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

NCT01894581 | Completed Results

• 2 other identifiers: 13-1420U54HD058155-05
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity; Fertility

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

Study Arms (2)

Obese Women

EXPERIMENTAL

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.

Dietary Supplement: LOVAZA; Drug: GnRH

Normal Weight

ACTIVE COMPARATOR

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.

Dietary Supplement: LOVAZA; Drug: GnRH

Interventions

LOVAZA DIETARY_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.

Also known as: Omega-3-acid ethyl esters

Normal Weight; Obese Women

GnRH DRUG

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

Also known as: Gonadorelin (GnRH)

Normal Weight; Obese Women

Eligibility Criteria

• Age: 18 Years - 42 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-42 at study entry
• Regular menstrual cycles every 25-40 days
• BMI at least 30 kg/m2 (obese) or between 18.5 and 25 kg/m2 (normal)
• Good general health
• Prolactin and thyroid-stimulating hormone (TSH) within normal laboratory ranges at screening, baseline hemoglobin \>11 gm/dl.

You may not qualify if:

• Diagnosis of polycystic ovary syndrome (by ultrasound or hyperandrogenic symptoms)
• Fish or seafood allergy or hypersensitivity (e.g., anaphylactic reaction) to omega-3-acid ethyl esters or any component of the formulation
• Coagulopathy or receiving therapeutic anticoagulation (due to potential for interaction with omega-3 FA)
• History of chronic disease affecting hormone production, metabolism or clearance (including diabetes mellitus)
• Abnormal renal or liver function at screening
• Current use of thiazolidinediones or metformin (known to interact with reproductive hormones)
• Use of hormones affecting hypothalamic output (HPO) axis (such as hormonal contraceptives) within three months of entry
• Strenuous exercise (\>4 hours of intense physical activity per week)
• Pregnancy
• Breast-feeding
• Current active attempts to conceive
• History of significant recent weight loss or gain

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of Colorado Denver Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Related Publications (2)

• Bauer JL, Kuhn K, Bradford AP, Al-Safi ZA, Harris MA, Eckel RH, Robledo CY, Malkhasyan A, Johnson J, Gee NR, Polotsky AJ. Reduction in FSH Throughout the Menstrual Cycle After Omega-3 Fatty Acid Supplementation in Young Normal Weight but not Obese Women. Reprod Sci. 2019 Aug;26(8):1025-1033. doi: 10.1177/1933719119828099. Epub 2019 Feb 17.

  PMID: 30773100 DERIVED

• Al-Safi ZA, Liu H, Carlson NE, Chosich J, Harris M, Bradford AP, Robledo C, Eckel RH, Polotsky AJ. Omega-3 Fatty Acid Supplementation Lowers Serum FSH in Normal Weight But Not Obese Women. J Clin Endocrinol Metab. 2016 Jan;101(1):324-33. doi: 10.1210/jc.2015-2913. Epub 2015 Nov 2.

  PMID: 26523525 DERIVED

MeSH Terms

Conditions

Obesity

Interventions

Omacor; Gonadotropin-Releasing Hormone

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Dr. Alex Polotsky
• Organization: University of Colorado Denver

alex.polotsky@ucdenver.edu

303-724-2001

Study Officials

• Alex Polotsky, MD, MS

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2013
• First Posted: July 10, 2013
• Study Start: July 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: February 2, 2017
• Results First Posted: July 13, 2016

Record last verified: 2016-12

Locations

US (1)