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Homocysteine levels correlate with AVSS-RigiScan test parameters in men with erectile dysfunction

Homocysteine levels correlate with AVSS-RigiScan test parameters in men with erectile dysfunction Background: Although elevated homocysteine levels have been shown to affect penile erection, the relationship between homocysteine and erection at the tip or base of the penis has not been extensively studied. Results: We found that homocysteine levels were negatively correlated with the average event rigidity of the base (r = -0.2225, p = 0.0142). Homocysteine levels were also negatively correlated with the average maximum rigidity of the base (r = -0.2164, p = 0.0171). In particular, homocysteine levels were negatively correlated with ∆ Tumescence of the tip (r = -0.1866, p = 0.0404). Similarly, homocysteine was negatively correlated with ∆ Tumescence of the base (r = -0.2257, p = 0.0128). Conclusion: Our data showed that homocysteine inhibits penile erection. At the same time, homocysteine levels were negatively correlated with the parameters of the AVSS-RigiScan test. Keywords: Audio-visual sexual stimulation (AVSS) test, Erectile function (ED), RigiScan plus, Homocysteine Résumé Contexte: Bien qu’il ait été démontré que des niveaux élevés d’homocystéine affectaient l’érection pénienne, la rela- tion entre homocystéine et érection à l’extrémité ou à la base du pénis n’a pas été étudiée de manière approfondie. Résultats: Nous avons constaté que les niveaux d’homocystéine étaient négativement corrélés avec la rigidité moyenne de la base (r = -0,2225, p = 0,0142). Les taux d’homocystéine étaient également négativement corrélés avec la rigidité maximale moyenne de la base (r = -0,2164, p = 0,0171). En particulier, les taux d’homocystéine étaient négativement corrélés avec la tumescence Δ de l’extrémité (r = -0,1866, p = 0,0404). De même, l’homocystéine était négativement corrélée avec la tumescence Δ de la base (r = -0,2257, p = 0,0128). Conclusions: Nos données ont montré que l’homocystéine inhibe l’érection pénienne. Dans le même temps, les niveaux d’homocystéine étaient négativement corrélés avec les paramètres du test AVSS-RigiScan. Mots‑clés: Stimulation sexuelle audiovisuelle (AVSS), Fonction érectile, RigiScan Plus, Homocystéine Introduction Erectile dysfunction (ED), one of the most common types *Correspondence: yougang_feng@zmu.edu.cn; lhj1789@sns120.com of male sexual dysfunction, is the consistent inability of Department of Urology, Suining Central Hospital, Suining 629000, Sichuan the penis to achieve or maintain an erection sufficient for Province, China satisfactory sexual intercourse and is a chronic condition Full list of author information is available at the end of the article © The Author(s) 2023. 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The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Qian et al. Basic and Clinical Andrology (2023) 33:3 Page 2 of 7 that affects men’s physical and mental health [1]. Accord - for normal erectile hardness by AVSS, and AVSS testing ing to the Massachusetts Male Aging Study (MMAS), after oral PDE5i is more objective and accurate in identi- ED affects half of men aged 40–70  years and up to 70% fying psychological and organic ED [9]. of older men [2]. The largest European multicentre pop - Studies have shown that patients with high levels of ulation-based study of older men (40–79 years) reported Hcys are at increased risk of developing ED [10]. HHcys that the prevalence of erectile dysfunction ranged from 6 leads to reduced expression and activation of endothe- to 64%, depending on the age group, and that the preva- lial nitric oxide enzyme (NOS). A study by Giovannone lence increased annually with age, with an average preva- concluded that the Hcys level is an early predictor of ED lence of 30% [3]. ED also has a high prevalence in China, that is superior to Doppler ultrasound [11]; that study and a study based on a five-item International Index of revealed that increased Hcys levels in patients with mild Erectile Function questionnaire showed that the preva- ED were present before abnormal Doppler ultrasound lence of ED was 40.56% at an age of at least 40  years in values were observed. Al-Hunayan et  al. compared 97 5210 men from 30 provinces and autonomies [4]. There patients exhibiting type 2 diabetes mellitus with vascu- are many risk factors for ED, including age, physical dis- lar ED and 97 type 2 diabetic patients without ED in a eases, medications, lifestyles, and living conditions [5]. case‒control study, demonstrating that HHcys is a major According to the available studies, ED is usually associ- determinant of ED in diabetic patients [12]. A cross-sec- ated with systematic diseases such as diabetes mellitus, tional study by Salvio  et al. who collected clinical data, hyperlipidaemia, coronary artery disease, peripheral vas- Hcys levels, and penile ultrasound Doppler data from 126 cular disease, and cerebrovascular disease [6]. Athero- patients with ED of arterial origin for analysis showed sclerosis is a systemic pathological change of the blood that Hcys levels were associated with penile blood flow vessels that also affects the cavernous arteries and may velocity parameters in basal penile duplex ultrasound, lead to altered blood flow at the penile level. Among the demonstrating the role of Hcys levels in vasculogenic ED cardiovascular risk factors affecting the development of [13]. atherosclerosis, hyperhomocysteinemia (HHcys) plays Therefore, the present study aimed to investigate the a core role and is associated with oxidative stress and correlation between serum homocysteine levels and endothelial dysfunction [7]. audio-visual sexual stimulation and RigiScan (AVSS- RigiScan, a monitor of penile rigidity, has 2 testing RigiScan) test parameters in men with erectile dysfunc- modes: nocturnal and proactive. The nocturnal mode tion to further clarify the relationship between serum is mainly used for continuous monitoring during the homocysteine levels and erectile dysfunction in men and nighttime sleep state, and the proactive mode is mainly to provide reliable data support for clinical application. used for monitoring by audio-visual sexual stimulation (AVSS) during the waking state. The NRT-RigiScan test and AVSS-RigiScan test have their own advantages in Materials and methods clinical application, and the correlation between the two Inclusion and exclusion criteria tests is high [8]. The current majority view is that the Ninety-nine patients with a diagnosis of erectile dysfunc- AVSS-RigiScan test is simple, practical, quick and inex- tion who attended the male outpatient clinic of Suin- pensive and is suitable for initial aetiologic screening of ing Central Hospital from October 2021 to March 2022 ED patients in general. There is no standardized norma - were selected for inclusion in the case group. Twenty- tive reference standard for the AVSS-RigiScan test, and two men without sexual dysfunction who underwent a most clinical centres refer to the NPTR-RigiScan