Predictors of erectile dysfunction among male patients with idiopathic interstitial pneumonias

Background Sexual dysfunction is a neglected area among patients with idiopathic interstitial pneumonias (IIPs). Hence, the aim of this study is to identify the prevalence of erectile dysfunction (ED) and its predictors in male patients with IIPs. Patients and methods A total 65 male patients (45 IIPs and 20 controls) were assessed; clinical data, testosterone levels, pulmonary function tests, arterial blood gases, and self-reported questionnaires on erectile function. Results The prevalence of ED was 66.7 and 11.1% of them presented with severe ED. The mean age of the patients was 33.4±5.9 years. Of the patients, 60% were smokers and 17.8% were nonsmokers. Regarding comorbid manifestations, 26.7% was hypertensive, 51.1% had diabetes mellitus, 42.2% with dyslipidemia, and 17.8% had ischemic heart disease. The mean duration since the diagnosis of IIPs was 7.46±2.77 years, whereas the mean time since evolution of ED was 2.17±1.3 years. A significant decrease in mean arterial oxygen tension (PaO2) and oxygen saturation (SaO2) were observed in the IIPs group. Also, the mean diffusion lung capacity for carbon monoxide (DLCO%) and testosterone level were decreased. A significant decrease in testosterone level among patients with severe diffusion defect was observed (P=0.000). The most predictors for ED were PaO2 (≤60 mmHg), SaO2 (≤88%), and DLCO≤60%. Conclusion ED is a common problem in patients with IIPs. Thus, physicians should keep in mind that IIPs patients need a comprehensive sexual evaluation. This is the first study to report that low PaO2, SaO2, and DLCO≤60% were the predictor risk factors.


Introduction
Idiopathic interstitial pneumonias (IIPs) are heterogeneous diffuse parenchymal lung disorders of unknown etiology characterized by inflammation and/ or fibrosis of pulmonary parenchyma. Idiopathic pulmonary fibrosis (IPF) is the most common and severe form of IIP accounting for up to 65%. Other less common entities include nonspecific interstitial pneumonia (IP), desquamative IP, and cryptogenic organizing pneumonia [1].
According to the WHO, sexual health is a state of physical, emotional, mental, and social well-being in relation to sexuality. This means that sexual health has to be seen from a holistic perspective, including physical, psychological, and social aspects of wellbeing. Sexuality is an important aspect of quality of life that is usually neglected in research studies. In clinical practice, the physicians almost focus on fertility, pregnancy, or contraception, whereas sexual function is not addressed [2].
By definition, erectile dysfunction (ED) is a permanent insufficiency in achieving an adequate erection to have a satisfactory sexual life [3]. Decreased testosterone levels are responsible for loss of sexual desire and function, in addition to the aging process that have led to a decrease in libido and erectile function in men [4,5]. Low testosterone level and ED have been reported among men with chronic pulmonary diseases. The presence of clinical manifestations such as dyspnea, chronic cough, muscle weakness, and diminished physical activity are all major factors for decreased sexual activity [6,7]. In fact, physicians generally ignore sexual dysfunction during their evaluation which is considered a significant comorbidity. Thus, still this topic is a neglected area of research and discussion. The aim of this study is to highlight and draw attention to this important issue.
The purpose of this study was to address the predictors and frequency of ED in patients with IIPs.  [1,8].

Patients and methods
An informed consent was obtained from the patients. The study was approved by the Faculty of Medicine Ethics Committee.

Inclusion criteria
The selection criteria include all patients who were recruited to the Chest Department and diagnosed as IIPs were selected for the analysis. Baseline highresolution computed tomography scans were evaluated in all patients according to guidelines [1,8].

Exclusion criteria
(1) Patients with occupational form of interstitial lung disease (ILD), sarcoidosis, and collagen vascular disease associated ILD. (2) Patients who use medication that may interfere with serum testosterone hormone levels (such as sildenafil and other oral agents for ED). (3) Patients with malignancy, significant renal, hepatic, metabolic, or endocrine disturbances or neurological diseases were excluded.
All patients were subjected to the following: (  [11]. (5) Serum total testosterone. A measure of 2 ml venous blood samples was obtained from all patients to measure total testosterone levels. The serum levels of testosterone was measured by chemiluminescent enzyme-labeled immunoassay using Immulite 1000. Total testosterone kit from Siemens 06603687, cat LKTW1 was used [12].

Statistical analysis
The statistical package for the social sciences (SPSS, version 16; SPSS Inc., Chicago, Illinois, USA) software was used to evaluate the data. The results were presented as mean±SD and frequency tables. For comparisons between the two groups, the significance test for the difference between two means (Student's ttest), and for the categorical comparisons, the χ 2 -tests were used. A P value of less than 0.05 was considered of statistical significance.

