Trends in Testosterone Replacement Therapy Use from 2003 to 2013 among Reproductive-Age Men in the United States.

PURPOSE: Although testosterone replacement therapy use in the United States has increased dramatically in the last decade, to our knowledge trends in testosterone replacement therapy use among reproductive-age men have not been investigated. We assessed changes in testosterone replacement therapy use and practice patterns among 18 to 45-year-old American men from 2003 to 2013 and compared them to older men. MATERIALS AND METHODS: This is a retrospective, cross-sectional analysis of men 18 to 45 and 56 to 64 years old who were enrolled in the Truven Health MarketScan® Commercial Claims Databases throughout each given calendar year from 2003 to 2013, including 5,094,868 men in 2013. Trends in the yearly rates of testosterone replacement therapy use were calculated using Poisson regression. Among testosterone replacement therapy users, the Cochran-Armitage test was used to assess temporal trends in age, formulation type, semen analysis and serum testosterone level testing during the 12 months preceding the documented use of testosterone replacement therapy. RESULTS: Between 2003 and 2013, there was a fourfold increase in the rate of testosterone use among 18 to 45-year-old men from 29.2/10,000 person-years to 118.1/10,000 person-years (p <0.0001). Among testosterone replacement therapy users, topical gel formulations were initially most used. Injection use then doubled between 2009 and 2012 (23.5% and 46.2%, respectively) and surpassed topical gel use in 2013. In men 56 to 64 years old there was a statistically significant threefold increase in testosterone replacement therapy use (p <0.0001), which was significantly smaller than the fourfold increase in younger men (p <0.0001). CONCLUSIONS: In 2003 to 2013, testosterone replacement therapy use increased fourfold in men 18 to 45 years old compared to threefold in older men. This younger age group should be a focus for future studies due to effects on fertility and unknown long-term sequelae.

Sexual Health Outcomes in Adults with Complete Male Epispadias.

PURPOSE: Complete male epispadias is a rare congenital anomaly characterized by failed closure of the entire penopubic dorsal urethra. Epispadias repair is typically performed during infancy, and resultant genitourinary abnormalities can have a marked impact on adult life. We assess long-term post-reconstruction sexual health and fertility outcomes in adults with complete male epispadias. MATERIALS AND METHODS: A total of 132 patients 18 years or older with complete male epispadias who had undergone reconstruction were identified from a prospectively maintained, institutionally approved database. Patients who could be contacted were asked to complete a telephone survey regarding sexual function. Reconstructive history and clinical details were obtained by chart/database review. RESULTS: Of 132 patients with complete male epispadias 74 met inclusion criteria and 15 (20%) completed the questionnaire. Seven patients (47%) reported currently being in a relationship. Although 12 patients (80%) reported overall satisfactory sexual intercourse, 11 (73%) admitted to 1 or more problems with sexual function, including abnormal ejaculation (53%), diminished sensation (20%) and difficulty maintaining an erection (20%). When questioned regarding the importance of fertility on a scale of 0 to 5 using a Likert-type item the response of 10 patients (67%) was 4 points or greater. Five patients (33%) reported having impregnated a sexual partner. Although 4 patients (27%) had suspicion of fertility problems, only 2 (13%) reported having abnormal semen analyses. CONCLUSIONS: This is one of few studies examining post-reconstruction sexual health and function in adults with complete male epispadias. Although small, our study demonstrates that patients are able to engage in relationships, participate in sexual intercourse and impregnate their partners. These results highlight sexual concerns and outcomes that may be of use when counselling patients with complete male epispadias and their families.

Robotic real-time near infrared targeted fluorescence imaging in a murine model of prostate cancer: a feasibility study.

