CONCLUSION Estrogen with an osteoblast P4R-acting progestin ( EPT ) in these five published RCT provides Level 1 evidence that MPA caused significantly greater annual percent spinal BMD gains than the same dose of ET .
OBJECTIVE To assess whether progesterone ( P4 ) or osteoblast P4 receptor-acting progestin ( P ) contributed to estrogen ( E ) therapy-related  increased areal bone mineral density ( BMD ) in r and omized controlled trials ( RCT ) with direct r and omization to estrogen ( ET ) or estrogen-progestin ( EPT ) therapy .
Cyclic medroxyprogesterone treatment increases bone density: a controlled trial in active women with menstrual cycle disturbances.
OBJECTIVE Bone loss occurs in young women who experience amenorrhea or ovulatory disturbances . The purpose of this study was to determine whether bone loss could be prevented by simulating a more normal hormonal pattern , using treatment with cyclic medroxyprogesterone , with or without calcium supplementation , in physically active women with disturbed menstruation . DESIGN This study was a 1-year r and omized , double-blind , placebo-controlled trial . Women who were stratified by menstrual cycle disturbance were r and omized into four groups . The outcome variable was the change in spinal bone density measured by dual energy techniques . SETTING A large metropolitan area . PARTICIPANTS Sixty-one healthy , normal-weight physically active premenopausal women aged 21 to 45 years who experienced amenorrhea , oligomenorrhea , anovulation , or short luteal phase cycles completed the study . INTERVENTION Therapies were cyclic medroxyprogesterone ( 10 mg/day for 10 days per month ) and calcium carbonate ( 1,000 mg/day of calcium ) in four groups : ( A ) ( n = 16 ) cyclic medroxyprogesterone plus calcium carbonate ; ( B ) ( n = 16 ) cyclic medroxyprogesterone with calcium placebo ; ( C ) ( n = 15 ) placebo medroxyprogesterone with active calcium ; or ( D ) ( n = 14 ) both medroxyprogesterone and calcium placebos . RESULTS The initial bone density ( mean = 1.12 g/cm2 ) did not differ by group ( P = 0.85 ) . The 1-year bone density change was strongly related to treatment with medroxyprogesterone ( P = 0.0001 ) and weakly to calcium ( P = 0.072 ) treatment . Bone density increased significantly ( + 1.7 % + /- 0.5 % , + /- SEM , P = 0.004 ) in the medroxyprogesterone-treated groups ( A and B ) , did not change in the calcium-treated group ( C ) ( -0.7 % + /- 0.6 % , P = 0.28 ) , and decreased on both placebos ( D ) ( -2.0 % + /- 0.6 % , P = 0.005 ) . CONCLUSIONS Cyclic medroxyprogesterone increased spinal bone density in physically active women experiencing amenorrhea or ovulatory disturbances . POTENTIAL CLINICAL SIGNIFICANCE : Amenorrhea , oligomenorrhea , anovulation , and short luteal phase cycles are common in premenopausal women and associated with  spinal bone loss occurring at a stage of life when bone density would normally be stable or increasing . This controlled trial shows a significant gain in bone in women in the cyclic medroxyprogesterone intervention group , whereas those subjects in the placebo group  lost bone .  Calcium supplementation appeared to be helpful but did not reach statistical significance . The implication s of these findings for the prevention of osteoporosis warrant further investigation
CONCLUSION Estrogen with an osteoblast P4R-acting progestin ( EPT ) in these five published RCT provides Level 1 evidence that MPA caused significantly greater annual percent spinal BMD gains than the same dose of ET .
OBJECTIVE To assess whether progesterone ( P4 ) or osteoblast P4 receptor-acting progestin ( P ) contributed to estrogen ( E ) therapy-related  increased areal bone mineral density ( BMD ) in r and omized controlled trials ( RCT ) with direct r and omization to estrogen ( ET ) or estrogen-progestin ( EPT ) therapy .