Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause
Rossouw et al, April 4, 2007, JAMA, vol 297, No. 13, pgs 1465-1476
 
Context. The timing of initiation of hormone therapy may influence its effect on cardiovascular disease.
 
Objective. To explore whether the effects of hormone therapy on risk of cardiovascular disease vary by age or years since menopause began.
 
Design, setting and participants. Secondary analysis of the Women’s Health Initiative (WHI) randomized controlled trial of hormone therapy in which 10739 post-menopausal women who had undergone a hysterectomy were randomized to conjugated equine estrogens (CEE) or placebo, and 16608 post-menopausal women who had not had a hysterectomy were randomized to CEE plus medroxyprogesterone acetate ( CEE+ MPA )or placebo. Women aged 50 to 79 years were recruited to the study from 40 US clinical centres between September 1993 and October 1998.
 
Results. In the combined trials, there were 396 cases of CHD and 327 cases of stroke in the hormone therapy group vs 379 cases of CHD and 239 cases of stroke in the placebo group.
 
For women with less than 10 years since menopause began, the hazard ratio (HR) for CHD was 0.76, 10-19 years, 1.10, and 20 or more years, 1.28.
 
The estimated absolute excess risk for CHD for women within 10 years of menopause was -6 per 10000 person years, for women 10-19 years since menopause began, 4 per 10000 person years, and for women 20 or more years from menopause onset, 17 per 10000.
 
For the age group of 50-59 years, the HR for CHD was 0.93, and the absolute excess risk was -2 per 10000 person years, 60-69 years, 0.98, and -1 per 10000 person years, and 70-79 years, 1.26 and 19 per 10000 person years.
 
Hormone therapy increased the risk of stroke, HR = 1.32. Risk did not vary significantly by age or time since menopause.
 
There was a non-significant tendency for the effects of hormone therapy on total mortality to be more favourable in younger than older women, HR of 0.70 for 50-59 years, 1.05 for 60-69 years, and 1.14 for 70-79 years.
 
Conclusions. Women who initiated hormone therapy closer to menopause tended to have reduced CHD risk compared with the increased CHD risk among women more distant from menopause, but this trend does not meet our criterion for statistical significance. A similar non-significant trend was observed for total mortality but the risk of stroke was elevated regardless of years since menopause. These data should be considered in regard to the short-term treatment of menopausal symptoms.