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.
Observational study based on data from the prospective Nurses’ Health Study II; information regarding calcium and vitamin D intake was gathered from food frequency questionnaires (FFQ) used in the study.
Study Population and Assessment
The Nurses’ Health Study II included 116,430 women, aged 25 to 42 in 1989 (when the prospective study began). Baseline information regarding age, height, ethnicity, age at menarche, and maternal and paternal education level was gathered 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 the intake of 131 foods, beverages, and supplements during the preceding year. Covariates such as BMI and physical activity were also identified at each follow-up.
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 its duration.
Study Parameters Assessed
Vitamin D intake, calcium intake, and age of onset of menopause
After adjusting for age, pack-years of smoking, BMI, parity, lifetime duration of breastfeeding, age at menarche, physical activity, percentage of total calories from vegetable protein, alcohol intake, and calcium intake, women in the highest quintile of dietary intake of vitamin D (median consumption of 528 IU/d) had a 17% lower risk of early menopause than women with the lowest intake (median consumption 148 IU/d) (P=0.03). There was also a 13% lower risk of early menopause in women who consumed the most dietary calcium compared to women with the lowest intake of calcium.
When a woman experiences menopause before the age of 45, she is at increased risk of osteoporosis, cardiovascular issues, cognitive decline, and premature mortality.
Conversely, supplemental vitamin D was not associated with a decreased 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.
According to the Centers for Disease Control and Prevention, most women experience menopause between the ages of 45 and 55.1 When a woman experiences menopause before the age of 45, she is at increased risk of osteoporosis, cardiovascular issues, cognitive decline, and premature mortality.2-4 Although genetic factors were once thought to be the key drivers of age of menopause onset, we now know that diet and lifestyle can also play a role.5
This study looks specifically at 2 key dietary nutrients—vitamin D and calcium. Both of these nutrients influence female reproductive organs. For example, the ovaries are replete with vitamin D receptors. Deficiencies of vitamin D and calcium are each associated with gynecological and reproductive health conditions 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 influence ovarian health. For instance, vitamin D increases messenger RNA expression of anti-Müllerian hormone (AMH), a paracrine regulator of ovarian follicle development.8,9 An increase in AMH is associated with a reduction in accelerated aging of the ovaries.10 In a randomized, double-blind study of young women, Dennis and colleagues found that one-time supplementation of high dose (50,000 IU) vitamin D3 led to a mean increase of 12.9±3.7% of AMH over the subsequent week.11 With regard to the lack of effect of supplemental vitamin D on early menopause in this present study by Purdue-Smithe et al, the authors speculated that the number of women who took vitamin D supplements was too small to see a relationship. Of the 86,234 women in the study, only 40 took vitamin D supplements above 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 quantities of vitamin D also have high quantities of calcium, making it impossible to accurately adjust for the impact of each nutrient without the other. Thus, overall, the impact of dietary vitamin D on premature ovarian failure cannot be assumed to be independent of calcium, and vice versa.
This is the first study that we are aware of that looks specifically at vitamin D and calcium related to early menopause risk. It builds upon a more robust collection of studies linking these nutrients with improved fertility,12,13 presumably due to the same underlying effect of increasing AMH. Women with decreased AMH are at increased risk for both infertility and premature menopause.14
Given the impact of dietary vitamin D and calcium on increasing AMH, this study underscores the association of modifiable lifestyle factors with premature ovarian aging. Reducing the risk of early menopause will also lower the risk of comorbid conditions such as cognitive decline, osteoporosis, cardiovascular issues, and premature death.15-17
- Centers for Disease Control and Prevention. Women’s Reproductive Health. https://www.cdc.gov/reproductivehealth/womensrh/index.htm. Updated February 17, 2017. Accessed August 2017.
- Wellons M, Ouyang P, Schreiner PJ, Herrington DM, Vaidya D. Menopause. 2012;19(10):1081-1087.
- van Der Voort DJ, van Der Weijer PH, Barentsen R. Early menopause: increased fracture risk at older age. Osteoporos Int. 2003;14(6):525-530.
- Bove R, Secor E, Chibnik LB, et al. Age at surgical menopause influences cognitive decline and Alzheimer pathology in older women. Neurology. 2014;82(3):222-229.
- Dorjgochoo T, Kallianpur A, Gao YT, et al. Dietary and lifestyle predictors of age at natural menopause and reproductive span in the Shanghai Women’s Health Study. Menopause. 2008;15(5):924-933.
- Li HW, Brereton RE, Anderson RA, Wallace AM, Ho CK. Vitamin D deficiency is common and associated with metabolic risk factors in patients with polycystic ovary syndrome. Metabolism. 2011;60(10):1475-1481.
- Harris HR, Chavarro JE, Malspeis S, Willett WC, Missmer SA. Dairyfood, calcium, magnesium, and vitamin D intake and endometriosis: a prospective cohort study. Am J Epidemiol. 2013;177(5):420-430.
- Irani M, Seifer DB, Grazi RV, et al. Vitamin D supplementation decreases TGF-bata1 biovailability in PCOS: a randomized placebo-controlled trial. J Clin Endocrinol Metab. 2015;100:4307-4314.
- Garg D, Tal R. The role of AMH in the pathophysiology of polycystic ovarian syndrome. Reproductive BioMedicine Online. 2016;33:15-28.
- Nelson SM, Telfer EE, Anderson RA. The aging ovary and uterus: new biological insights. Hum Reprod Update. 2013;9(1):67-83.
- Dennis NA, Houghton LA, Pankhurst MW, et al. Acute supplementation with high dose vitamin D3 increases serum anti-mullerian hormone in young women. Nutrients. 2017;9(7):719-727.
- Paffoni A, Ferrari S, Vigano P, et al. Vitamin D deficiency and infertility: insights from in vitro fertilization cycles. J Clin Endocrinol Metab. 2014;99(11):E2372-2376.
- Grundmann M, von Versen-Hoynck F. Vitamin D—roles in women’s reproductive health? Reprod Biol Endocrinol. 2011;9:146.
- Mahran A, Abdelmeged A, El-Adawy AR, et al. The predictive value of circulating anti-Mullerian hormone in women with polycystic ovarian syndrome receiving clomiphene citrate: a prospective observational study. J Clin Endocrinol Metab. 2013:98:4170-4175.
- Toffanello ED, Coin A, Perissinotto E, et al. Vitamin D deficiency predicts cognitive decline in older men and women: The Pro.V.A. Study. Neurology. 2014;83(24):2292-2298.
- Lips P, Gielen E, van Schoor NM. Vitamin D supplements with or without calcium to prevent fractures. BoneKEy Reports. 2014;3(512).
- Chowdhury R, Kunutsor S, Vitezova A, et al. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomized intervention studies. BMJ. 2014;348:g1903.