ResearchPad - reproductive-endocrinology:-reproductive-function-and-dysfunction-on-development Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[MON-029 Polycystic Ovary Syndrome (PCOS) in Adolescent Girls:Toward a Simple On-Treatment Predictor of Post-Treatment Ovulation Rate]]> There is no approved treatment for adolescent girls with PCOS. The vast majority of these patients are guided into a trajectory that starts with oral contraceptive (OC) treatment, leads into oligo-anovulatory subfertility, then into the use of assisted reproductive techniques, and ultimately into pregnancies with a double-to-triple risk for complications (such as gestational diabetes, preeclampsia and preterm birth) potentially with lifelong sequelae in the offspring.

Evidence is converging into the insight that adolescent PCOS is frequently driven by hepato-visceral fat excess (“central obesity”) ensuing from a mismatch between (rather restrictive) prenatal and (rather abundant) postnatal nutrition, on a background of genetic susceptibility (Trends Endocrinol Metab 2018;29:815). This insight has prompted the exploration of an alternative PCOS treatment that aims at reducing the central-fat excess (without causing weight loss in non-obese girls) in order to normalize the entire phenotype, including ovulation rate.

So far, this alternative approach has been tested in two randomized controlled pilot studies that were performed in non-obese girls with PCOS and with no need for contraception (total N=62; age 16 yr; BMI 24 Kg/m2; treatment for 1 year; ovulation assessment during the post-treatment year). In these studies, the effects of an OC were compared to those of SPIOMET, which is a low-dose combination of spironolactone (= a mixed anti-androgen and -mineralocorticoid, also activating brown adipose tissue; Diab Ob Metab 2019;21:509), pioglitazone and metformin (= two insulin sensitizers acting through different mechanisms).

Pooled results of the pilot studies confirm the first report (J Adolesc Health 2017;61:446) that SPIOMET has more normalizing effects than OC; there were approximately 3-fold more ovulations post-SPIOMET than post-OC; normovulation occurred only post-SPIOMET; anovulation was >10-fold more frequent post-OC.

Pooled results also disclosed two new features of adolescent PCOS: low concentrations of circulating CXCL14 (= a brown adipokine, signaling activity in brown adipose tissue; Cell Metab 2018;28:750) and miR-451a (= an inhibitor of THRSP-mediated hepatic lipogenesis; Mol Cell Endocrinol 2018;474:260), both of which remain abnormally low on OC, but normalize on SPIOMET treatment. The on-treatment Z-scores of fasting insulin and miR-451a explained together approximately 50% of the variation in post-treatment ovulation rates. This simple duo, if validated in larger and more diverse PCOS populations, may become a first on-treatment predictor of post-treatment ovulation rate.

<![CDATA[MON-033 Androgen Increases the Accumulation of Advanced Glycation End Products in Granulosa Cells by Activating ER Stress in PCOS]]> Polycystic ovarian syndrome (PCOS) is associated with hyperandrogenism. Previously we found that androgen activated endoplasmic reticulum (ER) stress in granulosa cells of antral follicles in PCOS, contributing to ovarian fibrosis (1) and growth arrest of antral follicles (2). In addition, recent studies demonstrated the accumulation of advanced glycation end products (AGEs) in granulosa cells from PCOS patients, which contribute to its pathology. Based on these findings, we hypothesized that androgen upregulates the expression of the receptor for AGEs (RAGE) in granulosa cells of antral follicles by activating ER stress. This in turn, increases the accumulation of AGEs in these cells. In the present study, we found that testosterone induced the expression of RAGE and accumulation of AGE in cultured human granulosa-lutein cells (GLCs). These effects were inhibited with the treatment of tauroursodeoxycholic acid (TUDCA), a clinically available ER stress inhibitor agent. Knockdown of the transcription factor C/EBP homologous protein (CHOP), an unfolded protein response (UPR) factor activated by ER stress, inhibited the testosterone-induced RAGE expression and AGE accumulation. Pretreatment with flutamide, as well as knockdown of androgen receptor decreased the testosterone-induced RAGE expression. Expression of RAGE was increased in GLCs obtained from patients with PCOS. Concomitantly, the expression of RAGE and the accumulation of AGE was increased in granulosa cells of antral follicles from PCOS patients and dehydroepiandrosterone (DHEA)-induced PCOS mice. Administration of the RAGE inhibitor, FPS-ZM1 or TUDCA to PCOS mice, reduced the expression of RAGE and the accumulation of AGE in granulosa cells of antral follicles, accompanied by a reduction of atretic follicles and improvement in the estrous cycle. In summary, our findings indicate that hyperandrogenism in PCOS increases the expression of RAGE and accumulation of AGEs in the ovary by activating ER stress. The potential therapeutic benefit of targeting the AGE-RAGE system, either with a RAGE inhibitor or an ER stress inhibitor agents, may serve as a novel approach for the treatment of PCOS. (1) Takahashi et al. Sci Rep. 2017;7(1):10824. (2) Azhary et al. Endocrinol. 2019;160(1):119–132

