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Vitamin D and calcium from food, but not supplements, were associated with a decreased risk for early menopause, and the hormones in dairy food may partly explain why, scientists said.

Compared with women with the least amount of vitamin D in their diet, those with the most were 17% less likely to undergo menopause before the age of 45 (hazard ratio 0.83; 95% CI 0.72-0.95; P=0.03), reported researchers led by Alexandra Purdue-Smithe, a graduate student at the University of Massachusetts Amherst.

However, compared with women who did not take vitamin D supplements, those who took the recommended daily allowance of 600 IUs or more had no significant change in risk (HR 1.29; 95% CI 0.94-1.77; P=0.10), Purdue-Smithe and colleagues reported online in the American Journal of Clinical Nutrition.

Compared with women with the least amount of calcium in their diet, those with the most were 13% less likely to undergo early menopause (HR 0.87; 95% CI 0.76-1.00; P=0.03), the study found.

Surprisingly, women who took the recommended daily allowance of calcium (1,000 mg) or more had a significantly increased risk of early menopause compared with those who did not take calcium supplements (odds ratio 1.60; 95% CI 1.19-2.17; P=0.02). The researchers speculated that many of these women may have been taking calcium supplements prescribed by a doctor for conditions that affect sex-steroid hormones, such as autoimmune diseases or a family history of osteoporosis.

“Laboratory evidence relating vitamin D to some of the hormonal mechanisms involved in ovarian aging provided the foundation for our hypothesis. However, to our knowledge, no prior epidemiologic studies have explicitly evaluated how vitamin D and calcium intake may be related to risk of early menopause,” Purdue-Smithe said in a statement.

When the investigators examined the effect of dietary vitamin D and calcium obtained from dairy and non-dairy sources, they found significant risk reductions only for the vitamins that came from dairy. “We think that our findings for dietary vitamin D may be driven, at least in part, by dairy foods themselves,” Purdue-Smithe told MedPage Todayvia email.

“Dairy foods are a rich source of steroid hormones, such as progesterone. Higher intake of progesterone from dairy may influence levels of circulating sex hormones, which in turn may influence ovarian function during the reproductive years.” Ongoing research is exploring this possibility, she said.

Early menopause affects about 10% of women in Western countries and has been associated with an increased risk for osteoporosis, cognitive decline, cardiovascular disease, and premature death, she noted.

“In addition to placing women at higher risk of adverse future health outcomes, early menopause is also problematic as women are increasingly delaying childbearing into their later reproductive years. Fertility declines drastically during the 10 years leading up to menopause, so early menopause can have profound psychological and financial implications for couples who are unable to conceive as they wish. As such, it is important to identify modifiable risk factors for early menopause, such as diet.”

The researchers analyzed data from the Nurses’ Health Study II. This prospective epidemiological study included 116,430 female U.S. registered nurses who were 25 to 42 years old in 1989 when they responded to a detailed baseline questionnaire asking about lifestyle behaviors and medical conditions. Follow-up questionnaires have been mailed biennially. In addition, food-frequency questionnaires were mailed every 4 years since 1989 through 2011. These questionnaires assessed both diet and supplement use.

The investigators identified 2,041 cases of early menopause over 1.13 million person-years of follow-up, using Cox proportional hazards regression to analyze the relationships between vitamin D and calcium intake and incident early menopause, while accounting for potential confounding factors.

However, because higher intake of vitamin D and calcium from foods could simply be a marker for better nutrition and overall health, the researchers took into account other factors including vegetable intake, alcohol use, body-mass index, and smoking. “The large size of this study allowed us to consider a variety of potential correlates of a healthy lifestyle that might explain our findings; however, adjusting for these factors made almost no difference in our estimates,” Purdue-Smithe said.

Apart from the possible effects of hormones in dairy food, vitamin D and calcium themselves may protect against ovarian aging, the investigators suggested. “Several potential mechanisms supporting this hypothesis have been proposed — namely the ability of vitamin D to modify messenger-RNA expression of anti-Müllerian hormone, a glycoprotein secreted by granulosa cells during early follicle development that correlates with the overall age at menopause and may play a role in regulating ovarian aging.”

As for why the study found no risk reduction with supplements, Purdue-Smithe said the answer probably has more to do with the low number of patients in the study taking high doses of supplements, rather than any potential for reduced bioavailability or absorption of vitamins from supplements. “For example, there were only 40 women who consumed vitamin D above 600 IU/d in our population. Therefore, the availability of statistical power for these analyses was considerably lower than for our analyses for vitamin D from dietary sources,” she said.

Other limitations of the study included the reliance on self-reports of diet, and the fact that the Nurses’ Health Study II is a predominantly white cohort, the investigators noted — “Our findings should be replicated in more diverse populations.”

In addition, the researchers noted, the majority of a person’s vitamin D is obtained by cutaneous synthesis during sunlight exposure, and dietary and supplemental intake of vitamin D represent a small overall contribution to circulating plasma 25-(OH)D.

Nevertheless, further studies to assess the relationship between dietary vitamin D and calcium and early menopause are warranted, the team concluded.

Menopause