Why Did We Stop Treating Women with Hormones Over 20 Years Ago?
The Women's Health Initiative (WHI) Study: A Turning Point in Women's Health
The Women’s Health Initiative (WHI), launched by the National Institutes of Health (NIH) in 1993, was one of the largest and most comprehensive studies of postmenopausal women’s health. The WHI study aimed to evaluate the benefits and risks of hormone therapy (HT), particularly its effects on heart disease, fractures, and certain cancers. Over 27,000 healthy postmenopausal women aged 50-79 participated in the study.
Why We Stopped Using Hormones in Women
The WHI study was designed with two primary arms:
- Estrogen Plus Progestin (E+P): This group included women with a uterus who received a combination of estrogen and progestin.
- Estrogen Alone (E-Alone): This group included women without a uterus who received estrogen alone.
The study was intended to last 8.5 years, but the Estrogen Plus Progestin arm was halted prematurely in July 2002, after just 5.2 years. The decision to stop the study early was based on an interim analysis that revealed several concerning findings:
- Increased Risk of Breast Cancer: There was a significant 26% relative increase in the risk of invasive breast cancer among women taking the combined estrogen-progestin therapy. However, this increase represented an absolute risk increase of about 1 additional case per 1,000 women per year (or 10 additional cases per 10,000 women per year).
- Cardiovascular Risks: The study found a higher incidence of coronary heart disease, strokes, and blood clots in the hormone therapy group compared to the placebo
- Other Health Risks: There was also an increased risk of stroke and venous thromboembolism (blood clots).
While the study did observe some benefits, such as a reduction in hip and vertebral fractures and a decrease in colorectal cancer risk, these benefits were overshadowed by the significant risks.
Has Anything Changed Since?
he impact of the WHI study was profound, leading to a dramatic reduction in hormone therapy prescriptions for postmenopausal women. However, it is important to recognize that the study has been critiqued over the years, particularly regarding the following aspects:
- Age of Participants: The average age of participants was 63, which is older than the typical age at which women begin hormone therapy (usually in their early 50s). This older age group may not accurately reflect the risks and benefits for younger women starting hormone therapy closer to menopause.
- Synthetic Hormones: The WHI used synthetic hormones, specifically conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA). These forms of hormones may have different risk profiles compared to bioidentical hormones, which are now more commonly used.
- Participant Dropout: Participants could opt out of the study, which may have introduced selection bias and affected the study’s outcomes.
- Asymptomatic Participants: Many women in the study were not experiencing severe menopausal symptoms, which raises questions about the applicability of the findings to women who seek hormone therapy for symptom relief.
Critiques and the Path Forward
The WHI study undoubtedly brought to light the potential risks associated with hormone therapy, but it also left us with important questions. The absolute risk increase for breast cancer, for instance, was relatively small, raising debates about how these findings should influence clinical practice.
Moving forward, it’s crucial to close the gap in hormone therapy management. We need to better understand which women are most likely to benefit from hormone therapy and who may be at risk. This means considering factors such as age, symptom severity, and the type of hormones used. Hormone therapy, when appropriately prescribed, can still offer significant benefits for many women, and it is our responsibility as healthcare providers to ensure that women receive the right treatment for their individual needs.
The WHI study was a turning point in how we view hormone therapy for postmenopausal women. While it revealed significant risks, it also sparked ongoing debates about the relative versus absolute risks and the applicability of the findings to younger, symptomatic women.
Today, we must continue to refine our approach to hormone therapy, ensuring that women receive the care they need without unnecessary risks.
For those interested in a deeper dive into the relative vs. absolute risk discussion, I encourage you to explore the following sources:
- National Institutes of Health (NIH): WHI Follow-up Study
- American Family Physician: WHI 20-Year Follow-Up
- Rossouw JE, Anderson GL, Prentice RL, et al. “Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial.” JAMA. 2002;288(3):321-333.
This blog offers a comprehensive overview of the reasons behind the shift in hormone therapy practices following the WHI study. If you’re interested in learning more about how we can bridge the gap in hormone therapy today, stay tuned for further discussions.