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 .
Esterified estrogen therapy in postmenopausal women. Relationships of bone marker changes and plasma estradiol to BMD changes: A two-year study
Objective To determine the relationships among bone mineral density changes , bone marker changes , and plasma estrogens in postmenopausal women receiving estrogen replacement therapy .  Design A total of 406 postmenopausal women received 1,000 mg calcium and continuous esterified estrogens ( 0.3 mg , 0.625 mg , or 1.25 mg ) or placebo daily for up to 24 months . Bone mineral density and bone marker measurements were determined at 6-month intervals ; plasma estrogens were measured in a subset after 12 , 18 , and 24 months . Results Esterified estrogens produced significant increases in bone mineral density ( lumbar spine , hip ) compared with baseline and placebo at 6 , 12 , 18 , and 24 months . Bone markers decreased from baseline with all esterified estrogen doses relative to placebo . Bone marker changes at 6 months correlated negatively with bone mineral density changes at 24 months ( correlation coefficient range = −0.122 to −0.439 ) . The strongest correlation was noted for spine bone mineral density changes and serum osteocalcin . Mean plasma estrogen levels increased with esterified estrogen dose , and bone mineral density changes correlated positively with plasma estrogen levels . Positive bone mineral density changes were noted in treatment groups with plasma estradiol levels at and above 25 pg/mL. Conclusions Esterified estrogens , at doses from 0.3 mg to 1.25 mg/day , unopposed by progestin , increase bone mineral density of the spine and hip in postmenopausal women .  These bone mineral density changes correlated significantly with bone marker changes at 6 months and with plasma estrogens at 12 , 18 , or 24 months . Data variability minimizes the predictive value of the bone marker changes in monitoring individual therapy
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 .