Observational studies and placebo-controlled clinical trials have both found that supplemental doses have a therapeutic effect in these patients.
About 30% of menstruating women have premenstrual syndrome (PMS).1,2 But in most cases, the symptoms may be mild enough to not warrant serotonin reuptake inhibitors (SSRIs) or drospirenone-containing OCs. Still, even mild premenstrual symptoms can impact a women's quality of life.
Premenstrual dysphoric disorder (PMDD), the most severe form of premenstrual symptoms, has been found in about 5% of menstruating women, and has been shown to have the same adverse impact on quality of life as dysthymia and nearly as much as that of major depressive disorder.2 Moderate-to-severe PMS, experienced by approximately 20% to 30% of women, has been shown to have adverse effects on relationships with spouses, partners, and children; similarly it can interfere with work efficacy and use up health-care resources.2-5 Even women with mild symptoms use a wide variety of self-help methods, including exercise, herbs, and nutritional supplements, suggesting that many of these women are really suffering.1,6
What does the research indicate?
Calcium supplements were first reported as a possible treatment for PMS in a small crossover trial that compared calcium carbonate, 1,000 mg daily, with placebo.9 Symptoms improved in 73% of the women during the time they were taking calcium, compared with only 15% while taking placebo. A wide variety of symptoms improved, including negative affect, water retention, and pain.
The same investigators conducted a large placebo-controlled trial of calcium carbonate, 1,200 mg daily.10 Four hundred ninety-seven women with prospectively evaluated premenstrual symptoms were randomized for 3 months of treatment. The results were similar to those in the earlier trial; the calcium group reported an overall 48% reduction in total symptom scores, compared with a 30% reduction in the placebo group. About one third of the study group was taking oral contraceptives. Subgroup analyses showed that the women taking OCs benefited just as much as those who were not taking them. The researchers hypothesized that women with PMS have an underlying defect in calcium regulation, and as a result have secondary hyperparathyroidism and vitamin D deficiency.11,12 A placebo-controlled trial examining the effect of calcium with vitamin D, given in the luteal phase only, is in progress [Personal communication, Thys-Jacobs, 2006].
EPIDEMIOLOGICAL DATA also support a relationship between high calcium and vitamin D intake and lower risk of PMS. In 2005, Bertone-Johnson and colleagues analyzed data from a subset of women enrolled in the Nurses' Health Study II, a large prospective cohort study.13 Calcium from food sources and vitamin D from all sources were compared between two groups: 1,057 women free from PMS at the baseline survey in 1991, but who were given that diagnosis sometime in the next 10 years; and 1,968 women who reported no diagnosis of PMS over the same 10 years. Women who had a high intake of either of these nutrients were less likely to have reported a diagnosis of PMS. This study suggests that dietary intake of both calcium and vitamin D might help prevent PMS.
Several questions remain regarding the role of calcium and vitamin D therapy for PMS, however. Although the epidemiologic study showed an independent effect of vitamin D, this vitamin has not been tested as an isolated supplement. Like-wise, calcium plus vitamin D has not been compared "head-to-head" with any other therapeutic approach. Based on the effect size compared to placebo for PMS, it should be similar or better than most other complementary/alternative medicines. Similarly, the possible additive benefit of combining calcium/vitamin D with other proven therapies has not been studied. Finally, calcium/vitamin D has not been studied in women with PMDD. For women with PMDD, SSRIs, drospirenone-containing OCs, or ovulation suppression are probably more effective.14
Recommendations for clinical practice