Have you read? Best of the best: clinical research

Bruno Jorge Pereira
University of Beira Interior
Covilhã, Portugal

Urology Department of Centro Hospitalar e Universitário Cova da Beira (CHUCB) And Health Sciences Faculty of the University of Beira Interior (FCS-UBI)
Covilhã, Portugal

Female Sexuality

Both S, Lew-Starowicz M, Luria M, et al. Hormonal Contraception and Female Sexuality:
Position Statements from the European Society of Sexual Medicine (ESSM).
J Sex Med 2019; 16: 1681-1695.

Hormonal contraception is available worldwide in many different forms. Although the safety and efficacy of contraceptives have been extensively examined, little is known about their impact on female sexual function, and the evidence on the topic is controversial. This paper aimed to review the available evidence about the effects of hormonal contraceptives on female sexuality in order to provide a position statement and clinical practice recommendations on behalf of the European Society of Sexual Medicine. Several aspects of female sexuality have been investigated, including desire, orgasmic function, lubrication and vulvovaginal symptoms, pelvic floor and urological symptoms, partner preference, and relationship and sexual satisfaction. The effects of hormonal contraceptives on sexual function have not been well studied and remain controversial. Available evidence indicates that a minority of women experience a change in sexual functioning with regard to general sexual response, desire, lubrication, orgasm, and relationship satisfaction. The pathophysiological mechanisms leading to reported sexual difficulties such as reduced desire and vulvovaginal atrophy remain unclear. Insufficient evidence is available on the correlation between hormonal contraceptives and pelvic floor function and urological symptoms.

Davis SR, Baber R, Panay N, et al. Global Consensus Position Statement on the Use of Testosterone Therapy for Women. J Sex Med 2019; 16: 1331-1337 | Climacteric. 2019; 22(5): 429-434 | Maturitas 2019; 128: 89-93 |
J Clin Endocrinol & Metabol 2019; 104(10): 4660-4666

This Statement is being simultaneously published in the journals Climacteric, Maturitas, Journal of Sexual Medicine, and Journal of Clinical Endocrinology and Metabolism on behalf of the International Menopause Society, The European Menopause and Andropause Society, The International Society for Sexual Medicine, and The Endocrine Society, respectively.

The international panel concluded the only evidence-based indication for testosterone therapy for women is for the treatment of HSDD, with available data supporting a moderate therapeutic effect. There are insufficient data to support the use of testosterone for the treatment of any other symptom or clinical condition, or for disease prevention. Meta-analyses of the available data show no severe adverse events during physiological testosterone use, with the caveat that women at high cardiometabolic risk were excluded from study populations. The safety of long-term testosterone therapy has not been established. It was considered of utmost importance that the diagnosis of HSDD involves a full clinical assessment and that other factors contributing to FSD must be identified and addressed before testosterone therapy is initiated. A blood total testosterone level should not be used to diagnose HSDD. Treatment should only be with formulations that achieve blood concentrations of testosterone that approximate premenopausal physiological concentrations. As no approved female product is presently approved by a national regulatory body, male formulations can be judiciously used in female doses and blood testosterone concentrations must be monitored regularly. The panel highlighted the pressing need for more research into testosterone therapy for women and the development and licensing of products indicated specifically for women.

Erectile Dysfunction

Jenkins LC, Hall M, Deveci S, et al. An Evaluation of a Clinical Care Pathway for the Management of Men with Nonorganic Erectile Dysfunction.
J Sex Med 2019; 16: 1541-1546.

