Type 2 diabetes mellitus (DM), polycystic ovarian syndrome (PCOS), obstructive sleep apnea (OSA), and obesity represent four large and growing patient populations. A great deal of scientific and clinical knowledge has been developed for them individually, and significant advancements made. Taken as a group, however, the interrelationships are not as well understood. The purpose of this systematic review is to identify the body of existing research that ties them together and then to identify and discuss the prevailing themes, particularly for cause-and-effect mechanisms. PubMed, Google Scholar, and ScienceDirect were used to identify systematic reviews and meta-analysis articles to establish the broadest reach. Initially, 434 articles were carefully screened, out of which 22 most relevant studies were reviewed. Five important themes were distilled from these papers based on continued and consistent emphasis in the literature. These themes include topics such as the importance of considering visceral obesity rather than Body Mass Index (BMI), the most effective treatment approaches, including mounting support for melatonin and circadian rhythm management, the results of OSA in its feed-forward contribution to hormone imbalance, the role of non-obesity-related risk factors to PCOS and OSA such as age and genetic predisposition, and growing evidence to suggest the importance of mental health as a comorbidity in addition to the more traditional ones such as cardiovascular pathology. A new framework for investigating the interaction across these four disorders is offered that includes a revised perspective on the specific role of PCOS, perhaps being further upstream relative to the others. There currently exists a lack of well-designed randomized controlled trials in this particular area of medicine, an endeavor we believe could result in significant value, particularly as it relates to treatment approaches.
Introduction & Background
Consider the following prevalence data: Diabetes mellitus (DM) remains a “giant” at 463 million people, or 9.3% of the population, projecting to 578 million by 2030 . Polycystic ovarian syndrome (PCOS) has been reported in 21% of women of reproductive age worldwide . Forty percent of women who are 18 and older are overweight, with 15% obese (BMI > 30) . Nine hundred and thirty-six million adults globally experience mild obstructive sleep apnea (OSA), and 425 million show severe symptomology .
Martins and Conde explored the shared mechanisms connecting OSA and metabolic derangements, but their review focused on gender differences and not on the PCOS population . Li et al. explored bariatric surgery for women with PCOS in a 2019 meta-analysis . Findings were encouraging: surgery not only reduce BMI but also abnormal menstruation and DM prevalence. However, it reviewed a specific interventional approach. Missing is a broad assessment of reviews specifically investigating causal linkages and mechanisms amongst DM, PCOS, obesity, and OSA.
PCOS is an endocrine disorder, with androgens, insulin, and progesterone outside of normal ranges. Small cysts can be observed on the outer edges of the enlarged ovaries. Symptoms include menstrual irregularity, hair loss, and acne. Obesity is frequently observed. OSA results from upper airway blockage during sleep, and features snoring and daytime sleepiness. Obesity is at the top of the list of causes. Swollen tonsils, cardiovascular dysfunction, and endocrine disorders have also been implicated .
Is obesity a cause or effect of PCOS and OSA? We assess current evidence from review articles, identify established cause-and-effect relationships, and summarize findings of interest to endocrinologists, OB-GYNs, any healthcare provider concerned with BMI management, and even dentists, who play an increasing role in the screening for and treatment of OSA .
Two co-authors independently conducted article search and retrieval. The date of the last search was March 23, 2022.
Keywords: insulin resistance, obstructive sleep apnea, polycystic ovary syndrome
Filters: “All Fields,” with no historical timeline filter
Keywords: polycystic ovary syndrome, obstructive sleep apnea, hyperandrogenism, obesity, insulin resistance
Filters: Since 2018 (five years), and Type = Review Articles
Keywords: insulin resistance, metabolic dysfunction, obstructive sleep apnea, polycystic ovary syndrome
Filters: No historical timeline filters, and Type = Review/Research Articles
Apart from the five years time frame filter for Google Scholar, and type filter of review/research articles for Science Direct, no other criteria were used, including peer review, publication status, setting (hospital vs. out-patient), location, original publication language, or any population attributes. Additionally, keywords were chosen (“insulin resistance” instead of “diabetes”) to avoid dilution by extremely broad topic headings. Each article was qualified based on relevance to the topic (author discretion) - initially at the title and abstract level and subsequently upon detailed review. The decision was made post-review to limit the assessment of remaining papers to only systematic reviews and meta-analysis publications. All qualified articles were available in full-text format. Critical appraisal was independently performed using the scale for the assessment of narrative review articles (SANRA) tool by two co-authors to grade the aggregate level of quality of the literature being reviewed . This systematic review was done according to the PRISMA guidelines.
Four hundred and thirty-four studies were initially returned (Figure 1). Twenty-two duplicates were excluded, and 412 studies were screened from the abstracts. Another 362 articles were excluded based on lack of relevancy at the abstract level. The remaining 50 studies were reviewed in detail for relevancy; 21 were disqualified. Of the 29 remaining papers, seven were discarded as a result of not being review articles.
It can be seen in Table 2 that the largest number of studies, with six total, was published out of the United States. China and the United Kingdom each had three, followed by Turkey and Iran with two each. In total, 10 different countries were represented.
Several key findings were identified in our review.
Mental Health May Be an Important Confounding Variable and Comorbidity
Kahal et al. (2018) offer a search of eight databases with no filters, yielding six studies and 252 patients . The authors stated that the relationship between OSA and obesity in women with PCOS is unclear. In terms of future research direction, fertility, mental health, cardiovascular health, and risk for Type 2 DM were highlighted. Mental health is interesting as it has been proposed as a key measure for assessing outcomes. Dokras et al. evaluated women with PCOS using the Short Form-36 tool, which includes attributes such as social functioning and mental health. All six studies exhibited a risk of bias for confounding variables. The paper points out that both OSA and PCOS independently are correlated with depressed mood, an area identified for targeted research [32-33]. The fact that having poor quality sleep would lead to poor mood comes as no surprise. The confounding role of PCOS is less understood .
Shah’s review covers co-morbidities, with themes including cardiovascular disease and, again, mood disorders . For patients specifically co-diagnosed with mental health disorders, one of the studies reviewed demonstrated that mindfulness programs vs. placebo control resulted in not only improved mental health measures but also physiological reduction of salivary cortisol levels . Dwivedi et al. additionally summarized comorbidities . Noted were cardiovascular disease, OSA, fertility and ovulation, and what the authors referred to as, “psychosocial elements.” In terms of lifestyle vs. biopharmaceutical interventions, they suggest that drugs should constitute the primary treatment plan. Oral contraceptives are mentioned for increased androgen levels and anovulation; citrate is mentioned for infertility. Finally, it is noted that PCOS patients should be screened for OSA in a clinical setting.
OSA May Be Exerting a Feed-Forward Impact in the Form of Hormone Imbalances
Carneiro et al. specifically reviewed cardiovascular disease as a comorbidity with obesity and OSA . They explored OSA-related hormones that act on vasoconstrictor system activation (angiotensin II and endothelin), aldosterone, hypothalamic-pituitary-adrenal (HPA) axis products (such as cortisol), IGF-1, sex hormones, and even leptin [36-42]. They concluded that angiotensin II may actually contribute to renal disease. Here, it stimulates a highly potent vasogenic cytokine (vs. acting as a pressor agent) . Given the causal effect of DM on renal dysfunction, it is easy to see how an OSA-driven renal pathology is an area for further research. Their hypothesis is drawn from animal studies in which losartan (angiotensin receptor blocker) did not preempt blood pressure rise in rats with hypoxia . OSA as a source of hormonal imbalances, as opposed to a result of them, would lend support to positioning it earlier in the cause-and-effect flow stack than previously thought.
Distribution of Body Fat (Visceral Adiposity) Is Likely More Important Than Raw BMI in Considering a Patient’s Weight
The Carneiro review also posits that “obesity is not just obesity.” BMI is not an appropriate measure they argue, at least in terms of predictive value for OSA. This view holds support from other literature [45-46]. OSA prevalence has been observed at increased levels in patients with increased waist circumference, waist-to-hip ratio, and neck circumference [47-48]. Ortiz-Flores et al. argued that diet should be the first-line treatment . The key aims acknowledge the sub-classification of obesity. They include achieving redistribution of body fat, curtailing excessive androgen levels, and improving insulin resistance. Escobar-Morreale et al. also proposed surgery as an option and noted improved outcomes across reproductive parameters, androgen levels, insulin sensitivity, and resolution of ovulatory dysfunction in patients (BMI > 35) post-surgery .
