Friday, April 16, 2010

From Harvard, With Love

More good news on the benefits of hormone therapy if taken within the first 10 years of menopause, not after. -- SG

Untangling the Relations Between Hormone Therapy and Coronary Heart Disease
Analysis showed no evidence of excess CHD risk during the first 2 years of combined hormone therapy initiated within 10 years of menopause; cardioprotection might develop after 6 years.
Risk for coronary heart disease (CHD) that is associated with use of hormone therapy (HT) might depend on time elapsed since initiation of use and could be limited to women who begin HT long after menopause (JW Womens Health Jul 31 2008). In an analysis of data from 16,608 postmenopausal women who participated in the Women's Health Initiative (WHI) randomized trial of conjugated equine estrogens plus medroxyprogesterone acetate (E+P) versus placebo, investigators sought to estimate the effect of continuous E+P HT on CHD risk over time in relation to the number of years since menopause. The researchers calculated adherence-adjusted hazard ratios (HRs) and CHD-free survival curves. Adherence-adjusted HRs also were calculated from Nurses' Health Study (NHS) data.
Overall, continuous use of E+P HT compared with no use was associated with CHD HRs of 2.36 (95% confidence interval, 1.55–3.62) for the first 2 years of use and 1.69 (95% CI, 0.98–2.89) for the first 8 years. For women who used HT within 10 years after menopause, CHD HRs were 1.29 (95% CI, 0.52–3.18) for the first 2 years of use and 0.64 (95% CI, 0.21–1.99) for the first 8 years. The CHD-free survival curve for continuous HT use initially fell below the curve for no use, but the two curves crossed at approximately 6 years after study entry (95% CI, 2–10 years; P for between-curve differences, 0.44).

Comment: In 2002, initial WHI findings indicated that E+P HT was associated with excess risk for CHD. Although subsequent WHI reports have suggested that this risk is related to patient age and recency of menopause, many clinicians and women continue to believe that HT raises CHD risk. The authors note that "the available evidence suggests that [E+P HT] does not reduce the risk for CHD during the first 3 to 6 years of use in women who initiated therapy close to menopause," and that "a possible cardioprotective effect of [E+P HT] among women within 10 years of menopause was apparent only after approximately 6 years of use." By our interpretation, the pooled WHI and NHS data provide reassurance that E+P HT that is initiated within 10 years of menopause is not associated with excess risk for CHD. HT usually is initiated for bothersome vasomotor symptoms soon after menopause in women who are in their 50s. In making decisions with patients about HT use, clinicians should find recently updated North American Menopause Society guidelines to be useful. These guidelines emphasize that treatment of vasomotor symptoms is the main indication for HT and advise that HT not be prescribed for cardioprotection.
— JoAnne M. Foody, MD, and Andrew M. Kaunitz, MD
Published in Journal Watch Women's Health April 8, 2010

Toh S et al. Coronary heart disease in postmenopausal recipients of estrogen plus progestin therapy: Does the increased risk ever disappear? A randomized trial. Ann Intern Med 2010 Feb 16; 152:211

Department of Population Medicine, Harvard Medical School/Harvard Pilgrim Health Care Institute, 133 Brookline Avenue, 6th Floor, Boston, MA 02215, USA.

BACKGROUND: Estrogen plus progestin therapy increases the risk for coronary heart disease (CHD) in postmenopausal women. However, this increased risk might be limited to the first years of use and to women who start therapy late in menopause. OBJECTIVE: To estimate the effect of continuous estrogen plus progestin therapy on CHD risk over time and stratified by years since menopause. DESIGN: Women's Health Initiative randomized, double-blinded, placebo-controlled trial. ( registration number: NCT00000611) SETTING: 40 U.S. clinical centers. PATIENTS: 16 608 postmenopausal women with an intact uterus at baseline from 1993 to 1998. INTERVENTION: Conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo. MEASUREMENTS: Adherence-adjusted hazard ratios and CHD-free survival curves estimated through inverse probability weighting. RESULTS: Compared with no use of hormone therapy, the hazard ratio for continuous use of estrogen plus progestin therapy was 2.36 (95% CI, 1.55 to 3.62) for the first 2 years and 1.69 (CI, 0.98 to 2.89) for the first 8 years. For women within 10 years after menopause, the hazard ratios were 1.29 (CI, 0.52 to 3.18) for the first 2 years and 0.64 (CI, 0.21 to 1.99) for the first 8 years, and the CHD-free survival curves for continuous use and no use of estrogen plus progestin crossed at about 6 years (CI, 2 years to 10 years). LIMITATION: The analysis may not have fully adjusted for joint determinants of adherence and CHD risk. Sample sizes for some subgroup analyses were small. CONCLUSION: No suggestion of a decreased risk for CHD was found within the first 2 years of estrogen plus progestin use, including in women who initiated therapy within 10 years after menopause. A possible cardioprotective effect in these women who initiated therapy closer to menopause became apparent only after 6 years of use. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

PMID: 20157135 [PubMed - indexed for MEDLINE]

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