Effect of COVID‐19 infection on the erectile function

Abstract

Objective

It has been understood that COVID‐19, which has become a global pandemic in a short time, is a disease affecting multiple organs and systems. Some of the organs and systems affected by the disease also play a role in the pathophysiology of erectile dysfunction (ED), which led us to consider the possible effects of the disease on the erectile function. In this study, we aimed to evaluate changes in the erectile functions of patients with COVID‐19 among those that had previously diagnosed with mild and moderate ED in our urology outpatient clinic.

Material and methods

Eighty‐one patients aged 18–65 years who were confirmed to have COVID‐19 were included in the study. According to disease severity, these patients were divided into two groups as mild (non‐hospitalized, n = 60) and moderate (hospitalized but did not require intensive care, n = 21). The patients’ pre‐ and post‐disease scores in the five‐item International Index of Erectile Function (IIEF‐5) ​​and hormone panel results were compared.

Results

The changes in the IIEF‐5 scores of the patients from the pre‐disease to the post‐disease period were statistically significant for both the mild and moderate groups (p < 0.05). When these changes were compared between the mild and moderate groups, the difference was not statistically significant (p = 0.156). There was also no statistically significant change in the testosterone, follicle‐stimulating, luteinizing, and prolactin hormone levels before and after the disease.

Conclusion

In this study, we determined that SARS‐CoV‐2 infection caused deterioration in existing ED in sexually active male individuals, regardless of the severity of the disease.

1. INTRODUCTION

Shortly after being first reported in the Wuhan city of China in early December 2019, coronavirus disease 2019 (COVID‐19) became a pandemic with a global impact. The disease was found to be caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). ¹ With the SARS‐CoV‐2 infection turning into a pandemic, 237 million people have so far been infected and 4.8 million people have died across the world. ² It has been determined that the virus is transmitted from person to person through direct contact and small droplets. ³ At the early stages of the disease, symptoms such as dry cough, fatigue, fever, difficulty in breathing, myalgia, loss of taste and smell, and diarrhea may be seen, while some patients present with life‐threatening clinical signs, including acute respiratory distress syndrome. ⁴ Damage to other target organs, such as the cardiovascular system and kidneys has also shown that the disease actually affects a large area and may have systemic consequences. ⁵

Vasculogenic, hormonal, psychogenic, anatomical and medical treatment‐related factors may play a role in the pathophysiology of erectile dysfunction (ED). In many cases, more than one pathophysiological mechanism may be involved, all adversely affecting the erectile function. ⁶ Recent studies have shown that SARS‐CoV‐2 infection can affect the cardiovascular system and also affect hormone levels by affecting the gonads in male individuals. ^{7 , 8} It is inevitable that the consequences of the disease are difficult to predict and the anxiety it creates in people who have contracted the virus also have negative consequences on their mental health. ⁹ In addition, the prevalence of ED in patients who had COVID‐19 was found to be 28% in the first prevalence study conducted on the subject and evaluating real‐life data. ¹⁰ In light of this information as previously hypothesized, it is possible that SARS‐CoV2 infection, which affects multiple organs and systems can also have adverse effects on the psychological health of infected individuals, which may lead to the development of ED or worsen existing ED in this patient population. ¹¹

The rapid spread of COVID‐19 across the world has led scientists to conduct studies to understand the effects of the disease on the human body in the short and long term. In our study, we aimed to evaluate changes in the erectile status of patients with SARS‐CoV‐2 infection among those that had been diagnosed with mild and moderate ED in our urology outpatient clinic in the pre‐disease period.

2. MATERIAL AND METHOD

This study was conducted in accordance with the principles of the Declaration of Helsinki after obtaining permission from the Scientific Research Platform of the Turkey Ministry of Health and ethical approval from the local ethics committee (İRB number: H.R.U/21.18.13). From the database of our tertiary healthcare center, patients aged 18–65 years who presented to the urology outpatient clinic due to ED between March 2020 and June 2021 and were subsequently confirmed to have COVID‐19 disease based on the reverse transcription polymerase chain reaction (PCR) test of a combined oro‐nasopharyngeal swab sample were retrospectively screened. Of the total 159 male patients screened, 68 patients were excluded for various reasons, including a history of transurethral or major pelvic surgery, ED caused by radical prostatectomy, diagnosis of testicular atrophy or hypogonadism or treatment for these conditions, steroid and/or exogenous testosterone use, hyperprolactinemia, malignancy, absence of International Index of Erectile Function (IIEF) scores, and unavailability of medical records. In addition, ten patients who were treated in the intensive care unit were excluded from the study because their number was not sufficient to form a severely symptomatic group. As a result, 81 patients were included in the sample and called for a follow‐up evaluation after a minimum of 2 weeks following the PCR confirmation of SARS‐CoV‐2 infection. Written informed consent was obtained from all the patients, and their detailed medical history was taken. Age, smoking status, body mass index (BMI), COVID‐19 treatment applied, comorbid diseases, and history of surgery were questioned in detail.

