Results from the first autologous grafting of adult human testis tissue: a case report.

Fertility restoration using autologous testicular tissue transplantation is relevant for infertile men surviving from childhood cancer and, possibly, in men with absent or incomplete spermatogenesis resulting in the lack of spermatozoa in the ejaculate (non-obstructive azoospermia, NOA). Currently, testicular tissue from pre-pubertal boys extracted before treatment with gonadotoxic cancer therapy can be cryopreserved with good survival of spermatogonial stem cells. However, strategies for fertility restoration, after successful cancer treatment, are still experimental and no clinical methods have yet been developed. Similarly, no clinically available treatments can help men with NOA to become biological fathers after failed attempts of testicular surgical sperm retrieval. We present a case of a 31-year-old man with NOA who had three pieces of testis tissue (each ∼2 × 4 × 2 mm3) extracted and cryopreserved in relation to performing microdissection testicular sperm extraction (mTESE). Approximately 2 years after mTESE, the thawed tissue pieces were engrafted in surgically created pockets bilaterally under the scrotal skin. Follow-up was performed after 2, 4, and 6 months with assessment of reproductive hormones and ultrasound of the scrotum. After 6 months, all engrafted tissue was extracted and microscopically analyzed for the presence of spermatozoa. Furthermore, parts of the extracted tissue were analyzed histologically and by immunohistochemical analysis. Active blood flow in the engrafted tissue was demonstrated by doppler ultrasound after 6 months. No spermatozoa were found in the extracted tissue. Histological and immunohistochemical analysis demonstrated graft survival with intact clear tubules and normal cell organization. Sertoli cells and spermatocytes with normal morphology were located near the basement membrane. MAGE-A and VASA positive spermatogonia/spermatocytes were detected together with SOX9 positive Sertoli cells. Spermatocytes and/or Sertoli cells positive for γH2AX was also detected. In summary, following autologous grafting of frozen-thawed testis tissue under the scrotal skin in a man with NOA, we demonstrated graft survival after 6 months. No mature spermatozoa were detected; however, this is likely due to the pre-existing spermatogenic failure.

Can nerve monitoring during radical prostatectomy improve functional outcomes? A randomised trial.

OBJECTIVE: To explore how the use of the ProPep® Nerve Monitoring System (ProPep Surgical, Austin, TX, USA) for intraoperative specific sparing of the pudendal nerve fibres influences postoperative functional outcomes after unilateral nerve-sparing (UNS) or non-nerve-sparing (NNS) robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: We randomised 100 men undergoing UNS or NNS RARP to ProPep nerve monitoring during RARP (intervention) or standard of care RARP (control). Functional outcomes were assessed at 3, 6, and 12 months using the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), the International Prostate Symptom Score, the Danish Prostate Symptom Score, the International Index of Erectile Function, the Erection Hardness Scale, and 24-h pad tests. The primary outcome was the difference in ICIQ-SF score between the groups at 12 months. Secondary outcomes included differences in the remaining outcome measures and continence rates at all time points. Continence was defined as the use of no pads and the answer 'Never' to the question: 'How often do you experience urinary incontinence?' or a urine loss of <8 g on the 24-h pad test. RESULTS: A total of 82 patients were included in the per-protocol analysis at 12 months with 41 in each group. At 12 months the mean ICIQ-SF scores were 5.37 (95% confidence interval [CI] 3.71-7.03) and 5.66 (95% CI 4.05-7.27) for the intervention and control groups, respectively (P = 0.8). There were no statistically significant differences in any of the remaining outcomes. However, the continence rate was higher in the intervention group at 6 months (63% vs 44%, P = 0.09). CONCLUSIONS: Intraoperative nerve monitoring did not result in better functional outcomes following UNS or NNS RARP. Larger studies are needed to explore if ProPep can reduce the time to continence after RARP.

Development and validation of 3-dimensional simulators for penile prosthesis surgery.

