REVIEW URRENT C OPINION

The relationship between sleep disorders and testosterone Gary Wittert

Purpose of review This review describes evolving concepts and recent data on the relationship between serum testosterone levels and normal and disordered sleep. Recent findings Sex-related differences in circadian rhythms and sleep physiology are in part due to organizational and activational effects of sex steroids. Testosterone affects the organization of circadian rhythms and the timing, but not the duration, of sleep. Increasing testosterone during puberty leads to later bedtimes. The diurnal variation in testosterone depends on sleep rather than circadian rhythm or season. Pubertal onset is heralded, well before virilization, by a luteinizing hormone level at least 3.7 U/l during sleep. Total sleep deprivation lowers testosterone, but sleep restriction only does so if it occurs in the first half of the night. The recovery of testosterone from sleep disruption is impaired in old as compared with young rodents. In men with obstructive sleep apnoea (OSA), low testosterone is related to obesity rather than the OSA itself, and improves with weight loss but inconsistently with continuous positive airway pressure (CPAP). Testosterone treatment only transiently worsens severity of OSA, which need not be considered a contraindication to its use. Summary Testosterone treatment is unlikely to benefit sleep in men with secondary hypogonadism, for example due to obesity or depression, in contrast to the management of the underlying abnormality. Keywords circadian rhythm, puberty, sleep, testosterone

INTRODUCTION Sleep is characterized by a stereotypical series of events divided into nonrapid-eye movement (NREM) and rapid-eye movement (REM) sleep. The first two phases of NREM sleep (phases 1 and 2) are light and often alternate with brief waking episodes. Two deeper phases of NREM sleep (phases 3 and 4) together known as slow wave sleep (SWS) tend to occur predominantly in the earlier part of the night and become lighter thereafter. Usually four to six cycles of REM sleep occur at intervals of approximately 90 min becoming longer and more frequent over the course of the night. Wakefulness is maintained by neuronal projections from the lateral hypothalamus. The ventrolateral preoptic nucleus (VLPO) is critical for the onset and maintenance of sleep and the regulation of SWS. REM sleep is induced by the increased firing of glutamatergic and cholinergic neurons in the dorsolateral pons. Circadian rhythm is regulated

by the suprachiasmatic nucleus (SCN) to which sensing circuits project light from the eyes, and from which neuronal circuits project indirectly (subparaventricular zone, dorsomedial hypothalamus and median preoptic area), and to a limited extent directly, to the VLPO (among other sleep regulating nuclei), thereby integrating photo-periodic cues with mechanisms regulating sleep [1,2 ]. This review describes evolving concepts and recent data on the relationship between serum testosterone levels and normal and disordered sleep. &&

Discipline of Medicine and Freemasons Foundation Centre for Men’s Health, University of Adelaide, Adelaide, South Australia, Australia Correspondence to Gary Wittert, Discipline of Medicine, Level 6, Eleanor Harrald Building, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. Tel: +61 88222 5502; fax: +61 8223 3870; e-mail: gary.wittert@ adelaide.edu.au Curr Opin Endocrinol Diabetes Obes 2014, 21:239–243 DOI:10.1097/MED.0000000000000069

1752-296X ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

www.co-endocrinology.com

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Androgens

KEY POINTS

sleep, but are more likely to report poor quality sleep [2 ]. The implications of sex-specific differences in recovery from sleep deprivation and adaptation to shift work on humans remain to be determined. &&

 The activity of the hypothalamo-pituitary-gonadal axis and consequently plasma levels of testosterone vary in a diurnal manner that is dependent on sleep rather than circadian rhythm or season.  The onset of puberty is heralded by an LH level during sleep that is at least 3.7 U/l.  Total sleep deprivation lowers plasma testosterone levels in men, but sleep restriction only does so if it occurs in the first half of the night.  Testosterone has an effect on timing of sleep; increasing levels during puberty lead to later bedtimes, but not to the overall duration of sleep.  In men with OSA, low plasma testosterone levels are related to obesity rather than the OSA itself and consistently improve with weight loss but not CPAP.  The administration of testosterone to men with OSA induces transient worsening of severity due to the effect of testosterone on the hyperoxic ventilatory recruitment threshold. OSA should not be considered a contraindication to testosterone treatment if it is clinically required.