diag- health examination or premarital examination during nostic criteria. Wang et  al. studied 1169 ED patients the same period were included in the control group. Par- aged 18–67  years by the AVSS-RigiScan test and found ticipants were grouped and analysed retrospectively. All that a basal rigidity of over 60% was sustained for at least participants provided informed consent (which included 8.75 min, with an average event rigidity of the tip reach- a statement of confidentiality of responses and the right ing at least 43.5% and that of the base reaching at least to stop answering at any time) and were given answers 50.5%; an average maximum rigidity of the tip reach- to any questions regarding the significance of the sur - ing at least 62.5% and that of the base reaching at least vey items. The inclusion criteria for participants were as 67.5%; ∆tumescence (increase in tumescence or maxi - follows: age from 40 to 75  years; regular sexual activity mum − minimum tumescence) of the tip measuring within the last six months; and International Index of at least 1.75  cm and that of the base measuring at least Erectile Function (IIEF-5) ≤ 21. Subjects were excluded 1.95 cm; and a total tumescence time measuring at least from the study according to the following criteria: abnor- 29.75 min [9]. The number of times attaining total tumes - mal sex hormones, cardiovascular accident within the cence at least once can be used as a reference criterion last 6 months, medication affecting serum homocysteine Qian  et al. Basic and Clinical Andrology (2023) 33:3 Page 3 of 7 levels or testosterone levels within the last 3 months, his- adjusted, and the basal values were recorded for 15  min tory of genital surgery, and history of genital trauma. with quiet rest. A 30-min erotic video was shown to each patient individually, followed by stimulation of rigidity Study design and tumescence for the next 30  min. All recorded data A detailed history, physical examination, laboratory were transferred to a computer and analysed using RigiS- evaluation, and erectile function examination (i.e., can software. audio-visual sexual stimulation (AVSS) test) was admin- istered to all participants in the study. All patients’ gen- Statistical analysis eral information included age, IIEF-5 score, and Erection The Statistical Package for Social Sciences (SPSS) version Hardness Scale (EHS) score. The following biochemi - 18.0 (SPSS Inc., Chicago, IL) for Microsoft Windows was cal parameters were considered: glucose, total choles- used for the statistical analysis of the data. Data baselines terol (TC), triglycerides (TGs), high-density lipoprotein are expressed as the mean ± standard deviation (SD). (HDL) cholesterol, low-density lipoprotein (LDL) cho- The Mann‒Whitney U test was used to compare the lesterol, apolipoprotein A1 (ApoA1), apolipoprotein B case group and control group between groups. The data (ApoB), lipoprotein (a), fructosamine (FMN), homo- were divided into subgroups 1 (Hcys ≥ 15  µmol/l) and 2 cysteine (Hcys), and testosterone (T). Normal ranges for (Hcys < 15 µmol/l) according to homocysteine levels. The adults were 3.88–6.38  mmol/L (glucose), < 5.17  mmol/l Mann‒Whitney U test was performed for comparisons (cholesterol), < 1.70  mmol/L(TG), > 1.04  mmol/L between subgroups. Pearson’s test or Spearman’s test (HDL), < 3.12  mmol/L (LDL), 1.00–1.60  g/L (ApoA1), (normal or nonnormal distribution) was used to test the 0.6–1.1  g/L (ApoB), ≤ 300  mg/l (lipoprotein(a)), correlation between two variables. The threshold for sig - 1.10–2.15  mmol/L (FMN), < 15  µmol/l(Hcys), 4.94– nificance was p value < 0.05. 32.01 nmol/l (T). The audio-visual sexual stimulation (AVSS) test was Results monitored by the RigiScan plus device using the RigiS- All participants underwent general data collection can plus proactive mode. Participants were monitored and biochemical parameter assessments and com- in a quiet, comfortable, warm, softly lit room with- pleted the AVSS-RigiScan test. In the baseline analysis, out external disturbances, with a calm and comfort- the ED and non-ED groups were divided according to able mood, free of all distractions. The patient was given IIEF-5. The clinical characteristics of participants with 20 mg of oral vardenafil, and after 30 min, the RigiScan ED and participants with normal erectile function are plus was fixed on the patient’s right thigh according to shown in Table  1. The mean age of the ED patients was the instructions. The 3D VR glasses were put on and 49.38 ± 0.66 years, and the mean homocysteine value was Table 1 Comparison of clinical and laboratory data between the non-ED group and the ED group Non‑ED group (N = 22) ED group (N = 99) Mann‒Whitney U p Age (years) 37.14 ± 1.86 49.38 ± 0.62 326.5 < 0.0001 IIEF-5 22.91 ± 0.23 11.83 ± 0.49 0 < 0.0001 EHS 2.82 ± 0.11 2.12 ± 0.07 505.5 < 0.0001 Glucose (mmol/L) 5.59 ± 0.18 6.53 ± 0.23 708.5 0.0107 TC (mmol/L) 5.38 ± 0.23 5.63 ± 0.11 930 0.2868 TG (mmol/L) 2.38 ± 0.57 2.03 ± 0.12 1028 0.6843 HDL (mmol/L) 1.08 ± 0.04 1.18 ± 0.029 865.5 0.1339 LDL (mmol/L) 3.25 ± 0.17 3.44 ± 0.09 953.5 0.3643 ApoA1 (g/L) 1.49 ± 0.04 1.51 ± 0.03 1066 0.8798 ApoB (g/L) 0.88 ± 0.04 0.96 ± 0.02 878.5 0.1581 lipoprotein(a) (mg/L) 137.1 ± 20.58 193.7 ± 18.99 997 0.5386 FMN (mmol/L) 1.84 ± 0.04 1.96 ± 0.03 760 0.0273 T (mmol/L) 21.50 ± 1.48 18.77 ± 0.74 826 0.0777 Hcys (µmol/L) 11.70 ± 0.53 14.03 ± 0.50 704 0.0098 Data are expressed as the mean ± standard deviation; P values for the ED group and non-ED group were derived from Mann‒Whitney U test (for continuous dependent variables) ED Erectile function, IIEF-5 International Index of Erectile Function, EHS Erection Hardness Scale, TC Total cholesterol, TG Triglycerides, HLD High-density lipoprotein cholesterol, LDL Low-density lipoprotein cholesterol, ApoA1 apolipoprotein A1, ApoB Apolipoprotein B, FMN Fructosamine, T Testosterone, Hcys Homocysteine Qian et al. Basic and Clinical Andrology (2023) 33:3 Page 4 of 7 Table 2 Instrumental data (AVSS-RigiScan) of patients with normal versus high levels of homocysteine Subgroup 1 Subgroup 2 Mann‒Whitney U p (hcy ≥ 15 µmol/L) (hcy < 15 µmol/L) average event rigidity of the tip (%) 30.80 ± 2.70 35.33 ± 1.67 1083 0.0904 average event rigidity of the base (%) 39.87 ± 1.92 48.90 ± 1.68 876.5 0.0034 average maximum rigidity of the tip (%) 58.23 ± 2.63 64.15 ± 1.86 1061 0.0679 average maximum rigidity of the base (%) 63.07 ± 2.38 73.49 ± 1.58 797.5 0.0007 ∆Tumescence of the tip (cm) 1.93 ± 0.15 2.27 ± 0.10 1051 0.0593 ∆Tumescence of the base (cm) 2.32 ± 0.11 2.58 ± 0.08 1053 0.0611 Data are expressed as the mean ± standard deviation; P values for Subgroup 1 and Subgroup 2 were derived from the Mann‒Whitney U test AVSS Audio-visual sexual stimulation, hcy Homocysteine, ∆Tumescence Increase in tumescence or maximum − minimum tumescence Table 3 Correlation coefficients of HCY values with clinical Table 4 Correlation coefficients of HCY values with AVSS- parameters RigiScan test parameters r 95% CI p r 95% CI p Age (years) 0.237 0.061–0.398 0.009 average event rigidity of the