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

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT01894581
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 39
• Location: 1
• Arms: 2
• Duration (Months): 5
• Patients Per Site Per Month: 7.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obesity; Fertility	Dietary Supplement: LOVAZA; Drug: GnRH	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Effects of Dietary Omega-3 Fatty Acids on Reproductive Hormones in Obese Women
• Study Start Date: Jul 1, 2014
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Obese Women 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; 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.; Other Names: Omega-3-acid ethyl esters ; Drug: GnRH; An intravenous bolus of exogenous GnRH (75 ng/kg dosing based on total body weight) will be administered at 6 hours.; Other Names: Gonadorelin (GnRH)
Active Comparator: Normal Weight 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; 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.; Other Names: Omega-3-acid ethyl esters ; Drug: GnRH; An intravenous bolus of exogenous GnRH (75 ng/kg dosing based on total body weight) will be administered at 6 hours.; Other Names: Gonadorelin (GnRH)

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 42 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Denver Anschutz Medical Campus	Aurora	Colorado	United States	80045

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Alex Polotsky, MD, MS, University of Colorado, Denver

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT01894581
• Other Study ID Numbers: 13-1420; U54HD058155-05
• First Posted: Jul 10, 2013
• Last Update Posted: Feb 2, 2017
• Last Verified: Dec 1, 2016

• Additional relevant MeSH terms: Prolactin Release-Inhibiting Factors

Study Results

Participant Flow

Recruitment Details	39 regularly menstruating obese and normal-weight women were recruited from the community through campus-wide advertisements.
Pre-assignment Detail	Potential participants were screened out if they had polycystic ovary syndrome, allergies to seafood, used medications known to affect reproductive hormones, used exogenous sex steroids within the last 3 months, exercised vigorously more than 4 hours weekly, or were attempting pregnancy. Eligible subjects then had a baseline physical examination.

Arm/Group Title	Obese	Normal Weight
Arm/Group Description	BMI >= 30 kg/m2	BMI 18-25 kg/m2
Period Title: Overall Study
STARTED	20	19
COMPLETED	15	12
NOT COMPLETED	5	7

Baseline Characteristics

Arm/Group Title	Obese	Normal Weight	Total
Arm/Group Description	BMI >= 30 kg/m2	BMI 18-25 kg/m2	Total of all reporting groups
Overall Participants	20	19	39
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.8 (1.2)	28.4 (1.2)	31.6 (5.3)
Sex/Gender, Customized (participants) [Number]
Female	15 75%	12 63.2%	27 69.2%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	15 75%	12 63.2%	27 69.2%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	37.8 (1.5)	21.8 (.5)	31.6 (9.1)

Outcome Measures

1. Primary Outcome

Title	Change in the Average LH Pulse Amplitude
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Obese	Normal Weight
Arm/Group Description	BMI >= 30 kg/m2	BMI 18-25 kg/m2
Measure Participants	15	12
Mean (Standard Deviation) [IU/L]	-.04 (.2)	.4 (.4)

Adverse Events

Time Frame	During approximately one menstrual cycle.
Adverse Event Reporting Description	Adverse event data were collected for the duration of the participant's participation, which was approximately one menstrual cycle. Data were from all subjects were collected from June of 2013 to February of 2015.
Arm/Group Title	Obese		Normal Weight
Arm/Group Description	BMI >= 30 kg/m2		BMI 18-25 kg/m2
All Cause Mortality
	Obese		Normal Weight
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Obese		Normal Weight
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Obese		Normal Weight
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.