<![CDATA[MON-LB010 Cyclic Progesterone Therapy for Androgenic Polycystic Ovary Syndrome (PCOS) - A Systematic Review of the Literature]]> Women living with androgenic PCOS (WLWP) experience unpredictable oligomenorrhea1 and are at increased risk for endometrial cancer2. Oral micronized progesterone (OMP) given cyclically (14 days/cycle or 4 weeks, Cyclic OMP), in luteal phase doses3 (300 mg at bedtime) as a “luteal phase replacement” therapy would be likely to effectively treat both. In addition, evidence suggests PCOS is causally related to rapid pulsing of GnRH and LH 4; OMP normalizes LH pulsatility if androgen levels are not elevated 4. Previous searches did not find progesterone therapy for PCOS 5. Our research question: Does the peer-reviewed literature provide evidence for prescribing cyclic progesterone therapy in PCOS? Literature search methods used Medline (Ovid) and PubMed for published articles. Our search terms were: “polycystic ovary syndrome”, “androgenic PCOS”, and, “micronized progesterone.” We sought publications with eligible women participants having androgenic PCOS, drug exposures (cyclic

OMP, vaginal progesterone, and in varying doses and durations) and specific outcomes (biochemical or patient-reported data or both) in all languages. We excluded reviews and practice guidelines but searched bibliographies for missed citations. Results discovered 18 articles in combined Medline (n=6) and PubMed (12) searches. After excluding duplicates, articles on estradiol (E2) alone E2 with OMP therapy, five eligible articles remained. We read all in full detail.

Progesterone therapy was beneficial for WLWP as, even in sub-therapeutic doses (<300 mg at bedtime) and in cycles of too short durations (<14 days), it decreased luteinizing hormone (LH) 6,7 and total testosterone 7 levels. Vaginal progesterone (200 mg, b.i.d for 2 to 12 weeks) added to letrozole ovulation induction increased the pregnancy rate from 0 to 21% 8. Although present data suggest Cyclic OMP withdrawal predictively causes flow, we found no evidence it improved women’s cycle-related experiences nor decreased acne and hirsutism. Women-reported data on Cyclic OMP for improving androgenic PCOS cycle regularity, daily experiences and risks for endometrial cancer are needed.

Reference: 1Azziz R Nat Rev Dis Primers 2016;2:16057. 2Barry J Hum Reprod Update 2014; 20:748. 3Simon J Fertil Steril 1993;60:26. 4Blank S Hum Reprod Update 2006;12:351. 5Teede H Clin Endocrinol (Oxf) 2018;89:251. 6Livadas S Fertil Steril 2010;94:242. 7Bagis T J Clin Endocr Met 2002;87:4536. 8Montville C Fertil Steril. 2010;94:678.

<![CDATA[MON-040 11-Oxygenated C19 Steroids in Polycystic Ovarian Syndrome]]> BACKGROUND: Polycystic ovarian syndrome (PCOS), an endocrine and reproductive disorder consisting of hyperandrogenism, menstrual dysfunction and ovarian changes, affects 6–20% of reproductive aged women worldwide. While hyperandrogenemia is traditionally determined by evidence of elevated testosterone (T), this hormone can be difficult to accurately measure in women with relatively lower circulating levels compared to men. Recent studies have suggested that four adrenal androgens known as 11-oxygenated C19 steroids (11OxyAs), specifically 11-ketotestosterone (11KT), may be good alternative markers for hyperandrogenism in PCOS. Using a multiethnic population seeking evaluation for PCOS symptomatology, we sought (1) to investigate the utility of 11OxyAs to differentiate women with and without NIH PCOS relative to classical androgens such as T, androstenedione (A4) and DHEAS levels, and (2) to evaluate the relationship of 11OxyAs to clinical findings of androgen excess.

