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The Role of Diallyl Thiosulfinate Associated with Nuciferine And Cai_Stesura Seveso 27/03/18 09:29 Pagina 59 DOI: 10.4081/aiua.2018.1.59 ORIGINAL PAPER The role of diallyl thiosulfinate associated with nuciferine and diosgenin in the treatment of premature ejaculation: A pilot study Tommaso Cai 1, Andrea Cocci 2, Giamartino Cito 2, Bruno Giammusso 3, Alessandro Zucchi 4, Francesco Chiancone 5, Maurizio Carrino 5, Francesco Mastroeni 6, Francesco Comerci 7, Giorgio Franco 8, Alessandro Palmieri 9 1 Department of Urology, Santa Chiara Regional Hospital, Trento, Italy; 2 Department of Urology, University of Florence, Florence, Italy; 3 Department of Andrology, Policlinico Morgagni, Catania, Italy; 4 Department of Urology, University of Perugia, Perugia, Italy; 5 Department of Urology, Cardarelli Hospital, Naples, Italy; 6 Department of Urology, Azienda Ospedaliera Papardo, Messina, Italy 7 Urologist, Bologna, Italy; 8 Department of Urology, Sapienza University of Rome, Rome, Italy; 9 Department of Urology, University of Naples, Federico II, Naples, Italy. Summary Objective: To assess the efficacy and safety with prevalence rates of 20-30%, probably affecting of an association of diallyl thiosulfinate with every man at some point in his life (2, 3). It may result nuciferine and diosgenin in the treatment of a group of patients in unsatisfactory sexual intercourse for both partners, suffering from premature ejaculation (PE), primary or second- decreasing sexual self-confidence and self-esteem and ary to erectile dysfunction (ED). resulting in an overall reduction of quality of life (QoL) Materials and methods: From July 2015 to October 2016, 143 (4). Lifelong PE occurs within 30-60 seconds after vagi- patients (mean age 25.3; range 18-39) affected by PE complet- ed the study and were finally analyzed in this phase I study. nal penetration with nearly every coitus, interesting All patients, after clinical assessment and laboratory evaluation about > 85% of men affected by this dysfunction, where- were asked to take an association of diallyl thiosulfinate with as about 10-20% of men ejaculate within 1-2 minutes nuciferine and diosgenin as oral tablet, once a day, on alternate (5). Acquired PE is commonly due to sexual perform- days, for three months. At the baseline and after three months ance anxiety (6), psychological or relationship problems of treatment, each patient was asked to complete the following (6), erectile dysfunction (ED) (7), occasionally prostatitis questionnaires: International Index of Erectile Function (8), hyperthyroidism (9), or during withdrawal/detoxifi- (IIEF-5), Premature Ejaculation Diagnostic Tool (PEDT), cation from prescribed (10) or recreational drugs (11). Male Sexual Health Questionnaire (MSHQ). In addition, men with this dysfunction are usually older, Results: A statistical significant improvement in terms of erec- have a higher mean body max index and a greater inci- tile function, comparing the IIEF-5 value at baseline and fol- low-up visit was found (respectively IIEF-5: 8.7 vs 14.01; dence of comorbid disease and ED associated to lifelong, p<0.001). Moreover, at follow-up visit, 97/143 men (67.8%) variable and subjective PE (12, 13). Although the patho- referred a subjective improvement of the erection quality and a physiologic mechanism of lifelong PE is not fully under- better control of the ejaculation (PROs). The IELT improved stood, it is shown that psychosocial, as well as organic too between the baseline evaluation and the follow-up visit factors play a key role in the aetiology (14-16). Several (p < 0.001). studies demonstrated that patients with PE have more Conclusion: In conclusion, our study, even if supported by pre- dorsal penile nerves, increasing glands penile hypersen- liminary results, showed how Diallyl Thiosulfinate, Nuciferine sivity and hyperexcitability (17). Moreover, they also and Diosgenin is able to improve the control of ejaculation in usually have other abnormal autonomic reflex pathways patients suffering from PE, primary or secondary to ED without for the ejaculatory process, including shorter bulbo-cav- any significant adverse effects. ernosal latency time and higher bulbo-cavernosal evoked KEY WORDS: Diosgenin; Muciferine; Thiosulfinate; Plant extracts; potentials (18, 19). For this reason, pharmacologic ther- Premature ejaculation; Treatment. apy that reduce glands penile hypersensivity should be effective for the treatment of PE. Medications, coun- Submitted 6 December 2017; Accepted 12 December 2017 selling and sexual techniques, that may delay ejacula- tion, can help the patients to improve sexual intercourse. However, a combination of these factors could be the INTRODUCTION best choice of treatment to improve efficacy and mini- Premature ejaculation (PE) is defined as uncontrolled mize