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HT skin cream, patch formulations associated with lower risk for MI
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Regimen and route of application may modify the effects of hormone therapy on risk for myocardial infarction in menopausal women, according to study findings.
During 1995 to 2001, researchers in Denmark followed a cohort of 698,098 healthy Danish HT users aged 51 to 69 years. The researchers analyzed a prescription registry and identified 4,947 MI incidents. The risk for MI was not increased after comparing current HT users and women who never used HT (RR=1.03; 95% CI, 0.95-1.11). Broken down by age, the risk for MI was as follows: 51 to 54 years, RR=1.24 (95% CI, 1.02-1.51); 55 to 59 years, RR=0.96 (95% CI, 0.82-1.12); 60 to 64 years, RR=1.11 (95% CI, 0.97-1.27); and 65 to 69 years, RR=0.92 (95% CI, 0.80-1.06).
However, younger women who were longer users of HT were at increased risk for MI — a risk that was not observed in older women. Continuous HT use was associated with the highest risk for MI among women of all ages. Analysis revealed an increased risk for MI with oral unopposed estrogen therapy and a lower risk with dermal formulations (P=.04). Increased risk for MI was not associated with use of unopposed estrogen, tibolone or cyclic combined therapy as well as with progestagen type or estrogen dose. – by Katie Kalvaitis
Eur Heart J. 2008;29:2660-2668.
Lokkegaard et al reported two main findings: Among women who received combined estrogen–progestin therapy, continuous vs. cyclic progestin administration was associated with higher coronary heart disease risk, and among women receiving unopposed estrogen, transdermal vs. oral therapy was associated with lower CHD risk. These observations have biologic plausibility. The discrepant risks for CHD and breast cancer in the Women’s Health Initiative between the combined estrogen–progestin trial (risk increased) and the unopposed estrogen trial (risk not increased) have fueled hypotheses that variations in progestin regimens may play a role in mediating the adverse risks associated with HT use. In addition, transdermal estrogen (which affects hemostasis less than oral estrogen) could potentially confer less cardiovascular risk, but data from randomized clinical trials to support this hypothesis are currently lacking.
The results from Lokkegaard et al are therefore intriguing and will likely stimulate future research aimed at disentangling the relationships between postmenopausal HT and CV risk. However, one important limitation of the study was that information on several major CV risk factors for the study population was unavailable, substantially increasing the likelihood of residual confounding. Further, the findings must be taken for what they are — observational data. Among the many lessons learned from the Women’s Health Initiative HT trials, these trials’ results highlighted the unavoidable limitations of observational data. It would therefore be premature to change clinical practice based on these findings.
Although an extensive observational literature has described protective effects of postmenopausal HT on CV risk, the now well-known Women’s Health Initiative HT trials’ results demonstrated increased CHD risk among women randomly assigned to combined therapy with oral conjugated equine estrogen and medroxyprogesterone acetate. Since publication of this landmark trial’s results, many hypotheses to explain the discrepancies between the observational and randomized trials have been proposed. Much attention has been devoted to methodologic issues (including compliance bias and residual confounding in observational studies) as well as biologic factors (including differing clinical characteristics of the study populations and differences in the preparations, timing and duration of HT regimens.)
– Emily Szmuilowicz, MD
Endocrine Today Editorial Board member