Sex Hormone Changes In Male Patients With Obstructive Sleep Apnea Hypopnea Syndrome

BackgroundObstructive sleep apnea hypopnea syndrome (OSAHS) is a common disease, with snoring, sleep accompanied by apnea or hypoventilation, recurrent hypoxemia, hypercapnia and sleep disorders at night, resulting in breathing with open mouth, increased nocturia, dry and bitter mouth in the morning, dizziness, headache, daytime drowsiness, weary, inattention, memory loss and a series of symptoms, bringing to the troubled life of patients and their families. The preliminary investigation prevalence rate is3.62%in Shanghai of China. The survey of Young et al found that9%of women and24%of men in the people of30to60-year-old had sleep apnea, and2%of women and4%of men reached the diagnostic criteria of sleep apnea syndrome (OSAHS). Due to the presence of nocturnal hypoxemia, sleep apnea hypopnea syndrome cause damage of systemic multisystem. Clinical statistics show that the prevalence of pulmonary heart disease, cerebrovascular disease is significantly higher than normal, and OSAHS patients with coronary heart disease prevalence is3to4times of the normal human. OSAHS also causes damage to the endocrine system. Due to recurring sleep fragmentation, intermittent hypoxia, hypercapnia, OSAHS make the hypothalamic-pituitary-gonadal axis produce a certain suppression and injury, leading to the disorder of the body environment in vivo, sex hormone secretion abnormalities, and can cause sexual dysfunction, personality changes, and the emergence of the depression, osteoporosis and other complications.PurposeDue to nocturnal hypoxemia, sleep apnea hypopnea syndrome make multi-system cause damage,leading to the suppression and injury of hypothalamic-pituitary-gonadal axis and the disorder of the body environment in vivo. This paper examines whether men with OSAHS exist abnormal secretion of sex hormones and the relationship between sex hormones and polysomnography (PSG) indicators.MethodRetrospective study contains91hospitalized patients in Nanfang Hospital Sleep Medicine Center from March2011to February2012.All patients underwent overnight sleep monitoring,and there were OSAHS group and non-OSAHS group according to the apnea-hypopnea index (AHI). All patients must be excluded from chronic diseases, such as chronic obstructive pulmonary disease, heart failure, liver and kidney failure, thyroid dysfunction, insomnia, the typical history of mental disorders and history of drug use affecting sex hormone metabolism.All patients had a history of using unified standard program record, in addition to age, the use of tobacco and alcohol, hobbies, and mental state during the day, history of cardiovascular and cerebrovascular disease, focusing on records of height, weight, neck circumference, chest circumference, abdominal circumference, and calculated the body mass index (BMI). All patients must have PSG at least7hours. PSG use the Embla polysomnography instrument (U.S. Embla),and monitoring indicators include that EEG, EOG, jaw EMG, ECG, nose and mouth airflow, snoring, body position, thoracoabdominal movements, and blood oxygen saturation. The PSG analysis though computer automatically, then correct frame-by-frame manually, and each frame is30s. Sleep stages and related events are mainly based on the guidelines of the American Academy of Sleep Medicine. In the day of the end of PSG, all patients were taken forearm superficial venous blood at rest and make the measurement of sex hormone.The six sex hormones including testosterone, follicle stimulating hormone (FSH), luteinizing hormone(LH),prolactin(PRL),estradiol(E2),and progesterone, using the application of electrochemiluminescence assay.After collecting all the information, it had statistical processing and analysis of experimental data using SPSS13.0. Experimental data was indicated using the mean±standard deviation (x±s), the comparison of the two groups was using two independent samples t-test,three sets of measurement data was using analysis of variance, correlation analysis between the two factors was using Pearson correlation analysis, and multiple linear regression analysis was carried on.The difference was statistically significant at P<0.05.Result(1) Basic data:a total of91men were enrolled in the study, the age range is from20years old to72years old, the average age is43.8±9.1years old;the BMI range is from18.59kg/m2to45.72kg/m2, average BMI is28.00±4.00kg/m2.There were two groups, including OSAHS group (n=79)and non-OSAHS group(n=12). All91patients were for the six hormones test.(2) The comparison of the basic data between OSAHS group and non-OSAHS group:age and chest circumference were not statistically significant difference respectively between OSAHS group and non-OSAHS group (P>0.05). Neck circumference and snore age were statistically significant difference separately between OSAHS group and non-OSAHS group (P<0.05). BMI and abdominal circumference were statistically significant difference respectively between OSAHS group and non-OSAHS group (P<0.01).(3) The comparison of sleep monitoring indicators between the OSAHS group and non-OSAHS group:sleep efficiency, the ratio of light sleep, deep sleep and fast moving eye movement in the whole sleep time between OSAHS group and non-OSAHS group were not statistically significant difference respectively (P>0.05).The number of awakening and average oxygen saturation were statistically significant difference separately between OSAHS group and non-OSAHS group (P<0.05). AHI, lowest oxygen saturation and oxygen drop index difference were statistically significant difference respectively between OSAHS group and non-OSAHS group (P<0.01).(4) The comparison of the measured value of the six sex hormones between OSAHS group and non-OSAHS group:testosterone was statistically significant difference between OSAHS group and non-OSAHS group (P<0.01). The other five sex hormones (follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol and progesterone) were not statistically significant difference separately between OSAHS group and non-OSAHS group (P>0.05).(5) Testosterone in light, medium and heavy OSAHS group was no statistically significant difference (P>0.05).