Aromatase Inhibition Ameliorates Decreased LH Output Found in Obese Women.

In obese ovulatory women, serum luteinizing Hormone (LH) and follicle stimulating hormone (FSH) are lowered compared with normal weight women. This relative hypogonadotropic hypogonadism represents a potential etiology for overall decreased fertility in obesity. The objective was to determine if administration of an aromatase inhibitor (AI) to ovulating obese women would normalize LH and FSH by interrupting estradiol negative feedback.

Induction of the LH Surge in Premenarchal Girls Confirms Early Maturation of the Hypothalamic-Pituitary-Ovarian Axis.

Purpose: To determine whether premenarchal girls exhibit positive estradiol feedback similar to regularly cycling adult women when given exogenous estradiol.

Methods: This was a prospective clinical cohort study at 2 institutions. Nine girls and 6 women received a 7-day course of transdermal estradiol designed to produce physiologic, mid-cycle circulating estradiol levels.

Evidence for disruption of normal circadian cortisol rhythm in women with obesity.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis may play a role in the pathogenesis of comorbidities encountered in obesity, including the relative hypogonadotropic hypogonadism that we and others have observed. We sought to examine serum cortisol profiles throughout the day and evening in a sample of normal weight women and women with obesity. In this cross-sectional study, regularly cycling obese (n = 12) and normal weight (n = 10) women were recruited.

Acute recapitulation of the hyperinsulinemia and hyperlipidemia characteristic of metabolic syndrome suppresses gonadotropins.

Objective: To determine the effect of lipid/heparin versus saline infusion, with or without concurrent euglycemic hyperinsulinemia, on serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Obesity is associated with hyperlipidemia, insulin resistance, and relative hypogonadotropic hypogonadism. It was hypothesized that acutely elevated fatty acids and insulin would impair gonadotropin secretion.

Corpus luteum as a novel target of weight changes that contribute to impaired female reproductive physiology and function.

Unlabelled: Obesity and malnutrition are associated with decreased fecundity in women. Impaired reproductive capacity in obese women is often attributed to anovulation. However, obese women with ovulatory cycles also have reduced fertility, but the etiology of their impaired reproduction is only partially understood.

Use of a levonorgestrel-containing intrauterine system with supplemental estrogen improves symptoms in perimenopausal women: a pilot study.

Objective: The aim of this study was to compare perimenopausal symptomatology using a levonorgestrel-containing intrauterine system (LNG-IUS) + low-dose transdermal estradiol (TDE) with LNG-IUS alone.

Methods: The trial was a double-blind, randomized, controlled pilot trial. Regularly cycling women aged 38 to 52 years, with at least one self-reported symptom (hot flashes, bloating, headache, adverse mood, or poor sleep), were randomized to either LNG-IUS + low-dose TDE gel (intervention) or LNG-IUS alone (control).

Omega-3 Fatty Acid Supplementation Lowers Serum FSH in Normal Weight But Not Obese Women.

Context: Dietary omega-3 fatty acids delay ovarian aging and promote oocyte quality in mice.

Objective: To test whether dietary supplementation with omega-3 polyunsaturated fatty acids (PUFA) modulates reproductive hormones in reproductive-age women.

Design: Prospective interventional study.

Estradiol Priming Improves Gonadotrope Sensitivity and Pro-Inflammatory Cytokines in Obese Women.

Context: Obesity is associated with a pro-inflammatory state and relative hypogonadotropic hypogonadism. Estrogen (E2) is a potential link between these phenomena because it exhibits negative feedback on gonadotropin secretion and also inhibits production of pro-inflammatory cytokines.

Objective: We sought to examine the effect of estrogen priming on the hypothalamic-pituitary-ovarian axis in obesity.

Joint MiRNA/mRNA expression profiling reveals changes consistent with development of dysfunctional corpus luteum after weight gain.

Obese women exhibit decreased fertility, high miscarriage rates and dysfunctional corpus luteum (CL), but molecular mechanisms are poorly defined. We hypothesized that weight gain induces alterations in CL gene expression. RNA sequencing was used to identify changes in the CL transcriptome in the vervet monkey (Chlorocebus aethiops) during weight gain.

Adiposity Alters Genes Important in Inflammation and Cell Cycle Division in Human Cumulus Granulosa Cell.

Objective: To determine whether obesity alters genes important in cellular growth and inflammation in human cumulus granulosa cells (GCs).

Methods: Eight reproductive-aged women who underwent controlled ovarian hyperstimulation followed by oocyte retrieval for in vitro fertilization were enrolled. Cumulus GC RNA was extracted and processed for microarray analysis on Affymetrix Human Genome U133 Plus 2.

Measurement of estradiol, estrone, and testosterone in postmenopausal human serum by isotope dilution liquid chromatography tandem mass spectrometry without derivatization.

Background: A high-throughput, sensitive, specific, mass spectrometry-based method for quantitating estrone (E1), estradiol (E2), and testosterone (T) in postmenopausal human serum has been developed for clinical research. The method consumes 100μl human serum for each measurement (triplicates consume 300μl) and does not require derivatization. We adapted a commercially available 96-well plate for sample preparation, extraction, and introduction into the mass spectrometer on a single platform.

Evidence of GnRH antagonist escape in obese women.

Context: Assisted reproductive technology (ART) cycle cancelation rates are increased among overweight and obese women; however, the reasons for this are not completely clear. Premature luteinization due to inadequate endogenous gonadotropin suppression is a possibility for this higher risk of cancellation.

Objective: The objective of the study was to investigate the impact of female obesity on the pharmacokinetics of cetrorelix (GnRH antagonist).

Luteal phase dynamics of follicle-stimulating and luteinizing hormones in obese and normal weight women.

Objectives: Female obesity is a state of relative hypogonadotrophic hypogonadism. The aim of this study is to examine gonadotrophin secretion and response to gonadotrophin-releasing hormone (GnRH) in the luteal phase of the menstrual cycle and to investigate the pharmacodynamics and pharmacokinetics of endogenous and exogenous luteinizing hormone (LH) in obese women.

Design: Participants underwent a luteal phase frequent blood sampling study.

Profound reduction of ovarian estrogen by aromatase inhibition in obese women.

Objective: It was hypothesized that aromatase inhibitor (AI)-induced interruption of estradiol negative feedback would modulate the reproductive hormone profile of obese women.

Methods: Regularly cycling women aged 18-40 years with a BMI of 18-25 kg/m(2) (normal weight, n = 10) or >30 kg/m(2) (obese; n = 12) were given AI daily for 7 days. Urinary hormone profiles were compared between groups.