Reproductive Hormonal Alterations in Obesity, AIMS #1 & #2
Overview
- Phase
- Not Applicable
- Intervention
- Cetrorelix
- Conditions
- Obesity
- Sponsor
- University of Colorado, Denver
- Enrollment
- 62
- Locations
- 1
- Primary Endpoint
- Changes in Luteinizing Hormone (LH) Pulse Amplitude (Aim 1)
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
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:
- 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)
- 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)
Detailed 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
Investigators
Eligibility Criteria
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
Arms & Interventions
BMI ≥30 kg/m2
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.
Intervention: Cetrorelix
BMI ≥30 kg/m2
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.
Intervention: Gonadorelin-GnRH
BMI ≥30 kg/m2
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.
Intervention: Recombinant LH
BMI ≥30 kg/m2
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.
Intervention: Letrozole
BMI 18-25 kg/m2
* 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.
Intervention: Cetrorelix
BMI 18-25 kg/m2
* 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.
Intervention: Gonadorelin-GnRH
BMI 18-25 kg/m2
* 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.
Intervention: Recombinant LH
BMI 18-25 kg/m2
* 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.
Intervention: Letrozole
Outcomes
Primary Outcomes
Changes in Luteinizing Hormone (LH) Pulse Amplitude (Aim 1)
Time Frame: Measured hourly and averaged over the 12 hour study visit
Luteinizing Hormone (LH) Pulse Amplitude was measured hourly during the 12 hour study visit, and was compared between the obese and normal weight groups.
Changes in Luteinizing Hormone (LH) Pulse Amplitude (Aim 2)
Time Frame: Measured hourly and averaged over the 12 hour study visit
Luteinizing Hormone (LH) Pulse Amplitude was measured hourly during the 12 hour study visit, and was compared between the obese and normal weight groups.
Changes in Pregnanediol Glucuronide (PdG) (Aim 2)
Time Frame: Averaged over the length of menstrual cycle
Pregnanediol glucuronide (PdG) was collected daily over the course of one menstrual cycle and averaged.
Secondary Outcomes
- Changes in Follicle Stimulating Hormone (FSH) (Aim 1)(Measured hourly and averaged over the 12 hour study visit)
- Changes in Follicle Stimulating Hormone (FSH) (Aim 2)(Measured hourly and averaged over the 12 hour study visit)