ResearchPad - clinical-studies-in-female-reproduction-i https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[SAT-016 Analytical Performance and Clinical Value of AMH Testing]]> https://www.researchpad.co/article/elastic_article_8628 The clinical uses for of anti-Mullerian hormone (AMH) measurements have risen dramatically over the past 5 years. This increase has been driven by the release of fully automated immunoassay systems with European and FDA approval of AMH measurements for assessing ovarian reserve in women presenting at fertility clinics. Most recently the MenoCheck® AMH method was cleared by FDA as an aid in determining menopausal status in women over the age of 40. Arguably much, of the increased use of AMH measurements is due more to greater test availability for infertility than to strong data supporting its clinical utility. Furthermore, few clinicians realize that the current methods for measuring AMH utilize antibodies with difference specificities, non-commutable calibrator materials, and significantly difference analytical performance characteristics.

This presentation will summarize the analytical validation of MenoCheck® AMH methodology and results of the assessment of clinical value. This method is calibrated with recombinant human AMH in a non-covalent complex associated with the cleaved N-terminal portion of the AMH prohormone protein (the major circulating form of AMH) and demonstrates commutability with native human AMH. Validation studies conformed with published Clinical Laboratory Standards Institute guidelines. Values generated by the method were not commutable to other widely available methods based on method comparison studies using control materials or unadulterated serum from normally cycling women. Clinical value assessment was possible only because of a limit of quantitation enabling measurement of AMH in the majority of perimenopausal women. SWAN study specimens carefully annotated with relevant clinical information, including date of their final menstrual period, were available from women sampled and examined during their menopausal transition. The impact of method-specific differences among the various assay systems and their implications for intended clinical use of AMH testing will be discussed. Clinicians and translational investigators must consider these technical specifications when ordering and interpreting results from AMH testing.

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<![CDATA[SAT-010 Non-Classic POR Deficiency as a Cause of Menstrual Disorders &amp; Infertility]]> https://www.researchpad.co/article/elastic_article_8615 P450 oxidoreductase deficiency (PORD) is an autosomal recessive disease caused by bi-allelic mutations of the POR gene. It is responsible for decreased activity of several P450 enzymes including CYP21A2, CYP17A1 and CYP19A1 that are involved in adrenal and/or gonadal steroidogenesis. PORD is typically diagnosed in neonates and children with ambiguous genitalia and/or skeletal abnormalities. Adult-onset PORD has been very seldom reported and little is known about the optimal way to investigate and treat such patients. In this series, we report five women aged 19-38 years, who were referred for unexplained oligo-/amenorrhea and/or infertility. Genetic testing excluded 21-hydroxylase deficiency (21OH-D), initially suspected due to increased 17-hydroxyprogesterone (17-OHP) levels. Extensive phenotyping, steroid profile by mass spectrometry, pelvic imaging and next-generation sequencing of 84 genes involved in gonadal and adrenal disorders were performed in all patients. In Vitro Fertilization (IVF) followed by frozen embryo transfer under glucocorticoid suppression therapy was performed in two patients. All patients had oligomenorrhea or amenorrhea. None had hyperandrogenism. Low-normal serum estradiol (E2) and testosterone levels contrasted with chronically increased serum progesterone (P) and 17-OHP levels, which further increased after ACTH administration. Despite excessive P, 17OH-P and 21-deoxycortisol rises after ACTH stimulation suggesting non-classic 21-hydroxylase deficiency, CYP21A2 sequencing did not support this hypothesis. Basal serum cortisol levels were low to normal, with inadequate response to ACTH in some women, suggesting partial adrenal insufficiency. Pelvic imaging revealed bilateral ovarian macrocysts in all women. All patients were found to harbor rare bi-allelic POR mutations classified as pathogenic according to American College of Medical Genetics standards. IVF was performed in two women after retrieval of a normal oocyte number despite very low E2 levels during controlled ovarian hyperstimulation. Frozen embryo transfer under glucorticoid suppression therapy led to successful pregnancies. These observations suggest that diagnosis of PORD must be considered in infertile women with chronically elevated P and 17OH-P levels and ovarian macrocysts. Differentiation of this entity from non-classic 21-hydroxylase deficiency is important, as the multiple enzyme deficiency requires a specific management. Successful fertility induction is possible by IVF, providing that P levels be sufficiently suppressed by glucocorticoid therapy prior to implantation.