Tasali et al. looked at the link between OSA and PCOS . They focused on “visceral adiposity” and argued that elevated BMI is not the right measure. The mechanism offered is that visceral fat is more active from a metabolic standpoint. Other researchers have found that visceral fat specifically is more highly correlated with OSA . They speculated that males show a higher prevalence of OSA than females because the ratio of visceral fat as a percentage of total body fat is higher in men. Visceral obesity is further explored by Vgontzas et al. . They reinforced that sleep apnea can be a causal factor in PCOS, regardless of obesity. They proposed a bi-directional model and feed-forward between OSA and insulin resistance. They were clear that both visceral obesity and insulin resistance are multi-factorial, owing to genetic and environmental risk factors. Taken together, visceral obesity and insulin insensitivity lead to sleep apnea. It is further suggested that the resulting sleep apnea can accelerate metabolic derangements. They argued that treatment should focus on diet, exercise, and sleep as opposed to pharmaceuticals.
Neven et al. provided a summary of the diagnosis and treatment of PCOS . It reviewed the Rotterdam diagnostic criteria, which require any two of oligo-ovulation, anovulation, clinical hyperandrogenism, biochemical hyperandrogenism, or polycystic ovaries . They call for lifestyle modification as the first-line treatment approach, suggesting that it improves reproductive, metabolic, psychological, and cardiovascular comorbidities. Witchel et al. suggested poor clinical PCOS diagnosis performance, specifically blaming unclear criteria and physician knowledge gaps . They offer a de novo set of diagnostic criteria and emphasize the importance of early identification of “at risk” patients. They suggest that a PCOS diagnosis should also prompt the evaluation of applicable family members, reinforcing both the genetic component and the effectiveness of early intervention via lifestyle modification. An interesting point is made that successful treatment of OSA actually has no impact on DM and that the forward-looking focus of OSA in PCOS patients should be the management of symptoms. Obesity alone does not account for the OSA prevalence in women with PCOS.
Sam and Tasali looked specifically at the role that OSA may play in metabolic disorders within the PCOS patient population . Contrary to the lack of a clear association, as suggested by Kahal et al. (2018), these authors point to the increased prevalence of OSA occurring later in life, a point based on smaller studies. The larger studies they assessed showed that the OSA-PCOS link is not completely accounted for by obesity . Ehrmann’s review looked at aspects of the OSA-PCOS connection, including sex differences related to epidemiology, sex steroids, body fat distribution, and comorbidity of PCOS with cardiovascular disease . There is an agreement with the conclusions from Sam and Tasali - obesity alone cannot fully account for the prevalence of OSA with PCOS. In one of the papers reviewed, Fogel et al. demonstrated that PCOS patients were more likely to have disordered breathing while sleeping and daytime sleepiness, even when controlling for BMI .
Ip et al. looked at the link between OSA and DM . They pointed out that, at a minimum, OSA exerts independent (from obesity) effects. Schmiedt et al. looked from the insulin resistance angle and assessed mechanisms for insulin increasing steroid levels in women with PCOS . An important contribution was its emphasis on how steroid levels are increased. Sex hormone-binding globulin levels are reduced with increased insulin. Increased androgens levels result from the direct stimulation of thecal cell secretion by insulin. This elevation occurs as a result of increasing two enzymes, in particular, CYP17A1 and p450scc [54-56]. Barber et al. focused on mechanisms of pathology and treatment approaches. Mechanisms trinucleotide repeats, as well as second messenger signaling pathways . Mohlig et al. suggested that the number of CAG repeats within the androgen receptor gene directly contributes to insulin resistance in patients with PCOS . Again, there is no direct tie to obesity, per se. Barber et al. have shown that the phosphatidylinositol 3-kinase pathway, which mediates the effect of glucose uptake into skeletal muscle, features a post-receptor defect . They state that the PCOS population includes obese women who have developed PCOS for other reasons.
Helvaci and Yeldiz reviewed aging and menopause as a correlating to PCOS . They suggested the risk of cardiovascular disease is no difference between women with and without PCOS. They mentioned challenges with following generational cohorts. They are also skeptical about interpreting a direct linkage between PCOS and OSA. Limitations are pointed out: cross-sectional design, small sample sizes, selection bias, range and variability of BMI values, and ongoing confounding factors. The meta-analysis referencing the eight studies with these flaws found a 32% prevalence (95% CI of 13%-55%) of OSA in PCOS women . They conclude that “it is difficult to determine a causal link between PCOS and OSA based on these reports.” Celik et al. elaborated on the theme of PCOS in women of advanced age . The literature reviewed was mixed on whether or not PCOS in these women persists vs. healthy control counterparts. Although confirmation is given for the classic PCOS comorbidities, including obesity, insulin resistance, DM, hypertension, and cardiovascular disease, the causal linkage - at least in older women - is left as an unanswered question.