Methods: Using the University of California, San Francisco PCOS Tissue Bank, serum samples from 131 women seen for a PCOS evaluation were selected sequentially and identified as PCOS or non-PCOS (controls) based on meeting NIH criteria at the time of evaluation. In addition to obtaining gonadotropin and metabolic profiles, classical androgens and 11OxyAs were measured using mass spectrometry. The relationship of these androgens to modified Ferriman-Gallwey (mFG) scores and ovarian morphology were also assessed.

Results: Out of 131 women selected, 83 met NIH PCOS criteria at the time of evaluation and 48 did not (controls). Age and BMI did not differ among the two groups. As expected, total T, A4 and LH were all significantly higher in NIH PCOS. A trend towards higher HOMA-IR levels was also seen in NIH PCOS, but this did not reach statistical significance (3±3.9 mg/dL vs. 1.9±1.7 mg/dL, p = 0.12). No difference was seen in all four 11OxyAs between NIH PCOS and controls. Unlike previous studies, we also did not find mean 11KT levels to exceed that of T in both controls (T 393±143 pg/mL vs. 11KT 389±206 pg/mL) and PCOS (T 530±245 pg/mL vs. 11KT 388±201 pg/mL). In addition, no relationship was seen between HOMA-IR and 11β-hydroxyandrostenedione (11OHA4) or 11-ketoandrostenedione (11KA4) levels. Within PCOS, DHEAS and A4 were noted to have a weak but inverse relationship to BMI (r2 0.05 p = 0.05; r2 0.08 p = 0.007), whereas no correlation was seen between any of the four 11OxyAs or T and BMI. Lastly, 11OxyAs, T, and A4 levels did not predict mFG scores or polycystic ovarian morphology.

Conclusions: 11OxyAs levels were not statistically higher among women with NIH PCOS compared to at risk women who did not meet NIH criteria. There was no significant relationship between these androgens and mFG scores or ovarian morphology. Further studies are necessary to show the utility of 11OxyAs levels as a marker for hyperandrogenism or metabolic risk.

<![CDATA[MON-030 Intermediate Hyperglycemia and Type 2 Diabetes in Women with Polycystic Ovary Syndrome: Findings from Large Caucasian Cohort]]> Background: Insulin secretory defects and insulin resistance exists in women with polycystic ovary syndrome (PCOS) and are prerequisites for the development of type 2 diabetes (T2D). Objective: To determine the prevalence of T2D, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), as well as the factors associated with these dysglycemic conditions. Participants: 1614 women with PCOS of Caucasian origin (Rotterdam criteria) with a mean age 25.14±5.56 years and BMI 27.34±7.09 kg/m2 comprised the study group, whereas 359 normally ovulating, not hyperandrogenic women of comparable age and BMI, served as controls. Design: Observational study. Setting: Outpatient clinics of tertiary hospitals. Main Outcome and Measures: Clinical, biochemical, hormonal and ovarian ultrasound as well oral glucose tolerance test were performed in all subjects participating in the study. Diabetes and intermediate hypeglycemia was categorised according to WHO criteria and PCOS subgroups was based on the Rotterdam criteria. Results: In the PCOS group 2.2%, 9.5% and 12,4% of subjects had T2D, IGT and IFG, respectively. In control group 1,11%, 7.5% and 8.9% had T2D, IGT and IFG, respectively. When the existence of T2D was stratified according to age and BMI, no difference was found among age and BMI subgroups or PCOS subgroups. Namely in patients aged 17-22 years, T2D was detected in 3 lean and 2 obese subjects. The corresponding distribution for patients aged 22-30 years was 4 lean, one overweight and 2 obese, whereas in those older than 31 years, 2 overweight and 5 obese suffered from T2D. Free Androgen Index (FAI), waist to hip ratio (WHR) and LDL levels were significantly higher in T2D subjects in comparison to PCOS women with normal glucose metabolism. Diagnosis of T2D was significantly associated with Free Androgen Index (r: 0.469, p<0.05), while subjects with either IFG and IGT had positive association with BMI, WHR, FAI and HOMA-IR. In controls, T2D, IGT and IFG were positively associated with BMI and androgen concentrations. Conclusions: The prevalence of T2D and IGT is significantly higher in our large cohort of PCOS women in comparison to controls. The existence of T2D is irrespective of age and BMI, and seems to be inherent for PCOS women. Hence, the evaluation of glycemic status in women with PCOS using OGTT is supported.

