The Relationship between Allergic Disease and Sexual Dysfunction: A Scoping Review

Sexual dysfunction (SD) is one of the most common health issues worldwide. It has been estimated that 52% of males and 56.6% of females experience this psychosomatic illness globally [1] that leads to impaired quality of life (QoL) and increased socioeconomic burden [2‒4]. SD can be categorized into problems related to sexual desire/interest, arousal, orgasm, and sexual pain [5]. Mental illnesses, substance-use disorders, and the use of psychotropic medications are some major causes of impotence [6‒8]. In addition, there are studies that corroborate the relationships between sexual disturbance and systemic disorders, such as cardiovascular diseases [9], dementia [10], obstructive sleep apnea [11], and cancer [12]. The comorbidities of SD call for timely assessment and management for the biopsychosocial problem.

Allergic diseases, including but not limited to asthma, allergic conjunctivitis, allergic rhinitis, atopic dermatitis, and urticaria, present a wide spectrum of clinical manifestations that are mostly attributed to immunoglobulin E-mediated hypersensitivity reactions following exposure to allergens [13]. Poorer life quality, higher morbidity and mortality rates can ensue from severe illnesses [14‒16]. Moreover, psychophysiologic stress, psychiatric disorders, along with anomalous behaviors and psychogenic motives are also associated with allergic disease [17, 18]. Given its profound impact on many aspects of our lives, allergic disease remains a global health challenge demanding proper management in terms of symptomatic control and disease eradication to address associated comorbid conditions and health implications.

Since SD and allergic disease are associated with certain physiological and psychological disorders, potential mechanisms underlying both disease entities may share mutual features. To date, not many studies have focused on the link between SD and allergic disease, and the lack of synthesized data regarding the pathomechanism, associations, treatment, and clinical implications of these two important but understudied topics warrants further investigations. Therefore, we conducted this first scoping review to investigate the relationship between SD and allergic disease with the aim of providing new insights for clinicians to expedite disease evaluation and management.

This is a scoping review written based on PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation and Joanna Brigg’s Institute Reviewer’s Manual for Scoping Reviews [19, 20]. The present review was registered on the Open Science Framework (OSF) (DOI: https://doi.org/10.17605/OSF.IO/DEQUY).

A comprehensive literature search was executed in the following electronic databases: PubMed, MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science for articles published before January 15, 2023. The keywords for search were (asthma OR allergic conjunctivitis OR allergic rhinitis OR allergic disease) AND (impotence OR erectile dysfunction OR sexual dysfunction OR sexual disorder OR sexual malfunction). The references of the identified articles were also viewed for more extensive inclusion if necessary.

Studies were identified from five electronic databases. After removing duplicates, two authors (T.Y.C. and Y.C.S.) worked as a pair to screen the remaining records. During the study-screening process, any inconsistency between the investigators was resolved via discussions and consulting a third author (C.W.L.).

Available study types such as cross-sectional studies, interventional trials, and observational studies that investigated the correlation between allergic diseases and sexual malfunction were included. The evaluation of sexual malfunction should involve at least one of the following scales: Female Sexual Function Index (FSFI) and International Index of Erectile Function (IIEF-5) because both scales served as the most commonly used clinical tool to evaluate SD, which could facilitate data synthesis and interpretation. Other scales such as Arizona Sexual Experiences Scale (ASEX) [21], sex hormone levels [22], generic health-related QoL [23], Respiratory Experiences with Sexuality Profile, and Intimate Physical Contact Scales [24] were also reported if included in the individual study for comparisons. We also excluded case reports, case series, commentaries, letters, conference abstracts, review articles, meta-analyses, book chapters, studies published in languages other than English, and studies performed on animals.

The data were mainly extracted with Excel spreadsheet recordings by our authors (Y.C.S.) and were cross-examined by the other two authors (T.Y.C. and C.W.L.). Data that were excerpted from the articles included the title of the article, author, country of the study, year of publication, study design, sample size, age of the subjects, disease samples involved, and scores of FSFI and IIEF.

Risk of bias and quality of evidence of the articles were assessed by two authors (T.Y.C. and Y.C.S.) working independently. Cochrane risk of bias tool [25] was adopted to examine the risk of bias, while the quality of evidence was evaluated with the aid of Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines [26].