The 81 patients who met the study criteria were divided into two groups: mild (non‐hospitalized; n = 60) and moderate (hospitalized for oxygen therapy but did not require intensive care, n = 21). All the patients were called for a follow‐up evaluation after the confirmation of their recovery by PCR test negativity. During this evaluation, the patients completed the five‐item IIEF (IIEF‐5) questionnaire and underwent hormone panel testing. Considering the circadian rhythm of testosterone release, venous serum samples were obtained in the morning (8–10 a.m.). The mild and moderate groups were compared in terms of the IIEF‐5 values and hormone panel results before and after COVID‐19. The sexual function was assessed using the erectile function domain of the IIEF‐5, based on a total score of 25. ¹² The two groups were compared in terms of the hormone levels and IIEF‐5 results before and after COVID‐19.

3. STATISTICAL ANALYSIS

All statistical analyses were performed using the Statistical Package for the Social Sciences version 25.0 (SPSS 25) for Windows (IBM SPSS Inc., Chicago, IL). Whether the data were normally distributed was evaluated using the Kolmogorov–Smirnov and Shapiro–Wilk tests. Variables with a normal distribution were presented as mean ± standard deviation, and those without a normal distribution as median values with minimum and maximum ranges. Categorical variables were expressed as numbers and percentages. Comparisons between the groups of continuous variables were performed using the t‐test for independent variables showing a normal distribution, the Mann–Whitney U‐test for those that were not normally distributed, and the chi‐square test for categorical data. The t‐test and Wilcoxon test were used to compare the IIEF‐5 scores before and after COVID‐19 in independent groups. A p‐value below 0.05 was considered to be statistically significant.

3.1. Power analysis

All statistical analysis of the study was reviewed and errors were corrected. Sample size calculation was obtained with the G * Power program (Heinrich Heine University‐Düsseldorf‐Germany). The effect size was calculated from our findings. While effect size was 0.3, Type 1 error in the study was 0.05, and the power of the study was 80%, the sample size should be at least 64. This result shows that the sample size is sufficient. The relevant sentence was added to the statistical analysis part of the paper.

4. RESULTS

In order to obtain patient data obtained in the study, the files of 81 adult male patients were examined. Table 1 shows the demographic information and clinical characteristics of the patients according to the severity of the disease. Accordingly, the mean age of the patients was 55.21 ± 6.59 years in the mild COVID‐19 group and 57.76 ± 6.94 years in the moderate COVID‐19 group. There was no significant difference between the two groups in relation to BMI and smoking status of the patients. It was determined that the rate of diabetes mellitus was higher in the moderate COVID‐19 group (p = 0.014). There was no significant difference between the groups in terms of the time from the first presentation to the positive test result and the mean time from the negative test result to the second presentation (Table 1).

TABLE 1.

Demographic data and clinical features of the patients according to mild and moderate COVID‐19 groups

Characteristics	Mild (n = 60)	Moderate (n = 21)	p‐Value
Age (years)	55.21 ± 6.59	57.76 ± 6.94	0.137 a
BMI (kg/m2)	28.08 ± 3.94	27.80 ± 3.89	0.782 a
Smoker, n (%)	35 (58.3%)	12 (57.1%)	0.924 b
Diabetes mellitus, n (%)	12 (20%)	10 (47.6%)	0.014 b
Time between first admission to positive oropharyngeal swab (days)	197.63 (61–258)	218.45 (45–346)	0.083 c
Time between last negative oropharyngeal swab to second admission (days)	117.58 (31–158)	112.39 (45–166)	0.169 c

Note: The results are shown as mean ± standard deviation. BMI: body mass index; SD: standard deviation. Bold indicates significant p‐values.

^aStudent's t‐test.

^bChi‐square test.

^c Mann–Whitney U‐test.

The changes in the IIEF‐5 scores from the pre‐disease to the post‐disease period were statistically significant in both the mild and moderate COVID‐19 groups (p < 0.05). However, when these changes were compared between the two groups, no statistically significant difference was observed significant (p = 0.156). The pre‐disease hormone parameters of the patients were similar in both COVID‐19 groups. In addition, no statistically significant change was observed in the testosterone, follicle‐stimulating hormone, luteinizing hormone (LH) and prolactin hormone levels of the patients before and after the disease (Table 2).