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<![CDATA[SAT-029 AMH Is Higher Across the Menstrual Cycle in Early Post-Menarchal Girls Than in Ovulatory Women]]> https://www.researchpad.co/article/elastic_article_8531 Ovaries of young girls contain healthy and degenerating follicles from the primordial to antral stage, suggesting coordination of growth and atresia. At age 6 yrs, antral follicle (AF) number and size increase; by late puberty, AF count is higher than at any other life stage. The discovery of AMH, a biomarker of AFs, has facilitated the study of the immature ovary. AMH, a granulosa cell product of pre-antral and small AFs, inhibits primordial follicle growth and AF selection. As a marker of AF count, AMH should be highest during puberty, yet cross-sectional studies suggest that AMH peaks in the mid-20’s. In the current studies we compared AMH levels in early post-menarchal girls and regularly cycling adults. The rich phenotypic data available for this adolescent cohort (Sun 2019) was used to investigate further the relationship between AMH, LH, FSH, and sex steroids, and the propensity for anovulatory cycles (ANOV) in girls. 23 healthy girls (12.8–17.6 yrs;1.7±0.2 yrs post-menarche; 56% overweight/obese [OB]) underwent hormone measurements and pelvic ultrasounds during 2 consecutive menstrual cycles. Cycles were classified as ovulatory (OV) based on an LH and E2 peak and P4 >1.65 ng/mL (Sun 2019). AMH was measured in a random subset of samples (5x/subject) with the Ansh ultrasensitive ELISA. Maximum average ovarian volume (VOL) was calculated in the absence of a dominant follicle. Hormones were compared with data from 32 historic adult controls (18–34 yrs; 44% OB) with regular cycles (Lambert-Messerlian 2016). In adults, AMH was measured during the follicular and luteal phase of an OV (5x/subject) using the Ansh assay. AMH was compared among groups using a mixed model. AMH (in adults), LH (in both) and androgens (in girls) were natural log-transformed (ln) before analysis. 11 girls had 2 OV, 5 girls had 1 OV, and 5 girls had no OV; 2 could not be classified due to loss to follow-up. Girls had higher AMH than women (5.2 ± 0.3 vs. 3.3 ± 0.4 ng/mL; p<0.01) and girls with more OV tended to have lower AMH than those with ANOV (2 OV 4.5 ± 0.2, 1 OV 5.7 ± 1.1, 0 OV 6.8 ± 1.1 ng/mL; p=0.1). In girls, AMH correlated with ln_LH (r=0.4, p=0.02), ln_a’dione (r=0.4, p=0.04), ln_testosterone (r=0.5, p=0.02) and VOL (r=0.6, p=0.01) but not with FSH, E2, or BMI. In women, AMH correlated with E2 (r=-0.4, p=0.03) and not with ln_LH or BMI. Within-person variability in AMH was similar in girls and adults (CV 18%). During the early post-menarchal years, AMH levels exceed those of adults with OV, particularly among girls with ANOV, and correlate with LH and androgens. The finding of higher AMH in adolescents is consistent with previous studies demonstrating a peak in AF count during this stage of development. Investigation into how the normal ovary matures and is pruned of excess AFs, either by increased recruitment and growth or by atresia, may provide insights into the pathogenesis of PCOS, wherein follicles are arrested at the pre-antral and antral stage.

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<![CDATA[SAT-002 Does the Age of Women Influence the Evaluation of Ovarian Reserve Through the Determination of Antimullerian Hormone and Follicle Count?]]> https://www.researchpad.co/article/elastic_article_7189 INTRODUCTION: Oocyte number and quality are known to decline with age. However, fertility varies significantly even among women of the same age. Given that maternal age has been delayed in recent years, an ovarian biomarker that could reflect follicular activity with precision and accuracy is needed in reproductive medicine.

In recent years, two key methods, the concentration of serum antimüllerian hormone (AMH), which reflects the number of small antral follicles and is predictive of ovarian response, and antral follicle count (AFC) performed by ultrasonography, have emerged as preferred methods for assessing ovarian reserve.

