Hormone replacement therapy (HRT) for women has long been a controversial topic in the medical field. While it has been used to treat symptoms of menopause such as hot flashes, night sweats, mood swings, and prevention of bone loss, there have been concerns about the potential increased risk of breast cancer, heart disease, and stroke.
Historical Perspective
The Women’s Health Initiative (WHI) was a landmark, long-term study launched in 1991* to investigate strategies for preventing the leading causes of death, disability, and frailty in postmenopausal women, specifically targeting cardiovascular disease, cancer, and osteoporosis. Ultimately, it aimed to fill significant knowledge gaps by studying these chronic conditions in older women, who were often excluded from research studies.
While the broader initiative encompassed multiple studies, its core aims were carried out through three major clinical trials.** Among these was the Hormone Therapy Trial which aimed to evaluate whether the use of estrogen plus progestin, or estrogen alone, could prevent cardiovascular disease, breast and colon cancers, and osteoporotic fractures.
In 2002, the WHI gained worldwide attention after the “estrogen plus progestin” arm of the trial was abruptly stopped because researchers found that it increased the risk of breast cancer, stroke, heart disease, and blood clots. These unexpected results led to widespread concern and a re-evaluation of HRT practices among women and their healthcare providers and influenced guidelines concerning HRT for years to come.
Recent Research and Updated Guidelines
However, recent research has challenged the hesitance surrounding HRT, shedding new light on its benefits and risks, and leading to updated guidelines on its use. A large-scale study (1) based on the records of ten million senior Medicare women from 2007 to 2020, suggests that the implications of HRT use beyond age 65 years vary by type of hormone, type of administration, and dosage.
These findings are in line with the 2022 HRT Position Statement of The Menopause Society (2) which states there is no general rule for stopping hormone therapy in a woman based on age alone. The statement goes on to say that for healthy women with persistent hot flashes, continuing hormone therapy beyond age 65 is a reasonable option if there is appropriate counseling and regular reassessment of risks and benefits.
Personalized Approach
One of the key takeaways from recent research is the importance of an individualized approach to treatment. Not all women will experience the same benefits or risks from HRT, and each person’s medical history, risk factors, and symptoms must be thoroughly reviewed and considered before prescribing HRT.
Types of HRT and Administration
There are different types of HRT available for women, including estrogen-only and combination therapy with estrogen and progestin. Estrogen-only therapy may be safer for women who have had a hysterectomy, while combination therapy may be best for women with an intact uterus.
The use of a combination estrogen and progestin therapy was found to increase the risk of breast cancer, but this risk can be mitigated using low doses of transdermal or vaginal progestin. Choosing low-dose and non-oral types of administration may also be important for older women.
Progestin usage resulted in significant risk reduction in endometrial cancer, ovarian cancer, ischemic heart disease, congestive heart failure, and venous thromboembolism (blood clot).
Timing and Duration of Treatment
There is widespread agreement that the best time to start HRT is generally within ten years of menopause onset or before age 60, a concept known as the “timing hypothesis”. This strategy is believed to maximize benefits like symptom relief and cardiovascular protection while minimizing risks. It may also have the greatest impact on bone health and reducing the risk of osteoporosis-related fractures. Periodic monitoring and re-evaluation of the benefits and potential risks of continuing therapy is crucial.
HRT and Osteoporosis
Estrogen, a hormone that naturally declines during menopause, plays a critical role in maintaining bone density and strength. Therefore, HRT that contains estrogen may help improve bone health and reduce the risk of osteoporosis-related fractures.
The SWAN study, or Study of Women’s Health Across the Nation (3), is a large, longitudinal research study that aims to understand the menopausal transition and its effects on women’s health. Launched in 1994, one aspect of the study focused on the impact of HRT on bone health. Results suggest that women who used HRT had higher bone mineral density compared to women who did not use HRT.
In Summary
Overall, the latest research suggests that HRT can be a safe and effective treatment for menopausal symptoms when used appropriately. By taking a personalized approach to treatment, considering the timing of treatment, and weighing the benefits and risks of therapy as well as the alternatives, women and their healthcare provider can make evidence-based decisions about which approach is best.
Keep in mind, whichever direction you choose to go, HRT or not, doing the right exercises and eating well to support bone health must always be part of your bone health plan.
See you in Strong Bones class!
* While the original clinical trials ended in 2005, the initiative transitioned into long-term “Extension Studies” that continue to track the health of the original participants. Approximately 42,000 women, now aged between 78 and 108, remain actively involved by providing annual health updates.
In early 2025, the Department of Health and Human Services planned to terminate the program’s contracts, however, following pushback from the medical community, the funding was reinstated in April 2025, ensuring the study could continue. The current extension phase is approved through January 31, 2026.
**The other two major trials were the Dietary Modification Trial and the Calcium and Vitamin D Trial. The former aimed to determine if a low-fat diet high in fruits, vegetables, and grains could reduce the risk of breast cancer, colorectal cancer, and heart disease, and the latter examined whether daily supplementation of calcium and vitamin D could reduce the incidence of osteoporotic fractures and colorectal cancer.
Citations
- Biak SH, et al. Use of Menopausal Hormone Therapy Beyond Age 65 Years and its Effects on Women’s Health Outcomes by Types, Routes, and Doses. Menopause 2024 May; 31(5):363-371.
- The 2022 Hormone Therapy Position Statement of The North American Menopause Society Advisory Panel. The 2022 Hormone Therapy Position Statement of The North American Menopause Society. Menopause 2022 Jul 1;29(7):767-794.
- https://www.swanstudy.org