BACKGROUND: The acquisition of skills in penile prosthesis surgery has many limitations mainly due to the absence of simulators and models for training. Three-dimensional (3D) printed models can be utilized for surgical simulations, as they provide an opportunity to practice before entering the operating room and provide better understanding of the surgical approach. AIM: This study aimed to evaluate and validate a 3D model of human male genitalia for penile prosthesis surgery. METHODS: This study included 3 evaluation and validation stages. The first stage involved verification of the 3D prototype model for anatomic landmarks compared with a cadaveric pelvis. The second stage involved validation of the improved model for anatomic accuracy and teaching purposes with the Rochester evaluation score. The third stage comprised validation of the suitability of the 3D prototype model as a surgical simulator and for skill acquisition. The third stage was performed at 3 centers using a modified version of a pre-existing, validated questionnaire and correlated with the Rochester evaluation score. OUTCOME: We sought to determine the suitability of 3D model for training in penile prosthesis surgery in comparison with the available cadaveric model. RESULTS: The evaluation revealed a high Pearson correlation coefficient (0.86) between questions of the Rochester evaluation score and modified validated questionnaire. The 3D model scored 4.33 ± 0.57 (on a Likert scale from 1 to 5) regarding replication of the relevant human anatomy for the penile prosthesis surgery procedure. The 3D model scored 4.33 ± 0.57 (on a Likert scale from 1 to 5) regarding its ability to improve technical skills, teach and practice the procedure, and assess a surgeon's ability. Furthermore, the experts stated that compared with the cadaver, the 3D model presented greater ethical suitability, reduced costs, and easier accessibility. CLINICAL IMPLICATIONS: A validated 3D model is a suitable alternative for penile prosthesis surgery training. STRENGTHS AND LIMITATIONS: This is the first validated 3D hydrogel model for penile prosthesis surgery teaching and training that experts consider suitable for skill acquisition. Because specific validated guidelines and questionnaires for the validation and verifications of 3D simulators for penile surgery are not available, a modified questionnaire was used. CONCLUSION: The current 3D model for penile prosthesis surgery shows promising results regarding anatomic properties and suitability to train surgeons to perform penile implant surgery. The possibility of having an ethical, easy-to-use model with lower costs and limited consequences for the environment is encouraging for further development of the models.

Platelet-rich plasma therapy in erectile dysfunction and Peyronie's disease: a systematic review of the literature.

PURPOSE: Platelet-rich plasma (PRP) as a regenerative therapy has gained interest in the field of andrology for the treatment of erectile dysfunction (ED) and Peyronie's disease (PD). This systematic review aims to critically evaluate the current evidence on the use of PRP for these conditions. METHODS: We performed a systematic literature search according to the PRISMA guidelines using PubMed and Scopus databases in December 2023. Studies were included if they evaluated the effect of PRP therapy for ED or PD in humans. RESULTS: We identified 164 articles, 17 of which were included, consisting of 11 studies on ED, 5 studies on PD, and 1 study on both. We included four randomized controlled trials, 11 prospective cohort studies, and three retrospective cohort studies including a total of 1099 patients. The studies on ED and PD generally showed small to moderate benefits with mild and transient side effects and no major adverse events were reported. General limitations included variations in PRP protocols, small sample sizes, short follow-up periods, and lack of control groups except in the three randomized trials on ED and the one on PD. CONCLUSION: The literature on PRP therapy in andrology is limited and difficult to interpret due to variations in protocols and methodological drawbacks. Further research is necessary to determine the optimal preparation and treatment protocols for PRP therapy and clarify its effectiveness in andrology.

Robot-assisted partial nephrectomy in patients aged 75 years or older - comparing the risk of complications with their younger counterparts.

