The role of estradiol in male reproductive function.

Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen, also plays a critical role in male sexual function. Estradiol in men is essential for modulating libido, erectile function, and spermatogenesis. Estrogen receptors, as well as aromatase, the enzyme that converts testosterone to estrogen, are abundant in brain, penis, and testis, organs important for sexual function. In the brain, estradiol synthesis is increased in areas related to sexual arousal. In addition, in the penis, estrogen receptors are found throughout the corpus cavernosum with high concentration around neurovascular bundles. Low testosterone and elevated estrogen increase the incidence of erectile dysfunction independently of one another. In the testes, spermatogenesis is modulated at every level by estrogen, starting with the hypothalamus-pituitary-gonadal axis, followed by the Leydig, Sertoli, and germ cells, and finishing with the ductal epithelium, epididymis, and mature sperm. Regulation of testicular cells by estradiol shows both an inhibitory and a stimulatory influence, indicating an intricate symphony of dose-dependent and temporally sensitive modulation. Our goal in this review is to elucidate the overall contribution of estradiol to male sexual function by looking at the hormone's effects on erectile function, spermatogenesis, and libido.

Comparison of microdissection testicular sperm extraction, conventional testicular sperm extraction, and testicular sperm aspiration for nonobstructive azoospermia: a systematic review and meta-analysis.

OBJECTIVE: To investigate the relative differences in outcomes among microdissection testicular sperm extraction (micro-TESE), conventional testicular sperm extraction (cTESE), and testicular sperm aspiration (TESA) in men with nonobstructive azoospermia. DESIGN: Systematic review and meta-analysis. SETTING: Outpatient academic and private urology clinics. PATIENTS(S): Men with nonobstructive azoospermia. INTERVENTION(S): Micro-TESE, cTESE, or TESA. MAIN OUTCOME MEASURE(S): Sperm retrieval (SR). RESULT(S): Fifteen studies with a total of 1,890 patients were identified. The weighted average age of the patients was 34.4 years, the follicular stimulating hormone level was 20.5 mIU/mL, the T was 373 ng/dL, and the testicular volume was 13.5 mL. In a direct comparison, performance of micro-TESE was 1.5 times more likely (95% confidence interval 1.4-1.6) to result in successful SR as compared with cTESE. Similarly, in a direct comparison, performance of cTESE was 2.0 times more likely (95% confidence interval 1.8-2.2) to result in successful SR as compared with TESA. Because of inconsistent reporting, evaluation of other procedural characteristics and pregnancy outcomes was not possible. CONCLUSION(S): Sperm retrieval was higher for micro-TESE compared with cTESE and for cTESE compared with TESA. Standardization of reported outcomes as well as combining all available SR data would help to further elucidate the SRs of these procedures.

Outcomes of microdissection testicular sperm extraction in men with nonobstructive azoospermia due to maturation arrest.

OBJECTIVE: To evaluate sperm retrieval in men with nonobstructive azoospermia and maturation arrest (MA) undergoing microdissection testicular sperm extraction (micro-TESE). DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENT(S): Men with nonobstructive azoospermia and MA who underwent micro-TESE. INTERVENTION(S): Microdissection TESE. MAIN OUTCOME MEASURE(S): Sperm retrieval rate (SRR). RESULT(S): A total of 211 patients (13%) had a histologic finding of MA at the most advanced level. The overall SRR was 52%. A total of 146 patients were classified as having early MA (arrest at the primary spermatocyte stage), and 65 as having late MA (early spermatid stage). The SRR in men with early, vs. late, MA was 40% vs. 78%. Of the 211 men with MA, 51 had diffuse MA (100% of tubules showed MA). The SRR was significantly lower in men with diffuse vs. focal MA (35% vs. 57%). On multivariable analysis, late MA and higher follicle-stimulating hormone levels were positively associated with successful sperm retrieval. CONCLUSION(S): Sperm were successfully identified in up to one half of the men with MA after micro-TESE. Among men with MA, late MA seems to be the best predictor of successful sperm retrieval with micro-TESE.

Can Serum Testosterone Be Used as a Marker of Overall Health?

Low serum testosterone has been associated with obesity, type 2 diabetes, metabolic syndrome, and atherosclerosis. Individuals with these comorbidities are at increased risk of premature death and other adverse health effects. Clinical data portend low testosterone as a risk factor for developing these conditions which are supported by the hypogonadal-obesity-adipocytokine hypothesis. The authors support comprehensive evaluation for these comorbid conditions in men found to have low serum testosterone.

Long-term oncological outcomes of a phase II trial of neoadjuvant chemohormonal therapy followed by radical prostatectomy for patients with clinically localised, high-risk prostate cancer.

OBJECTIVE: To determine long-term oncological outcomes of radical prostatectomy (RP) after neoadjuvant chemohormonal therapy (CHT) for clinically localised, high-risk prostate cancer. PATIENTS AND METHODS: In this phase II multicentre trial of patients with high-risk prostate cancer (PSA level >20 ng/mL, Gleason ≥8, or clinical stage ≥T3), androgen-deprivation therapy (goserelin acetate depot) and paclitaxel, carboplatin and estramustine were administered before RP. We report the long-term oncological outcomes of these patients and compared them to a contemporary cohort who met oncological inclusion criteria but received RP only. RESULTS: In all, 34 patients were enrolled and followed for a median of 13.1 years. Within 10 years most patients had biochemical recurrence (BCR-free probability 22%; 95% confidence interval [CI] 10-37%). However, the probability of disease-specific survival at 10 years was 84% (95% CI 66-93%) and overall survival was 78% (95% CI 60-89%). The CHT group had higher-risk features than the comparison group (123 patients), with an almost doubled risk of calculated preoperative 5-year BCR (69% vs 36%, P < 0.01). After adjusting for these imbalances the CHT group had trends toward improvement in BCR (hazard ratio [HR] 0.76, 95% CI 0.43-1.34; P = 0.3) and metastasis-free survival (HR 0.55, 95% CI 0.24-1.29; P = 0.2) although these were not statistically significant. CONCLUSIONS: Neoadjuvant CHT followed by RP was associated with lower rates of BCR and metastasis compared with the RP-only group; however, these results were not statistically significant. Because this treatment strategy has known harms and unproven benefit, this strategy should only be instituted in the setting of a clinical trial.

Changes in pathologic outcomes and operative trends with robot-assisted laparoscopic radical prostatectomy.

INTRODUCTION: We hypothesized that there is a reverse stage migration, or a shift toward operating on higher-risk prostate cancer, in patients undergoing robot-assisted laparoscopic prostatectomy (RALP). We therefore evaluated the stage of disease at the time of surgery for patients with prostate cancer at a large tertiary academic medical center. MATERIALS AND METHODS: After institutional review board approval, we reviewed all patients that had undergone robotic prostatectomy. These patients were separated into three categories: An early era of 2005-2008, intermediate era of 2009-2010, and a current era of 2011-2012. RESULTS: A total of 3451 patients underwent robotic prostatectomy from 2005 to 2012. The proportion men with clinical T1 tumors declined from 88.3% in the early era to 72.2% in the current era (P < 0.0001). Men with preoperative biopsy Gleason 6 disease decreased from the early to the current era (P < 0.0001), while men with preoperative biopsy Gleason ≥ 8 showed the opposite trend, increasing from the early to the current era (P = 0.0002). From the early to the current era, the proportion of patients with National Comprehensive Cancer Network (NCCN) low risk prostate cancer decreased, while those with NCCN intermediate and high-risk disease increased. The proportion of pathologic T3 disease increased from 15.5% in the early to 30.6% in the current era (P < 0.0001). On the other hand, the proportion of pathologic T2/+ SMS (surgical margin status) decreased from 6.6% in the early era to 3.1% in the current era (P = 0.0002). CONCLUSIONS: We have demonstrated a reverse stage migration in men undergoing robotic prostatectomy. Despite the increasing proportion of men with extra-capsular disease undergoing RALP, the surgical margin status has remained similar. This could reflect both the changing dynamics of the population opting for surgery as well as the learning curve of the surgeons.

