11-oxygenated androgens and their relation to hypothalamus-pituitary-gonadal-axis disturbances in adults with congenital adrenal hyperplasia.

CONTEXT: Hypothalamus-pituitary-gonadal (HPG)-axis disturbances are a common phenomenon in patients with classic congenital adrenal hyperplasia (CAH). 11-oxygenated androgens have been suggested to play a role in this context. DESIGN: Cross-sectional single center study including 89 patients (N = 42 men, N = 55 women) with classic CAH. MAIN OUTCOME MEASURES: Differences in steroid markers in men with hypogonadism and women with secondary amenorrhea with a special focus on 11-ketotestosterone (11KT) and 11ß-hydroxyandrostenedione (11OHA4). RESULTS: Hypogonadotropic hypogonadism was present in 23 % of men and 61 % of those women currently not on contraceptives suffered from irregular menstrual cycles or amenorrhea. Testicular adrenal rest tumor (TART) was documented in 28 % of men. 11KT (3.5x) and 11OHA4 (5.7x) among other adrenal steroids were significantly elevated in men with hypogonadism and in women with amenorrhea in comparison to those with a regular cycle (11KT: 5.2x; 11OHA4: 3.7x). 11-oxygenated androgens were not higher in men with TART than in those without. There was a negative association of 11KT and 11OHA4 with FSH but not with LH in men. As expected, all steroids were strongly correlated with each other and cases of disproportionally elevated 11-oxygenated androgens that could explain for HPG-disturbances or TART in otherwise controlled patients were rare and also found in eugonadal individuals. CONCLUSIONS: In CAH, 11-oxygenated androgens are elevated in women with menstrual disturbances and in men with hypogonadotropic hypogonadism. Due to the close correlation of 11-oxygenated androgens with other adrenal steroids it remains to be shown if their measurement is superior to conventional markers of androgen control.

Menstrual dysfunction in polycystic ovary syndrome: association with dynamic state insulin resistance rather than hyperandrogenism.

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.

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.

Serum levels of allopregnanolone, progesterone and testosterone in menstrually-related and postmenopausal migraine: A cross-sectional study.

BACKGROUND: Reduced blood or cerebrospinal fluid levels of allopregnanolone are involved in menstrual cycle-linked CNS disorders, such as catamenial epilepsy. This condition, like menstrually-related migraine, is characterized by severe, treatment-resistant attacks. We explored whether there were differences in allopregnanolone, progesterone and testosterone serum levels between women with menstrually-related migraine (MM, n = 30) or postmenopausal migraine without aura who had suffered from menstrually-related migraine during their fertile age (PM, n = 30) and non-headache control women in fertile age (FAC, n = 30) or post-menopause (PC, n = 30). METHODS: Participants were women with migraine afferent to a headache centre; controls were female patients' acquaintances. Serum samples obtained were analyzed by HPLC-ESI-MS/MS. RESULTS: In menstrually-related migraine and postmenopausal migraine groups, allopregnanolone levels were lower than in the respective control groups (fertile age and post-menopause) (p < 0.001, one-way analysis of variance followed by Tukey-Kramer post-hoc comparison test) while progesterone and testosterone levels were similar. By grouping together patients with migraine, allopregnanolone levels were inversely correlated with the number of years and days of migraine/3 months (p ≤ 0.005, linear regression analysis). CONCLUSION: Decreased GABAergic inhibition, due to low allopregnanolone serum levels, could contribute to menstrually-related migraine and persistence of migraine after menopause. For the management of these disorders, a rise in the GABAergic transmission by increasing inhibitory neurosteroids might represent a novel strategy.

Screening for Androgen Excess in Women: Accuracy of Self-Reported Excess Body Hair Growth and Menstrual Dysfunction.

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.

Anti-Müllerian Hormone and Ovarian Morphology in Women With Hypothalamic Hypogonadism.

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.

Hyperprolactinemia as a prognostic factor for menstrual disorders in female adolescents with advanced chronic kidney disease.

