Sleep disorders impact hormonal regulation: unravelling the relationship among sleep disorders, hormones and metabolic diseases

Abstract

Sleep plays a crucial biological role, and mounting evidence suggests that sleep disorders negatively impact health. In contemporary society, sleep disorders, such as sleep deprivation, insomnia, disrupted sleep-wake disorders, and circadian rhythm disorders, are widespread. Sleep disorders affect hormone production and secretion, which lead to endocrine changes, including impaired glucose tolerance, decreased insulin sensitivity, hepatic steatosis, and increased inflammatory responses, all of which accelerate the onset of various diseases. To support optimal metabolic and cardiovascular health, maintaining a consistent sleep schedule and practicing good sleep hygiene are essential.

Introduction

Sleep status is a widely acknowledged concern in modern society [1], as adequate sleep is a fundamental pillar of human health [2]. Through the regulation of the hypothalamic-pituitary-adrenal (HPA) axis, hypothalamic-pituitary-gonadal (HPG) axis, and hypothalamic-pituitary-thyroid (HPT) axis, sleep plays a pivotal role in modulating hormone secretion, consequently impacting endocrine function and metabolism [3]. Nevertheless, sleep disorders have emerged as a prevailing social trend [4]. Studies have revealed a significant decline in average human sleep duration, with contemporary populations sleeping 1.5 h less than those living in the previous century, and the prevalence of short sleep duration has surged from 11.8–24.1% [5, 6]. Sleep disorders include insomnia disorders, sleep-related breathing disorders, central disorders of hypersomnolence (insufficient sleep syndrome), circadian rhythm sleep-wake disorders, sleep-related movement disorders and parasomnias [7]. Sleep disorders increase inflammatory markers and accelerate the development of diabetes, obesity, metabolic syndrome and all-cause mortality [8]. Therefore, effective interventions for sleep disorders and maintenance of appropriate sleep hygiene is crucial for sustaining good health [9].

Sleep is highly organized and periodic, and it is divided into two distinct stages, namely, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. NREM sleep can be further classified into three stages-N1, N2, and N3. As these stages progress, sleep transforms gradually from wakefulness to deeper restorative states, ultimately entering REM sleep. Typically, a complete sleep cycle in healthy individuals lasts approximately 90 min, and the proportion of Slow-wave sleep (SWS) progressively decreases with age [10, 11]. The transition between NREM and REM sleep is closely associated with the interaction of monoaminergic and cholinergic neurons, which mutually inhibit each other [12]. NREM sleep constitutes approximately two-thirds of total sleep time in healthy adults, and it is characterized by a high-amplitude, low-frequency electroencephalogram (EEG), low-amplitude electromyography (EMG) signals, and minimal eye movements [11, 13, 14]. SWS, the N3 phase of NREM sleep, typically occurs during the initial half of the biological night [15]. In contrast, REM sleep predominantly occurs during the latter part of the biological night and is distinguished by low-amplitude, high-frequency EEG coupled with low EMG signals, rapid eye movements, and muscle atonia. REM sleep plays a crucial role in memory consolidation and dream generation [3, 13, 14].

With regard to the effects of sleep on hormones, research has indicated that NREM sleep suppresses thyroid stimulating hormone (TSH) secretion and activates the vagus nerve, which promotes growth hormone (GH) release and reduces cortisol levels, thereby improving glucose metabolism [16, 17]. In contrast, REM sleep regulates testosterone (TT) secretion rhythms, with prolonged REM latency resulting in a delayed elevation of TT levels [18]. An increased proportion of REM sleep also reduces leptin levels, which may explain the link between sleep deprivation and obesity [19]. Additionally, the sympathetic nervous system is activated by REM sleep, elevating blood pressure, disrupting insulin secretion, and increasing diabetes risk. These findings suggest that disrupted sleep architecture may impact metabolic health through multiple endocrine pathways [20].