AIM: To assess the influence of women’s age in the association between AMH serum level and antral follicle count by ultrasonography in the evaluation of ovarian reserve

SUBJECTS AND METHODS: 49 women between 25 and 45 years old who attended our laboratory with request for AMH and transvaginal ultrasound in early follicular phase were included in the study. In all of them serum AMH was tested using an electrochemiluminescence immunoassay (ECLIA) on a Roche Diagnostic Cobas e801 analyzer. Transvaginal ultrasonography follicle count was performed in both ovaries by Philips affinity 70 on first days of the menstrual cycle. Statistical analysis was performed through SPSS 23 software.

RESULTS: Median and ranges of the variables are the following: AMH: 0.78 (<0.03-9.98) ng/ml and AFC: 6 (1.0-60.0) follicles. AMH and AFC were negatively associated with age (r: -0.302, p< 0.01; r: -0.267 p<0.01, respectively). AMH showed a positive correlation with AFC (r=0.567,p<0.01). We then divided the study population in two subgroups, according to age: Group 1, women <40 years old(n=28) and Group 2, women ≥40 years old (n=21).Considering AMH= 1ng/ml and AFC = 7, the cut-off value used routinely in our institution, we calculated the Kappa coefficient in each group to test the degree of agreement between these two variables, with the following results: Group 1, Kappa= 0.4510, CI 95% [0.1566 – 0.7453], p= 0.0088; Group 2, Kappa= -0.0370, CI 95% [-0.4371 – 0.3630], p=ns.

CONCLUSION: despite the positive correlation found between AMH levels and AFC in the whole group, Kappa values show that in women younger than 40 years serum AMH>1 ng/ml is a good predictor of AFC >7, but this agreement is lost in women above this age, with the cut-off values used in this study. These results must be confirmed with a larger group of women.

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<![CDATA[SAT-006 A New Concept for the Endocrinology of Pre-Eclampsia: The Role of Spiral Steroids]]> https://www.researchpad.co/article/elastic_article_6920 Background: In 1987, Graves observed that during the 3rd trimester, some patients with pre-eclampsia had high levels of unknown materials that could be detected with assays for digoxin (DLM). In 2018, we characterized a new candidate for the DLM, Ionotropin. It is a phosphocholine (PC) ester of a novel steroid with 23 carbon atoms. As Ionotropin shares structural features (a) with spironolactone (both have spiral lactones in the E-ring) and (b) with digoxin (E-ring lactone and 3α-5β configuration), we have proposed that Ionotropin may function as a potassium (K+) sparing diuretic. This suggestion is supported by the observations that [1] patients who cannot make Ionotropin (7-dehydrosterol reductase deficiency) are K+ wasting and [2] breast cyst fluids with high K+ levels also have high Ionotropin levels.

Hypothesis: During the 3rd trimester, fetal requirements for K+ reach a maximum, fetal blood pressure increases and aldosterone signaling is blocked. This blockage leads to fetal sodium (Na+) wasting and is essential for formation of amniotic fluid. These events are consistent with a normal role for an unknown endogenous K+ sparing hormone and would be the basis for a modest elevation of maternal DLM during the 3rd trimester. Our hypothesis is that if any of the functions were inadequate, then the fetal-placental unit would synthesize excess PC-spiral steroids; the woman would exhibit symptoms of K+ sparing hormone excess (hypertension and proteinuria) and would be diagnosed with pre-eclampsia.

Experimental Results: We have just reported a pilot study associating elevated PC esters of spiral steroids in women with pre-eclampsia. In brief, 12 of 19 women had elevated levels of at least one of the PC steroids (Z-score > 2) when compared to the levels in 20 pregnant women matched for gestational age and fetal sex. There are two basic mechanisms for this dichotomy: (a) there may be episodic secretion with of a DLM with a short half-life or (b) there may be two different underlying biochemical causes. In prior studies, there has been no indication of episodic secretion of DLM similar to that observed with glucocorticoids, Ionotropin or other PC spiral steroids.

Discussion: There are two basic types of K+ sparing diuretics. Type A: Spironolactone functions by regulating the NaK-ATPase. Type B: Triamterene functions by blocking synthesis of epithelial Na+ channels. Thus, Type A would have high levels of spiral steroids and Type B would have low levels of spiral steroids. Type A patients would be expected to have higher risk of long-term consequences when compared to the Type B patients.

Conclusion: The recognition of the division of pre-eclampsia into two separate diseases might be the key observation for developing Type-specific diagnosis and therapy. For example, a Type A patient might benefit from a low salt diet but that diet would not be expected to benefit a patient with Type B disease.