<![CDATA[MON-032 Excessive Ovarian Sympathetic Activity Impairs Embryonic Development and Causes Reproductive and Metabolic Dysfunction]]> Nerve growth factor is a member of the neurotrophin family and within the ovary, it plays an important role in sympathetic innervation and in the development and maintenance of folliculogenesis. Despite its critical role, excessive levels of ovarian NGF may lead to ovarian pathology and to the development of features of polycystic ovary syndrome (PCOS), which is the most common endocrine disorder among women of reproductive age. Here, using a transgenic mouse model overexpressing NGF selectively in the ovary (17NF mice), we studied how ovarian sympathetic hyperactivity affects embryonic development and reproductive and metabolic function in adulthood. Firstly, we showed that ovarian NGF excess caused growth restriction in the developing female fetuses, which was driven by defects in the placenta function. Moreover, the 17NF fetuses experienced a reduction of germ cell number along with delayed gonocyte and primary oocyte maturation. The adult 17NF mice displayed irregular cyclicity and aberrant ovarian expression of steroidogenic genes and epigenetic markers. The ovarian sympathetic hyperactivity also led to increased systemic sympathetic outflow, indicated by increased circulating dopamine levels, and to metabolic dysfunction in adulthood. The 17NF mice had increased adiposity, impaired glucose metabolism and decreased energy expenditure. The subcutaneous and parametrial fat depots displayed impaired function due to ovarian NGF excess, wherein the subcutaneous fat increased mass by enhanced preadipocyte differentiation and enlarged adipocyte size, while the parametrial fat had smaller adipocyte size and a modest increase in stimulated lipolysis. These defects also led to hepatic steatosis. Overall, our findings indicate that ovarian sympathetic hyperactivity has deleterious effects on whole-body homeostasis and leads to impaired embryonic development and to reproductive and metabolic defects in adult life.

<![CDATA[MON-039 Prenatal Anti-Mullerian Hormone (pAMH) Exposure in Mice Induces Changes in Pubertal Onset, Fertility, and Stress Response in Both Male and Female Offspring]]> Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, classically presenting with disrupted ovulation, polycystic ovaries, and androgen excess, as well as many non-reproductive comorbidities. For instance, PCOS patients exhibit increased stress reactivity and higher rates of depression and anxiety compared to the general population. The prenatal anti-Mullerian hormone (pAMH)-induced model of PCOS was recently shown to recapitulate reproductive phenotypes in female mice, however little remains known about the consequences of pAMH exposure. We first aimed to expand upon this model by investigating pAMH-induced effects on offspring of both sexes. Pregnant dams on a C57Bl/6 background received daily i.p. injections of either AMH (0.12 mg/kg/d) or VEH late in gestation. Offspring were born into 4 groups (pAMH vs. VEH females, pAMH vs. VEH males) and assessed starting at weaning for changes in body weight, anogenital distance, pubertal onset, estrous cyclicity, fertility, and reproductive senescence. Statistical differences were determined by t-test or 2-way ANOVA when applicable, and significance set at p<0.05. As expected, pAMH increased anogenital distance in females but not males. Pubertal onset was delayed not only in females as previously reported, but also in males. Additionally, pAMH adult females showed significant disruptions in estrous cycling at P60 (increased time spent in diestrus, decreased number of cycles, increased cycle length), only mild disruptions by P90, then robust disruptions at 8 mo, 10 mo, and 12 mo of age that were distinct from reproductive senescence. When paired with wildtype untreated mates for a fertility assay starting at 3 mo of age, pAMH females had smaller and fewer number of litters, while pAMH males showed only delayed plugging behavior. Although pAMH males showed no difference in testis weight, pAMH females also had significantly reduced ovarian and uterine weights in diestrus. Interestingly, during the fertility assay, we found increased fetal death from both the pAMH females and males, even though pAMH males were paired with wildtype untreated females. We hypothesized that the increased fetal death could be the result of an pAMH-induced stress phenotype in both sexes. Using a simple stress response test measuring defecation and urination during exposure to a novel environment, we found that pAMH robustly increased stress response in both sexes at multiple timepoints. We also assessed glucocorticoid response to a restraint stress paradigm in adult females. While we observed no differences in baseline serum corticosterone levels, the pAMH group showed increased peak levels followed by a prolonged elevation levels after 2 hr. Together, these results enhance existing knowledge of the effects of pAMH exposure by demonstrating alterations in both male and female mice on both reproductive and non-reproductive measures.

