Supplementation with calcium and vitamin D does not appear to influence the number of menopause-related vasomotor, mood, or sleep symptoms in older women, according to a new study.
A secondary analysis of the Women’s Health Initiative Calcium/Vitamin D Supplementation Trial found no difference in the number of menopausal symptoms reported by women randomly assigned to receive elemental calcium carbonate 1000 mg with vitamin D 400 IU daily (CaD) and those reported by the placebo group of the study during approximately 6 years of follow-up.
The findings should not be generalized to all menopausal women, however, because the average age of women at baseline in the current investigation was 64 years, whereas the prevalence of menopause-related hot flashes in particular peaks in women in their early 50s, write Erin S. LeBlanc, MD, MPH, from the Kaiser Permanente Center for Health Research in Portland, Oregon, and colleagues in an article published online June 1 in Maturitas.
In addition, the study looked specifically at prevalence of symptoms, not severity. “[C]onsistent with our a priori analysis plan, we examined whether women had menopausal symptoms, regardless of symptom severity. We were therefore unable to determine if calcium and vitamin D influenced symptom severity such as daily number of hot flashes.”
For the study, investigators followed 34,157 women aged 50 to 79 years at 40 clinical sites from the mid-1990s to 2005, for an average of 5.7 years, and assessed multiple menopausal symptoms, including hot flashes, emotional well-being, fatigue, and sleep disturbances.
The study’s primary outcome was the total number of symptoms, independent of severity, at a given time. Secondary outcomes include the energy/fatigue and emotional well-being subscales of the Short Form 36 Health Survey and a sleep disturbance construct.
Of the study population, 17,101 women were assigned to receive daily calcium/vitamin D supplements, and 17,056 received a placebo.
“Women in the CaD arm did not have a different number of symptoms at follow-up compared to women taking the placebo,” the authors report. Specifically, women in the supplement group reported an average of 6.26 menopausal symptoms over the course of the study compared with an average of 6.32 symptoms in the placebo group.
“Similarly, there was no difference between sleep disturbance, emotional well-being, or energy/fatigue at follow-up in those who were randomized to CaD supplementation compared to those taking the placebo,” the authors write, noting also that there was no evidence that hormone therapy was an effect modifier of the association between the CaD group and symptoms overall or individual symptoms after adjustment for multiple testing.
The investigators had hypothesized that vitamin D would improve menopausal symptoms via several possible mechanisms, including the mitigation of the menopausal decline in serotonin, which has known effects on thermoregulation and the possible connection between decreasing estrogen and subclinical vitamin D deficiency.
Despite evidence of a possible link between calcium supplementation and hot flashes in some populations, “[w]e hypothesized that the potential favorable effects of vitamin D on menopause-related symptoms would outweigh the potential negative effects of calcium,” the authors explain.
Most women transitioning through menopause will experience symptoms including hot flashes, mood disturbances, and muscle aches. In many women, these symptoms are severe enough to adversely affect their quality of life, work performance, and personal relationships. Current treatments for menopause-related symptoms, such as menopausal hormone therapy, antidepressants, and anticonvulsants, may have significant side effects and serious long-term adverse consequences. In addition, after treatment is discontinued, these symptoms may recur or even develop de novo. It is therefore important to investigate possible determinants of menopause-related symptoms so that new therapies can be developed.
There are several mechanisms whereby vitamin D could potentially improve menopausal symptoms. A menopausal decline in serotonin, a neurotransmittor with known effects on thermoregulation, could contribute to hot flashes. In animal models, vitamin D prevents this serotonin decline. Alternatively, estrogen increases the activity of the enzyme responsible for activating vitamin D. The fall in estrogen that occurs during the menopausal transition could uncover previously subclinical vitamin D deficiency. Vitamin D supplementation can improve mood and muscle aches in nonmenopausal populations, but its effects on a menopausal population have not been well studied.
Conversely, calcium may stimulate the production of a vasodilator neuropeptide, calcitonin gene-related peptide (CGRP), which has been positively linked to occurrence of menopausal hot flashes. Indeed, taking calcium supplements has been linked to a higher likelihood of having hot flashes in breast cancer survivors.
We examined the effect of 1000 mg of elemental calcium carbonate plus 400 IU of vitamin D3 (CaD) on menopause-related symptoms in women who participated in the Women’s Health Initiative randomized, placebo-controlled Calcium/Vitamin D Supplementation Trial (CaD). We hypothesized that the potential favorable effects of vitamin D on menopause-related symptoms would outweigh the potential negative effects of calcium. Therefore, we believed that women given calcium and vitamin D would experience fewer menopausal symptoms during follow-up than women given the placebo.
Erin S. LeBlanc, Haley Hedlin, FeiFei Qin, Manisha Desai, Jean Wactawski-Wende, Nancy Perrin, JoAnn E. Manson, Karen C. Johnson, Kamal Masaki, Frances A. Tylavsky, Marcia L. Stefanick
The findings did not support these hypotheses, they write, noting that the results “do not suggest that menopausal women should take calcium plus vitamin D at these doses to improve vasomotor, mood, or sleep complaints.”
Dr LeBlanc and one coauthor report that their institution has received grant funding from Amgen, Bristol-Meyers Squibb, and AstraZeneca for unrelated research projects. Another coauthor reports that her institution has received investigator-initiated grant support from Mars Symbioscience for an unrelated research project. The Women’s Health Initiative program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health.
Maturitas. Published online June 1, 2015.