Background:

Hormone therapy plays an important role in the clinical management of menopausal symptoms. Because of an increased risk of harms, hormone therapy is currently not recommended for the primary prevention of chronic conditions.

Purpose:

To update evidence on the effectiveness of hormone therapy in reducing risk of chronic conditions, its adverse effects, and differences among population subgroups for the U.S. Preventive Services Task Force.

Data Sources:

We searched MEDLINE, the Cochrane Library, and Embase for English-language articles (through October 12, 2021). We conducted searches for unpublished literature by searching ClinicalTrials.gov, HSRProj, the World Health Organization’s International Clinical Trials Registry Platform, and NIH RePORTER. In addition, we reviewed reference lists of pertinent review articles and studies meeting our inclusion criteria. We conducted surveillance of the literature through June 1, 2022.

Study Selection:

We dually reviewed the literature and included randomized, placebo-controlled trials and large controlled cohort studies that provided information on the primary prevention of chronic conditions with hormone therapy and reported health outcomes.

Data Extraction:

We abstracted details about participants, study design, analysis, followup, and results; study quality and strength of evidence were rated using established criteria.

Data Synthesis:

Twenty fair- or good-quality trials and three large controlled cohort studies met eligibility criteria. The Women’s Health Initiative was the largest study and most applicable to the target population.

Results of our review indicate differences in the risk-benefit profile between treatment formulations. Women using estrogen only had statistically significantly lower risk (per 10,000 women over 6.8 to 7.2 years) of diabetes (134 fewer cases) and fractures (388 fewer cases) than women taking placebo. However, risk (per 10,000 women over 5.4 to 7.1 years) was statistically significantly increased for gallbladder disease (377 more cases), stroke (79 more cases), and venous thromboembolism (77 more cases).

Women using estrogen plus progestin therapy experienced statistically significantly lower risk (per 10,000 women over 5.0 to 5.6 years) for colorectal cancer (34 fewer cases), diabetes (78 fewer cases), and fractures (230 fewer cases) than women taking placebo. Risk (per 10,000 women over 4 to 5.6 years) of invasive breast cancer (51 more cases), probable dementia (88 more cases), gallbladder disease (260 more cases), stroke (52 more cases), and venous thromboembolism (120 more cases) was statistically significantly increased compared with women taking placebo. The risk of urinary incontinence (562 more cases per 10,000 women) was increased during a followup of 1 year.

Meta-analyses rendered no statistically significant differences in all-cause mortality between women receiving hormone therapy and those receiving placebo (over 2 to 7.2 years for estrogen-only therapy and over 3.2 to 5.6 years for estrogen plus progestin therapy).

Limitations:

Few trials or subgroup analyses were powered for prevention outcomes. No comparative evidence on type, dose, and mode of delivery of hormone therapy is available. The applicability of results to younger women who initiate hormone therapy to manage menopausal symptoms and to women of non-White ethnic backgrounds might be limited.

Conclusions:

Women undergoing hormone therapy for the primary prevention of chronic conditions experience some beneficial effects but also an increased risk of harms.