BACKGROUND & AIM: More elderly patients are diagnosed with kidney tumors where partial nephrectomy is technically possible. We investigated whether patients ≥ 75 years old had an increased risk of complications following robot-assisted partial nephrectomy (RAPN) compared to younger patients. METHODS: Retrospective, consecutive study including patients who underwent RAPN between May 2016 - April 2023. Preoperative data, operative data and complications within 90 days were recorded by patient record review. Complications were classified according to Clavien-Dindo (CD). RESULTS: 451 patients underwent RAPN and a postoperative complication was recorded in 131 (29%) patients of which 28 (6%) were CD ≥ III. Any postoperative complication was recorded in 24/113 patients (21%) < 55 years, 40/127 patients (31%) 55-64 years, 45/151 patients (42%) 65-74 years, and 22/60 patients (37%) ≥ 75 years. Comparable numbers for a CD ≥ III postoperative complication were 2/113 (2%) < 55 years, 6/127 (7%) 55-64 years, 12/151 (8%) 65-74 years, and 5/60 (8%) ≥ 75 years. In multivariate logistic regression analysis, patients ≥ 75 years had a non-significant increased risk of complications when controlling for preoperative variables (OR 1.82 [95% CI 0.80-4.13]) or perioperative variables (OR 1.98 [95% CI 0.86-4.58]) compared to patients < 55 years. Two patients died postoperatively. Both were ≥ 75 years (2/60, 3%). DISCUSSION AND CONCLUSIONS: Selected patients ≥ 75 years can undergo RAPN without a significantly increased risk of postoperative complications. However, a mortality rate of 3% in this age group indicates that these patients are frail when postoperative complications occur.

CYP7B1 as a Biomarker for Prostate Cancer Risk and Progression: Metabolic and Oncogenic Signatures (Diagnostic Immunohistochemistry Analysis by Tissue Microarray in Prostate Cancer Patients-Diamond Study).

We aimed to analyze the association between CYP7B1 and prostate cancer, along with its association with proteins involved in cancer and metabolic processes. A retrospective analysis was performed on 390 patients with prostate cancer (PC) or benign prostatic hyperplasia (BPH). We investigated the interactions between CYP7B1 expression and proteins associated with PC and metabolic processes, followed by an analysis of the risk of biochemical recurrence based on CYP7B1 expression. Of the 139 patients with elevated CYP7B1 expression, 92.8% had prostate cancer. Overall, no increased risk of biochemical recurrence was associated with CYP7B1 expression. However, in a non-diabetic subgroup analysis, higher CYP7B1 expression indicated a higher risk of biochemical recurrence, with an HR of 1.78 (CI: 1.0-3.2, p = 0.05). PC is associated with elevated CYP7B1 expression. In a subgroup analysis of non-diabetic patients, elevated CYP7B1 expression was associated with an increased risk of biochemical recurrence, suggesting increased cancer aggressiveness.

Robot-assisted radical cystectomy with intracorporeal urinary diversion: a Danish 11-year series.

OBJECTIVES: To evaluate the oncological and perioperative outcomes from a large, single-centre, robot-assisted radical cystectomy (RARC) cohort performed with intracorporeal urinary diversion (ICUD). PATIENTS AND METHODS: Patients who underwent RARC because of bladder cancer or recurrent carcinoma in situ from June 2009 until August 2020 at Herlev and Gentofte Hospital were prospectively and consecutively included. Kaplan-Meier survival analysis was used to estimate recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). A Cox proportional hazards model was used to identify individual predictors of outcomes. Multiple logistic regression analysis was used to identify predictors of high-grade complications (Clavien-Dindo Grade ≥III). RESULTS: A total of 542 patients were included. The median (interquartile range) follow-up was 5.3 (2.73-8.06) years. In all, 78 patients (14%) were converted to open surgery; 15 (3%) during cystectomy and 63 patients (12%) were converted from ICUD to extracorporeal urinary diversion. The 5-year RFS, CSS and OS rates were 63% (95% confidence interval [CI] 59%-68%), 75% (95% CI 72%-80%) and 67% (95% CI 63%-72%), respectively. Pathological non-organ-confined disease (tumour stage >T2 or positive lymph nodes) predicted poorer RFS, CSS and OS. Reconstruction with a neobladder (20% of cases) compared to an ileal conduit was the only predictor of high-grade complications (odds ratio 2.54, 95% CI 1.46-4.43; P < 0.001). CONCLUSION: A RARC with ICUD is feasible as a standard surgical procedure for bladder cancer with only a few patients converted to open surgery. In our hands reconstruction with a neobladder was a strong predictor for high-grade complications.