SEX, SEX STEROIDS AND THE MECHANISMS REGULATING CIRCADIAN RHYTHM AND SLEEP Androgen receptors are present in both VLPO neurons [2 ] and the SCN [3]. In the SCN, androgens acting via androgen receptors modulate the response to photic input and therefore the circadian regulation of activity in males [4,5 ,6]. It is proposed that one androgen-dependent system modulates SCN responsiveness to light, and another modulates SCN timekeeping and locomotor activity in a dose-dependent manner [7 ]. There is also, at least in mice, an independent effect of sex chromosomes to regulate circadian control of motor activity [5 ]. The intrinsic circadian period is shorter in women than men, explaining the tendency for women, on average, to have earlier bedtimes and waking times than men and to exhibit a greater preference for morning activities [4]. A similar phenomenon is seen in female mice and has been shown to be mediated by both sex chromosome and oestrogen-dependent effects [5 ,8 ]. Male mice have more total sleep and NREM sleep than female mice, an effect that is predominantly due to the effects of ovarian sex steroids in females [9]. By contrast in humans, women tend to go to bed earlier than men and get more total &&

SLEEP AND THE REGULATION OF TESTOSTERONE Testosterone production varies in a diurnal manner but, unlike melatonin and cortisol, is not under circadian control, that is, its production is not linked to the light–dark cycle and the SCN, but is directly dependent on sleep. This phenomenon is first seen in older prepubertal boys with a sleeprelated increase in the amplitude of the pulses of luteinizing hormone (LH) secretion [10] and responsiveness to GnRH and GnRH agonist beginning about 2 years prior to the onset of puberty being clinically evident. A critical LH level during sleep (3.7 U/l) that heralds the onset of pubertal virilization has now been established, and corresponds to an LH of at least 14.8–19 U/l 4 h after administration of GnRH agonist [11 ]. The increase in LH production begins with the onset of SWS and reaches a peak at the time of the first REM episode. Approximately 3 h or so of SWS is required, irrespective of whether it occurs during the day or at night, for peak testosterone production to occur [12] and levels remain stable thereafter while sleep is maintained. After waking, the plasma concentration of testosterone declines in proportion to the duration of time awake [12]. A recent review concludes that there is limited evidence for seasonal variations in testosterone production [13 ]. &&

&

&&

&

&&

&&

240

www.co-endocrinology.com

&

EFFECTS OF TESTOSTERONE ON SLEEP Recent data have shown, at least in rats, that gonadal steroids have a much greater effect on sleep behaviour in females than in males. The sex-specific pattern of responsivity is organizationally mediated by early exposure of the ventral lateral preoptic area (VLPO) to gonadal steroids [14 ]. This may explain the very small effect of gonadectomy and replacement of testosterone on sleep architecture in male rodents [15], and the observation that in humans the relationship between testosterone and sleep quality appears to be largely mediated by obesity [16]. A recent review addresses, among other topics, sex-related differences in sleep requirements [2 ]. On average, women go to bed earlier than men (at least up until the time of the menopause), sleep longer, but also report poorer sleep quality. On the basis of rodent studies, this appears to be largely driven by the effect of oestrogen and progesterone &&

&&

Volume 21  Number 3  June 2014

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Testosterone and sleep Wittert

on sleep duration and architecture, and recent data suggest that estradiol consolidates circadian sleep wake rhythms in females [17]. After middle age, and increasingly with ageing thereafter, there is deterioration in sleep quality. It has been hypothesized that this may be, at least in part, because of the lower testosterone levels in ageing men [18]. Most of the age-related decrease in testosterone can be explained by increasing fat mass and associated burden of chronic disease rather than age per se [19] and obesity is independently associated with poorer sleep quality [20], which improves when weight is lost. Moreover, in men with stage 3–5 chronic renal disease and not on dialysis, serum total testosterone levels have been shown to be independently associated with cognitive function and depressive behaviour but not with sleep disorders [21]. Another recent study suggested that in younger men with depression, those with lower plasma testosterone levels reported poorer subjective sleep quality; however, covariates including obesity status, medication use and smoking, all known to affect testosterone, were not adjusted for in this study [22]. Therefore, the extent to which increasing age, obesity, chronic disease status and testosterone interact to affect sleep quality remains to be fully elucidated, but on the basis of current data, the role of endogenous testosterone seems limited. Recent work has shown that in obese men with obstructive sleep apnoea (OSA) and low plasma testosterone levels, testosterone treatment results in a worsening of indices of severity at 6–7 weeks that is no longer apparent at 18 weeks [23 ]. This phenomenon may be the result of an interaction between changes in serum testosterone and hyperoxic ventilatory recruitment threshold and the oxygen desaturation index at 6–7 weeks that is not seen at 18 weeks [24]. Although these data argue that testosterone treatment is probably safer than previously considered in people with, even untreated, OSA, it is unlikely that testosterone treatment is of benefit for sleep in men. And, in young men engaging in resistance exercise and taking anabolic steroids, there is a reduction in sleep efficiency and an alteration of sleep architecture [25]. &&