This review explores the bidirectional relationship among sleep disorders, hormonal imbalances, and metabolic diseases. Understanding these mechanisms is crucial for developing targeted interventions to mitigate the risk of metabolic diseases in individuals with chronic sleep disorders.

Sleep and hormones

The synthesis, secretion, and release of hormones are tightly associated with circadian rhythms and are regulated by sleep. Therefore, sleep disorders, such as sleep deprivation, altered sleep-wake cycles, and sleep disturbances, may significantly impair hormone metabolism, potentially giving rise to endocrine diseases and impacting overall health [21]. For example, sleep disorders activate the HPA axis, resulting in elevated levels of cortisol, which not only perpetuate further activation of the HPA axis but also contribute to heightened arousal and can exacerbate insomnia [22]. During a sleep-depriving experience, increased activity of the HPT axis is one of the most notable endocrine changes, including a significant increase in TSH, which leads to significantly elevated levels of thyroid hormones. Despite the negative feedback of thyroid hormones on the HPT axis, the increase in TSH levels is more pronounced [23]. Additionally, alterations in sleep patterns disrupt the HPG axis, influencing the release of GH [21].

Cortisol

Cortisol, a steroid hormone, is part of the larger family of glucocorticoids produced by the HPA axis, and it is influenced by the 24-hour circadian rhythm. The majority of cortisol is bound to carriers, such as corticosteroid-binding globulin and albumin, while the remaining cortisol is free in serum [24, 25]. Cortisol not only increases the duration and intensity of NREM sleep but also inhibits REM sleep. Under normal sleep conditions, cortisol gradually increases at night and peaks within the first hour after waking in the morning [26]. Sleep deprivation, sleep disruption, and sleep dysregulation activate the HPA axis and the sympathetic nervous system, resulting in elevated cortisol levels [3].

Growth hormone

GH is released from the anterior pituitary gland in a pulsatile manner. GH is essential for growth and development, as it mediates the metabolism of lipids, carbohydrates and proteins during growth [27]. Increased secretion of GH during sleep is strongly linked to growth, muscle development, and tissue regeneration and repair [28]. The secretion of GH is dependent on sleep; a GH surge occurs in the first 90 min of nighttime sleep, and this peak diminishes with sleep deprivation, indicating a significant correlation between GH release and the first occurrence of SWS during the night [16, 29].

Thyroid hormones

Stimulated by thyrotropin-releasing hormone (TRH) produced by the hypothalamus, the pituitary gland secretes and releases TSH. In turn, TSH stimulates the release of thyroxine (T4), which is converted to triiodothyronine (T3). T3 plays a vital role in metabolism, thermogenesis, cellular growth, and development. T3 and T4 exert negative feedback regulation of this pathway. The secretion of TSH follows a circadian rhythm, characterized by an increase prior to sleep, achieving its highest concentration at night and subsequently exhibiting a decrease upon waking [30, 31]. Rodrigues reported that REM sleep deprivation induces central hypothyroidism, leading to decreased TSH secretion and reduced circulating T4 levels. Concurrently, the enhanced activity of deiodinase type 2 (D2) in brown adipose tissue (BAT) increases the systemic conversion rate of T4 to T3, ultimately resulting in elevated circulating T3 levels [32]. Similarly, Everson and Nowak reported that total sleep deprivation induces central hypothyroidism by suppressing TRH secretion [33].

Follicle-stimulating hormone and luteinizing hormone

The anterior pituitary synthesizes and secretes gonadotropins, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH), both of which are glycoprotein hormones [34]. FSH stimulates the conversion of androgens to estrogens, promotes follicular growth and maturation, and induces sperm production along with TT [35]. FSH and LH coregulate the proliferation and maturation of reproductive cells [36]. Layman et al. [37] reported that FSH levels are positively correlated with sleep duration and that women with short sleep duration (<8 h per day) have 20% lower FSH levels than those with normal sleep duration (≥ 8 h per day) after adjusting for age and body mass index (BMI).