tip (%) -0.158 -0.327–0.021 0.084 IIEF-5 -0.212 -0.377- -0.035 0.020 average event rigidity of the base (%) -0.223 -0.386—-0.046 0.014 average maximum rigidity of the tip -0.165 -0.334–0.014 0.071 HCY Homocysteine, IIEF-5 International Index of Erectile Function average maximum rigidity of the base -0.216 -0.380—-0.040 0.017 ∆ Tumescence of the tip -0.187 -0.353—-0.008 0.040 14.03 ± 0.50 µmol/l. The mean age of the 22 healthy indi - ∆ Tumescence of the base -0.226 -0.389—-0.049 0.013 viduals in the control group was 37.14 ± 1.86  years, and HCY Homocysteine, AVSS Audio-visual sexual stimulation, ∆Tumescence Increase the mean homocysteine value was 11.70 ± 0.53  µmol/l. in tumescence or maximum − minimum tumescence The non-ED group had higher homocysteine levels than the ED group, with a statistically significant difference between the two groups (p = 0.0098). The data were rigidity of the base (r = -0.2225, p = 0.0142) (Fig.  1a). divided into subgroup 1 (Hcys ≥ 15 µmol/l) and subgroup Homocysteine levels were negatively correlated with 2 (Hcys < 15  µmol/l) according to homocysteine levels. the average maximum rigidity of the base (r = -0.2164, Table  2 shows a comparison of the parameters of the p = 0.0171) (Fig.  1b). In particular, homocysteine levels AVSS-RigiScan test between the two groups. The results were negatively correlated with ∆Tumescence of the tip for average event rigidity of the tip, average maximum (r = -0.1866, p = 0.0404) (Fig. 1c). Similarly, homocysteine rigidity of the tip, ∆ tumescence of the tip, and ∆ tumes - was negatively correlated with ∆ Tumescence of the base cence of the base were all lower for subgroup 1 than for (r = -0.2257, p = 0.0128) (Fig.  1d). From Table  5, we can subgroup 2 but were not significantly different. The aver - conclude that the average event rigidity of the base was age event rigidity of the base was lower in subgroup 1 negatively correlated with age (r = -0.2088, p = 0.0215), than in subgroup 2, with a statistically significant differ - glucose values (r = -0.202, p = 0.0263), and homocysteine ence (p = 0.0034). The average maximum rigidity of the levels (r = -0.2225, p = 0.0142). With the current data, we base was lower in subgroup 1 than in subgroup 2, and the cannot draw a linear correlation between average event difference was statistically significant (p = 0.0007). rigidity of the base and cholesterol, triglycerides, HDL, Table  3 shows the correlation analysis between LDL, lipoprotein A1, lipoprotein B, lipoprotein (a), fruc- homocysteine and the basic clinical information and tosamine, and testosterone at this time. biochemical parameters. It can be concluded that homo- cysteine was positively correlated with age (r = 0.2366, Discussion p = 0.009) and negatively correlated with the IIEF-5 The relationship between homocysteine and erectile dys - score (r = -0.2123, p = 0.0194). Table  4 shows the rela- function was discussed as early as 2004 when Jones R. W tionship between homocysteine values and AVSS-RigiS- et  al. established a rabbit model of erectile dysfunction can test results. It can be seen that the current data do due to HHcys [14]. The results of several previous stud - not allow for a linear correlation between homocyst- ies have shown a significant correlation between HHcys eine and the average event rigidity and average maxi- and erectile dysfunction. The association between homo - mum rigidity of the tip. We found that homocysteine cysteine, vitamins, and folic acid and erectile dysfunction levels were negatively correlated with the average event was evaluated in a cross-sectional study based on 1318 Qian  et al. Basic and Clinical Andrology (2023) 33:3 Page 5 of 7 Fig. 1 Correlation between Hcys levels and AVSS-RigiScan test parameters. a Hcys levels were negatively correlated with the average event rigidity of the base (r = -0.2225; p = 0.0142). Hcys: Homocysteine. b Hcys levels were negatively correlated with the average maximum rigidity of the base (r = -0.2164; p = 0.0171). Hcys: Homocysteine. c Hcys levels were negatively correlated with ∆Tumescence of the tip (r = -0.1866, p = 0.0404). Hcys: homocysteine. ∆Tumescence: increase in tumescence or maximum − minimum tumescence. d Hcys levels were negatively correlated with ∆ Tumescence of the base (r = -0.2257, p = 0.0128). Hcys: Homocysteine. ∆Tumescence: increase in tumescence or maximum − minimum tumescence Table 5 Correlation coefficients of the average event rigidity of Wang et  al. based on 119 patients with erectile dysfunc- the base by clinical parameter tion showed that patients with erectile dysfunction with HHcys were 13.42 times more likely to develop vasogenic r 95% CI p erectile dysfunction than patients without HHcys [16]. Age -0.209 -0.373—-0.031 0.022 Giovannone et al. included 431 participants in their study glucose -0.202 -0.367—-0.024 0.026 and showed that plasma homocysteine levels were asso- TC 0.095 -0.085–0.269 0.299 ciated with the severity of erectile dysfunction and that TG 0.021 -0.159–0.198 0.823 the homocysteine level was expected to be a predictor of HDL -0.075 -0.251–0.105 0.412 the development of erectile dysfunction [11]. The results LDL 0.115 -0.065–0.288 0.208 of this study were consistent with previously reported ApoA1 -0.109 -0.282–0.071 0.233 findings, with a statistically significant difference in the ApoB 0.095 -0.085–0.269 0.301 erectile dysfunction group compared to the control lipoprotein(a) -0.028 -0.205–0.152 0.764 group (p = 0.0098). FMN -0.047 -0.223–0.133 0.612 Since the invention of the RigiScan by Bradley et  al. T -0.029 -0.206–0.150 0.752 in 1985 [17], nocturnal penile erectile rigidity tests and Hcys -0.2225 -0.3857 to -0.04579 0.0142 audio-visual sexual stimulation tests have been widely used in the field of urology and andrology. The RigiS - TC Total cholesterol, TG Triglycerides, HLD High-density lipoprotein cholesterol, LDL low-density lipoprotein cholesterol, ApoA1 Apolipoprotein A1, ApoB can, which is produced by GOTOP in the United States, Apolipoprotein B, FMN Fructosamine, T Testosterone, Hcys Homocysteine is used to assess the aetiology and severity of ED and can objectively and effectively identify psychological participants by Chen et  al., which showed a significant and organic ED and has been included in the official association between homocysteine and erectile dysfunc- ED treatment guidelines of the American and European tion, most significantly in men over 60  years old and Association of Urology [18]. The use of RigiScan in the in those living alone (single) [7, 15]. A recent study by diagnosis of nocturnal penile erection and rigidity has Qian et al. Basic and Clinical Andrology (2023) 33:3 Page 6 of 7 been recognized as an effective tool for distinguishing to impaired basal NO production, free radical formation, psychological erectile dysfunction from organic erectile and subsequent endothelial damage [24]. Reduced NO dysfunction [9]. In the previously reported literature on production and decreased cGMP concentrations lead to the association between homocysteine and erectile dys- decreased