Estrogen Sensitivity and Ovulatory Dysfunction in Obesity

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01381016
First received: June 22, 2011
Last updated: January 24, 2014
Last verified: January 2014
  Purpose

The sole purpose of this study is to evaluate pathophysiology of disease. The disease state that is being evaluated is the obesity-related alterations in reproductive hormones

  • The obesity epidemic in the United States is advancing at an accelerated pace. It is estimated that by 2015, 41% of U.S. adults will be obese as defined by a body mass index (BMI) of greater than 30 kg/m2. The U.S. government's 2010 Dietary Guidelines regard obesity as the single greatest health hazard in this century. Female adult obesity is associated with menstrual cycle irregularities, ovulatory dysfunction and a higher risk of obstetrical complications. This reproductive phenotype of obesity is worsened by further increases in BMI and is not solely due to anovulatory infertility. While the association of adiposity with subfertility is well documented in population studies, the underlying mechanisms remain poorly understood. The main objective of this proposal is to clarify the nature of the obesity-related reproductive endocrine abnormalities and identify potential etiologies amenable to therapy.
  • Hypothesis: The hypothalamic-pituitary axis is abnormally sensitive to estradiol negative feedback in obesity.

Condition Intervention
LH Pulsatility
Obesity
Reproduction
Drug: Estradiol, Lutrelef or gonadorelin

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Estrogen Sensitivity and Ovulatory Dysfunction in Obesity

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Luteinizing hormone pulse amplitude [ Time Frame: 1-2 Years ] [ Designated as safety issue: No ]
    The study is powered on luteinizing hormone pulse amplitude because it is the clinical outcome for which the most data is available. The primary comparison is whether there is a significant reduction in the pulse amplitude in the obese between the pre- and post-treatment periods and whether there is no change in the pulse amplitude in the normal weight patients between the pre and post-treatment periods.


Estimated Enrollment: 20
Study Start Date: June 2011
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Control
Group 1 "Control": Normal weight (BMI 18-25 kg/m2)
Drug: Estradiol, Lutrelef or gonadorelin
Other Name: Climara, GnRH
Experimental: Experimental
Group 2 "Experimental": Obese (BMI >30 kg/m2)
Drug: Estradiol, Lutrelef or gonadorelin
Other Name: Climara, GnRH

Detailed Description:
  • Design: paired assessments Pre and Post estrogen administration in obese and normal weight women
  • AIM 1: To test the pituitary and hypothalamic responsiveness in obesity, we will examine the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) pulsatility during frequent blood sampling.
  • AIM 2: To test the ovarian responsiveness in obesity, we will examine urinary reproductive hormones (E1c, estrone conjugates, and Pdg, pregnanediol glucuronide) over an entire menstrual cycle.
  • AIM 3: To test the hypothesis that central adiposity is associated with reproductive hormone alterations in obesity, we will quantitatively assess body composition by dual energy x-ray absorptiometry (DXA).
  Eligibility

Ages Eligible for Study:   18 Years to 42 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 18-42 at study entry
  • Regular menstrual cycles every 25-40 days
  • BMI 18- 25 kg/m2 or ≥30kg/m2
  • Good general health
  • Prolactin and thyroid-stimulating hormone (TSH) within normal laboratory ranges at screening
  • Baseline hemoglobin >11 gm/dl.

Exclusion Criteria:

  • Positive screen for Activated Protein C resistance
  • Any contraindications to exogenous estrogen, including previous thromboembolic events or stroke, history of an estrogen-dependent tumor, active liver disease, undiagnosed abnormal uterine bleeding, hypertriglyceridemia, smoking, hypertension
  • History of chronic disease affecting hormone production, metabolism or clearance (including diabetes mellitus) or abnormal renal or liver function at screening, such as elevated aspartate or alanine aminotransferases or elevated blood urea nitrogen (BUN) or creatinine
  • Current use of thiazolidinediones or metformin (known to interact with reproductive hormones)
  • Use of hormones affecting hypothalamic-pituitary ovarian axis within three months of enrollment
  • Strenuous exercise (>4 hours per week)
  • Pregnancy, breast-feeding or current active attempts to conceive
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01381016

Locations
United States, Colorado
University of Colorado, Anschutz Medical Campus
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01381016     History of Changes
Other Study ID Numbers: 11-0293
Study First Received: June 22, 2011
Last Updated: January 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Colorado, Denver:
LH pulsatility
Obesity
Reproduction

Additional relevant MeSH terms:
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Estradiol
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 25, 2014