The Importance of Circadian Rhythms in Women’s Health

NUNM students have many opportunities to explore topics, research and areas of practice that interest them. From broad elective choices to research study participation and self study, our students choose the doctor they want to become. Here, Jessica Zadra, naturopathic doctoral student, shares her research and perspectives on the importance of circadian rhythms in women’s health. 

Circadian rhythms refer to the array of biological rhythms within the human body and almost all organisms studied on earth that cycle on a near 24 hour clock.

These rhythms are generated by a core of biological clocks present in nearly every cell of the human body and regulated by a ‘master clock’ in the brain. This master circadian clock is comprised of a group of neurons called the suprachiasmatic nucleus (SCN) located in the hypothalamus, which helps our body coordinate function based on the time of day. This is how your body knows when it’s appropriate to wake up, to go to sleep, etc. Ultimately, circadian rhythms are physiological and behavioral changes that follow a daily cycle and influence critical bodily functions such as hormone release, temperature, eating habits, digestion, mood, and sleep.

Why are these cycles so important?

The most familiar circadian rhythm is the sleep-wake cycle. This is a light-related rhythm, which naturally aligns to the environment’s external light-dark cycle. The SCN controls the production of both melatonin and cortisol via the information it receives about incoming light. When this cycle is properly regulated, we generally sleep well, have consistent energy throughout the day, and maintain normal hunger-satiety homeostasis. On the other hand, both chronobiology (the study of circadian rhythms) and a growing number of health studies, have linked circadian rhythm disruption (CRD) with an increased risk of chronic diseases and illnesses that impact the central nervous system, immune and reproductive systems, metabolic organs, cardiovascular health, and endocrine functions.[1] In addition to these links, studies have further concluded that women may actually be slightly more susceptible to, and effected by, CRD.

As insomnia is reported at nearly twice the rate in women than in men, multiple studies have looked at the sex differences in sleep and wake patterns. These studies have proposed that the variances in our internal clocks may play a substantial role in these differences. For example, one study found that women have a shorter intrinsic circadian period and are more likely than men to have biological days that are shorter than 24 hours, the difference being an average of 6 minutes.[2] While 6 minutes may not seem like a lot, the experiment concludes that the small difference would account for a nearly half-hour earlier onset of melatonin secretion in women.

A more recent 2016 study further concluded that women tend to fall asleep and wake earlier than men on an average of about 2 hours, putting women practically in a different time zone.[3] This study, which was of the first to control for oral contraceptive use and menstrual cycle phase, observed advances in rhythms of body temperature, sleep, and alertness in women. This suggests an increased susceptibility to sleep and wake disturbances indicative of circadian variation in women.[3] It is important to note that this study observed these differences primarily in the mid-follicular and mid-luteal phases, illuminating how the menstrual cycle may influence and be influenced by circadian rhythms. The regulation of circadian rhythms, particularly the sleep-wake cycle, is an important aspect of women’s health to consider – especially as it relates to fertility and menopause.

Circadian Rhythms and Fertility

In animal models, disturbance of circadian timing by either a genetic manipulation or the disruption of the light-dark cycle has resulted in impaired fertility and early gestational complications.[4] A 2016 systematic review demonstrates how mutations of clock genes (CRD) resulted in a disruption of the pre-ovulatory luteinizing hormone (LH) surge and other hormonal profiles, which ultimately impacted fertility in animals.[4] Furthermore, the same review found that bright light exposure/therapy mimicking the natural light-dark cycle influenced the ovulatory cycle in multiple studies, increasing levels of prolactin, follicule stimulating hormone (FSH) and LH secretion.[4]

While we do not have many human studies that have directly looked at how CRD impacts fertility, there is substantial evidence of associations between CRD and impaired reproductive health via analysis of female shift workers. A 2014 meta-analysis of 15 studies with more than 100,000 women included found that shift workers had an increased rate of infertility (11.3%) in addition to an increased rates of menstrual disruptions (16.05%).[5] While there are multiple pathways in which circadian rhythms and sleep may influence fertility, these findings suggest that CRD may have the ability to impact conception.

Circadian Rhythms and Menopause

Many people are most likely familiar with the fact that women going through menopause often experience insomnia. This is partially due to reduced levels of hormones like estrogen and progesterone, both of which have sleep protective benefits. However, insomnia associated with menopause may be additionally influenced by reduced levels of melatonin that have been shown to decrease with age, specifically as women approach menopause. As our circadian rhythms greatly influence the production of melatonin, as mentioned above, experts have proposed that the disturbance of the circadian system is of substantial relevance, both in regard to the sleep-disturbing symptoms and to the direct impairment of sleep regulation in menopausal and postmenopausal women.[6]

It has been additionally observed that a reduction in melatonin is associated with an increased risk of breast cancer. Night shift work reportedly increases this risk, possibly due to melatonin suppression.[6] Attempting to realign circadian rhythms may be an effective way to naturally boost melatonin secretion. This is supported by evidence showing that supplementation of melatonin may be helpful in treating menopausal symptoms, depending on the individual.[6]

What can we do then, to realign our circadian clocks and harvest the benefits of being in sync with our natural circadian cycles?

  1. Light Exposure – Maybe you have heard already that it is important to get adequate light exposure during the day, followed by a decrease in such an exposure in the evening. While this concept seems rather basic, the environment in which many of us live in today is often not conducive to this natural rhythm. What does this light exposure look like? The type of light we need is blue light exposure, ideally from the sun, for a minimum of 15 minutes in the day. You can also recreate this exposure by using a light therapy device. Practical tips: exercise (go on a walk, run etc.) in the morning, open as many windows/curtains during the day as possible, use sunlight spectrum light bulbs (only during the day), and set your computer screen to the brightest setting.
    The flip side of this is limiting this same type of blue light exposure in the evening, especially in the 2-3 hours leading up to bed. At this time red and yellow wave lengths are in our favor. This can mean simply dimming lights and/or using more natural light sources (fire, candles) limiting screen exposure, or using devices that help shield blue light wave length at night.
    Practical tips: download the free F.lux app on your computer, phones, etc. that minimizes blue light exposure based on your particular time zone. There are also many amber tinted glasses for purchase you can wear in the evening if you don’t mind looking like Bono.
  2. Exercise – Of course there is an exercise component! Increasing evidence has made it clear that exercise has significant positive effects on our circadian clock, and, secondary to light exposure, can restore dysregulated circadian rhythms.[7] This may be partially due to the clock genes in our skeletal muscle, which is an integral component of our ‘master clock.’ Practical Tip: While evidence is mixed on the best time to exercise, though many findings point towards the mornings, it is important to note that intense activity during the evening may delay melatonin production.[8] Regardless, the consensus seems to be that establishing a routine is actually of more importance as it relates to circadian rhythm entrainment.
  3. Practice Sleep Hygiene – Practicing good sleep hygiene can mean a number of things, such as limiting caffeine and alcohol consumption and reducing noise and stress before bedtime. Additionally, sleeping in a completely dark, cool room may be non-negotiable for many as light exposure disrupts melatonin production, and cooler sleep temperatures are more in line with our natural circadian activity.[9] Practical tips: Use blackout curtains at night or purchase a sleeping mask if you have a room that lets in light at night. If you are easily disrupted by noise, try experimenting with different white noise soundscapes.

There are many other factors that may help with circadian rhythm entrainment such as time restricted feeding, maintaining a stabilized blood sugar, stress reduction, embracing seasonal changes and allowing your body to rest more during the winter. If any of these sound interesting to you, I encourage you to investigate them further.

References

  1. Sulli G, Manoogian ENC, Taub PR, Panda S. Training the circadian clock, clocking the drugs, and drugging the clock to prevent, manage, and treat chronic diseases. Trends Pharmacol Sci. 2018; 39(9): 812-827. doi: 10.1016/j.tips.2018.07.003[1]
  2.  Duffy JF, Cain SW, Chang A-M, et al. Sex difference in the near-24-hour intrinsic period of the human circadian timing system. Proc Natl Acad Sci. 2011; 108(Supplement 3): 15602-15608. doi: 10.1073/pnas.1010666108[2]
  3. Boivin DB, Shechter A, Boudreau P, Begum EA, Ng Ying-Kin NMK. Diurnal and circadian variation of sleep and alertness in men vs. naturally cycling women. Proc Natl Acad Sci U S A. 2016; 113(39): 10980-10985. doi: 10.1073/pnas.1524484113[3]
  4. Goldstein CA, Smith YR. Sleep, circadian rhythms, and fertility. Curr Sleep Med Rep. 2016; 2(4): 206-217. doi: 10.1007/s40675-016-0057-9[4]
  5. Stocker LJ, Macklon NS, Cheong YC, Bewley SJ. Influence of shift work on early reproductive outcomes: a systematic review and meta-analysis. Obstet Gynecol. 2014; 124(1): 99-110. doi: 10.1097/AOG.0000000000000321[5]
  6. Jehan S, Jean-Louis G, Zizi F, et al. Sleep, melatonin, and the menopausal transition: What are the links? Sleep Sci. 2017; 10(1): 11-18. doi: 10.5935/1984-0063.20170003[6]
  7. Hower IM, Harper SA, Buford TW. Circadian rhythms, exercise, and cardiovascular health. J Circadian Rhythms. 2018; 16(1): 7. doi: 10.5334/jcr.164[7]
  8. Oral O, Kara E, Akdogan I, Isbilir M, Bekir H. Relationship between melatonin and exercise. Int Türkbilim J. 2014; 2: 1-15. https://www.researchgate.net/publication/269279180_RELATIONSHIP_BETWEEN_MELATONIN_AND_EXERCISE[8]
  9. Okamoto-Mizuno K, Mizuno K. Effects of thermal environment on sleep and circadian rhythm. J Physiol Anthropol. 2012; 31(1): 14. doi: 10.1186/1880-6805-31-14[9]

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