Estrogen Sensitivity and Ovulatory Dysfunction in Obesity

Obesity Clinical Trial

Official title:

Estrogen Sensitivity and Ovulatory Dysfunction in Obesity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01381016
• Other study ID #: 11-0293
• Status: Completed
• Phase: N/A
• First received: June 22, 2011
• Last updated: April 2, 2015
• Start date: June 2011
• Est. completion date: January 2013

Study information

• Verified date: April 2015
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 42 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Infertility
• Obesity

Intervention

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

Locations

Country	Name	City	State
United States	University of Colorado, Anschutz Medical Campus	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

References & Publications (2)

Jain A, Polotsky AJ, Rochester D, Berga SL, Loucks T, Zeitlian G, Gibbs K, Polotsky HN, Feng S, Isaac B, Santoro N. Pulsatile luteinizing hormone amplitude and progesterone metabolite excretion are reduced in obese women. J Clin Endocrinol Metab. 2007 Jul;92(7):2468-73. Epub 2007 Apr 17. — View Citation

Rochester D, Jain A, Polotsky AJ, Polotsky H, Gibbs K, Isaac B, Zeitlian G, Hickmon C, Feng S, Santoro N. Partial recovery of luteal function after bariatric surgery in obese women. Fertil Steril. 2009 Oct;92(4):1410-5. doi: 10.1016/j.fertnstert.2008.08.025. Epub 2008 Sep 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Luteinizing Hormone Pulse Amplitude	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.	Baseline	No
Primary	Luteinizing Hormone Pulse Amplitude		Post estradiol at one month	No

External Links

•   PI Profile