What are the main risks associated with hormone replacement therapy?

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    Last Updated: October 13, 2024

    HRT may increase the risk of blood clots (venous thromboembolism), breast cancer, stroke, and dementia.[1] However, these risks are influenced by several factors, including the type or combination of hormones used, the dosage form (e.g., oral pill, patch, vaginal cream), a woman's age or time since menopause onset, and personal or family medical history. For example, HRT for local use in the vagina is not significantly absorbed into the blood and does not seem to contribute to the above risks (accordingly, it also does not improve hot flashes).[2][3]

    To put the potential risks (and benefits) of HRT into context, let’s imagine we have a group of 1,000 postmenopausal women and we follow them for 5–7 years. Compared to women who are not receiving HRT, the group of 1,000 women taking HRT might experience the following:[1]

    Estrogen*Estrogen + Progesterone
    Stroke8 more cases5 more cases
    Invasive Breast CancerNo difference5 more cases
    Venous Thromboembolism8 more cases12 more cases
    DementiaNo difference9 more cases
    Colorectal CancerNo difference3 less cases
    Fractures39 less cases23 less cases
    Type 2 Diabetes13 less cases8 less cases

    * Taking estrogen alone is only appropriate for women who have had their uterus removed, due to an increased risk of endometrial cancer when estrogen is taken without progesterone.[4]

    Importantly, these numbers are based on studies that primarily used oral HRT in postmenopausal women over 60. Some research suggests that when HRT is started within 10 years of menopause onset, or before the age of 60, there is little to no increased risk of stroke or dementia.[5][6][2] Additionally, observational research suggests that transdermal HRT (e.g., topical gel or patch) may not carry the same risk of blood clots as oral HRT.[7][8] This may be due to how the medications interact with the liver. Oral HRT must first pass through the liver before entering the blood, and this interaction can increase the production of several proteins that promote clotting. In contrast, transdermal HRT absorbs directly into the blood through the skin, bypassing the liver, which allows for lower overall doses and reduced production of clotting proteins.[8]

    Ultimately, the choice for or against HRT needs to be made in consultation with a healthcare provider and on a case-by-case basis depending on one's unique situation.