Abstract

Polycystic ovary syndrome is one of the most common endocrine disorders in women of reproductive age. Features of PCOS are hyperandrogenism, chronic anovulation and polycystic ovaries on ultrasonography. Follicle development is a complex and carefully orchestrated phenomenon, involving gonadotropins and a rapidly expanding list of other intraovarian regulators, such as brain-derived neurotrophic factor (BDNF). The aim of this study is to evaluate BDNF in plasma and in follicular fluid in women affected by PCOS and in normal menstruating women. In PCOS patients the BDNF levels in plasma and in follicular fluid are higher than values obtained in healthy controls. Therefore we can hypothsize that high levels of luteinizing hormone, probably increase the secretion of BDNF in PCOS patients.

Abstract

Objectives: The primary objective of this multicenter study is to evaluate the relative impact of insulin resistance (IR) and body mass index (BMI) in women with polycystic ovary syndrome (PCOS) on (1) Key hemodynamic/thrombogenic variables, (2) Oocyte quality and early embryo development, (3) Fetal growth, placental function and adverse obstetric outcome.
Secondary objective: To establish a PCOS database and biobank facilitating future basic and interventional research related to PCOS.
Design: A cross-sectional and longitudinal cohort study at four University Hospitals in Denmark.
Population inclusion: About 200 women fulfilling the Rotterdam Criteria and 100 women without PCOS recruited from 2010 to 2012.
Methods: The impact of PCOS, as well as the impact of IR and BMI on the hormonal, metabolic and hemostatic key variables will be analyzed combining conventional, molecular techniques and selected gene analysis. Oocytes will be characterized by gene expression of granulosa and cumulus cells and the early embryo development will be followed by time lapse microscopy. Fetal growth will be assessed by repeated ultrasound measurements, and the pregnancy outcome compared to maternal and fetal biochemical markers of growth and inflammation and clinical pregnancy complications.
Main outcome measures: Metabolic and hemostatic risk-biomarkers, oocyte and embryo quality, adverse pregnancy outcome, fetal growth and placental function in women with PCOS.

Abstract

The polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disorder, also associated with the metabolic syndrome. Serum high sensitivity C-reactive protein (hs-CRP), a marker of low-grade chronic inflammation is a potent predictor of cardiovascular events, closely linked to metabolic syndrome features and higher in patients with PCOS. However, hs-CRP in lean patients with PCOS has not been fully evaluated and few data are available. We aimed to investigate the relation between glucose intolerance and hs-CRP levels in lean patients with PCOS, and to evaluate the possible relationship between hs-CRP and PCOS by evaluating PCOS-related metabolic abnormalities in Korean women. We consecutively recruited 115 lean (BMI < 25kg/m2) patients diagnosed with PCOS and 103 lean healthy controls. The PCOS group was divided two groups: impaired glucose regulation (IGR) and normal glucose tolerance group (NGT). In lean patients with PCOS, hs-CRP level was higher in the IGR group than in the NGT group (0.60 ± 1.37 versus 0.18 ± 0.46, pBonf = 0.023) and other metabolic risk factors were also higher in the IGR group than in the NGT group. And there were close relationships between hs-CRP level and metabolic risk factor, such as 2 h postprandial insulin level in the lean patients with PCOS.

Abstract

Context: Functional hypothalamic amenorrhea (FHA) related to hypoestrogenism and hormonal status may influence skeletal homeostasis and body composition. The study aimed to evaluate hormones concentrations, body composition and bone strength in FHA cases.
Patients and methods: Total body scans using DXA method (DPX-L, GE Lunar) were performed
in a group of 27 women aged 21.8 years ± 3.9 with FHA related to weight loss. References of healthy control subjects were used to calculate Z-scores (age and gender matched), SD-scores (height and gender matched), and SDs-scores (weight and gender matched). Whole skeleton bone mineral content (TBBMC, g) and density (TBBMD, g/cm2), lumbar spine (L2–L4) bone mineral density (SBMD; g/cm2), lean body mass (LBM, g) and fat mass (FM, g) were investigated. Relative bone strength index was calculated as the TBBMC/LBM ratio. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, testosterone, and prolactin (PRL) concentrations were assayed to characterize hormonal profile of FHA cases.
Results: Hormonal evaluation in patients with FHA revealed significantly decreased serum concentrations of gonadotropins and estradiol. Serum LH concentrations were 1.47 ± 0.89 mIU/ml, FSH 4.44 ± 1.94 mIU/ml. Estradiol concentrations in serum were 27.08 ± 13.10 pg/ml. As evidenced by Z-scores, FHA cases had decreased SBMD, TBBMD and TBBMC Z-scores of −1.23 ± 0.90 (p < 0.0001), −0.72 ± 0.86 (p < 0.001), and −0.90 ± 1.40 (p < 0.01), respectively. Reduced FM, LBM and FM/LBM ratio Z-scores of −1.80 ± 2.28 (p < 0.001), −0.59 ± 1.49 (p < 0.05) and −0.74 ± 1.55 (p < 0.05), but not TBBMC/LBM Z-score of −0.54 ± 2.14 (ns) were noted in FHA cases compared with healthy control cases. TBBMC, TBBMD, TBBMC/LBM when BH- or BW-matched were normal as evidenced by SD-scores and SDs-scores. SBMD remained reduced when BH-matched (SD-score = –0.40 ± 0.86; p < 0.05) whereas FM and FM/LBM were lower than expected in healthy, both compared to BH and BW-dependent references. The length of amenorrhea in months negatively correlated with SBMD Z-score (R = –0.39, p < 0.05), and SD-scores for SBMD (R = –0.48), TBBMD (R = –0.43), TBBMC (R = –0.46) (all p < 0.05) and positively with SDs-scores for FM (R = 0.44, p < 0.05).
Conclusion: Patients with FHA were characterized by lower concentrations of serum FSH, LH and estradiol concentrations. Moreover, FHA cases had decreased FM and an imbalanced relationship between BW, FM, and LBM. Despite reduced BMD and BMC, bone strength was not significantly affected by FHA.

Abstract

Context: Obesity has emerged as one of the leading medical challenges of the 21st century. The resistance of this disorder to effective, long-term treatment can be traced to the fact that body fat stores are subject to homeostatic regulation in obese individuals, just as in lean individuals. Because the growing obesity epidemic is linked to a substantial increase in daily energy intake, a key priority is to delineate how mechanisms governing food intake and body fat content are altered in an obesogenic environment.
Evidence Acquisition: We considered all relevant published research and cited references that represented the highest quality evidence available. Where space permitted, primary references were cited.

Evidence Synthesis: The increase of energy intake that has fueled the U.S. obesity epidemic is linked to greater availability of highly rewarding/palatable and energy-dense food. Obesity occurs in genetically susceptible individuals and involves the biological defense of an elevated body fat mass, which may result in part from interactions between brain reward and homeostatic circuits. Inflammatory signaling, accumulation of lipid metabolites, or other mechanisms that impair hypothalamic neurons may also contribute to the development of obesity and offer a plausible mechanism to explain the biological defense of elevated body fat mass.
Conclusions: Despite steady research progress, mechanisms underlying the resistance to fat loss once obesity is established remain incompletely understood. Breakthroughs in this area may be required for the development of effective new obesity prevention and treatment strategies.

Abstract

Context: Functional ovarian reserve (FOR) has recently been demonstrated to differ with ovarian genotypes of the FMR1 gene and is currently routinely determined with anti-Müllerian hormone (AMH) and FSH. Both, however, reflect distinctively different stages of folliculogenesis.
Objectives: To better understand how AMH and FSH reflect FOR, we evaluated both hormones in association with in vitro fertilization (IVF) by determining how they associate with oocyte yields, considered the most accurate available measure of FOR.
Design and Setting: Using a series of logistic regressions, we assessed AMH and FSH per oocyte retrieved (AMHo and FSHo) in only first IVF cycles and determined whether at different ages and/or based on ovarian FMR1 genotypes and subgenotypes AMHo and/or FSHo are associated with clinical pregnancy chances in IVF.