OBJECTIVE: To evaluate the detection of near-infrared fluorescence from prostate tumors stained with a prostate-specific membrane antigen (PSMA)-targeted tracer developed in our institution with a novel robotic imaging system. METHODS: Prostate cancer cell lines PC3-pip (PSMA positive) and PC3-flu (PSMA negative) were implanted subcutaneously into 6 immunodeficient mice. When tumors reached 5 mm, a PSMA-targeted fluorescent conjugate was injected intravenously. The first 3 mice underwent near-infrared imaging immediately and hourly up to 4 hours after injection to determine the time necessary to obtain peak fluorescence and were killed. The last 3 mice were imaged once preoperatively and were euthanized 120 minutes later. Excision of the tumors was performed by using a novel robotic imaging system to detect near-infrared fluorescence in real time. Specimens were submitted for pathology. RESULTS: In the first 3 mice, we found 120 minutes as the time needed to observe peak fluorescence from the PSMA-positive tumors. We identified discrete near-infrared fluorescence from 2 of 3 PSMA-positive tumors with the robotic imaging system. Surgical margins were negative for all excised specimens except for one PSMA-negative tumor. CONCLUSIONS: Real-time near-infrared fluorescence imaging of prostate cancer is feasible with a novel robotic imaging system. Further research is needed to optimize the signal intensity detectable from prostate cancer with our tracer. Toxicologic studies are needed before its clinical use.

Optimization of spermatogenesis-regulating hormones in patients with non-obstructive azoospermia and its impact on sperm retrieval: a multicentre study.

UNLABELLED: Study Type - Therapy (outcomes) Level of Evidence 2a What's known on the subject? and What does the study add? Clomiphene citrate, hCG and human menopausal gonadotropin (hMG) are widely used in treatment of oligospermia, because they increase FSH and testosterone which are essential for spermatogenesis. Finding a sperm in non-obstructive azoospermia for intracytoplasmic sperm injection is a challenge and much effort is required to reach the optimum method of sperm retrieval. The study shows that a new protocol of clomiphene citrate, hCG and hMG in the treatment of non-obstructive azoospermia achieves an increase in the levels of FSH, LH and total testosterone to the target levels that we set. Our target level of FSH was 1.5 times its initial level and for serum testosterone it was 600-800 ng/dL. Using our described medical treatment protocol in cases of non-obstructive azoospermia, sperm may be found in patients' ejaculate (~11%) and if they remain azoospermic they will have a greater likelihood of sperms being obtained in testicular sperm extraction. OBJECTIVE: To evaluate the effect of optimizing serum level of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone on sperm retrieval for intracytoplasmic sperm injection. PATIENTS AND METHODS: A total of 612 patients with non-obstructive azoospermia were evaluated with routine history, physical examination and hormonal assessment. Of these, 116 patients underwent microsurgical (micro)-testicular sperm extraction (TESE) without any medical treatment and formed the control group and the remaining 496 patients were administered clomiphene citrate in a titrated dose. Patients were classified into four groups according to their response to clomiphene citrate. Group 1: patients with an obvious increase in FSH and total testosterone (n = 372). Group 2: patients showing an increase in FSH with no or little increase in LH and total testosterone (n = 62). For these patients we continued with clomiphene citrate and added human chorionic gonadotrophin (hCG). Group 3: patients with no increase in the levels of the three hormones (n = 46). Group 4: included patients with continuously decreasing serum testosterone levels in response to the increasing dose of clomiphene citrate (n = 16). Accordingly, patients in groups 3 and 4 discontinued clomiphene citrate and started hCG and human menopausal gonadotropin (hMG). Semen analyses were performed periodically and, in patients who remained azoospermic, micro-TESE was performed. RESULTS: Sperm were noted in 54 patients (10.9%) in semen analysis after treatment in all groups (with no significant difference) at a mean (sd) concentration of 2.3 (4.1) million/mL. For the 442 patients who remained azoospermic after treatment, successful sperm retrieval was significantly higher (57%) compared with the control group (33.6%). CONCLUSION: For patients with non-obstructive azoospermia, clomiphene citrate, hCG and hMG administration, leading to an increased level of FSH and total testosterone, results in an increased rate of sperm in the ejaculate and increased likelihood of successful micro-TESE.

Role of TMPRSS2-ERG gene fusion in negative regulation of PSMA expression.