Another paper from Kahal investigated the prevalence of OSA in women with PCOS . Seventeen studies (n=648 in aggregate) were selected. Thirty-five percent of PCOS women had OSA (95% CI of 22.2%-48.9%). Helvaci et al. concluded that 32% of these two data points support one another. The Kahal (2020) review discovered that OSA prevalence was higher in obese women, including an Odds Ratio of 3.83 (95% CI of 1.43-10.24). This sub-analysis was limited to eight studies and 957 women. Piri-Gharaghie et al. focused on genetic factors as a contributor to PCOS . A summary of the known PCOS genes was provided (CYP11A1, CYP17, androgen receptor, sex hormone-binding globulin (SHBG), the insulin gene, and the insulin receptor gene). They remain non-committal on lifestyle and controllable risk factor modification vs. drugs. It is suggested based on available evidence that while lifestyle modifications can improve PCOS-associated abnormalities, environmental insults such as smoking, pollution, and dietary toxins unmask the genetic predisposition [60-61].
Livadas et al. describe a “controversial association” between PCOS and diabetes . Menopausal women are identified as being at risk for PCOS. This positioning of a “can’t miss” diagnosis is clinically relevant. They also favor lifestyle modification over pharmacological intervention. While there is some argument that obesity is a contributing factor to OSA in women with PCOS, there is also little doubt that it is not the sole contributor. Evidence also points to aging and genetic predisposition based on mechanisms ranging from trinucleotide repeats to defective receptors.
Circadian Rhythms and Melatonin Represent Viable Treatment Approaches
Spinedi et al. reviewed melatonin as a therapy. Dysfunction of the melatonin receptor has been linked to an increased risk of developing PCOS . In contrast to the “diet first” approach supported by Ortiz-Flores et al. these authors favor insulin sensitizers and secretagogues. Sam and Ehrmann (2019) summarized links between sleep disturbances and PCOS . They touch on melatonin, establishing support for Spinedi. The study cited, however, was only n=26 . Melatonin had previously been proposed by Li et al. SNPs in the melatonin receptor gene were associated with PCOS in a Genome-Wide Association Study of n=500 women . Hajimehdipoor et al. emphasized that sleep hygiene should be included with diet and exercise . Obesity and even insulin resistance are the result of low-quality sleep and have been demonstrated to contribute to PCOS [64-65].
A New, Revised Framework
We offer a new, slightly revised framework, depicted in Figure 2. PCOS, the least diagnosed of the conditions, is the starting point. It represents a diagnostic call-to-action that builds awareness around the most targeted patient profile, females of reproductive age.
Although PCOS and OSA both feature awareness campaigns in the market, OSA benefits from having an entire dental sleep medicine academy focused on it . Several feed-forward causal effects flow downstream, including hormone imbalances. Obesity is labeled as visceral adiposity and not BMI. Insulin resistance in our model is attributed to PCOS, not the other way around. The resulting derangements manifest as OSA. As sleep deficit accumulates, there is an alteration in lipid metabolism and an increase in the sympathetic drive. OSA can include up to 30 discrete breathing interruptions of 10 seconds or greater per hour . The alteration in lipid metabolism as the body fights to breathe, in what is essentially a “fight or flight” response, eventually leads to beta-cell dysfunction and glucose intolerance. The final common pathway is DM. This framework also allows a forward flow from PCOS to DM that does not depend on obesity. The diabetic state feeds back to several points earlier before it, most notably insulin resistance, which supports the PCOS-to-OSA flow path.
It is paramount to recognize that while BMI is a popularized measurement tool, it offers little value in assessing PCOS, OSA, and DM interrelationships. Numerous papers offered alternative methods such as neck circumference and waist-to-hip ratio. Treatment plans may be able to better target redistribution of fat, as opposed to reduction of BMI. Treatment overall remains controversial, with most research favoring non-pharmacological management as first-line. Melatonin and circadian rhythm management may play a role in patient care. Surgery has also been proposed as an intervention.
