Effect of progestogen and progestogen type on hemostasis measures in postmenopausal women

In Brief Objective: The contribution of progestogen therapy or progestogen type to risks and benefits of estrogen treatment is inadequately characterized. We examined the effect of conjugated equine estrogens (CEE) with and without concomitant progestogen treatments on changes in hemostasis measures among Postmenopausal Estrogen/Progestin Intervention participants. Design: Postmenopausal Estrogen/Progestin Intervention was a clinical trial that randomized 875 postmenopausal women to one of five arms: placebo, CEE alone, CEE with cyclic micronized progesterone (MP), CEE with cyclic medroxyprogesterone acetate (MPA), and CEE with continuous MPA. Twelve hemostasis assays were measured in a substudy at baseline and 12 and 36 months. Using 12- and 36-month changes in hemostasis measures, we calculated change ratios for two comparisons of active treatments: CEE+MPA versus CEE and CEE+MPA versus CEE+MP. Results: Hemostasis measures were available for 288 women. Compared with women assigned to CEE alone, 12-month increases in factor VIIc and protein C among women assigned to CEE+MPA were relatively smaller (ratios: 0.94 [95% CI: 0.89-0.98] and 0.96 [95% CI: 0.92-1.00]), respectively. Compared with women assigned to CEE+MP, women assigned to CEE+MPA had smaller increases in factor VIIc and larger decreases in plasminogen activator inhibitor-1 antigen at 12 months (ratios: 0.94 [95% CI: 0.90-0.98] and 0.70 [95% CI: 0.53-0.93], respectively). Thirty-six month ratios were similar to these. Women assigned to CEE+MPA had smaller increases in protein C than those assigned CEE+MP at 36 months only (ratio: 0.95 [95% CI: 0.91-0.99]). No other associations were significant. Conclusions: We found modest yet significant differences in hemostasis measure changes when comparing progestogen use and progestogen type in postmenopausal women using CEE. The contribution of progestogen therapy or progestogen type to risks and benefits of estrogen treatment is inadequately characterized. This study examined the effect of conjugated equine estrogens with and without concomitant progestogen treatments on changes in 12 hemostasis measures and found modest yet significant differences in changes when comparing progestogen use and progestogen type in postmenopausal women.