vascular smooth muscle diastolic function, as function, the diagnostic application of RigiScan in noc- well as impaired endothelium-dependent vasodilatory turnal penile tumescence and rigidity (NPTR), was used responses, causing endothelial dysfunction, which leads in most studies to evaluate erectile function, and few to various vascular diseases, including ED [25]. studies used AVSS-RigiScan for erectile function evalu- ation. There are no AVSS-RigiScan evaluation criteria in Limitations of the study any of the guidelines, including the EAU. Therefore, few We should also be concerned about some limitations researchers have used AVSS-RigiScan to evaluate erec- of this study. First, this study was a single-centre study, tile function in literature reports. In the diagnosis of ED, which may have implications for external validation. Sec- AVSS-RigiScan is a more widely used tool than NPTR- ond, the relatively small sample size may limit the gener- RigiScan. Compared to NPTR testing, penile erection alizability of the results. Third, repeated AVSS-RigiScan during AVSS testing is more similar to erotic and reflex tests were performed to ensure diagnostic accuracy. erection activity, which is relatively simple, economical, In addition, a comprehensive series of blinded valida- less time-consuming, more physiologically consistent, tion studies are necessary to determine the relationship and unaffected by sleep [8, 19–21]. In a study by Wang between homocysteine and AVSS-RigiScan test param- et  al., standardized Chinese AVSS-RigiScan evaluation eters. What we also need to acknowledge is the lack of criteria were established by the AVSS-RigiScan test used psychometric tests to assess erectile function, which in combination with oral phosphodiesterase-5 inhibitors is a study limitation. For participants with abnormal [9]. It has been shown that administration of phospho- AVSS-RigiScan test results, we did not perform further diesterase-5 inhibitors before AVSS-RigiScan testing not examinations, including the NPTR-RigiScan test and only avoids or reduces the shortcomings of the routine noninvasive arterial Doppler ultrasonography. AVSS-RigiScan but also improves its diagnostic proper- ties [20, 22, 23]. Therefore, in this study, the AVSS-RigiS - can test was performed to evaluate erectile function, Conclusion and the participants were given 20  mg of oral vardena- We can conclude that homocysteine levels are inhibitory fil 30  min before the test. In our study, the aim was to to penile erectile function and negatively correlate with investigate the correlation between serum homocysteine average event rigidity of the base and average maximum levels and AVSS-RigiScan test parameters in men with rigidity of the base in the AVSS-RigiScan test. This also erectile dysfunction. The results of the correlation anal - confirms that homocysteine is a potential indicator for ysis in Table  3 also show that homocysteine levels were the diagnosis of ED. negatively correlated with the average event rigidity of the base (r = -0.2225, p = 0.0142) and the average maxi- mum rigidity of the base (r = -0.2164, p = 0.0171). Table 5 Abbreviations AVSS: Audio-visual sexual stimulation; ED: Erectile function; MMAS: Massachu- also shows that the average event rigidity of the base was setts Male Aging Study; Hhcys: Hyperhomocysteinemia; Hcys: Homocysteine; negatively correlated with age (r = -0.2088, p = 0.0215), SAM: S-adenosylmethionine; SAH: S-adenosylhomocysteine; SPSS: Statistical glucose (r = -0.202, p = 0.0263) and homocysteine Package for Social Sciences; NPTR: Nocturnal penile tumescence and rigidity; IIEF-5: International Index of Erectile Function-5; EHS: Erection Hardness Scale; (r = -0.2225, p = 0.0142). NOS: Nitric oxide enzyme; eNOS: Endothelial nitric oxide synthase; TC: Total According to the present study, oxidative stress is the cholesterol; TG: Triglycerides; HLD: High-density lipoprotein cholesterol; LDL: main biochemical mechanism leading to homocysteine- Low-density lipoprotein cholesterol; ApoA1: Apolipoprotein A1; ApoB: Apoli- poprotein B; FMN: Fructosamine; T: Testosterone. induced cell damage and endothelial dysfunction. HHcys induces ED by altering virtually every component of NO Acknowledgements metabolism, including NOS expression, localization, None to declare. activation, and activity. HHcys significantly reduces the Authors’ contributions expression of endothelial nitric oxide synthase (eNOS) Xin Qian participated in the research design; the acquisition, analysis, and protein in a dose-dependent manner. Initially, endothe- interpretation of the data; and the drafting of the paper. Xing Tao and Yang- yang Gong took part in the statistical analysis. Can Ran provided important lial cells can increase NO synthesis and release to protect advice for this paper. Yougang Feng and Hongjian Liu contributed to the themselves and detoxify HHcys, which in turn leads to research design, critical revision of the paper, and approval of the submitted the formation of the S-nitroso homocysteine, a potent and final versions. All authors read and approved the manuscript. vasodilator. However, this defence mechanism is lim- Funding ited, and prolonged exposure to HHcys eventually leads This study did not receive funds. Qian  et al. Basic and Clinical Andrology (2023) 33:3 Page 7 of 7 Availability of data and materials 13. Salvio G, Ciarloni A, Cordoni S, Cutini M, Muti ND, Finocchi F, et al. Homo- The datasets used and/or analysed during the current study are available from cysteine levels correlate with velocimetric parameters in patients with the corresponding author on reasonable request. erectile dysfunction undergoing penile duplex ultrasound. Andrology. 2022;10(4):733–9. 14. Jones RW, Jeremy JY, Koupparis A, Persad R, Shukla N. Cavernosal Declarations dysfunction in a rabbit model of hyperhomocysteinaemia. BJU Int. 2005;95(1):125–30. Ethics approval and consent to participate 15. Lai WK, Kan MY. Homocysteine-Induced Endothelial Dysfunction. Ann All participants provided written informed consent to participate in this study. Nutr Metab. 2015;67(1):1–12. This study protocol was reviewed and approved by the RESEARCH PROJECT 16. Wang X, Zhang F, Guo L, Ma Z, Liao L, Yuan M. Significance of hyperho - ETHICAL REVIEW APPLICATION FORM, SUINING CENTRAL HOSPITAL, approval mocysteinaemia as an effective marker for vasculogenic erectile dysfunc- number: LLSLH20220032. tion: a cross-sectional study. Transl Androl Urol. 2022;11(3):397–406. 17. Bradley WE, Timm GW, Gallagher JM, Johnson BK. New method for Consent for publication continuous measurement of nocturnal penile tumescence and rigidity. 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Choose BMC and benefit from om: : Stimulation and RigiScan Test for the Diagnosis of Erectile Dysfunction. Chin Med J. 2018;131(12):1465–71. fast, convenient online submission 10. Demir T, Comlekci A, Demir O, Gulcu A, Calypkan S, Argun L, et al. Hyper- homocysteinemia: a novel risk factor for erectile dysfunction. Metabolism. thorough peer review by experienced researchers in your field 2006;55(12):1564–8. rapid publication on acceptance 11 Giovannone R, Busetto GM, Antonini G, De Cobelli O, Ferro M, Tricarico S, support for research data, including large and complex data types et al. Hyperhomocysteinemia as an Early Predictor of Erectile Dysfunc- tion: International Index of Erectile Function (IIEF) and Penile Doppler • gold Open Access which fosters wider collaboration and increased citations Ultrasound Correlation With Plasma Levels of Homocysteine. Medicine maximum visibility for your research: over 100M website views per year (Baltimore). 2015;94(39):e1556. 12. Al-Hunayan A, Thalib L, Kehinde EO, Asfar S. Hyperhomocysteinemia is a At BMC, research is always in progress. risk factor for erectile dysfunction in men with adult-onset diabetes mel- litus. Urology. 2008;71(5):897–900. Learn more biomedcentral.com/submissions http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Basic and Clinical Andrology Springer Journals

