http://orcid.org/0000-0002-7854-0133
Abstract
Objective: This study aims to investigate the effect of smoking on sexual functions in AS patients.
Patients and methods: A total of 67 male AS patients with a median age of 34 years (range: 18–57) reporting sexual activity at least for the past 4 weeks period were included. Patients were divided into smokers (Group 1, n = 47) and non-smokers (Group 2, n = 20). Fagerström test for nicotine dependence, smoking history, exhaled carbon monoxide test were recorded for smoking AS patients. Visual analogue scale (VAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Quality of Life (ASQoL), International Index of Erectile Function (IIEF), Beck Depression Inventory (BDI) were filled for both groups.
Results: There was no significant difference between smokers and non-smokers in all evaluation parameters. BASMI scores were significantly lower in the mild dependency subgroup as compared to those with moderate or severe dependency (p = .005 and p = .007, respectively). Total IIEF score and IIEF categories correlated significantly with BASDAI, BASFI, BASMI, ASQoL, pain, fatigue, and cumulative smoking. BDI showed an inverse correlation with the IIEF score and IIEF category (p < .001 r = –0.520, p < .001 r = –0.508, respectively).
Conclusions: Sexual function in AS patients is associated with the pain, fatigue, disease activity, functional status, quality of life, depression as well as the cumulative exposure to smoking, and that sexual functions tend to decline with increasing degree of cigarette dependency.
Introduction
Ankylosing spondylitis (AS) is a chronic, inflammatory disorder mainly involving the sacroiliac joints and the spine [Citation1], and occurring in younger males [Citation2,Citation3]. AS may adversely affect the quality of life (QoL) through pain, fatigue, stiffness, and loss of spinal mobility [Citation4].
QoL is a subjective measure that may be influenced by a variety of causes [Citation5], and sexual functions represent an important component of QoL [Citation6–8]. Previous studies have suggested that sexual functions may be adversely affected in rheumatoid disorders both due to disease-related factors and medical treatment [Citation9]. Studies on the effect of AS on sexual functions are scarce, with conflicting results, some reporting no difference between AS patients and healthy controls [Citation10,Citation11], while others reporting sexual dysfunction due to erectile dysfunction (ED) and reduced libido [Citation12–14].
ED is a disorder of multi-factorial aetiology that can have a negative impact on QoL and that is thought to arise from a complex interplay between organic or psychogenic factors. The reported prevalence of ED in men between 40 and 70 years of age is 52% [Citation15]. Aging, chronic diseases, cardiovascular disorders, and hyperlipidaemia have been reported as important risk factors for ED [Citation16,Citation17]. Smoking is also the most important risk factor defined for ED. Cigarette smoking is thought to result in ED through causing peripheral arterial disease [Citation18,Citation19].
In the same time, cigarette smoking is one of the most important risk factors for rheumatic diseases [Citation20]. So far, there have been many studies investigating the effect of smoking on illness in AS [Citation21–24]. Cigarette smoking is not only thought to play a role in the progression of AS, but also in its development. Our review of literature has revealed a scarcity of data on the effect of cigarette smoking on sexual functions in patients with AS. Thus, in the light of these data, we decided to examine the effect of cigarette smoking on sexual functions in AS patients.
Patients and methods
A prospective, observational study was planned and the study protocol was approved by the local ethics committee (2011-KAEK-25 2016/12-06). A total of 67 male AS patients with a median age of 34 years (range: 18–57) reporting sexual activity at least for the past 4 weeks period were included. Exclusion criteria included the presence of significant neurological or endocrinological disorders; systemic conditions such as hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and renal failure; use of antidepressants; mental retardation; severe arthritis; age <18 or >65; absence of sexual partners or marital status; and use of prosthetic devices. All patients were given information on the purpose of the study and signed the written informed consent document.
Patients were divided into smokers (Group 1, n = 47) and non-smokers (Group 2, n = 20). Patients with no smoking history or abstinence from smoking at least for one year were included in Group 2, while those who quit smoking earlier than 1 year ago were excluded from the study.
Evaluation parameters
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
The discomfort experienced by the patient in terms of fatigue, axial pain, peripheral pain, morning stiffness, discomfort upon touch and pressure, and the general discomfort due to the disease are marked on a 10-cm horizontal visual analogue scale (VAS) by the patient. The total BASDAI score ranges between 0 and 10 [Citation25].
Bath Ankylosing Spondylitis Metrology Index (BASMI)
Five simple clinical measurements best reflecting the axial status are performed including the cervical rotation, tragus-wall distance, lateral flexion, modified Schober and intermalleolar distance. For each measurement, a total transformed score is calculated, with a total score range between 5 and 15. Lower scores reflect better disease status [Citation26].
Bath Ankylosing Spondylitis Functional Index (BASFI)
It is a 10-question measurement scale used to determine the extent of functional disability in AS patients. A respond to each question is marked on a 10-cm horizontal VAS, the average of which gives the BASFI score (range: 0–10) [Citation27].