OSA can be prevalent in the PCOS population without obesity. And even in obese PCOS patients presenting with OSA, obesity is likely not the exclusive causal factor. Factors include advancing age and genetic predisposition for insulin resistance. We have offered a slightly modified framework to describe their interrelationship. PCOS is introduced as the most upstream diagnosis, exerting a forward effect that culminates most directly as OSA. Both of these pathologies taken together exert a causal effect on insulin resistance and ultimately, DM. Then, DM closes a feedback loop back up across all predisposing factors. Obesity in these patients can initially result directly from the PCOS. Finally, this literature highlights the importance of mental health comorbidities. In addition to others like cardiovascular diseases, they may represent an important consideration to the patient management continuum, from diagnosis to measurement of outcomes. RCTs analyzing benefits of drug-based vs. lifestyle modification treatments in obese patients with PCOS, DM, and OSA, would be of value to the scientific and clinical communities.
- Saeedi P, Petersohn I, Salpea P, et al.: Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019, 157:107843. 10.1016/j.diabres.2019.107843
- Deswal R, Narwal V, Dang A, Pundir CS: The prevalence of polycystic ovary syndrome: A brief systematic review. J Hum Reprod Sci. 2020, 13:261-71. 10.4103/jhrs.JHRS_95_18
- World Health Organization: Obesity and overweight. (2022). Accessed: June 25, 2022: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
- Benjafield AV, Ayas NT, Eastwood PR, et al.: Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis. Lancet Respir Med. 2019, 7:687-98. 10.1016/S2213-2600(19)30198-5
- Martins FO, Conde SV: Gender differences in the context of obstructive sleep apnea and metabolic diseases. Front Physiol. 2021, 12:792633. 10.3389/fphys.2021.792633
- Li YJ, Han Y, He B: Effects of bariatric surgery on obese polycystic ovary syndrome: a systematic review and meta-analysis. Surg Obes Relat Dis. 2019, 15:942-50. 10.1016/j.soard.2019.03.032
- Jonas DE, Amick HR, Feltner C, et al.: Screening for obstructive sleep apnea in adults: an evidence review for the U.S. Preventive Services Task Force. Agen Health Res Qual. 2017, 2017
- Gottlieb DJ, Punjabi NM: Diagnosis and management of obstructive sleep apnea: A review. JAMA. 2020, 323:1389-400. 10.1001/jama.2020.3514
- Baethge C, Goldbeck-Wood S, Mertens S: SANRA-a scale for the quality assessment of narrative review articles. Res Integr Peer Rev. 2019, 4:5. 10.1186/s41073-019-0064-8
- Kahal H, Kyrou I, Uthman O, et al.: The association between obstructive sleep apnea and metabolic abnormalities in women with polycystic ovary syndrome: a systematic review and meta-analysis. Sleep. 2018, 41:10.1093/sleep/zsy085
- Shah R: Emerging topics in cardiometabolic and psychologic sequelae, pathogenesis, and treatment of polycystic ovarian syndrome: A review. Children (Basel). 2019, 6:10.3390/children6080089
- El Hayek S, Bitar L, Hamdar LH, Mirza FG, Daoud G: Poly cystic ovarian syndrome: an updated overview. Front Physiol. 2016, 7:124. 10.3389/fphys.2016.00124
- Carneiro G, Zanella MT: Obesity metabolic and hormonal disorders associated with obstructive sleep apnea and their impact on the risk of cardiovascular events. Metabolism. 2018, 84:76-84. 10.1016/j.metabol.2018.03.008
- Ortiz-Flores AE, Luque-Ramírez M, Escobar-Morreale HF: Polycystic ovary syndrome in adult women. Med Clin (Barc). 2019, 152:450-7. 10.1016/j.medcli.2018.11.019
- Tasali E, Van Cauter E, Ehrmann DA: Polycystic ovary syndrome and obstructive sleep apnea. Sleep Med Clin. 2008, 3:37-46. 10.1016/j.jsmc.2007.11.001