Homocysteine levels correlate with AVSS-RigiScan test parameters in men with erectile dysfunction

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Abstract

Background: Although elevated homocysteine levels have been shown to affect penile erection, the relationship between homocysteine and erection at the tip or base of the penis has not been extensively studied. Results: We found that homocysteine levels were negatively correlated with the average event rigidity of the base (r = -0.2225, p = 0.0142). Homocysteine levels were also negatively correlated with the average maximum rigidity of the base (r = -0.2164, p = 0.0171). In particular, homocysteine levels were negatively correlated with ∆ Tumescence of the tip (r = -0.1866, p = 0.0404). Similarly, homocysteine was negatively correlated with ∆ Tumescence of the base (r = -0.2257, p = 0.0128). Conclusion: Our data showed that homocysteine inhibits penile erection. At the same time, homocysteine levels were negatively correlated with the parameters of the AVSS-RigiScan test. Keywords: Audio-visual sexual stimulation (AVSS) test, Erectile function (ED), RigiScan plus, Homocysteine Résumé Contexte: Bien qu’il ait été démontré que des niveaux élevés d’homocystéine affectaient l’érection pénienne, la rela- tion entre homocystéine et érection à l’extrémité ou à la base du pénis n’a pas été étudiée de manière approfondie. Résultats: Nous avons constaté que les niveaux d’homocystéine étaient négativement corrélés avec la rigidité moyenne de la base (r = -0,2225, p = 0,0142). Les taux d’homocystéine étaient également négativement corrélés avec la rigidité maximale moyenne de la base (r = -0,2164, p = 0,0171). En particulier, les taux d’homocystéine étaient négativement corrélés avec la tumescence Δ de l’extrémité (r = -0,1866, p = 0,0404). De même, l’homocystéine était négativement corrélée avec la tumescence Δ de la base (r = -0,2257, p = 0,0128). Conclusions: Nos données ont montré que l’homocystéine inhibe l’érection pénienne. Dans le même temps, les niveaux d’homocystéine étaient négativement corrélés avec les paramètres du test AVSS-RigiScan. Mots‑clés: Stimulation sexuelle audiovisuelle (AVSS), Fonction érectile, RigiScan Plus, Homocystéine Introduction Erectile dysfunction (ED), one of the most common types *Correspondence: yougang_feng@zmu.edu.cn; lhj1789@sns120.com of male sexual dysfunction, is the consistent inability of Department of Urology, Suining Central Hospital, Suining 629000, Sichuan the penis to achieve or maintain an erection sufficient for Province, China satisfactory sexual intercourse and is a chronic condition Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Qian et al. Basic and Clinical Andrology (2023) 33:3 Page 2 of 7 that affects men’s physical and mental health [1]. Accord - for normal erectile hardness by AVSS, and AVSS testing ing to the Massachusetts Male Aging Study (MMAS), after oral PDE5i is more objective and accurate in identi- ED affects half of men aged 40–70  years and up to 70% fying psychological and organic ED [9]. of older men [2]. The largest European multicentre pop - Studies have shown that patients with high levels of ulation-based study of older men (40–79 years) reported Hcys are at increased risk of developing ED [10]. HHcys that the prevalence of erectile dysfunction ranged from 6 leads to reduced expression and activation of endothe- to 64%, depending on the age group, and that the preva- lial nitric oxide enzyme (NOS). A study by Giovannone lence increased annually with age, with an average preva- concluded that the Hcys level is an early predictor of ED lence of 30% [3]. ED also has a high prevalence in China, that is superior to Doppler ultrasound [11]; that study and a study based on a five-item International Index of revealed that increased Hcys levels in patients with mild Erectile Function questionnaire showed that the preva- ED were present before abnormal Doppler ultrasound lence of ED was 40.56% at an age of at least 40  years in values were observed. Al-Hunayan et  al. compared 97 5210 men from 30 provinces and autonomies [4]. There patients exhibiting type 2 diabetes mellitus with vascu- are many risk factors for ED, including age, physical dis- lar ED and 97 type 2 diabetic patients without ED in a eases, medications, lifestyles, and living conditions [5]. case‒control study, demonstrating that HHcys is a major According to the available studies, ED is usually associ- determinant of ED in diabetic patients [12]. A cross-sec- ated with systematic diseases such as diabetes mellitus, tional study by Salvio  et al. who collected clinical data, hyperlipidaemia, coronary artery disease, peripheral vas- Hcys levels, and penile ultrasound Doppler data from 126 cular disease, and cerebrovascular disease [6]. Athero- patients with ED of arterial origin for analysis showed sclerosis is a systemic pathological change of the blood that Hcys levels were associated with penile blood flow vessels that also affects the cavernous arteries and may velocity parameters in basal penile duplex ultrasound, lead to altered blood flow at the penile level. Among the demonstrating the role of Hcys levels in vasculogenic ED cardiovascular risk factors affecting the development of [13]. atherosclerosis, hyperhomocysteinemia (HHcys) plays Therefore, the present study aimed to investigate the a core role and is associated with oxidative stress and correlation between serum homocysteine levels and endothelial dysfunction [7]. audio-visual sexual stimulation and RigiScan (AVSS- RigiScan, a monitor of penile rigidity, has 2 testing RigiScan) test parameters in men with erectile dysfunc- modes: nocturnal and proactive. The nocturnal mode tion to further clarify the relationship between serum is mainly used for continuous monitoring during the homocysteine levels and erectile dysfunction in men and nighttime sleep state, and the proactive mode is mainly to provide reliable data support for clinical application. used for monitoring by audio-visual sexual stimulation (AVSS) during the waking state. The NRT-RigiScan test and AVSS-RigiScan test have their