Testosterone and Sleep Apnea: Support for Sleep Theory

(Excessive testosterone to DHEA ratio may produce Apnea During Sleep)

Note: My work regarding the ratio of DHEA to testosterone first produced my hypothesis that the direction of DHEA caused by testosterone could change the competition for DHEA such that some tissues experienced reduced function. (“Androgens in Human Evolution,Rivista di Biologia / Biology Forum 2001; 94: 345-362. If your library does not subscribe to Rivista ,you may find this at: http://anthropogeny.com/Androgens%20in%20Human%20Evolution.htm .) This document is based on that hypothesis. Various findings, included here, support this idea. Since that time it has occurred to me that DHEA and testosterone work together; if testosterone is low, then the effects of DHEA are reduced. Since my explanation of sleep includes low DHEA at night, both high testosterone and low testosterone will reduce sleep DHEA and trigger sleep apnea and reduce muscle tone in the throat, the same thing. This effect of low testosterone is appearing in the literature. This does not negate my explanation of sleep nor that low DHEA is involved in sleep apnea; it further supports it. (“DHEA, Estradiol, Testosterone, and the Relevance of Their Ratio …The Androgen Receptor …and the Secular Trend,” at: http://anthropogeny.com/Androgen%20Receptor%20and%20Secular%20Trend.html )

Copyright 1997, 2012, 2016 by James Michael Howard, Fayetteville, Arkansas, U.S.A.

This is new additional support for my sleep theory .

In 1994, it was determined that testosterone makes obstructive sleep apnea worse. This is the finding of the following research from 1994. Following this quotation, however, one can see that it is not a simple effect of testosterone on airway passages.

"Testosterone is thought to play a role in the pathogenesis of obstructive sleep apnea (OSA), but the mechanism is unclear. We present a case in which testosterone administration induced or exacerbated OSA in a 13-year-old male. We demonstrated that exacerbation of OSA by testosterone was associated with an increase in upper airway collapsibility during sleep, and that this improved after cessation of hormone administration. Our data strongly suggest that the mechanism by which testosterone administration may induce or exacerbate OSA is through an influence on neuromuscular control of upper airway patency during sleep." (American Journal of Respiratory and Critical Care Medicine 1994; 149: 530)

This report is supported by some earlier reports. However, some reports suggest that testosterone replacement in hypogonadal men significantly increases "both apneas and hypoapneas" but that this is a "highly variable event with some subjects demonstrating large increases in apneas and hypoapneas when androgen [testosterone] was replaced, whereas others had little change in respiration during sleep." This report also studied airway dimensions and concluded that "Upper airway dimensions, on the other hand, were unaffected by testosterone. These results suggest that testosterone contributes to sleep-disordered breathing through mechanisms independent of anatomic changes in the upper airway." (Journal of Applied Physiology 1986; 61: 618)

Another study of testosterone replacement in hypogonadal men produced some similar results, along with some additional information that allows me to apply my theory of sleep and produce an explanation of the connection of testosterone and sleep apneas.

"Obstructive sleep apnoea developed in one man and markedly worsened in another man in association with testosterone administration. Both of these subjects also exhibited marked decreases in oxygen saturation with the development of cardiac dysrhythmias during sleep and large increases in haematocrit. The remaining three hypogonadal men did not demonstrate significant sleep apnoea either on or off testosterone. The percentage of sleep time spent in REM sleep increased from 14 +/- 3% to 22 +/- 2% when the men were receiving testosterone (P less than 0.01), but the episodes of sleep apnoea tended to occur during non-REM sleep. We conclude that in some hypogonadal men, replacement dosages of testosterone may affect ventilatory drives and induce or worsen obstructive sleep apnoea. The obstructive sleep apnoea syndrome is a potential complication of testosterone therapy." (Clinical Endocrinology 1985; 22: 713)

Testosterone appears to produce apneas due to collapse of the airway and apneas that occur without collapse of the airway. I developed a theory of sleep that may explain this apparent paradox. (For full detail, I invite you to read my theory of sleep on the webpage.) It is my hypothesis that the hormone, dehydroepiandrosterone (DHEA), is necessary for activation of the nervous system. This has allowed me to produce a theory of sudden infant death syndrome (SIDS), based on too little DHEA during sleep to maintain functions of the brainstem. When I was working on my theory of SIDS, it became quite apparent that infants who produce too much testosterone are more prone to SIDS. This has allowed me to explain the connection of testosterone with apneas in men.

