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

University of Colorado Denver (CU Denver)

Status: Completed

Conditions: Fertility; Obesity

Treatments: Drug: GnRH; Dietary Supplement: LOVAZA

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01894581

13-1420

U54HD058155-05 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment: 39 patients

Sex: Female

Ages: 18 to 42 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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39 participants in 2 patient groups

Obese Women

Experimental group

Description:

Women with a BMI of greater than or equal to 30 kg/m2 underwent all study interventions, including taking 5 g daily of LOVAZA. Women underwent 8 hours of frequent blood sampling every 10 minutes both at baseline and after LOVAZA supplementation. Each frequent blood sampling included IV administration of GnRH at 6 hours.

Treatment:

Dietary Supplement: LOVAZA

Drug: GnRH

Normal Weight

Active Comparator group

Description:

Women with a BMI of between 18-25 kg/m2 underwent all study interventions, including taking 5 g daily of LOVAZA for one cycle. Women underwent 8 hours of frequent blood sampling every 10 minutes both at baseline and after LOVAZA supplementation. Each frequent blood sampling included IV administration of GnRH at 6 hours.

Treatment:

Dietary Supplement: LOVAZA

Drug: GnRH