Determinants of sexual function in male patients with systemic lupus erythematosus

Abstract

Objectives

Our study aims to describe the association between SLE and sexual function, analysing demographic variables, comorbidities and other disease-related factors. As an exploratory objective, the impact of asking about sexual function during outpatient consultation was evaluated.

Methods

From 2018 to 2019, we invited sexually active men diagnosed with SLE to complete questionnaires that evaluated their sexual function and quality of life. Additionally, patients were asked if they believed they had sexual dysfunction, whether they would be interested in receiving specialized sexual care, and if they considered SLE to be detrimental to their sexual function. Epidemiological and disease-related data were retrieved from the patients’ clinical records.

Results

We included 124 men with SLE. Twenty-two (18%) patients answered positively when asked if they believed they had sexual dysfunction. These patients had lower overall erectile function scores and lower physical function scores than those who did not consider they had sexual dysfunction. In the multivariable analysis, factors that were associated with better sexual function were high physical function (B = 0.126, p = .031), lower BMI (B = 0.53, p = .010) and the patient’s perception of normal sexual function (B = 13.0, p < .001). Comorbidities associated with worse sexual function were type 2 diabetes (B = −8.1, p = .017) and a history of thrombosis (B = −5.12, p = .019).

Conclusion

Sexual function of male patients with SLE is impaired, independently of disease activity, chronic disease damage or pharmacological treatment. A simple question about perception of sexual function in the outpatient clinic can be used to help determine which patients could benefit from a multidisciplinary intervention to improve sexual health.

Keywords

Sexual dysfunction systemic lupus erythematosus male

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect every organ and system. Although SLE is more prevalent in women,¹ men usually present with higher disease activity, morbidity and mortality.^2–4

Pregnancy, fertility and sexual experiences in female SLE patients have been previously described in the literature; however, equivalent information regarding male patients is almost non-existent. A recent meta-analysis suggested that the risk of sexual dysfunction was higher in men with SLE than in the general population,⁵ and prior publications have described the negative effects that SLE has on erectile function,^6,7 genital anthropometric measurements,⁸ sperm quality⁹ and reproductive hormone levels.¹⁰ Although these constitute important advances in the field, other components of sexual function remain neglected.

Most methods that evaluate the effectiveness of treatment and outcomes in SLE focus on biological markers and physical findings of disease activity. However, the impact of SLE should not be reduced to these metrics. A shift towards patient-centred outcomes has brought forward aspects that were previously overlooked by physicians but that can be of great concern to patients. One such aspect is sexual and reproductive health.

Therefore, our study aims to describe the global effect of SLE on male sexual function and to explore how it relates to clinical, demographic and disease-specific variables. As a secondary objective, we analysed if asking patients simple questions about their sexual function provided information that was comparable with standardized methods for evaluating sexual function.

Methods

We conducted a cross-sectional study in a tertiary centre in Mexico City. From March 2018 to February 2019, we included sexually active men ≥16 years old who met the ACR criteria for SLE.¹¹ Patients with other rheumatologic diseases (except for secondary antiphospholipid syndrome) were excluded. Furthermore, patients with previous genitourinary surgery, chronic viral infections or history of cancer were excluded. This study was approved by the ethics committee at our institution (IRE-2926-19-20-1). Patients answered the 15-item International Index of Erectile Function (IIEF-15), which evaluates the relevant domains of male sexual function (i.e. erectile function, orgasmic function, sexual desire, intercourse satisfaction and overall satisfaction),¹² the 36-item Short Form Health Survey (SF-36), which appraises health-related quality of life (HRQoL),^13–15 and the Health Assessment Questionnaire disability index (HAQ-DI).¹⁶ These questionnaires were answered privately without any input from the recruiter. Participants also provided their answers to three additional questions: ‘(1) Do you think you have sexual dysfunction? (2) Do you consider that your disease (SLE) influences your sexual function? (3) In case of having sexual dysfunction, would you be interested in receiving care from a specialist?’. The possible answers to each of these questions were ‘yes’, ‘no’ and ‘I don’t know’. These questions were meant to explore patients’ self-perception and to determine their willingness to receive further treatment.