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<![CDATA[SAT-023 Osteosarcopenia in Reproductive-Aged Women with Polycystic Ovary Syndrome: A Multicenter Case-Control Study]]> https://www.researchpad.co/article/elastic_article_6560 Osteosarcopenia is defined by the loss of skeletal muscle and bone mass and/or function usually associated with aging. Osteosarcopenia shares common risk factors and pathophysiological mechanisms with polycystic ovary syndrome (PCOS), including obesity and endocrine aberrations. Relationship between osteosarcopenia and PCOS has biological plausibility yet remains unclear. We hypothesized (1) reproductive-aged women with PCOS would exhibit early signs of osteosarcopenia evidenced by decreased appendicular skeletal muscle index (appendicular skeletal muscle mass/weight (kg) × 100 = SMI%), and bone mineral density (BMD); and (2) SMI% and BMD are aggravated by endocrine disruptions in PCOS. The SMI% and BMD of 203 women (18 – 48 y) were compared across 4 groups: (1) PCOS (hyperandrogenism and oligoamenorrhea), (2) hyperandrogenism and eumenorrhea (HA), (3) normoandrogenic oligoamenorrhea (OA), and (4) Controls. Associations between endocrine measures and SMI% and BMD were evaluated by partial correlations and all comparisons were adjusted for age and obesity. Women with PCOS exhibited reduced total SMI% (mean [95% confidence interval]; 26.2% [25.1 – 27.3] vs. 28.8% [27.7 – 29.8]), lower-extremity SMI% (LESMI%; 57.6% [56.7 – 60.0] vs. 62.5% [60.3 – 64.6]), and total BMD (1.11 [1.08 – 1.14] vs. 1.17 [1.14 – 1.20] g/cm2) compared to Controls. Women with PCOS also had decreased upper (0.72 [0.70 – 0.74] vs. 0.73 [0.71 – 0.76] g/cm2) and lower (1.13 [1.10 – 1.16] vs. 1.15 [1.12–1.18] g/cm2) limb BMD compared to the HA group. Insulin sensitivity evidenced by Matsuda index was declined in PCOS group compared to Controls, yet was positively associated with SMI% in all groups (All: P ≤ 0.05). The OA group exhibited exaggerated insulin-like-growth-factor-1 (IGF-1) compared to Controls (P = 0.01) that had negative associations with LESMI% (r = -0.90; P < 0.01). Only Controls showed positive associations between IGF-1 and upper (r = 0.84) and lower (r = 0.72) limb BMD (All: P < 0.01). Unlike PCOS group, estradiol (r = 0.64) and the ratio of luteinizing hormone to follicle-stimulating hormone (r = 0.54) were positively associated with BMD (All: P < 0.05) in OA group. Also, unlike PCOS group, IGF binding protein-2 (IGFBP-2) was positively associated with muscle or bone mass in other groups. Specifically, IGFBP2 was associated with SMI% in Controls (r = 0.45) and HA (r = 0.67), with LESMI% in OA (r = 0.91), and with upper limb BMD (r = 0.98) in HA groups (All: P < 0.05). Reproductive-aged women with PCOS exhibited early signs of osteosarcopenia likely owing to their unique metabolic and endocrine alterations. Perturbations in insulin signaling and function may drive muscle and bone loss in PCOS. Understanding the biological mechanisms and management strategies that may delay or prevent the development of osteosarcopenia is recommended to improve the musculoskeletal health and associated long-term comorbidities of PCOS.

