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Summary

Doing night shifts actually means that one’s sleep pattern is disrupted. Sleep is crucial not only for complete physical rest after the day’s activities, but more importantly as a period for the brain and hormonal system to repair damages that occurred during the wake period. Prolonged deprivation of sleep eventually may lead to death. Thus, night shifts should not be regarded just as working in different timelines, but as a potential cause for severe health problems that may be the result of a challenge to the circadian rhythm. Data from the Nurses’ Health Study now reveal an association between rotating night shifts and age at menopause [1]. This prospective study followed its participants by biennial detailed questionnaires, and the focus of the current analysis was on a subgroup of nurses who were working in a rotating night shift schedule (alternating day and night shifts). The study recruited nurses between the ages 25-42 when it started in 1989; 61% of 80884 women reported working rotating night shifts prior to 1989 and 38% reported working rotating night shifts between 1989 and 2011. Of women who reported working rotating night shifts prior to 1989, the mean (SD) cumulative duration was 70.5 (67.5) months. Of those who reported rotating night shifts only after the 1989 baseline, the mean cumulative duration worked over follow-up was 36.9 (46.6) months. Working rotating night schedules was less common with age. By the end of the follow-up period in 2013, 27456 women, who had reached natural menopause, were eligible for analysis (main reasons for removal from the list were missing data or use of hormone therapy). After multivariate adjustments, the results indicated a small increase in risk for earlier menopause, especially in younger women and in those with longer periods of rotating night shift work pattern.

Commentary

As it is well documented, age at natural menopause has important implications on women’s health. Earlier menopause has various potential serious adverse outcomes, including a higher mortality risk [2]. Many factors were identified as having an impact on age at menopause, some genetic, some metabolic or medication-related or environmental. The current study adds another possible etiology which might be associated with alternating night shifts. Basically, any change in the normal sleep pattern could affect the nocturnal melatonin secretion. In humans, the circadian rhythm of melatonin release from the pineal gland is highly synchronized with the habitual hours of sleep, and the daily onset of melatonin secretion is well correlated with the onset of the steepest increase in nocturnal sleepiness. Serum melatonin levels were reported to be significantly lower (and the time of peak melatonin values was delayed) in elderly subjects with insomnia compared with age-matched subjects with no insomnia. Exogenous melatonin reportedly induces drowsiness and sleep, and may ameliorate sleep disturbances, including the nocturnal awakenings associated with old age particularly during the peri-menopausal period [4]. There is evidence that melatonin is a neuroendocrine regulator of fertility. In seasonally breeding animals, melatonin inhibits pituitary responses to gonadotropin-releasing hormone or its pulsatile secretion. Serum melatonin concentrations are increased in women with hypothalamic amenorrhea. These findings suggest that changes in melatonin secretion may affect the production of sex steroids [5]. By the same token, circadian rhythm disruption may have an impact on various aspects of menopause via suppression of melatonin [6]. The observation that nighttime melatonin levels sharply decrease with age and that it is associated with sleep disturbances, has led some to speculate that melatonin may play a role in the menopausal transition [4]. Also, we found evidence indicating that a) molecular circadian clock genes exist in human luteinized granulosa cells, and b) there might be a decreased expression of some of these genes in older women (comparing women aged18-33 to 39-45 years old)[7]. This decline may partially explain the decreased fertility and steroidogenesis of reproductive aging. Despite a convincing theoretical, pathophysiological explanation for an association of age at menopause and being engaged in frequent night shifts, such a concrete consequence has not been well validated in an adequate number of studies, and therefore should be considered with caution. Furthermore, additional multifactorial relations might be involved, for example stress or fatigue which accompany such shifts. Stock and colleagues summarized their findings by saying that the degree to which observed effects of rotating night shifts on age at natural menopause are due to circadian disruption is uncertain due to potential residual confounders [1].

Author(s)

  • Amos Pines
    Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
  • Amnon Brzezinski
    The Hebrew University Hadassah Medical School, Jerusalem, Israel

Citations

  1. Stock D, Knight JA, Raboud J, et al. Rotating night shift work and menopausal age. Human Reproduction 2019;34:539–48.
    https://www.ncbi.nlm.nih.gov/pubmed/30753548
  2. Faubion SS, Kuhle CL, Shuster LT, Rocca WA. Long-term health consequences of premature or early menopause and considerations for management. Climacteric 2015;18:483-91.
    https://www.ncbi.nlm.nih.gov/pubmed/25845383
  3. Pines A. Sleep duration and midlife women’s health. Climacteric 2017;20:528-30.
    https://www.ncbi.nlm.nih.gov/pubmed/28613955
  4. Jehan S, Jean-Louis G, Zizi F, et al. Sleep, melatonin, and the menopausal transition: what are the links? Sleep Sci 2017;10:11-18.
    https://www.ncbi.nlm.nih.gov/pubmed/28966733
  5. Srinivasan V, Spence WD, Pandi-Perumal SR, Zakharia R, Bhatnagar KP, Brzezinski A. Melatonin and human reproduction: shedding light on the darkness hormone. Gynecol Endocrinol 2009;25:779-85.
    https://www.ncbi.nlm.nih.gov/pubmed/19905996
  6. Pines A. Circadian rhythm and menopause. Climacteric 2016;19:551-52.
    https://www.ncbi.nlm.nih.gov/pubmed/27585541
  7. Brzezinski A, Saada A, Miller H, Brzezinski-Sinai NA, Ben-Meir A. Is the aging human ovary still ticking?: Expression of clock-genes in luteinized granulosa cells of young and older women. J Ovarian Res 2018;11:95.
    https://www.ncbi.nlm.nih.gov/pubmed/30463623
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