Narrative synthesis of the included studies was performed due to the nature of the scoping review with less comparable data based on the individual allergic disease. Features such as country of the study, study designs, the involved diseases, populations, and main findings of interest were enlisted.

The results of the literature selection are shown in Figure 1. The search strategy yielded 2,178 records. The titles and abstracts of 1,641 records were scrutinized for evaluation of relevance after the removal of 537 duplicates. Among all, 1,608 articles were eliminated due to irrelevant titles and abstracts. Thirty-three studies received further assessment of eligibility. Of all the studies, 21 studies were excluded because of the lack of outcomes of interest, inappropriate article type, and unrelated content. Eventually, 12 full-text articles were included for further analysis.

The characteristics of the 12 studies are presented as Table 1. All of the retrieved studies were observational type: seven of them were cross-sectional studies, three of them could be classified as case-control studies, and two articles were identified as studies of retrospective or prospective cohorts. There are six articles [27‒32] delving into the correlation between asthma and sexual malfunction:, 4 studies [33‒36] investigating the relationship between rhinitis and sexual disorder and 2 studies [37, 38] reporting the impact of urticaria and atopic dermatitis on SD.

Sample sizes of selected articles ranged from dozens to nearly 300 patients [27‒38]. All of the recruited studies focused on the influences of impaired sexual function brought by allergic diseases. Among them, 5 research studies [27‒29, 31, 37] included only females, 3 projects [34‒36] recruited merely male participants, whereas 4 other studies [30, 32, 33, 38] recruited both genders. All studies [27‒38] contained a control group.

Online supplementary Table S1 (for all online suppl. material, see https://doi.org/10.1159/000533403) displayed our evaluation for risk of bias of each retrieved article, and generally, the risk of bias was not high according to our assessment in consideration of selection, comparability, and exposure. The quality of evidence was low as the included investigations were all observational studies, leading to low baseline ratings and results for all studies (online suppl. Table S2).

Five reports [27, 29‒32] exhibited the significantly higher total FSFI or IIEF score in healthy control groups. The total FSFI score of the asthmatic group was 25.96 ± 9.1, while the control group averaged 29.90 ± 5.1 in Skrzypulec’s project [28]. The distinctly better subscales of FSFI such as sexual arousal, lubrication, orgasm, sexual satisfaction, and pain in healthy participants were also displayed by Skrzypulec et al. [28]. The large gap of FSFI total score was illustrated in Reda’s case-control study as well (asthmatic patients: 12.956 ± 10.3, healthy control: 25.423 ± 5.521) [31]. The research executed in Pakistan suggested that total FSFI was lower in asthmatics than healthy women (22.72 ± 9.74 vs. 29.19 ± 5.04, p = 0.002) [29]. Başar’s results [27] demonstrated that the controls’ average FSFI score was 27.0 ± 5.1 in contrast to the asthmatic patients’ 22.8 ± 5.6. Kilic and his colleague [32] also reported that the IIEF score of their asthmatic participants was 20.40 ± 6.70, but their counterparts could score 25.55 ± 1.70; furthermore, they discovered that the 19 patients classified as well-controlled can score nearly 5 and 10 points higher in the IIEF score than those regarded as partly and poorly controlled, respectively. Similar findings were also shown in Soto Campos’ article [30], which not only revealed significantly different FSFI (22.14 ± 9.47 vs. 26.57 ± 6.84, p < 0.005) and IIEF scores (59.50 ± 12.57 vs. 64.33 ± 8.28, p < 0.05) among asthmatic and healthy individuals but also disclosed a positive correlation between the level of asthma control and sexual functional score.

The study by Mohammad et al. [34] demonstrated that mean sexual function score was rated lower in patients with allergic rhinitis. Another three studies [33, 35, 36] examined the effect of allergic rhinitis therapy on sexual function, which was presented as the improvement of FSFI or IIEF. The significantly worse overall mean IIEF score was observed in allergic patients when compared with healthy men (49.8 ± 9.5 vs. 56.6 ± 9.8) [35]. After administering intranasal corticosteroids, the IIEF score rose to 51.0 ± 6.7, which was a significant progress. The pretreatment IIEF-5 score was also apparently lower than those of the control group in Cakan’s study [36]; local steroids and antihistamines showed their magnificent effect on the increased IIEF score as well. The pretreatment FSFI and IIEF scores were 72.13 ± 12.09 and 53.88 ± 13.87, respectively, which differed statistically from 78.3 ± 8.43 and 67.05 ± 6.04 recorded by the controls in Kirmaz’s study [33]; moreover, both overall sexual function scores surged significantly after the treatment. Collectively, these reports implied that there is an inverse association between sexual function and severities of allergic nasal diseases.