While there exists little literature on this specific topic, this study was conducted to assess the outcomes of men with nonorganic ED treated medically. All patients had normal hormone profiles and vascular assessment and were given a trial of a PDE5i. If no improvement, intracavernosal injection (ICI) therapy was administered. All patients met a mental health professional. 116 men with a mean age or 38 ± 19 (range 16-57) years were studied. 21% had mild ED, 47% had moderate ED, and 32% had severe ED. 81% of patients responded to PDE5i with a penetration hardness erection on follow-up. However, only 68% had a consistently good response. The mean Erectile Function domain score on PDE5i improved from 18 ± 11 to 22 ± 6, and for PDE5i responders it was 27 ± 4. 28% of men attempted ICI, all obtaining consistently functional erections. At a mean time point of 11 ± 5 months, 83% of those responding to PDE5i had ceased due to a lack of need. 11% of those using ICI continued to use them 6 months after starting ICI; the remainder had been transitioned back to PDE5i. Of the 29 patients in the latter subgroup, 66% were no longer using PDE5i consistently due to a lack of need. In conclusion, medical management of nonorganic ED utilizing the process of care model results in cure in a large proportion of such patients. The transient use of ICI in some patients permits successful PDE5i rechallenge.

Capogrosso P, Ventimiglia E, Boeri L, et al. Should We Tailor the Clinical Management of Erectile Dysfunction According to Different Ages?
J Sex Med 2019; 16: 999-1004.

This study intent to investigate the relationship between erectile function (EF), sexual satisfaction, and mood status among patients seeking medical help for ED. Data from 765 patients presenting at a single center for ED were analyzed. Patients were categorized as young (<50 years), middle-aged (>50 and 65 years), and old (>65 years) individuals and completed the IIEF and the BDI. Compared with older men, young and middle-aged patients showed significantly higher IIEF-OS and IIEF-Intercourse Satisfaction scores for increasing IIEF-EF scores. Older men showed no difference in terms of satisfaction scores for mild ED and normal EF status. At linear regression analysis, both IIEF-EF and age were significantly associated with sexual satisfaction. The interaction term between age and EF was also significant, suggesting that the older the patients, the higher the feeling of sexual satisfaction for the same EF status. Overall, 25% of patients reported depressive symptoms. Logistic regression analysis showed a 40% risk of depressive symptoms for patients <45 years with severe ED compared to a risk <20% for a man >65 years of age with the same EF status. Treating older patients with mild ED may not lead to a further improvement in sexual satisfaction as compared with younger patients with the same ED severity thus supporting the need for a comprehensive psychological counseling in younger ED patients.

Zhao B, Hong Z, Wei Y, et al. Erectile Dysfunction Predicts Cardiovascular Events as an Independent Risk Factor: A Systematic Review and Meta-Analysis.
J Sex Med 2019; 16: 1005-1017.

This review aims to assess whether ED was a risk factor for CV events. The protocol of this meta-analysis is available from PROSPERO (CRD42018086138). 25 eligible studies involving 154,794 individuals were included. Compared with those of men without ED, the CVD risk of ED patients was significantly increased by 43%, CHD was increased by 59%, stroke was increased by 34%, and all-cause mortality was increased by 33%. Older individuals with ED (>55 years), those with ED of a shorter duration (<7 years), and those with higher rates of diabetes (>20%) and smoking (>40%) were more prone to develop CVD. Additionally, severe ED was proven to predict higher CVD and all-cause mortality risk. The standardized model proposed here can be properly applied for screening early CV events. The evidence suggests the need for diligent observation of at-risk men and reinforces the importance of early treatment to prevent CV events.

Sexual Dysfunction

Miranda EP, Taniguchi H, Cao DL, et al. Application of Sex Aids in Men with Sexual Dysfunction: A Review.
J Sex Med 2019; 16: 767-780.

This article aims to summarize medical literature regarding scientific uses of the most common sex aids in men with sexual dysfunction and assess their clinical applicability. An extensive literature review was done and authors present a comprehensive review of the most common sex aids currently available: pornography, lubricants, constriction bands, dildos, vibrators, vacuum devices, external erectile support devices, and aids to positioning. They also discuss their indications, outcomes, precautions, and complications in order to have a comprehensive understanding of the sexual dynamics of individuals and couples combined with the appropriate integration of sex aids that may have a positive effect in the treatment of male sexual dysfunctions.

Russo GI, Mauro M, Cocci A et al. on behalf of EAU-YAU Men’s Health Working Group. Consulting “Dr. Google” for Sexual Dysfunction: A Contemporary Worldwide Trend Analysis.
Int J Impot Res 2019; doi:10.1038/s41443-019-0203-2.