own advantages in Materials and methods clinical application, and the correlation between the two Inclusion and exclusion criteria tests is high [8]. The current majority view is that the Ninety-nine patients with a diagnosis of erectile dysfunc- AVSS-RigiScan test is simple, practical, quick and inex- tion who attended the male outpatient clinic of Suin- pensive and is suitable for initial aetiologic screening of ing Central Hospital from October 2021 to March 2022 ED patients in general. There is no standardized norma - were selected for inclusion in the case group. Twenty- tive reference standard for the AVSS-RigiScan test, and two men without sexual dysfunction who underwent a most clinical centres refer to the NPTR-RigiScan diag- health examination or premarital examination during nostic criteria. Wang et  al. studied 1169 ED patients the same period were included in the control group. Par- aged 18–67  years by the AVSS-RigiScan test and found ticipants were grouped and analysed retrospectively. All that a basal rigidity of over 60% was sustained for at least participants provided informed consent (which included 8.75 min, with an average event rigidity of the tip reach- a statement of confidentiality of responses and the right ing at least 43.5% and that of the base reaching at least to stop answering at any time) and were given answers 50.5%; an average maximum rigidity of the tip reach- to any questions regarding the significance of the sur - ing at least 62.5% and that of the base reaching at least vey items. The inclusion criteria for participants were as 67.5%; ∆tumescence (increase in tumescence or maxi - follows: age from 40 to 75  years; regular sexual activity mum − minimum tumescence) of the tip measuring within the last six months; and International Index of at least 1.75  cm and that of the base measuring at least Erectile Function (IIEF-5) ≤ 21. Subjects were excluded 1.95 cm; and a total tumescence time measuring at least from the study according to the following criteria: abnor- 29.75 min [9]. The number of times attaining total tumes - mal sex hormones, cardiovascular accident within the cence at least once can be used as a reference criterion last 6 months, medication affecting serum homocysteine Qian  et al. Basic and Clinical Andrology (2023) 33:3 Page 3 of 7 levels or testosterone levels within the last 3 months, his- adjusted, and the basal values were recorded for 15  min tory of genital surgery, and history of genital trauma. with quiet rest. A 30-min erotic video was shown to each patient individually, followed by stimulation of rigidity Study design and tumescence for the next 30  min. All recorded data A detailed history, physical examination, laboratory were transferred to a computer and analysed using RigiS- evaluation, and erectile function examination (i.e., can software. audio-visual sexual stimulation (AVSS) test) was admin- istered to all participants in the study. All patients’ gen- Statistical analysis eral information included age, IIEF-5 score, and Erection The Statistical Package for Social Sciences (SPSS) version Hardness Scale (EHS) score. The following biochemi - 18.0 (SPSS Inc., Chicago, IL) for Microsoft Windows was cal parameters were considered: glucose, total choles- used for the statistical analysis of the data. Data baselines terol (TC), triglycerides (TGs), high-density lipoprotein are expressed as the mean ± standard deviation (SD). (HDL) cholesterol, low-density lipoprotein (LDL) cho- The Mann‒Whitney U test was used to compare the lesterol, apolipoprotein A1 (ApoA1), apolipoprotein B case group and control group between groups. The data (ApoB), lipoprotein (a), fructosamine (FMN), homo- were divided into subgroups 1 (Hcys ≥ 15  µmol/l) and 2 cysteine (Hcys), and testosterone (T). Normal ranges for (Hcys < 15 µmol/l) according to homocysteine levels. The adults were 3.88–6.38  mmol/L (glucose), < 5.17  mmol/l Mann‒Whitney U test was performed for comparisons (cholesterol), < 1.70  mmol/L(TG), > 1.04  mmol/L between subgroups. Pearson’s test or Spearman’s test (HDL), < 3.12  mmol/L (LDL), 1.00–1.60  g/L (ApoA1), (normal or nonnormal distribution) was used to test the 0.6–1.1  g/L (ApoB), ≤ 300  mg/l (lipoprotein(a)), correlation between two variables. The threshold for sig - 1.10–2.15  mmol/L (FMN), < 15  µmol/l(Hcys), 4.94– nificance was p value < 0.05. 32.01 nmol/l (T). The audio-visual sexual stimulation (AVSS) test was Results monitored by the RigiScan plus device using the RigiS- All participants underwent general data collection can plus proactive mode. Participants were monitored and biochemical parameter assessments and com- in a quiet, comfortable, warm, softly lit room with- pleted the AVSS-RigiScan test. In the baseline analysis, out external disturbances, with a calm and comfort- the ED and non-ED groups were divided according to able mood, free of all distractions. The patient was given IIEF-5. The clinical characteristics of participants with 20 mg of oral vardenafil, and after 30 min, the RigiScan ED and participants with normal erectile function are plus was fixed on the patient’s right thigh according to shown in Table  1. The mean age of the ED patients was the instructions. The 3D VR glasses were put on and 49.38 ± 0.66 years, and the mean homocysteine value was Table 1 Comparison of clinical and laboratory data between the non-ED group and the ED group Non‑ED group (N = 22) ED group (N = 99) Mann‒Whitney U p Age (years) 37.14 ± 1.86 49.38 ± 0.62 326.5 < 0.0001 IIEF-5 22.91 ± 0.23 11.83 ± 0.49 0 < 0.0001 EHS 2.82 ± 0.11 2.12 ± 0.07 505.5 < 0.0001 Glucose (mmol/L) 5.59 ± 0.18 6.53 ± 0.23 708.5 0.0107 TC (mmol/L) 5.38 ± 0.23 5.63 ± 0.11 930 0.2868 TG (mmol/L) 2.38 ± 0.57 2.03 ± 0.12 1028 0.6843 HDL (mmol/L) 1.08 ± 0.04 1.18 ± 0.029 865.5 0.1339 LDL (mmol/L) 3.25 ± 0.17 3.44 ± 0.09 953.5 0.3643 ApoA1 (g/L) 1.49 ± 0.04 1.51 ± 0.03 1066 0.8798 ApoB (g/L) 0.88 ± 0.04 0.96 ± 0.02 878.5 0.1581 lipoprotein(a) (mg/L) 137.1 ± 20.58 193.7 ± 18.99 997 0.5386 FMN (mmol/L) 1.84 ± 0.04 1.96 ± 0.03 760 0.0273 T (mmol/L) 21.50 ± 1.48 18.77 ± 0.74 826 0.0777 Hcys (µmol/L) 11.70 ± 0.53 14.03 ± 0.50 704 0.0098 Data are expressed as the mean ± standard deviation; P values for the ED group and non-ED group were derived from Mann‒Whitney U test (for continuous dependent variables) ED Erectile function, IIEF-5 International Index of Erectile Function, EHS Erection Hardness Scale, TC Total cholesterol, TG Triglycerides, HLD High-density lipoprotein cholesterol, LDL Low-density lipoprotein cholesterol, ApoA1 apolipoprotein A1, ApoB Apolipoprotein B, FMN Fructosamine, T Testosterone, Hcys Homocysteine Qian et al. Basic and Clinical Andrology (2023) 33:3 Page 4 of 7 Table 2 Instrumental data (AVSS-RigiScan) of patients with normal versus high levels of homocysteine Subgroup 1 Subgroup 2 Mann‒Whitney U p (hcy ≥ 15 µmol/L) (hcy < 15 µmol/L) average event rigidity of the tip (%) 30.80 ± 2.70 35.33 ± 1.67 1083 0.0904 average event rigidity of the base (%) 39.87 ± 1.92 48.90 ± 1.68 876.5 0.0034 average maximum rigidity of the tip (%) 58.23 ± 2.63 