Ankylosing Spondylitis Quality of Life (ASQoL)
It is an 18-item scale with a “yes or no” type of response to each question. The total number of “yes” responses yields the total score. It is a reliable and validated measure [Citation28].
Pain and fatigue
These were assessed using a VAS, and patients were asked to rate their symptoms on a 10-cm horizontal scale between 0 (none) and 10 (intractable).
Assessment of the psychological status
Beck Depression Inventory (BDI) was used for this purpose [Citation29].
Daily number of cigarettes and cumulative smoking history (pack-year)
A pack-year is 20 cigarettes smoked/day for one year. It is calculated by multiplying the number of years the person has smoked by the number of packs of cigarettes [Citation30].
Fagerström Test for Nicotine Dependence (FTND)
This is a standard tool for assessing nicotine dependence consisting of six questions regarding cigarette smoking. The dependency is calculated in a scale range between 1 and 10 points [Citation31]. Patients are categorised into subgroups of mild dependency (1–4 points), moderate dependency (5–7 points), and severe dependency (8–10 points).
Carbon-monoxide in exhaled air (Exh. CO)
A PICO Smokerlyzer (piCO + smokerlyzer Bedfont Micro Breathalyser, Kent, UK, 2015) device was used for quantification using “parts per million” (ppm) units [Citation32].
International Index of Erectile Function (IIEF-5) [Citation33]
Erectile dysfunction was classified into five categories based on the scores: severe (5–7), moderate (8–11), mild to moderate (12–16), mild (17–21), and no ED (22–25). Both scores and the corresponding categories were recorded.
Statistical analysis
Statistical Package for Social Sciences (SPSS) (IBM Corp., Released 2015, IBM SPSS Statistics for Windows, Version 23.0, Armonk, NY) was used for data analysis. Numerical values were expressed by the median (med) and minimum–maximum values (min–max), and their distribution was tested with the Kolmogorov–Smirnov test. Categorical values were evaluated with percentages. Median values in smokers and non-smokers were compared using the Mann–Whitney U test. The median values in subgroups of mild–moderate, and severe dependency based on FTND were assessed with the Kruskal–Wallis test. Then, the Mann–Whitney U test was re-utilized for values with statistical significance. The chi-square test was used for the comparison of percentages, while Spearman’s correlation test was used for the evaluation of dependency. For statistical significance, the p value was set at a level of less than .05.
Results
The mean age of the 67 AS patients included in the study was 35 ± 9.3 years, and the median body mass index was 24 kg/m2 (range: 17.3–33.5 kg/m2). The median time of onset of disease symptoms was 120 months (range: 12–444 months). Cigarette smokers comprised 70% of the patients (n = 47). The average cigarette consumption was 20/day (3–60), the cumulative consumption of cigarettes was 15 (1–60) pack/year, median FTND score was 6 (1–10), median Exh. CO was 14 (2–24) ppm. shows the clinical and demographic characteristics of the patients.
Table 1. Clinical, demographic, and psychological characteristics and IIEF scores of AS patients.
There were no differences between smokers (Group 1, n = 47) and non-smokers (Group 2, n = 20) with regard to BMI, duration of disease, pain, fatigue, BASDAI, BASFI, BASMI, ASQoL, NSAID-DMARD-anti TNF use, IIEF, and BDI (p > .05) ().
Table 2. Comparison of clinical, demographic, psychological, and sexual functions in smoker (Group 1) and non-smoker (Group 2) AS patients.
A comparison of the median values in subgroups with mild, moderate, and severe dependency showed no significant differences in pain (VAS), fatigue (VAS), BASDAI, BASFI, ASQoL, and IIEF scores, while BASMI scores () were significantly lower in the mild dependency subgroup as compared to those with moderate or severe dependency (p = .005 and p = .007, respectively). However, there was no statistically significant difference between moderate and severe dependency (p = .58) ().
Table 3. Disease parameters and comparison of IIEF scores according to the severity of dependency.
Table 4. Comparison of BASMI scores in smoker AS patients according to dependency category.
Total IIEF score and IIEF categories correlated significantly with BASDAI, BASFI, BASMI, ASQoL, pain (VAS), fatigue (VAS), and cumulative smoking (). BDI showed an inverse correlation with the IIEF score and IIEF category (p < .001 r = –0.520, p < .001 r = –0.508, respectively).
Table 5. Association between IIEF scores and clinical and psychological parameters, intensity of smoking and dependency level in AS patients.
Discussion
Our results showed a significant negative correlation between erectile function and pain, fatigue, disease activity, functional status, physical mobility, disease related QoL, depression, and cumulative smoking in male patients with AS. Also, increasing levels of cigarette dependency were associated with a parallel increase in BASMI scores and a worsening in sexual function.
