Reproductive Hormonal Alterations in Obesity

November 15, 2016 updated by: University of Colorado, Denver

Reproductive Hormonal Alterations in Obesity, AIMS #1 & #2

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)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

62

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Clinical Translational Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Drug: Cetrorelix
Abolishes pituitary sensitivity to GnRH.
Other Names:
  • Cetrotide
Drug: Gonadorelin-GnRH
GnRH is used to stimulate the pituitary gland to produce LH and FSH.
Other Names:
  • Lutrepulse
Drug: Recombinant LH
Used to stimulate ovarian function in women.
Other Names:
  • Luveris
Drug: Letrozole
An aromatase inhibitor.
Other Names:
  • Femara
Experimental: 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.
Drug: Cetrorelix
Abolishes pituitary sensitivity to GnRH.
Other Names:
  • Cetrotide
Drug: Gonadorelin-GnRH
GnRH is used to stimulate the pituitary gland to produce LH and FSH.
Other Names:
  • Lutrepulse
Drug: Recombinant LH
Used to stimulate ovarian function in women.
Other Names:
  • Luveris
Drug: Letrozole
An aromatase inhibitor.
Other Names:
  • Femara

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Measured hourly and averaged over the 12 hour study visit
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.
Measured hourly and averaged over the 12 hour study visit
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.
Averaged over the length of menstrual cycle

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Follicle Stimulating Hormone (FSH) (Aim 1)
Time Frame: Measured hourly and averaged over the 12 hour study visit
Follicle-stimulating hormone was measured hourly during the 12 hour study visit, and was compared between the obese and normal weight groups.
Measured hourly and averaged over the 12 hour study visit
Changes in Follicle Stimulating Hormone (FSH) (Aim 2)
Time Frame: Measured hourly and averaged over the 12 hour study visit
Follicle-stimulating hormone was measured hourly during the 12 hour study visit, and was compared between the obese and normal weight groups.
Measured hourly and averaged over the 12 hour study visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Colorado, Denver

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

  • Principal Investigator: Nanette Santoro, MD, University of Colorado, Denver

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2010

Primary Completion (Actual)

July 1, 2013

Study Completion (Actual)

July 1, 2013

Study Registration Dates

First Submitted

September 21, 2011

First Submitted That Met QC Criteria

October 20, 2011

First Posted (Estimate)

October 24, 2011

Study Record Updates

Last Update Posted (Estimate)

January 12, 2017

Last Update Submitted That Met QC Criteria

November 15, 2016

Last Verified

November 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 09-0977
  • U54HD058155 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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