Robot-assisted laparoscopic varicocelectomy in a pediatric population.

PURPOSE: To present our experience with robot-assisted laparoscopic varicocelectomy in a pediatric population. METHODS: We reviewed 49 consecutive cases performed by the same experienced surgeon. One-to-four veins were ligated at the internal ring of the inguinal canal, while the testicular artery and lymphatics were spared. Information on patient characteristics, surgical time, complications, and recurrences were collected. RESULTS: Median patient age was 14 (range 10-17) years. Forty-eight had left-sided varicoceles and one had a bilateral varicocele. Forty-five were grade 3. All patients were referred due to discomfort/pain and 20 also had reduced testicular size. The median operating time from skin incision was 48 min (31-89 min) and the median console time was 18 min (7-55 min). Forty-seven patients were discharged the same day. Two patients experienced pain and problems urinating, respectively. These issues had resolved by the first post-operative day. There were no other complications, but at 6 months, eight recurrences were noted (16%). Scrotal complaints had subsided in all patients. Catch-up growth of the affected testicles was seen in 19/20 cases. CONCLUSION: Robot-assisted laparoscopic varicocelectomy is feasible and safe in a pediatric population but with a relatively high recurrence rate.

The impact of asexual trait and porn addiction in a young men healthy cohort.

In the present study, we aimed to evaluate the association between asexual trait, erectile dysfunction (ED) and porn addiction in a community sample of young men. Between August 2019 and October 2019, a total of 559 young male adults were subjected to an online survey sponsored by social networks with the aim of assessing their sexual habits. The following questionnaires were administered: The International Index of Erectile Function (IIEF-5), Masturbation Erection index (MEI), Pornography Craving Questionnaire (PCQ) and Asexuality Identification Scale (AIS). The overall rate of ED according to IIEF-5 was 26.0% (165/478), the rate of ED according to MEI was 16.9% (81/478) and the rate ED in patients with AIS ≥23 indicating asexual trait was 10.0% (48/478). We found that IIEF-5 was positively associated with MEI (b = 0.32; p < .01) and negatively with AIS (b = -0.36; p < .01) and MEI was negatively associated with AIS (b = -0.36; p < .01). We found that MEI (odds ratio [OR]: 0.86; p < .01) and IIEF-5 (OR: 0.89; p < .01) were inversely associated with asexual trait. The presence of asexual trait can hide a greater risk of finding ED both in intercourse or masturbation. These results should be taken into consideration during the general assessment of the patient with sexual problems.

E-Sexual Health: A Position Statement of the European Society for Sexual Medicine.

BACKGROUND: Opportunities and pitfalls of e-health have been described and assessed in various health domains, but in the field of sexual health, the respective literature is limited. AIM: The aim of this document is to present the European Society of Sexual Medicine's (ESSM) current position statement on e-sexual health. METHODS: This statement article is an expert opinion-based proposal that was developed under the auspices of the ESSM with input from the e-sexual health subcommittee of the ESSM Scientific Committee. OUTCOMES: ESSM statements were provided on four domains: health information for patients, e-learning for professionals, health interventions, and health research. RESULTS: e-Sexual health is the use of information and communication technologies for sexual health including sexual health care, surveillance, education, knowledge, and research. Quality indicators have to be applied on Web pages that provide sexual health information, e-learning can increase educational opportunities for professionals, online treatment interventions can be effective but needs to be available to the public, and online health research can provide access to difficult to reach populations. CLINICAL IMPLICATIONS: The ESSM acknowledges the necessity for the use of information and communication technologies to meet the sexual health needs of citizens and patients and also the professional needs of sexual healthcare providers, in an evidence-based manner. STRENGTHS & LIMITATIONS: ESSM statements on this topic were provided based on expert opinion and summarize the ESSM position in this field. CONCLUSION: The ESSM believes that e-sexual health can provide opportunities for the improvement of the sexual health of the population. Kirana PS, Gudeloglu A, Sansone A, et al. E-Sexual Health: A Position Statement of the European Society for Sexual Medicine. J Sex Med 2020;17;1246-1253.