(6) The relationship between serum testosterone levels in patients with OSAHS and basic information indicators:There was a statistically significant negative correlation between serum testosterone levels and neck circumference (r=-0.268, P=0.017), abdominal circumference (r=-0.385, P=0.000), and BMI (r=-0.302, P=0.007). There was not a statistically significant correlation between serum testosterone level and age (r=0.107, P=0.347), disease duration (r=-0.19, P=0.869), and chest circumference (r=-0.104, P=0.360). (7) The relationship between serum testosterone levels in patients with OSAHS and sleep monitoring indicators:There was not a statistically significant correlation between serum testosterone level and AHI (r=0.004, P=0.972), the average oxygen saturation (r=0.150, P=0.187), the lowest blood oxygen saturation (r=0.147, P=0.196), and the oxygen drop index correlation (r=-0.005, P=0.967).(8) Linear regression analysis:Testosterone was as dependent variable, and age, neck circumference, BMI, AHI, mean oxygen saturation were as the independent variable. The regression equation is:testosterone=10.381+0.014×sleep incubation period-0.061×6.Conclusion(1) It can be seen from the description that the basic information reflecting the degree of obesity including in neck circumference, abdominal circumference and BMI (body mass index) in OSAHS group is higher than the non-OSAHS group, and the difference was statistically significant. It indicates that obese snorers are more prone to sleep apnea syndrome.The potential causes of OSAHS include that changes in upper airway structure and function. Neck obesity will increase the instability of the pharynx, or even collapse.Fat accumulation can cause upper respiratory pressure changes and steatosis, causing the oppression of the upper respiratory tract, and are more likely to have obstruction in the upper airway, resulting in OSAHS. In the study of1351cases of patients maded by Shepard and Hoffstein in Canada found that more men than women, and found that neck circumference has the strongest correlation with AHI in many variables. Therefore, the size of the neck circumference may be one of the determinants of the apnea and snoring.Waist circumference, intra-abdominal fat and excessive accumulation of vi sceral fat in OSAHS patientsin is another important risk resulting in obese pati ents with OSAHS. Vgontzas made a precise determination of the accumulation of visceral fat, and confirmed by CT. It points out that male obese patients with OSAHS have more visceral adipose tissue in the abdomen, and are signi ficantly higher than the control group with the same BMI index but not with OSAHS. So visceral fat is more dangerous risk factors of OSAHS.(2) Time of awakening is more frequent in OSAHS group than in non-0SAHS group,and it indicates that patients with sleep apnea syndrome have sle ep fragmentation and lower quality of sleep. During sleep, pharyngeal tongue muscles become relax and tongue retropulses. When inhaling, the role of negat ive pressure in the chest make the soft palate and tongue fall into the poste rior pharyngeal wall,resulting in occlusion in the upper airway,and apnea.When respiratory stops, carbon dioxide becomes retention and oxygen partial pressur e drop in vivo,and they stimulate breathing receptors in the central respiratory.At the same time,brain arousal response emerges, pharynx and tongue muscle start to contract, when airway pressure breaking through the mechanical obstr uction of the upper airway, the reopening of the upper airway, breathing return ed,body carbon dioxide exclude,oxygen partial pressure rise and patients sleep again. Since then it enters the next apnea. It should be pointed out that, apne a is mainly accompanied with reaction of the brain waves, and patient behavio r may still be in the sleep state.(3) AHI, oxygen drop index indicators reflecting the severity of the disease are higher, and average oxygen saturation and lowest oxygen saturation are lo wer in OSAHS group compared with the non-OSAHS group, respectively.(4) This study found that testosterone is lower in patients with OSAHS c ompared with non-OSAHS group,and it had statistically significant difference.I t was consistent with the study of Gambineri A. The foreign study found that serum luteinizing and testosterone levels is below the normal control group in patients with OSAHS,and after surgery (uvulopalatopharyngoplasty surgery), te stosterone levels incr-ease in their body, suggesting that testosterone levels may be associated with the degree of hypoxia of sleep. Testosterone’s reduction i n patients with OSAHS may be the disorder of the hypothalamic-pituitary-gona dal axis, causing to endocrine abnormalities. But testosterone values are still w ithin the normal reference range in OSAHS group, it is consistent with finding s of Luboshitzky R(5) The study also found that serum testosterone levels in patients with OS AHS were nothing with AHI, mean oxygen, oxygen drop index,which reflect the severity of OSAHS. But it had correlation with neck circumference, abdom inal circumference, BMI, reflecting the degree of obesity.The majority of pati ents with OSAHS were obesity, and obesity could make the excess fat of nec k accumulate in the upper airway, thus affecting the airway diameter and com pliance. In addition, the increase in neck circumference caused the oppression of the upper airway in the supine position, and was also one of the reasons that cause airway narrow. Lots of studies had confirmed that, abdomen or upp er body obesity had stronger link with free testosterone levels than other form s of obesity.Excessive abdominal obesity may promote the formation and tran sformation of the local glucocorticoid, thereby it destroied the balance of the h ypothalamic-pituitary-adrenal axis resulting in the decline of androgen levels. Derby CA also found obesity were largely predicted reduction of testosterone and sex hormone-binding globulin. And in multivariate linear regression analy sis of this study, only abdominal circumference was into the equation, and so cent-ral obesity body mass index was a better predictor than BMI in forecasti ng testosterone. In summary, OSAHS caused the disorders of the endocrine system especia lly the reduction of testosterone,and changes had nothing to do with the sever ity of apnea-hypopnea index (AHI),but had something to do with the degree o f obesity. Sex hormone disorders may lead to a series of complications, such as sexual function decreasing, depression, osteoporosis, and so on. Therefore, it is important to make an effort in weight loss in order to prevent the occur rence of OSAHS actively.