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 .
Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial.
OBJECTIVE To report the histological findings of the endometrium of postmenopausal women who were r and omized to receive placebo , estrogen only , or one of three estrogen plus progestin ( E+P ) regimens in the Postmenopausal Estrogen/Progestin Interventions ( PEPI ) Trial . DESIGN A 3-year multicenter , r and omized , double-masked , placebo-controlled trial . PARTICIPANTS A total of 596 postmenopausal women aged 45 through 64 years without contraindication to hormone therapy . INTERVENTION Participants were r and omized and stratified in equal numbers to one of the following treatments in 28-day cycles : placebo , 0.625 mg/d of conjugated equine estrogens ( CEE ) , 0.625 mg/d of CEE plus 10 mg/d of medroxyprogesterone acetate ( MPA ) for the first 12 days , 0.625 mg/d of CEE plus 2.5 mg/d of MPA , or 0.625 mg/d of CEE plus 200 mg/d of micronized progesterone ( MP ) for the first 12 days . OUTCOME MEASURE Histology of endometrium collected at baseline , annual , or unscheduled visits by biopsy , curettage , or hysterectomy . ANALYSIS Intention to treat . RESULTS During follow-up women assigned to estrogen alone were more likely to develop simple ( cystic ) , complex ( adenomatous ) , or atypical hyperplasia than those given placebo ( 27.7 % vs 0.8 % , 22.7 % vs 0.8 % , and 11.8 % vs 0 % , respectively ) for the same types of hyperplasia ( P < .001 ) . Participants administered one of the three E+P regimens had similar rates of hyperplasia as those given placebo ( P = .16 ) . The occurrence of hyperplasia was distributed evenly across the 3 years of the trial . Women taking estrogens alone also had more unscheduled biopsies ( 66.4 % vs 8.4 % ; P < .001 ) and curettages ( 17.6 % vs 0.8 % ; P < .001 ) than women receiving placebo . The number of surgical procedures was similar for women receiving placebo and women receiving the E+P regimens ( P = .38 ) . Of the 45 women with complex ( adenomatous ) or atypical hyperplasia , study medications were discontinued in all , and the biopsy results of 34 ( 94 % ) of 36 women with hyperplasia reverted to normal with progestin therapy . The remainder had dilatation and curettage ( n = 2 ) or hysterectomy with ( n = 2 ) or without ( n = 6 ) prior medical therapy , or refused further biopsies ( n = 1 ) . One woman developed adenocarcinoma of the endometrium while receiving placebo . CONCLUSIONS At a dosage of 0.625 mg , the daily administration of CEE enhanced the development of endometrial hyperplasia . Combining CEE with cyclic or continuous MPA or cyclic MP protected the endometrium from hyperplastic changes associated with estrogen-only 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 .