Cover of Menopausal Hormone Therapy for the Primary Prevention of Chronic Conditions

Menopausal Hormone Therapy for the Primary Prevention of Chronic Conditions

Systematic Review to Update the 2002 and 2005 U.S. Preventive Services Task Force Recommendations

Evidence Syntheses, No. 93


Investigators: , MD, MPH, , MA, , MBBS, and , BA.


Oregon Evidence-based Practice Center
Rockville (MD): Agency for Healthcare Research and Quality (US); .
Report No.: 12-05168-EF-1

Structured Abstract


Menopausal hormone therapy to prevent chronic conditions, such as cardiovascular disease and cancer, is currently not recommended because of its adverse effects.


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

Data Sources:

We searched MEDLINE (January 2002 to November 30, 2011), Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through third quarter 2011), Scopus, and reference lists.

Study Selection:

We included English-language, randomized, placebo-controlled trials that evaluated the prevention of new conditions rather than treatment of existing conditions and reported health outcomes.

Data Extraction:

We abstracted details about participants, study design, analysis, followup, and results; study quality was rated using established criteria.

Data Synthesis:

Nine fair-quality trials provided data for outcomes. The Women’s Health Initiative (WHI) reported most of the results, had 11 years of followup, and was most applicable to the target population. Participants in the WHI estrogen only trial had more risk factors for cardiovascular disease and fewer for breast cancer than those in the estrogen plus progestin trial. In WHI, compared with placebo, estrogen plus progestin reduced fractures (46/10,000 women-years) and increased invasive breast cancer (8/10,000), stroke (9/10,000), deep vein thrombosis (12/10,000), pulmonary embolus (9/10,000), lung cancer death (5/10,000), gallbladder disease (20/10,000), dementia (22/10,000), and urinary incontinence (872/10,000). Estrogen only reduced fractures (56/10,000) and invasive breast cancer incidence (8/10,000) and death (2/10,000), and increased stroke (11/10,000), deep vein thrombosis (7/10,000), gallbladder disease (33/10,000), and urinary incontinence (1271/10,000). Among subgroup analyses, there were no consistent differences by age and comorbidities.


Few trials or subgroup analyses were powered for prevention outcomes; 40 to 50 percent of WHI participants discontinued their medications by the end of the trial.


Both hormone therapy regimens decreased fractures but increased stroke, thromboembolic events, gallbladder disease, and urinary incontinence. Estrogen plus progestin increased breast cancer and probable dementia, while estrogen alone decreased breast cancer.