Google Trends (GT) is a free, easily accessible search tool which can be used to analyze worldwide “big data” on the relative popularity of search terms over a specific period of time. To determine worldwide public interest in Peyronie’ disease (PD), erectile dysfunction (ED), premature ejaculation (PE) treatments, their penetrance, variation, and how they compare over time. The results showed that for PD it has been a decreased interest for Drug (AAPC: −3.1%, p < 0.01), ESWT (AAPC: −3.1%, p < 0.01), and vacuum therapy (AAPC: −1.2%, p < 0.01). In the field of ED, we observed trends toward an increased interest in prosthetic surgical treatment (AAPC: +1.7%, p = 0.4), for prostaglandins (AAPC: +0.7%, p=0.7), for traction (AAPC: +0.6%, p=0.1) and for ESWT (AAPC: +1.8%, p=0.4), but without statistical significance. On the contrary, we observed a slight reduction of search for Vacuum device (AAPC: −1 %, p < 0.01). The interest in PE decreased from 2004 to today (AAPC: −1%, p < 0.01), for surgical treatment (AAPC: −3.1%, p < 0.01), drug treatment (AAPC: −3.1%, p < 0.01), and for psychotherapy (AAPC: −6.7%, p < 0.01). On the contrary, the interest in spray drugs has increased significantly (AAPC: +5.1%, p < 0.01). Patients are searching the web for sexual diseases treatment options. Understanding people inquisitiveness together with degree of knowledge could be supportive to guide counseling in the decision-making-process and put effort in certifying patient information, avoiding them to fall in the pernicious trap of ‘fake-news’.

Capogrosso P, Frey A, Jensen CFS, et al. Low-Intensity Shock Wave Therapy in Sexual Medicine—Clinical Recommendations from the European Society of Sexual Medicine (ESSM).
J Sex Med 2019; 16: 1490-1505.

LISWT has been investigated for the treatment of uroandrological disorders including ED, PD and chronic CP/CPPS with controversial findings. 11 RCTs and 5 meta-analyses investigated LISWT for ED. RCTs provided controversial results on the efficacy of LISWT and were affected by high heterogeneity and the small number of patients included. Pooled-data analysis showed an overall positive effect in terms of erectile function improvement but reported small estimates and included a largely heterogeneous cohort of patients. 4 RCTs and 1 meta-analysis assessed LISWT for PD. All trials showed positive findings in terms of pain relief but no effect on penile curvature and plaque size. Inclusion criteria vary widely among studies, and further investigation is needed. 5 RCTs investigated LISWT for CP/CPPS. Data showed a possible effect on pain relief, although there is no evidence supporting that pain relief was maintained or any improvement in pain over time. LISWT is a safe and well-tolerated procedure but its efficacy for the treatment of ED is doubtful and deserves more investigation. Patients reporting pain associated with PD may benefit from LISWT, although no effect is expected on disease progression. LISWT is not a primary treatment for CP/CPPS, but it may be considered as an option to relieve pain.

Dwarica DS, Garbe Collins G, Fitzgerald C, et al. Pregnancy and Sexual Relationships Study Involving WOmen and MeN (PASSION Study).
J Sex Med 2019; 16: 975-980.

PASSION Study intent to assess for sexual dysfunction in heterosexual couples during pregnancy by performing a cross-sectional study of pregnant women in the third trimester and their partners with a self-reported questionnaire, the Golombok-Rust Inventory of Sexual Satisfaction (GRISS) questionnaire. 52 couples were enrolled at or after 35 weeks’ gestation. The mean age was 29.0 ± 6.4 and 31.3 ± 6.9 years for women and men, respectively. 60% of couples were married, and the remainder were cohabitating and in a committed relationship. When analyzing the results of the GRISS questionnaire for both partners, a significant difference was seen in mean avoidance of sex between women and men (3.31 vs 2.63) and non-sensuality (3.54 vs 2.75). Women reported more of a decrease in communication about sex when compared with their partners (3.79 vs 3.23). Vaginismus was more problematic during pregnancy than before (mean 4.17), and frequency of intercourse was decreased (mean 4.93) based on GRISS scores. Pregnant couples reported decreased frequency of intercourse and more pain with intercourse in women. Women were more likely to avoid intercourse and reported more problems with communication regarding sexual needs. Overall sexual satisfaction and function were not problematic for these couples during pregnancy based on the GRISS scale.