Demographic information, anthropometric data, disease activity history, comorbidities, laboratory measurements, antibody profile, current medication use, SLEDAI¹⁷ and SLICC¹⁸ scores were collected. Active disease was defined as a SLEDAI score ≥6 points. To explore different aspects associated with sexual function, patients were categorized into two groups: those who believed that they had sexual dysfunction and those who believed that they did not have sexual dysfunction (based on their answer to the question ‘Do you think you have sexual dysfunction?’). According to this distinction, we compared different variables between the groups. Variables were described in terms of means (standard deviation) or medians (interquartile range), and statistical comparisons of candidate variables were made by Student’s t-test, Mann–Whitney U, χ² test or Wilcoxon rank-sum test, when appropriate.

Furthermore, we investigated which variables were related to a higher IIEF-15, and therefore better sexual function, using linear regression analyses. All variables that had a p value <.3 on the first analysis or that have been previously reported to be associated with sexual function were included in the univariable regression models. Beta coefficients with 95% CIs and p values were recorded. If the univariable regression resulted in a p value <.2, variables were added to a multivariable regression model. Backward selection took place until all included variables had a p < .05. Age and BMI were added to the final model as correction factors. Results were confirmed by fitting a full regression model with all variables that were initially selected to be entered in the univariable regression models, followed by backward selection. All data was analysed using STATA V.15, using a value of p < .05 as the level of statistical significance.

Results

We included 124 men diagnosed with SLE. Their mean age was 36.8 ± 11.8 years, with a median time from diagnosis of 9.3 years (IQR: 4–11). Median SLEDAI score at the moment of the study was 2 points (IQR: 0–6). Other demographic, clinical and laboratory variables are presented in Table 1. Overall IIEF 15 scores and specific domains can be seen on Graph 1. Twenty-two (18%) patients reported sexual dysfunction, defined as answering positively to the question: ‘Do you think you have sexual dysfunction?’. Factors associated with self-reported sexual dysfunction in the univariate analysis were age (p = .004), disability measured by HAQ-DI (p < .001), lower scores in the physical domain in the SF-36, Type 2 diabetes (T2D) (p = .003) and patient-reported sexual dysfunction (p = .001). In the multivariable analysis, higher physical function scores on SF-36 (B = 0.126 [0.012–0.24], p = .031), BMI (B = 0.53 [0.13–0.94], p = .010) and the perception of normal sexual function (B = 13.0 [7.5–18.5], p < .001) correlated with better sexual function (measured by IIEF-15). Factors related with a worse sexual function were T2D (B = −8.1 [−14.6 to −1.5], p = .017) and a history of thrombosis (B = −5.12 [−9.4 to −0.87], p = .019). These results are described in Table 2.

Table 1.

Comparison between multiple variables according to patients perceived sexual function.

