May 28, 2012 — Menopausal hormone therapy (HRT) reduced risk of fractures but increased risk for stroke, thromboembolic events, gallbladder disease, and urinary incontinence, according to a systematic review of articles published after 2002. Whereas estrogen alone decreased the risk for breast cancer, estrogen plus progestin increased risk for probable dementia and breast cancer. This new review, published online May 29 in the Annals of Internal Medicine, will be used to update the US Preventive Services Task Force recommendations.
"Menopausal hormone therapy to prevent chronic conditions is currently not recommended because of its adverse effects," write Heidi D. Nelson, MD, MPH, from the Oregon Health & Science University in Portland, and colleagues.
"The current indications for use from the U.S. Food and Drug Administration include short-term treatment of menopausal symptoms, such as vasomotor hot flashes or urogenital atrophy, and prevention of osteoporosis."
For the systematic review, Dr. Nelson and colleagues searched MEDLINE for articles published from January 2002 to November 2011, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews through the third quarter of 2011, Scopus, and bibliographies of retrieved articles. They limited inclusion to studies that were randomized, placebo-controlled trials of menopausal hormone therapy; evaluation of primary prevention of chronic conditions; and English-language publication since 2002.
Data were extracted regarding participants, study design, analysis, follow-up, and findings. Using established criteria, 2 investigators independently rated study quality.
The investigators identified 9 fair-quality trials meeting the inclusion criteria. Most of the findings came from the Women's Health Initiative (WHI), with 11 years of follow-up and collection of data most relevant to postmenopausal American women.
In the WHI, estrogen plus progestin therapy was associated with 46 fewer fractures per 10,000 woman-years. However, women taking HRT had an increased risk for invasive breast cancer (8 more per 10,000 woman-years), stroke (9 more per 10,000 woman-years), deep venous thrombosis (12 more per 10,000 woman-years), pulmonary embolism (9 more per 10,000 woman-years), lung cancer death (5 more per 10,000 woman-years), gallbladder disease (20 more per 10,000 woman-years), dementia (22 more per 10,000 woman-years), and urinary incontinence (872 more per 10,000 woman-years).
The risk for breast cancer was greater in women who previously used oral contraceptives or menopausal estrogen plus progestin therapy, or who were current smokers.
Estrogen-only therapy reduced the risk for several adverse outcomes, including fracture (56 fewer per 10,000 woman-years), invasive breast cancer (8 fewer per 10,000 woman-years), and mortality (2 fewer per 10,000 woman-years). However, the treatment increased risks for stroke (11 more per 10,000 woman-years), deep venous thrombosis (7 more per 10,000 woman-years), gallbladder disease (33 more per 10,000 woman-years), and urinary incontinence (1271 more per 10,000 woman-years).
The investigators could not identify subgroups based on age or comorbid conditions in which outcomes of menopausal HRT were consistently different.
Limitations of this review included those inherent in the trials themselves, such as low adherence, high dropout rate, insufficient power to detect risks for some outcomes, and assessment of few regimens.
"Continuing research is needed on such long-term outcomes as cancer and death to fully understand the implications of hormone therapy," the reviewers conclude.
The Agency for Healthcare Research and Quality funded this study and has financial relationships with some of its authors. Disclosures can be viewed at on the journal's Web site .
Ann Intern Med. Published online May 29, 2012. Full text