|Year : 2019 | Volume
| Issue : 1 | Page : 79-85
Is chronic obstructive pulmonary disease a risk factor for erectile dysfunction? A cross-sectional, comparative study
Hamada Kawshty1, Mahmoud A.S Makki2, Walid A Elmorsy3, Maher A Shabaan4, Ahmad A Ahmad5
1 Department of Chest Diseases, Al-Azhar University Hospital, Assiut, Egypt
2 Department of Dermatology and Andrology, Egypt
3 Department of Clinical Pathology, Egypt
4 Department of Physioloogy, Faculty of Medicine, Egypt
5 Department of Radiology, Al-Azhar University Hospital, Assiut, Egypt
|Date of Submission||02-Oct-2019|
|Date of Acceptance||28-Apr-2019|
|Date of Web Publication||12-Sep-2019|
Department of Chest Diseases, Al-Azhar University Hospital, Alforsan Building, Al-azhar street, Assiut, 71524
Source of Support: None, Conflict of Interest: None
Background Sexual dysfunction is a common problem in chronic obstructive pulmonary disease (COPD).
Aim To evaluate the sexual activity in patients with COPD.
Patients and methods A total of 100 male patients with COPD (diagnosed and staged according to the American Thoracic Society guidelines) and 96 healthy volunteers (controls) with normal pulmonary function were included. After clinical evaluation, pulmonary function test, arterial blood gas, and hormonal profiles such as follicle-stimulating hormone, leutenizing hormone, and testosterone (total and free) were measured and compared. Participants were asked to answer the International Index of Erectile Function questionnaire as a method to diagnose and classify impotency.
Results Varying degrees of erectile dysfunction (ED) was detected in 78 (78%) patients with COPD and 56 (58.3%) of controls. The mean score of ED was found to be significantly (P<0.000) lower in comparison with the controls with significantly correlated with age, smoking index, percentage of forced expiratory volume in the first second, percentage of forced vital capacity, FEV/EVC ratio, PaO2, PaCO2, oxygen saturation (SaO2), total testosterone, and 6-min walk test. The smoking index, PaCO2, follicle-stimulating hormone, and leutenizing hormone were found to be significantly higher in patients with COPD compared with controls whereas percentage of forced expiratory volume in the first second, percentage of forced vital capacity, PaO2, SaO2, and BMI were significantly lower in patients with COPD. The results of 6-min walk test test between the two groups reveal highly significant decrease in physical fitness in patients with COPD than normal controls.
Conclusion ED is a frequent problem in patients with COPD. Hypoxemia, smoking, limitation of physical activity, and hormonal imbalance are thought to be responsible mechanisms for ED in patients with COPD.
Keywords: chronic obstructive pulmonary disease, erectile dysfunction, sex hormones
|How to cite this article:|
Kawshty H, Makki MA, Elmorsy WA, Shabaan MA, Ahmad AA. Is chronic obstructive pulmonary disease a risk factor for erectile dysfunction? A cross-sectional, comparative study. Al-Azhar Assiut Med J 2019;17:79-85
|How to cite this URL:|
Kawshty H, Makki MA, Elmorsy WA, Shabaan MA, Ahmad AA. Is chronic obstructive pulmonary disease a risk factor for erectile dysfunction? A cross-sectional, comparative study. Al-Azhar Assiut Med J [serial online] 2019 [cited 2019 Oct 20];17:79-85. Available from: http://www.azmj.eg.net/text.asp?2019/17/1/79/266734
| Introduction|| |
Chronic obstructive pulmonary disease (COPD) is ‘a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by vital exposure to noxious particles or gases’ . The inflammation reported in COPD has systemic aspects and is not restricted to the lungs . Comorbidities can be seen as one or more concomitant diseases either directly or indirectly associated with COPD , and they include cardiovascular diseases, lung cancer, obstructive sleep apnea, malnutrition, skeletal muscle dysfunction, osteoporosis, cachexia, anemia, gastroesophageal reflux, depression, and anxiety ,,. Systemic disorders result in decreased libido and erectile dysfunction (ED) by affecting the sexual function in males . Androgen levels rise to peak levels at around the ages of 20–40 years and begin to decline when 40s inititates in males . Depression, anger, muscle and joint pain, anxiety, sleep disorders, fatigue, poor concentration and memory, decreased libido, ED, and reduced ejaculate output volume and speed were symptoms of androgen deficiency . ED is outlined as a permanent insufficiency in achieving and/or pursuing an adequate and necessary erection to have satisfactory sexual activity .