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<![CDATA[SAT-018 Androgen Actions in Adipose Tissue and the Brain Are Key Mediators in the Development of Polycystic Ovary Syndrome]]> https://www.researchpad.co/article/elastic_article_6379 Polycystic ovary syndrome (PCOS) is a complex disorder characterised by endocrine, reproductive and metabolic abnormalities. Despite PCOS being the most common endocrinopathy affecting women of reproductive age, its etiology is poorly understood so there is no cure and symptom-oriented treatment is suboptimal. Elucidation of the underlying mechanisms involved in the pathogenesis of PCOS would pave the way for the development of new interventions for PCOS. Hyperandrogenism is the most consistent feature observed in PCOS patients, and recently aberrant neuroendocrine signalling and adipose tissue function have been proposed as playing a pathogenic role in the development of experimental PCOS. To investigate the role of adipose tissue and the brain as potential key sites for androgen receptor (AR)-mediated development of PCOS, we combined an adipocyte and brain-specific ARKO knockout (AdBARKO) mouse model with a dihydrotestosterone (DHT)-induced mouse model of PCOS. Wildtype (WT) and AdBARKO prepubertal mice were implanted with a blank or DHT implant and examined after 12 weeks. In WT control females, DHT exposure induced the PCOS reproductive traits of cycle irregularity, ovulatory dysfunction and reduced follicle health. In contrast, these reproductive features of PCOS were absent in DHT-treated AdBARKO females. The PCOS metabolic characteristics of increased adiposity, adipocyte hypertrophy and hepatic steatosis were induced by DHT in WT females. Despite DHT treatment, AdBARKO females displayed normal white adipose tissue weight, and adipocyte hypertrophy and hepatic steatosis were not evident. However, as with WT mice, DHT treatment induced increased fasting glucose levels in AdBARKO females. These results demonstrate that adipose tissue and the brain are key loci for androgen-mediated actions involved in the developmental origins of PCOS. These findings support targeting adipocyte and neuroendocrine AR-driven pathways in the future development of novel therapeutic strategies for PCOS.

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<![CDATA[SAT-017 Relationship Between Vitamin D Levels and Signs of Polycystic Ovary Syndrome]]> https://www.researchpad.co/article/elastic_article_6291 An analysis of the structure of the causes of infertility shows that up to almost 25% of women of reproductive age ovulation disorders are observed. Hormonal disorders leading to the absence of ovulation, began to play a leading role in the etiology of infertility, special vitamin D deficiency, while today it has been established that its D receptors (VDR) are localized in most organs, including reproductive ones. VDR affect the expression of 1000 genes and play a crucial role in the implementation of sex hormones function.

The aim of the study was to assess the vitamin D level in women of reproductive age, depending on the presence of signs of PCOS and waist circumference (WC).

71 women from 19 to 44 years old were examined of these, 41 patients were diagnosed with PCOS and impaired ovulatory function, in 30 patients the ovulatory cycle was preserved, and signs of PCOS were not detected. The level of vitamin 25 (OH) D3 in the serum of the subjects was evaluated by tandem chromato-mass spectrometry at the ArchiMed clinic of new medical technologies, Moscow.

In the recommendations of the Canadian “The Vitamin D society”, 40-60 ng/ml the optimal level of serum vitamin D, a concentration of 20-40 ng/ml insufficiency, <20 ng/ml as a deficiency.

Vitamin D deficiency was detected in 57% of women in both groups, with a pronounced deficiency (<10 ng/ml) in 17%, insufficiency was observed in 43% of cases, a sufficient level was not detected in any of the subjects. The average level of vitamin D in patients with PCOS was 18.2 (2 to 32.3) ng/ml, the value in patients without signs of PCOS was 18.5 (6.8 to 31) ng/ml.

Comparison of the vitamin D value with WC showed that in women with PCOS with an WC <80 cm the value of this indicator was 18.8 ng/ml, and for WC ≥ 80 cm it was statistically significantly lower - 13.3 ng/ml (p<0.05).

Conclusion. High prevalence of vitamin D deficiency among patients of reproductive age, with no differences in the magnitude of this indicator depending on the presence of signs of PCOS and persistent ovulation.

Difference was established between the levels of vitamin D in patients with PCOS depending on the waist circumference - its insufficiency increases with an increase in WC.

The results of the study suggest that the deficiency of vitamin D in the body increases with the aggravation of hormonal dysfunction in PCOS, which should be taken into account by specialists during the management of this category of patients and the treatment of infertility.

