Dysregulation of FSH in Obesity: Functional and Statistical Analysis

Dysregulation of Follicle Stimulating Hormone (FSH) in Obesity: Functional and Statistical Analysis

Excess maternal weight, especially obesity, influences almost every aspect of fertility, from conception to problems during pregnancy. The investigators will use novel statistical methods to clarify the hormonal changes behind reproductive health conditions. A better understanding of reproductive hormonal changes in obese women may offer a way to identify new treatments.

Hypothesis. Insufficient FSH (Follicle-stimulating hormone) pulsatility, as seen in obesity, results in inadequate folliculogenesis and reduced ovarian steroid and protein production.

AIM: To test the hypothesis that insufficient FSH pulsatility, as seen in obesity, results in inadequate folliculogenesis and reduced ovarian steroid and protein production. The investigators will determine if exogenous FSH administered in a pulsatile fashion results in a significant increase of ovarian hormones in obese women. Serial inhibin B and E2 levels will be measured in obese and normal weight women undergoing frequent blood sampling studies before and after GnRH (Gonadotropin-releasing hormone) antagonist blockade.

Inclusion Criteria:

• Age between 21 to 39 years old with regular menstrual cycles every 25-40 days
• Body mass of 18.5 kg/m2-24.9kg/m2 (normal weight controls) or greater than 30.0 kg/m2 (obese group)
• Prolactin and thyroid-stimulating hormone (TSH) within normal laboratory ranges at screening
• Baseline hemoglobin >11 gm/dl.

Exclusion Criteria:

• Diagnosis of polycystic ovary syndrome (PCOS), defined by the 2003 Rotterdam criteria as suggested by 2012 NIH Workshop
• History of chronic disease affecting hormone production, metabolism or clearance or use of thiazolidinediones or metformin (known to interact with reproductive hormones)
• Use of hormones affecting hypothalamic-pituitary-gonadal (HPO) axis (such as hormonal contraceptives) within 3 months of entry
• Strenuous exercise (>4 hours of intense physical activity per week)
• Pregnancy
• Breast-feeding
• Current attempts to conceive
• Significant recent weight loss or gain