EFFECTS OF TESTOSTERONE ON CIRCADIAN RHYTHM In contrast to the limited effects of testosterone on sleep quality or duration, there is evidence from animal studies that testosterone modulates the organization and function of the SCN [3] including the responsiveness of the SCN to light and local motor activity [8 ]. In rats, there are pubertal &

changes in circadian phase that are more pronounced in males than in females and that are partially dependent on gonadal steroids. Removal of the testes in male mice almost completely abolishes, and testosterone treatment restores, the normal evening activity onset bout [26]. In humans, at adolescence, there is a shift to a preference for a later bedtime (evening chronotype), an effect that is considerably more marked in boys than in girls [27,28 ,29 ]. At least in young men, higher testosterone levels are associated with a more pronounced evening chronotype without affecting sleep duration [30 ]. &

&

&&

EFFECT OF SLEEP ABNORMALITIES ON TESTOSTERONE Apart from self-reported insomnia, the common sleep abnormalities in men are the result of circadian rhythm disruption usually due to shift-work, sleep restriction and sleep-disordered breathing. There is no evidence that circadian rhythm disruption per se effects production of testosterone provided adequate sleep is obtained. The effects of sleep restriction and sleep disordered breathing are discussed in the following section.

Sleep restriction Recent studies confirm that total sleep deprivation results in a low morning testosterone level [31,32]. Interestingly, sleep deprivation in men was also associated with lower reactive aggression and it was suggested that testosterone but not cortisol plays a role in the relationship between sleep and reactive aggression in men [32]. In contrast to total sleep deprivation, restriction of sleep to 4 h between 0:400 and 08:00 h for five nights in 14 healthy men had no adverse effect on morning testosterone levels [33]. Although this study may apparently seem inconsistent with a previous study in which morning and subsequent wake time testosterone levels were lower in response to sleep restriction [34], the most likely explanation for the difference is the timing of sleep. In the study that showed a reduction in morning testosterone, sleep was permitted until 05:30 h and testosterone levels would have progressively declined during the awake-period thereafter. This would be consistent with the known physiology described above. Further evidence to support this contention is work showing that total sleep deprivation and 4.5 h of sleep deprivation restricted to the first half of the night markedly decreased morning testosterone in contrast to normal sleep duration or sleep loss in the first half of the night [35 ].

1752-296X ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

&

www.co-endocrinology.com

241

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Androgens

Although recent data suggest that age per se has only a very small and probably by itself insignificant effect on plasma testosterone levels [19], there is evidence to suggest that the HPG axis is less resilient in older individuals. It has recently been shown in male Wistar rats that paradoxical sleep deprivation (PSD) lowers plasma testosterone levels to a greater extent in older than in younger animals. After 3 days of PSD, 5 days of sleep recovery results in an almost normalized testosterone level in young animals but not in the older group [36].

Sleep-disordered breathing Apart from snoring, the commonest form of sleepdisordered breathing is OSA. OSA is commonly considered to be a cause of low testosterone levels; there is, however, very little evidence that it is due to a direct effect OSA independent of obesity [37]. Similarly, although there are some data that treatment of OSA with continuous positive airway pressure (CPAP) increases serum testosterone levels, the overwhelming weight of evidence suggests that is not the case whether it is evaluated over very short time periods such as one night [38], or for as long as 39 months and even when compliance is measured and adjusted for [37].

