Estrogen Sensitivity and Ovulatory Dysfunction in Obesity

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-06-30

Study Completion Date

2013-01-31

Brief Summary

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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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Detailed Description

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* 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).

Conditions

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Obesity Infertility

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Group 1 - Normal Weight

Group 1: Normal weight (BMI 18-25 kg/m2)

Subjects were instructed to apply 0.1 mg/d transdermal estrogen (Estradiol) for one month. Pituitary response was assessed to determine how estradiol administration altered pituitary sensitivity to Gonadotropin-releasing hormone - GnRH. 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.

Group Type OTHER

Estradiol

Intervention Type DRUG

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

Gonadotropin-releasing hormone (GnRH)

Intervention Type DRUG

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

Progesterone

Intervention Type 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.

Group 2 - Obese

Group 2: Obese (BMI \>30 kg/m2)

Subjects were instructed to apply 0.1 mg/d transdermal estrogen (Estradiol) for one month. Pituitary response was assessed to determine how estradiol administration altered pituitary sensitivity to Gonadotropin-releasing hormone - GnRH. 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.

Group Type EXPERIMENTAL

Estradiol

Intervention Type DRUG

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

Gonadotropin-releasing hormone (GnRH)

Intervention Type DRUG

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

Progesterone

Intervention Type 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.

Interventions

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Estradiol

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

Intervention Type DRUG

Gonadotropin-releasing hormone (GnRH)

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

Intervention Type DRUG

Progesterone

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.

Intervention Type DRUG

Other Intervention Names

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Climara, transdermal estrogen Lutrelef or gonadorelin acetate Prometrium or medroxyproge sterone acetate

Eligibility Criteria

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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

Minimum Eligible Age

18 Years

Maximum Eligible Age

42 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes