Hormone Therapy for Menopause: Timing, Safety, and Best Candidates

Hot flashes, night sweats, and other vasomotor symptoms (VMS) that come with menopause remain among the most disruptive symptoms of midlife for many women. Although hormone therapy has long been the most effective treatment, lingering concerns about cardiovascular, cancer, and clotting risks have left many patients untreated. Recent evidence emphasizes that timing, dose, and formulation determine whether hormone therapy is safe and beneficial—not just age.

At The Menopause Society 2025 Annual Meeting, Stephanie S. Faubion, MD, MBA, FACP, MSCP, IF, medical director of The Menopause Society and director of the Mayo Clinic Center for Women’s Health, outlined a clear message: hormone therapy remains the most effective treatment for VMS, but using it requires mindful patient selection and shared decision-making.

Understanding Vasomotor Symptoms

Vasomotor symptoms, commonly known as hot flashes and night sweats, affect up to 80% of women during the menopausal transition.2 These symptoms arise from declining estrogen levels that disrupt thermoregulation, leading to episodic heat surges, sweating, and sleep disturbances. Untreated, they can persist for years and significantly impair quality of life, mood, and cognitive function.

Hormone therapy, which replaces estrogen with or without progesterone, is considered the gold standard for treating VMS in most women.1 “Hormone therapy is the first-line therapy and the most effective therapy for vasomotor symptoms,” Faubion emphasized.

Indications and Contraindications

Hormone therapy requires mindful patient selection and shared decision-making. | Image credit: Vitalii Vodolazskyi – stock.adobe.com

FDA-approved indications for hormone therapy include moderate to severe VMS, prevention of osteoporosis, and management of premature menopause or early estrogen deficiency. Indirect benefits may include improvements in mood, sleep, and sexual function.

However, Faubion cautioned that not all patients are candidates for systemic estrogen use. Contraindications include unexplained vaginal bleeding, a history of estrogen-sensitive cancers such as breast or endometrial cancer, prior stroke or myocardial infarction, inherited or acquired high risk for venous thromboembolism (VTE), and severe liver disease.

The “timing hypothesis” suggests that the safety and benefits of hormone therapy depend largely on when treatment begins relative to menopause onset. Faubion explained that women who start therapy before age 60 or within 10 years of their final menstrual period tend to experience the greatest symptom relief and cardiovascular protection, with minimal risk of adverse events. On the other hand, initiating therapy later, when atherosclerosis and vascular aging are more advanced, may minimize the treatment’s benefits. The primary benefits of estrogen and hormone therapy appear to be between ages 35 and 55 years—the typical perimenopause period.3

Who Is the Best Fit for Hormone Therapy?

According to Faubion, ideal candidates for hormone therapy are women younger than 60 years or who had their last menstrual period within 10 years who have bothersome symptoms such as hot flashes, mood instability, or sleep disturbances.1 Other favorable considerations include low cardiovascular and breast cancer risk and no contraindications with treatments. Concerns around bone density and patient preferences also play important roles.

So, why not use custom compounded hormones? According to Faubion, there is a lack of safety and efficacy data with this practice and too much batch-to-batch variability, and these don’t come with package inserts, which can confuse patients.

“If you’re giving them all the same doses and giving them the same levels, it’s the antithesis of individualized therapy,” she added.

Instead, she said the focus should be on individualizing therapy through evidence-based formulations. Transdermal administration may offer additional safety advantages over oral formulations, showing less of an impact on clotting factors, blood pressure, triglycerides, and inflammatory markers.

When to Start and Stop Therapy

Despite her description of the “ideal candidate” for initiating hormone therapy, Faubion noted there is no “magic age” for discontinuation. Long-term use may be appropriate for healthy women with ongoing symptoms or elevated risk of fracture; duration should depend on symptoms, health status, and personal preference Faubion said.

When the uterus is still present after menopause, progestogen must be included to prevent endometrial cancer, while low-dose vaginal estrogen for genitourinary symptoms can be continued indefinitely. Ultimately, Faubion urged clinicians to move beyond one-size-fits-all thinking.

Managing Chronic Conditions Alongside Menopause

Most women approaching menopause have at least 1 chronic condition.4 Among women aged 55 and older, 4 in 5 of them live with at least 1 chronic condition, with half managing 2 or more and 20% managing 3 or more. These conditions include:

• Hypertension: affecting 30% of women globally, hypertension becomes more prevalent in women than men after age 50.1 In hormone therapy, transdermal estrogen is preferred, as it has a neutral effect on blood pressure, whereas oral estrogen or synthetic progestogens may increase it.
• Obesity: nearly half of US women aged 40 to 59 years live with obesity, increasing the risk for cardiovascular disease, VTE, and more frequent or severe hot flashes. Observational studies suggest transdermal estrogen reduces cardiovascular risk and mortality in these patients.
• Diabetes: hormone therapy has been shown to improve insulin sensitivity and glycemic control, reducing the risk of type 2 diabetes by up to 30%. In women with diabetes, transdermal routes are preferred for lower VTE risk and favorable metabolic effects.
• History of clotting: VTE risk rises with age but is lower when hormone therapy begins within 10 years of menopause. Lower-dose or transdermal preparations can further mitigate risk.
• Hereditary cancer risk: For women with BRCA mutations or prior oophorectomy, hormone therapy does not appear to increase breast cancer risk and may improve quality of life.

References

1. Faubion SS. Hormone treatment for vasomotor symptoms. Presented at: The Menopause Society 2025 Annual Meeting; October 21, 2025; Orlando, FL.
2. Avis NE, Crawford SL, Greendale G, et al. Duration of menopausal vasomotor symptoms over the menopause transition. JAMA Intern Med. 2015;175(4):531-539. doi:10.1001/jamainternmed.2014.8063
3. Mikkola TS, Clarkson TB, Notelovitz M. Postmenopausal hormone therapy before and after the women's health initiative study: what consequences? Ann Med. 2004;36(6):402-413. doi:10.1080/07853890410035430
4. Percentage of adults age 55 and over (total, male & female), with one or more, two or more, or three or more of a possible six chronic conditions: United States, 2008. CDC. September 2009. Accessed October 21, 2025. https://www.cdc.gov/nchs/data/health_policy/adult_chronic_conditions.pdf