsevier]