Type of Menopause, Age at Menopause, and Risk of Developing Obstructive Sleep Apnea in Postmenopausal Women

Tianyi Huang; Brian M. Lin, Susan Redline; Gary C. Curhan; Frank B. Hu; Shelley S. Tworoger


Am J Epidemiol. 2018;187(7):1370-1379. 

In This Article

Abstract and Introduction


Despite established sex differences and longstanding hypotheses of sex hormone influence in the etiology of obstructive sleep apnea (OSA), we have found no studies that evaluated type of menopause and age at menopause, which affect postmenopausal hormonal milieu, in relation to OSA risk in women. We followed 50,473 postmenopausal women from the Nurses' Health Study during 2002–2012 and 53,827 postmenopausal women from the Nurses' Health Study II during 1995–2013, with 1,712 and 2,560 incident OSA diagnoses, respectively. Compared with natural menopause, the pooled hazard ratio for OSA was 1.27 (95% confidence interval (CI): 1.17, 1.38) for surgical menopause by hysterectomy/oophorectomy. The association remained the same after further accounting for age at menopause (hazard ratio = 1.26, 95% CI: 1.15, 1.38). The risk associated with surgical menopause was higher among women who were not obese as well as among women who never used hormone therapy (P for interaction < 0.05). Earlier menopause was associated with higher OSA risk prior to adjustment for type of menopause (comparing those aged <40 years versus those aged 50–54 years, hazard ratio = 1.21, 95% CI: 1.08, 1.35; P for trend = 0.008), although no association was observed after the adjustment. Surgical as compared with natural menopause was independently associated with higher OSA risk in postmenopausal women. Our results provide additional evidence for a role for sex hormones, particularly abrupt hormonal changes, in modulating OSA risk.


Obstructive sleep apnea (OSA) is a chronic and highly prevalent disorder in adults that poses an increased risk for cardiometabolic diseases and premature death.[1–3] Prior investigations have consistently reported that OSA is more common among men than women and that there is a significant increase in incidence in women after menopause.[4–10] Differences in endogenous sex hormones, such as estrogen and progesterone, are postulated to play a major role in these observations. This hypothesis is further supported by some,[11–13] but not all,[14–16] studies suggesting that ostmenopausal hormone therapy (HT) may be inversely associated with OSA. However, few studies have evaluated other important hormonal factors in relation to OSA risk.

Each year, more than 300,000 US women receive prophylactic oophorectomies, often at the time of hysterectomy.[17] Bilateral oophorectomy in premenopausal women results in surgically induced menopause that abruptly reduces the production of endogenous sex hormones.[18] Early menopause, either naturally occurring or induced by surgery, radiation, or chemotherapy, is associated with shorter lifetime exposure to endogenous sex hormones. A growing body of evidence suggests that early cessation of the production of endogenous sex hormones, such as estrogen, is detrimental for women's long-term health. Early onset of menopause, particularly as a result of bilateral oophorectomy, has been adversely associated with cardiovascular disease, cognitive decline, and mortality.[17,19–21] It remains unknown whether these menopausal factors also influence OSA risk, given that depletion of estrogen and progesterone may act in the pathogenesis of OSA.[10] We therefore examined risk of developing OSA according to type of menopause and age at menopause in 2 independent prospective cohorts of US women. We hypothesized that both surgical menopause (as compared with natural menopause) and early-onset menopause (regardless of type of menopause) were independently associated with higher OSA risk in postmenopausal women.