Markedly lower sexual function score in females with chronic spontaneous urticaria (CSU) was reported by Ertaş et al. [37], and the negative correlation (r = −0.363, p = 0.006) between disease activity and FSFI score was confirmed. Another original study [38] found that the FSFI and IIEF scores differed considerably between healthy controls and urticaria patients; besides, omalizumab and antihistamine are capable of treating the symptoms of urticaria and enhancing sexual function simultaneously.

This scoping review is the first comprehensive assessment of the extant literature in regard to the relationship between SD and allergic diseases. The studies examined in this review not only demonstrated significant differences in sexual function scores between healthy individuals and allergic patients but also highlighted the benefits of treating underlying allergic diseases for improving sexual function in victims experiencing SD.

For asthma and SD, five studies [27, 29‒32] revealed significantly lower total FSFI or IIEF scores in asthmatic patients, while the study of Skrzypulec et al. [28] reported better FSFI subscales in healthy individuals. Patients with well-controlled asthma had higher sexual function scores than those with partially or poorly controlled asthma [30, 32].

In terms of allergic rhinitis and SD, Mohammad’s project [34] reported lower mean sexual function scores in patients with allergic rhinitis. Additionally, three studies [33, 35, 36] examining the effect of treating allergic rhinitis on sexual function demonstrated additional advantages of local corticosteroids spray and antihistamines in improving sexual function scores remarkably. With regard to urticaria and SD, two studies [37, 38] found lower sexual function scores in patients with CSU compared to those of healthy controls. Moreover, Durmaz’s research [38] identified omalizumab and antihistamines as effective treatments for improving symptoms of both urticaria and sexual function.

Large-scale research studies have already pointed out the higher occurrences of sexual malfunction in patients of various allergic diseases [39‒43]. Some etiopathogeneses have been explored, including primarily inflammation, psychological factors, hormonal changes, sleep disorders, sexual behavior-related allergic reactions, social economic status, and medications.

In female patients, the release of pro-inflammatory cytokines may trigger neurochemical cascades that further modulate the neural circuitries of motivation and reward, resulting in the impairment of sexual function [44]. Animal studies have suggested that these cytokines, such as interleukin-1 (IL-1) and tissue necrosis factor-alpha (TNF-α), may lead to reduced interest in female sexual behavior through the synthesis of prostaglandin-E₂, which involves inflammatory processes [45‒47].

In male patients, high levels of TNF-α have been associated with erectile dysfunction (ED) that arises from the impaired vascular response to acetylcholine followed by endothelial dysfunction [48, 49]. Impaired gonadal production of testosterone caused by IL-6 and TNF-α may lead to ED as well [50, 51]. Experiments conducted on TNF-α-knockout mice indicated reduced responses to adrenergic nerve stimulation, along with increased non-adrenergic non-cholinergic (NANC) signaling and endothelium-dependent smooth muscle relaxation in the corpus cavernosum, facilitating erectile responses in the tested subjects. Conversely, decreased responses to increasing concentration of acetylcholine may allow TNF-α to reduce endothelial and neuronal nitric oxide synthase expressions on endothelial cells and NANC nerves, respectively, causing impaired cavernosal relaxation [52]. Additionally, TNF-α can induce changes in extracellular matrix deposition by smooth muscle cells, establishing a pro-fibrotic milieu characterized by reduced elasticity and compliance that results in impaired erectile responses [48].

Elevated serum levels of soluble intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been reported in patients with perennial allergic rhinitis [53]. Additionally, increased level of soluble VCAM-1 can pose a negative prognostic impact on peripheral arterial disease [54]. Pro-inflammatory cytokines release can lead to upregulation of adhesion molecules, which may in turn contribute to the development or exacerbation of ED [35, 55].

