Objective: Clinical trials in menopause have undergone much scrutiny over the years. This has led to significant shifts in the treatment of symptomatic menopause and a substantial impact on women. We aim to delineate the key studies contributing to this controversy and highlight new directions specifically related to menopausal hormone therapy (HT) and vascular disease risk.
Methods: We performed a search of sentinel studies delineating the risks and benefits of HT in otherwise healthy postmenopausal women. Using PubMed we input the following search terms: hormone replacement therapy, cardiovascular disease, coronary artery disease, coronary atherosclerosis, myocardial infarction, angina, coronary heart calcification, carotid intimal thickness, lipids, and/or lipoproteins. We included studies of menopausal women (surgical or natural) using combined estrogen/progestogen therapy or estrogen-only therapy that looked at cardiovascular disease risk factors or outcomes. Studies were evaluated for inclusion by the authors; however, this is not intended to be a systematic or an exhaustive analysis.
Results: In women close to the time of menopause, there is a decreased risk of subclinical and clinical coronary heart disease with menopausal HT. Additionally, HT confers a significant benefit to vasomotor symptoms of menopause, bone health, and colorectal cancer. There is an increased risk of venous thromboembolism with oral formulations that appears mitigated with transdermal estradiol. Mixed data regarding breast cancer risk are available, with some studies suggesting an increased risk of invasive breast cancer with estrogen/progestogen therapy and a null effect with estrogen-only therapy. Other more long-term epidemiologic studies identify a decreased risk.
Conclusions: The available literature suggests that HT is a viable option for the primary prevention of cardiovascular disease in postmenopausal women. Newer trials will likely verify this assessment. If this is enough to change clinical practice, however, remains to be seen given the general fear of HT by many with prescriptive authority, and also the women in our care.