Pharmacologic doses of medroxyprogesterone may cause bone loss through glucocorticoid activity: An hypothesis

A number of studies suggest that progestagens may have beneficial effects on bone metabolism. C-21 Progestin medroxyprogesterone acetate (MPA) is one of the most commonly prescribed progestins for hormone replacement therapy and in gynecologic practice. However, it appears that MPA with significant glucocorticoid (GC) activity may decrease bone density. In this review, we argue that bone loss associated with MPA administration is caused by decreased osteoblast differentiation as a result of MPA occupying the GC receptor, since increasing GC receptor occupancy beyond that reached at normal (= optimal) GC concentrations attenuates osteoblast differentiation. We propose that progestins with no GC activity may be a better choice for progestagen therapy to achieve more beneficial effects on bone metabolism. affinity for the glucocorticoid (GC) receptor have beneficial effects on bone density, whereas progestins with significant affinity for the GC receptor may not improve bone density. In this review, we will focus in particular on the question of whether medroxyprogesterone acetate (MPA) is an appropriate progestin to use for progestagen therapy in view of its considerable GC activity on bone.