- Vgontzas AN, Bixler EO, Chrousos GP: Metabolic disturbances in obesity versus sleep apnoea: the importance of visceral obesity and insulin resistance. J Intern Med. 2003, 254:32-44. 10.1046/j.1365-2796.2003.01177.x
- Neven AC, Laven J, Teede HJ, Boyle JA: A summary on polycystic ovary syndrome: Diagnostic criteria, prevalence, clinical manifestations, and management according to the latest international guidelines. Semin Reprod Med. 2018, 36:5-12. 10.1055/s-0038-1668085
- Witchel SF, Teede HJ, Peña AS: Curtailing PCOS. Pediatr Res. 2020, 87:353-61. 10.1038/s41390-019-0615-1
- Sam S, Tasali E: Role of obstructive sleep apnea in metabolic risk in PCOS. Curr Opin Endocr Metab Res. 2021, 17:46-51. 10.1016/j.coemr.2021.01.002
- Ehrmann DA: Metabolic dysfunction in pcos: Relationship to obstructive sleep apnea. Steroids. 2012, 77:290-4. 10.1016/j.steroids.2011.12.001
- Ip M, Mokhlesi B: Sleep and glucose intolerance/diabetes mellitus. Sleep Med Clin. 2007, 2:19-29. 10.1016/j.jsmc.2006.12.002
- Schmiedt RA, Tiuca RA, Tilinica RM: Insulin resistance as risk factor for the development of type 2 diabetes mellitus: a systematic approach. Sciendo. 2021, 67:187-192. 10.2478/amma-2021-0033
- Barber TM, Hanson P, Weickert MO, Franks S: Obesity and polycystic ovary syndrome: Implications for pathogenesis and novel management strategies. Clin Med Insights Reprod Health. 2019, 13:1179558119874042. 10.1177/1179558119874042
- Helvaci N, Yildiz BO: The impact of ageing and menopause in women with polycystic ovary syndrome. Clin Endocrinol (Oxf). 2021, 10.1111/cen.14558
- Çelik Ö, Köse MF: An overview of polycystic ovary syndrome in aging women. J Turk Ger Gynecol Assoc. 2021, 22:326-33. 10.4274/jtgga.galenos.2021.2021.0077
- Kahal H, Kyrou I, Uthman OA, et al.: The prevalence of obstructive sleep apnoea in women with polycystic ovary syndrome: a systematic review and meta-analysis. Sleep Breath. 2020, 24:339-50. 10.1007/s11325-019-01835-1
- Tohid Piri-Gharaghie: Polycystic ovary syndrome and genetic factors influencing its development: A review article. Perso Med Jr. 2021, 6:23.
- Livadas S, Anagnostis P, Bosdou JK, Bantouna D, Paparodis R: Polycystic ovary syndrome and type 2 diabetes mellitus: A state-of-the-art review. World J Diabetes. 2022, 13:5-26. 10.4239/wjd.v13.i1.5
- Spinedi E, Cardinali DP: The Polycystic ovary syndrome and the metabolic syndrome: A Possible chronobiotic-cytoprotective adjuvant therapy. Int J Endocrinol. 2018, 2018:1349868. 10.1155/2018/1349868
- Sam S, Ehrmann DA: Pathogenesis and consequences of disordered sleep in PCOS. Clin Med Insights Reprod Health. 2019, 13:1179558119871269. 10.1177/1179558119871269
- Bahman M, Hajimehdipoor H, Afrakhteh M, Bioos S, Hashem-Dabaghian F, Tansaz M: The Importance of sleep hygiene in polycystic ovary syndrome from the view of Iranian traditional medicine and modern medicine. Int J Prev Med. 2018, 9:87. 10.4103/ijpvm.IJPVM_352_16
- Barnard L, Ferriday D, Guenther N, Strauss B, Balen AH, Dye L: Quality of life and psychological well being in polycystic ovary syndrome. Hum Reprod. 2007, 22:2279-86. 10.1093/humrep/dem108
- Dokras A, Sarwer DB, Allison KC, et al.: Weight loss and lowering androgens predict improvements in health-related quality of life in women with PCOS. J Clin Endocrinol Metab. 2016, 101:2966-74. 10.1210/jc.2016-1896
- Finn L, Young T, Palta M, Fryback DG.: Sleep-disordered breathing and self-reported general health status in the Wisconsin sleep cohort study. Sleep. 1998, 21:701-706. 10.1093/sleep/21.7.701
