Estrogen Sensitivity and Ovulatory Dysfunction in Obesity
This study is ongoing, but not recruiting participants.
Sponsor:
University of Colorado, Denver
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01381016
First received: June 22, 2011
Last updated: March 15, 2013
Last verified: March 2013
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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:
MedlinePlus related topics:
Obesity
Drug Information available for:
Estradiol
Estradiol cypionate
Estradiol valerate
Estradiol acetate
Gonadorelin
Estradiol hemihydrate
Gonadorelin hydrochloride
U.S. FDA Resources
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 2013 |
| Estimated Primary Completion Date: | October 2013 (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 More Information
Additional Information:
Publications:
| 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: | March 15, 2013 |
| 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 May 23, 2013