Estrogen

Humans possess four types of estrogens, namely, estrone (E1), estradiol (E2), estriol (E3), and estetrol (E4) [38]. E2 is the primary estrogen during female reproductive processes, exhibiting the highest activity and playing crucial roles in follicular growth, ovulation, and maintenance of female sexual characteristics [21]. However, the relationships between estrogen levels and sleep duration remain unclear across different populations [39–41]. Estrogen lessens the homeostatic sleep need, with the median preoptic nucleus (MnPO) acting as a link between E2 and sleep. E2 affects sleep by attenuating the action of adenosine A_2A receptors on the MnPO, inducing an increase in arousal episodes and significantly inhibiting NREM sleep, particularly during dark-phase NREM sleep [14].

Testosterone

TT, secreted by Leydig cells in the interstitial tissue of the testes, is the most important sex hormone in males [42]. The majority of TT is bound to sex hormone-binding globulin (SHBG) or albumin, with only a small fraction existing in the circulation as free TT [43]. Plasma TT levels exhibit a pronounced circadian rhythm, characterized by increasing levels with prolonged sleep duration, achieving peak levels in the early morning hours [42]. Luboshitzky et al. [44] reported that the nocturnal rhythm of TT is associated with REM sleep, with young men reaching peak levels during the first REM sleep episode and maintaining this level until awakening. Thus, disruption in sleep structure, especially a decrease in the frequency or efficiency of REM sleep, directly affects TT hormone levels. In turn, low TT levels inversely impact sleep quality, leading to increased episodes of awakenings and decreased durations of SWS [45].

Prolactin

Prolactin (PRL) is a peptide hormone primarily synthesized and secreted by the pituitary gland, and it is inhibited by dopamine (DA) from the hypothalamus [46, 47]. PRL receptors are widely distributed throughout the body, including the pancreas, liver, small intestine, and adipose tissue [48, 49]. In addition to regulating lactation, PRL also regulates reproduction, growth, development, energy metabolism, immunity, angiogenesis, and other functions [46, 50]. Studies have demonstrated that PRL is regulated mainly by the sleep-wake cycle, and the plasma concentration of PRL exhibits a sleep-dependent pattern, with higher levels during sleep and lower levels during wake [51]. Therefore, lack of sleep causes the levels of PRL to decrease [52].

Melatonin

Melatonin is an indole hormone produced by the pineal gland, and it is synthesized with a 24-hour circadian rhythm under the control of the suprachiasmatic nucleus (SCN) in the hypothalamus [53, 54]. In mammals, melatonin levels are higher at night and lower during the day, exerting regulatory effects on the sleep-wake cycle through its rhythmic secretion [55, 56]. As a multifunctional hormone expressed in the retina, SCN, peripheral tissues, and organs, melatonin regulates circadian rhythms, stabilizes the sleep-wake cycle, reduces oxidative stress, increases the expression of antioxidant enzymes, affects vasoconstriction, influences dilation, modulates immune function, and reduces inflammation [57, 58] (Fig. 1).

Fig. 1.

Secretion and release of hormones related to sleep in the human body. TRH, thyrotropin-releasing hormone; GnRH, gonadotropin-releasing hormone; CRH, corticotropin-releasing hormone; GHRH, growth hormone-releasing hormone; PRH, prolactin-releasing hormone; ACTH, adrenocorticotropic hormone; TSH, thyroid-stimulating hormone; FSH, follicle-stimulating hormone; LH, luteinizing hormone; T3, triiodothyronine; T4, thyroxine; E2, estradiol; TT, testosterone; GH, growth hormone, PRL, prolactin (Figure created by FigDraw)

Relationship between hormones and metabolic diseases

Type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a complex chronic disease caused by dysregulation of carbohydrate, lipid, and protein metabolism, characterized by relative insulin deficiency and peripheral insulin resistance (mainly in skeletal muscle, liver, and adipose tissue), leading to dysfunction of pancreatic β-cells [59–61]. A prospective study has revealed a U-shaped association between sleep duration and T2DM, indicating that both short and long sleep durations significantly elevate the risk of T2DM compared to the reference range of 7–8 h per day [62].