The casual link between cigarette smoking and ED involves a number of pathophysiological, biochemical, and clinical mechanisms. Smoking leads to vascular endothelial injury via reduced endothelial nitric oxide activity and reduces vaso-relaxation. Furthermore, it results in an imbalance of oxidative and anti-oxidative mechanisms, increasing the production of pro-inflammatory cytokines such as IL-1 β, IL-6, and TNF-α. The clinical consequence of this process is the vasospasm of the penile arteries and severe atherosclerosis caused by the impaired arterial blood flow [Citation34]. In another study, it was emphasised that, low testosterone levels may be associated with atherosclerosis and ED [Citation35].
Until now, numerous studies have examined the association between ED and smoking in normal populations, while our literature review did not reveal much published evidence regarding the association between ED and the intensity of cigarette consumption and dependency in AS patients. According to our results, IIEF scores were negatively correlated with the cumulative dose of smoking in AS patients. However, there was no correlation between IIEF scores and smoking status as well as dependency. In a recent study, current smoking status was found to be associated with ED in AS patients [Citation8]. In another study examining a sample from the normal population showed a link between smoking and ED, with increased risk with increasing doses of smoking [Citation36]. He et al. found a link between smoking and ED risk (without clinical vascular disease), showing a higher risk in smokers than in non-smokers [Citation37]. On the other hand, Chew et al. proposed an explanation for the association between heavy smoking, ED, and cardiovascular disorder [Citation38].
A higher prevalence of ED was found among smokers as compared to non-smokers in the normal population and increasing cigarette exposure was associated with increasing risk levels in the study by Millett et al. [Citation39]. However, in the current study, we failed to detect meaningful differences between smokers and non-smokers in terms of disease parameters, psychological status, and IIEF scores. A study comparing current smokers (>10 cigarettes/day) with ex-smokers and non-smokers, the former group of individuals were found to have a higher risk of ED [Citation40,Citation41]. In this study, ex-smokers were regarded as “non-smokers” according to the protocol, which might have an impact on our results. Also, small sample size may also account for some of the results observed.
Among our participants, those with higher degree of dependency were found to have higher BASMI scores. Also, IIEF scores tended to decline with increasing dependency. Previous studies showed that smoking and the intensity of smoking were associated with accelerated radiographic progression and a negative effect on physical mobility [Citation22,Citation25]. Furthermore, increased BASMI scores has been shown as one of the reasons for sexual dysfunction in AS patients [Citation10,Citation42,Citation43]. Our findings also suggest that smoking may also cause an increase in BASMI scores and with a resultant decrease in IIEF scores.
Despite some studies reporting similar prevalence of ED in AS patients and healthy controls [Citation10], majority of the evidence indicates higher occurrence of sexual dysfunction in this group of patients as compared to healthy populations [Citation13,Citation43–46]. Fatigue and pain have been proposed to have an inhibitory effect on sexual functions in patients with rheumatoid disorders [Citation47]. In line with this, several studies reported an association between the sexual dysfunction in AS and poor disease status, poor physical function, poor mobility, toxic effect of drugs used for the treatment of AS, and poor psychological status [Citation12,Citation43,Citation46,Citation48]. Similarly, according to our results there were significant correlations between BASDAI, BASFI, BASMI, pain and fatigue and IIEF score and category. Again, consistent with the reports of Sarıyıldız et al., there was a correlation between ASQoL and ED.
Earlier studies reported higher rates of depression among male AS patients than among healthy controls [Citation13,Citation45]. Also, an increased co-occurrence of psychological disorders has been reported in AS patients, in whom the psychological status may be affected by the functional limitations and clinical symptoms [Citation49]. Additionally, depression may have indirect effects on sexual functions [Citation46]. It has been reported that, the cause of depression in obese men is related to the unbalance between oestrogen and testosterone, which are sex hormones, and ED [Citation50]. Our results corroborate the previous reports by showing a significant association between IIEF scores and depression.
The most important limitations of our study are the lack of sample counts and the fact that we do not evaluate ex-smokers and include them in non-smokers. We did not categorise patients according to their smoking intensity.
In conclusion, these observations suggest that sexual function in AS patients is associated with the pain, fatigue, disease activity, functional status, QoL, depression as well as the cumulative exposure to smoking, and that sexual functions tend to decline with increasing degree of cigarette dependency. Therefore, we hold the view that smoking and dependency may be considered to represent a risk factor responsible for sexual dysfunction seen in AS patients. However, further studies with larger sample size are warranted to better elucidate this association. Also, we believe that studies examining cessation strategies for cigarette smoking may provide further insights on the effect of stopping smoking on sexual functions in AS patients.
Acknowledgements
Informed consent was obtained from all the patients.
Ethical approval was obtained from institutional research committee (2011-KAEK-25 2016/12-06) and with the 1964 Helsinki declaration and comparable ethical standards.
Disclosure statement
No potential conflict of interest was reported by the authors.
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