BACKGROUND: In adolescents with chronic kidney disease (CKD), menstrual disorders (MD) are common, which can make the management of CKD difficult and can sometimes delay renal transplantation. This study aimed to identify the usefulness of hormonal measurements in adolescents with CKD and their relationships with MD during a 1-year follow-up. METHODS: A prospective cohort study was designed. Adolescents with CKD stages IV and V were included. Through clinical files and via interview, the ages at puberty onset, menarche and the date of last menstruation were identified. A 1-year follow-up was conducted over a menstrual cycle calendar. At the beginning of follow-up, routine hormonal profiles (thyroid profiles, prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol) were assessed. We compared the hormonal profiles of the patients with and without MD (wMD vs. woMD). Comparisons between groups were made by Wilcoxon and Fisher's tests. Logistic regression analysis was used. RESULTS: Fifty-seven patients, including 30 patients classified as wMD, were analyzed. The median age was 15 years, and the median time of CKD evolution was 18 months. There were no differences in general and biochemical characteristics between patients wMD and woMD. In terms of hormonal measurements, the levels of thyroid-stimulating hormone (TSH) and prolactin were higher in the wMD patients. A prolactin level ≥ 36.8 ng/ml was a risk factor for presenting with MD (RR 34.4, p = 0.002). CONCLUSIONS: Hyperprolactinemia is correlated with MD in adolescents with CKD.

Menstrual problems in adolescence: relationship to serum vitamins A and E, and systemic inflammation.

BACKGROUND: Vitamin status and inflammatory mechanisms may be related to menstrual cycle abnormalities. We investigated the associations between serum fat soluble vitamin (vitamins A and E) concentrations and biomarkers of inflammation and antioxidant status with menstrual characteristics, primary dysmenorrhea (PD) and premenstrual syndrome (PMS) in healthy adolescents. METHODS: A total of 897 adolescent girls either suffering from PMS (n = 134), PD (n = 322), PMS and PD (n = 293) or healthy adolescents (n = 148) were recruited. Serum vitamin A and E, high-sensitivity C-reactive protein (hs-CRP), antibody titers to Hsp27 (anti-Hsp27), serum prooxidant-antioxidant balance (PAB), WBC, mean platelet volume (MPV), and platelet distribution width (PDW) and RBC distribution width (RDW) were measured. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and RDW-to-platelet ratio (RPR) were calculated. RESULTS: Girls with long bleeding periods had lower concentrations of serum vitamin E compared to those who reported a normal period duration. There were significantly differences between the groups reporting oligomenorrhea, regular menses and polymenorrhea with respect to NLR, RPR, MPV and PDW. Logistic regression demonstrated that the presence of both PMS and PD was positively related to higher serum hs-CRP, PAB and NLR, while serum vitamin A level was inversely related to the presence of PMS. CONCLUSIONS: We found that serum vitamin A, hs-CRP, PAB and NLR are significantly associated with the presence of PMS and PD. Inflammatory processes may contribute to the etiology, symptoms and severity of menstrual disorders. Prospective studies are needed to elucidate the possibility of targeting oxidative stress and inflammatory process for the amelioration of menstrual symptoms.

Prostatic-specific antigen (PSA) levels in patients with polycystic ovary syndrome (PCOS): a meta-analysis.

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.

Relationship Between Etonogestrel Concentrations and Bleeding Patterns in Contraceptive Implant Users.

OBJECTIVE: To estimate whether serum etonogestrel concentrations influence bleeding patterns and related side effects in contraceptive implant users. METHODS: We conducted a prospective cross-sectional study with healthy, reproductive-aged women using etonogestrel implants for 12-36 months. Participants completed a brief questionnaire to assess their current bleeding pattern and any experience of abnormal bleeding with the implant. We then measured serum etonogestrel concentrations. We also reviewed the charts of participants to determine whether a prescription for oral contraceptive pills was ever given for treatment of implant-related bothersome bleeding. We performed multivariable logistic regression to test for associations between serum etonogestrel concentrations and both bleeding patterns and related side effects. RESULTS: We enrolled 350 women, and 59.4% reported having experienced abnormal bleeding with the contraceptive implant. Only 14.9% of participants reported amenorrhea and 37.7% reported monthly periods. Among participants with reviewable medical records (n=253), roughly 20% had received a prescription for oral contraceptive pills during implant use. Increasing serum etonogestrel concentrations were significantly associated with increasing odds of reporting abnormal bleeding (adjusted odds ratio [aOR] 1.005, P=.015) and increasing odds of having received an oral contraceptive pill prescription (aOR 1.008, P=.002). For every 100 pg/mL increase in serum etonogestrel concentration, contraceptive implant users in this study had 1.6 times the odds of reporting abnormal bleeding and 2.3 times the odds of having received a prescription as treatment for bothersome bleeding. CONCLUSION: We found both objective and subjective evidence that higher levels of progestin from the contraceptive implant were associated with bleeding side effects experienced by women in this study. Pharmacologic variation may influence the side effects women experience with a variety of hormonal contraceptive methods, in turn affecting patient satisfaction and discontinuation rates.

