To clot, or not to clot: The dilemma of hormone treatment options for menopause

Thromb Res. 2022 Oct;218:99-111. doi: 10.1016/j.thromres.2022.08.016. Epub 2022 Aug 19.


Untreated menopause may have serious health implications, but treatments can have dangerous side effects. We evaluate menopausal symptoms as well as available treatments -the routes of administration and their effect on blood coagulation. Menopausal females may experience hot flushes, vulva- and vaginal atrophy and osteoporosis. Many treatments are available to relieve these symptoms such as Conjugated Equine Estrogen and bioidentical hormones. The routes of administration include oral and transdermal. Hormones that are administered orally undergo a hepatic first pass metabolism. The by-products have a lower efficacy and possibly enhanced side effects. Furthermore, hormone treatments influence the coagulation cascade through coagulation factors or their regulators. Increased coagulation poses a risk for venous thromboembolism. Currently a definite conclusion on whether the side effects from hormone treatments exceed the risk of untreated menopause cannot be made. However, a more individualised approach to hormone treatments may be the most feasible solution to this dilemma.

Keywords: Bioidentical hormones; Coagulation; Conjugated Equine Estrogen; Estradiol; Estrogen; Hormone Replacement Therapy; Menopause; Oral; Progesterone; Transdermal; VTE.

Publication types

  • Review

MeSH terms

  • Estradiol
  • Estrogen Replacement Therapy / adverse effects
  • Estrogens / therapeutic use
  • Estrogens, Conjugated (USP)* / adverse effects
  • Estrogens, Conjugated (USP)* / therapeutic use
  • Female
  • Hot Flashes / chemically induced
  • Hot Flashes / drug therapy
  • Humans
  • Menopause
  • Thrombosis* / etiology


  • Estrogens
  • Estrogens, Conjugated (USP)
  • Estradiol