- Stefanaki C, Bacopoulou F, Livadas S, Kandaraki A, Karachalios A, Chrousos GP, Diamanti-Kandarakis E: Impact of a mindfulness stress management program on stress, anxiety, depression and quality of life in women with polycystic ovary syndrome: a randomized controlled trial. Stress. 2015, 18:57-66. 10.3109/10253890.2014.974030
- Jin ZN, Wei YX: Meta-analysis of effects of obstructive sleep apnea on the renin-angiotensin-aldosterone system. J Geriatr Cardiol. 2016, 13:333-43. 10.11909/j.issn.1671-5411.2016.03.020
- Allahdadi KJ, Cherng TW, Pai H, Silva AQ, Walker BR, Nelin LD, Kanagy NL: Endothelin type A receptor antagonist normalizes blood pressure in rats exposed to eucapnic intermittent hypoxia. Am J Physiol Heart Circ Physiol. 2008, 295:H434-40. 10.1152/ajpheart.91477.2007
- Pratt-Ubunama MN, Nishizaka MK, Boedefeld RL, Cofield SS, Harding SM, Calhoun DA: Plasma aldosterone is related to severity of obstructive sleep apnea in subjects with resistant hypertension. Chest. 2007, 131:453-9. 10.1378/chest.06-1442
- Carneiro G, Togeiro SM, Hayashi LF, Ribeiro-Filho FF, Ribeiro AB, Tufik S, Zanella MT: Effect of continuous positive airway pressure therapy on hypothalamic-pituitary-adrenal axis function and 24-h blood pressure profile in obese men with obstructive sleep apnea syndrome. Am J Physiol Endocrinol Metab. 2008, 295:E380-4. 10.1152/ajpendo.00780.2007
- Izumi S, Ribeiro-Filho FF, Carneiro G, Togeiro SM, Tufik S, Zanella MT: IGF-1 levels are inversely associated with metabolic syndrome in obstructive sleep apnea. J Clin Sleep Med. 2016, 12:487-93. 10.5664/jcsm.5672
- Suri J, Suri JC, Chatterjee B, Mittal P, Adhikari T: Obesity may be the common pathway for sleep-disordered breathing in women with polycystic ovary syndrome. Sleep Med. 2016, 24:32-9. 10.1016/j.sleep.2016.02.014
- Ulukavak Ciftci T, Kokturk O, Bukan N, Bilgihan A: Leptin and ghrelin levels in patients with obstructive sleep apnea syndrome. Respiration. 2005, 72:395-401. 10.1159/000086254
- Avguštin N, Rotar Ž, Pajek J, Kovač D, Osredkar J, Lindič J: The predictive value of urinary vascular endothelial growth factor (VEGF) on worsening kidney function in proteinuric chronic kidney disease. Clin Nephrol. 2017, 88:10-3. 10.5414/CNP88FX03
- Zoccal DB, Bonagamba LG, Oliveira FR, Antunes-Rodrigues J, Machado BH: Increased sympathetic activity in rats submitted to chronic intermittent hypoxia. Exp Physiol. 2007, 92:79-85. 10.1113/expphysiol.2006.035501
- Martinez-Rivera C, Abad J, Fiz JA, Rios J, Morera J: Usefulness of truncal obesity indices as predictive factors for obstructive sleep apnea syndrome. Obesity (Silver Spring). 2008, 16:113-8. 10.1038/oby.2007.20
- Drager LF, Lopes HF, Maki-Nunes C, et al.: The impact of obstructive sleep apnea on metabolic and inflammatory markers in consecutive patients with metabolic syndrome. PLoS One. 2010, 5:e12065. 10.1371/journal.pone.0012065
- Cizza G, de Jonge L, Piaggi P, et al.: Neck circumference is a predictor of metabolic syndrome and obstructive sleep apnea in short-sleeping obese men and women. Metab Syndr Relat Disord. 2014, 12:231-41. 10.1089/met.2013.0093
- Onat A, Hergenç G, Yüksel H, Can G, Ayhan E, Kaya Z, Dursunoğlu D: Neck circumference as a measure of central obesity: associations with metabolic syndrome and obstructive sleep apnea syndrome beyond waist circumference. Clin Nutr. 2009, 28:46-51. 10.1016/j.clnu.2008.10.006
- Escobar-Morreale HF, Santacruz E, Luque-Ramírez M, Botella Carretero JI: Prevalence of 'obesity-associated gonadal dysfunction' in severely obese men and women and its resolution after bariatric surgery: a systematic review and meta-analysis. Hum Reprod Update. 2017, 23:390-408. 10.1093/humupd/dmx012
- Young T, Peppard PE, Taheri S: Excess weight and sleep-disordered breathing. J Appl Physiol (1985). 2005, 99:1592-9. 10.1152/japplphysiol.00587.2005
