What is the Connection Between Low Testosterone and Circadian Syndrome?

Low testosterone in men is becoming a bigger problem with each passing decade. But what is the most significant cause of hypogonadism (the technical term for low testosterone)? It isn’t diet. It’s not environmental toxins or concussions, though they can affect a guy’s levels. It isn’t even drinking Bud Light. As you might surmise from the article’s title, the most significant cause of low testosterone is circadian syndrome, a condition related to a disrupted circadian rhythm and sleep debt.

A new study shows how much of a problem this is for American men. In this article, I’ll discuss some of the key findings and what we can do about them.

What is the prevalence of low testosterone?

The most current research shows that 20-50% of U.S. males have testosterone deficiency.1Kwong JCC, Krakowsky Y, Grober E. Testosterone deficiency: a review and comparison of current guidelines. J Sex Med. (2019) 16:812–20. doi: 10.1016/j.jsxm.2019.03.262 The cutoff for clinically diagnosed testosterone deficiency is a blood level 300 ng/dl, which is where the data comes from, suggesting that up to half of American men have low testosterone. In comparison, optimal testosterone levels are between 800-1200 ng/dl. 

The problem is likely worse than that, as American men are less likely to get a checkup with their doctor than women, and even if they do, their doctors rarely check testosterone levels.

What happens to men with low testosterone?

Low testosterone leads to physical, mental, and sexual problems, including:

  1. Physical Changes: increased body fat, decreased muscle mass and strength, fragile bones, hot flashes, fatigue, and increased cholesterol levels.2Mulligan, T., Frick, M. F., Zuraw, Q. C., Stemhagen, A., & McWhirter, C. (2006). Prevalence of hypogonadism in males aged at least 45 years: the HIM study. International Journal of Clinical Practice, 60(7), 762-769.
  2. Mental and Emotional Changes: changes in mood and mental capacity, including feelings of depression, irritability, trouble concentrating, and impaired memory.3Shores, M. M., Sloan, K. L., Matsumoto, A. M., Moceri, V. M., Felker, B., & Kivlahan, D. R. (2012). Increased incidence of diagnosed depressive illness in hypogonadal older men. Archives of General Psychiatry, 61(2), 162-167.
  3. Sexual Dysfunction: reduced sexual desire, fewer spontaneous erections, and infertility.4Khera, M. (2016). Male hormones and men’s quality of life. Current Opinion in Urology, 26(2), 152-157.

In many cases, as men develop any of these health problems, the health problems themselves lead to a greater decline in testosterone, which worsens the problems, which further tanks testosterone. You must break the downward cycle, and sleep is likely the most important place to start.

What is Circadian Syndrome (CircS)?

According to the study authors,

CircS is primarily diagnosed based on hypertension, dyslipidemia, central obesity, diabetes, short sleep duration, and depression. Each of those symptoms is mainly governed by circadian rhythms, which are major regulators in almost every aspect of human health and metabolism.

Association between the prevalence rates of circadian syndrome and testosterone deficiency in US males: data from NHANES (2011–2016)

The Circadian Syndrome is diagnosed when a person has at least 4 of the following:

  1. Central obesity: waist circumference ≥102 cm (40 inches);
  2. High triglycerides (TG): TG ≥150 mg/dl or using TG-lowering drugs
  3. Low high-density lipoprotein cholesterol: high-density lipoprotein cholesterol <40 mg/dl
  4. High blood pressure: systolic blood pressure ≥130 mmHg or using antihypertensive drugs
  5. High fasting glucose: fasting glucose ≥100 mg/dl or using anti-diabetic drugs
  6. Short sleep duration: sleep duration <6 h/day on average
  7. Depression: score ≥10 on the Patient Health Questionnaire (PHQ-9). You can access the PHQ-9 here.

How often do you hear a medical expert refer to high blood pressure, high cholesterol or triglycerides, belly fat, depression, or type II diabetes as issues related to circadian rhythm? Probably never.

Instead, the knee-jerk reaction is prescribing drugs to deal with these issues. The drugs don’t deal with the cause. They just temporarily reduce the symptoms. 

When you think about it, the best way to maximize pharmaceutical sales is to get people to live lifestyles that compromise sleep. I’m not suggesting that would ever happen, though.

What causes Circadian Syndrome? 

Testosterone levels ebb and flow over the course of a 24-hour cycle. They peak between 8 am – 9 am, which is why you should always get yours tested during that timeframe. Getting a testosterone test later in the day may show you have low testosterone when you really don’t.

Your circadian rhythm master switch is called the suprachiasmatic nucleus (SCN) in your hypothalamus. 

The primary input to the SCN is light information, which is relayed through the retinohypothalamic tract, allowing external light conditions to synchronize the body’s circadian rhythms. However, multiple factors can affect the functioning and regulation of the SCN and, subsequently, the circadian rhythm.

  1. Light: Light is the most significant influencer of the SCN and, therefore, our circadian rhythm. Light exposure, particularly at certain wavelengths (blue light), can shift the phase of the circadian clock.5Lockley SW, Brainard GC, Czeisler CA. High sensitivity of the human circadian melatonin rhythm to resetting by short wavelength light. The Journal of Clinical Endocrinology & Metabolism. 2003 Sep 1;88(9):4502-5.
  2. Age: Aging can cause changes in the circadian rhythm. Research shows that the amplitude of circadian rhythms decreases with age and that there is often a phase advance where people tend to favor earlier sleep and wake times.6Hofman MA, Swaab DF. Living by the clock: The circadian pacemaker in older people. Ageing Research Reviews. 2006 May 1;5(1):33-51.
  3. Genetics: Certain genes, such as CLOCK, PER, CRY, and others, play a crucial role in the generation and regulation of circadian rhythms. Mutations or dysfunctions in these genes can disrupt the normal circadian rhythm.7Takahashi JS. Transcriptional architecture of the mammalian circadian clock. Nature Reviews Genetics. 2017 Mar;18(3):164-79.
  4. Temperature: The core body temperature rhythm can affect the SCN, which is why it’s important to keep your bedroom cool.8Buhr ED, Yoo SH, Takahashi JS. Temperature as a universal resetting cue for mammalian circadian oscillators. Science. 2010 Oct 15;330(6002):379-85.
  5. Social and Behavioral Factors: Changes in daily routines, shift work, jet lag, exercise, and meal times can affect the SCN and shift the body’s circadian rhythm.9Wright KP, McHill AW, Birks BR, Griffin BR, Rusterholz T, Chinoy ED. Entrainment of the human circadian clock to the natural light-dark cycle. Current Biology. 2013 Aug 19;23(16):1554-8.
  6. Marijuana Use: The use of marijuana can alter the sleep-wake cycle, impacting both sleep onset and sleep architecture.10Gates, P. J., Albertella, L., & Copeland, J. (2014). The effects of cannabinoid administration on sleep: a systematic review of human studies. Sleep Medicine Reviews, 18(6), 477-487. While some users report it helps them fall asleep, frequent use can disrupt sleep patterns and lead to dependence on marijuana for sleep induction.
  7. Diseases and Medical Conditions: Various diseases and conditions can affect the functioning of the SCN and disrupt circadian rhythms. This includes neurodegenerative diseases such as Alzheimer’s disease, mood disorders like depression and bipolar disorder, and even cancer.11Musiek ES, Holtzman DM. Mechanisms linking circadian clocks, sleep, and neurodegeneration. Science. 2016 Nov 25;354(6315):1004-8.,12Li JZ, Bunney BG, Meng F, Hagenauer MH, Walsh DM, Vawter MP, Evans SJ, Choudary PV, Cartagena P, Barchas JD, Schatzberg AF. Circadian patterns of gene expression in the human brain and disruption in major depressive disorder. Proceedings of the National Academy of Sciences. 2013 Jun 11;110(24):9950-5.,13Savvidis C, Koutsilieris M. Circadian rhythm disruption in cancer biology. Molecular Medicine. 2012 Dec;18(1):1249-60.
  8. Drugs and Medications: Certain medications can affect the SCN and circadian rhythms. For example, medications such as benzodiazepines, beta-blockers, and melatonin can shift circadian rhythms.14Morin LP. Nocturnal light and nocturnal rodents: similar regulation of disparate functions?. Journal of Biological Rhythms. 2013 Aug;28(2):95-106.
  9. Alcohol and Substance Use: Use of substances like alcohol can also disrupt the normal functioning of the SCN, affecting the sleep-wake cycle and other circadian rhythms.15Ruby CL, Brager AJ, DePaul MA, Prosser RA, Glass JD. Chronic ethanol attenuates circadian photic phase resetting and alters nocturnal activity patterns in the hamster. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2009 Sep;297(3):R729-37.
  10. Diet and Nutrition: Changes in feeding time can reset peripheral circadian clocks (the ones outside of the SCN), but not the central clock in the SCN. However, high-fat diets can alter the normal functioning of the SCN and disrupt circadian rhythms.16Kohsaka A, Laposky AD, Ramsey KM, Estrada C, Joshu C, Kobayashi Y, Turek FW, Bass J. High-fat diet disrupts behavioral and molecular circadian rhythms in mice. Cell Metabolism. 2007 Nov 7;6(5):414-21.

How Circadian Syndrome Leads to Low Testosterone

This is where things become really fascinating. And complicated.

The hypothalamic-pituitary-gonadal (HPG) axis is the primary hormonal system involved in the regulation of testosterone production. This axis consists of the hypothalamus (a small region of the brain), the pituitary gland (located at the base of the brain), and the gonads (testes in males).17Tahara Y, Aoyama S, Shibata S. (2017). The mammalian circadian clock and its entrainment by stress and exercise. The Journal of Physiological Sciences, 67(1), 1-10.

In response to signals from the suprachiasmatic nucleus, the hypothalamus releases gonadotropin-releasing hormone (GnRH). This GnRH then signals the pituitary gland to produce and release two other hormones: luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Of these, LH is the primary driver of testosterone production in the testes.

When circadian rhythms are disrupted, it can alter the normal pattern of GnRH release from the hypothalamus.18Selmaoui, B., & Touitou, Y. (2003). Reproducibility of the circadian rhythms of serum cortisol and melatonin in healthy subjects: a study of three different 24-h cycles over six weeks. Life sciences, 73(26), 3339-3349. This disruption can result in a mismatch between the timing of LH release and the responsiveness of the testes to LH. The SCN controls the rhythmic release of GnRH and LH, so when the circadian rhythm is disrupted, it can decrease testosterone production.

Sleep, particularly the REM phase, has been associated with increased testosterone production.19Luboshitzky R, Zabari Z, Shen-Orr Z, Herer P, Lavie P. (2001). Disruption of the nocturnal testosterone rhythm by sleep fragmentation in normal men. The Journal of Clinical Endocrinology & Metabolism, 86(3), 1134-1139. When REM sleep is compromised, testosterone levels don’t rise. Also, REM is essential for brain function, so you not only compromise testosterone production by living in sleep debt, but you also age your brain and compromise your ability to think critically.

Practical Summary

There’s an old adage many men still subscribe to: “Sleep when you die.” Such a thought process made sense hundreds of years ago, when you couldn’t work late into the night because you didn’t have artificial light. Today, watching evening television or using our electronic devices leads us to stay up much later than we should.

One other source of sleep disruption worth mentioning is gaming. It’s a topic I hope to explore in future articles, but here are a couple of staggering statistics you should be aware of:

  • adults aged 18-34 make up 38% of the U.S. gaming population, and 76% of gamers are over 18 years old
  • almost 10% of gamers play more than 20 hours per week

Gaming stimulates your sympathetic nervous system and cortisol levels, the worst thing you could do before getting ready to sleep. This is a “fight or flight” response. The problem is, when you’re gaming, you don’t fight or flee. You sit on your butt as your body releases these hormones and neurotransmitters designed for physical activity. 

I believe the gaming trend will get worse over time, especially as augmented reality technology improves. This will make our health problems even worse, including the negative effects on testosterone, creating overweight and obese men who’s only motivation is to get to the next level of a video game.

The bottom line is that if men are going to maintain the mental and physical attributes that make men, men, they need to maintain optimal testosterone levels. Protecting the quantity and quality of their sleep is the first place to start.

Photo by Jongsun Lee on Unsplash

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