The antiinflammatory properties of medroxyprogesterone acetate.

Medroxyprogesterone Acetate To the Editor: I have read the article by Wakatsuki et al1 with considerable interest. The study showed that the continuous oral treatment of postmenopausal women for 3 months with conjugated equine estrogens (CEE) (0.625 mg/day) alone or with medroxyprogesterone acetate (MPA) at the dose of 2.5 mg/day, significantly increased serum C-reactive protein (CRP) and amyloid A protein (SAA) levels. This effect was attenuated by the concurrent administration of MPA at the dose of 5 mg/day. CEE alone significantly decreased the concentration of E-selectin, but the concentrations of intracellular adhesion molecule (ICAM-1) and vascular cellular adhesion molecule (VCAM-1) did not change significantly. Concentrations of ICAM-1, VCAM-1, and E-selectin were all significantly reduced among postmenopausal women treated with CEE plus MPA 5 mg/day. The authors conclude that because androgens have antiinflammatory properties,2 androgenic progestins such as MPA (?) may attenuate proinflammatory effects of estrogens and may actually be responsible for the favorable effect of estrogen-progestogen combinations on inflammatory markers such as cellular adhesion molecules (ICAM-1, VCAM-1, E-selectin) and acute phase proteins (CRP and SAA) in postmenopausal women undergoing hormonal replacement therapy. MPA is a 17 -hydroxyprogesterone derivative and it is structurally related to progesterone and not testosterone.3 In addition to binding to progesterone receptor, MPA may interact with the glucocorticoid receptor.4 Progesterone and its derivatives have antiinflammatory and immunosuppressive properties that are relevant for maintenance of pregnancy.5 Because MPA is not a 19nortestosterone derivative (androgenic progestin), its antiinflammatory properties can be attributed to its ability to interact with the progesterone and glucocorticoid receptors, not the androgen receptor.