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<![CDATA[SAT-022 Adrenal Androgen Production Is Maintained While Ovarian Estrogens Fall Following the Final Menstrual Period in the Study of Women’s Health Across the Nation (SWAN)]]> https://www.researchpad.co/article/elastic_article_6246 The aim of this study was to clarify changes in sex steroids at the final menstrual period (FMP). We have shown previously that estradiol (E2) declines substantially in the 4-year period around the FMP, but hypothesize that testosterone (T) declines modestly and adrenal Δ5 androgens dehydroepiandrosterone (DHEA) and androstenediol (Adiol) remain unchanged. Methods: Liquid chromatography tandem mass spectrometry (LC-MS/MS) and immunoassay was used in approximately annual samples collected before and following FMP in 1490 women. We estimated time-related changes in each log-transformed androgen using piecewise linear mixed modeling, with knots (slope changes) at FMP-2 yrs and FMP+2 yrs as seen for E2. These models then were re-estimated for subgroups with different time courses identified using group-based trajectory modeling. Results: In the full sample, T was generally stable, although time course varied by subgroup, with a significant decrease of 5%/year in T in [FMP-2yrs, FMP+2yrs] only in the lowest T women. For DHEA and Adiol, declines were similar across all 3 time segments and across subgroups. Mean circulating androgen concentration declined modestly (P> 0.05) from five years before to five years following FMP. However, when stratified only the lowest 7% of circulating T declined significantly (p< 0.05) in the four years surrounding FMP when mean circulating E2 declined. This trajectory divergence of the lower circulating T suggests a different, non-adrenal source that is decreased at FMP which may be useful in clarifying ovarian versus adrenal testosterone production during the post-menopause. Paired results from samples collected before and following FMP in the same subjects indicate mean circulating E2 is less than 5% of mean circulating T suggesting that a relatively large portion of circulating E2 may be largely a result of peripheral conversion of adrenal androgens. Longitudinal LC-MS/MS analyses of circulating E2 and T indicate that the principal change in sex steroid influence at menopause is largely a decrease and dampening of ovarian and not adrenal steroid production.

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<![CDATA[SAT-024 Investigating Racial and Ethnic Comorbidity Patterns of Polycystic Ovary Syndrome]]> https://www.researchpad.co/article/elastic_article_5901 Polycystic ovary syndrome (PCOS) is a highly heterogenous reproductive endocrine disorder that affects up to 15% of women and is one of the leading causes of infertility. However, its genetic etiology remains poorly understood. Additionally, PCOS patients have a greater risk of having metabolic disorders, such as insulin resistance and cardiovascular diseases, but it is estimated that up to 75% of women remain undiagnosed. Delayed treatment and care can exacerbate comorbid conditions and be detrimental to high risk populations like African American and Hispanic women. We aim to characterize genetic and environmental variables contributing to PCOS and understand its shared etiological features with metabolic disorders. To do this, we developed two algorithms to identify diverse PCOS patients using medical records. The broad algorithm used a combination of PCOS-related billing codes (Code Based) and identified a large dataset (N = 8,340) who exhibited diverse PCOS symptoms, while the strict algorithm required PCOS keywords in addition to billing codes (Regex Based). The strict algorithm identified a smaller cohort of patients (N = 4,593) who exhibited more classically diagnoseable PCOS characteristics according to Rotterdam and NIH criteria. Using both datasets, we tested PCOS case status against 1,853 phenotypes in the medical database using a logistic regression model and identified comorbidity patterns for women of European and African descent. We observed that European descent women consistently had more distinct phenotypes associated with PCOS case status than African American women. Next, we examined the interacting effects of self-reported race on PCOS case status and found four significant phenotypes (p < 6.25e-4) in our Regex Based algorithm. African American women with PCOS had greater odds of being diagnosed with “Early onset of delivery” (p = 1.3e-4, OR = 1.86), “Hereditary hemolytic anemias” (p =1.8e-4, OR = 0.65), and “Other hereditary hemolytic anemias” (p = 3.7e-04, OR = 0.90). Meanwhile, European descent women had greater odds of being diagnosed with “Hypertensive chronic kidney disease” (p = 1.7e-04, OR = 0.68). Results show that European and African American women have unique metabolic comorbidity patterns and it may also indicate that clinical PCOS diagnostic standards vary between these groups with possible disparity-causing effects.