CONCLUSION There are significant sex-related differences in both circadian rhythms and sleep physiology that are in part sex chromosome dependent and in part due to organizational and activational effects of sex steroids. At least in so far as sleep is concerned, estradiol has a significant effect in women, but in men testosterone has limited, if any, significant effects on sleep quality or sleep duration. Nevertheless, testosterone does influence the organization of circadian rhythms and the timing of sleep. Ageing is associated with a number of changes to sleep, but as long as good health is preserved, only limited changes, of doubtful clinical significance, to the production of testosterone occur. The extent to which sleep disruption affects testosterone production and whether the amount is similar in older as compared with young men is unclear. Whether the recovery from sleep disruption in older men is significantly impaired as it is in rodents is also unclear. Similarly, the effect of varying degrees of obesity on the normal physiology of sleep-related testosterone production and any interaction with advanced age, medication, alcohol or disease state remains to be determined. The findings that OSA is not a determinant of testosterone independent of obesity and the lack of effect of CPAP on 242

www.co-endocrinology.com

testosterone highlight the importance of weight loss as an adjunct in the treatment of OSA. And, although sleep-disordered breathing does not appear to affect testosterone independent of obesity, whether this is necessarily true under all circumstances, for example advanced age also requires further investigation. OSA should not be considered a contraindication to testosterone treatment if it is clinically required. Finally, the effect of estradiol or the ratio between testosterone and estradiol on sleep physiology in men is also an area that remains to be investigated. But for now, it seems reasonable to say that there is no basis to consider that testosterone treatment will benefit sleep in men with secondary hypogonadism due to obesity, depression or medication use and so on in contrast to the management of the underlying abnormality. Acknowledgements Funding was received from the National Health and Medical Research Council, Project Grant #627227, the ResMed Foundation and the Freemasons Foundation. Conflicts of interest There are no conflicts of interest.

REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Brown RE, Basheer R, McKenna JT, et al. Control of sleep and wakefulness. Physiol Rev 2012; 92:1087–1187. 2. Bailey M, Silver R. Sex differences in circadian timing systems: implications && for disease. Front Neuroendocrinol 2014; 35:111–139. This is a comprehensive review of the sex differences in sleep arousal systems, the circadian timing system and the hypothalamo-pituitary-gonadal axis. It also examines sex-related differences in response to dysfunction and disease 3. Karatsoreos IN, Butler MP, Lesauter J, Silver R. Androgens modulate structure and function of the suprachiasmatic nucleus brain clock. Endocrinology 2011; 152:1970–1978. 4. Duffy JF, Cain SW, Chang AM, et al. Sex difference in the near-24-h intrinsic period of the human circadian timing system. Proc Natl Acad Sci USA 2011; 108 (Suppl 3):15602–15608. 5. Kuljis DA, Loh DH, Truong D, et al. Gonadal- and sex-chromosome-dependent && sex differences in the circadian system. Endocrinology 2013; 154:1501– 1512. In this elegant study, genetic models are used to better understand the relative roles of sex steroids (both activational and organizational) and sex chromosomes in circadian regulation in male and female mice. A potential limitation is that although the XXM mice do develop testes, they are small and dysfunctional, the mice are infertile and the degree to which they produce testosterone uncertain; very low levels have been measured using a direct immunoassay. 6. Mong JA, Baker FC, Mahoney MM, et al. Sleep, rhythms, and the endocrine brain: influence of sex and gonadal hormones. J Neurosci 2011; 31:16107– 16116. 7. Butler MP, Karatsoreos IN, LeSauter J, Silver R. Dose-dependent effects of & androgens on the circadian timing system and its response to light. Endocrinology 2012; 153:2344–2352. This study shows the existence of one androgenic mechanism that modulates SCN responsiveness to light, and another that modulates SCN timekeeping and locomotor activity in a dose-dependent manner. Androgens modulate the SCN’s response to photic input rather than affecting the inherent period of oscillators in the absence of light.

