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

Not Applicable

Completed

• Conditions: Fertility; Obesity
• Interventions: Dietary Supplement: LOVAZA; Drug: GnRH

• Registration Number: NCT01894581
• Lead Sponsor: University of Colorado, Denver

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-07-03
• Study First Submitted QC: 2013-07-09
• Study First Posted: 2013-07-10
• Study Start: 2014-07
• Primary Completion: 2014-12
• Study Completion: 2014-12
• Results First Submitted: 2016-06-02
• Results First Submitted QC: 2016-06-02
• Results First Posted: 2016-07-13
• Status Verified: 2016-12
• Last Update Submitted: 2016-12-08
• Last Update Posted: 2017-02-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 39

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Obese Women	LOVAZA	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.
Normal Weight	LOVAZA	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.
Normal Weight	GnRH	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.
Obese Women	GnRH	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.

Primary Outcome Measures

Name	Time	Method
Change in the Average LH Pulse Amplitude	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.	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.

Trial Locations

Locations (1)

University of Colorado Denver Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States