Vitamin D and calcium can reduce the risk of early menopause

Relation

Purdue-Smithe AC, Whitcomb BW, Szegda KL, et al. Vitamin D and calcium intake and risk of early menopause.AJCN. 2017;105(6):1493-1501.

Draft

Observational study based on data from the prospective Nurses' Health Study II; Information on calcium and vitamin D intake was collected from food frequency questionnaires (FFQ) used in the study.

Study population and assessment

The Nurses' Health Study II included 116,430 women ages 25 to 42 in 1989 (when the prospective study began). Basic information on mother's and father's age, height, ethnicity, age at menarche, and educational level was collected in 1989; Follow-up information was collected in 1991, 1995, 1999, 2003, 2007, and 2011 with a follow-up rate of ≥89%. The FFQs assessed intake of 131 foods, beverages, and supplements over the past year. Covariates such as BMI and physical activity were also identified at each follow-up visit.

Women diagnosed with cancer before the first follow-up in 1991 were excluded (n=391). After this and other exclusions were applied, 86,234 women remained in the study for the duration.

Study parameters assessed

Vitamin D intake, calcium intake and age at menopause onset

Key insights

After adjusting for age, pack-years of smoking, BMI, parity, lifetime duration of breastfeeding, age at menarche, physical activity, percentage of total calories from plant protein, alcohol intake, and calcium intake, women in the highest quintile of dietary vitamin D intake (median intake of 528 IU/d) had a 17% lower risk of early menopause than women with the lowest intake (median intake of 148 IU/d) (P=0.03). There was also a 13% lower risk of early menopause in women who got the most calcium from food compared to women with the lowest calcium intake.

If a woman reaches menopause before age 45, she is at increased risk of osteoporosis, cardiovascular problems, cognitive decline and premature mortality.

Conversely, supplemental vitamin D was not associated with a reduced risk of early menopause, and supplemental calcium intake was positively associated with early menopause.

Women with the highest intakes of vitamin D and calcium were also younger and more physically active, had a lower BMI, drank less alcohol and were less likely to smoke.

Clinical implications

According to the Centers for Disease Control and Prevention, most women experience menopause between the ages of 45 and 55.¹If a woman reaches menopause before age 45, she is at increased risk of osteoporosis, cardiovascular problems, cognitive decline and premature mortality.^2-4Although it was once thought that genetic factors were the most important determinants of age at onset of menopause, we now know that diet and lifestyle can also play a role.⁵

This study specifically looks at 2 important dietary nutrients – vitamin D and calcium. Both nutrients affect the female reproductive organs. For example, the ovaries are packed with vitamin D receptors. Vitamin D and calcium deficiencies have each been linked to gynecological and reproductive diseases such as polycystic ovary syndrome (PCOS) and endometriosis.^6.7

In this study, dietary vitamin D and dietary calcium were each associated with a lower risk of early menopause. This makes sense because both vitamin D and calcium affect ovarian health. For example, vitamin D increases messenger RNA expression of anti-Müllerian hormone (AMH), a paracrine regulator of ovarian follicle development.^8.9An increase in AMH is associated with a reduction in accelerated ovarian aging.¹⁰In a randomized, double-blind study of young women, Dennis and colleagues found that a single supplementation with high-dose (50,000 IU) vitamin D3 resulted in a mean increase of 12.9 ± 3.7% in AMH in the following week.¹¹Regarding the lack of effect of vitamin D supplementation on early menopause in this present study by Purdue-Smithe et al. The authors speculated that the number of women taking vitamin D supplements was too small to see a connection. Of the 86,234 women in the study, only 40 took vitamin D supplements over 600 IU per day.

The other relevant aspect of this study is that it was not possible to completely distinguish the effects of vitamin D from the effects of calcium. Foods with high amounts of vitamin D also have high amounts of calcium, making it impossible to accurately adjust the effects of each nutrient without the other. Overall, it cannot be assumed that the effect of dietary vitamin D on premature ovarian failure is independent of calcium and vice versa.

This is the first study we know of that specifically looks at vitamin D and calcium in relation to the risk of early menopause. It builds on a more robust body of studies linking these nutrients to improved fertility,^12,13presumably due to the same underlying effect of increasing AMH. Women with low AMH have an increased risk of infertility and premature menopause.¹⁴

Given the influence of dietary vitamin D and calcium on AMH elevation, this study highlights the association of modifiable lifestyle factors with premature ovarian aging. Reducing the risk of early menopause also reduces the risk of comorbidities such as cognitive decline, osteoporosis, cardiovascular problems and premature death.^15-17