Prostate specific membrane antigen (PSMA) is overexpressed in prostatic adenocarcinoma (CaP), and its expression is negatively regulated by androgen stimulation. However, it is still unclear which factors are involved in this downregulation. TMPRSS2-ERG fusion is the most common known gene rearrangement in prostate carcinoma. Androgen stimulation can increase expression of the TMPRSS2-ERG fusion in fusion positive prostate cancer cells. The purpose of this investigation is to determine whether PSMA expression can be regulated by the TMPRSS2-ERG gene fusion. We employed two PSMA positive cell lines: VCaP cells, which harbor TMPRSS2-ERG fusion, and LNCaP cells, which lack the fusion. After 24 hours of androgen treatment, TMPRSS2-ERG mRNA level was increased in VCaP cells. PSMA mRNA level was dramatically decreased in VCaP cells, while it only has moderate change in LNCaP cells. Treatment with the androgen antagonist flutamide partially restored PSMA expression in androgen-treated VCaP cells. Knocking down ERG by siRNA in VCaP cells enhances PSMA expression both in the presence and absence of synthetic androgen R1881. Overexpressing TMPRSS2-ERG fusions in LNCaP cells downregulated PSMA both in the presence or absence of R1881, while overexpressing wild type ERG did not. Using PSMA-based luciferase reporter assays, we found TMPRSS2-ERG fusion can inhibit PSMA activity at the transcriptional level. Our data indicated that downregulation of PSMA in androgen-treated VCaP cells appears partially mediated by TMPRSS2-ERG gene fusion.

Dipstick pseudohematuria: unnecessary consultation and evaluation.

PURPOSE: While many primary care providers advocate routine screening urinalyses, a heme positive dipstick test often leads to a false-positive diagnosis of hematuria, or pseudohematuria. Thus, American Urological Association guidelines recommend urological evaluation for asymptomatic patients only for at least 3 red blood cells per high power field in 2 of 3 microscopic urinalyses. We determined the percentage of patients referred for asymptomatic hematuria undergoing unnecessary consultation and studies. MATERIALS AND METHODS: Patients were retrospectively identified if seen for initial consultation associated with CPT 599.7X, hematuria. Among these patients those referred for evaluation of asymptomatic nonmacroscopic hematuria were identified, and referral patterns, ancillary tests, procedures and findings were examined. RESULTS: Of 320 new patient visits with diagnosis code 599.7X, 91 were referred for asymptomatic, nonmacroscopic hematuria. Of these patients only 37 (41%) had microscopic urinalyses before referral and only 22 (24%) had microscopic urinalyses showing 3 or more red blood cells per high power field. Of the 69 patients referred without confirmed microhematuria approximately 25% had true microhematuria and 15 with no true hematuria had undergone imaging before referral. The Medicare reimbursement value for the evaluation of these 69 patients was $44,901. Of these patients 35 underwent cystoscopy and only 1 (with true microhematuria) had a malignancy. CONCLUSIONS: Positive dipstick heme tests should always be confirmed by microscopic urinalysis before urological referral or evaluation. Education of referring physicians regarding the American Urological Association guidelines could possibly help limit costly and potentially harmful, unnecessary evaluation of patients without true microhematuria.

Genitourinary sarcoidosis.

Genitourinary involvement of sarcoidosis can mimic many common urologic conditions. Although sarcoidosis is a benign inflammatory condition, it can present much like malignant or infectious conditions; thus, failed diagnosis can lead to unnecessary medications or surgical procedures. In addition, management choices for patients with scrotal findings have important implications for future fertility. Thus, this uncommon condition should be on the differential diagnosis for any urologic patient. The authors report on a patient with a scrotal mass as his presenting symptom of sarcoidosis and review the diagnosis, implications, and management of sarcoidosis involving all potential sites in the urinary tract.

Prenatal and postnatal management of hydronephrosis.

