Chapter 3. Impact of estrogens on hemostasis.

Area of Science:

• Endocrinology
• Hematology
• Pharmacology

Background:

• Estrogens are known to increase the risk of arterial and venous thrombosis by affecting coagulation and anticoagulation factors.
• The precise molecular mechanisms underlying estrogen-induced thrombosis remain unclear, but variations in estrogen type, dose, and route of administration may influence thrombotic risk.

Purpose of the Study:

• To review the hemostatic effects of different estrogens, including ethinyl estradiol (EE), estradiol (E2), and estetrol (E4), in the context of hormonal contraception and hormone therapy.
• To assess the impact of these estrogens on venous thromboembolism (VTE) risk.

Main Methods:

• Review of existing literature on estrogen effects on hemostatic markers and VTE risk in premenopausal and postmenopausal women.
• Comparison of hemostatic profiles associated with different estrogen-based contraceptives and hormone therapies.

Main Results:

• Ethinyl estradiol (EE) and estradiol (E2) in combined oral contraceptives (COCs) show minimal to weaker hemostatic effects, with EE's VTE risk being dose-dependent.
• The novel estrogen estetrol (E4) appears to have a neutral hemostatic effect.
• Hormone therapy (HT) with conjugated equine estrogens (CEE) increased VTE risk; results for oral E2 are mixed, and transdermal HT may have a lesser impact.

Conclusions:

• Estrogen type, dose, and route significantly influence hemostatic balance and VTE risk.
• Estetrol (E4) shows promise as a safer alternative due to its neutral hemostatic profile.
• Further research is needed to fully elucidate the VTE risk associated with various estrogen formulations, particularly transdermal HT.