Volume 21  Number 3  June 2014

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Testosterone and sleep Wittert 8. Ehlen JC, Hesse S, Pinckney L, Paul KN. Sex chromosomes regulate night& time sleep propensity during recovery from sleep loss in mice. PLoS one 2013; 8:e62205. This study using the same genetic models as the one above shows that sleep propensity is sex linked and following sleep loss is regulated differently in male and female mice resulting from both sex chromosome and sex steroid dependent mechanisms. 9. Paul KN, Dugovic C, Turek FW, Laposky AD. Diurnal sex differences in the sleep-wake cycle of mice are dependent on gonadal function. Sleep 2006; 29:1211–1223. 10. Wu FC, Butler GE, Kelnar CJ, et al. Ontogeny of pulsatile gonadotropin releasing hormone secretion from midchildhood, through puberty, to adulthood in the human male: a study using deconvolution analysis and an ultrasensitive immunofluorometric assay. J Clin Endocrinol Metab 1996; 81:1798–1805. 11. Rosenfield RL, Bordini B, Yu C. Comparison of detection of normal puberty in && boys by a hormonal sleep test and a gonadotropin-releasing hormone agonist test. J Clin Endocrinol Metab 2012; 97:4596–4604. A sleep peak LH level of at least 3.7 U/l predicted pubertal testicular activation with 100% accuracy. LH of at least 14.8 and at least 19.0 U/l 4 h after GnRH agonist, respectively, predicted puberty with 100% sensitivity/94% specificity and 100% specificity/94% sensitivity. Overweight pubertal boys had transiently prolonged responses to GnRH agonist. LH stimulation of testicular androgen production plays a role in stimulating testicular tubule growth once a critical level of FSH is achieved. Despite the findings, it must be noted that this is a relatively small (and interrupted) cross-sectional study of normal puberty. It used two different LH (and FSH) assays with an attempt at cross-calibration. The critical serum LH referred to is the peak during intensive (20 min) sleep-time sampling. These data should not be translated to practice with the assumption that a random morning serum LH will be informative. Further validation of cut-offs using GnRH analogues to demarcate normal from delayed puberty is required. 12. Axelsson J, Ingre M, Akerstedt T, Holmback U. Effects of acutely displaced sleep on testosterone. J Clin Endocrinol Metab 2005; 90:4530–4535. 13. Smith RP, Coward RM, Kovac JR, Lipshultz LI. The evidence for seasonal & variations of testosterone in men. Maturitas 2013. [Epub ahead of print] A thorough review of the evidence relating to whether there are seasonal variations in testosterone levels, although there is some evidence to support the notion that inconsistencies preclude such a conclusion. 14. Cusmano DM, Hadjimarkou MM, Mong JA. Gonadal steroid modulation of && sleep and wakefulness in male and female rats is sexually differentiated and neonatally organized by steroid exposure. Endocrinology 2014; 155:204– 214. This study describes that sex differences in sleep are mediated by organizational/ activational effects of gonadal steroids in an analogous manner to the way they affect sex differences in behaviour. 15. Paul KN, Laposky AD, Turek FW. Reproductive hormone replacement alters sleep in mice. Neurosci Lett 2009; 463:239–243. 16. Barrett-Connor E, Dam TT, Stone K, et al. The association of testosterone levels with overall sleep quality, sleep architecture, and sleep-disordered breathing. J Clin Endocrinol Metab 2008; 93:2602–2609. 17. Schwartz MD, Mong JA. Estradiol modulates recovery of REM sleep in a timeof-day-dependent manner. Am J Physiol Regul Integr Comp Physiol 2013; 305:R271–R280. 18. Miller CM, Rindflesch TC, Fiszman M, et al. A closed literature-based discovery technique finds a mechanistic link between hypogonadism and diminished sleep quality in aging men. Sleep 2012; 35:279–285. 19. Shi Z, Araujo AB, Martin S, et al. Longitudinal changes in testosterone over five years in community-dwelling men. J Clin Endocrinol Metab 2013; 98:3289–3297. 20. Resta O, Foschino Barbaro MP, Bonfitto P, et al. Low sleep quality and daytime sleepiness in obese patients without obstructive sleep apnoea syndrome. J Intern Med 2003; 253:536–543. 21. Afsar B. Relationship between total testosterone, cognitive function, depressive behavior, and sleep quality in chronic kidney disease patients not on dialysis. Clin Exp Nephrol 2013; 17:59–65.