Loss of sexual desire and function has been associated with decreased testosterone levels ,,,,, which along with a decrease in libido and erectile function in males are also caused by aging ,. Low levels of testosterone and ED have been documented in males with chest diseases, such as COPD, asthma, and obstructive sleep apnea syndrome ,. Muscle weakness, diminished physical activity, coughing, and dyspnea are among the most common causes of decreased sexual activity in patients with COPD .
The aim of this study is to assess the causes and frequency of ED in patients with COPD and to investigate the characteristics associated with ED in patients with COPD.
| Patients and methods|| |
A total of 100 outpatients who had been diagnosed with COPD, according to the American Thoracic Society guidelines  and followed in outpatient clinic and 96 healthy volunteers with normal pulmonary function were included in this cross-sectional comparative study between May 2017 and April 2018. The study protocol was approved by the institutional ethics committee, and written informed consent was obtained from all participants.
The patients with the diagnosis of pulmonary diseases other than COPD, diabetes mellitus, malignancy, COPD exacerbations within past 3 months, low mental status, coronary heart disease, history of alcoholism, impaired health, any urogenital abnormality, or receiving any hormonal or psychological treatments were excluded.
Medical history of the patients was taken. Demographics, clinical symptoms, the history of smoking habit (as pack-years), and comorbidities were recorded.
All patients underwent standard spirometery, and COPD was diagnosed when forced expiratory volume in the first second (FEV1) over forced vital capacity (FVC) was less than 70% and the reversibility of FEV1 was less than 12%. Spirometric parameters were determined with spirometry using Medical Equipment Europe; Hammelburg Measurements, Hammelburg, Germany. The severity of COPD was graded based on the GOLD classification as mild, moderate, severe, and very severe .
Assessment of ED was carried out on all participants using the International Index of Erectile Function (IIEF-5) Questionnaire. It is a self-applied five-question index developed by Rosen et al.  that is intended to evaluate erectile function. The maximum score is 25 points, and classification is as follows: 1–11 points, moderate to severe; 12–21 points, mild; and 22–25 points, no ED. Severity was assessed as follows: 0, no ED; 1 degree, mild ED; 2°, mild to moderate ED; 3°, moderate ED; and 4°, severe ED ,.
Physical fitness in all participants was assessed using the 6-min walk test (6-MWT). It was performed according to standard procedure and was used as a measure of exercise capacity. Patients were asked to run on a 20-m course over a 6-min period. Then the distances covered by the patients during this time interval minutes were recorded .
Arterial blood gas analysis (Easy Stat-Blood gas analyzer; Medica corporation, Bedford, MA 01730, USA), which was obtained from the radial artery, was performed at rest and in a sitting position.
Levels of serum testosterone (total), follicle-stimulating hormone (FSH), and leutinizing hormone (LH) concentration were measured using VIDAS (BioMerieux, Craponne, France). Free testosterone measurement was done using ELISA (5325-300; Monobid, lake forest, CA 92630, USA) according to the manufacturer instructions.
Penile Duplex was performed to exclude any peripheral vascular diseases that could be the cause of ED rather than COPD.
Statistical analysis of data consisted of descriptive analyses of the variables expressed as mean±SD, calculation of Pearson’s correlation coefficient, and analyses of the differences between the groups by independent-sample t-test and χ2 for continues data and categorical data, respectively. P values of less than 0.05 were considered significant.
| Results|| |
The characteristics of male patients with COPD and healthy controls are shown in ([Table 1]). Both patients with COPD and healthy controls were age matched without significant difference (61.53±9.76 and 59.79±11.05 years, respectively; P>0.05). The mean duration of COPD was found as 62.72±7.9 months. There were nine (9%) mild, 42 (42%) moderate, 33 (33%) severe, and 16 (16%) very severe patients according to GOLD criteria.
|Table 1 Characteristics, pulmonary function tests, arterial blood samples, and serum and sex hormone levels of patients with chronic obstructive pulmonary disease and controls|
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The mean BMI, FEV%, FVC%, and FEV1/FVC were significantly lower in patients with COPD compared with healthy controls (P<0.05). Moreover, patients with COPD had a significant decrease in PaO2 and SO2 (60.9±8.53 and 92.88±2.72, respectively) versus healthy control group (90.51±2.99 and 95.98±1.82, respectively) and a significant increase in PaCO2 (47.57±11.87) compared with the healthy control group (39.37±2.88) ([Table 1]). The 6-MWT values were significantly decreased in patients with COPD (P<0.05; [Table 1]).