Sexual Motivators and Endorsement of Models Describing Sexual Response of Men Undergoing Androgen Deprivation Therapy for Advanced Prostate Cancer.

BACKGROUND: Androgen deprivation therapy (ADT) administered against metastatic prostate cancer has significant side effects including sexual dysfunction. AIM: To assess sexual interest and motivators for sex during ADT and to find out what model of sexuality best describes the sexual experience for men during this treatment. METHODS: A questionnaire was mailed to patients who had received ADT for ≥6 months. Patients were asked to choose all relevant entities from a list of sexual motivators and between models of sexuality described by Masters and Johnson (excitement and physical experiences), Kaplan (sexual desire), and Basson (intimacy and closeness to partner). Erectile function was assessed by the Erection Hardness Scale, and sexual satisfaction was measured on a scale from 0 to 10. OUTCOMES: Sexual activity, erectile function, sexual satisfaction, and motivators for sexual interest in the study subjects as well as the proportion of participants who endorsed either of the 3 models of sexuality. RESULTS: A total of 173 men were invited, and 76 returned the questionnaires (44%). The median age was 76 (range 69-80) years, and the median duration of ADT was 30 months. A total of 62 men had been sexually active before ADT, and of these, 2 were still active. Another 29 were interested in sexual activity. 3 men endorsed the Masters and Johnson model, whereas the remaining participants did not endorse any of the models. The motivators for sexual interest were feeling an emotional connection to the partner (n = 16), sexual desire (n = 10), satisfaction of the partner (n = 8), fear that the partner would leave (n = 4), achieving orgasm (n = 3), and a desire to feel masculine (n = 1). No one was interested in sexual activity to reduce stress or to maintain confidence. Only 1 patient had erections sufficient for penetrative intercourse, and the median sexual satisfaction for the entire group was 0 (interquartile range: 0-5). CLINICAL IMPLICATIONS: Sexuality and sexual function should be addressed in men undergoing ADT. STRENGTHS & LIMITATIONS: The main strength of our study is that we are the first to explore both motivators for sexual activity and endorsement of sexual models in men undergoing ADT. The study is limited by the relatively low number of participants and the response rate of 44%. CONCLUSION: ADT is detrimental to sexual function. However, many patients maintain an interest in sexual activity, which does not fit our established models. Rather, factors such as keeping an emotional connection with a partner play a role. Fode M, Mosholt KS, Nielsen TK, et al. Sexual Motivators and Endorsement of Models Describing Sexual Response of Men Undergoing Androgen Deprivation Therapy for Advanced Prostate Cancer. J Sex Med 2020;17:1538-1543.

Patient-reported outcomes from a single-centre prospective post-marketing study on Collagenase Clostridium Histolyticum injections for Peyronie's disease.

The aim of this study was to evaluate patient-reported outcomes of Collagenase Clostridium Histolyticum (CCHi) for Peyronie's Disease. Patients treated with 2-4 cycles of CCHi between 01/2016 and 08/2018 were asked to fill out the "bother domain" of the Peyronie's Disease Questionnaire (PDQ) at scheduled appointments for injections. CCHi cycles involved two injections (0.58 mg) separated by 48-72 hr. During the study, 34 patients were treated, seven patients were excluded due to incomplete baseline values. Mean (standard deviation) PDQ bother domain baseline score was 11.1 (2.6). ANOVA demonstrated statistically significant effects of injections (p < .001) with a decrease in PDQ bother domain scores 6 weeks after the 1st cycle (9.9 [3.3], p = .013), 6 weeks after the 2nd cycle (8.2 [4.0], p = .009) and 6 weeks after the 3rd cycle (6.5 [3.6], p < .001). After 2-4 cycles of CCHi treatment, patients reported changes in penile curvature as "Worse" (0), "No Change" (2), "Little decrease" (10), Decrease (10) and "Significant decrease" (4). After completion of CCHi treatment, 82% of patients still reported that vaginal intercourse was difficult or impossible. Patients with Peyronie's Disease undergoing CCHi treatment reported statistically significant decreases in PDQ bother domain scores. However, most patients still report difficulty with intercourse after treatment.