<![CDATA[MON-043 Sleep Disturbances in Women with and Without Polycystic Ovary Syndrome (PCOS) and Their Association with Lifestyle Factors (Diet, Physical Activity and Sitting Time)]]> Sleep disturbances in women with and without polycystic ovary syndrome (PCOS) and their association with lifestyle factors (diet, physical activity and sitting time)

Bennett C1, Mansfield DR2, Mo L2, Hodge A3, Joham A4, 5, Cain SW6, Blumfield M1, Teede H4, 5, Moran LJ4

1. Be Active Sleep and Eat (BASE) Facility, Department of Nutrition and Dietetics, School of Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria

2. Monash Lung and Sleep, Monash Health, Clayton, Victoria

3. Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria

4. Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria

5. Diabetes and Vascular Medicine Unit, Monash Health, Clayton, Victoria

6. Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University, Clayton, Victoria

Sleep disturbances are a risk factor for poorer lifestyle behaviours. While PCOS is associated with a higher prevalence of sleep disturbances, the relationship between sleep and lifestyle behaviours is unknown in PCOS. Self-reported data from the Australian Longitudinal Study on Women’s Health young cohort (31–36 years, n=6067, n=464 PCOS, n=5603 non-PCOS) were collected on PCOS, anthropometry, physical activity, sedentary behaviour, diet (74-item validated food frequency questionnaire) and sleeping behaviour (sleep quantity and adverse sleep symptoms). Multivariate regression models controlled for sleeping behaviour, BMI, age, marital status, education, income and area of residence. Women with PCOS reported greater adverse sleep symptoms, higher energy intake, diet quality (dietary guidelines index (DGI)), fibre intake and sedentary time and lower glycaemic index, compared to women without PCOS. This was not maintained for energy intake and sedentary behaviour on adjustment for confounders. For diet quality, there was an interaction between PCOS and sleep disturbances. Only for women with fewer sleep disturbances (~8 hours sleep/no adverse sleep symptoms) was PCOS associated with better diet quality (DGI higher by 3.14±0.86, p<0.001), with no differences in diet quality for women with poorer sleep. Lifestyle behaviours in women with PCOS appear to be influenced by sleep quality and quantity.

