Reduction in FSH Throughout the Menstrual Cycle After Omega-3 Fatty Acid Supplementation in Young Normal Weight but not Obese Women

Abstract

Dietary fish oil restores ovarian function in subfertile rats, which is thought to be associated with decreased transcription of follicle-stimulating hormone (FSH) β-subunit. We have previously demonstrated a reduction in early follicular serum FSH levels in normal weight but not obese women after treatment with omega-3 polyunsaturated fatty acids (PUFA). Herein, we report the effect of supplementation with omega-3 PUFA on urinary reproductive hormones across the whole menstrual cycle. This interventional study included 17 eumenorrheic women, aged 24-41 years. One month of daily morning urine was collected before and after 1 month of omega-3 PUFA supplementation with 4 g of eicosapentaenoic acid and docosahexaenoic acid daily. Measurements included urinary FSH, luteinizing hormone (LH) and estrogen and progesterone metabolites, plasma fatty acid composition, and markers of endoplasmic reticulum stress. Compliance with dietary supplementation was verified by significantly reduced ratios of omega-6 to omega-3 PUFA for all subjects after treatment (P < .01). After 1 month of omega-3 PUFA supplementation, urinary FSH was significantly decreased in normal weight, but not obese women, in both follicular and luteal phases (-28.4% and -12.6%, respectively, both P = .04). No significant changes were seen in LH or sex steroids for either weight group. The selective and specific decrease in FSH suggests that omega-3 PUFA supplementation merits further investigation in normal weight women with decreased fertility and/or diminished ovarian reserve.

Trial registration: ClinicalTrials.gov NCT01894581.

Keywords: FSH; LH; fertility; obesity; omega-3 polyunsaturated fatty acids.

Figure 1.

Impact of omega-3 polyunsaturated fatty acid (PUFA) supplementation on plasma omega-6 to omega-3 ratio. Levels in normal weight (NW; blue) and obese (red) women both at baseline (solid bars) and after 1 month of omega-3 supplementation (hashed bars) are shown. Differences between NW and obese women were not significant both at baseline and post omega-3 supplementation. Data represent mean ± standard error of the mean. *P < .01.

Figure 2.

Effect of omega-3 polyunsaturated fatty acid (PUFA) supplementation on urinary gonadotropins. Daily morning urine was assayed for luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and normalized to creatinine. Cycles were aligned based on the Day of Luteal Transition (Day 0). Data are from normal weight (NW) women (blue; n = 7) and obese women (red; n = 10). For each hormone, NW subjects are compared at baseline (open circles, solid line) and after omega-3 supplementation (closed circles, dashed line; panel A for LH; panel D for FSH). Obese subjects are compared at baseline (open circles, solid line) and after omega-3 supplementation (closed circles, dashed line; panel B for LH; panel E for FSH). Error bars indicate standard error of the mean for group composites. Panels C and F represent data for area under the curve (AUC) at baseline (solid bars) and post omega-3 supplementation (hashed bars) by menstrual cycle phase. All significant differences between LH and FSH measurements are indicted by asterisk, as follows. All other comparisons performed on the LH and FSH measurements were not significant *P = .02. **P = .04. ***P = .01. Data are medians; error bars indicate interquartile range (IQR).

Figure 3.

Effect of omega-3 polyunsaturated fatty acid (PUFA) supplementation on urinary estrone conjugates (E1c) and pregnanediol-3-glucuronide (Pdg). Daily morning urine was assayed for E1c and Pdg, normalized to creatinine. Cycles were aligned based on the day of luteal transition (Day 0). Data are from normal weight (NW) women (blue; n = 7) and obese women (red; n = 10). For each hormone, NW and obese subjects are compared in the baseline month (A and D, respectively) and post omega-3 supplementation (B and E, respectively). Error bars indicate standard error of the mean for group composites. Panels C and F represent data for area under the curve (AUC) depicted as area at baseline (solid bars) and post omega-3 supplementation (hashed bars) by menstrual cycle phase. *P = .03. Data are medians; error bars indicate interquartile range (IQR).