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Researchers propose a mechanism to explain the relationship between low vitamin D status and increased risk for breast cancer

Posted on: February 17, 2016   by  Amber Tovey


A new randomized controlled trial found that vitamin D repletion in women led to reduced sex hormones.

Researchers continue to provide evidence supporting the theory that sufficient vitamin D levels are related to a reduced risk of breast cancer. There are many possible mechanisms to explain this relationship. In an attempt to understand the role of vitamin D in breast cancer, researchers conducted a randomized controlled trial (RCT) to evaluate the effects of vitamin D supplementation on sex hormones in obese women.

Obesity is a risk factor for post-menopausal breast cancer. Elevated sex hormones are thought to be partially responsible for this, since adipose tissue is the primary site of aromatase production. Aromatase is an enzyme used to synthesize estrogen, and inhibiting its action is used as a treatment for breast cancer. Since low vitamin D levels are associated with both breast cancer risk and obesity, researchers hypothesized that vitamin D supplementation in conjunction with weight loss would lower sex hormones.

The researchers randomized 280 overweight or obese women to one of two groups: weight loss + 2000 IU of vitamin D daily or weight loss + placebo. At baseline, all women had insufficient vitamin D levels as defined by levels between 10 and 32 ng/ml. The weight loss program included both diet and exercise. The goals of the program were to reduce calorie intake to 1,200 to 2,000 daily and to partake in at least 45 minutes of moderate to vigorous intensity exercise 5 days per week. The researchers aimed for a 10% reduction in body weight from the program.

After 12 months, the researchers compared sex hormone levels between both groups. They wanted to know whether vitamin D supplementation reduced testosterone and estradiol, since elevated levels of both are related to an increased risk of breast cancer. In addition, they wanted to see if vitamin D supplementation increased sex hormone-binding globulin (SHBG) levels, as increased SHGB levels are linked to a reduced risk of breast cancer. Here is what they found:

  • There were no significant differences in sex hormone levels between the two groups (p > 0.05).
  • A greater increase in vitamin D levels was associated with a greater increase in SHBG and a larger reduction in estradiol (p < 0.05).

Not all women who were given vitamin D supplements became sufficient in vitamin D, leaving researchers curious about the effects of vitamin D sufficiency on sex hormone levels. Thus, the researchers compared women who were randomized to vitamin D whose vitamin D status remained insufficient (n=32) to women who became replete (n=53). They found that replete women showed greater reductions in estradiol, testosterone and a greater increase SHBG, even after adjusting for differences in weight loss (p < 0.05).

The researchers summarized their results,

“Although our results suggest no overall benefit of 2,000 IU/day vitamin D supplementation on reducing sex hormone concentrations beyond the effect of weight loss alone in postmenopausal women, a greater increase in 25(OH)D was significantly associated with decreases in free and bioavailable estradiol, and increases in SHBG.”

They went on to state,

“Repletion to levels at least 32 ng/mL was associated with significantly greater rises in SHBG and significant reductions in bioavailable estradiol, and free and bioavailable testosterone, compared with women whose circulating 25(OH)D remained below 32 ng/mL; these effects were independent of total weight loss.”

While the study possessed interesting findings, it leaves many questions unanswered due to its limitations. The study should have used a higher dosage to ensure that a larger proportion of the women would achieve sufficiency. One cannot reap the benefits of vitamin D until they are able to obtain healthy levels. In addition, there was a very low compliance rate with only 55% of participants returning supplement bottles to ensure that they took the correct amount of supplements. This means that the potential effects of vitamin D on sex hormone levels were likely underestimated. Therefore, further RCTs are warranted.


Tovey, A. & Cannell, JJ. Researchers propose a mechanism to explain the relationship between low vitamin D status and increased risk for breast cancer. Vitamin D Council Blog & Newsletter, 2016.


Mason, C. et al. Effects of vitamin D supplementation during weight loss on sex hormones in postmenopausal women. The Journal of the North American Menopause Society, 2016.

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