Nothing to disclose: CB, DM, LM, AH, AJ, SC, MB, HT, LM

<![CDATA[MON-035 Does Androgen Exposure Result in Germline Transmission of PCOS-Like Phenotypes and Can It Be Reversed?]]> Daughters of women with polycystic ovary syndrome (PCOS) are more likely to be diagnosed with PCOS, including reproductive and metabolic dysfunctions. Our recent research has demonstrated that dihydrotestosterone (DHT) exposure during late pregnancy results in transgenerational transmission of PCOS susceptibility to female offspring. But it remains unclear whether the transmission of the PCOS-like phenotypes is induced by in utero environment or via germ cell reprogramming, and whether treatment by exercise or androgen receptor blocker, flutamide, can prevent disease transmission. To model PCOS condition, donor mice were implanted with a continuous releasing DHT or vehicle pellet at 4 weeks of age. A subset of DHT exposed F0 donors had either free access to running wheels or were implanted with a slow-releasing flutamide pellet. Mice were exposed with or without treatment for either 6 weeks before IVF or 10 weeks prior to phenotypic testing. Here we present the phenotype of the F0 donors and the result of IVF to generate first (F1) and second (F2) generation offspring. Donors weigh more already after 2 weeks of DHT exposure and had more fat mass with larger adipocyte size, impaired glucose tolerance, and heavier kidney after 10 weeks of androgenization, which was reversed by both flutamide and exercise intervention. Moreover, DHT exposure increased circulating androgens and donors were completely acyclic. Simultaneous treatment with flutamide reversed the elevated androstenedione, testosterone, and restored estrus cyclicity, indicating that androgen receptor blocker can reverse hyperandrogenemia and reproductive dysfunction, whereas exercise failed to improve these phenotypes. After 6 weeks of exposure or treatment, donor oocytes were superovulated for IVF. Fewer oocytes per donor were found in androgenized + flutamide lineage, but no significant difference was observed in oocyte to two-cell embryo conversion rate after fertilization among all groups. Although the number of live offspring at weaning was similar among all groups, a trend of more F1 male than female offspring was found in both androgenized and androgenized + exercise lineage. Similar results were obtained in the F1 females when generating F2 offspring by IVF, which androgenized + flutamide lineage showed fewer oocytes per donor upon superovulation and more F2 male than female offspring was obtained in androgenized lineage at weaning. We here show that the androgenized donors develop clear PCOS-like phenotypes and give rise to more male than female F1 and F2 offspring. While blocking androgen receptor reverses both metabolic and reproductive disturbance in the donor, it also shows a negative impact on the donor and F1 female oocyte maturation process, although number of offspring via IVF is not affected. Excercise, however, only reverses the metabolic phenotypes in the F0 donor mice with no impact on IVF outcome.

<![CDATA[MON-LB6 Association Between Sex Steroid and Metabolic Parameters in Cord Blood With Placental Fatty Acid Transporter in Obese Pregnant Women]]> Obesity reduces maternal insulin sensitivity and alters sex steroid serum concentrations. However, it is not clear if these changes are reflected in the fetal circulation. On the other hand, similar to other metabolic tissues, modifications in sex steroid concentrations and metabolic parameters could modify the transport and metabolism of fatty acids (FA) in the placenta increasing their availability for the fetus. Therefore, we aimed to study, in pregnant women with normal-weight and obesity, sex steroid serum concentrations in cord blood and their relationship with the gene expression of FA transporters and of molecules related with FA metabolism in the placenta. We included 26 pregnant women with normal-weight and 26 pregnant women with obesity without pregnancy complications. At term of pregnancy, mixed cord blood and placenta samples were collected and stored at -80°C. Serum concentrations of dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), androstenedione, testosterone, estrone, estradiol, estriol, insulin and TNF-α were measured by RIA or ELISA. Glycemia and lipid profile were also analyzed. In placental samples, the gene expression of MFSD2A, CD36, FABP4, SLC27A4, PPARG, LPL and DGAT were determined by quantitative PCR. No differences were observed in sex steroid concentrations and metabolic parameters between groups. On the other hand, the gene expression of MFSD2A, CD36 and FABP4 were higher in placentas from women with obesity compared to women with normal-weight (P = 0.050, P = 0.037 and P = 0.038, respectively). When distributed according to fetal sex, cholesterol levels were higher in cord blood of women with obesity and female fetuses (P = 0.005), whereas glycemia was lower in women with obesity and male fetuses (P = 0.045). In turn, the gene expression of CD36 and FABP4 were higher (P = 0.024 and P = 0.034, respectively), whereas MFSD2A tended to be higher (P = 0.092) only in placentas from women with obesity and male fetuses. Moreover, in women with obesity and male fetuses, glycemia was positively correlated with MFSD2A (r = 0.650; P = 0.022), and in women with obesity and female fetuses FABP4 was inversely correlated with triglyceride levels (r = -0.580; P = 0.048). In conclusion, these data suggest that modifications in placental steroidogenesis do not affect sex steroid serum concentrations in the fetal circulation. On the other hand, metabolic parameters in cord blood of pregnant women with obesity are associated with an abnormal expression of FA transporters in placental tissue.

