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 | |
|---|---|---|
| Stroke | 8 more cases | 5 more cases |
| Invasive Breast Cancer | No difference | 5 more cases |
| Venous Thromboembolism | 8 more cases | 12 more cases |
| Dementia | No difference | 9 more cases |
| Colorectal Cancer | No difference | 3 less cases |
| Fractures | 39 less cases | 23 less cases |
| Type 2 Diabetes | 13 less cases | 8 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.
References
- ^Gartlehner G, Patel SV, Reddy S, Rains C, Schwimmer M, Kahwati LHormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.JAMA.(2022-Nov-01)
- ^Mehta J, Kling JM, Manson JERisks, Benefits, and Treatment Modalities of Menopausal Hormone Therapy: Current Concepts.Front Endocrinol (Lausanne).(2021)
- ^Pavlović RT, Janković SM, Milovanović JR, Stefanović SM, Folić MM, Milovanović OZ, Mamillapalli C, Milosavljević MNThe Safety of Local Hormonal Treatment for Vulvovaginal Atrophy in Women With Estrogen Receptor-positive Breast Cancer Who Are on Adjuvant Aromatase Inhibitor Therapy: Meta-analysis.Clin Breast Cancer.(2019-Dec)
- ^Nappi REThe 2022 hormone therapy position statement of The North American Menopause Society: no news is good news.Lancet Diabetes Endocrinol.(2022-Dec)
- ^Boardman HM, Hartley L, Eisinga A, Main C, Roqué i Figuls M, Bonfill Cosp X, Gabriel Sanchez R, Knight BHormone therapy for preventing cardiovascular disease in post-menopausal women.Cochrane Database Syst Rev.(2015-Mar-10)
- ^Kim JE, Chang JH, Jeong MJ, Choi J, Park J, Baek C, Shin A, Park SM, Kang D, Choi JYA systematic review and meta-analysis of effects of menopausal hormone therapy on cardiovascular diseases.Sci Rep.(2020-Nov-26)
- ^Vinogradova Y, Coupland C, Hippisley-Cox JUse of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases.BMJ.(2019-Jan-09)
- ^Rovinski D, Ramos RB, Fighera TM, Casanova GK, Spritzer PMRisk of venous thromboembolism events in postmenopausal women using oral versus non-oral hormone therapy: A systematic review and meta-analysis.Thromb Res.(2018-Aug)