Different changes in postmenopausal hemostasis measure with, without concomitant progestogen

Results from the Postmenopausal Estrogen/Progestin Intervention study revealed that postmenopausal women receiving conjugated equine estrogens experienced modest but significant differences in hemostasis measure with and without concomitant progestogen treatments.

Researchers randomly assigned 875 postmenopausal women to five different arms: conjugated equine estrogens alone; conjugated equine estrogens plus cyclic micronized progesterone; conjugated equine estrogens plus cyclic medroxyprogesterone acetate; conjugated equine estrogens plus continuous cyclic medroxyprogesterone acetate; or placebo. They measured hemostasis assays at baseline, 12 months and 36 months. Hemostasis change ratios were compared for conjugated equine estrogens alone vs. conjugated equine estrogens plus cyclic medroxyprogesterone acetate and for conjugated equine estrogens plus cyclic micronized progesterone vs. conjugated equine estrogens plus cyclic medroxyprogesterone acetate.

Examination of hemostasis measures for 288 women revealed smaller 12-month increases in factor VIIc (ratio: 0.94; 95% CI, 0.89-0.98) and protein C (ratio: 0.96; 95% CI, 0.92-1.00) among women assigned to conjugated equine estrogens plus cyclic medroxyprogesterone acetate compared with women assigned to conjugated equine estrogens alone.

Women assigned to conjugated equine estrogens plus cyclic medroxyprogesterone acetate also had larger 12-month decreases in plasminogen activator inhibitor 1 antigen (ratio: 0.70; 95% CI, 0.53-0.93) compared with women assigned to conjugated equine estrogens plus cyclic micronized progesterone. The changes were also similar at 36 months.

When the researchers compared women assigned to conjugated equine estrogens plus cyclic medroxyprogesterone acetate and women assigned to conjugated equine estrogens plus cyclic micronized progesterone, the addition of cyclic medroxyprogesterone acetate was associated with smaller increases in protein C at 36 months only (ratio: 0.95; 95% CI, 0.91-0.99). – by Katie Kalvaitis

Menopause. 2008;15:6.

The study by Smith et al is a follow-up of the PEPI study in which researchers looked at various conjugated equine estrogens plus progestogen combinations as well as conjugated equine estrogens alone. In this study the researchers looked at procoagulants in women on these preparations and found no consistent effect that would modify thrombotic risk. Thus the mechanism by which hormones cause thrombosis is unclear and there was no clear effect of the progestins.

– Michelle P. Warren, MD

Endocrine Today Editorial Board member