Varying degrees of ED were detected in 78 (78%) patients with COPD. According to International Index of Erectile Function (IIEF-5) Questionnaire, there were 10 (10%) mild, 11 (11%) mild to moderate, 26 (26%) moderate, and 31 (31%) severe type of ED among patients with COPD and 56 (58.3%) age-matched controls ([Table 2]) had some degree of severity of ED, with a significant relationship between the stage of COPD and the presence of ED (P<0.05; [Table 3] and [Table 4]).
|Table 2 The percentage of patients with chronic obstructive pulmonary disease and controls according to degree of erectile dysfunction|
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|Table 3 The relation between the erectile dysfunction status and chronic obstructive pulmonary disease degree in patients with chronic obstructive pulmonary disease|
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|Table 4 The mean erectile dysfunction scores and degree of severity of erctile dysfunction in patients with chronic obstructive pulmonary disease and controls|
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Mean ED score for IIEF was found to be significantly decreased in patients with COPD than in normal controls (12.45±7.67 vs. 17.66±5.64) (P<0.05). Logistic regression analysis was employed to predict the probability of ED and parameters which influenced that. The predictor variables were participants’ age, BMI, smoking index, 6-MWT, FEV1%, FVC%, FEV1/FVC (%), total testosterone, free testosterone, FSH, and LH. [Table 5] shows the logistic regression coefficients, Wald test, and odds ratio with 95% confidence interval for each of the predictors. Employing a 0.05 criterion of statistical significance, 6-MWT, total testosterone, and degree of COPD, but no other variable, had significant partial effects. The significant odds ratios for these variables were calculated while holding all other variables constant. Patients presented with decrease in physical activity and serum level of total testosterone were more likely to have ED, otherwise more severe COPD degree was more likely to have ED ([Table 6]).
|Table 5 The relation between erectile dysfunction status and smoking index degree in studied participants.|
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|Table 6 Logistic regression analysis of confounding variables to predict sexual dysfunction in studied participants (N=196)|
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| Discussion|| |
COPD is the fifth leading cause of death in the world but will be the third leading cause of death by 2020 . GOLD guidelines state that sexual activity should be evaluated in all patients with COPD, but they do not include ED as one of the possible comorbidities of COPD . In spite of some studies having reported ED as a common comorbidity in patients with COPD, this is still an underresearched area ,. Moreover, the information about the effect of the respiratory symptoms on sexual activity among patients with COPD is sparse .
Sexuality is a lifelong necessity to procreate . Therefore, our aim in this study is to evaluate the sexual activity in patients with COPD and interpret the risk factors that can cause diminished sexual activity, libido, and ED.
In the present study, the percentage of ED in patients with COPD was 78%. The mean age of patients with COPD was 61.53±9.76 years. In comparison, 58.3% had varying degree of ED among controls, and their mean age was 59.79±11.05. IIEF-5 score was significantly decreased in patients with COPD than in normal controls, which is similar with other studies ,,,. This high prevalence of ED in COPD makes it an important and unignorable problem for patients with COPD.
Patients with COPD are at a significantly higher risk of developing ED compared with the general population regardless of age. Both patients with COPD and healthy controls in our study were age matched without significant difference (61.53±9.76 vs. 59.79±11.05; P>0.05). In COPD groups, we documented a significant negative correlation between age and ED score (R=−0.42, P<0.05). Our results are also in agreement with Kahraman et al.  who documented a significant correlation between age and ED.
There is evidence that both psychogenic and organic problems are related to sexual dysfunction in patients with COPD ,. However, the definitive mechanism of ED development in patients with COPD remains unclear.
First, hormonal imbalances should be considered, though the relationship between testosterone and ED is controversial. Androgen deficiency can induce depression, anxiety, anger, fatigue, and sleep disorders . Testosterone contributes to muscle mass and the body’s response to exercise but is also directly associated with sexual functioning in men . Hypogonadism and lower testosterone levels have been reported in males with COPD ,,. It has been established that men with COPD have lower total testosterone levels than men without COPD. A recent systematic review involving a meta-analysis of data from nine case–control studies found that men with COPD have less total testosterone than age-matched men without COPD . We demonstrated that patients with COPD with ED had statistically lower testosterone levels, which shows that hormonal imbalance may play a key role in the etiology of ED in COPD.
Therefore, a link between gonadal status and sexual dysfunction in men with COPD is likely. In observational studies by Collin et al. , adults with COPD who had low free serum testosterone levels were over three times more likely to have ED than adults with COPD who did not have low testosterone levels.