Comparison of questionnaires used for screening and symptom identification in hypogonadal men.

Late-onset hypogonadism (LOH) is typically defined as the cluster of symptoms appearing in aging men and accompanied by a decrease in serum testosterone levels. The identification of a simple screening tool with a high level of sensitivity and specificity to predict LOH has remained a challenge. To identify men with LOH, a variety of self-administered questionnaires have been developed including The Saint Louis University Androgen Deficiency in the Aging Male (ADAM) Questionnaire, The Quantitative ADAM (qADAM) Questionnaire, The Aging Male Symptoms (AMS) rating scale, The Massachusetts Male Aging Study (MMAS) questionnaire and The New England Research Institutes (NERI) hypogonadism questionnaire. The applicability of these questionnaires in the clinical setting is debated because some of the symptoms associated with LOH could be attributed to the natural process of aging and comorbidities. The goal of this review is to compare the utility and the validity of the different LOH questionnaires.

Risks of testosterone replacement therapy in men.

Testosterone replacement therapy (TRT) is a widely used treatment for men with symptomatic hypogonadism. The benefits seen with TRT, such as increased libido and energy level, beneficial effects on bone density, strength and muscle as well as cardioprotective effects, have been well-documented. TRT is contraindicated in men with untreated prostate and breast cancer. Men on TRT should be monitored for side-effects such as polycythemia, peripheral edema, cardiac and hepatic dysfunction.

Microsurgical epididymal sperm aspiration: indications, techniques and outcomes.

Microsurgical epididymal sperm aspiration (MESA) refers to retrieval of sperm-containing fluid from optimal areas of the epididymis that are selected and sampled using high-power optical magnification provided by an operating microscope. Retrieved sperm are subsequently used for intracytoplasmic sperm injection (ICSI) to induce fertilization and pregnancy. MESA is considered by many experts to be the gold standard technique for sperm retrieval in men with obstructive azoospermia given its high yield of quality sperm, excellent reported fertilization and pregnancy rates, and low risk of complications. However, MESA must be performed in an operating room, requires microsurgical skills and is only useful for reproduction using ICSI. Herein we present an overview of the evaluation of candidate patients for MESA, the technical performance of the procedure and the outcomes that have been reported.

Predictive factors of successful microdissection testicular sperm extraction.

Azoospermia in men requires microsurgical reconstruction or a procedure for sperm retrieval with assisted reproduction to allow fertility. While the chance of successful retrieval of sperm in men with obstructive azoospermia approaches >90%, the chances of sperm retrieval in men with non-obstructive azoospermia (NOA) are not as high. Conventional procedures such as fine needle aspiration of the testis, testicular biopsy and testicular sperm extraction are successful in 20-45% of men with NOA. With microdissection testicular sperm extraction (micro-TESE), the chance of successful retrieval can be up to 60%. Despite this increased success, the ability to counsel patients preoperatively on their probability of successful sperm retrieval has remained challenging. A combination of variables such as age, serum FSH and inhibin B levels, testicular size, genetic analysis, history of Klinefelter syndrome, history of cryptorchidism or varicocele and histopathology on diagnostic biopsy have provided some insight into the chance of successful sperm retrieval in men with NOA. The goal of this review was to evaluate the preoperative factors that are currently available to predict the outcome for success with micro-TESE.