Metabolic consequences of gonadotropin-releasing hormone agonists vs orchiectomy: a randomized clinical study.

OBJECTIVES: To compare the metabolic changes between men with advanced prostate cancer commenced on a gonadotropin-releasing hormone (GnRH) agonist and those treated with orchiectomy. PATIENTS AND METHODS: Fifty-eight hormone-naive men with advanced prostate cancer were randomly assigned (1:1) to either subcapsular orchiectomy or triptorelin 22.5 mg/24 week depot injections. The participants were followed for 48 weeks, with study visits at baseline, 12, 24 and 48 weeks. The primary endpoint was changes in fasting plasma glucose. Secondary endpoints included changes in body composition (i.e. weight, fat mass, visceral adipose tissue [VAT], subcutaneous adipose tissue [SAT], lean body mass [LBM] and android/gynoid fat [AG] ratio) assessed with dual X-ray absorptiometry, serum lipid profiles, and insulin resistance evaluated during an oral glucose tolerance test. Linear mixed models were used to analyse the between-group differences. RESULTS: No treatment differences in the changes in fasting plasma glucose (0.2 mmol/L, 95% confidence interval [CI] -0.1, 0.4; P = 0.32) were observed. The orchiectomy group experienced greater increases in total fat mass (+2.06 kg, 95% CI 0.55, 3.56), SAT (+133 cm3 , 95% CI 22, 243) and weight (+3.30 kg, 95% CI 0.74, 5.87) at 48 weeks than did the triptorelin group (all P < 0.05), with the increases in fat mass being moderately correlated with increases in insulin resistance (P < 0.001). No differences in changed VAT, LBM or AG ratio were observed between the groups. The pooled analyses, combining data from both groups, showed androgen deprivation therapy (ADT) to significantly increase fat mass, SAT, VAT, serum cholesterols (total, high-density lipoprotein and low-density lipoprotein) and all measures of insulin resistance over time, while LBM decreased as compared with baseline values (all P < 0.05). These changes were apparent after only 12-24 weeks of ADT. CONCLUSIONS: Androgen deprivation therapy leads to adverse changes in body composition and increased insulin resistance and serum cholesterols, with changes already observed after only 12-24 weeks of treatment. This study further demonstrates that orchiectomy causes greater increases in fat accumulation compared with GnRH agonists and that these increases are associated with an increase in insulin resistance.

Effects of Preoperative Atorvastatin Treatment On Erectile Function After Radical Prostatectomy: Results From a Subgroup of ESTO1, a Randomized, Double-Blind, Placebo-Controlled Study.