Second, hypoxemia is reported as an important factor for ED in some studies  through different mechanisms, one of them is the reduction in nitric oxide (NO) synthase activity with increasing vasoconstriction , and the presence of dyspnea was found as the main reason of sexual dysfunction in COPD owing to hypoxemia. Erections are hemodynamic events caused by penile arteries dilatation and smooth muscle fiber relaxation, which are the results of neurological, neurochemical, and endocrine mechanisms. The relaxation of smooth muscles of corpus cavernosum is because of a nonadrenergic–noncholinergic nervous system mediated by NO. NO is a gas that diffuses into target tissues, where it activates guanylate cyclase and catalyzes the formation of cGMP from GTP. cGMP initiates a cascade of intracellular events and reduces intracellular calcium, which leads to relaxation of penis smooth muscles . NO synthesis is mediated by NO synthase, which requires both l-arginine and O2 as substrates. O2 is involved in penis erection mechanism through regulation of NO synthesis in the corpus cavernosum tissue. Hypoxia causes a major reduction of NO synthase activity. This suggests that O2 can be a rate-limiting factor for NO production in the penile corpus cavernosum . In addition, chronic hypoxia is an important risk associated with pathological conditions, including ED. Recent trials have shown that inadequate oxygen supply impairs nitric oxide synthesis, which subsequently reduces the functional integrity of penile smooth muscles ,. It has been suggested that ED in COPD may be due to persistent exposure to a hypoxic environment .
Similar to the studies by Kahraman et al. , Turan et al. , and Hasan et al. , we demonstrated that patients with COPD with ED had statistically lower O2 levels, with a strong positive significant correlation between hypoxemia and ED score in the patients with COPD (R=0.352, P<0.05), which show that hypoxemia may play a key role in the etiology of ED in COPD.
The second mechanism of hypoxemia to induce ED is decreased level of testosterone. Low levels of testosterone were demonstrated in hypoxemic patients with COPD, and the changes were correlated with the degree of hypoxemia ,, as hypoxemia suppressed the hypothalamic–pituitary–testicular axis . In the present study, serum testosterone (total and free) levels of patients with COPD were found to be lower than that of the control group, with a significant correlation serum androgen and ED score.
These results are in agreement with Kahraman et al.  who showed higher levels of FSH and LH, whereas testosterone level was significantly lower in the COPD group.
Another factor leading to the sexual problems secondary to hypoxemia is the reduction of exercise capacity, dyspnea, and general physical deconditioning. This can also be a reason for issues with sexual functioning ,,. This corresponds with our result, as there was a significant reduction in 6-MWT values in patients with COPD (P<0.05), with a positive significant correlation between 6-MWT and ED score. These findings are compatible with the results of Hasan et al. and Daabis et al. who found that 6-MWT values were significantly decreased in patients with COPD (P<0.05) ,. In addition, testosterone contributes to muscle mass and the body’s response to exercise and is also directly associated with sexual functioning in men . So, low level of testosterone affects the ED by deferent mechanisms. Fletcher and Martin  specified that decreasing functional capacity is positively correlated with sexual dysfunctions. Moreover, Koseoglu et al.  reported that ED severity increased with increasing COPD severity, representing low functional capacity.
Third, respiratory or general symptoms of COPD could also contribute to sexual dysfunction by somatophysical effects. Dyspnea, cough, muscular weakness, and the associated reduction of physical activity can directly influence sexual activity in patients with COPD ,.
In the present study, correlation analyses showed a significant positive correlation between IIEF-5 and FEV1%, FVC%, PEF%, PaO2, SO2, and 6-MWT, which means that the severity of sexual dysfunction is increased with the increased severity of COPD, indicated by the decline in FEV1, PaO2, and SO2 and the deterioration in the 6-MWT parameters. Furthermore, we reported severe ED in 62.5% of patients with very severe COPD. These results show the importance of examining sexual dysfunction in male patients with COPD, especially in the very severe COPD subgroup.
In addition to physiological consequences of lung disease, COPD is also associated with psychological and sociological responses which can negatively influence sexual interest, arousal, and behavior. Collins et al. , for instance, suggested that physical limitations arising from COPD may make men take a much more passive approach to sexuality or to avoid sexual activity altogether.
In patients with COPD, fear of dyspnea and reduced exercise tolerance may limit the sexual activity of patients . Besides, misconceptions, ignorance, and poor physical or psychological health are common in this patient population and contribute to sexual dysfunction .
Another risk factor for ED in COPD is found to be smoking. Our study showed a negative correlation between the IIEF score and smoking amount (pack-years). Smoking was found to be an independent correlation for ED in COPD . Thus, smoking cessation may reduce the chance of developing ED. This result is in accordance with Turan et al. , who reported a negative correlation between the IIEF score and smoking amount.
| Conclusion|| |
Sexual dysfunction is a frequent problem in patients with COPD. Hypoxemia, aging, smoking, and the limitation of physical activity are thought to be the mechanisms associated with ED in COPD. The severity of ED correlated with the severity of physical limitation determined by the deterioration of the 6-MWT and by the severity of decline in the FEV1. It is vital for a medical practitioner to question the sexual functions in patients with COPD. Smoking cessation, increased physical activities, and prevention of hypoxemia may help sexual functions.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]