Slide 1: Menopausal Hormone Therapy. Women’s Health Initiate (WHI) 2002

Slide 2: Why? The Nurse’s Health Study – a series of prospective cohort studies in the 1970s-1980s, found hormone therapy (HT) to be associated with decreased CV risk. WHI sought to follow-up evaluating the risks and benefits of HT in postmenopausal women, this time in a randomized and controlled fashion.

Primary outcome: rate of CV disease. Primary adverse event: rate of invasive breast cancer.

Slide 3: How? Study population: 16,608 post menopausal women (ages 50-79) randomized to estrogen plus progestin or placebo. Follow up timeline. 6 weeks phone call. 6 months clinical visit. 12 months clinical visit. 18 month clinical visit. 24 months clinical visit. 3 and 6 years EKG. Annual mammograms. 40 study centers. 63.3 mean age. 5.2 years mean follow-up. 40% former smokers, 10% current smokers in both groups.

Slide 4: What happened? Compared to placebo, estrogen plus progesterone group have global index for risk, absolute risk (AR) increase +0.19%. Total CV events AR increase +0.25%, color cancer AR reduction -0.06%, total fractures AR reduction -0.44%, stroke AR increase +0.08%, invasive breast cancer AR increase 0.08%, venous thromboembolism AR increase +0.17%.

Only nominal statistical significance p<0.05 Global index = risk summary of CV disease, stroke, cancer, and other adverse events Slide 5: What did critics say? Authors say "over 1 year, 10,000 women taking estrogen plus progestin compared with placebo might experience 7 more CHD events, 8 more strokes, 8 more PEs, 8 more invasive breast cancers, 6 fewer colorectal cancers, and 5 fewer hip fractures. WHI studies only effect of continuous HT, what about cyclic HT. Mean age of EHI study population is age 63. Can results be generalized to younger, recently menopausal women in their 50s? The difference in CV events and strokes are statistically nonsignificant after adjustments to correct for multiple analyses over time. What is statistically significant may not be clinically significant. For example, how does one view the +0.08% increased risk in breast cancer? Slide 6: Further studies. 2009. DOPS-RCT N=1,006. Early menopausal HT reduced risk of mortality, HF, and MI without increased risk of cancer, VTE, or stroke. 2014. KEEPS-RCT, N=727. Early menopausal HT reduced vasomotor symptoms, improved sexual function, and maintained bone density with a neutral impact on carotid intima-media thickness (CIMT). 2016. ELITE-RCT, N=643. Early HT initiation within 6 years of menopause was associated with less progression of CIMT as compared to late HT initiation greater than 10 years after menopause. 2022. Per current guidelines from USPSTF and ACOG. HT is a safe and effective option for otherwise healthy women experiencing moderate to severe menopausal vasomotor symptoms.