Reprint of “Use of medroxyprogesterone acetate for hormone therapy in postmenopausal women: Is it safe?”

• Few clinical studies have questioned the safety of MPA for HT.
• Increased breast cancer risk due to AR signaling disruption by MPA is questionable.
• Whether or not MPA used for HT contributes to CHD development is not clear.
• Studies on brain function in younger postmenopausal women are lacking.
• Use of MPA for HT in younger postmenopausal women can be considered safe.

Medroxyprogesterone acetate (MPA) has been in clinical use for over 30 years, and was generally considered to be safe until the results of long-term studies of postmenopausal hormone therapy (HT) using treatment with conjugated equine estrogens (CEE) combined with MPA and CEE alone suggested that MPA, and perhaps other progestogens, may play a role in the increased risk of breast cancer and cardiovascular diseases. This review examines critically the safety of MPA in terms of breast cancer and cardiovascular disease risk, and its effects on brain function. Research into mechanisms by which MPA might cause adverse effects in these areas, combined with the available clinical evidence, suggests a small increase in relative risk for breast cancer and stroke, and a decline in cognitive function, in older women using MPA with an estrogen for postmenopausal HT. However, short-term (less than 5 years) use of MPA with an estrogen in the years immediately after the onset of menopause for the management of vasomotor symptoms does not appear to be associated with any increased risk of these disorders.