64.15 ± 1.86 1061 0.0679 average maximum rigidity of the base (%) 63.07 ± 2.38 73.49 ± 1.58 797.5 0.0007 ∆Tumescence of the tip (cm) 1.93 ± 0.15 2.27 ± 0.10 1051 0.0593 ∆Tumescence of the base (cm) 2.32 ± 0.11 2.58 ± 0.08 1053 0.0611 Data are expressed as the mean ± standard deviation; P values for Subgroup 1 and Subgroup 2 were derived from the Mann‒Whitney U test AVSS Audio-visual sexual stimulation, hcy Homocysteine, ∆Tumescence Increase in tumescence or maximum − minimum tumescence Table 3 Correlation coefficients of HCY values with clinical Table 4 Correlation coefficients of HCY values with AVSS- parameters RigiScan test parameters r 95% CI p r 95% CI p Age (years) 0.237 0.061–0.398 0.009 average event rigidity of the tip (%) -0.158 -0.327–0.021 0.084 IIEF-5 -0.212 -0.377- -0.035 0.020 average event rigidity of the base (%) -0.223 -0.386—-0.046 0.014 average maximum rigidity of the tip -0.165 -0.334–0.014 0.071 HCY Homocysteine, IIEF-5 International Index of Erectile Function average maximum rigidity of the base -0.216 -0.380—-0.040 0.017 ∆ Tumescence of the tip -0.187 -0.353—-0.008 0.040 14.03 ± 0.50 µmol/l. The mean age of the 22 healthy indi - ∆ Tumescence of the base -0.226 -0.389—-0.049 0.013 viduals in the control group was 37.14 ± 1.86  years, and HCY Homocysteine, AVSS Audio-visual sexual stimulation, ∆Tumescence Increase the mean homocysteine value was 11.70 ± 0.53  µmol/l. in tumescence or maximum − minimum tumescence The non-ED group had higher homocysteine levels than the ED group, with a statistically significant difference between the two groups (p = 0.0098). The data were rigidity of the base (r = -0.2225, p = 0.0142) (Fig.  1a). divided into subgroup 1 (Hcys ≥ 15 µmol/l) and subgroup Homocysteine levels were negatively correlated with 2 (Hcys < 15  µmol/l) according to homocysteine levels. the average maximum rigidity of the base (r = -0.2164, Table  2 shows a comparison of the parameters of the p = 0.0171) (Fig.  1b). In particular, homocysteine levels AVSS-RigiScan test between the two groups. The results were negatively correlated with ∆Tumescence of the tip for average event rigidity of the tip, average maximum (r = -0.1866, p = 0.0404) (Fig. 1c). Similarly, homocysteine rigidity of the tip, ∆ tumescence of the tip, and ∆ tumes - was negatively correlated with ∆ Tumescence of the base cence of the base were all lower for subgroup 1 than for (r = -0.2257, p = 0.0128) (Fig.  1d). From Table  5, we can subgroup 2 but were not significantly different. The aver - conclude that the average event rigidity of the base was age event rigidity of the base was lower in subgroup 1 negatively correlated with age (r = -0.2088, p = 0.0215), than in subgroup 2, with a statistically significant differ - glucose values (r = -0.202, p = 0.0263), and homocysteine ence (p = 0.0034). The average maximum rigidity of the levels (r = -0.2225, p = 0.0142). With the current data, we base was lower in subgroup 1 than in subgroup 2, and the cannot draw a linear correlation between average event difference was statistically significant (p = 0.0007). rigidity of the base and cholesterol, triglycerides, HDL, Table  3 shows the correlation analysis between LDL, lipoprotein A1, lipoprotein B, lipoprotein (a), fruc- homocysteine and the basic clinical information and tosamine, and testosterone at this time. biochemical parameters. It can be concluded that homo- cysteine was positively correlated with age (r = 0.2366, Discussion p = 0.009) and negatively correlated with the IIEF-5 The relationship between homocysteine and erectile dys - score (r = -0.2123, p = 0.0194). Table  4 shows the rela- function was discussed as early as 2004 when Jones R. W tionship between homocysteine values and AVSS-RigiS- et  al. established a rabbit model of erectile dysfunction can test results. It can be seen that the current data do due to HHcys [14]. The results of several previous stud - not allow for a linear correlation between homocyst- ies have shown a significant correlation between HHcys eine and the average event rigidity and average maxi- and erectile dysfunction. The association between homo - mum rigidity of the tip. We found that homocysteine cysteine, vitamins, and folic acid and erectile dysfunction levels were negatively correlated with the average event was evaluated in a cross-sectional study based on 1318 Qian  et al. Basic and Clinical Andrology (2023) 33:3 Page 5 of 7 Fig. 1 Correlation between Hcys levels and AVSS-RigiScan test parameters. a Hcys levels were negatively correlated with the average event rigidity of the base (r = -0.2225; p = 0.0142). Hcys: Homocysteine. b Hcys levels were negatively correlated with the average maximum rigidity of the base (r = -0.2164; p = 0.0171). Hcys: Homocysteine. c Hcys levels were negatively correlated with ∆Tumescence of the tip (r = -0.1866, p = 0.0404). Hcys: homocysteine. ∆Tumescence: increase in tumescence or maximum − minimum tumescence. d Hcys levels were negatively correlated with ∆ Tumescence of the base (r = -0.2257, p = 0.0128). Hcys: Homocysteine. ∆Tumescence: increase in tumescence or maximum − minimum tumescence Table 5 Correlation coefficients of the average event rigidity of Wang et  al. based on 119 patients with erectile dysfunc- the base by clinical parameter tion showed that patients with erectile dysfunction with HHcys were 13.42 times more likely to develop vasogenic r 95% CI p erectile dysfunction than patients without HHcys [16]. Age -0.209 -0.373—-0.031 0.022 Giovannone et al. included 431 participants in their study glucose -0.202 -0.367—-0.024 0.026 and showed that plasma homocysteine levels were asso- TC 0.095 -0.085–0.269 0.299 ciated with the severity of erectile dysfunction and that TG 0.021 -0.159–0.198 0.823 the homocysteine level was expected to be a predictor of HDL -0.075 -0.251–0.105 0.412 the development of erectile dysfunction [11]. The results LDL 0.115 -0.065–0.288 0.208 of this study were consistent with previously reported ApoA1 -0.109 -0.282–0.071 0.233 findings, with a statistically significant difference in the ApoB 0.095 -0.085–0.269 0.301 erectile dysfunction group compared to the control lipoprotein(a) -0.028 -0.205–0.152 0.764 group (p = 0.0098). FMN -0.047 -0.223–0.133 0.612 Since the invention of the RigiScan by Bradley et  al. T -0.029 -0.206–0.150 0.752 in 1985 [17], nocturnal penile erectile rigidity tests and Hcys -0.2225 -0.3857 to -0.04579 0.0142 audio-visual sexual stimulation tests have been widely used in the field of urology and andrology. The RigiS - TC Total cholesterol, TG Triglycerides, HLD High-density lipoprotein cholesterol, LDL low-density lipoprotein cholesterol, ApoA1 Apolipoprotein A1, ApoB can, which is produced by GOTOP in the United States, Apolipoprotein B, FMN Fructosamine, T Testosterone, Hcys Homocysteine is used to assess the aetiology and severity of ED and can objectively and effectively identify psychological participants by Chen et  al., which showed a significant and organic ED and has been included in the official association between homocysteine and erectile dysfunc- ED