Menopausal hormone therapy and sleep-disordered breathing: evidence for a healthy user bias

Observational studies suggest that menopausal hormone therapy protects against sleep-disordered breathing, but such findings may be biased by a "healthy user effect." When the Women's Health Initiative Study reported in 2002 that estrogen-progestin therapy increases heart disease risk, many women discontinued hormone therapy. We investigate healthy user bias in the association of hormone therapy with sleep-disordered breathing in the Sleep in Midlife Women Study.

A total of 228 women aged 38 to 62 years were recruited from the Wisconsin Sleep Cohort Study. They underwent polysomnography to measure apnea-hypopnea index, at home semiannually from 1997 to 2006, and in the sleep laboratory every four years (n = 1828 studies). Hormone therapy was recorded monthly. Linear models with empirical standard errors regressed logarithm of apnea-hypopnea index on hormone use with a pre- or post-July 2002 interaction, adjusting for menopause and age.

The association of hormone therapy and sleep-disordered breathing was heterogeneous (P < .01); apnea-hypopnea index among users was 15% lower in the early period (95% confidence interval, -27% to -1%), but similar to nonusers in the late.

Hormone therapy was negatively associated with sleep-disordered breathing only until the Women's Health Initiative results were publicized. Hormone therapy may have been a marker for healthfulness in the early period, creating a spurious association with sleep-disordered breathing.