Bioidentical Progestins The Postmenopausal Estrogen-Progestin Intervention (PEPI) trials provided a multicentered, randomized controlled trial that, among other things, compared conjugated equine estrogen plus medroxyprogesterone acetate with conjugated equine estrogen plus natural or micronized progesterone (104). The trial compared 12 days of 10 mg of medroxyprogesterone acetate with 200 mg of micronized progesterone. The micronized progesterone provided equal protection of the endometrium and was better at protecting the beneficial effects of the conjugated equine estrogen on the lipid profile. Patients reported that micronized progesterone had significantly fewer side effects than medroxyprogesterone acetate. This was the case in several other trials (105,106). Given these data, there is no reason not to prescribe micronized progesterone. The arm of the Women’s Health Initiative that was prematurely discontinued was the conjugated equine estrogen/medroxyprogesterone acetate arm. The conjugated equine estrogen– alone arm was continued. The role and the effect of medroxyprogesterone acetate should be closely examined. In ovariectomized rhesus monkeys, E2 plus medroxyprogesterone acetate interfered with ovarian estrogen protection against coronary vasospasm. E2 plus micronized progesterone protected against coronary vasospasm. Given the increased cardiovascular risks in women taking conjugated equine estrogen and medroxyprogesterone acetate, combined with the positive data from PEPI, micronized progesterone is an excellent choice for patients who are taking systemic estrogen who still have a uterus.
Table 13.11 Progesterone and Wild Yam Creams
Natural progesterone was used as a single agent in the treatment of menopausal symptoms. The typical dose is 100 mg per day. More research is needed to demonstrate efficacy.
Yam Creams, Progesterone Creams Yam creams and progesterone creams, which are both sold over the counter, are distinctly different products. Yam creams should, by definition, not contain progesterone, but rather should contain phytoprogesterones, plant products that are progesterone-like (Table 13.11). Progesterone creams, by contrast, should contain progesterone. Part of the challenge is that there is a large media presence asserting that progesterone creams can solve all that ails menopausal women. These creams are not regulated by the FDA. Their content is highly variable, ranging from 700 mg progesterone per ounce to less than 2 mg per ounce in products whose names imply that they are progesterone creams, not yam creams. The absorption of these products is highly variable.
Wild yam creams (which refer to the genus name Dioscorea villosa, rather than the fact that they are grown in the wild) are applied topically. They contain steroidal saponins, including diosgenin, and claim to affect estrogen steroidogenesis. Although these are interesting products, studies of their safety and efficacy are needed. In one double-blind, placebo-controlled crossover study, after a 4-week baseline period, patients received 3 months of active treatment and 3 months of placebo. Symptom diaries were maintained at baseline and then for 1 week of each month. Blood and salivary hormone levels as well as serum lipids were assessed at baseline, 3 months, and 6 months. At 3 months there were no significant side effects and no change in levels of blood pressure, weight, lipid levels, follicle-stimulating hormone, glucose, estradiol, or progesterone. In terms of symptom relief, the placebo and yam cream had a minor effect on the number and severity of ﬂashes. Wild yam creams appear to be free of side effects, and they appear to have little effect on menopausal symptoms (107).