For much of the late 20th century, hormone replacement therapy (HRT) was routinely prescribed to millions of women transitioning through menopause. It was heralded not only for its ability to relieve the often-debilitating symptoms of menopause—such as hot flashes, mood changes, sleep disturbances, and vaginal dryness—but also for its perceived protective benefits against cardiovascular disease and osteoporosis.
However, that confidence was shaken in 2002 with the publication of the Women’s Health Initiative (WHI) study, a large randomized controlled trial sponsored by the National Institutes of Health. The WHI included more than 160,000 postmenopausal women and evaluated the effects of combined estrogen and progestin therapy (as well as estrogen alone in women without a uterus). To the shock of the medical community, the study found an increased risk of breast cancer, stroke, and cardiovascular events among women taking combined HRT. The media coverage was swift and alarming, and HRT prescriptions plummeted overnight.
The Aftermath of the WHI and Reassessment
The WHI had a profound effect on both physicians and patients. Many clinicians became hesitant to prescribe HRT, and millions of women were left to navigate menopausal symptoms without pharmacologic support. However, in the two decades since the WHI, a more nuanced understanding of its findings has emerged.
Importantly, the average age of women enrolled in the WHI was 63—well beyond the typical age of menopause onset—and many were more than 10 years past their last menstrual period. Subsequent reanalysis of WHI data has shown that the risks of HRT are highly age-dependent and vary according to time since menopause, underlying health status, and type of hormone therapy used.
In particular, women who begin HRT within 10 years of menopause onset (often between ages 45 and 55) appear to derive significant symptom relief and may experience a reduction in all-cause mortality without an elevated risk of cardiovascular events. In contrast, initiating HRT in older women or those with preexisting vascular disease carries greater risk.
Current Understanding of the Risks
Today, HRT is considered safe and effective for many healthy women in early menopause, when used appropriately. However, it is not without risks, and careful patient selection is critical. Here’s a breakdown of the major risks:
- Breast Cancer: Combined estrogen-progestin therapy is associated with a modest increase in breast cancer risk after about 3–5 years of use. Estrogen-only therapy (for women without a uterus) does not appear to increase the risk and may even reduce it.
- Venous Thromboembolism (VTE): Oral HRT, particularly estrogen taken by mouth, increases the risk of blood clots. Transdermal estrogen (patches, gels) does not carry the same risk and may be preferred in women with VTE risk factors.
- Stroke: The risk of ischemic stroke increases slightly with HRT, especially in women older than 60. Again, transdermal delivery may reduce this risk.
- Cardiovascular Disease: In younger women, especially those within 10 years of menopause, HRT does not appear to increase heart disease risk and may be cardioprotective. In older women or those starting HRT late, the risks are higher.
Who Are Good Candidates for HRT?
HRT remains the most effective treatment for vasomotor symptoms (e.g., hot flashes, night sweats) and genitourinary syndrome of menopause (vaginal dryness, painful intercourse, urinary frequency). Ideal candidates often include:
- Women under age 60 or within 10 years of menopause
- Those with moderate to severe vasomotor symptoms affecting quality of life
- Women with early menopause or primary ovarian insufficiency (POI) are at risk for osteoporosis, cardiovascular disease, and cognitive decline
- Those without a personal history of breast cancer, active liver disease, or history of thromboembolism
For these women, the benefits of symptom relief, improved bone health, and potentially improved metabolic and cardiovascular profiles generally outweigh the risks when therapy is started early and monitored carefully.
Who Should Avoid HRT?
HRT is generally not recommended for:
- Women with a personal history of breast cancer or estrogen-sensitive malignancies
- Those with active or past venous thromboembolism, especially if provoked by estrogen
- Women with uncontrolled hypertension or cardiovascular disease
- Those with active liver disease
Individualized Therapy: Modern Best Practice
Today, the approach to HRT is highly personalized. Factors such as age, time since menopause, severity of symptoms, type of symptoms, medical history, and route of administration (oral vs. transdermal) are all considered.
Conclusion
The story of hormone replacement therapy has evolved from enthusiasm to fear, and now, to thoughtful reconsideration. While the WHI raised important safety concerns, its initial interpretation led to an overly cautious retreat from a therapy that remains the most effective option for many women navigating the challenges of menopause.
The current evidence supports the use of HRT in appropriately selected women, especially those who are younger and closer to the onset of menopause. As always, patient-centered care—with clear discussion of risks, benefits, and individual goals—is essential.
With this renewed understanding, hormone therapy can reclaim its place as a valuable tool in improving the quality of life for women in their menopausal transition and beyond.
Please note: ChatGPT was used to help generate this article-
Read Also: Longevity Unveiled: Exploring Peter Attia’s Guide to Healthy Aging
Milt McColl, MD, June 2025
Call The Village Doctor at (650) 851-4747 or Contact us to learn more about the practice.