treatment guidelines of the American and European tion, most significantly in men over 60  years old and Association of Urology [18]. The use of RigiScan in the in those living alone (single) [7, 15]. A recent study by diagnosis of nocturnal penile erection and rigidity has Qian et al. Basic and Clinical Andrology (2023) 33:3 Page 6 of 7 been recognized as an effective tool for distinguishing to impaired basal NO production, free radical formation, psychological erectile dysfunction from organic erectile and subsequent endothelial damage [24]. Reduced NO dysfunction [9]. In the previously reported literature on production and decreased cGMP concentrations lead to the association between homocysteine and erectile dys- decreased vascular smooth muscle diastolic function, as function, the diagnostic application of RigiScan in noc- well as impaired endothelium-dependent vasodilatory turnal penile tumescence and rigidity (NPTR), was used responses, causing endothelial dysfunction, which leads in most studies to evaluate erectile function, and few to various vascular diseases, including ED [25]. studies used AVSS-RigiScan for erectile function evalu- ation. There are no AVSS-RigiScan evaluation criteria in Limitations of the study any of the guidelines, including the EAU. Therefore, few We should also be concerned about some limitations researchers have used AVSS-RigiScan to evaluate erec- of this study. First, this study was a single-centre study, tile function in literature reports. In the diagnosis of ED, which may have implications for external validation. Sec- AVSS-RigiScan is a more widely used tool than NPTR- ond, the relatively small sample size may limit the gener- RigiScan. Compared to NPTR testing, penile erection alizability of the results. Third, repeated AVSS-RigiScan during AVSS testing is more similar to erotic and reflex tests were performed to ensure diagnostic accuracy. erection activity, which is relatively simple, economical, In addition, a comprehensive series of blinded valida- less time-consuming, more physiologically consistent, tion studies are necessary to determine the relationship and unaffected by sleep [8, 19–21]. In a study by Wang between homocysteine and AVSS-RigiScan test param- et  al., standardized Chinese AVSS-RigiScan evaluation eters. What we also need to acknowledge is the lack of criteria were established by the AVSS-RigiScan test used psychometric tests to assess erectile function, which in combination with oral phosphodiesterase-5 inhibitors is a study limitation. For participants with abnormal [9]. It has been shown that administration of phospho- AVSS-RigiScan test results, we did not perform further diesterase-5 inhibitors before AVSS-RigiScan testing not examinations, including the NPTR-RigiScan test and only avoids or reduces the shortcomings of the routine noninvasive arterial Doppler ultrasonography. AVSS-RigiScan but also improves its diagnostic proper- ties [20, 22, 23]. Therefore, in this study, the AVSS-RigiS - can test was performed to evaluate erectile function, Conclusion and the participants were given 20  mg of oral vardena- We can conclude that homocysteine levels are inhibitory fil 30  min before the test. In our study, the aim was to to penile erectile function and negatively correlate with investigate the correlation between serum homocysteine average event rigidity of the base and average maximum levels and AVSS-RigiScan test parameters in men with rigidity of the base in the AVSS-RigiScan test. This also erectile dysfunction. The results of the correlation anal - confirms that homocysteine is a potential indicator for ysis in Table  3 also show that homocysteine levels were the diagnosis of ED. negatively correlated with the average event rigidity of the base (r = -0.2225, p = 0.0142) and the average maxi- mum rigidity of the base (r = -0.2164, p = 0.0171). Table 5 Abbreviations AVSS: Audio-visual sexual stimulation; ED: Erectile function; MMAS: Massachu- also shows that the average event rigidity of the base was setts Male Aging Study; Hhcys: Hyperhomocysteinemia; Hcys: Homocysteine; negatively correlated with age (r = -0.2088, p = 0.0215), SAM: S-adenosylmethionine; SAH: S-adenosylhomocysteine; SPSS: Statistical glucose (r = -0.202, p = 0.0263) and homocysteine Package for Social Sciences; NPTR: Nocturnal penile tumescence and rigidity; IIEF-5: International Index of Erectile Function-5; EHS: Erection Hardness Scale; (r = -0.2225, p = 0.0142). NOS: Nitric oxide enzyme; eNOS: Endothelial nitric oxide synthase; TC: Total According to the present study, oxidative stress is the cholesterol; TG: Triglycerides; HLD: High-density lipoprotein cholesterol; LDL: main biochemical mechanism leading to homocysteine- Low-density lipoprotein cholesterol; ApoA1: Apolipoprotein A1; ApoB: Apoli- poprotein B; FMN: Fructosamine; T: Testosterone. induced cell damage and endothelial dysfunction. HHcys induces ED by altering virtually every component of NO Acknowledgements metabolism, including NOS expression, localization, None to declare. activation, and activity. HHcys significantly reduces the Authors’ contributions expression of endothelial nitric oxide synthase (eNOS) Xin Qian participated in the research design; the acquisition, analysis, and protein in a dose-dependent manner. Initially, endothe- interpretation of the data; and the drafting of the paper. Xing Tao and Yang- yang Gong took part in the statistical analysis. Can Ran provided important lial cells can increase NO synthesis and release to protect advice for this paper. Yougang Feng and Hongjian Liu contributed to the themselves and detoxify HHcys, which in turn leads to research design, critical revision of the paper, and approval of the submitted the formation of the S-nitroso homocysteine, a potent and final versions. All authors read and approved the manuscript. vasodilator. However, this defence mechanism is lim- Funding ited, and prolonged exposure to HHcys eventually leads This study did not receive funds. Qian  et al. Basic and Clinical Andrology (2023) 33:3 Page 7 of 7 Availability of data and materials 13. Salvio G, Ciarloni A, Cordoni S, Cutini M, Muti ND, Finocchi F, et al. Homo- The datasets used and/or analysed during the current study are available from cysteine levels correlate with velocimetric parameters in patients with the corresponding author on reasonable request. erectile dysfunction undergoing penile duplex ultrasound. 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Al-Hunayan A, Thalib L, Kehinde EO, Asfar S. Hyperhomocysteinemia is a At BMC, research is always in progress. risk factor for erectile dysfunction in men with adult-onset diabetes mel- litus. Urology. 2008;71(5):897–900. Learn more biomedcentral.com/submissions

Journal

Basic and Clinical Andrology – Springer Journals

Published: Mar 23, 2023

Keywords: Audio-visual sexual stimulation (AVSS) test; Erectile function (ED); RigiScan plus; Homocysteine; Stimulation sexuelle audiovisuelle (AVSS); Fonction érectile; RigiScan Plus; Homocystéine

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