Twenty-six postmenopausal women (mean age, 57.3 years) received 0.625 mg/day of conjugated equine estrogens and 2.5 mg of medroxyprogesterone acetate (Prempro; Wyeth) or 0.625 mg/day of conjugated equine estrogens and 20 mg twice a day of transdermal progesterone cream (Pro-gest; Transitions for Health). After six months, each woman was switched to the alternate treatment for an additional six months. Endometrial biopsies were performed at the end of each treatment period. Seventy-seven percent of the women preferred progesterone cream to medroxyprogesterone acetate (p < 0.001). Of the 52 post-treatment endometrial biopsies performed, 40 revealed atrophic endometrium and 12 showed proliferative endometrium (7 in the medroxyprogesterone acetate group and 5 in the progesterone cream group). There was no evidence of endometrial hyperplasia in any of the specimens. The incidence of vaginal spotting was similar in the two groups.

Comment: The results of this pilot study suggest that a low-dose of transdermal progesterone has a similar effect on the endometrium as does medroxyprogesterone acetate in postmenopausal women receiving conjugated equine estrogens. A larger study is needed to confirm that such a small dose of natural progesterone is sufficient to prevent endometrial hyperplasia in women received estrogen-replacement therapy. Nevertheless, the results are encouraging, considering that medroxyprogesterone acetate causes numerous side effects and low-dose natural progesterone is generally well tolerated. As an added benefit, some studies suggest that transdermal application of progesterone can reverse osteoporosis in postmenopausal women, although other studies have failed to confirm that finding.

Leonetti HB, et al. Transdermal progesterone cream as an alternative progestin in hormone therapy. Altern Ther 2005;11(6):36-38.