Herzog et al. investigated the influence of sleep architecture on glucose metabolism and reported that auditory stimulation-induced suppression of SWS without alteration of total sleep duration leads to glucose metabolism dysfunction. SWS normally inhibits the secretory activity of the HPA axis and modulates the sympathovagal balance. When SWS is suppressed, cortisol levels and sympathetic nervous system activity significantly increase, thereby disrupting glucose homeostasis. Compared to wakefulness, glucose demand is substantially reduced during SWS. Therefore, SWS suppression elevates cerebral energy expenditure, consequently increasing systemic glucose requirements. Obstructive sleep apnea (OSA) is a common sleep disorder characterized by recurrent collapse of the upper airway during sleep. Symptoms of OSA include loud snoring, frequent awakenings from sleep, and excessive daytime sleepiness. OSA causes intermittent hypoxia in patients, leading to sleep fragmentation and ultimately suppressed SWS. Consequently, individuals with OSA are more susceptible to developing T2DM [63, 64]. Additionally, sleep disorders activate both the HPA axis and sympathetic nervous system, leading to enhanced β-adrenergic signaling, which upregulates nuclear factor-kappa B (NF-κB). The upregulation of NF-κB promotes the expression of several inflammatory markers, including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) [39, 65], which directly leads to elevated blood glucose levels and insulin resistance [66].

The peak secretion of GH is related to stable glucose levels during sleep, which counteracts the effects of insulin on the liver and peripheral glucose metabolism by increasing the release and uptake of free fatty acids (FFAs), thereby resisting hypoglycemia caused by prolonged fasting during sleep [45]. The kidney is also a direct target of GH. Increased circulating GH levels in patients with diabetes mellitus influence podocyte and mesangial cells, leading to podocyte hypertrophy, mesangial dilation, glomerular basement membrane (GBM) thickening, loss of glomerular permeability, and proteinuria, thus driving the progression of diabetic nephropathy [67]. Thus, reduced GH levels resulting from sleep disorders significantly increase the risk of diabetes and its complications.

During sleep disturbances, elevated thyroid hormone levels affect glucose metabolism via their actions on multiple organ systems. In the gastrointestinal tract, thyroid hormones accelerate gastrointestinal peristalsis, thereby enhancing glucose absorption. In the liver, thyroid hormones increase phosphoenolpyruvate carboxykinase (PEPCK) activity, stimulating gluconeogenesis. In adipose tissue, thyroid hormones promote lipolysis, elevating serum FFA levels and subsequently inducing insulin resistance [68].

There is a certain relationship between sex hormones and sleep. Michels et al. [69] reported that the levels of E2 and progesterone in the luteal phase increase with the extension of sleep time. Compared to women with normal sleep patterns, women who work night shifts have lower TT levels, which affects glucose homeostasis. Previous studies have demonstrated that physiological elevations in PRL enhance phosphorylation of signal transducer and activator of transcription 5 (STAT5), increase β-cell proliferation in rats, increase β-cell neogenesis in rats, and reduce menin expression, thereby promoting β-cell mass [49, 70]. Compared with normal sleep, total sleep deprivation significantly reduces PRL levels by disrupting the activity of the HPG axis, thereby increasing the risk of diabetes [52, 71].

Obesity

Obesity is caused primarily by an imbalance between energy consumption and energy intake [72]. Obesity is associated with a higher prevalence of cardiovascular disease (CVD), T2DM, hypertension, certain cancers, and sleep apnea [73]. A 7.5-year follow-up study conducted on elderly individuals in the United States has reported a negative correlation between sleep duration and weight; individuals who sleep less than 5 h per night have a higher risk of obesity compared to those who sleep 7–8 h per night [74]. Similarly, a meta-analysis of prospective cohort studies has reported that compared to 7 h per day, the risk of obesity increases by 9% for each hour of sleep lost [75]. By conducting nocturnal polysomnographies, Taheri et al. reported a U-shaped relationship between sleep duration and BMI after adjusting for confounding factors [76]. However, Sivertsen et al. [77] reported a curvilinear relationship between BMI and sleep duration in girls but a linear relationship with sleep duration in boys.