My theory suggests that all genes use DHEA to function. Testosterone causes the genes of "testosterone target tissues" to absorb extra DHEA for their functions. For example, this is why men have larger, more powerful muscles than women. So, the increased testosterone of men reduces the availability of DHEA, therefore, I suggest sleep apneas occur more in men because of reduced availability of DHEA for proper nervous stimulation. According to my theory of DHEA function, all tissues compete for DHEA. Therefore, in a man of low DHEA, administering testosterone as in the report above, will cause some tissues to absorb extra DHEA and reduce already low DHEA. This may cause either the nervous stimulation of the airways to decline, resulting in a collapsed airway, or it may reduce the DHEA so low that the brainstem ceases to function momentarily, as in SIDS. This situation would produce the apnea in which the airways do not collapse. Of course, the brainstem malfunction and airway collapse could occur simultaneously. This could explain the variability of effects of administration of testosterone in the quotation, above. Some of the men may be hypogonadal because of a poorly functioning pituitary-adrenal-gonadal axis, caused by low DHEA with low testosterone as a secondary consequence. Some of the men may have simply not produced much testosterone along with ample amounts of DHEA. This second group would represent those individuals in whom testosterone administration had no effect on sleep at all.

I have suggested that testosterone stimulates testosterone target tissues, which absorb extra DHEA. This effect should stimulate some increase in the production of DHEA. In my theory of sleep, I suggest that REM sleep is a time when the low levels of DHEA of night increase slightly to maintain brainstem function. This means that testosterone administration during sleep should increase REM sleep; this in fact is reported in the quotation above. I have suggested that DHEA is necessary for nervous system function, so I would expect apneas, caused by too low DHEA, to occur during non-REM sleep, which is a time of the lowest levels of DHEA, according to my theory of sleep and SIDS. This is reported above: "...but the episodes of sleep apnoea tended to occur during non-REM sleep."

I suggest the reason men exhibit more sleep apneas than women, and why testosterone administration in some individuals induces sleep apneas, is due to abnormally low DHEA during sleep. This low DHEA can manifest itself as lack of nervous support of the muscles of the airway, lack of support of brainstem function, or a combination of both.

Added in Support of Above

Mayo. Clin. Proc. 1998 Mar; 73(3): 246-8 "Obstructive sleep apnea due to endogenous testosterone production in a woman" Dexter DD, Dovre EJ Department of Neurology, Midelfort Clinic, Eau Claire, Wisconsin 54701, USA.

"Obstructive sleep apnea (OSA) is a common condition characterized by snoring, recurrent episodes of cessation of breathing (obstructive apneas), disrupted sleep, and excessive daytime somnolence. Associated serious complications are hypertension, increased risk of heart disease, stroke, and increased susceptibility to industrial and motor vehicle accidents. OSA is considerably more common in men than in women. In postmenopausal women, the incidence of OSA increases. These factors suggest that reproductive hormones have a role in the cause of OSA. Treatment with testosterone has been reported to cause OSA in men, and exogenous androgen administration has been reported to cause OSA in one woman. In a review of the English literature, we found no previous reports of OSA that was induced by endogenous testosterone in women. Herein we describe a nonobese 70-year old woman with clinically significant OSA and a benign testosterone-producing ovarian tumor. After successful removal of the tumor, her OSA resolved, and her testosterone level normalized. This unique case supports the theory of male hormonal (testosterone) influence in the OSA syndrome.