Pour permettre une fécondité chez l'homme, l'azoospermie nécessite une reconstruction par microchirurgie ou une procédure de récupération de spermatozoïdes avec assistance médicale à la procréation. Alors que les chances d'une extraction positive de spermatozoïdes chez les hommes qui présentent une azoospermie obstructive atteignent plus de 90%, ces chances ne sont pas aussi grandes chez les hommes qui ont une azoospermie non obstructive (NOA). Les procédures conventionnelles telles que l'aspiration à l'aiguille fine du testicule, la biopsie testiculaire et l'extraction testiculaire de spermatozoïdes sont couronnées de succès chez 20-45% des hommes avec NOA. En cas d'extraction de spermatozoïdes testiculaires par microdissection (micro-TESE), les chances d'un prélèvement positif peuvent aller jusqu'à 60%. Malgré cette augmentation des chances, la possibilité d'informer les patients avant l'intervention de leurs chances d'avoir un prélèvement de spermatozoïdes positif reste un défi. La combinaison de variables telles l'âge, les taux sériques de FSH et d'inhibine B, le volume testiculaire, les analyses génétiques, un antécédent de syndrome de Klinefelter, de cryptorchidie ou de varicocèle, et l'histopathologie du tissu recueilli lors d'une biopsie diagnostique, a fourni un aperçu des chances d'obtenir un prélèvement positif de spermatozoïdes chez les hommes avec NOA. L'objectif de cette revue est d'évaluer les facteurs préopératoires qui sont actuellement disponibles pour prédire une issue positive à une micro-TESE.

Vasectomy reversal in humans.

Vasectomy is the most common urological procedure in the United States with 18% of men having a vasectomy before age 45. A significant proportion of vasectomized men ultimately request vasectomy reversal, usually due to divorce and/or remarriage. Vasectomy reversal is a commonly practiced but technically demanding microsurgical procedure that restores patency of the male excurrent ductal system in 80-99.5% of cases and enables unassisted pregnancy in 40-80% of couples. The discrepancy between the anastomotic patency rates and clinical pregnancy rates following vasectomy reversal suggests that some of the biological consequences of vasectomy may not be entirely reversible in all men. Herein we review what is known about the biological sequelae of vasectomy and vasectomy reversal in humans, and provide a succinct overview of the evaluation and surgical management of men desiring vasectomy reversal.

Reduction en masse in a 7-year-old boy: an interesting case.

Reduction en masse is a complication of inguinal hernia reduction in which a hernia is reduced back into the peritoneal cavity, but a loop of bowel remains trapped inside the hernia sac after reduction. Reduction en masse can be difficult to diagnose because of generalized and nonspecific symptoms. We describe a 7-year-old boy with an atypical presentation of reduction en masse after hernia reduction. The patient was a previously healthy child who presented with a mildly painful right inguinal mass of 1 day duration. An incarcerated hernia was noted, and after reduction, the pain dissipated for a short period, only to return with pain in the right lower quadrant and generalized peritoneal irritation. At surgical exploration, a reduction en masse was definitively diagnosed, and the incarcerated bowel was released from the hernia sac.

Posterior reconstruction before anastomosis improves the anastomosis time during robot-assisted radical prostatectomy.

BACKGROUND AND OBJECTIVES: Our goal was to evaluate posterior reconstruction of the rhabdosphincter during robot-assisted radical prostatectomy and determine whether this technique decreased anastomotic time of a surgeon in training to perform vesicourethral reconstruction. METHODS: We reviewed the first 25 robot-assisted prostatectomies performed by 2 urology surgeons in training (surgeon 1 and surgeon 2). The patient populations were matched for age, Gleason score, clinical stage, and PSA. Whereas surgeon 1 performed the vesicourethral anastomosis without posterior reconstruction, surgeon 2 reapproximated Denonvilliers' fascia of the posterior bladder to the rhabdosphincter. Time for each surgeon to complete the anastomosis and clinical factors was compared. RESULTS: Surgeon 1 had a median anastomosis time of 25 minutes (range, 17 to 48), whereas surgeon 2 had a median anastomosis time of 15 minutes (range, 10 to 30) (P<0.001). Biopsy Gleason score, pathological tumor stage, perineural invasion, median age at the time of surgery, PSA, prostate weight, and estimated blood loss were not significantly different between surgeons (P>0.05). Pathological Gleason score (P=0.045) and total console time (surgeon 1-216 minutes, surgeon 2-176 minutes; P=0.002) were significantly different between surgeons. CONCLUSION: Posterior reconstruction prior to anastomosis decreases anastomosis time for robotic surgeons in training.