	All patients	Believe they have SD	Believe they do not have SD	SD vs no SD (p value)
Demographics
Total, n (%)	124	22	102
Age, mean (SD)	36.84 (11.83)	45.55 (10.58)	34.96 (11.27)	.0001
In a relation, n (%)	65 (52.42)	16 (72.73)	39 (45.88)	.068
Sexual relations only with women, n (%)	115 (92.74)	22 (100)	93 (91.17)	.351
Disease duration, years, median (IQR)	9.39 (4–11)	9.40 (6–10)	9.19 (4–11)	.5288
BMI, kg/m², mean (SD)	26.59 (4.87)	27.22 (6.40)	26.45 (4.50)	.5029
Smoking, n (%)	42 (33.87)	9 (40.91)	33 (32.35)	.5915
Comorbidities
Type 2 diabetes mellitus, n (%)	13 (10.48)	5 (22.73)	8 (7.84)	.039
Hypertension, n (%)	31 (25)	9 (40.91)	22 (21.57)	.057
Dyslipidaemia, n (%)	44 (35.48)	9 (40.91)	35 (34.31)	.558
Antiphospholipid syndrome, n (%)	24 (19.35)	6 (27.27)	18 (17.65)	.300
Thrombosis, n (%)	30 (24.19)	7 (31.82)	23 (22.25)	.357
Arterial thrombosis, n (%)	7 (5.65)	3 (13.64)	4 (3.92)	.073
Diagnosis of major depressive disorder, n (%)	7 (5.64)	0 (0)	7 (6.86)	.206
Patient reported outcomes
IIEF Global Score, median (IQR)	64 (52–69)	44 (39–56)	65 (59–70)	<.005
IIEF domain 1, median (IQR)	27 (22–29)	16 (12–23)	28 (24–30)	<.005
IIEF domain 2, median (IQR)	12 (10–14)	8 (6–10)	12 (11–14)	<.005
IIEF domain 3, median (IQR)	10 (7–10)	7 (5–9)	10 (8–10)	<.005
IIEF domain 4, median (IQR)	8 (6–9)	6 (5–7)	8 (7–9)	<.005
IIEF domain 5, median (IQR)	8 (8–10)	8 (6–8)	8 (8–10)	.0201
HAQ-DI, median (IQR)	0 (0–0.13)	0 (0–0.25)	0 (0–0.13)	.4712
SF-36 physical component score, median (IQR)	74.16 (59.39–86.93)	63.31 (46.11–75.97)	75.26 (60.69–88.47)	.0372
Physical functioning, median (IQR)	85 (70–95)	72.50 (35–85)	87.50 (75–100)	.001
SF-36 mental component score, median (IQR)	68.80 (56.62–75.94)	65.73 (46.11–75.97)	69.06 (57.81–76.04)	.3530
Perception of sexual function alterations due to SLE, n (%)	28 (22.58)	12 (54.55)	16 (15.69)	<.001
Disease activity
SLEDAI, median (IQR)	2 (0–6)	1.50 (0–4)	4 (2–6)	.0082
SLICC, median (IQR)	0 (0–1)	1 (1–1)	0 (0–1)	.0097
Complement C3, mean (SD)	104.78 (31.61)	114.55 (43.16)	103.32 (29.56)	.2343
Complement C4, mean (SD)	19.76 (11.26)	24.69 (12.66)	19.02 (10.92)	.0904
Anti-dsDNA, median (IQR)	17.30 (1.90–98)	15.65 (3.25–71.10)	17.30 (1.70–118.40)	.8260
Laboratory features
Haemoglobin, g/dl, mean (SD)	15.30 (2.84)	15.11 (2.90)	15.35 (2.83)	.7224
Leukocytes, cells/μl × 10³, mean (SD)	6.04 (2.29)	6.0 (1.83)	6.05 (2.38)	.9353
Lymphocytes, cells/μl, mean (SD)	1370.90 (768.76)	1308.82 (681.75)	1384 (788.91)	.6777
Platelets, cells/μl × 10³, mean (SD)	214.66 (71.61)	198.50 (68.02)	218.18 (72.22)	.2444
Creatinine, mg/dl, median (IQR)	0.93 (0.83–1.18)	0.90 (0.83–1.07)	0.94 (0.83–1.22)	.6159
MDRD ml/min/1.73 m², mean (SD)	93.24 (39.98)	90.35 (38.18)	93.87 (40.51)	.7095
Antiphospholipid antibodies	49 (39.52)	11 (50)	38 (37.25)	.267
LDL, mean (SD)	51.67 (18.98)	48.82 (17.96)	52.74 (19.52)	.5482
HDL, mean (SD)	4.17 (1.02)	3.85 (0.90)	4.25 (1.04)	.2033
Current immunosuppressive treatment
Prednisone, n (%)	65 (52.42)	13 (59.09)	52 (50.98)	.490
Azathioprine, n (%)	35 (28.23)	4 (18.18)	31 (30.39)	.248
Antimalarial, n (%)	79 (63.71)	16 (72.73)	63 (61.76)	.332
Methotrexate, n (%)	5 (4.03)	2 (9.09)	3 (2.94)	.184
Mycophenolate mofetil, n (%)	53 (42.74)	10 (45.45)	43 (42.16)	.777
Cyclophosphamide, n (%)	60 (48.39)	10 (45.45)	50 (49.02)	.762

Table 2.

