Individualizing Hormone Therapy to Minimize Risk

Accurate Assessment of Risks and Benefits

Donna Shoupe


Women's Health. 2011;7(4):475-485. 

In This Article

Cardiovascular Protection

A total of 40 years of trials support the cardiovascular protection of estrogen.[2,4–13,31–37] A few of the studies are highlighted below:

  • The Nurses Health Study followed over 70,000 women for over 30 years. They reported that the 0.3 mg dose of conjugated estrogen therapy was associated with a significant reduction in both major coronary disease 0.58 (95% CI: 0.37–0.92) and stroke 0.43 (95% CI: 0.22–0.83);[5,8]

  • Both arms of the WHI reported a major reduction in new cases of diabetes during the 7-year trial. This is an important morbidity that was inexplicably omitted from the arbitrary and invalidated 'global index' used by the WHI authors;[3,18]

  • The WHI Coronary-Artery Calcification (CAC) studied 1064 women, randomized on the estrogen only arm of the WHI between age 50–59 years, with computed tomography of the heart. After 7.4 years on the study, the women who had taken estrogen had a significantly lower calcium score (30–40% reduction) compared with those taking placebo. (83.1 vs 123.1; p = 0.02). Women adherent to therapy or at least 5 years had a 64% reduction in score (p = 0.001).[2] An accompanying editorial wrote "The results of WHI-CAC are clear and striking: women randomly assigned to receive estrogen had significantly less coronary-artery calcification than women randomly assigned to receive placebo";[38]

  • In a randomized study of 222 postmenopausal women 45 years of age or older without preexisting cardiovascular disease but with low-density lipoprotein cholesterol levels ≥130 mg/dl, the average rate of progression of subclinical atherosclerosis was lower in those taking estradiol compared with controls. (-0.0017 mm/year vs 0.0036 mm/year); the difference between average progression rates was 0.0053 mm/year (95% CI: 0.0001–0.0105 mm/year; p = 0.046). In women not on lipid-lowering medication (n = 77), the difference between average rates of progression between placebo versus estradiol was even greater at 0.0147 mm/year (95% CI: 0.0055–0.0240; p = 0.002);[9]

  • In a meta-analysis of 23 randomized controlled trials, women starting HRT <10 years after menopause or <60 years of age had significantly lowered risk of cardiovascular disease (Table 2);[33]

  • Data from 23 trials, with 39,049 participants followed for 191,340 patient-years, concluded that hormone therapy reduced the risk of CHD events in younger postmenopausal women (OR: 0.68; 95% C I: 0.48–0.96). For older women, hormone therapy increased the risk the first year (OR: 1.47; 95% CI: 1.12–1.92), then reduced events after 2 years (OR: 0.79; 95% CI: 0.67–0.93).[37]


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