Written by Kevin Liu
Spoon Feed
Estrogen and progestin increased risks of coronary artery disease (CAD), non-fatal myocardial infarction (MI), breast cancer, and venous thromboembolism (VTE), outweighing potential benefits like fracture reduction in healthy postmenopausal women.
Hormones, hype, and health hazards
At the end of the 20th century, observational studies suggested that postmenopausal hormone replacement therapy (HRT) reduced the incidence of CAD in women, at the cost of a higher risk for endometrial cancer and VTE. This multicentered, double-blinded RCT, published by the Women’s Health Initiative (WHI) in 2002, included over 16,000 women with an intact uterus to evaluate the use of estrogen plus progestin therapy on the incidence of skeletal fractures, CAD, breast cancer, and thrombosis.
HRT v.s. Placebo:
- HRT higher CAD mortality or non-fatal MI (0.37%/yr vs. 0.30%/yr, HR 1.29; 95%CI 1.02-1.63)
- HRT higher rates of invasive breast cancer (0.38%/yr vs. 0.30%/yr, HR 1.26; 95%CI 1.00-1.59)
- HRT higher rates of non-fatal MI (0.30%/yr vs. 0.23%/yr, HR 1.32; 95%CI 1.02-1.72)
- HRT higher rates of non-fatal stroke (0.21%/yr vs. 0.14%/yr, HR 1.50; 95%CI 1.08-2.08)
- HRT higher rates of VTE/PE (0.34%/yr vs. 0.16%/yr, HR 2.11; 95%CI 1.58-2.82)
- HRT lower rates of fracture including hip and vertebral (1.47%/yr vs. 1.91%/yr, HR 0.76; 95%CI 0.69-0.85)
- HRT lower rates of colorectal cancer (0.10%/yr vs. 0.16%/yr, HR 0.63; 95%CI 0.43-0.92)
Limitations of the study include a high discontinuation of the treatment arm (42%) and a high crossover to the treatment arm (10.7%). In addition, the results of the study cannot be generalized to estrogen- or progestin-only therapy.
How will this change my practice?
HRT was once widely recommended in postmenopausal women to prevent chronic conditions like osteoporosis and heart disease; however, this landmark trial altered clinical guidelines by revealing significant risks. In real-world practice, discussions of initiating HRT involve shared decision making about the risks vs benefits. Alternatives like vaginal estrogen, pelvic floor exercises, and antidepressants are often used for postmenopausal symptoms and avoid the risks of HRT.
Source
Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002 Jul 17;288(3):321-33. doi: 10.1001/jama.288.3.321. PMID: 12117397