Testosterone Deficiency

Kwong JCC, Krakowsky Y, Grober E. Testosterone Deficiency (TD): A Review and Comparison of Current Guidelines.
J Sex Med 2019; 16: 812-820.

This article compares current guidelines on the evaluation and management of TD to provide clarity for patients and clinicians, as well as to highlight areas of controversy. Key aspects in the approach were compared, with a focus on the biochemical definition (cutoff) for low testosterone (T), principles of management, and recommendations for testosterone therapy (TTh) in special patient populations. Guidelines from the Canadian Medical Association Journal, American Urological Association, European Association of Urology, Endocrine Society, International Society for Sexual Medicine, and British Society for Sexual Medicine were included for review. Recommendations were generally consistent across guidelines. Key differences include the biochemical cutoff for low T, and recommendations for patients with low to normal T, prostate cancer, or cardiovascular disease. The authors highlight several case scenarios in which management differs depending on the guideline adopted.

Prematre Ejaculation

Atalay HA, Sonkaya AR, Ozbir S, et al. Are There Differences in Brain Morphology in Patients with Lifelong Premature Ejaculation?
J Sex Med 2019; 16: 992-998.

This study aimed to investigate whether patients with lifelong PE exhibit macrostructural or microstructural alterations of the parts of the brain involved in the male sexual response. 42 healthy participants and 54 lifelong PE patients were enrolled. Lifelong PE was diagnosed according PEDT and IELT. By using a voxel-based morphometry method from whole-brain T1-weighted magnetic resonance imaging the authors found that the mean volume of the caudate nucleus was significantly larger in the lifelong PE patients compared with healthy controls. Moreover, caudate nucleus volume was positively correlated with PEDT score and negatively correlated with the IELT. However, cortex morphology and the other subcortical volumes were not significantly different between the 2 groups. In conclusion, microstructural alterations in deep gray matter nuclei might be a useful parameter for studying the mechanism of the neurobiology underlying PE.

Peyronie’s Disease

Porst H, Burri A, the European Society for Sexual Medicine (ESSM) Educational Committee. Current Strategies in the Management of Peyronie’s Disease (PD)—Results of a Survey of 401 Sexual Medicine Experts Across Europe.
J Sex Med 2019; 16: 901-908.

This study aimed to investigate the current status quo in the management of PD across European experts in sexual medicine. Members of the ESSM and of various andrology and urology societies across Europe, with the majority (78%) being urologists, were contacted via e-mail and newsletters and asked to fill in an online questionnaire. 401 participants responded to the entire survey, with 277 reporting treating PD patients themselves and knowing this penile entity very well. Of the physicians treating PD patients, 94% performed penile palpation, and 74% perform ultrasonography. 45% assessed the degree of penile curvature by means of intravenous drug testing, but only 17% measured it accurately with a goniometer. Penile length, flaccid or in erect state, was measured by only 39% or 25%, respectively. Only 45% assessed testosterone. Primary treatment options were oral (65%), counseling (57%), and topical/local therapy (30%). Among oral drug users, tadalafil 5 mg was the most commonly used (57%), followed by vitamin E (40%). Regarding intralesional therapy, collagenase clostridium histolyticum was the leading drug (34%), followed by calcium channel blockers (17%). Considering surgical procedures, the original Nesbit technique was the preferred procedure (33%). 36% of the specialists expressed their dissatisfaction with the currently available treatment options, and 64% reported the impression that their patients were mostly dissatisfied with the treatment outcomes. Innovative and presumably multi-modal treatment protocols for PD are urgently needed.


