Background   Vasomotor symptoms (VMS) including hot flashes and night sweats are common and disabling symptoms of menopause. They can also occur due to estrogen/androgen deprivation from cancer treatment. VMS require comprehensive assessment (see Fast Fact #261) as they often appear with other symptoms such as sleep disturbances, mood disorders, and arthralgia. This Fast Fact reviews hormonal pharmacological interventions for VMS. Hormone therapy (HT) is the most effective treatment for VMS (1) and significantly improves quality of life. In patients with cancer, however, the decision-making to pursue HT for VMS is more complex; clinicians should collaborate closely with the patient’s treating cancer specialists before prescribing HT.  Women’s health clinicians, gynecologists, and urologists are other resourceful specialists for patients with VMS and serious illness. 

Estrogen therapy  Estradiol is chemically identical to endogenous estrogen (2) and can be delivered systemically through transdermal or oral routes.  

• Transdermal (TD) estradiol is the gold standard for treating VMS. It is available as a patch, gel, and spray. Because it is absorbed through the skin, it bypasses the hepatic first-pass effect and avoids prothrombotic changes and therefore does not significantly increase VTE risk (3). There is a growing body of research examining the use of TD estrogen as androgen suppression for men with prostate cancer, which avoids low estrogen levels and is associated with less VMS (4).
• Oral estradiol is associated with a small increased risk of venous thrombosis or stroke (5). Risk factors such as obesity, smoking, increasing age, and thrombophilia further increase this risk.
• Vaginal suppositories have minimal systemic absorption and therefore are not effective for VMS. They are primarily used for genitourinary symptoms (see Fast Fact #511).
• Premenopausal women who enter cancer treatment–related menopause usually need higher, more physiologic estrogen doses than postmenopausal women because their estrogen levels drop abruptly and more severely. Collaboration with clinical pharmacists on dosing is recommended.
• Common adverse effects of all systemic estrogen therapy include breast tenderness, vaginal bleeding, headache, nausea, abdominal bloating, and skin irritation with TD formulations (6).    

Progesterone Therapy  Progesterone is indicated for women with an intact uterus, as unopposed estrogen monotherapy can cause endometrial hyperplasia and increase the risk of endometrial cancer. Progesterone has additional hormonal benefits through stimulating GABA production, promoting relaxation, reducing anxiety, and improving quality of sleep. Micronized progesterone (bioidentical form of progesterone extracted from plants) is preferred due to a more favorable cardiovascular and metabolic profile compared to older synthetic progestins (7). It closely mimics natural ovarian progesterone and is available as an oral capsule. Standard hormone HT protocols use progesterone at a steady, continuous dose rather than dose cycling. Side effects are mild – mood changes, bloating, and withdrawal bleeding.    

Changing perspectives on hormone therapy   HT became controversial in the early 2000s due to Women’s Health Initiative (WHI) study that suggested increased risks of coronary heart disease (CHD) events, venous thromboembolism (VTE), stroke, and invasive breast cancer. However, more recent interpretations indicate these risks may are overstated.  

• CHD events and death: Younger menopausal women (<60 years) using HRT to treat vasomotor symptoms do not appear to be at an increased risk of dying or experiencing CHD events. (9)
• VTE and stroke: Subgroup analysis from the initial WHI study suggests that when HT is initiated within 10 years of symptom onset, the overall risk of both VTE and stroke are very low in otherwise healthy, young (<60) and postmenopausal women (8). Meta-analysis further confirms that non-oral (transdermal) HT does not significantly increase VTE risk, even in women with preexisting VTE risk factors (10). The North American Menopause Society (NAMS) 2022 guidelines state that the attributable risk of stroke is rare and statistically insignificant. (11)
• Breast cancer: Estrogen-only HT does not increase breast cancer risk (13), and micronized progesterone appears to have no increased/lower breast cancer risk than older, synthetic progestins used in the WHI study (14). HT should generally be avoided in patients with a history of breast cancer because of concerns regarding the potential risk of cancer recurrence, and its use should only be considered after careful multidisciplinary assessment of risks and benefits. 

Patients with serious illness   Among patients with limited prognoses, HT should be individualized focusing on symptom alleviation and quality of life through shared decision-making (15,16). While data on HT in patients with serious illness remain limited, potential benefits include relief of VMS and GU symptoms, improvements in mood and sleep quality, and fracture prevention. Potential risks of VTE, stroke, and cardiovascular disease should be assessed considering recent data suggesting that previous risks may have been overestimated. For most non-hormone-sensitive cancers (e.g., breast cancer, uterine cancer, prostate cancer), HT can be considered but it is a complex clinical analysis.  Close collaboration with cancer specialists is necessary (14). 

