Mediators of Abnormal Reproductive Function in Obesity (MARO)

• Status: Completed
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: Female

Summary

The study is seeking to understand how being overweight and obese makes women less fertile. The studies the investigators have done so far indicate that there is a hormone or other substance produced by fat that goes into the blood and reduces reproductive hormones in women who are overweight and obese. The present study will try to find the most promising substances by studying small numbers of women and trying to remove the substances that are causing the problem.

Hypothesis: A circulating factor or factors, either hormonal, inflammatory or metabolic, causes relative pituitary hypofunction and correction of this reproductive deficit will allow obese women with infertility who have failed to reduce their body weight to normal to conceive, and may also prevent the horizontal passage of an adverse metabolic phenotype to the offspring.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Colorado, Denver
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Treatments: Aspirin; Eicosapentaenoic acid ethyl ester; Estradiol; Hormones; Insulin; Menthol; Pioglitazone; Testosterone

Criteria

Inclusion Criteria:

Women aged 18-39* who meet the following criteria will be enrolled:

*Women age 40-60 can be enrolled in Group A

• BMI at least 30 kg/m2 (Groups B and C only)

• No history of chronic disease affecting hormone production, metabolism or clearance

• No use of medications known to alter or interact with reproductive hormones or insulin metabolism (e.g. thiazolidinediones, metformin)

• No use of reproductive hormones within 3 months of enrollment

• No medical conditions that are known to affect urinary hormone excretion or that may interfere with urinary hormone measurement (Groups B and C only)

• No history of or active bladder cancer (Group C only, since pioglitazone is contraindicated in individuals with bladder cancer)

• Normal prolactin and thyroid stimulating hormone levels at screening

• History of regular menstrual cycles every 25-40 days

• Use of a reliable method of contraception (female or male partner sterilization; intrauterine device (IUD); abstinence; diaphragm)

• Hemoglobin A1c <6%

Exclusion Criteria:

Women aged 18-39* who meet the following criteria will be enrolled:

*Women age 40-60 can be enrolled in Group A

• BMI at least 30 kg/m2 (Groups B and C only)

• No history of chronic disease affecting hormone production, metabolism or clearance

• No use of medications known to alter or interact with reproductive hormones or insulin metabolism (e.g. thiazolidinediones, metformin)

• No use of reproductive hormones within 3 months of enrollment

• No medical conditions that are known to affect urinary hormone excretion or that may interfere with urinary hormone measurement (Groups B and C only)

• No history of or active bladder cancer (Group C only, since pioglitazone is contraindicated in individuals with bladder cancer)

• Normal prolactin and thyroid stimulating hormone levels at screening

• History of regular menstrual cycles every 25-40 days

• Use of a reliable method of contraception (female or male partner sterilization; IUD; abstinence; diaphragm)

• Hemoglobin A1c <6%