Bone mineral density and response to treatment in men younger than 50 years with testosterone deficiency and sexual dysfunction or infertility.

PURPOSE: Testosterone deficiency is a known risk factor for osteopenia and osteoporosis in older men. Less is known about the impact of testosterone deficiency on bone mineral density in younger men. MATERIALS AND METHODS: We retrospectively reviewed the charts at an andrology/infertility clinic and identified 399 men younger than 50 years who underwent baseline dual energy x-ray absorptiometry and had total testosterone less than 350 ng/dl or free testosterone less than 1.5 ng/dl. Additional analysis was done in a subgroup of 75 men (18.8%) in whom dual energy x-ray absorptiometry was repeated after treatment at a mean ± SD of 30.4 ± 16.2 months. The determination of osteoporosis or osteopenia was based on T-scores (osteopenia less than -1.0 and osteoporosis less than -2.5) of the lumbar spine and left hip. RESULTS: Of all 399 men 141 (35.3%) had bone mineral density consistent with osteopenia at the lumbar spine (137) and/or the total hip (19). In 11 men (2.75%) bone mineral density was consistent with osteoporosis at the lumbar spine. On multivariate analysis higher body mass index was independently associated with increased bone mineral density at the spine (p <0.0001) as well as the hip (p <0.001). Testosterone treatment in 43 men increased spine bone mineral density (p <0.001). Significant decreases in spine bone mineral density developed in 21 men treated with clomiphene citrate or anastrazole (p = 0.003). No significant change was noted in hip bone mineral density for any treatment. CONCLUSIONS: More than a third of men younger than 50 years with testosterone deficiency and infertility or sexual dysfunction had decreased bone mineral density. Testosterone treatment increased bone mineral density while estrogen modulators such as clomiphene citrate or aromatase inhibitors decreased bone mineral density. These results suggest that dual energy x-ray absorptiometry may be warranted in young men with testosterone deficiency.

Medical hypothesis: loss of the endocrine function of the prostate is important to the pathophysiology of postprostatectomy erectile dysfunction.

INTRODUCTION: Three decades after the first nerve-sparing radical prostatectomy, postoperative erectile dysfunction (ED) remains a challenging and common problem. Despite considerable advances and improvements in surgical techniques, full recovery of erectile function remains elusive even for young, potent men. This suggests, ipso facto, that factors other than surgical technique must be important to recovery of erectile function. AIM: This study aims to review evidence that the prostate is an endocrine gland with contributions to local and systemic concentrations of 5α-dihydrotestosterone (5α-DHT), a potent androgen shown to be critical to penile physiology. METHODS: Literature review of human and animal studies related to endocrine role of prostate and postoperative recovery of erectile function. MAIN OUTCOME MEASURES: Effect of 5α-DHT on erectile function and recovery after surgical injury. RESULTS: We advance the following hypothesis: "Loss of endocrine function of the prostate, specifically reduced local 5α-DHT concentration plays a major role in the failure of full recovery of erectile function following anatomic nerve-sparing radical prostatectomy." CONCLUSIONS: We propose two separate, yet interrelated, mechanisms whereby the loss of 5α-DHT interferes with postoperative recovery of erectile function: (i) 5α-DHT contributes to cavernous nerve integrity and its ability to recover from surgical insult. (ii) 5α-DHT is important to the structural/functional integrity of penile tissues and erectile physiology. Kacker R, Morgentaler A, and Traish A. Medical hypothesis: Loss of the endocrine function of the prostate is important to the pathophysiology of postprostatectomy erectile dysfunction.

Robotic partial nephrectomy versus laparoscopic partial nephrectomy: a single laparoscopic trained surgeon's experience in the development of a robotic partial nephrectomy program.

OBJECTIVES: We evaluated whether the surgical approach during the implementation of a robotic kidney surgery program influenced perioperative and oncologic outcomes. METHODS: We prospectively evaluated a single institution experience with minimally invasive partial nephrectomy between 2006 and 2010. The study cohort comprised 86 consecutively treated patients who underwent laparoscopic partial nephrectomy (LPN, N = 59) or robotic-assisted (RPN, N = 27) partial nephrectomy by a single surgeon. RESULTS: There was no difference between the LPN and RPN cohort in terms of gender, age, operative side, American Society of Anesthesiology score, or preoperative estimated glomerular filtration rate (eGFR). An early unclamping technique was used for 22 (82%) patients in the RPN cohort and 6 (10%) patients in the LPN cohort. (P < 0.001). Warm ischemia time was lower in the RPN cohort (mean 18.5 vs. 28.0 min, P = <0.001) as result of majority undergoing early unclamping. There was no difference in operative time, estimated blood loss, length of stay, transfusion rate, positive surgical margin, or postoperative decrease in eGFR. There was no difference in mean eGFR decrease after early unclamping (16%) versus traditional clamping (22%); however, 11 (29%) patients had greater than 50% decrease in eGFR after traditional clamping versus 0 patients after early unclamping (P = 0.014). CONCLUSION: Patients undergoing RPN during implementation of a robotic kidney surgery program when compared with LPN appear to have equivalent perioperative outcomes and oncologic efficacy. RPN patients had surgery later in our minimally invasive partial nephrectomy experience, and these results may not be generalizable to laparoscopic and/or robotic naïve surgeons.