References 

1. Crandall, C. J., Mehta, J. M., & Manson, J. E. (2023). Management of menopausal symptoms: A review. JAMA, 329(5), 405–420.
2. The Endocrine Society. (2017). Postmenopausal hormone therapy: An Endocrine Society scientific statement. The Journal of Clinical Endocrinology & Metabolism, 102(7), 2126–2143.
3. American College of Obstetricians and Gynecologists. (2013). Postmenopausal estrogen therapy: Route of administration and risk of venous thromboembolism (Committee Opinion No. 556). Obstetrics & Gynecology, 121(4), 887–890.
4. Langley RE, Gilbert DC, Mangar S, et al. Transdermal Estradiol Patches in Locally Advanced Prostate Cancer. New England Journal of Medicine. 2026;394(13):1199-1211. doi:10.1056/NEJMoa2511781. PMID: 41880608.
5. Vinogradova, Y., Coupland, C., & Hippisley‑Cox, J. (2019). Use of hormone replacement therapy and risk of venous thromboembolism: Nested case‑control studies using the Research and CPRD databases. BMJ, 364, k4810.
6. Chang, J. G., Lewis, M. N., & Wertz, M. C. (2023). Managing menopausal symptoms: Common questions and answers. American Family Physician, 108(1), 28–39.
7. Foschi, M., Groccia, G., Rusce, M. L., Medaglia, C., Aio, C., Sponzilli, A., Setti, V., Battipaglia, C., & Genazzani, A. D. (2025). Estradiol and micronized progesterone: A narrative review about their use as hormone replacement therapy. Journal of Clinical Medicine, 14(20), 7328.
8. Yanachkova, V., Vasileva‑Slaveva, M., Kostov, S., & Yordanov, A. (2025). Reconsidering hormone replacement therapy: Current insights on utilisation in premenopausal and menopausal women: An overview. Journal of Clinical Medicine, 14(20), 7156.
9. Nudy, M., Chinchilli, V. M., & Foy, A. J. (2019). A systematic review and meta-regression analysis to examine the “timing hypothesis” of hormone replacement therapy on mortality, coronary heart disease, and stroke. American Journal of Therapeutics, 26(1), e91–e100.
10. Rovinski, D., Ramos, R. B., Fighera, T. M., Casanova, G. K., & Spritzer, P. M. (2018). Risk of venous thromboembolism events in postmenopausal women using oral versus non‑oral hormone therapy: A systematic review and meta‑analysis. Thrombosis Research, 168, 83–95.
11. The North American Menopause Society. (2022). The 2022 hormone therapy position statement of The North American Menopause Society. Menopause, 29(7), 767–794.
12. Rossouw, J. E., Aragaki, A. K., Manson, J. E., Szmuilowicz, E. D., Harrington, L. B., Johnson, K. C., Allison, M., Haring, B., Saquib, N., Shadyab, A. H., Rexrode, K. M., Liu, L., & LaCroix, A. Z. (2025). Menopausal hormone therapy and cardiovascular diseases in women with vasomotor symptoms: A secondary analysis of the Women’s Health Initiative randomized clinical trials. JAMA Internal Medicine, 185(11), 1330–1339.
13. U.S. Preventive Services Task Force. (2022). Hormone therapy for the primary prevention of chronic conditions in postmenopausal persons: US Preventive Services Task Force recommendation statement. JAMA, 328(17), 1740–1746.
14. Mishra, G. D., Davies, M. C., Hillman, S., Chung, H.‑F., Roy, S., Maclaran, K., & Hickey, M. (2024). Optimizing health after early menopause. The Lancet, 403(10430), 958–968.
15. MacLennan, A. H. (2011). HRT in difficult circumstances: Are there any absolute contraindications? Climacteric, 14(4), 409–417.
16. Flores, V. A., Pal, L., & Manson, J. E. (2021). Hormone therapy in menopause: Concepts, controversies, and approach to treatment. Endocrine Reviews, 42(6), 720–752.

Authors’ Affiliations:  1Icahn School of Medicine at Mount Sinai, New York NY; 2University of Colorado Anschutz Cancer Center, Denver CO; 3Lund University, Lund Sweden; 4Harvard Medical School, Boston MA.
Version History:  First published February 2012. 2nd Edition by Sean Marks in September 2015; 3rd Edition by Laura Minikel MD in November 2024. Reviewed and updated again in July 2026.
Conflicts of Interest: None to report.