TABLE 2.

Comparison of hormone levels and International Index of Erectile Function (IIEF‐5) scores before and after COVID‐19 according to mild and moderate COVID‐19 groups

Parameters	Mild mean ± SD	Moderate Mean ± Sd	p value
IIEF‐5 scores
Before COVID‐19	18.10 ± 4.50	16.27 ± 4.43
After COVID‐19	15.38 ± 5.18	12.31 ± 3.45
p‐Value a	<0.001	0.001
Δ IIEF‐5 scores	2.71 ± 3.59	4.14 ± 4.77	0.156 a
Total testosterone (ng/dl)
Before COVID‐19	412.24 ± 122.81	454.19 ± 196.85	0.192 a
After COVID‐19	394.11 ± 113.58	435.01 ± 154.19	0.093 a
p‐Value b	0.155	0.174
Folicle‐stimulating hormone (IU/L)
Before COVID‐19	36.63 ± 5.41	34.53 ± 4.46	0.412 a
After COVID‐19	35.47 ± 4.81	36.39 ± 4.51	0.354 a
p‐Value b	0.382	0.251
Luteinising hormone (IU/L)
Before COVID‐19	8.95 ± 1.4	9.1 ± 1.1	0.641 a
After COVID‐19	7.92 ± 0.9	8.7 ± 1.2	0.549 a
p‐Value b	0.192	0.341
Prolactin (ng/ml)
Before COVID‐19	7.19 ± 1.2	7.74 ± 1.4	0.348 a
After COVID‐19	8.4 ± 1.3	7.92 ± 1.3	0.257 a
p‐Value b	0.274	0.189

Notes: The results are shown as mean ± standard deviation. SD: standart deviation.

^aStudent's t‐test. Bold indicates significant p‐values.

^bPaired t‐test test.

^Δ: Change.

5. DISCUSSION

In this study, we found that the male patients who presented to our outpatient clinic with mild and moderate ED complaints and subsequently tested positive for SARS‐Cov2 infection had impaired erection functions, regardless of the severity of the disease.

ED is defined as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance. ¹³ Vasculogenic, hormonal, psychogenic, anatomical, and medical treatment‐related factors may play a role in the pathophysiology of ED. In most cases, more than one pathophysiological mechanism coexists, all adversely affecting erectile function. ⁶ ED is the most common male sexual health problem, affecting 13%–28% of men aged 40–80 years, and its prevalence increases with age. ¹⁴ Causes such as endothelial dysfunction, subclinical hypogonadism, deterioration of psychological state, and impaired pulmonary hemodynamics all contribute to the potential onset of ED. ¹¹ While there are no conclusive data on whether having had a COVID‐19 infection can lead to ED, the men at highest risk of developing serious complications secondary to COVID‐19 also have a higher risk of ED. This group consists of the elderly, diabetics, people with cardiovascular disease, overweight/obese individuals, and those with multiple comorbidities. Therefore, during the ongoing COVID‐19 pandemic, it should be taken into account that ED may develop or worsen in men who have had the disease. ¹⁵ The common symptoms of COVID‐19 are fever, dry cough, fatigue, and shortness of breath, but manifestations of multiple organs or systems, such as cardiovascular, urinary and gastrointestinal systems, and liver damage have also been reported. ¹⁶ The complications of COVID‐19 include the dysfunction of the heart, brain, lung, liver, kidney, and coagulation system. COVID‐19 can lead to myocarditis, cardiomyopathy, ventricular arrhythmia, and hemodynamic instability. ¹⁷ These findings suggest that COVID‐19 is a disease that affects multiple organs and systems.

Research into the host cell penetration, penetration, and replication processes has provided a better understanding of the pathogenesis of SARS‐CoV‐2, an RNA virus. ¹⁸ Studies investigating the pathogenesis of SARS‐CoV‐2 have revealed that the virus uses a binding receptor called angiotensin‐converting enzyme 2 (ACE2) to enter the host cell. SARS‐CoV‐2 binds to the ACE2 receptor and enters the cell through the type 2 transmembrane serine protease 2 (TMPRSS2) enzyme found in the host cell. ¹⁹ ACE2 and TMPRSS2 are expressed in host target cells, particularly alveolar epithelial type II cells. ²⁰ They are also expressed in the digestive, cardiovascular and urinary systems, and testicular tissue. ^{21 , 22} In light of this information, Zou et al. constructed a risk map of COVID‐19 using RNA sequencing datasets to evaluate the expression of the ACE2 receptor in various tissues and cells. According to this risk map, in addition to the respiratory system, cardiovascular, renal, gastrointestinal, and urogenital systems were also shown to be potentially vulnerable to the virus due to ACE2 expression. ²¹ Findings concerning the presence of both ACE2 and TMPRSS2 in male genital tissue provide evidence that the gonadal involvement of SARS‐CoV‐2 may occur in male patients, which would undoubtedly cause hormonal problems. ^{23 , 24} The disruption of gonadal hormones and a notable increase in serum prolactin (PRL) have been found in male patients infected with SARS‐CoV‐2. ^{25 , 26} High PRL levels can suppress the pituitary gland and subsequently reduce gonadotropins. ²⁷ This may result in a decrease in testosterone, which plays an important role in erectile physiology, and thus leading to the deterioration of the erectile function. In another study examining the effects of COVID‐19 on sex hormones in men, it was shown that serum LH and prolactin levels were significantly higher in patients with this disease compared to healthy men, but there was no change in serum testosterone levels. The authors explained this finding by stating that the impaired testosterone production in the early stage was temporarily compensated by LH stimulus, but then clinical hypogonadism might occur if this compensation was insufficient. ²⁵ Contrary to the literature, in our study, no significant difference was found between the hormone levels before and after the disease in mild or moderate COVID‐19 groups.

The possible effect of testosterone levels in men on the prognosis of COVID‐19 is currently a separate focus of interest for research in the literature. In the study conducted by Salonia et al. in which they compared male patients admitted with symptomatic COVID‐19 and healthy male patients, it was determined that the total testosterone level of the infected group at the time of admission was significantly lower. In addition, they found an association between low testosterone levels and a high risk of intensive care unit admission and death. ²⁸ Similarly, in another study conducted by Vena et al. a significant relationship was found between acute hypoxemic respiratory failure and low testosterone levels. ²⁹ Contrary to the studies mentioned above, we observed no significant difference between the pre‐disease testosterone levels of the mild and moderate COVID‐19 groups (412.24 ± 122.81 and 454.19 ± 196.85, respectively; p = 0.192). The possible reasons for this are, unlike these two studies, the acute testosterone level of the patients at the time of admission due to infection was not evaluated. Testosterone levels before infection were found in the records of the patients and these values were compared with the severity of the disease. In addition, the exclusion of severe symptomatic cases and the low number of our patients may be other possible reasons. In the other study of Salonia et al. in which 121 patients with COVID‐19 infection examined the testosterone change at the time of admission and during the 7‐month period, It has been reported that total testosterone levels return to normal over time in men recovering from COVID‐19, but more than 50% of them have persistent hypogonadism at 7 months of follow‐up. They also stated that the higher the burden of comorbid conditions at admission, the less likely the testosterone levels to improve over time. ³⁰ In our study, similar to the study by Salonia et al., it was found that the testosterone levels of patients in the mild and moderate symptomatic group before they had the infection decreased after the infection. However, this change was not found to be significant. As we mentioned above, the exclusion of severe symptomatic cases and the low number of our patients can be shown as possible reasons for the insignificant decrease in testosterone.

Endothelial dysfunction plays an important role in the pathogenesis of ED and coronary artery disease. ³¹ Recent studies have shown that the vascular endothelium can also be infected by SARS‐CoV‐2, resulting in vascular endothelial cell damage. Furthermore, the disruption of renin–angiotensin regulation due to ACE2 reduction and the consequent exacerbation of endothelial dysfunction may lead to endotheliitis. ^{32 ,33} Kresch et al. examined patients who had symptomatic COVID‐19 infection and subsequently developed severe ED. The authors took tissue samples at the time of penile prosthesis implantation and as a result of the histopathological examination, they stated that the systemic effect of COVID‐19 or widespread endothelial damage caused by the virus directly affecting the vascular endothelium could have a negative impact on penile vascular flow and lead to the deterioration of the erectile function. ³⁴ In another study, Sivritepe et al. evaluated changes in the IIEF scores of 80 sexually active male patients hospitalized due to symptomatic COVID‐19 infection. According to the evaluations they performed during hospitalization and at the third month after discharge, there was a positive correlation between ED and the interleukin‐6 level. The authors attributed this correlation to the vascular consequences of possible interleukin‐6‐related inflammation. ³⁵ In our study, the deterioration in the erectile functions of mild and moderate symptomatic patient groups may have also been due to the possible widespread‐systemic effect of COVID‐19.

