Reproductive Hormonal Alterations in Obesity

University of Colorado Denver (CU Denver)

Status: Completed

Conditions: Obesity

Treatments: Drug: Recombinant LH; Drug: Letrozole; Drug: Cetrorelix; Drug: Gonadorelin-GnRH

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01457703

U54HD058155 (U.S. NIH Grant/Contract)

09-0977

Details and patient eligibility

About

The purpose of this study is to determine why obese women have lower hormone levels and less fertility than women of normal body weight. The proposal will examine the reproductive system at the level of the brain and the ovary to define the changes that happen leading to lowered hormone production. Women will be studied throughout a menstrual cycle and given medications that will test how well their pituitary gland can make hormones that stimulate the ovary (luteinizing hormone (LH) and follicle stimulating hormone (FSH)). They will also be given a medication to abolish estrogen production in the body and their response to this medication will be assessed. Finally, the ovary's ability to produce progesterone after ovulation will be examined.

--Hypotheses:

1. Obese women have reduced pituitary sensitivity to exogenous gonadotropin-releasing hormone (GnRH), but normal clearance of exogenous LH. (comparative study of obese compared to normal weight women)
2. Obese women have abnormally increased sensitivity to estradiol negative feedback which will be reversed by an aromatase inhibitor. (comparative study of obese compared to normal weight women)

Full description

AIM 1: test the hypothesis that reduced pituitary sensitivity to GnRH-induced LH and FSH secretion causes the relative hypogonadotropic hypogonadism of obesity AIM 2: test the hypothesis that the hypothalamic-pituitary axis is abnormally sensitive to estradiol negative feedback in obesity

Enrollment: 62 patients

Sex: Female

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Aged 18-40 at study entry
• BMI either 18-25 kg/m2 or ≥30 kg/m2
• prolactin (PRL) and thyroid-stimulating hormone (TSH) within normal laboratory ranges at screening
• Baseline hemoglobin >11 gm/dl
• History of regular menstrual cycles every 25-35 days if BMI 18-25 kg/m2
• History of regular menstrual cycles every 25-40 days if BMI ≥30 kg/m2

Exclusion criteria

• History of chronic disease affecting hormone production, metabolism or clearance
• Use of medications that are known to alter or interact with reproductive hormones (e.g., thiazolidinediones, metformin)
• Use of hormones within three months of enrollment
• Excessive exercise (>4 hours per week)
• Pregnancy, breast-feeding or current active attempts to conceive

Trial design

62 participants in 2 patient groups

BMI ≥30 kg/m2

Active Comparator group

Description:

Group 2: * BMI ≥30 kg/m2 * History of regular menstrual cycles every 25-40 days Gonadorelin-GnRH (Lutrepulse), GnRH antagonists - Cetrorelix (Cetrotide), Recombinant LH (Luveris) were administered in Aim 1. GnRH or gonadorelin (Lutrepulse) and Letrozole were administered in Aim 2.

Treatment:

Drug: Gonadorelin-GnRH

Drug: Letrozole

Drug: Cetrorelix

Drug: Recombinant LH

BMI 18-25 kg/m2

Experimental group

Description:

* BMI 18-25 kg/m2 * History of regular menstrual cycles every 25-35 days Gonadorelin-GnRH (Lutrepulse), GnRH antagonists - Cetrorelix (Cetrotide), Recombinant LH (Luveris) were administered in Aim 1. GnRH or gonadorelin (Lutrepulse) and Letrozole were administered in Aim 2.

Treatment:

Drug: Gonadorelin-GnRH

Drug: Letrozole

Drug: Cetrorelix

Drug: Recombinant LH