Free testosterone by direct and calculated measurement versus equilibrium dialysis in a clinical population.

INTRODUCTION: The value of clinically available free testosterone (FT) assays remains controversial. Here, we evaluate the agreement between the radioimmunoassay (RIA) and calculated FT (cFT) versus equilibrium dialysis (EqD), considered the gold standard. METHODS: Fifty-six consecutive men (aged 26-77) had blood samples assessed for FT, including men with treated and untreated testosterone deficiency (TD) and men without TD. Samples were split and tested by the two methodologies at a Quest Diagnostics national reference laboratory. cFT was calculated by the Vermeulen method. RESULTS: A robust correlation was noted for RIA and EqD (r = 0.966) and for cFT and EqD (r = 0.986). Strong correlations were observed for men receiving testosterone therapy and for men in the lowest and highest quartiles for total and FT. The correlation of total testosterone with FT was similar for cFT (r = 0.843), RIA (r = 0.806), and EqD (r = 0.809). Sex-hormone binding globulin (SHBG) was not correlated with any measure of FT. Bland-Altman analysis demonstrated similar bias for both cFT and RIA, although cFT consistently overestimated FT. Numerical values for RIA were approximately one seventh of EqD values. CONCLUSIONS: These results support the clinical use of both RIA and cFT as measures of FT. Due to numerical differences, each test requires its own set of reference values.

Estrogens in men: clinical implications for sexual function and the treatment of testosterone deficiency.

INTRODUCTION: The role of estrogens in male sexual function and the pathogenesis of testosterone deficiency remain controversial and poorly understood. AIMS: To review the distribution of estrogens in normal and testosterone deficient men, their potential role in sexual function, and the clinical implications of elevated estrogens during testosterone therapy. METHODS: A comprehensive, broad-based literature review was conducted on the role of estrogens in male sexual function and testosterone deficiency. RESULTS: Estrogens elicit a variety of physiological responses in men and may contribute to modulation of sexual function. In the absence of testosterone deficiency, elevations in estrogens do not appear to be harmful and estrogens may help maintain some, but not all, sexual function in castrated men. While the therapeutic use of estrogens at pharmacologic doses has been used to suppress serum testosterone, naturally occurring elevations of estrogens do not appear to be a cause of low testosterone. During testosterone replacement, estrogens may rise and occasionally reach elevated levels. There is a lack of evidence that treatment of elevated estrogen levels during testosterone replacement has benefit in terms of male sexuality. CONCLUSION: Further research on the importance of estrogens in male sexual function is needed. Current evidence does not support a role of naturally occurring estrogen elevations in testosterone deficiency or the treatment of elevated estrogens during testosterone therapy.

Selection of ideal candidates for neuromodulation in refractory overactive bladder.

Sacral neuromodulation is a minimally invasive, reversible treatment option that has been approved by the US Food and Drug Administration for patients with urgency/frequency and urge incontinence. While long-term success rates are high, the high treatment cost and the need for operative revision or explantation in cases of failure make the selection of ideal candidates particularly important. Because predictive factors for success and the exact mechanism of action are not known, physicians must rely on a preimplantation test procedure, either in the office or in the operating room, to select patients for implantation of a pulse generator. In this paper, we review the recent literature on performing a test procedure with both temporary and permanent leads and the selection of optimal candidates for sacral neuromodulation therapy.

Decreased stone-free rates after percutaneous nephrolithotomy for high calcium phosphate composition kidney stones.