<![CDATA[MON-034 Impact of Race and Obstructive Sleep Apnea on Glucose and Insulin Regulation in Women with PCOS]]> 15) were included in these analyses; women with mild OSA were excluded. Insulin secretion rates (ISR) during the OGTT were derived by deconvolution of C-peptide levels 4. Area under the curve (AUC) response to the glucose challenge was calculated using the trapezoidal method. BMI and age did not differ between races in PCOS women without OSA (BMI [kg/m2]: 36.3±1.2 vs. 37.2±1.1, p=0.58; Age [yr]: 27.7±0.8 vs. 27.2±0.8, p=0.65; for NHW and AA respectively), or in PCOS women with OSA (BMI [kg/m2]: 42.8±1.7 vs. 44.7±2.0, p=0.50; Age [yr]: 31.4±1.6 vs. 28.6±1.6, p=0.18; for NHW and AA respectively). OSA severity was similar in NHW and AA PCOS women without OSA (AHI: 1.5±0.2 vs 2.1±0.2, p=0.076), and PCOS women with OSA (AHI: 32.0±4.9 vs. 28.3±4.4, p=0.26). Higher glucose responses during the OGTT were observed in NHW PCOS women with OSA compared to both NHW (AUC: 18,965±648 vs. 15,797±371, p=0.0004) and AA (AUC: 18,965±648 vs. 15,801±497, p=0.0005) PCOS women without OSA. Glucose responses did not differ significantly between AA PCOS women with OSA and AA PCOS women without OSA (AUC: 17,104±965 vs. 15,801±497, p=0.15). Similarly, ISR was higher in NHW PCOS women with OSA compared to both NHW (AUC: 5,648±488 vs. 3,907±231, p=0.0006) and AA (AUC: 5,648±488 vs. 3,981±235, p=0.0011) PCOS women without OSA. ISR did not differ significantly between AA PCOS women with OSA and AA PCOS women without OSA (AUC: 4,827±461 vs. 3,981±235, p=0.09). CONCLUSIONS: OSA has a greater impact on glucose and ISR during an oral glucose challenge in NHW compared to AA women with PCOS. Future studies would benefit from including race when evaluating metabolic outcomes in women with PCOS. References: 1Fogel et al., J Clin Endocrinol Metab. 2001: 86:1175–1180. 2Kapsimalis et al., Sleep. 2002; 25:499–506. 3Kapsimalis et al., Sleep. 2002; 25:412–419. 4Polonsky et al., J Clin Invest. 1986 Jan; 77(1):98–105. ]]> <![CDATA[MON-LB9 Cyclic Progesterone Therapy in Androgenic Polycystic Ovary Syndrome (PCOS) - Person-Related 6-Month Experience Changes]]> <![CDATA[MON-LB8 A Preconception Lifestyle Intervention Maintained Throughout Pregnancy Improves Some Gestational and Neonatal Outcomes in Women With Obesity and Infertility]]> <![CDATA[MON-037 Vitamin D Levels in Women with Polycystic Ovary Syndrome: Influence of Obesity]]> <![CDATA[MON-042 The Effect of Exercise Training on Reproductive and Cardiometabolic Outcomes in Women with Polycystic Ovary Syndrome: A Pilot Randomized Controlled Trial]]> <![CDATA[MON-041 Diagnostic Performance of Ovarian Morphology for Anovulatory Conditions in Lean and Overweight Women]]> 25kg/m2). By contrast, the diagnostic performance of OV declined when BMI was considered. FNPO discriminated between HA-Anov and NA-Anov in lean women (AUC=0.77) whereas OV discriminated between anovulatory conditions in women with overweight or obesity (AUC=0.76). FNPO, but not OV, differentiated between NA-Anov and controls – albeit thresholds were lower for women in lean (>22 follicles) versus overweight categories (>38 follicles). Conclusion: Ovarian morphology has diagnostic potential for anovulatory conditions – but its performance is impacted by BMI status. OV differentiated between HA and NA status, whereas follicle counts discriminated anovulatory conditions from controls suggesting differential roles for FNPO and OV in reproductive dysfunction. Consideration of BMI improved diagnostic performance in some cases, however the overlap in morphological features between NA- and HA-Anov is too extensive to propose condition-specific thresholds at this time. ]]> <![CDATA[MON-031 A Gene Expression Profile of the Adolescent Breast and the Impact of Obesity]]> <![CDATA[MON-LB7 Assessment of Endothelial Dysfunction by Flow Mediated Dilation in Postmenopausal Women]]>