Risks and benefits of menopausal hormone therapy

ABSTRACT

Menopausal hormone therapy (MHT) was widely used to improve quality of life by controlling menopausal symptoms, including vasomotor symptoms and urogenital atrophy. Furthermore, observational studies consistently reported beneficial effects of MHT on late problems of menopause, such as osteoporosis, coronary heart disease (CHD), and possibly dementia. However, circumstances changed abruptly after the 2002 publication of the first findings from the Women's Health Initiative (WHI) study, which was conducted in postmenopausal women (average age, 63 years) using conventional doses of conjugated equine estrogen (CEE) and medroxyprogesterone acetate. CEE with medroxyprogesterone acetate increased the risk of breast cancer and did not prevent CHD. However, CEE alone showed a tendency to decrease the risk of both breast cancer and CHD, with significant differences between the two therapies. A subgroup analysis by age and years since menopause led to a timing hypothesis regarding the effects of MHT on CHD. Indeed, CEE alone in women aged 50 to 59 significantly reduced CHD risk by 35% after 13 years of follow-up. In 2015, a Cochrane meta-analysis of MHT trials reported a 48% reduction in CHD, no change in stroke, and most importantly, a 30% decrease in total mortality in women with less than 10 years since menopause. Long-term follow-up of WHI participants confirmed beneficial impacts of CEE on breast cancer incidence and mortality. Further, fracture reduction in women with osteopenia was observed during the intervention phase of the WHI study. If initiated early after menopause, MHT could again be considered to improve menopause-related quality of life and decrease all-cause mortality.