Results
Of the 65 male participants enrolled, 45 male patients with IIPs and 20 were volunteers. Sociodemographic characteristics of all patients are presented in Table 1.
The mean age and BMI were 33.4±5.9 years and 24.4 ±3.34 kg/m 2 . No significant differences were observed regarding age and BMI when compared with the control group; 75.6% of patients with IIPs had children, whereas 24.4% of them were having no children. The IIPs group consisted of patients with a history of smoking; 60% were current smokers, 22.2% were former smokers, and 17.8% were nonsmokers. The mean duration since diagnosis of IIPs was 7.46 ±2.77 years; in contrast, the mean time since evolution of ED was 2.17±1.3 years. Regarding the presence of comorbid manifestation, this study demonstrated that 26.7% were hypertensive, 51.1% had diabetes mellitus, 42.2% with dyslipidemia, and finally 17.8% of patients presented with ischemic heart disease. In the IIPs group, total testosterone level was significantly decreased (5.53 ± 1.47 vs. 7.31 ± 1.35 ng/dl) ( Table 1).
Arterial blood gases showed that mean PaO 2 and mean oxygen saturation (SaO 2 ) decreased in the IIPs group.
Moreover, we demonstrated that pulmonary function along with mean DLCO% values in the IIPs group were lower 51.9±17.06% (Table 2).
Using the IIEF-5, this study demonstrated that the prevalence of ED in male patients with IIPs was 66.7%, defined as a score of less than 22. Patients with IIPs had various degrees of ED, 26.7% of them had mild ED; in contrast, 11.1% had severe ED (Table 3).
On comparing total testosterone level with severity of diffusion, a statistically significant decrease in total testosterone level among patients with severe diffusion defect was observed (P=0.000) ( Table 4).

Figure 3
Positive correlation between total testosterone level and diffusion lung capacity for carbon monoxide (DLCO%) (r=0.828, P=0.000).   dyslipidemia, and ischemic heart disease were not considered as predictors of ED.

Discussion
IP is not only a pulmonary limited disease but also a chronic illness, which presents with diverse behavior and comorbidities. The presence of comorbidities such as infection, gastroesophageal reflux, pulmonary hypertension, lung cancer, cardiovascular diseases, and obstructive sleep apnea can develop at any time during the course of the disease and, if unidentified and untreated may impair the quality of life, and ultimately impact on disease progression [13]. Obvious sexual dysfunctions such as ED are not included as one of comorbidities among male patients with IIPs that may cause disruption in their natural daily life [14]. Hence, the purpose of this study was to spotlight on this issue as a possible comorbidity among a large proportion of male patients with IIPs and potential risk factors.
Several factors may be anticipated that it will affect sexual activity and ED including the aging process and generally poor health. Also, physical and psychological problems and prescribed medications can decrease sexual activity [15]. Dunn et al. [16] reported that 34% of the general population had sexual problems and ED was the most common sexual disorder. Another study showed that the prevalence of ED increases with age [17].
In our study, we demonstrated that the overall prevalence of ED among male patients with IPs was 66.7%. We evaluated the severity of ED and found that 26.7 had mild and 11.1% had severe ED. Similarly, a recent study by Floe et al. [18] studied the prevalence of ED among 89 patients with IPF and reported that 70% of patients had ED and 44% of them had severe ED. Furthermore, Kahraman et al. [19] investigated the incidence of ED and the factors affecting its frequency in chronic obstructive pulmonary disease patients and reported that 55 (78.6%) of the chronic obstructive pulmonary disease patients had various degrees of ED.
The endocrine function plays a significant role in the regulation of erectile function. Several studies demonstrated that a proper endocrine milieu is necessary: Any alteration of one or more sex hormones can cause ED. Therefore, testosterone is considered as a key factor in sexual function [20]. This study reported a significant decrease in testosterone level among the IIPs group when compared with the control group. Also, a significant decline in hormone level with increase in severity of diffusion defect was observed.
The high prevalence of ED could be explained by the fact that sexual activity causes an increase in cardiopulmonary load. Thus, energy spent during orgasm is equal to the energy required for walking. Therefore, both decreased exercise tolerance and fear of dyspnea may limit sexual activity [7]. In addition, misperceptions, ignorance, and poor physical or psychological status as common factors may contribute to sexual dysfunction [21]. Previous studies have reported that more severe disease has a higher prevalence of ED [5,22].
A significantly lower mean PaO 2 and SaO 2 was observed among male patients with IIPs. Low level of SaO 2 is considered as another contributing factor for ED among those patients. A study conducted by Semple et al. [3] demonstrated that seven out of 10 hypoxemic patients with chronic pulmonary disease had no morning erection. Moreover, oxygen therapy had a role in improving sexual dysfunction. Hence, our findings support the fact that as hypoxia increases, the incidence of ED rises.
Furthermore, our results showed a positive correlation between testosterone levels and PaO 2 and SaO 2 . Likewise, a positive correlation was found between testosterone level and DLCO%. These findings were consistent with Karadag et al. [23]. We demonstrated that most predictors for ED among male patients with IIPs were PaO 2 (≤60 mmHg), SaO 2 (≤88%), and DLCO≤60%.
The major strengths of our study were the analysis of multiple clinical characteristics and comorbidities and the use of an international and valid questionnaire to determine the prevalence and severity of ED (IIEF-5). Second, we measured the sexual hormone level.

Conclusion
Sexuality and sexual dysfunction in patients with IIPs are often overlooked by the medical personnel. Of the patients studied, 66.7% of patients had ED. The most predictors for ED among male patients with IIPs were PaO 2 (≤60 mmHg), SaO 2 (≤88%), and DLCO≤60%. Thus, the physicians should keep in mind that patients with chronic fibrosing pneumonia need a comprehensive evaluation, including their sexual life.
All authors participated in the conception and design of the study. Also, they participated in data collection and statistical analysis and interpretation of data and have drafted the submitted article and revised it critically for important intellectual content. They participated in the final approval of the version to be submitted.

Financial support and sponsorship
Nil.

Conflicts of interest
There are no conflicts of interest.