22. Sankar JS, Hampson E. Testosterone levels and androgen receptor gene polymorphism predict specific symptoms of depression in young men. Gender Med 2012; 9:232–243. 23. Hoyos CM, Killick R, Yee BJ, et al. Effects of testosterone therapy on && sleep and breathing in obese men with severe obstructive sleep apnoea: a randomized placebo-controlled trial. Clin Endocrinol 2012; 77:599–607. Irrespective of baseline testosterone level, testosterone treatment in obese men with severe OSA results in worsening the oxygen desaturation index and nocturnal hypoxaemia at 7 weeks but not at 18 weeks. 24. Killick R, Wang D, Hoyos CM, et al. The effects of testosterone on ventilatory responses in men with obstructive sleep apnoea: a randomised, placebocontrolled trial. J Sleep Res 2013; 22:331–336. 25. Venancio DP, Tufik S, Garbuio SA, et al. Effects of anabolic androgenic steroids on sleep patterns of individuals practicing resistance exercise. Eur J Appl Physiol 2008; 102:555–560. 26. Iwahana E, Karatsoreos I, Shibata S, Silver R. Gonadectomy reveals sex differences in circadian rhythms and suprachiasmatic nucleus androgen receptors in mice. Hormones Behav 2008; 53:422–430. 27. Crowley SJ, Acebo C, Carskadon MA. Sleep, circadian rhythms, and delayed phase in adolescence. Sleep Med 2007; 8:602–612. 28. Hagenauer MH, Lee TM. The neuroendocrine control of the circadian system: & adolescent chronotype. Front Neuroendocrinol 2012; 33:211–229. This review details evidence for changes in the regulation of sleep by the circadian timekeeping system and adolescents and how these differ between men and women. 29. Hagenauer MH, Lee TM. Adolescent sleep patterns in humans and laboratory & animals. Hormones Behav 2013; 64:270–279. This comprehensive review examines the changes in behavioural and physiological sleep parameters during adolescence in nonhuman mammalian species, ranging from primates to rodents highlighting species-specific effects to deal with the build-up anticipation of sleep pressure that decreases at adolescence without necessitating a decrease in overall sleep need. 30. Randler C, Ebenhoh N, Fischer A, et al. Chronotype but not sleep length && is related to salivary testosterone in young adult men. Psychoneuroendocrinology 2012; 37:1740–1744. This study conducted in 106 male students shows that timing of sleep rather than duration of sleep is influenced by testosterone and that the higher the testosterone levels greater likelihood of words strongly evening orientation (evening chronotype). 31. Jauch-Chara K, Schmid SM, Hallschmid M, et al. Pituitary-gonadal and pituitary-thyroid axis hormone concentrations before and during a hypoglycemic clamp after sleep deprivation in healthy men. PLoS One 2013; 8:e54209. 32. Cote KA, McCormick CM, Geniole SN, et al. Sleep deprivation lowers reactive aggression and testosterone in men. Biol Psychol 2013; 92:249– 256. 33. Reynolds AC, Dorrian J, Liu PY, et al. Impact of five nights of sleep restriction on glucose metabolism, leptin and testosterone in young adult men. PLoS one 2012; 7:e41218. 34. Leproult R, Van Cauter E. Effect of 1 week of sleep restriction on testosterone levels in young healthy men. JAMA 2011; 305:2173–2174. 35. Schmid SM, Hallschmid M, Jauch-Chara K, et al. Sleep timing may modulate & the effect of sleep loss on testosterone. Clin Endocrinol 2012; 77:749– 754. This study shows that sleep loss in the early part of the night does not affect testosterone, whereas early awakening and wakefulness during the second part of the night reduces morning circulating testosterone concentrations. 36. Oh MM, Kim JW, Jin MH, et al. Influence of paradoxical sleep deprivation and sleep recovery on testosterone level in rats of different ages. Asian J Androl 2012; 14:330–334. 37. Wittert G. The relationship between sleep disorders and testosterone in men. Asian J Androl 2014; 16:262–265. 38. Vlkova B, Mucska I, Hodosy J, Celec P. Short-term effects of continuous positive airway pressure on sex hormones in men and women with sleep apnoea syndrome. Andrologia 2013. [Epub ahead of print]

1752-296X ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

www.co-endocrinology.com

243

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

The relationship between sleep disorders and testosterone.

This review describes evolving concepts and recent data on the relationship between serum testosterone levels and normal and disordered sleep...
188KB Sizes 2 Downloads 5 Views