FSH levels are positively correlated with sleep duration. FSH regulates cholesterol synthesis and increases circulating low-density lipoprotein cholesterol (LDL-C) levels by inhibiting the expression of low-density lipoprotein receptors (LDLRs) [78, 79]. Similarly, melatonin levels produced by the pineal gland are also positively correlated with sleep duration. Jie Yin et al. reported that melatonin reconfigures the gut microbiota to ameliorate lipid accumulation caused by a high-fat diet [80]. In addition, melatonin also regulates the metabolism of BAT to control energy expenditure [81, 82]. Sleep disorders trigger sympathetic overactivation, suppress pineal gland function, and markedly reduce melatonin levels, ultimately leading to hyperinsulinemia and excessive hepatic triglyceride (TG) accumulation [55, 83].

The studies on leptin and ghrelin conducted by Spiegel have paved the way for investigating sleep and appetite hormones [84, 85]. Leptin, produced by white adipose tissue, suppresses appetite [84, 86]. Under normal physiological conditions, leptin levels peak during nighttime sleep and then gradually decline, reaching their lowest level in late afternoon. A previous study has reported that plasma leptin levels are modulated by a circadian component and sleep [87]. When sleep is restricted, leptin levels in the body significantly decrease [84]. In contrast to the anorexic effects of leptin ghrelin, a hormone secreted by the stomach and duodenum, stimulates appetite [88]. The secretion of ghrelin follows a distinct circadian rhythm, with the lowest point in the morning, peaking in the afternoon, and gradually declining at night [89]. Consequently, ghrelin levels are significantly elevated after sleep restriction. Moreover, Spiegel et al. reported that changes in the ghrelin-leptin ratio induced by sleep restriction often lead to increased appetite for high-calorie foods, such as high-carbohydrate foods, further contributing to obesity [85]. In addition to leptin and ghrelin, the endocannabinoid (eCB) system plays an important role in regulating appetite and hedonic eating. eCBs stimulate appetite by enhancing the palatability of food, especially sweet and fatty tastes, thus promoting fat deposition [90]. The lowest levels of eCBs exist during the nighttime fasting period, while the highest eCB levels exist in the afternoon. Nevertheless, sleep restriction activates the eCB system, which increases peak levels and prolonged durations, thereby stimulating appetite and increasing the risk of obesity [91].

Metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is one of the most common etiologies of chronic liver disease, and it is closely associated with metabolic syndrome, which includes obesity, insulin resistance, T2DM, and dyslipidemia [92–94]. MASLD is generally regarded as the hepatic manifestation of metabolic syndrome [95]. In the absence of excessive alcohol consumption and with the accumulation of TG, steatosis gradually progresses to metabolic dysfunction-associated steatohepatitis (MASH; previously non-alcoholic steatohepatitis, NASH), fibrosis, cirrhosis, and MASH-related hepatocellular carcinoma (HCC) [92, 96]. Epidemiological studies have demonstrated a strong correlation between the development of MASLD and metabolic disorders, including obesity, metabolic syndrome, and insulin resistance [97]. Sleep disorders promote the development of MASLD by affecting insulin sensitivity, lipid metabolism, and inflammation [11]. Via a logistic regression model, Kim et al. [97] identified significant associations between short sleep duration and MASLD risk independent of confounding factors; they reported that this relationship exhibits gender-specific effects, as the association between sleep duration and MASLD risk is non-significant in males after adjusting for BMI.

