Issue: November 2015
September 30, 2015
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Discontinuing postmenopausal HT increases CV death risk

Issue: November 2015
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The withdrawal of postmenopausal hormone therapy can raise the risk for cardiovascular mortality and stroke, particularly in the first year after discontinuation and in recently menopausal women, according to research in The Journal of Clinical Endocrinology & Metabolism.

“Our findings question the safety of annual discontinuation practice to evaluate whether a woman could manage without HT,” Tomi S. Mikkola, MD, PhD, of the department of obstetrics and gynecology at Helsinki University Hospital, and colleagues wrote. “Our data also warrant further studies to compare the [CV] safety of immediate vs. tapered HT discontinuation.”

Mikkola and colleagues analyzed data from the National Reimbursement Register from 332,202 Finnish women aged 40 years or older who discontinued HT between 1994 and 2009. Researchers followed the cohort until a cardiac-related death, stroke or the end of the study period in 2009; death information was obtained from the National Cause of Death Register. Researchers compared the number of deaths in the cohort with the expected number of deaths in the age-standardized background population. Researchers also compared HT “stoppers” with HT users in a subanalysis.

The risk for CV death was significantly increased within the first HT posttreatment year, with a standardized mortality ratio (SMR) of 1.26 (95% CI, 1.16-1.37), whether HT exposure was for less than 5 years or more than 5 years. There was a reduction in SMR in follow-up after 1 year (0.75; 95% CI, 0.72-0.78). Risk for death from stroke also was increased in the first year post-HT treatment (SMR = 1.63; 95% CI, 1.47-1.79), but that risk was reduced in follow-up at 1 year (SMR = 0.89; 95% CI, 0.85-0.94). The risks for CV death and stroke were greater when compared with HT users for first posttreatment year and thereafter, according to researchers, with the risk further elevated in women who discontinued HT before age 60 years (SMR = 1.94; 95% CI, 1.51-2.48).

The risk for any-cause mortality also was significantly increased in the first year after HT discontinuation, with an SMR of 2.28 (95% CI, 2.23-2.34); however, that additional risk disappeared when follow-up was prolonged beyond 1 year.

“The higher risk for death in recently menopausal women as compared to [older] women may imply a higher sensitivity of arteries and heart toward estrogen in younger women, a feature that may have been reduced or lost in [older] women,” the researchers wrote. “Thus, our posttreatment data support the ‘window theory,’ suggesting that actual HT use may be protective against vascular events in younger but not in older women.” by Regina Schaffer

Disclosure: Three of the study researchers report working for EPID Research, a company that performs financially supported studies to several pharmaceutical companies. Mikkola reports no relevant financial disclosures.