Capece M, La Rocca R, Mirone V, et al. A Systematic Review on Ischemic Priapism and Immediate Implantation: Do We Need More Data?
Sex Med Rev 2018; 7: 530-534.

Ischemic priapism (IP) is the most common form of priapism. In cases of priapism persisting for >36 hours, conservative management usually fails, and the patients’ erectile tissue will be inevitably compromised, resulting in corporal fibrosis, shortening of the penis, and refractory erectile dysfunction. This review of nine studies (3 case reports and 6 retrospective analysis) intents to analyze the current literature with regard to the correlation between refractory ischemic priapism and immediate implantation of PP. All studies agreed that in patients with RIP, early insertion of a PP is a safe and effective procedure, and all studies but one preferred malleable implant to inflatable implants.


Santos-Iglesias P, Rana M, Walker L. A Systematic Review of Sexual Satisfaction in Prostate Cancer Patients.
Sex Med Rev 2019; XX: XXX-XXX.

This study aimed to conduct a literature review of studies that have examined sexual satisfaction in men diagnosed with and treated for PCa because research to this date has mostly focused on the impact of PCa on sexual satisfaction. A systematic review was conducted using Scopus and PubMed databases to identify studies that had assessed sexual satisfaction in men with PCa. 38 articles were found regarding sexual satisfaction in PCa. Overall, PCa treatments had a low to moderate impact on sexual satisfaction, and psychosocial interventions were more successful at improving sexual satisfaction than medical interventions. Sexual satisfaction was correlated to a large number of sexual, relational, psychological, and medical variables. This literature review shows very mixed results about the sexual satisfaction in men with PCa. Differences in research designs, methodologic limitations, and studies conducted a theoretically limit our understanding of the mechanisms that impact sexual satisfaction in men with PCa. We propose an alternative way of conducting research on sexual satisfaction by using solid theoretical models of sexual satisfaction.

Towe M, Huynh LM, El-Khatib F, et al. A Review of Male and Female Sexual Function Following Colorectal Surgery.
Sex Med Rev 2019; 7: 422-429.

Sexual function after colorectal surgery is a largely ignored topic. In patients being treated for colon and rectal cancers, the risk of sexual dysfunction after surgery is high and is influenced by multiple factors. Aim: To examine the factors involved with sexual dysfunction after colorectal surgery and review gender-specific sexual complaints most reported on in the literature. A comprehensive review of peer-reviewed publications on the topic was performed. The type of excision and surgical technique strongly influences sexual dysfunction risk, where newer nerve-preserving techniques seem to be associated with better sexual outcomes in contrast to more extensive surgeries. Adjunctive radiotherapy negatively affects sexual health when combined with surgical resection. The most common postoperative sexual complaints reported by men include erectile dysfunction, ejaculatory dysfunction, and dysorgasmia, whereas for women dyspareunia and poor lubrication are common. In conclusion, sexual morbidity after treatment for colorectal cancer is common and inadequately addressed by healthcare providers in the preoperative setting.


Burri A, Carvalheira A. Masturbatory Behavior in a Population Sample of German Women.
J Sex Med 2019; 16: 963-974.

Human masturbation is and has been a very heatedly and controversially discussed topic in human sexuality. This paper aims to conduct an explorative study on female masturbatory behavior to gain more insight into this nonreproductive sexual behavior and provide an empiric basis for future research. A total of 425 German women (mean age 26.6 years), 61.4% of whom were in a committed relationship, completed a comprehensive 76-item online survey consisting of study-specific, self-constructed questions and validated and standardized questionnaires. The majority (94.5%) of women indicated having masturbated at least once in their life, with a mean age at first masturbation of 14 years. 85.9% of women described masturbation as “genital self-stimulation until reaching orgasm”. The majority of women reported masturbating 2 or 3 times a week (26.8%) or once a week (26.3%). Factors independently associated with masturbation frequency were relationship status, orgasm frequency, openness to new experience, and body acceptance. Almost all women (91.5%) reported masturbating also when in a relationship. For the 5.5% of women who had never engaged in autoerotic stimulation, the 2 main reasons were “I hardly every feel sexual desire” and “sex is a partner-only thing”. 7.6% reported never experiencing an orgasm during masturbation, whereas 50.3% indicated that they always reached orgasm during autostimulation. The reasons cited for engaging in masturbation were manifold, ranging from sexual desire to relaxation and stress reduction. The most common fantasy included the partner; however, 20.7% fantasized about being “defenseless”, and 8.7% thought about a “disturbing” scenario that they chose not to elaborate further. For many women, masturbation does not represent “a partner substitute” to seek sexual pleasure, but rather is a stress coping and relaxation strategy.


