Erectile and sexual dysfunction in male and female patients with celiac disease: A cross‐sectional observational study

Abstract Introduction Sexual function is often impaired in patients with chronic illnesses. Several patients with chronic gastrointestinal and liver disorders have been shown to suffer from sexual dysfunction, and celiac disease is a highly prevalent gastroenterological disorder. Aim The aim of this study was to investigate the sexual function incidence and the risk factors for sexual dysfunction in both male and female celiac disease patients. Methods Two hundred and eighty‐four patients (170 females, 114 males) participated in this cross‐sectional observational study in an anonymous manner. Female sexual function was assessed through the Female Sexual Function Index questionnaire. Male sexual function was assessed through the International Index of Erectile Function‐5 questionnaire. Clinical‐demographic variables were recorded. We investigated differences in the patient‐reported outcomes among the different subgroups and whether there were clinical‐demographic predictors of sexual dysfunction in our setting. Main outcome measures Prevalence and assessment of sexual dysfunction in celiac disease patients. Results In the female group, 85 subjects (50%) had a total score compatible with sexual dysfunction: 43 (61.42%) showed low desire, 79 (46.47%) showed arousal disorder, 66 (38.82%) lubrication disorder, and 84 (49.41%) inability of obtaining an orgasm. Also, a large proportion of our female patients, 161 (94.70%), showed sexual discomfort during intercourse. In the male group, 79 patients (62.2%) showed scores compatible with normal erectile function, eight (7.01%) had mild erectile dysfunction, 24 (21.05%) mild to moderate erectile dysfunction, and three (2.63%) presented severe erectile dysfunction. Altered body mass index was significantly associated with sexual dysfunction both in male and female patients. Early age at diagnosis was a significant predictor of sexual dysfunction in male celiac disease patients. Conclusions A significant proportion of celiac disease patients present sexual dysfunction. Early age at diagnosis and high body mass index seem to predict sexual dysfunction in this clinical setting. Assessment of sexual function should be part of the initial evaluation of celiac disease patients in order to establish a prompt diagnosis and early treatment.

Conclusions: A significant proportion of celiac disease patients present sexual dysfunction. Early age at diagnosis and high body mass index seem to predict sexual dysfunction in this clinical setting. Assessment of sexual function should be part of the initial evaluation of celiac disease patients in order to establish a prompt diagnosis and early treatment.

K E Y W O R D S
celiac disease, FSFI, IIEF-5, sexual dysfunction

INTRODUCTION
Sexual dysfunctions (SD) are the most prevalent psychological disorder in the general population. The prevalence of SD in women varies from 40% to 50% irrespective of age. 1 In contrast prevalence of erectile dysfunction (ED) in men largely depends on age, ranging from 1% to 10% in those younger than 40 years, from 2% to 15% in those from 40 to 49 years, and from 20% to 40% in those between 60 and 69 years. 1 Mounting evidence indicates that a number of patients with chronic gastrointestinal and hepatic disorders may suffer from SD with a significant alteration of their quality of life. 2 According to the Diagnostic and Statistical Manual of Mental Disorder (DSM-V), SD are classified into four major categories which include, overall, disorders of sexual desire, arousal, orgasm, and sexual pain. 3 In males, the most prevalent disorder is related to ED followed by premature ejaculation, whereas in women dyspareunia, that is, pain during sexual intercourse, and hypoactive desire represent the most common sexual disorders. 4,5 The etiopathogenesis of SD is widely multifactorial and includes physiological, anatomical, and socio-cultural differences. 6 The pathogenesis of SD in chronic gastrointestinal disorders is multifactorial and may be contributed to by psychological problems, chronic inflammation with endothelial dysfunction, endocrine disturbance, or drug-related factors. 7 Evidence shows that untreated celiac disease (CD) patients had a significantly lower frequency of intercourse and an overall lower satisfaction regarding their sexual life, which drastically improve after gluten-free diet. 8 However, there are no studies that have systematically evaluated sexual function in CD patients using well-established questionnaires.
Therefore, this observational cross-sectional study was designed to assess sexual function in CD patients through validated questionnaires exploring female and male sexual activity. As secondary endpoints, the role of a number of clinical-demographic variables in the sexual function score of CD patients was established.

Study design and population
We conducted a cross-sectional observational study at the out-

Sexual dysfunction assessment in female patients
Female patients were given the Female Sexual Function Index (FSFI) questionnaire, a widely validated questionnaire used in clinical practice. 9,10 This questionnaire consists of 19 questions, each being part of a domain. It explores sexual desire (questions 1 and 2), sexual arousal (questions 3-6), lubrication (questions 7-10), orgasm (questions 11-13), sexual satisfaction (questions [14][15][16], and pain associated with sexual activity (questions [17][18][19]. Each domain has a minimum score (0 or 1.2) to a maximum score of 6. Each domain score is multiplied by a multiplier, resulting in a domain subscore. All subscores are summed to obtain the final score. The lower the total score, therefore, the less the impairment of female sexual function. The cutoff considered in order to detect female SD was ≤23.45. 11

Erectile dysfunction assessment in male patients
Male patients were administered the International Index of Erectile Function-5 (IIEF-5) questionnaire. 12,13 The questionnaire explores five

Analysis
Continuous variables were expressed as median (interquartile range) and ordinal variables, expressed as numerosity (percentage of total).
We proceeded to check the normality of distribution of the vari-

Baseline characteristics
The baseline characteristics of our cohort of 170 females (59.9%) and 114 males (40.1%) patients are illustrated in Table 1.