INTRODUCTION: Erectile dysfunction is common after radical prostatectomy because of damage to the cavernous nerves. Thus, it is important to identify new ways to avoid this problem. For example, statins have shown positive effects on erectile function and may have anti-inflammatory effects that improve recovery after surgery. AIM: The aim of this exploratory analysis of a subgroup from ESTO1, a randomized, double-blind, placebo-controlled study, was to evaluate the preoperative use of atorvastatin on erectile function after radical prostatectomy. METHOD: Patients were randomized to either 80 mg atorvastatin or placebo daily before undergoing radical prostatectomy from study inclusion to the day of surgery. Altogether 118 men with prostate cancer and scheduled for radical prostatectomy were asked to fill out the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire before surgery and at 3, 6, 9, and 12 months after surgery. MAIN OUTCOME MEASUREMENTS: The study was exploratory, with the main outcome being the overall difference between IIEF-5 scores in the 2 groups at 12 months. Several hypotheses generating sub-analyses were conducted. RESULTS: Overall, 85% filled out the IIEF-5 questionnaire before their operation and 85%, 81%, 78%, and 78% completed it at 3, 6, 9, and 12 months follow-up, respectively. 52% of men had information available at all time points. There were no statistically significant differences between the groups at baseline in either erectile function, comorbidities, or tumor characteristics. The median duration of use of atorvastatin and placebo before surgery was 27 and 25 days, respectively. Preoperative atorvastatin treatment had no statistically significant effect on erectile function after prostatectomy as compared with placebo, although IIEF-5 scores were higher at all time points in the statin arm. Furthermore, atorvastatin treatment compared with placebo improved IIEF-5 scores at 12 months after surgery when the cavernous nerves were at least partially intact bilaterally (P < .04, n = 65); however, after full bilateral or unilateral nerve-sparing, the difference was not statistically significant. CLINICAL IMPLICATION: Short-term statin treatment did not improve recovery of erectile function after prostatectomy; however, further studies are needed before final conclusions. STRENGTHS & LIMITATIONS: This was a randomized placebo-controlled study. Original ESTO1 study was designed to detect a difference in prostate cancer biomarkers. CONCLUSION: Short-term atorvastatin treatment before radical prostatectomy had no statistically significant effect on the recovery of erectile functions in a non-selected cohort of patients undergoing radical prostatectomy. Further studies will be needed to clarify the role of long-term atorvastatin use before and after prostatectomy. Siltari A, Riikonen J, Fode M, et al. Effects of Preoperative Atorvastatin Treatment On Erectile Function After Radical Prostatectomy: Results From a Subgroup of ESTO1, a Randomized, Double-Blind, Placebo-Controlled Study. J Sex Med 2019;16:1597-1605.

Luteinizing Hormone-Releasing Hormone Agonists are Superior to Subcapsular Orchiectomy in Lowering Testosterone Levels of Men with Prostate Cancer: Results from a Randomized Clinical Trial.

PURPOSE: Recent evidence suggests that reaching the lowest achievable levels of testosterone with androgen deprivation therapy delays disease progression and increases overall survival in men with advanced prostate cancer. The aim of this analysis was to compare posttreatment serum testosterone levels between patients undergoing subcapsular orchiectomy and patients treated with the luteinizing hormone-releasing hormone agonist triptorelin. MATERIALS AND METHODS: In this randomized clinical trial we included 58 consecutive hormone naïve men diagnosed with advanced prostate cancer at Herlev and Gentofte University Hospital, Herlev, Denmark from September 2013 to March 2015. Followup was 48 weeks. Participants were randomly assigned 1:1 to subcapsular orchiectomy or triptorelin 22.5 mg given as 24-week depot injections. Androgen status was measured by liquid chromatography-tandem mass spectrometry prior to treatment and after 12, 24 and 48 weeks. Between group differences in achieved hormone levels were analyzed by longitudinal Tobit regression. RESULTS: Triptorelin injections resulted in 29% lower testosterone levels (95% CI 17.2-41.7) compared to subcapsular orchiectomy (p <0.001). A significantly higher proportion of men receiving triptorelin had testosterone levels less than 20 ng/dl at 12 and 48 weeks compared to men undergoing orchiectomy (97% vs 79% and 100% vs 87%, respectively, p <0.05). There was no detectable difference in the adrenal androgen reduction between the treatment groups. CONCLUSIONS: The use of 24-week depot triptorelin injections results in significantly lower testosterone levels compared to subcapsular orchiectomy. To our knowledge this is the first randomized study to demonstrate a difference in treatment effect between surgical and medical castration on testosterone levels.

Prevalence and Predicting Factors for Commonly Neglected Sexual Side Effects to External-Beam Radiation Therapy for Prostate Cancer.

