Effects of Dietary Omega-3 Fatty Acids on Reproductive Hormones in Obese Women

University of Colorado, Denver39 enrolled

Overview

The United States has the highest prevalence of obesity among all countries surveyed in 2012 by the Organization for Economic Cooperation and Development. Maternal obesity is linked with anovulation, menstrual cycle abnormalities, subfertility, fetal loss, obstetrical complications and congenital anomalies. Changes in reproductive hormones and diminished oocyte quality have also been demonstrated. A gap of knowledge exists as the mechanisms underlying these harmful effects are poorly understood and no specific treatments exist. This proposal will test the hypothesis that dietary omega-3 fatty acids (FA) will improve the output of hypothalamicpituitary- ovarian axis in obese women. The investigators will perform paired assessments before and after supplementation in 10 obese and 10 normal weight women. To test the pituitary and hypothalamic output, the investigators will examine the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responsiveness during frequent blood sampling. To test the corpus luteum function, the investigators will examine urinary reproductive hormones (E1c, estrone conjugates, and pregnanediol glucuronide (Pdg)) over an entire menstrual cycle. The investigators ultimate goal is to collect preliminary data for an adequately powered randomized control trial.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Obesity Fertility

Interventions

LOVAZADIETARY_SUPPLEMENT

Subjects will be instructed to take 2 grams twice daily of oral omega-3-acid ethyl esters (Lovaza) starting with day 1 to 3 of their menstrual period. Each capsule contains 60mg of other omega-3 FA. On day 1 of their subsequent menstrual period, subjects will be instructed to discontinue.

GnRHDRUG

An intravenous bolus of exogenous GnRH (75 ng/kg dosing based on total body weight) will be administered at 6 hours.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 42 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age 18-42 at study entry 2. Regular menstrual cycles every 25-40 days 3. BMI at least 30 kg/m2 (obese) or between 18.5 and 25 kg/m2 (normal) 4. Good general health 5. Prolactin and thyroid-stimulating hormone (TSH) within normal laboratory ranges at screening, baseline hemoglobin \>11 gm/dl. Exclusion Criteria: 1. Diagnosis of polycystic ovary syndrome (by ultrasound or hyperandrogenic symptoms) 2. Fish or seafood allergy or hypersensitivity (e.g., anaphylactic reaction) to omega-3-acid ethyl esters or any component of the formulation 3. Coagulopathy or receiving therapeutic anticoagulation (due to potential for interaction with omega-3 FA) 4. History of chronic disease affecting hormone production, metabolism or clearance (including diabetes mellitus) 5. Abnormal renal or liver function at screening 6. Current use of thiazolidinediones or metformin (known to interact with reproductive hormones) 7. Use of hormones affecting hypothalamic output (HPO) axis (such as hormonal contraceptives) within three months of entry 8. Strenuous exercise (\>4 hours of intense physical activity per week) 9. Pregnancy 10. Breast-feeding 11. Current active attempts to conceive 12. History of significant recent weight loss or gain

Outcomes

Primary Outcomes

Change in the Average LH Pulse Amplitude

To test the pituitary and hypothalamic output, we examined LH secretion (unstimulated and in response to gonadotropin-releasing hormone (GnRH) stimulation) during 8-hour blood sampling studies at 10 min intervals. The primary outcome measure is the change in the average LH pulse amplitude for each patient from baseline to after supplementation.

Time frame: 10 minute intervals during 8 hour blood sampling studies. Subjects will undergo two menstrual cycles of study, one prior to dietary supplementation and one after supplementation.