Sexual function in female patients
The median FSFI score in our population of 170 female patients with CD was 23.5 (9.8-25.2) ( We also assessed whether the serum level of anti-transglutaminase antibodies had any influence on FSFI score and found no correlation (data not shown).

Sexual function in male patients
In our sample of 114 male participants, the general male sexual function median score, assessed as IIEF-5 score, was 23 (20-25) ( Table 3).
We found that pleasure-related scores during sexual activity were significantly higher in nonsmokers or ex-smokers compared with smokers (p = 0.001).

As shown in
A summary of sexual function scores as assessed by FSFI and IIEF-5 scores, according to BMI class and age, is reported in Figures 1 and 2.
Regarding the results of multivariate logistic regression analysis in the male group, we observed that neither age (p = 0. We also assessed whether the serum level of anti-transglutaminase antibodies had any influence on IIEF-5 score and found no correlation (data not shown).

DISCUSSION
This cross-selection observational study demonstrates that SD have a high incidence in CD patients. Half of our female patients reported an FSFI score suggestive for SD and complained of some kind of symptom related to their sexual life, including decreased desire, altered arousal or lubrication, difficulty in attaining orgasm, or some degree of discomfort at intercourse. In the male population, almost 70% of patients did not report any SD. The remaining 30% had some degree of ED that was mild to moderate in the majority of cases.
A normal sexual function is widely recognized as an important determinant of quality of life. This is often impaired in both males and females, with prevalence in the general population of 40%-50% in women independent of age and of 1%-10% in men younger than 40 years, 2%-15% in those from 40 to 49 years, and 20%-40% in those between 60 and 69 years and 43%, respectively. 1,15,16 SD are defined (according to the DSM-V) into four major categories (overall, disorders of sexual desire, arousal, orgasm and sexual pain). 3 In males, the most prevalent disorder is related to ED followed by premature ejaculation, whereas in women dyspareunia, that is, pain during sexual intercourse, and hypoactive desire represents the most common sexual disorders. 4,5 The etiopathogenesis of SD is widely multifactorial and includes physiological, anatomical, and socio-cultural differences. 6 It is well-known that several immune-mediated diseases could further affect sexual activity, both directly and indirectly, acting via medications and on body-image perceptions and desires. 15,16 Mounting evidence indicates that a number of chronic diseases may be associated with some degree of SD. 17 A number of patients with chronic gastroin-testinal and hepatic disorders have been demonstrated to suffer from SD with a significant alteration of their quality of life. 2 The pathogenesis of SD in chronic gastrointestinal disorders is multifactorial and may be contributed by psychological problems, chronic inflammation, endothelial dysfunction, endocrine disturbance, and drug related.
In this regard, CD is an immunologically mediated inflammatory disorder of the small bowel common enteropathy which may be associated to a number of extraintestinal manifestations involving different organs. 2 SD in CD patients might be contributed to by specific nutritional deficiencies because of the malabsorption and/or endocrine dysfunction such as androgen resistance or hyperprolactinemia. 18 Indeed, in untreated CD patients, the lack of conversion of testosterone to dihydrotestosterone has been demonstrated, because of a  26 showed that improving lifestyle in patients with obesity and infertility was associated, within 6 months, with increased sexual intercourse, improved vaginal lubrication as well as improved overall sexual function. On the other side, use of antianxiety or antidepressant drugs did not seem to be associated with altered sexual function in our female CD population.
In addition, as expressed in Section 3, we observed particularly low FSFI scores in the female population with no sexual partners. While this questionnaire should be prioritized toward a population that had or has sexual activity, it is also true that, given the non-negligible prevalence of SD that we observed in our CD population, CD could probably represent a barrier in the search for a sexual partner.
In the male CD population, we did not find any correlation with comorbidities. The only variables that were significantly associated to some degree of ED or worsened pleasure scores were bloating, self-employment, and active or previous smoking. Similarly, increasing age, early age at diagnosis, and high BMI significantly correlated with altered sexual function in male CD patients, even though, at multivariate analysis, these variables were not predictors of SD.
The present study presents different limitations. Firstly, because of its non-longitudinal nature, we do not have any data regarding SD prior to or after starting a gluten-free diet. Second, we did not have enough data to correlate SD to the degree of intestinal damage, as assessed by the Marsh-Oberhuber and Corazza-Villanacci scores. 27 Therefore, we cannot draw any conclusion whether the degree of intestinal damage at the diagnosis had a significant influence on the degree of SD.
Finally, our gender assessment did not fully explore sexual preference as well as the possible presence of nonbinary gender patients.

CONCLUSION
Our study demonstrates that the use of validated questionnaires may be useful for the assessment of sexual dysfunction in celiac disease patients. In this clinical setting, both female and male celiac disease patients show some degree of sexual dysfunction and this was more prevalent in females. Scores evaluating sexual pleasure, arousal, and dyspareunia in women and erectile dysfunction in men are the ones that are mainly impaired. Based on this study, we postulate that evaluation of sexual function through validated questionnaires should be part of the initial clinical assessment in celiac disease patients, in order to promptly identify symptoms of sexual dysfunction and start an early and appropriate therapeutic intervention.