INTRODUCTION: Changes in sexual function other than erectile dysfunction are sparsely investigated after radiation therapy for prostate cancer. AIM: To investigate orgasmic dysfunction, urinary incontinence during sexual activity, changes in penile morphology, and sensory disturbances in the penis in patients with prostate cancer treated with external-beam radiation therapy (EBRT). METHODS: In February 2015, men treated with EBRT at our center 3 months to 5 years previously (N = 519) received a study-specific questionnaire. This was developed from purpose-built questions and validated tools including the Erection Hardness Scale. All patients had received a radiation dose of 78 Gy. Androgen deprivation therapy was administered according to disease characteristics. MAIN OUTCOME MEASURES: Outcome measurements were prevalence rates and predictors of these side effects as identified by multivariate logistic regression analyses. RESULTS: One hundred nine patients were eligible (sexually active and had completed androgen deprivation therapy) for inclusion. Twenty-four percent reported anorgasmia, 44% reported a decreased intensity of their orgasms, and 40% reported that the time it took to reach orgasm had increased. Eleven percent reported anejaculation. Fifteen percent reported orgasm-associated pain. Only 4% reported urinary incontinence during sexual activity. Subjective penile length loss in excess of 1 cm was reported by 42%. Twelve percent reported an altered curvature of their penis after EBRT. Six percent reported painful erections. Twenty-seven percent reported decreased sensitivity in the penis after EBRT, 2% reported a cold sensation, and 2% reported paresthesia. Increasing time since final treatment increased the risk of penile sensory disturbances (odds ratio = 1.05; P = .028). CONCLUSION: Orgasmic dysfunction, changes in penile morphology, and sensory disturbances in the penis are common side effects of ERBT. Patients should be properly informed of the occurrence of these side effects before deciding which treatment to pursue. Frey A, Pedersen C, Lindberg H, et al. Prevalence and Predicting Factors for Commonly Neglected Sexual Side Effects to External-Beam Radiation Therapy for Prostate Cancer. J Sex Med 2017;14:558-565.

Effects of Tadalafil Once-Daily or On-Demand vs Placebo on Return to Baseline Erectile Function After Bilateral Nerve-Sparing Radical Prostatectomy--Results from a Randomized Controlled Trial (REACTT).

INTRODUCTION AND AIM: The multicenter, randomized, double-blind, double-dummy, placebo-controlled REACTT trial suggested that treatment with tadalafil once daily (OaD) started early after bilateral nerve-sparing radical prostatectomy (nsRP) for prostate cancer may contribute to erectile function (EF)-recovery, which was predefined as achieving an International Index of Erectile Function (IIEF)-EF score ≥22. Here, we report descriptive post-hoc analyses, using the more strict definition for EF-recovery of returning back to the pre-surgery IIEF-EF-level ("back-to-baseline analysis"). METHODS: REACTT included 422 men <68 years with adenocarcinoma of the prostate and preoperative IIEF-EF ≥22 who underwent nsRP at 50 centers from 9 European countries and Canada. Patients were randomized post-nsRP 1:1:1 to 9-month double-blind treatment (DBT) with tadalafil 5 mg OaD (n = 139), tadalafil 20 mg on-demand (pro-re-nata, PRN; n = 142), or placebo (n = 141), followed by 6-week drug-free washout (DFW) and 3-month open-label tadalafil OaD treatment (OLT). MAIN OUTCOME MEASURES: Proportion of patients returning to their preoperative IIEF-EF category (22-25 or ≥26) at the end of DBT, DFW, and OLT. RESULTS: Overall, 92.4% of patients had pre-surgery (baseline) IIEF-EF scores ≥26 (tadalafil OaD 94.2%, PRN 91.6%, placebo 91.5%), 7.4% had IIEF-EF 22-25. At the end of DBT, 22.3% of patients on tadalafil OaD had achieved "back-to-baseline" IIEF-EF, compared with 11.3% on tadalafil PRN and 7.8% on placebo. Of all 58 patients "back-to-baseline" at the end of DBT, only 1 PRN-group patient had started from a baseline IIEF-EF <26. The treatment-group difference at the end of DBT was not maintained after DFW. After 3 months of OLT with tadalafil OaD, the proportion of patients with "back-to-baseline" IIEF-EF had almost doubled in all 3 groups. CONCLUSION: Changing the definition for EF-recovery from IIEF-EF ≥22 to the more strict definition of "returning back-to-baseline IIEF-EF" had no major impact. Tadalafil OaD started early after nsRP improved drug-assisted EF, but had no effect on unassisted EF following treatment cessation after 9 months.