Low thrombin generation in postmenopausal women using estetrol.

Area of Science:

• Endocrinology
• Reproductive Medicine
• Pharmacology

Background:

• Estetrol (E4) is a novel estrogen used for vasomotor symptoms.
• E4 activates the nuclear estrogen receptor α (ERα) but antagonizes membrane-initiated pathways.
• Distinct E4 properties may lead to a low impact on hemostasis.

Purpose of the Study:

• To assess the effect of E4 on coagulation in postmenopausal women.
• Utilized the thrombin generation assay (TGA) to evaluate hemostasis.
• Investigated the impact of different oral E4 doses on coagulation parameters.

Main Methods:

• A multicenter, randomized, placebo-controlled study (NCT02834312) was conducted.
• Postmenopausal women received oral E4 (2.5-15 mg) or placebo daily for 12 weeks.
• Thrombograms and TGA parameters were analyzed at baseline and after 12 weeks.

Main Results:

• All E4 treatment groups maintained mean thrombograms within established reference ranges.
• Thrombin generation assay parameters remained within normal limits across all groups.
• No clinically relevant changes in coagulation were observed after 12 weeks of E4 treatment.

Conclusions:

• Oral estetrol (E4) demonstrates a neutral profile on hemostasis in postmenopausal women.
• Even the highest dose (15 mg) of E4 did not cause clinically significant alterations in coagulation.
• E4 appears to be a safe option regarding hemostatic effects for managing menopausal symptoms.