Variables associated with self-reported sexual dysfunction in the univariate and multivariate analysis.

	Univariable		Multivariable
	Coefficient (CI 95%)	p value	Coefficient	p value
Age, mean	−0.21 (−0.41 to −0.006)	.044	0.0033 (−0.17 to 0.17)	.97
HAQ-DI, median	−17.4 (−23.8 to −11.1)	<.001	−11.5 (−18.5 to −4.5)	.002
Physical functioning (SF36), median	0.327 (0.236 to −0.418)	<.001	0.126 (0.012 to 0.24)	.031
Physical role functioning (SF36), median	0.22 (0.135 to 0.305)	<.001
Bodily pain (SF36)	0.139 (0.0458 to 0.232)	.004
Vitality (SF36)	0.175 (0.0567 to 0.294)	.004
SLEDAI	0.327 (−0.200 to 0.855)	.222
SLICC	−3.836 (−6.39 to −1.29)	.003
Complement C3	.047 (−0.038 to 0.132)	.273
Complement C4	−0.166 (−0.403 to 0.0715)	.169
Antiphospholipid syndrome	−4.62 (−10.7 to 1.46)	.135
High Density Lipoprotein (HDL)	1.65 (−2.13 to 5.43)	.386
Type 2 diabetes mellitus	−11.66 (−1914 to −4.18)	.003	−8.1 (−14.6 to −1.5)	.017
Hypertension	−3.28 (−8.82 to 2.26)	.243
Thrombosis	−4.60 (−10.17 to 0.974)	.105	−5.12 (−9.4 to −0.87)	.019
Smoking	0.105 (−4.94 to 5.15)	.967
Cardiovascular disease	−3.13 (−22.0 to 15.8)	.744
Body mass index (BMI)	0.19 (−0.303 to 0.68)	.448	0.53 (0.13 to 0.94)	.010
NSAIDs	−0.729 (−6.58 to 5.13)	.806
Depression	−3.07 (−10.6 to 4.43)	.420
Having a partner	−2.52 (−7.3 to 2.26)	.298
Patient-reported preserved sexual function	16.2 (10.6 to 21.9)	<.001	13.0 (7.5 to 18.5)	<.001

Differences between patients who considered that they had sexual dysfunction and those who did not are shown in Table 1. Patients who self-reported sexual dysfunction had a lower overall IIEF-15 score (median: 44, IQR: 39–56) than those who did not (median: 65, IQR: 59–70, p < .005), as well as lower scores in most domains of the IIEF-15, as illustrated in Figure 1. Likewise, patients who believed they had sexual dysfunction reported lower physical function scores on the SF-36 (72.5 [IQR: 35–85] vs 87.5 [IQR: 75–100], p < .001). Differences between these two groups in the various domains on the SF-36 and IIEF-15 are presented in Figure 1. T2D was more prevalent in patients who believed they had sexual dysfunction (22.7 vs 7.84%, p = .039). Up to 86% of patients would agree to receive specialized care if diagnosed with sexual dysfunction.

Figure 1.

Median values and quartiles for each specific domain of the IIEF-15 in patients who reported they considered they had sexual dysfunction and those who responded they did not. * All categories are significantly different (p <.001) by the Mann–Whitney U test.

