Clinical trial NCT01894581: Effects of Dietary Omega-3 Fatty Acids on Reproductive Hormones in Obese Women
Official title: Effects of Dietary Omega-3 Fatty Acids on Reproductive Hormones in Obese Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Fertility
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2013-07-10
Enrollment: 39
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in the Average LH Pulse Amplitude
timeFrame: 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.
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Denver Anschutz Medical Campus
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Alex Polotsky, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.