A pandemic can be considered as a type of disaster affecting populations. It is inevitable that the psychological health of individuals affected by such disasters will also be affected. Sexual health is closely related to psychological health. The isolation of infected individuals, deaths due to the disease among family and friends, uncertainties in the treatment of the disease, and anxieties and concerns during the treatment are likely to affect the psychological health of individuals and/or aggravate existing disorders. ^{36 ‐ 38} Liu et al. reported that the risk of ED was increased by 39% in patients with depression, with the incidence of ED being 1.39 times higher in patients with depression than in those without depression. ³⁹ Similarly, Yin et al. determined that the ongoing global pandemic has also negatively affected the sexual lives of healthcare workers through its psychological effects. ⁴⁰ A recent study on the psychological impact of COVID‐19 on healthcare workers found that 29.8% of healthcare workers showed symptoms of stress, 24.1% anxiety, and 13.5% depression. ⁴¹ In the literature, the most common symptoms while in quarantine are listed as depressed mood, fear, irritability, and feeling of guilt. ^{42 , 43} Studies have also shown that as the quarantine period prolongs, mental health further deteriorates and symptoms of post‐traumatic stress disorder appear. ^{44 , 45} Due to COVID‐19 disease being new and having a wide range of outcomes from asymptomatic infection to death, psychological consequences are inevitable in individuals with this disease. The negative effects of COVID‐19 on infected individuals can also explain the deterioration of the sexual function of men in our study.

In order to achieve a good erection, adequate blood flow to the penis must be provided. It is clear that this requires a well‐functioning cardiopulmonary system. COVID‐19 targets vital organs, such as the heart and lungs, and it may take these systems up to 6 months to recover their functions after the disease, and there may sometimes be irreversible damage. ^{46 ,47} It is stated that the main cause of ED in lung patients is decreased functional capacity due to hypoxemia. ⁴⁸ In a multicenter prospective study, Sonnweber et al. reported that a significant percentage of post‐COVID‐19 patients presented with radiological pulmonary abnormalities and pulmonary dysfunction 100 days after diagnosis. However, the authors also noted a significant improvement in symptoms and cardiopulmonary status over time. ⁴⁹ In a study examining the possible mechanisms of the long‐term effects of COVID‐19 on sexual health; it is generally stated that the long‐term effects of the disease are proportional to the presence and severity of the accompanying non‐communicable diseases. ⁵⁰ Since we examined the short‐term results of our patients, we consider that the deterioration in IIEF‐5 scores may have been related to impaired exercise capacity and cardiopulmonary function associated with COVID‐19. There is a need for further studies examining long‐term outcomes in order to validate this hypothesis.

This study was conducted at a time when the long‐term effects of COVID‐19 were not yet clearly known, and therefore we consider our results to be valuable in terms of guiding future studies. However, our study also has certain limitations. The major limitations concerned the absence of a control group consisting of healthy individuals and the small number of patients. In addition, an objective evaluation with penile color Doppler ultrasound was not performed due to the invasive nature of this modality. In addition, the psychological status of patients exposed to COVID‐19 infection and how they were affected by the disease were not evaluated.

6. CONCLUSION

In this study, we determined that SARS‐CoV‐2 infection, which affects multiple organs and systems, caused deterioration in existing ED in sexually active male individuals, regardless of the severity of the disease. In line with the data we obtained from this study, we consider that there may be worsening of the erectile function as a different presentation of COVID‐19 disease, and the deterioration of the erectile function shown by the IIEF‐5 score can guide physicians. During this time when the unknown aspects of COVID‐19 are gradually coming to light, we emphasize that clinicians should be more careful about this disease that may have an effect on male sexual health. We consider that large‐scale prospective, randomized, controlled studies are needed in patients infected with SARS‐CoV‐2 in order to provide an understanding of molecular mechanisms that cause impairment in the erectile function.

AUTHOR CONTRIBUTIONS

Conception: Remzi Salar, Güven Erbay. Interpretation: Halil Ferat Önce. Collection of the data: Ahmet Şanlı, Ufuk Yavuz, Emre Kandemir, Harun Turel. Writing: Remzi Salar, Güven Erbay. Statistical analysis: Ahmet Şanlı, Güven Erbay. Editing: Remzi Salar, Güven Erbay. Management, funding: Remzi Salar.

FUNDING

This research did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors.

CONFLICTS OF INTEREST

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Salar R, Erbay G, Şanlı A, et al. Effect of COVID‐19 infection on the erectile function. Andrology. 2023;11:10–16. 10.1111/andr.13315

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request. cd_value_code=text