Vasomotor symptoms mediate ovarian aging and poor sleep in menopause

BOSTON — Declining levels of anti-Müllerian hormone, an indicator of ovarian aging, predict the onset of sleep disturbance during menopause, according to an analysis of data from the Study of Women’s Health Across the Nation.

However, vasomotor symptoms appear to mediate this association.

“New-onset sleep disturbance is common in midlife women (47% of study visits in our sample),” Hadine Joffe, MD, MSc, associate professor of psychiatry at Harvard Medical School, director of the Division of Women's Mental Health at Brigham and Women’s Hospital, and director of psycho-oncology research at Dana Farber Cancer Institute, told Endocrine Today.

Hadine Joffe

“The development of sleep disturbance in general, and multiple middle-of-the-night awakenings in particular, in midlife women is related to ovarian aging, as indicated by falling levels of the ovarian hormone anti-Müllerian hormone, but hot flashes and night sweats appear to be the main factor which explains this association between ovarian aging and new-onset sleep disturbance.”

Joffe and colleagues analyzed data from 1,098 women evaluated for new-onset sleep disturbance and 1,166 for awakenings. At enrollment in the SWAN study, the women were aged 42 to 52 years, were premenopausal or early perimenopausal and had no sleep disturbance. Over 13 years follow-up, they transitioned to postmenopause without hormone therapy, hysterectomy or bilateral oophorectomy. During annual visits, researchers recorded self-reported sleep disturbance (trouble falling asleep or staying asleep, or early waking), number of vasomotor symptoms and anti-Müllerian hormone (AMH) concentrations.

During a mean 6.4 years of follow-up, 519 (47%) reported sleep disturbance, and 493 (42%) reported awakenings. Among the sleep-disturbance cohort, 32% reported either frequent or infrequent vasomotor symptoms, as did 17% of the awakenings group. AMH levels were undetectable (< 2 pg/mL) in 68% of the women (mean: 5.0 ± 2.7 pg/mL; median: 34.5 pg/mL). After adjustment for age, race, study site and number of medical conditions, researchers found that AMH was inversely associated with new-onset sleep disturbance (HR = 0.90, 95% CI 0.82–0.998) and awakenings (HR = 0.90, 95% CI 0.81–0.995). Vasomotor symptoms were associated with AMH, new-onset sleep disturbance and awakenings (P < .0001 for all). After further adjustment for vasomotor symptoms, the associations with AMH and new-onset sleep disturbance or awakenings disappeared.

“The clinical implication is that menopause-related vasomotor symptoms are the main reason why women develop sleep problems and, in particular, middle-of-the-night awakenings, related to ovarian aging, so these symptoms should be assessed and targeted in treatment of sleep disturbance,” Joffe said. – by Jill Rollet

Reference :

Joffe H, et al. Poster LBSat-08. Presented at: The Endocrine Society Annual Meeting; April 1-4, 2016; Boston.

Disclosure: Joffe reports serving as an ad hoc consultant for Merck & Co., Mitsubishi-Tanabe, NeRRe Therapeutics, Noven, and SAGE Therapeutics, and as an investigator for Merck & Co.