Patients: We investigated 392 consecutive IVF patients of all ages, with among them 60.7% suffering from diminished FOR.
Interventions: Interventions included routine IVF cycles.
Main Outcome Measure: Clinical pregnancy rate in IVF cycle was assessed.
Results: FSHo, but not AMHo, was, overall, statistically associated with pregnancy chances in IVF. This association was further limited to women above age 38 yr. FSHo was also significantly associated with pregnancy chances in women with normal FMR1 genotype, although only almost reaching significance with heterozygous-normal/low. Normal-genotype patients also demonstrate significant interaction between FSHo and age in pregnancy outcome, although insignificant for all other FMR1 genotypes and subgenotypes and universally for AMHo.
Conclusions: AMHo and FSHo are representative of distinctively different components of FOR, likely influenced by different ovarian FMR1 genotypes and subgenotypes

Abstract

BACKGROUND Premature ovarian failure (POF) is currently managed by non-physiological sex steroid regimens which are inadequate at optimizing uterine characteristics. Previous short-term studies have demonstrated some benefits of a sex steroid replacement (SSR) regimen devised to replicate the physiological cycle. This study aimed to directly compare the effects of longer-term administration of physiological SSR (pSSR) and standard SSR (sSSR) regimens on the uterine volume, blood flow and endometrial thickness (ET) in women with POF.

METHODS In a controlled crossover trial, 34 women with POF were randomized to receive 12 months of 4-week cycles of transdermal estradiol and vaginal progesterone (pSSR) followed by 12 months of 4-week cycles of oral ethinylestradiol and norethisterone (sSSR), or vice versa. Each treatment period was preceded by a 2-month washout period. At 0, 3, 6 and 12 months of each treatment period, transvaginal ultrasound examined the uterine volume and ET, as primary end-points, and uterine artery resistance (UARI) and pulsatility indices (UAPI), as secondary end-points. Serum estradiol, progesterone and gonadotrophins were also measured.

RESULTS Of the 29 women eligible for the uterine analysis, 17 completed the entire study protocol, but 25 women contributed data to statistical analysis of treatment effect. There was a greater estimated mean ET with the use of pSSR (4.8 mm) compared to that with standard therapy (3.0 mm), with an estimated difference of 1.8 mm [95% confidence interval (CI), 0.7 to2.8, P=0.002]. The estimated mean uterine volume was also greater during physiological treatment (24.8 cm3) than during standard treatment (20.6 cm3), but the estimated difference of 4.2 cm3 (95% CI −0.4 to 8.7) was not statitsically significant, P=0.070. The small differences between the two treatments in the mean UARI and mean UAPI were not statistically significant. The estimated treatment differences were fairly constant across the treatment periods, suggesting that prolonged treatment does not increase response.

CONCLUSIONS pSSR has a greater beneficial effect upon ET in women with POF in comparison with standard therapy. A similar trend was seen for uterine volume. Further studies are required to optimize treatment and to assess pregnancy rate and outcome.

Abstract

Background: An increased risk of breast cancer is associated with alcohol consumption; however, it is controversial whether red wine increases this risk. Aromatase inhibitors (AIs) prevent the conversion of androgens to estrogen and occur naturally in grapes, grape juice, and red, but not white wine. We tested whether red wine is a nutritional AI in premenopausal women.

Methods: In a cross-over design, 36 women (mean age [SD], 36 [8] years) were assigned to 8 ounces (237 mL) of red wine daily then white wine for 1 month each, or the reverse. Blood was collected twice during the menstrual cycle for measurement of estradiol (E2), estrone (E1), androstenedione (A), total and free testosterone (T), sex hormone binding globulin (SHBG), luteinizing hormone (LH), and follicle stimulating hormone (FSH).

Results: Red wine demonstrated higher free T vs. white wine (mean difference 0.64 pg/mL [0.2 SE], p=0.009) and lower SHBG (mean difference −5.0 nmol/L [1.9 SE], p=0.007). E2 levels were lower in red vs. white wine but not statistically significant. LH was significantly higher in red vs. white wine (mean difference 2.3 mIU/mL [1.3 SE], p=0.027); however, FSH was not.

Conclusion: Red wine is associated with significantly higher free T and lower SHBG levels, as well as a significant higher LH level vs. white wine in healthy premenopausal women. These data suggest that red wine is a nutritional AI and may explain the observation that red wine does not appear to increase breast cancer risk.