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Completed

NCT Number: NCT01381016

Estrogen Sensitivity and Ovulatory Dysfunction in Obesity

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.

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Key information

Conditions

Obesity Body Weight Genital Diseases Infertility Nutrition Disorders Nutritional and Metabolic Diseases Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms Urogenital Diseases

Age range

18 year–42 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

University of Colorado, Anschutz Medical Campus

Aurora, Colorado, 80045, United States

About this study

  • 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).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Estradiol

Drug

Subjects were instructed to apply 0.1 mg/d transdermal estrogen for one month.

Other names: Climara, transdermal estrogen

Gonadotropin-releasing hormone (GnRH)

Drug

Pituitary response was assessed to determine how estradiol administration alters pituitary sensitivity to GnRH.

Other names: Lutrelef or gonadorelin acetate

Progesterone

Drug

Subjects who failed to initiate a menstrual period following 40 days on the patch were instructed to take 200 mg daily of progesterone for 10 days or as long as deemed necessary.

Other names: Prometrium or medroxyproge sterone acetate

Primary outcomes

  1. Luteinizing Hormone Pulse Amplitude

    Time frame: Baseline

    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.

  2. Luteinizing Hormone Pulse Amplitude

    Time frame: Post estradiol at one month

Sponsors and collaborators

Lead sponsor

University of Colorado, Denver

Other

Registry information

Important dates

Study start
2011
Primary completion
2013
Study completion
2013
First posted
Jun 27, 2011
Registry last updated
Apr 20, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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