Serum FSH level is lower in dysovulating than in ovulating non-PCOS obese women, independently of body mass index.

OBJECTIVES: The prevalence of ovulation disorder (OD) is 3-fold higher in obese than normal-weight women. Most ODs are associated with concomitant polycystic ovary syndrome (PCOS), but obesity by itself can cause OD, through mechanisms that remain poorly documented. The literature on obese non-PCOS women with OD is sparse. The aim of the present study was to analyze a population of obese non-PCOS women with OD to shed further light on the mechanism of ovulation disorder. MATERIAL AND METHODS: This retrospective observational study of infertile obese women without PCOS compared a control group without OD (n=45) to a study group with OD (n=30) (OD group). Clinical, hormonal, and ultrasound characteristics were collected between cycle days 2 and 5. Women older than 37 years and women with PCOM (polycystic ovarian morphology) or hormonal disorder were excluded. RESULTS: Body mass index (BMI) was significantly higher in the OD group, as were waist circumference and insulin and leptin serum levels. Conversely, serum follicle stimulating hormone (FSH) levels were significantly lower. After adjustment for BMI, only serum FSH level remained significantly different between the 2 groups. Discriminant analysis suggested that FSH may have a much stronger effect on OD than BMI. CONCLUSION: Low serum FSH level may contribute to OD in some obese women, independently of BMI. The pathophysiological mechanism of this finding and its impact on therapeutic strategies must be clarified.

Prevalence and reproductive manifestations of macroprolactinemia.

PURPOSE: Macroprolactinemia is characterized by predominance of macroprolactin molecules in circulation and generally has extra-pituitary origin. Macroprolactin is viewed as biologically inactive, therefore asymptomatic, and thus may not require any treatment or prolonged follow-up. In addition, data on prevalence of macroprolactinemia and its clinical manifestation are also rare. Therefore, the present study was aimed to find out prevalence of macroprolactinemia and its association, if any, with reproductive manifestations. MATERIAL AND METHODS: Macroprolactin was measured in 102 hyperprolactinemia cases (>100 ng/ml prolactin level), 135 physiological hyperprolactinemia cases (50 pregnant and 85 lactating females; >100 ng/ml prolactin level) and 24 controls. Poly ethylene glycol (PEG) precipitation method was carried out to screen macroprolactin. Prolactin recovery of <25% was considered overt macroprolactinemia. Detailed clinical data was recorded which included complete medical history, physical examination and hormone measurements besides CT/MRI for pituitary abnormalities. RESULTS: Prevalence of macroprolactinemia was 21.57% (22/102) in hyperprolactinemia (prolactin >100 ng/ml). There was no case of macroprolactinemia in physiological hyperprolactinemia, or healthy control females. Reproductive manifestations were present in 72.73% (16/22) macroprolactinemia cases, out of which macroprolactinemia was the sole cause of associated reproductive manifestations in 68.7% (11/16) cases. Reversal of reproductive dysfunction/s was observed in five cases with appropriate treatment for high macroprolactin. CONCLUSION: Macroprolactinemia prevalence was found to be 21.5%, out of which 72.73% cases had associated reproductive dysfunctions.

Basal and metoclopramide induced prolactin secretion in lean PCOS women.