Kominsky H, Beebe S, Shah N, Jenkins LC. Surgical Reconstruction for Penile Fracture: A Systematic Review.
Int J Impot Res 2019;

Penile fracture is a rare condition that describes the rupture of the corpus cavernosum following direct, high-pressure trauma to the erect penis. There is no standardized management algorithm. The authors performer a systematic review pf the past 10 years and determined that immediate penile exploration and tunica repair is considered the most common and current management of penile fractures with experts demonstrating that it leads to the fastest in recovery in erectile function and positive cosmetic outcomes. Additionally, they also determined that the specific algorithm can be variable—down to the suture material, use of catheterization, urethroplasty when involved, and length of recovery/follow-up. In the last several decades, men with penile fracture have been treated, in most cases, with immediate surgical intervention. This review highlights the varying practices regarding surgical exploration, injury repair, and postoperative management in men with a penile fracture. Immediate penile exploration and tunica repair have been the mainstay approach of management.

Morris BJ, Hankins CA, Lumbers ER, et al. Sex and Male Circumcision (MC): Women’s Preferences Across Different Cultures and Countries: A Systematic Review.
Sex Med 2019; 7: 145-161.

This review intent to perform a systematic review examining whether MC status influences women’s preference for sexual activity and the reasons for this, and whether women prefer MC for their sons. 29 publications with original data were included. In the overwhelming majority of studies, women expressed a preference for the circumcised penis. The main reasons given for this preference were better appearance, better hygiene, reduced risk of infection, and enhanced sexual activity, including vaginal intercourse, manual stimulation, and fellatio. In studies that assessed mothers’ preference for MC of sons, health, disease prevention, and hygiene were cited as major reasons for this preference. Cultural differences in preference were evident among some of the studies examined. Nevertheless, a preference for a circumcised penis was seen in most populations regardless of the frequency of MC in the study setting. In conclusion, women’s preferences generally favor the circumcised penis for sexual activity, hygiene, and lower risk of infection. The findings add to the already well-established health benefits favoring MC and provide important sociosexual information on an issue of widespread interest.

Gross MS, Reinstatler L, Henry GD, et al. Multicenter Investigation of Fungal Infections of Inflatable Penile Prostheses.
J Sex Med 2019; 16: 1100-1105.

This multicenter investigation reviews a database of IPP infections to examine for common patient and surgical factors related to IPP fungal infections. Analysis of 217 patients at 26 institutions who underwent salvage or device explant between 2001 and 2018. 26 patients (12%) with fungal infections were identified. 23 of 26 patients (83%) with a fungal IPP infection were either diabetic or overweight. 15 patients had undergone primary IPP implantation, and the other 11 had previously undergone an average of 1.7 IPP-related surgeries.

The average age at implantation was 63 years (range 31e92; median 63). 18 of the 26 patients with fungal infection had diabetes (69%). Ninety-one percent of implants were placed with IV antibiotics, consistent with current AUA guidelines: an aminoglycoside plus first-or second-generation cephalosporin or vancomycin or ampicillin/sulbactam or piperacillin/tazobactam. 65% (17 of 26) of infected IPPs had only fungal growth in culture. More than two-thirds of the fungal infections occurred in diabetic patients and 85% occurred in overweight or obese patients, suggesting that antifungal prophylaxis may be appropriate in these patients.