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<![CDATA[SAT-025 Increased Occurrence of Anemia, Gastrointestinal and Liver Diseases in Women with Turner Syndrome - a Nationwide Registry Study]]> https://www.researchpad.co/article/N5230b94b-2310-435b-b348-a151a70fa116 Background: Gastrointestinal disorders, such as celiac disease, inflammatory bowel diseases and liver disease have previously been described with increased occurrence in women with Turner syndrome. However, evidence towards increased occurrence of bleeding disorders and anemia are sparse. Likewise, the impact of hormone replacement therapy on gastrointestinal disorders remains unknown. Aim: To investigate the risk of bleeding disorders, anemia, gastrointestinal and hepatological disease in women with TS compared with the female background population and to assess the effect of HRT on these conditions. Design: National cohort study Method: 1,156 females with TS diagnosed during 1960–2014 were identified using the Danish Cytogenetic Central Registry and linked with personal-level data from the National Patient Registry and the Medication Statistics Registry. Statistics Denmark randomly identified 115,577 age-matched female controls. Negative binomial regression was used to analyze hospital discharge diagnoses. Medical prescriptions, mortality and the effect of hormone replacement therapy were estimated using stratified Cox regression. Results: The risk of anemia, coagulation disorders and gastrointestinal hemorrhage were all increased three-fold in women with TS compared with controls. Gastrointestinal disorders were twice as frequent in TS individuals, with a three-fold increased risk of inflammatory bowel disease and a twelve-fold increased risk of liver disease and elevated liver enzymes. Both gastrointestinal and hepatological mortality were increased three-fold in TS women. Conclusion: Anemia, gastrointestinal hemorrhage, inflammatory bowel disease is more frequent in women with Turner syndrome compared with controls. The risk of liver disease may be higher than previously reported.

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<![CDATA[SAT-015 Incidence and Predictors of Hypertension in a Cohort of Australian Women with and Without Polycystic Ovary Syndrome]]> https://www.researchpad.co/article/N83174307-3ed6-4939-ba87-d060858e35e0 <![CDATA[SAT-013 Segesterone Acetate (SA) Serum Levels with a Statistical Model of Continued Use of the SA/Ethinyl Estradiol (EE) Contraceptive Vaginal System]]> https://www.researchpad.co/article/N7598eebb-abb9-4658-81b4-e4a3b44e95c8 <![CDATA[SAT-020 Fluoxetine Administration Influences Serotonin-Driven Bone Remodeling During Lactation and Pregnancy Outcome in Mice]]> https://www.researchpad.co/article/Ne3e80914-28af-4819-97b4-f8f55005c4bf <![CDATA[SAT-019 The Associations of Kisspeptin with Reproductive Hormones and Oocyte Maturation in Infertile Patients Who Underwent IVF Treatment]]> https://www.researchpad.co/article/Nce2194c6-04b1-4ec3-b399-af82bbb8bd32 <![CDATA[SAT-021 Effects of E2/P4 Oral Capsules on Bone Turnover in Women with Vasomotor Symptoms]]> https://www.researchpad.co/article/N6f6ce411-75c6-4e6e-b983-d042d7ef7ca8 <![CDATA[SAT-LB2 Elevated Testosterone Secondary to Leydig Cell Hyperplasia in Bilateral Ovaries]]> https://www.researchpad.co/article/N3e4d6756-2b8b-4e95-9446-f4637de451c8 <![CDATA[SAT-LB3 Developing an Integrative Medicine Patient Care Protocol for Natural Fertility in Primary Infertile Couples: A Case Series]]> https://www.researchpad.co/article/N6b7a812e-69cb-42bd-89e2-ff0ad4731ffb <![CDATA[SAT-004 Prevalence of Abnormalities of Glucose Metabolism in Teenage Indian Girls with PCOS]]> https://www.researchpad.co/article/N508bbd59-d61a-4691-924e-04f4995b8ec5 200mg/dl), Impaired glucose tolerance (2 hour value > 140 -199 mg/dl) and Impaired fasting glucose (blood glucose level of 100–125 mg/dl) Results:Out of 106 girls with PCOS diagnosis;1 girl met criteria for diagnosis of type 2 diabetes mellitus (0.9%).15 had impaired glucose tolerance (14.1%). In addition, 2 girls with impaired glucose tolerance were also noted to have impaired fasting glucose (1.9%).Abnormalities of glucose metabolism had significant correlation with BMI(p-0.02),Waist circumference (p-0.01) and testosterone levels (p-0.02). Conclusions:In our series of adolescent PCOS subjects, we report the prevalence of abnormal glucose metabolism to be 14.1% which is quite significant. Based on our results, we recommend that all adolescent girls with a diagnosis of PCOS should undergo formal oral glucose tolerance testing. Further studies are necessary in this field, so as to make guidelines regarding the timing and frequency of this testing, as well as its utility in the clinical management of these girls. ]]> <![CDATA[SAT-027 Comparison of Estradiol by Mass Spectrometry Versus Immunoassay in Women Undergoing Menopause: Study of Womens Health Across the Nation (SWAN)]]> https://www.researchpad.co/article/N4f529bb8-51a4-4c92-944a-13ccde5be96b