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Effects of vitamin D supplementation during weight loss on sex hormones in postmenopausal women

Mason, Caitlin PhD; De Dieu Tapsoba, Jean PhD; Duggan, Catherine PhD; Imayama, Ikuyo MD, PhD; Wang, Ching-Yun PhD; Korde, Larissa A. MD, MPH; Stanczyk, Frank PhD; McTiernan, Anne MD, PhD

doi: 10.1097/GME.0000000000000600
Original Articles
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Objective: The aim of the study was to compare the effects of vitamin D3 supplementation versus placebo on serum sex hormones in postmenopausal women completing a 12-month diet + exercise weight loss program.

Methods: Two hundred eighteen overweight or obese women (50-75 y) with serum 25-hydroxyvitamin D at least 10 to less than 32 ng/mL (“insufficient”) were randomized to either weight loss + 2,000 IU/day oral vitamin D3, or to weight loss + daily placebo. Serum sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone were measured by radioimmunoassay before randomization and at 12 months. Mean changes were compared between groups (intent-to-treat) using generalized estimating equations.

Results: The 12-month changes in sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone did not differ between groups (all P > 0.05). However, a greater increase in serum 25-hydroxyvitamin D was associated with a greater increase in sex hormone-binding globulin (Ptrend = 0.01), and larger decreases in free and bioavailable estradiol (Ptrend = 0.04, Ptrend = 0.03, respectively). In post-hoc analyses, we compared women randomized to vitamin D whose serum 25-hydroxyvitamin D remained insufficient (n = 38), to women who became replete (25-hydroxyvitamin D ≥32 ng/mL; n = 53). Replete women showed greater reductions in bioavailable estradiol (−1.8 vs −0.7 pg/mL), free testosterone (−0.8 vs −0.3 pg/mL), and bioavailable testosterone (−1.8 vs −0.6 ng/dL), and a greater increase in sex hormone-binding globulin (10.6 vs 4.7 nmol/L) (all P < 0.05), even after adjusting for differences in total 12-month weight loss.

Conclusions: Overall, 12-month changes in sex hormone did not differ between groups. However, vitamin D repletion was associated with greater reductions in sex hormones during weight loss, with a possible dose-dependent effect. Future studies should test higher doses and target circulating 25-hydroxyvitamin D levels when measuring such effects.

1Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

2Department of Biostatistics, University of Washington, Seattle, WA

3Seattle Cancer Care Alliance, Seattle, WA

4Department of Medicine, University of Washington, Seattle, WA

5University of Southern California, Keck School of Medicine, Los Angeles, CA

6Department of Epidemiology, University of Washington, Seattle, WA.

Address correspondence to: Anne McTiernan, MD, PhD, Fred Hutchinson Cancer Research Center, Public Health Sciences Division, 1100 Fairview Ave N. Mailstop: M4-B874, Seattle, WA 98109. E-mail: amctiern@fredhutch.org

Received 6 August, 2015

Revised 19 November, 2015

Accepted 19 November, 2015

Funding/support: The study was supported by grants from the Breast Cancer Research Foundation, Susan G. Komen for the Cure Scientific Advisory Council Award 2010-2012, and the National Cancer Institute (NCI) R03 CA162482-01.

Financial disclosure/conflicts of interest: Dr Korde reports association with Amgen Advisory Board and Genomic Health Speaker's Bureau in the past. Dr Stanczyk reports association with Merck, Agile Therapeutics, and TherapeuticsMD. No other disclosures reported.

© 2016 by The North American Menopause Society.