Clinical Review


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We’re learning more about the long-term risks and benefits of hormone therapy, how to assess and treat osteoporosis, and the need for vitamin D


Much has changed in the management of menopausal women. The Women’s Health Initiative (WHI) and other trials shed light on the risk-benefit ratio of hormone therapy (HT) and significantly altered patterns of usage. A new fracture risk-assessment tool devised by the World Health Organization is now available for widespread use; it continues to be refined so that it can be applied to specific populations with greater accuracy. And the management of low bone mass and osteoporosis has evolved so that we can determine with greater precision exactly who merits our attention.

This year, the Update on Menopause describes:

  • a reanalysis of WHI data, focusing on the relationship between hormone therapy and the risk of coronary artery disease (CAD)
  • a study from Finland that explores the risk of endometrial cancer associated with various progestin regimens in women who are taking estrogen and who have an intact uterus
  • guidance from the North American Menopause Society and the National Osteoporosis Foundation on who, how, and when to evaluate for a likelihood of fracture
  • insight into the benefits of and need for vitamin D among menopausal women
  • information on a new selective estrogen-receptor modulator under development.

Hormone therapy and CAD: Is the glass half full…or half empty?

Toh S, Hernández-Díaz S, Logan R, Rossouw JE, Hernán MA. Coronary heart disease in postmenopausal recipients of estrogen plus progestin therapy: Does the increased risk ever disappear? A randomized trial. Ann Intern Med. 2010;152(4):211–217.

North American Menopause Society. Position Statement: Estrogen and progestogens use in postmenopausal women: 2010 position statement of The North American Menopause Society. Menopause. 2010;17(2):242–255. DOI: 10.1097/gme.0b013e3181d0f6b9. Accessed April 1, 2010.

When estrogen therapy is initiated within 10 years of menopause, it may reduce the risk of CAD, according to data from the WHI randomized trial and observational data.

The picture isn’t as clear in regard to estrogen-progestin HT. In a just-published study, Toh and colleagues reassessed data from the WHI trial of continuous oral conjugated equine estrogen plus medroxyprogesterone acetate versus placebo. They also compared the WHI findings with those of the large observational Nurses’ Health Study (NHS). Here are some of their findings:

  • participants became less consistent in taking study medication over time—a finding of many long-term studies. This trend prompted Toh and colleagues to adjust their analysis for adherence
  • among women who used HT within 10 years after the menopausal transition, the hazard ratio (HR) for CAD was 0.64 (95% confidence interval [CI], 0.21, 1.99) in the WHI and 0.68 (95% CI, 0.24, 1.91) in the NHS. Both hazard ratios suggest that the risk of CAD is lower in Ht users than in nonusers—although the difference is not significant
  • when investigators pooled the WHI and NHS findings, the hazard ratio for CAD associated with combination HT was 0.66 (95% CI, 0.31, 1.42). Note that, as the number of participants increases, the confidence limits narrow.

Toh and colleagues concluded that their analysis demonstrated no diminished risk of CAD with HT use. My reading of these data is different: Combination HT does not increase the risk of CAD in women who have been postmenopausal for less than 10 years.

Focus on risk was unbalanced

The question of whether combination HT reduces the risk of CAD in younger women is somewhat moot. I am not aware of any ObGyn in the United States who uses HT to prevent CAD, and the great majority of symptomatic women who consider initiating HT have been menopausal for less than a decade. For these reasons, I find the conclusions drawn by Toh and colleagues a bit mystifying—and the title they chose for their study may be misleading:

Coronary heart disease in postmenopausal recipients of estrogen plus progestin therapy: Does the increased risk ever disappear?

Nevertheless, fear that HT might increase the risk of CAD is common among symptomatic menopausal women and their physicians. What this important analysis can offer is reassurance to symptomatic women who have been menopausal for less than 10 years: namely, that HT—estrogen alone or estrogen plus progestin—does not increase the risk of myocardial infarction or death from CAD.


You should counsel symptomatic women who have been menopausal less than 10 years that short-term use of estrogen therapy or estrogen-progestin therapy does not appear to increase their risk of CAD.


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