PURPOSE: To our knowledge the most effective treatment in patients with renal stones containing calcium phosphate remains unknown. An inverse correlation exists between calcium phosphate stone composition and the stone-free rate of shock wave lithotripsy. It is unknown whether this is due to treatment type (shock wave lithotripsy) or to a feature unique to calcium phosphate stones. We determined whether calcium phosphate stone composition affects the stone-free rate of percutaneous nephrolithotomy. MATERIALS AND METHODS: Percutaneous nephrolithotomy was performed in 111 patients between 2001 and 2006 and stone fragments were analyzed for calcium phosphate composition. Patients were categorized into groups based on calcium phosphate content. All patients underwent preoperative computerized tomography. Patients were considered stone-free after percutaneous nephrolithotomy when fragments were 2 mm or less on noncontrast computerized tomography. RESULTS: A total of 213 percutaneous nephrolithotomies were performed. An increased percent of calcium phosphate was related to a decreased percutaneous nephrolithotomy success rate (p = 0.005), independent of preoperative stone burden (p = 0.8). Patients with greater than 60% calcium phosphate stones were significantly less likely to be stone-free after percutaneous nephrolithotomy than those with less calcium phosphate (60%, OR 2.45, 95% CI 1.103-5.4401 vs 80%, OR 3.72, 95% CI 1.33-10.44). CONCLUSIONS: High calcium phosphate renal stone content leads to a decreased stone-free rate. Further study is required to determine the mechanism of stone resilience as well as the most appropriate treatment modality in patients with high calcium phosphate composition kidney stones.

Radiographic parameters on noncontrast computerized tomography predictive of shock wave lithotripsy success.

PURPOSE: Accurate prediction of shock wave lithotripsy success for given patient and radiographic parameters will lead to improved selection of patients for shock wave lithotripsy vs more invasive treatment. In this study we determined which radiographic parameters are the most predictive of shock wave lithotripsy success, and present a method to incorporate these into current and future models based on nonradiographic parameters. MATERIALS AND METHODS: A retrospective case-control study was performed to determine average, maximum and standard deviation of stone attenuation values, stone size and skin-to-stone distance on preoperative noncontrast computerized tomography for 220 patients successfully treated with shock wave lithotripsy and 105 patients in whom shock wave lithotripsy failed. RESULTS: Average stone attenuation is the best independent predictor of shock wave lithotripsy success as determined by the Student t test (p <0.0001) and receiver operating characteristic curves. Odds and likelihood ratios are provided for shock wave lithotripsy success for incremental average HU cutoffs. An average HU cutoff can be established over which the refined probability of success is below an arbitrary minimally acceptable cutoff of a 60% stone-free rate. Using pre-test probabilities of shock wave lithotripsy success from nomograms in the literature, our data suggest that shock wave lithotripsy should be first line therapy for solitary 6 to 10 mm stones with an average stone attenuation of less than 1,000 and 640 HU for the proximal ureter and renal pelvis, respectively. CONCLUSIONS: Average stone attenuation is a convenient radiographic measure that can be used to refine a known probability of shock wave lithotripsy success. Clinical HU cutoff guidelines can be determined based on current or future predictive nomograms based on other parameters.

Can testosterone therapy be offered to men on active surveillance for prostate cancer? Preliminary results.

This report presents our experience with T therapy in a cohort of T-deficient men on active surveillance (AS) for Gleason 3 + 3 and Gleason 3 + 4 prostate cancer (PCa). A retrospective chart review identified 28 men with T deficiency who underwent T therapy (T group) for at least 6 months while on AS for PCa. A comparison group of 96 men on AS for PCa with untreated T deficiency (no-T group) was identified at the same institution. The AS protocol followed a modified Epstein criteria and allowed inclusion of men with a single core of low-volume Gleason 3 + 4 PCa. Mean age was 59.5 and 61.3 years, and mean follow-up was 38.9 and 42.4 months for the T and no-T groups, respectively. Of all 28 men in the T group, 3 (10.7%) men developed an increase in Gleason score while on AS. Of 22 men in the T group with Gleason 3 + 3 disease, 7 (31.8%) men developed biopsy progression including 3 men (13.6%) who developed Gleason 3 + 4 PCa. Of 6 men with Gleason 3 + 4 disease at baseline, 2 (33.3%) men developed an increase in tumor volume, and none developed upgrading beyond Gleason 3 + 4. All 96 men in the no-T group had Gleason 3 + 3 disease at baseline and, 43 (44.7%) developed biopsy progression, including 9 men (9.38%) with upgrading to Gleason 7 (3 + 4). Biopsy progression rates were similar for both groups and historical controls. Biopsy progression in men on AS appears unaffected by T therapy over 3 years. Prospective placebo-controlled trials of T therapy in T-deficient men on AS should be considered given the symptomatic benefits experienced by treated men.

Adult-Onset Hypogonadism.