The pathogenesis of MASLD is closely linked to inflammatory cytokines. Elevated levels of TNF-α promote lipolysis through several synergistic mechanisms during sleep disturbances as follows: (1) suppressing insulin receptor signaling to antagonize the antilipolytic action of insulin; (2) inhibiting Gi-protein-coupled adenosine receptor signaling to counteract the antilipolytic effects of adenosine; and (3) activating basal lipolysis via direct perilipin interactions. Consequently, increased TNF-α levels resulting from sleep disorders drives hepatic FFA accumulation from peripheral fat breakdown, thereby exacerbating MASLD risk. Furthermore, cortisol metabolism dysregulation associated with sleep disorders directly stimulates lipid mobilization and indirectly exacerbates lipolysis by disrupting glucose metabolism. These effects accelerate both hepatic steatosis and fibrosis progression [11, 97, 98].

The secretory activity of sex hormones, including estrogen and TT, has also been reported to be strongly influenced by sleep duration [52]. Heine et al. [99] reported that estrogen receptor-α knockout (αERKO) mice exhibit adipocyte proliferation, hypertrophy, insulin resistance, and impaired glucose tolerance compared with wild-type mice. In the development of MASLD, the gut microbiota and its metabolites, such as short-chain fatty acids (SCFAs), plays crucial roles. Estrogen delays the progression of MASLD by interfering with intestinal flora [100]. In addition, Jaruvongvanich et al. conducted meta-analyses and revealed gender differences in the association between TT and MASLD; low TT levels increase the risk of MASLD in males, while high TT levels are associated with MASLD in females [101]. The exact mechanisms involved in the gender-specific associations between TT and MASLD remain unclear. A genetic study has revealed that TT exhibits both unique and shared transcriptional pathways in males and females; males tend to express housekeeping genes, while females tend to express protein-coding genes. Thus, the difference between TT and MASLD may be mediated by divergent transcriptional mechanisms [102]. Further, sleep disorders modulate pituitary-gonadal activity, reducing the effects of estrogen and TT, which increases the prevalence of MASLD.

A systematic retrospective analysis of infertile patients with polycystic ovary syndrome (PCOS) has reported that these patients often experience low quality of life and poor sleep quality. Sleep disorders may lead to increased DA secretion, thereby reducing serum PRL levels. Zhang et al. suggested that PRL ameliorates hepatic steatosis through the PRL receptor (PRLR) and fatty acid translocase (FAT)/cluster of differentiation 36 (CD36). Therefore, decreased serum PRL levels may damage hepatocytes, thereby increasing the prevalence of MASLD [103, 104].

Melatonin, a hormone that regulates circadian rhythms and the sleep-wake cycle, has been reported to prevent liver damage by inhibiting oxidation, inflammation, hepatocyte proliferation, and hepatocyte apoptosis, thereby slowing the progression of MASLD to cirrhosis [53, 105].

Cardiovascular disease

CVD is one of the leading causes of death worldwide [106]. The occurrence and development of CVD is due mainly to the narrowing of blood vessels caused by atherosclerosis and thrombosis, which causes organ damage and leads to end-organ dysfunction [107]. Sleep deprivation can cause several CVDs, including coronary artery disease, arrhythmia, and hypertension, which may be related to the autonomic nervous system, endothelial function, metabolic regulation, inflammation, and the clotting system [108]. Sleep duration is U-shaped in relation to CVD, and both short and long sleep durations increase the risk of coronary heart disease and stroke [109]. A prospective study of 300,000 biological samples examining the association of sleep with CVD through a healthy sleep score has reported that short sleep duration (≤ 6 h), long sleep duration (≥ 9 h), insomnia, and snoring are associated with increased risk of CVD, with statistically significant associations after adjusting for BMI, hypertension, diabetes, and other factors [110]. Quyyumi et al. reported that 39% of patients with coronary artery disease sleep less than 6.5 h and that 35% of patients with coronary artery disease sleep more than 7.5 h [111].