relapse (20). Behavioural therapy essentially ejaculation either before or shortly after sexual penetra- include the “stop-start program” developed by Semans tion (1). It is a very common male sexual dysfunction (21), and its modification, the “squeeze” technique, pro- No conflict of interest declared. Archivio Italiano di Urologia e Andrologia 2018; 90, 1 59 Cai_Stesura Seveso 27/03/18 09:29 Pagina 60 T. Cai, A. Cocci, G. Cito, B. Giammusso, A. Zucchi, F. Chiancone, M. Carrino, F. Mastroeni, F. Comerci, G. Franco, A. Palmieri posed by Masters and Johnson (22). All these approaches tion, hormonal evaluation and patient self-administered need the partner’s cooperation for a long time, resulting questionnaires on sexual function, even submitted to the often difficult in the long term (23). Pharmacological partners. All the patients received a urological visit that therapy includes: selective serotonin reuptake inhibitors considered the development of external genitalia, the (SSRIs) antidepressants (24); dapoxetine (25); anaesthet- presence of phimosis and/or prepuce anomalies. At the ic creams (26) and phosphodiesterase type 5 inhibitors baseline, we collected the following hormonal profile (PDE5i) (27). Also some natural compounds (i.e. from all patients: serum follicle-stimulating hormone (FSH) Satureja montana, Tribulus terrestris, Phyllantus emblica) concentrations, prolactin levels, thyroid stimulating hor- proved to be efficient in improving sexual quality of life mone (TSH), luteinizing hormone (LH) and blood total in patients with PE (28). The role of nutraceuticals testosterone (TT). Each patient was asked to complete the seems, then, interesting in the management of PE. following questionnaires: International Index of Erectile The aim of this study was to assess the efficacy and safe- Function (IIEF-5), Premature Ejaculation Diagnostic Tool ty of Diallyl Thiosulfinate, Nuciferine and Diosgenin (PEDT) and Male Sexual Health Questionnaire (MSHQ). (CAMPEDEX-5®) in the treatment of patients affecting by PE, primary or secondary to ED. Questionnaires and PE status evaluation The IIEF-5 scale was used in order to evaluate the erec- tile function in the last six months considering the sever- MATERIALS AND METHODS ity of ED, classified as follow: severe (IIEF-5 ≤ 7), mod- erate (IIEF-5 between 8 and 11), mild-moderate (IIEF-5 Study design between 12 and 16), mild (IIEF-5 17-21), absent (IIEF- From July 2015 to October 2016, we enrolled, in a pilot 5 between 22 and 25). PEDT help to identify men who study, a total of 154 patients, affecting by PE, primary or may have a problem with ejaculating too soon during secondary to ED. Each patient signed a written fully sexual activity, considering the ejaculation as the release informed consent statement before being enrolled in the of semen after penetration. PEDT investigated the sever- study and accepted the trial voluntarily. After enrolment, ity of PE, classified as follow: absence of PE (PEDT ≤ 8), all patients were asked to take CAMPEDEX-5® oral tablet, probably PE (PEDT 9-10), certainly present PE (PEDT once a day, on alternate days, for three months (Figure 1). ≥ 11) (29). MSHQ-EjD is an abridged version of the 25- After 30 days all contacted by phone in order to be sure item MSHQ, seen as a validated, self-administered about the adherence to study protocol. After 3 months, all instrument for assessing the primary domains of erec- patients were evaluated with clinical evaluation and ques- tion, ejaculation, and sexual satisfaction in aging men. tionnaires in order to test the treatment efficacy and safety. MSHQ-EjD described three ejaculatory function items, investigating force (“in the past month, how would you rate Inclusion and exclusion criteria the strength or force of your ejaculation?”), volume item All men had been in stable, monogamous, heterosexual (“in the past month, how would you rate the amount or vol- relationship with at least one sexual intercourse a week ume of semen or fluid when you ejaculate?”), frequency item with a compliant female partner. Exclusion criteria were: (“in the past month, how often have you been able to ejacu- age < 18 years, history of a psychiatric or neurological late or “cum” when having sexual activity?), and one ejacu- disorder, alcohol or drug abuse, previous genitourinary lation bother item (“if you had any ejaculation difficulties or system trauma or surgery, spinal cord injury, previous have been unable to ejaculate, have you been bothered by radiotherapy, thyroid diseases, hypogonadism, currently this?”) (30). Ejaculatory function score, which is the sum taking a drug known to affect sexual function, such as of the ordinal responses to the three items, ranges from hormonal therapy for prostate cancer. 1 to 15, while bother scores ranges from 0 to 5. Furthermore,
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