Vitamin D Modestly Tied to Sex Hormones in Older Population

Marlene Busko

December 08, 2016

A generally "modest" link between levels of 25-hydroxy vitamin D (vitamin D) and sex hormones and no significant racial/ethnic differences have been identified using data from the Multi-Ethnic Study of Atherosclerosis (MESA) of black, white, Chinese, and Hispanic men and women aged 45 to 84.

Lower levels of vitamin D were associated with lower levels of sex-hormone–binding globulin (SHBG) and higher levels of free testosterone in men and women and lower levels of estradiol and higher levels of dehydroepiandrosterone (DHEA) in women — independent of body mass index (BMI) or self-reported health status.

Among women, a 10-ng/mL decrease in vitamin D was associated with an average decrease in SHBG of 8.29 nmol/L, after researchers accounted for differences in demographics and lifestyle.

However, apart from this relationship, "most of the adjusted differences in mean levels of sex hormones between vitamin D–deficient and optimal individuals were modest," Di Zhao, PhD, department of epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, and colleagues report.

Moreover, this study was "not able to confirm" previously reported associations between lower vitamin D concentrations and lower total testosterone or testosterone deficiency, they note.

Thus, "whether treating vitamin D deficiency can improve a low [testosterone] state directly is inconclusive at this time, and our data do not support a relationship beyond shared risk factors," Dr Zhao and colleagues caution.

"Future studies are needed to determine whether vitamin D supplementation influences sex hormone levels."

The study is published online and is scheduled for the January 2017 issue of Maturitas, the official journal of the European Menopause and Andropause Society.

Cross-sectional Analysis, Multiethnic Cohort

Having less than optimal vitamin D levels is believed to increase a person's risk of atherosclerotic cardiovascular disease, and this may be partly mediated by sex hormones such as testosterone and estradiol, the researchers write.

Lower levels of vitamin D have been linked with lower levels of testosterone in men, but the relationship was attenuated after correction for adiposity. Vitamin D is stored in fat cells; obese individuals have lower levels of vitamin D in serum, Dr Zhao and colleagues note.

Similarly, prior studies in women that looked at vitamin D and sex hormones have reported conflicting results in different populations using different adjustments for adiposity.

It was also unclear whether the relationship between vitamin D and sex hormones would differ in blacks, who have lower mean levels of vitamin D than whites.

Thus, the researchers aimed to examine the link between vitamin D and sex hormones in 3017 men and 2931 women with complete data who participated in MESA and were enrolled at six sites in the United States in 2000 to 2002.

On average, the participants were in their mid-60s, and 96% of the women were postmenopausal.

Their mean vitamin D level was around 26 ng/mL, and 31% of men and 32% of women were deficient in this vitamin (defined as <20 ng/mL [50 nmol/L]).

Each 10-ng/mL decrease in vitamin D was linked with significant differences in free testosterone and SHBG in men and women and estradiol and DHEA in women.

Change in Sex Hormone Levels per 10-ng/mL Decrease in Vitamin D*

Hormone Men, difference (95% CI) Women, difference (95% CI)
Total testosterone, nmol/L -0.18 (-0.38–0.01) -0.01 (-0.05–0.02)
Estradiol, nmol/L 0.002 (0.000–0.004) -0.01 (-0.01–0.00)
DHEA, nmol/L 0.03 (-0.23–0.29) 0.40 (0.19–0.62)
Free testosterone, % 0.02 (0.01–0.04) 0.06 (0.0–0.07)
SHBG, nmol/L -0.70 (-1.36–0.05) -8.29 (-10.13 to -6.45)
*Adjusted for age, race/ethnicity, study site, body mass index, smoking, education, exercise, and self-reported health status
DHEA=dehydroepiandrosterone
SHBG=sex-hormone–binding globulin

Following these preliminary findings, "prospective studies with serial measures of vitamin D and sex hormones are needed to determine any temporal relationships, and clinical trials are needed to evaluate whether treating a low vitamin D state can alter sex hormone levels," Dr Zhao and colleagues conclude.

The study was supported by a National Institutes of Health/National Institute of Neurological Disorders and Stroke grant and by the Blumenthal Scholars Fund for Preventive Cardiology Research. The MESA study was supported by the National Heart, Lung, and Blood Institute. The authors have no relevant financial relationships.

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Maturitas. Published online November 29, 2016. Abstract

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