In August 2015, an expert colloquium commissioned by the Sexual Medicine Society of North America (SMSNA) convened in Washington, DC, to discuss the common clinical scenario of men who present with low testosterone (T) and associated signs and symptoms accompanied by low or normal gonadotropin levels. This syndrome is not classical primary (testicular failure) or secondary (pituitary or hypothalamic failure) hypogonadism because it may have elements of both presentations. The panel designated this syndrome adult-onset hypogonadism (AOH) because it occurs commonly in middle-age and older men. The SMSNA is a not-for-profit society established in 1994 to promote, encourage, and support the highest standards of practice, research, education, and ethics in the study of human sexual function and dysfunction. The panel consisted of 17 experts in men's health, sexual medicine, urology, endocrinology, and methodology. Participants declared potential conflicts of interest and were SMSNA members and nonmembers. The panel deliberated regarding a diagnostic process to document signs and symptoms of AOH, the rationale for T therapy, and a monitoring protocol for T-treated patients. The evaluation and management of hypogonadal syndromes have been addressed in recent publications (ie, the Endocrine Society, the American Urological Association, and the International Society for Sexual Medicine). The primary purpose of this document was to support health care professionals in the development of a deeper understanding of AOH, particularly in how it differs from classical primary and secondary hypogonadism, and to provide a conceptual framework to guide its diagnosis, treatment, and follow-up.

Electrical and mechanical office-based neuromodulation.

Overactive bladder (OAB) is commonly encountered in urologic practice. Treatment algorithms begin with conservative therapy and pharmacotherapy with antimuscarinics. Some patients do not receive adequate relief from these methods or they do not tolerate side effects from pharmacotherapy. A test stimulation for sacral neuromodulation and percutaneous tibial nerve stimulation are office-based techniques that are commonly used as the next step in the algorithm of care in patients with OAB. These techniques are efficacious and approved by the Food and Drug Administration for treatment of overactive bladder and its associated symptoms.

Comparing costs of robotic, laparoscopic, and open partial nephrectomy.

UNLABELLED: Abstract Background and Purpose: Laparoscopic and robot-assisted partial nephrectomy (LPN and RPN) are common minimally invasive alternatives to open partial nephrectomy (OPN) for management of renal tumors. Cost discrepancies of these approaches warrants evaluation. We compared hospital costs associated with RPN, LPN, and OPN. PATIENTS AND METHODS: Costs were captured for 25 patients in each group who underwent RPN, LPN, or OPN at our institution between November 2008 and September 2010. Variable costs included operating room (OR) time, supplies, anesthesia, and inpatient care costs. Fixed costs included equipment purchase and maintenance. Impact of variable and fixed costs were estimated using sensitivity analysis. RESULTS: Overall variable costs were similar for RPN, LPN, and OPN ($6375 vs $6075 vs $5774, P=0.117, respectively). OR supplies contributed a greater cost for RPN and LPN than OPN ($2179 vs $1987 vs $181, P<0.0001, respectively), while inpatient stay costs were higher for OPN compared with LPN and RPN ($2418 vs $1305 vs $1274, P<0.0001, respectively). Sensitivity analysis of variable costs demonstrates that RPN and LPN can represent less costly alternatives to OPN if hospital stay for RPN and LPN is ≤2 days and OR time <195 and 224 minutes, respectively. Inclusion of fixed costs made OPN less expensive than LPN and RPN unless use of the robot increases and operative times are reduced. CONCLUSION: By minimizing OR time and hospital stay, RPN and LPN can be cost equivalent to OPN regarding variable costs. When including fixed costs, RPN and LPN were more costly than OPN, but equivalence may be possible with improvements in efficiency.

Primary vs. post-chemotherapy retroperitoneal lymph node dissection (RPLND) in patients with presence of teratoma at orchiectomy.

