Dysregulation of FSH in Obesity: Functional and Statistical Analysis

Not Applicable

Completed

• Conditions: Obesity; Fertility
• Interventions: Drug: Degarelix (GnRH antagonist); Drug: recombinant FSH; Drug: Cetrorelix

• Registration Number: NCT02478775
• Lead Sponsor: University of Colorado, Denver

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2015-05-07
• Study First Submitted QC: 2015-06-18
• Study First Posted: 2015-06-23
• Study Start: 2015-07
• Primary Completion: 2021-06-30
• Study Completion: 2021-06-30
• Results First Submitted: 2022-01-12
• Results First Submitted QC: 2022-03-15
• Results First Posted: 2022-04-07
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-10
• Last Update Posted: 2024-06-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 99

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Frequent Blood Sampling, Degarelix	Degarelix (GnRH antagonist)	Investigators will assess the change in inhibin B levels following repeated bolus dosing of recombinant FSH (rFHS) following Degarelix (GnRH antagonist) blockade over a 2-day period. This arm was terminated due to Adverse Events and the study was continued with the Cetrorelix product.
Frequent Blood Sampling, Cetrorelix	recombinant FSH	Investigators will assess the change in inhibin B levels following repeated bolus dosing of recombinant FSH (rFHS) following Cetrorelix blockade over a 2-day period.
Frequent Blood Sampling, Degarelix	recombinant FSH	Investigators will assess the change in inhibin B levels following repeated bolus dosing of recombinant FSH (rFHS) following Degarelix (GnRH antagonist) blockade over a 2-day period. This arm was terminated due to Adverse Events and the study was continued with the Cetrorelix product.
Frequent Blood Sampling, Cetrorelix	Cetrorelix	Investigators will assess the change in inhibin B levels following repeated bolus dosing of recombinant FSH (rFHS) following Cetrorelix blockade over a 2-day period.

Primary Outcome Measures

Name	Time	Method
Difference Between Peak Inhibin B	Every 10 minutes over 2 10-hour frequent blood sampling sessions.	This is defined as the maximum hormone value during Day 1 of the study subtracted from the maximum hormone value during Day 2.

Secondary Outcome Measures

Name	Time	Method
Peak Inhibin B Per Subject	Every 10 minutes over 10 hours on Day 1 and Day 2 of the study.	Peak inhibin B will be measured every 10 minutes during day 1 and day 2 of the study. The highest inhibin B value will be defined as the peak.
Peak E2 Per Subject	Every 10 minutes over 10 hours of Day 1 and Day 2 of the study.	E2 will be measured every 10 minutes on Day 1 and Day 2 of the study. The highest E2 value will be designated as the peak E2 value.

Trial Locations

Locations (1)

University of Colorado Clinical and Translational Research Center; 🇺🇸 Aurora, Colorado, United States