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Menopausal Hormone Therapy and Cardiovascular Disease: The Role of Formulation, Dose, and Route of Delivery

Chrisandra L Shufelt 1JoAnn E Manson 2 3

J Clin Endocrinol Metab. 2021 Apr 23;106(5):1245-1254.doi: 10.1210/clinem/dgab042.


Context: This mini-review provides an overview of menopausal hormone therapy (HT) and cardiovascular disease (CVD) risk, with a focus on the role of hormone formulation, dose, and route of delivery.

Methods: This summary is based on authors’ knowledge in the field of menopausal HT and supplemented by a PubMed search using the terms «menopause hormone therapy,» «transdermal,» «estradiol,» «conjugated estrogens,» «bioidentical,» «cardiovascular disease,» «lipoproteins,» «glucose,» «progestogens,» «low dose.»

Results: Available evidence indicates that oral unopposed estrogens have a favorable effect on lipoprotein levels, glycemia, insulin, and CVD risk; however, the addition of progestogens blunts the lipid-related effects. The progestogen with the smallest attenuating effect is micronized progesterone. Transdermal estrogens have less effect on coagulation, inflammation, and lipids than oral estrogens and observational studies suggest they pose a lower risk of venous thromboembolism and stroke than oral estrogens. Clinical effects of hormones were not consistently dose dependent.

Conclusions: Although HT continues to have an important role in menopause management, it is not recommended for primary or secondary CVD prevention. Different formulations, doses, and routes of delivery of HT have different effects on cardiometabolic markers and risks of clinical CVD events. However, long-term trials evaluating clinical outcomes with transdermal and other alternate HT regimens are limited.