Moreover, the levels of inflammatory markers such as C-reactive protein, IL-6, IL-1β, and TNF-α, as well as the levels of endothelial-prothrombotic markers like von Willebrand factor, tissue plasminogen activator, and fibrinogen, are significantly elevated in individuals with ED and negatively correlated with sexual performance [56]. Patients with atopic constitution may experience inflammation in the tissues of the central and peripheral nervous system that leads to nerve damage. Glial cell inflammation and activation can result in neuropathic pain [57, 58], which further contributes to sexual pain and loss of sexual desire.

Allergic diseases may impose stress, anxiety, and depression on patients [59, 60] that in turn reduce their libido and arousal and jeopardize sexual function and confidence [61, 62]. Başar et al. [27] reported statistically significant differences in the General Health Questionnaire and various subsets of health-related QoL scores between asthmatic and healthy individuals, which correlated with the FSFI scores. Likewise, Skrzypulec’s study [28] stated that women with asthma experienced deterioration in their general QoL, especially in aspects such as limitations due to physical health and emotional problems, social functioning, energy/fatigue, and emotional well-being.

In Durmaz’s study [38], a significant decrease in depression scores was observed in CSU patients who were treated with omalizumab. Additionally, these patients demonstrated a significant improvement in sexual function scores. Ertaş et al. [37] detected a strong association between angioedema, SD, and impaired QoL. In some cases, genital angioedema might contribute to sexual reluctance.

These findings suggest that allergic diseases can detrimentally impact various aspects of patients’ QoL, including sexual function and mental well-being. The identification and management of these problems are important to provide comprehensive care for allergic disease patients.

Both male and female allergic patients are found to have decreased serum testosterone levels [63, 64], which can lead to a decrease in sexual desire and impairment in erectile function [65]. Testosterone is thought to inhibit airway smooth muscle contraction and reduce type 2 inflammation, and there is also evidence suggesting that androgen therapy may be a potential treatment option for asthma [66]. On the other hand, Lokaj-Berisha’s research [63] indicated that elevated estrogen level in male allergic patients might be a result of secondary hypogonadism, while low level of estradiol may be associated with ED [67].

Furthermore, in one of our included studies, Kilic’s results [32] disclosed a significant decrease in testosterone levels among asthmatic patients in comparison to the control group. Nonetheless, the value was still within the normal range and did not reach the threshold for hypogonadism diagnosis in all cases. Additionally, there was no correlation between the level of testosterone and ED score among asthmatic patients, which could possibly be attributed to the small sample size according to the authors’ comment. Despite this, based on overall evidence, hormonal changes might influence sexual function with the aforementioned mechanisms, while more studies for better understanding are still required.

The inflammatory mediators released in allergic reactions may disrupt our sleep-wake cycle. In conditions such as asthma and allergic rhinitis, increased airway resistance can enhance the likelihood of sleep-disordered breathing [68]. Sleep disorders such as obstructive sleep apnea and insomnia also potentially lead to sexual function impairment [69, 70]. Managing the underlying allergic conditions, either through medication or surgery, has been found to ameliorate both sleeping quality and sexual function [71, 72].

Mohammad et al. [34] found that men with allergic rhinitis and rhinoconjunctivitis had worse sleeping quality compared to healthy controls. However, they did not observe significant differences in female counterparts. Moreover, allergic symptoms, such as nasal congestion, may lead to reduced oxygenation of the central nervous system, contributing to decreased sleeping quality and sleep disturbances [73‒75] that result in SD.

The same conclusion was drawn by Jalalia’s cohort [35] about the relationship between the severity of SD and sleeping quality and fatigue. Also, Seehuus et al. [69] displayed the connection between Insomnia Severity Index, FSFI, and IIEF beyond the shared effect of mental health stressors. Reed et al. [76] found a correlation between decreased libido, poor sleeping quality, and night sweats. For female SD, some studies found a correlation between poor sleeping quality and orgasmic difficulty and arousal problems [77, 78], while others suggested the relationship between sleep duration and next-day sexual desire regardless of fatigue [79, 80]. Although the underlying mechanism is uncertain, it is possible that neurovascular effects associated with poor sleeping quality contribute to this association, while sleep duration may influence the reporting of sexual problems.