Discussion

This work showed that the simple question: ‘Do you think you have sexual dysfunction?’ had a high predictive value to detect patients with lower IIEF-15 scores (B = 13.0, p < .001) and, consequently, worse sexual function. Although sexual function can be a delicate subject, a previous study reported that most patients would prefer that their rheumatologists actively inquired about their sexual function.⁶ This question could represent a good screening approach in routine care setting.

This study constitutes the first effort to describe how SLE can negatively impact sexual function and which variables seem to be associated with impaired sexual function. Notably, this analysis showed that SLE-specific variables, such as medication exposure, disease activity and cumulative damage, were not significantly associated with sexual function. Instead, we found that T2D and a history of thrombosis had the most negative impact on sexual function. This could be due to their association with accelerated atherosclerosis and endothelial dysfunction, which could directly affect erectile function,^19–22 which aligns with a previous study in which erectile dysfunction in men with SLE was associated with persistent lymphopenia and high-dose steroids, both of which have been associated with endothelial damage.⁶

It is notable that most patients (82%) in this study believed they did not have sexual dysfunction. An explanation for this finding might be related with the relatively low prevalence of moderate/severe erectile function (14.9%) since erectile function is the most prominent aspect of male sexual function. Thus, patients who have normal erectile function, but an impairment in some other domain of sexual function, may not consider these alterations to be as relevant. This might explain why most participants believed they had no sexual dysfunction and that SLE was not a factor associated with it.

Patients who reported having sexual dysfunction scored lower on HRQoL, particularly in the physical function domain. Deterioration in QoL has been previously linked with disease activity.^8,23–25 However, in this study, the association between lower physical functioning and lower sexual function was independent from SLE activity. This may point to either a direct association between sexual function and QoL, or an unexplored mediating factor.

Psychological variables are frequently affected in SLE patients,^26,27 and these variables could partially mediate the perception of altered sexual function in men with SLE, even in the setting of a normal function by standardized metrics. The identification of these underlying psychological factors could lead to the creation of holistic strategies that improve both sexual function and QoL. Further studies describing the association between QoL, sexual function and psychological aspects in patients with SLE are needed.

Most of the patients in our study would be willing to receive treatment in case of having some degree of sexual dysfunction. Treatment should always have a holistic approach and be constituted by both pharmacological and non-pharmacological interventions when appropriate.²⁸ Some non-pharmacological interventions that have shown to improve patient-centred outcomes include lifestyle modifications, such as smoking cessation, weight-loss and exercise.²⁹ Another possible intervention is cognitive-behavioural therapy as it has been shown to improve physical, social and mental function, while also lowering levels of depression and anxiety in SLE patients.^30,31 Patient-oriented research is essential to design new strategies for the management of lupus patients.³²

Some of the limitations of this study include its cross-sectional design, which minimizes the causal inferences that can be made regarding psychological variables and the perception of sexual function. Another important limitation is the lack of a specialized evaluation of these variables by experts, namely, a sexologist and a psychologist, since the evaluation consisted only in self-reports by the patients. Our study lacked any measurement of hormones involved in sexual function, such as testosterone, and we did not perform any screening test to rule out secondary causes of hypogonadism, including FISH or karyotype to rule out Klinefelter syndrome. Finally, we studied patients from a single centre with Latinx population, which could limit the external validity of our findings. A multicentre prospective study including addressing these issues could better describe sexual health in this group of patients.

We advise physicians to discuss sexual health in all men with SLE, focusing on patients’ experiences and expectations, and not merely on disease scores, which do not reflect patient-centred outcomes.^33,34 This study demonstrates that alterations in sexual function in men with SLE are not uncommon and are related to lower HRQoL, and that they can be easily identified by the use of a single question. This question can be used to determine which patients could benefit from a multidisciplinary intervention aimed at providing the best pharmacological or non-pharmacological treatment to improve sexual function. This ‘single-question approach’ could constitute an initial screening of sexual health in patients with SLE, and possibly other rheumatologic conditions, resulting in interventions that can lead to better outcomes for our patients.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Ana Barrera-Vargas

Javier Merayo-Chalico

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