What's the Latest on HR for Prevention?

Can hormone replacement therapy be used for prevention of chronic conditions?

Response from Jenny A. Van Amburgh, PharmD, CDE

Assistant Dean of Academic Affairs; Associate Clinical Professor, School of Pharmacy, Northeastern University; Director, Clinical Pharmacy Team; Director, Residency Program, Harbor Health Services, Inc., Boston, Massachusetts

Hormone replacement therapy (HRT) is the use of estrogen alone (for women who have had a hysterectomy) or combined with progestin (for women with an intact uterus). It is primarily used in menopausal women for relief of symptoms, particularly hot flashes. For many years, providers recommended that women continue to take HRT after menopause to prevent chronic conditions such as heart disease.[1]
It was not until the Women's Health Initiative (WHI) that HRT for chronic disease prevention was fully examined. The WHI, a long-term national health study, examined preventive measures for common causes of death and morbidity including cardiovascular disease, cancer, and osteoporosis in postmenopausal women. In addition to other components, the study compared women receiving hormone therapy vs women receiving placebo for the prevention of heart disease and osteoporosis and for risk for breast or colorectal cancer.[2]
Because of the alarming findings from the WHI, the trial ended early due to increased risks observed. For women on estrogen monotherapy, there was an increased risk for stroke and venous thromboembolism (VTE), no difference in heart attack risk and colorectal cancer, a decreased risk for fracture, and an uncertain risk for breast cancer occurrence.[3] Findings for women on estrogen-progestin therapy included, but were not limited to, increased risk for stroke, VTE, heart attack, and breast cancer and reduced risk for colorectal cancer and fractures.[4]
Long-term follow-up of WHI trial patients postintervention provided additional information regarding clinical outcomes of HRT.[5] After the 13-year median cumulative follow-up, researchers found that unopposed estrogen and estrogen-progestin therapy were associated with an increased risk for stroke, VTE, dementia (aged ≥ 65 years), gallbladder disease, and urinary incontinence. Self-reported outcomes regarding HRT included significant decrease in hip fractures, diabetes, and vasomotor symptoms.[5]
Other organizations besides the WHI have examined the use of HRT in postmenopausal women. The North American Menopause Society, American Heart Association, and American College of Obstetricians and Gynecologists all agree that HRT should not be used for the prevention of chronic conditions.[6] Even with demonstrated benefits, such as reduced risk for fracture, the US Preventive Services Task Force stated that the harmful effects of HRT likely outweigh beneficial preventive effects in most women.[6]
On the basis of the current evidence, the use of estrogen therapy with or without progestin for chronic disease prevention, regardless of age, is not supported.[5,6] HRT remains a reasonable option for treating moderate to severe menopausal symptoms in healthy women aged younger than 60 years or within 10 years after menopause.[7] If estrogen therapy is initiated, the lowest dose for the shortest time possible should be used.[8] Length of therapy should not exceed 5 years due to current safety data available.[1] HRT should not be recommended for women who have a history of breast cancer, coronary heart disease, previous VTE, active liver disease, or patients at increased risk for these conditions.[1] Providers should evaluate individual risk factors and treatment goals before initiating HRT.
The author wishes to acknowledge the assistance of Karrie E. Juengel, PharmD, Tayla N. Thompson, PharmD, and Clara C. Ofodile, PharmD, PGY1 Residents at Northeastern University -- School of Pharmacy, in collaboration with Federally Qualified Health Centers & the Program of All-Inclusive Care for the Elderly, Boston, Massachusetts


  1. Martin KA, Barbieri RL. Treatment of menopausal symptoms with hormone therapy. UpToDate. January 21, 2014. http://www.uptodate.com/contents/treatment-of-menopausal-symptoms-with-hormone-therapy Accessed March 27, 2014.
  2. National Institutes of Health. Women's Health Initiative. Updated September 21, 2010. http://www.nhlbi.nih.gov/whi/index.html Accessed January 20, 2014.
  3. Anderson GL, Limacher M, Assaf AR, et al; Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004;291:1701-1712. Abstract
  4. Rossouw JE, Anderson GL, Prentice RL, et al; Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002;288:321-333. Abstract
  5. Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. JAMA. 2013;310:1353-1368. Abstract
  6. US Preventive Services Task Force. Hormone replacement therapy for the prevention of chronic conditions in postmenopausal women. May 2005. http://www.uspreventiveservicestaskforce.org/uspstf05/ht/htpostmenrs.htm Accessed January 20, 2014.
  7. De Villiers TJ, Gass ML, Haines CJ, et al. Global consensus statement on menopausal hormone therapy. Climacteric. 2013;16:203-204. Abstract
  8. National Institutes of Health. Women's Health Initiative. Questions and answers about the WHI postmenopausal hormone therapy trials. April 2004. http://www.nhlbi.nih.gov/whi/whi_faq.htm Accessed January 20, 2014.


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Cite this article: Jenny A. Van Amburgh. What's the Latest on Hormone Replacement for Prevention? Medscape. Apr 03, 2014.