Research studies have indicated a negative impact on erectile function in cases of male SD associated with short sleep duration [81, 82]. Factors such as shift work, intense work missions, or unhealthy lifestyles are potential causes [83] as short sleep duration can lead to higher levels of serum cortisol and contraction of vascular smooth muscles [84], resulting in ED. Short sleep duration is also associated with autonomic nervous system alterations, characterized by increased sympathetic activity and decreased parasympathetic tone [85, 86] that lead to ED. Sleep restriction and fragmentation have been linked to lower levels of testosterone [87] in victims of sleep-related painful erections [88]. Various molecular mechanisms, such as nitric oxide, endothelin-1, and angiotensin, for endothelial dysfunction, along with the aforementioned inflammatory markers, are proposed as potential mechanisms underlying these relationships [89].

Sexual behaviors have been named potential triggers of allergic reactions or carriers of allergens. Allergens from food and drugs can be transmitted through body fluids such as saliva and semen. Various substances in condoms like latex, lubricants, spermicides, topical medications, and cosmetics can induce allergic reactions or contact dermatitis. Additionally, sexual activity itself can serve as a symptomatic trigger in patients with respiratory allergies, leading to conditions like honeymoon asthma and rhinitis [90]. Chaudhry et al. [29] found that female asthmatic patients tend to use condoms during sexual intercourse less frequently compared to women without asthma, which may be attributed to concerns regarding latex allergy or experiencing discomfort and pain following sexual intercourse with condoms.

Low educational level has been identified as a significant risk factor in the development of SD among asthmatic individuals [21]. This association may be due to a lack of knowledge about sex, leading to it being perceived as a taboo subject, ultimately resulting in a sense of powerlessness in their sexual experiences [28]. Moreover, unemployment status can exacerbate the situation, leading to emotional stress that further worsens asthmatic symptoms and increases the economic burden on patients. This, in turn, can contribute to noncompliance with asthma treatment and further heighten the risk of SD [31].

Among the studies included in this article, the majority of them were conducted in the Middle East, while only two studies took place in Europe, demonstrating regional discrepancies that may be attributed to various socioeconomic and ethnical factors. Nevertheless, previous research has highlighted a higher prevalence of allergic diseases, such as asthma, in English-speaking countries of higher socioeconomic status [91]. Based on the above, we speculate that allergic patients in the Middle East may experience more pronounced SD compared to those in Europe and North America, where SD may be less severe or overlooked [92, 93]. By contrasting the mature public health policies and advocacy in Western countries with the relative lack of health awareness exemplified by poorer hygiene, cigarette smoking, and pollution in socioeconomically disadvantaged nations, the underlying background differences may lead to disparate biopsychosocial burden and SD in allergic patients of different socioeconomic statuses. Future studies may focus more on the sociological, geographical, and ethnical aspects of the relationship between allergic diseases and sexual problems in different populations.

The use of corticosteroids and antihistamines in treating allergic diseases is a hidden threat to sexual function in that these medications potentially decrease testosterone levels [94]. Antihistamines, especially H₂ histamine receptor antagonists, can disrupt the luteinizing hormone/human chorionic gonadotropin signaling pathway and inhibit the relaxation of smooth muscles in the corpus cavernosum [95].

In our endeavor to investigate the connection between allergic conditions and SD, several studies revealed a positive correlation between better asthma control and higher FSFI and IIEF scores, while patients with allergic rhinitis and rhinoconjunctivitis demonstrated significantly lower FSFI or IIEF scores. CSU and atopic dermatitis [96, 97] have also been associated with increased risk of SD.

Based on six of our included studies [30, 32, 33, 35, 36, 38], sexual function improvement may benefit from the management of underlying allergic diseases. This finding suggests a potential link between the two conditions and holds therapeutic prospects for addressing SD in allergic patients. Kilic et al. [32] and Soto Campos et al. [30] observed higher sexual function scores in patients with well-controlled asthma compared to those with partially or poorly controlled asthma. Cakan [36] and Jalalia’s work [35] administered steroid and antihistamine intranasally to avoid systemic effects, while Kirmaz et al. [33] used oral desloratadine, a selective H₁ histamine receptor (HRH1) antagonist, to treat allergic rhinoconjunctivitis. All the above studies demonstrated improvement in the sexual function of patients after treatments. Durmaz’s findings [38] reported sexual function improvement in patients treated for CSU with either antihistamines or omalizumab. In the light of this study, the deleterious effect of antihistamine on sexual function may be confounded or surpassed by other factors like psychological stress and anxiety. In this case, antihistamine yields certain benefits in sexual health of allergic patients, such as the use of selective HRH1 blockers, which may mitigate the disruption of signaling pathways in the affected reproduction axes.

