SHORT-TERM EFFECTS OF HIGH-DOSE ORAL MEDROXYPROGESTERONE ACETATE ON BONE-DENSITY IN PREMENOPAUSAL WOMEN

Despite the widespread use of the C-21 progestin medroxyprogesterone a cetate (MPA) in hormone replacement therapy and gynecological practice , its effects on bone density are uncertain, with contradictory report s in the literature. We have examined the short term changes in bone d ensity at the lumbar spine (a predominantly trabecular site) and the f emoral neck (a predominantly cortical site) in 13 premenopausal women prescribed high dose MPA (50 mg/day) for gynecological disorders and i n 12 control subjects. Compared to basal values, lumbar spine bone min eral density (measured by dual energy x-ray absorptiometry) fell progr essively by a mean 2.4% at 6 months and 4.1% at 12 months (both P < 0. 01); in five subjects who continued the drug, it had fallen by a mean 5.9% at 20 months (P < 0.002). The spinal bone loss in the MPA users w as significantly greater than that in controls (P < 0.005 at 6 months; P < 0.01 at 12 months) and occurred despite a significant gain in bod y weight in the women using MPA (median, 3.5 kg at 6 months; P < 0.01) . In four subjects in whom bone density was measured 6 months after ce ssation of MPA, spinal bone density showed significant recovery (mean increment, 2.8%; P < 0.025). Femoral neck bone density measurements di d not differ between the groups. MPA induced amenorrhea in all subject s who continued with it beyond 6 months, and the amenorrheic subjects were estrogen deficient (median plasma estradiol, 70 pmol/L). We concl ude that, when given in doses sufficient to induce hypogonadism, MPA u se is associated with significant early loss of trabecular bone, which is probably the consequence of estrogen deficiency.