- The Rotterdam ESHRE/ASRM‐sponsored PCOS consensus workshop group: Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004, 19:41-7. 10.1093/humrep/deh098
- Lin TY, Lin PY, Su TP, et al.: Risk of developing obstructive sleep apnea among women with polycystic ovarian syndrome: a nationwide longitudinal follow-up study. Sleep Med. 2017, 36:165-9. 10.1016/j.sleep.2016.12.029
- Fogel RB, Malhotra A, Pillar G, Pittman SD, Dunaif A, White DP: Increased prevalence of obstructive sleep apnea syndrome in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2001, 86:1175-80. 10.1210/jcem.86.3.7316
- Li H, Chen Y, Yan LY, Qiao J: Increased expression of P450scc and CYP17 in development of endogenous hyperandrogenism in a rat model of PCOS. Endocrine. 2013, 43:184-90. 10.1007/s12020-012-9739-3
- Cadagan D, Khan R, Amer S: Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome. Reprod Biol. 2016, 16:53-60. 10.1016/j.repbio.2015.12.006
- Zeng X, Xie YJ, Liu YT, Long SL, Mo ZC: Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity. Clin Chim Acta. 2020, 502:214-21. 10.1016/j.cca.2019.11.003
- Möhlig M, Jürgens A, Spranger J, et al.: The androgen receptor CAG repeat modifies the impact of testosterone on insulin resistance in women with polycystic ovary syndrome. Eur J Endocrinol. 2006, 155:127-30. 10.1530/eje.1.02195
- Barber TM, McCarthy MI, Wass JA, Franks S: Obesity and polycystic ovary syndrome. Clin Endocrinol (Oxf). 2006, 65:137-45. 10.1111/j.1365-2265.2006.02587.x
- Helvaci N, Karabulut E, Demir AU, Yildiz BO: Polycystic ovary syndrome and the risk of obstructive sleep apnea: a meta-analysis and review of the literature. Endocr Connect. 2017, 6:437-45. 10.1530/EC-17-0129
- Khan MJ, Ullah A, Basit S: Genetic basis of polycystic ovary syndrome (PCOS): current perspectives. Appl Clin Genet. 2019, 12:249-60. 10.2147/TACG.S200341
- Amato P, Simpson JL: The genetics of polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2004, 18:707-18. 10.1016/j.bpobgyn.2004.05.002
- Shreeve N, Cagampang F, Sadek K, et al.: Poor sleep in PCOS; is melatonin the culprit?. Hum Reprod. 2013, 28:1348-53. 10.1093/humrep/det013
- Li C, Shi Y, You L, Wang L, Chen ZJ: Association of rs10830963 and rs10830962 SNPs in the melatonin receptor (MTNR1B) gene among Han Chinese women with polycystic ovary syndrome. Mol Hum Reprod. 2011, 17:193-8. 10.1093/molehr/gaq087
- Koren D, Dumin M, Gozal D: Role of sleep quality in the metabolic syndrome. Diabetes Metab Syndr Obes. 2016, 9:281-310. 10.2147/DMSO.S95120
- Jelodar G, Karami E: Effect of hydroalcoholic extract of Vitex Agnus castus fruit on ovarian histology in rat with induced Polycystic Ovary Syndrome (PCOS). J Babol Univ Med Sci. 2013, 13:96-102.
- American Academy of Dental Sleep Medicine: Snoring and sleep apnea. (2022). https://www.aadsm.org/for_patients.php.
- Borel AL: Sleep apnea and sleep habits: Relationships with metabolic syndrome. Nutrients. 2019, 11:10.3390/nu11112628
Diabetes, Polycystic Ovarian Syndrome, Obstructive Sleep Apnea, and Obesity: A Systematic Review and Important Emerging Themes
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Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.
Cite this article as:
Bambhroliya Z, Sandrugu J, Lowe M, et al. (June 25, 2022) Diabetes, Polycystic Ovarian Syndrome, Obstructive Sleep Apnea, and Obesity: A Systematic Review and Important Emerging Themes. Cureus 14(6): e26325. doi:10.7759/cureus.26325
Received by Cureus: April 21, 2022
Peer review began: June 02, 2022
Peer review concluded: June 11, 2022
Published: June 25, 2022
© Copyright 2022
Bambhroliya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.