Since the 1940s, vitamin E has been studied for the treatment of hot ﬂashes. Although some early studies showed promising results, other studies evaluating 200-to 600-IU doses failed to show an effect. There was one small trial with 51 women that showed an effect on hot ﬂashes of 400 IU daily, but it was suggested that up to 1,200 IU may be necessary to have an effect, doses which are too high to recommend. Vitamin E is an anticoagulant, and spontaneous subarachnoid hemorrhages were reported. One study examining vitamin E in menopausal patients with breast cancer found that after 4 weeks of 800 IU daily, the patients in the treatment arm had on average one less hot ﬂash per day. Although this finding was statistically significant, it was not significant clinically (67).
Premenstrual Symptoms and Menopause Black cohosh (Cimicifuga racemosa) has traditionally been used for relief of both PMS and menopause symptoms. It has been used in the Native American population for centuries and in Germany since 1950. Its most studied form is a brand called Remifemin, which is standardized to 1 mg of deoxyactein and is administered in a dose of 40 mg two times daily. Most early studies were uncontrolled, but later studies were more methodologically sound. Initially, it was felt that black cohosh decreased luteinizing hormone levels, but it is believed that it may behave like a selective estrogen receptor modulator (SERM), and act at serotonin receptors. It does not contain phytoestrogens and does not have an estrogenic effect on vaginal cytology. Additionally, there are no changes in hormone levels in women taking black cohosh. In laboratory studies, black cohosh actually suppresses rather than stimulates breast cells (68). Women taking black cohosh show significant improvement in menopausal symptoms, anxiety, and vaginal epithelium. It is well tolerated with no side effects noted. When compared with hormone therapy, black cohosh has comparable results, and women show improvements in hot ﬂashes, fatigue, irritability, and vaginal dryness. In a meta-analysis of randomized controlled trials of black cohosh, the authors concluded that there was a trend in reducing vasomotor symptoms. One study of 304 women demonstrated a decrease in the number and intensity of hot ﬂashes, improvement in mood, sleep, sweating, and sexual disorders. In a double-blind, placebo-controlled trial, black cohosh, 40 mg, was compared with conjugated estrogen, 0.6 mg, and placebo (69). The researchers monitored 62 women for 3 months and black cohosh was found to have effects equal to conjugated estrogen and to be superior to placebo in decreasing climacteric symptoms. Black cohosh had no effect on endometrial thickening as measured by vaginal ultrasonography, unlike conjugated estrogen, which had a significant increase in endometrial thickening. Additionally, both black cohosh and conjugated estrogen increased the vaginal superficial cells. In a trial comparing black cohosh to placebo and to estrogen over 12 months, black cohosh was found to be effective (70). In a large-scale, controlled, observational study of black cohosh alone and black cohosh in combination with St. John’s wort involving 6,141 women, both therapies were effective and well tolerated. For psychological symptoms, the combination was superior to black cohosh alone (71). Although many published studies have design weaknesses and more research is needed, black cohosh appears to be safe and may be efficacious for the treatment of menopausal symptoms. It should be started at 20 to 40 mg twice daily, standardized to 2.5 triterpenes The Commission E recommends 40 to 200 mg (72).