Aside from the above mechanisms, the difference of gender may also bring about distinct clinical presentations of allergic diseases and SD (Fig. 2). In male allergic patients, ED may be the primary cause of SD; this could potentially be attributed to factors such as inflammation, hormonal changes, short sleep duration, endothelial dysfunction, and autonomic dysfunction. Smoking, a definite risk factor in asthma and other airway diseases, can also be contributing, especially in this group of patients [28]. Among females, particularly the asthmatic patients, the most common SD was diminished arousal, followed by loss of desire and orgasm difficulty [25, 27]. The emotional well-being of the patients had a remarkable impact on the overall FSFI score, whereas domains such as intercourse satisfaction, lubrication, and pain were less affected by allergic diseases and showed minimal changes even after the improvement of allergic symptoms [31]. Based on these findings, we assume that psychological stress and depression play a primary role in SD of female allergic patients, which disinterest them to perform sexual activity.

In our perspective, there are still gaps in the understandings regarding the complex relationship between allergic diseases and SD. Although some studies have reported increasing prevalence of SD in allergic patients [40, 42, 43], the evidence remains inconclusive. As the current literature proposes a body of evidence that relates treating allergic diseases to potential improvement in sexual function, it is essential that future studies aim to address the knowledge gap regarding the mechanisms underlying this correlation and compare the effects of different treatment approaches for allergic disease on improving sexual function. Based on the present study, it is also noteworthy that disrupted sleep quality and duration have been linked to ED in males and decreased arousal and libido in females, making it a potential mediator connecting allergic conditions and sexual problems. Exploring the role sleep disturbance plays between the two disease entities warrants further investigation as well.

The study has some limitations. First, due to the lack of available data for statistical aggregation, a narrative review was conducted instead, and the narrative synthesis did not allow for weighting the analyzed studies. Secondly, the results may be affected by the methodological quality of the studies, since most of which were observational, with a potentially high risk of bias. Finally, we did not comprehensively analyze and discuss the scales other than FSFI and IIEF, given their infrequent utilization. Despite recognizing the equal importance of these evaluation tools, their limited applicability may pose challenges in integrating findings during article synthesis.

SD and allergic disease are interrelated based on the extant literature. The relationship can be reflected by the association between SD and allergic disorders such as asthma, allergic rhinitis, and urticaria. Inflammation, psychological factors, hormonal changes, sleep disorders, sexual behavior-related allergic reactions, social economic status, and the use of specific medications may play a role in the relationship as potential etiopathogenetic factors. Despite the insufficiency of investigations into the accurate pathomechanisms, this scoping review provides insights into the clinical implications of both entities in the hope of aiding evaluation and management of these two important and bothersome health issues. More research studies are warranted to further elucidate this complex relationship.

The authors would like to thank the data provided by all of the researchers for making this review.

An ethics statement is not applicable because this study is based exclusively on published literature.

The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or nonfinancial interest in the subject matter or materials discussed in this manuscript.

The authors declare that no funding was used to complete this study.

Ting-Yi Chiang and Yung-Chun Su: conception and design of the study, interpreting and critically appraising the literature, data acquisition, statistical analysis, and drafting and revising the manuscript. Hsiang-Ying Lee: interpreting and critically appraising the literature and drafting and revising the manuscript. Wei-Chen Chien: drafting and revising the manuscript. Hsiao-Chun Su: conception and design of the study and creating tables and figures. Chung-Wei Lin: conception and design of the study and drafting and revising the manuscript.

Ting-Yi Chiang and Yung-Chun Su contributed equally to this work.Edited by: D.Y. Wang, Singapore.

The data that support the findings of this study are openly available in references 27–38. Further inquiries can be directed to the corresponding author.