MPA: Medroxy-Progesterone Acetate Contributes to Much Poor Advice for Women

Abstract

The article in this issue by Irwin and colleagues from the laboratory of Roberta Diaz Brinton extends a multipart investigation on the differences in the neural actions of medroxyprogesterone acetate (MPA) vs. progesterone (P4, pregn-4-ene-3, 20-dione). This issue became critically important after the Women's Health Initiative (WHI) trial. This trial, which used conjugated equine estrogens alone (PremarinTR) or in conjunction with MPA to reduce the uterotrophic effect of equine estrogens (PremproTR), has turned women's health at menopause into a minefield. It is old news, but the combined hormone arm was ended prematurely because of increased incidence of breast cancer and the 11-year follow-up study found increased mortality attributable to breast cancer (1). Increased risk of dementia, stroke, and cognitive decline was also present in both arms relative to placebo in women aged 65 yr and older (2). While the WHI trial made a valuable contribution in revealing the risks associated with conjugated equine estrogens plus MPA treatment in postmenopausal women, it unfortunately generated considerable controversy in the field because it was interpreted as an indictment of postmenopausal hormone replacement, when in fact, it did not study hormone replacement at all: that would have required use of the natural hormones, estradiol and progesterone. The actions of the natural hormones are significantly different from those of Premarin and MPA. The Irwin et al. (3) study focuses on the progestin problem.