Polycystic ovary syndrome (PCOS) as well as hyperprolactinemia can cause infertility. In retrospective study the prolactin levels during the oral metoclopramide test among lean PCOS woman according to four phenotypes and free androgen index (FAI) were compared. The study population consisted of 314 lean PCOS women. The population was divided into four groups according to the FAI and menstrual cycle regularity. The group A consisted 126 women with FAI≥5 and irregular menstruation, the group B- 53 patients with FAI≥5 and regular menstruation. Group C- 70 patients with FAI<5 and irregular menstruation, group D - 65 patients with FAI<5 and regular menstruation. The ratio of prolactin value in 120th minute in the metoclopramide test to the basal prolactin value was higher in group D than in groups A and B. The prolactin basal concentration was higher in patients with FAI≥5 than in patients with FAI<5, (262.9 vs 228.9 µIU/ml; p<0.001). The ratio of prolactin in 60th minute (12.3 vs 16.7; p=0.006) and in the 120th minute (10.9 versus 13.3; p<0.001) of the metoclopramide test to the basal prolactin were lower in patients with FAI≥5. The prolactin secretion in lean PCOS women may be associated with their FAI.

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.

The Relationship between Vitamin D Status and the Menstrual Cycle in Young Women: A Preliminary Study.

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.

Menstrual Dysfunction in Girls From the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study.

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 ß-cell function and did not improve with 2 years of antihyperglycemic treatment.

Bariatric Surgery Improves Hyperandrogenism, Menstrual Irregularities, and Metabolic Dysfunction Among Women with Polycystic Ovary Syndrome (PCOS).

OBJECTIVE: To characterize the impact of bariatric surgery on reproductive and metabolic features common to polycystic ovary syndrome (PCOS) and to assess the relevance of preoperative evaluations in predicting likelihood of benefit from surgery. METHODS: A retrospective chart review of records from 930 women who had undergone bariatric surgery at the Cleveland Clinic Foundation from 2009 to 2014 was completed. Cases of PCOS were identified from ICD coding and healthy women with pelvic ultrasound evaluations were identified using Healthcare Common Procedure Coding System coding. Pre- and postoperative anthropometric evaluations, menstrual cyclicity, ovarian volume (OV) as well as markers of hyperandrogenism, dyslipidemia, and dysglycemia were evaluated. RESULTS: Forty-four women with PCOS and 65 controls were evaluated. Both PCOS and non-PCOS had significant reductions in body mass index (BMI) and markers of dyslipidemia postoperatively (p < 0.05). PCOS had significant reductions in androgen levels (p < 0.05) and percent meeting criteria for hyperandrogenism and irregular menses (p < 0.05). OV did not significantly decline in either group postoperatively. Among PCOS, independent of preoperative BMI and age, preoperative OV associated with change in hemoglobin A1c (ß 95% (confidence interval) 0.202 (0.011-0.393), p = 0.04) and change in triglycerides (6.681 (1.028-12.334), p = 0.03), and preoperative free testosterone associated with change in total cholesterol (3.744 (0.906-6.583), p = 0.02) and change in non-HDL-C (3.125 (0.453-5.796), p = 0.03). CONCLUSIONS: Bariatric surgery improves key diagnostic features seen in women with PCOS and ovarian volume, and free testosterone may have utility in predicting likelihood of metabolic benefit from surgery.

Endometrial receptivity and conception outcome among women with light menstrual bleeding of unidentified etiology.

OBJECTIVE: To investigate endometrial receptivity (ER), conception outcome, and other factors among women with light menstrual bleeding of unidentified etiology. METHODS: A prospective study was undertaken at a center in China. Between January 1, 2011, and December 31, 2014, women meeting the inclusion criteria (aged 20-35 years, without any history of pregnancy, desire to conceive, follicle-stimulating hormone <10 IU on second or third day of cycle, and regular menstrual periods) were enrolled. Participants with a menstrual blood volume of 5-20 mL formed the study group; others were in the control group. ER measures were obtained by transvaginal Doppler ultrasonography. Serum estradiol and progesterone levels were measured and items of prethrombotic state were screened in mid-luteal phase. Participants were followed up for 1 year to establish conception outcome. RESULTS: The ER (Salle) score was significantly lower in the study group (n=110) than in the control group (n=330; 9.41 ± 3.02 vs 15.67 ± 2.63, P<0.001). The natural rate of conception within 1 year was lower (60.0% [63/105] vs 72.1% [230/319], P=0.020), and the spontaneous abortion rate in early pregnancy was higher (34.4% [21/61] vs 18.1% [41/227], P=0.006) in the study group than in the control group. CONCLUSION: Women with light menstrual bleeding of unidentified etiology had an increased prevalence of low ER and poor conception outcome.