Controversy over HRT’s effect on CV risk unravelled
Hormone replacement therapy (HRT) with conjugated equinestrogens (CEE) plus medroxyprogeserone acetate (MPA) or CEE alone does not increase the risk of cardiovascular (CV) mortality among postmenopausal women, according to an expert who reviewed 18-year follow-up data of the Women’s Health Initiative (WHI) randomized trials at the Endocrinology, Diabetes & Metabolism Hong Kong (EDMHK) 2nd Annual Meeting.
“Based on updated data from the WHI Estrogen Plus Progestin and Estrogen-Alone studies, we should be reassured that HRT is still a safe treatment option for women with the indication to start,” said Dr Raymond Li of the Department of Obstetrics and Gynaecology, University of Hong Kong.
In the pooled cohort, no significant difference in the risk of CV mortality was demonstrated in the HRT vs placebo group (hazard ratio [HR], 1.00; 95 percent confidence interval [CI], 0.92 to 1.08; p=0.98). Comparable results were seen for coronary heart disease (CHD) mortality (HR, 0.97; 95 percent CI, 0.86 to 1.09; p=0.60) and stroke mortality (HR, 1.06; 95 percent CI, 0.90 to 1.24; p=0.47). [JAMA 2017;318:927-938]
Over a median follow-up of 5.6 years for the CEE plus medroxyprogesterone acetate (MPA) trial and 7.2 years for the CEE alone trial, neither treatment was significantly associated with CV disease (CVD) mortality during the intervention phase. Compared with placebo, the CVD HR for CEE plus MPA and CEE alone was 1.08 (95 percent CI, 0.78 to 1.48; p=0.65) and 1.01 (95 percent CI, 0.78 to 1.31; p=0.95), respectively. No statistically significant trends for CVD with age were observed in either trial during the intervention and post-intervention phases.
The double-blind, placebo-controlled, randomized WHI HRT trials recruited 27,347 postmenopausal women aged 50–79 years (median age, 63 years) in 1993–1998. Women with a uterus (n=16,608) were randomized to receive daily oral CEE (0.625 mg) plus MPA (2.5 mg) or placebo, while these with hysterectomy (n=10,739) were randomized to receive daily oral CEE (0.625 mg) alone or oral placebo.
The risk-benefit profile of HRT has been controversial. Initial results from the WHI trial showed that CEE plus MPA was associated with a significant increase in risk of CHD events vs placebo (HR, 1.29; 95 percent CI; 1.02 to 1.63). [JAMA 2002;288:321-333]
“However, subsequent studies showed that the benefits outweigh the risks in terms of CV protection if HRT is administered before the age of 60 years in those who are <10 years after menopause [relative risk, 0.52; 95 percent CI, 0.29 to 0.96], compared with placebo or no treatment. This is called the ‘window of opportunity’ hypothesis [in terms of achieving maximal reduction of CHD and minimizing the risks],” said Li. [Cochrane Database Syst Rev 2015;CD002229; Climacteric 2012;15:217-228]
This is in keeping with current North American Menopause Society (NAMS) position guidelines suggesting that HRT remains a safe and effective option for the symptomatic treatment of menopause when initiated in patients aged <60 years or within 10 years of menopause onset, and the NAMS caution of potentially increased risk of CHD for those who initiate HRT >10 years from menopause onset. [Menopause 2017;24:728-753]