OBJECTIVE: The presence of teratoma in the primary orchiectomy specimen creates controversies for subsequent management. Although predominant teratoma is less likely to metastasize, teratoma in the retroperitoneum may be less amenable to chemotherapy. In order to elucidate the issues about teratoma in the primary tumor, we reviewed differences between primary retroperitoneal lymph node dissection (P-RPLND) vs. post-chemotherapy RPLND (PC-RPLND) in patients with teratoma at orchiectomy. MATERIALS AND METHODS: Patients who had undergone RPLND at our institution from 2001 to 2008 were identified, and clinical charts reviewed. Eighty-three patients with teratoma at orchiectomy were identified and perioperative data were obtained. RESULTS: Of the 83 patients with teratoma at orchiectomy who underwent RPLND, 44 (53%) and 39 (47%) underwent primary and PC-RPLND, respectively. Median follow-up was 1.4 years. Of the 83 patients with primary teratoma at orchiectomy, there were 7 (8%) patients with pure teratoma and 76 (92%) patients with mixed histology. Of the patients with mixed histology, 72 (87%) patients had embryonal carcinoma and 36 (43%) had LVI. There were 19 (43%) positive lymph nodes for P-RPLND, of which 13 (30%) contained teratoma. For the PC-RPLND group, 30 (77%) of lymph nodes were positive, of which 28 (72%) contained teratoma. There were 3 (4%) recurrences overall, all of which recurred in the PC-RPLND group. There were 11 (13%) perioperative complications total. There were no deaths in either group. CONCLUSIONS: Patients with teratoma at orchiectomy were associated with other high risk features and are at significant risk for metastatic disease. Patients with post-chemotherapy retroperitoneal findings are at significant risk for viable GCT and/or teratoma and should undergo PC-RPLND.

Endourologic procedures for benign prostatic hyperplasia: review of indications and outcomes.

PURPOSE: To discern the positive and negative attributes of the various treatment modalities for benign prostatic hyperplasia. MATERIALS AND METHODS: A comprehensive literature review is presented for endoscopic treatment of the bladder outlet obstruction with an emphasis on current randomized controlled trials available comparing these treatment modalities. RESULTS: Transurethral resection of the prostate remains the gold standard when assessing alternative treatment options available for benign prostatic hyperplasia. Holmium laser enucleation of the prostate demonstrates equivalent efficacy with a more favorable risk profile. Photoselective vaporization, transurethral needle ablation, and transurethral microwave therapy have demonstrated safety and short-term efficacy; however, data on long-term efficacy are currently lacking. CONCLUSION: The current endoscopic methods may offer favorable safety and efficacy for the treatment of the bladder outlet obstruction. However, further research is needed to establish long-term efficacy for many of the currently available treatment options.

Radical retropubic prostatectomy and robotic-assisted laparoscopic prostatectomy: likelihood of positive surgical margin(s).

OBJECTIVES: To evaluate whether the surgical approach influenced the likelihood of a positive surgical margin (PSM) adjusting for known preoperative predictors of PSM, year of radical prostatectomy, body mass index, use of nerve sparing, and patient age at radical prostatectomy. METHODS: The study cohort comprised 950 consecutively treated men with clinically localized prostate cancer who underwent open radical retropubic (RRP, n = 346) or robotic-assisted (RALP, N = 604) prostatectomy by a single surgeon (J.P.R., J.C.H.) at the Brigham and Women's Hospital from 2005 to 2008 and had complete information on baseline patient and tumor characteristics. Univariate and multivariate logistic regression analyses were performed to identify clinical factors significantly associated with the likelihood of a PSM. RESULTS: Men undergoing RALP compared with RRP were more likely to have a PSM (adjusted odds ratio 1.9; 95% confidence interval: 1.2-3.1, P = .0095). Significant interaction (P = .0085) was noted between the type of surgical approach and whether nerve sparing was performed on the likelihood of a PSM. Specifically, a significantly lower PSM rate was observed for men undergoing nerve sparing and RRP compared with nerve sparing and RALP (7.6% vs 13.5%, P = .007), whereas opposite trend was noted (P = .09) for men undergoing a non-nerve-sparing approach. CONCLUSIONS: Men undergoing RALP compared with RRP seem to have a greater likelihood of a PSM. Further study is needed to delineate whether this increase is due to an intrinsic limitation of RALP or unknown confounders.

Outpatient double percutaneous endolaparoscopic extraction of large continent urinary reservoir stones--a new minimally invasive approach.

PURPOSE: We report an efficient new method of managing massive stone burdens in continent urinary reservoirs without urethral access, using the minimally invasive double percutaneous endolaparoscopic technique. PATIENTS AND METHODS: After first obtaining and dilating a percutaneous tract into the reservoir, a second access is established using a laparoscopic trocar under direct vision. Using endoscopic instruments, large stones are placed into a laparoscopic entrapment bag, fragmented (if necessary), and then transferred extracorporeally without any damage to the integrity or mucosa of the reservoir and without leaving behind any stone fragments. RESULTS: This technique was used successfully in 5 of 5 patients with continent reservoirs, achieving stone-free status without short-term or long-term (mean follow-up 32.4 months, range 9-61 months) complications. CONCLUSION: Double percutaneous endolaparoscopic stone extraction is a safe, effective, and minimally invasive method of managing continent urinary reservoir stones.