Topical progesterone cream has an antiproliferative effect on estrogen-stimulated endometrium.

Oral progestins have been the mainstay in hormone replacement therapy (HRT). However, their users have been plagued by bothersome side effects such as irritability, mood swings, bloating, and headache (1). These problems contribute to patients discontinuing HRT, thus denying them its long-term benefits. The health care community continues to search for clinically effective alternative progestins. Investigators have been skeptical of the clinical utility of topical progesterone cream (PC) (2). However, our placebo-controlled study demonstrated that patients experienced improvement in vasomotor symptoms through the use of PC (3). This systemic finding suggests a possible role for topical PC on the endometrium as well. To this end, we designed a randomized, double-masked, placebo-controlled study for postmenopausal women.