TT induces coronary vasodilation by regulating the activity of ion channels on vascular smooth muscle cells, including non-ATP-sensitive potassium channels and calcium-activated potassium channels [67]. Additionally, TT has protective effects on the vasculature by increasing nitric oxide (NO) production, enhancing endothelial cell movement, and promoting proliferation to prevent endothelial dysfunction [112]. Numerous studies have suggested that serum TT levels are inversely correlated with the incidence of major adverse cardiovascular events, as low TT levels increase the risk of aortic stenosis (AS), coronary artery disease, and coronary artery events [113]. E2 protects blood vessels by blocking monocyte adhesion, reducing foam cell formation, and resolving inflammation in plaques [112]. E2 also enhances the expression of protective heat shock proteins and improves the survival of myocardial cells, preventing apoptosis and reducing damage during myocardial ischemia and reperfusion [114]. Thus, sleep disorder-induced hypoestrogenemia may deteriorate vascular function and increase the risk of CVD.

Maintaining optimal sleep hygiene may protect the cardiovascular system by enhancing melatonin secretion. Previous studies have demonstrated that melatonin protects the cardiovascular system through multiple pathways as follows: (1) resisting oxidative stress-induced damage; (2) increasing the expression of the optic atrophy 1 (OPA1) mitochondrial fusion protein to inhibit mitochondrial fission and then reduce myocardial reperfusion injury; (3) elevating renal NO levels to protect blood pressure; and (4) enhancing arterial plaque stability and reducing plaque formation [57, 115]. Therefore, sleep disorders that lead to decreased melatonin levels may significantly elevate the risk of developing CVDs (Fig. 2).

Fig. 2.

Function of short sleep duration in metabolic diseases. HPA, hypothalamic-pituitary-adrenal; NF-κB, nuclear factor-kappa B; CRP, C-reactive protein; IL-6, interleukin-6; GH, growth hormone; PEPCK, phosphoenolpyruvate carboxykinase; FFA, free fatty acid; E2, estradiol; TT, testosterone; PRL, prolactin; STAT5, signal transducer and activator of transcription 5; T2DM, type 2 diabetes mellitus; FSH, follicle-stimulating hormone; LDL-C, low-density lipoprotein cholesterol; TG, triglyceride; eCB, endocannabinoid; TNF-α, tumor necrosis factor-alpha; MASLD, metabolic dysfunction-associated steatotic liver disease; NO, nitric oxide; OPA1, optic atrophy 1; CVD, cardiovascular disease

Conclusion

This review highlights the strong connections among sleep disturbances, hormonal imbalances, and metabolic diseases. Emerging evidence on sleep architecture, function, and underlying mechanisms has revealed that sleep disorders significantly disrupt circadian rhythms, leading to hormonal dysregulation and increased risks for various metabolic diseases. Consequently, maintaining adequate sleep duration and consistent sleep hygiene are crucial for enhancing overall health, including metabolic and cardiovascular health, while reducing risk of chronic diseases. However, the complex interplay among sleep, hormonal regulation, and metabolic diseases presents significant challenges for developing targeted therapies. Thus, advancing mechanistic investigations remains imperative to elucidate these relationships.

Author contributions

JJ and GY were responsible for the conception and design of the review. The original draft of the manuscript and figures were written by YJ and CB, and all authors provided feedback and revised subsequent versions of the manuscript. JJ conducted the final revision of the manuscript. All authors reviewed and approved the final version for submission.

Funding

This work was supported by the Social Development Project of Jiangsu Province (BE2023757), the National Natural Science Foundation of Jiangsu Province (BK20231251), and the sixth phase 333 s level talent training project of Jiangsu Province (tackling bottleneck technology) (BRA2022008), Doctoral Research Initiation Fund (jdfyRC2020010), Clinical Medical Science and Technology Development Foundation of Jiangsu University (JLY2021209), Key project for Medical Education Collaborative Innovation Fund of Jiangsu University (JDY2022005) and the Beigu Talent Cultivation Program of Affiliated Hospital of Jiangsu University (BGYCA202207).

Data availability

No datasets were generated or analysed during the current study.

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Competing interests

The authors declare no competing interests.