The majority of pregnant women in the U.S. undergo prenatal ultrasonography and approximately 0.5% of these examinations will detect fetal malformations. Up to one-half of these abnormalities include the genitourinary system and the most common urological finding is hydronephrosis. Some conditions associated with prenatal hydronephrosis portend a poor prognosis, while others can follow a fairly benign course. This review focuses on the definition and prenatal assessment of hydronephrosis, fetal intervention, and postnatal management.

Routine perioperative chemotherapy instillation with initial bladder tumor resection: a reconsideration of economic benefits.

BACKGROUND: Level-1 evidence has demonstrated decreased recurrence of low-grade bladder tumors when initial transurethral resection (TUR) is followed by perioperative instillation (PI) of chemotherapy. A meta-analysis determined that the number needed to treat (NNT) was 8.5 patients to prevent 1 recurrence. No benefit was demonstrated for tumors classified as T0, tumor in situ, or T2; thus, patients with those tumors were excluded from the analysis, which potentially may have resulted in underestimating the true NNT. Economic benefits were suggested, but cost calculations were not presented. The objectives of the current analysis were to recalculate the NNT considering patients who previously were excluded and to examine the economic implications based on various management alternatives for tumor recurrence. METHODS: For each study that was included in the current meta-analysis, the number of patients excluded because of 'inappropriate' pathology results was determined. A potentially more accurate NNT was calculated, and pertinent Medicare reimbursements were obtained to estimate costs. RESULTS: The added cost for 8.5 patients who underwent inpatient TUR to receive PI was $1711. Inpatient TUR ($7025) was extremely costly compared with hospital outpatient TUR ($2666), ambulatory surgery center TUR ($2113), and physician office fulguration ($1167). Although the inclusion of patients who previously were excluded resulted in a recalculated NNT of 9.6 patients, the authors used a more conservative NNT if 8.5 patients to estimate the economic impact of the 'best-case scenario.' CONCLUSIONS: Routine PI significantly lowered the overall cost if recurrences were managed in the inpatient setting, but these benefits were offset mostly or completely by outpatient management in the United States. Thus, the authors concluded that the decision to use routine PI of chemotherapy should be based on clinical effects and not on presumed economic benefits.

How to evaluate 'dipstick hematuria': what to do before you refer.

Although major health organizations do not support screening for hematuria by dipstick testing, millions of patients without symptoms are tested yearly. Since urinary dipstick tests for hematuria have a high false-positive rate, patients with positive dipstick results require microscopic urinalysis before the diagnosis of hematuria can be made. Primary care physicians can help protect patients from the anxiety, costs, and risks of an unnecessary urologic workup by adhering to the principles of early hematuria management.

Targeted treatment of prostate cancer.

Over a half century ago, Charles Huggins demonstrated the response of prostate cancer to androgen deprivation therapy. Subsequently, many discoveries and evolving findings continued to support a research rationale focused on the androgen receptor (AR) as a key target for prostate cancer. More recently, preliminary trials have suggested that other targets could also be useful in the treatment of prostate cancer, and the proposed strategies for treatment have ranged from targeted toxins to immunotherapeutic agents. We provide an overview of some of these approaches, with an emphasis on those that employ prostate specific membrane antigen (PSMA) as a target.

Laparoscopic renal-adrenal surgery in patients on oral anticoagulant therapy.

PURPOSE: Patients requiring chronic anticoagulation are theoretically at increased risk for hemorrhage or thromboembolism perioperatively. Experience with laparoscopic renal/adrenal surgery in patients on chronic warfarin is limited. We assessed hemorrhagic/thromboembolic complications in this group of patients. MATERIALS AND METHODS: The records of 787 patients undergoing laparoscopic renal/adrenal surgery were retrospectively reviewed. A total of 25 patients on chronic oral anticoagulation with warfarin were identified. The indications for warfarin therapy as well as perioperative management were reviewed. Clinical parameters, including operative time, estimated blood loss, hemorrhagic/thromboembolic complications and transfusions, were documented and compared with those in patients not receiving chronic anticoagulation. RESULTS: Atrial fibrillation (56% of cases) and a prosthetic mitral valve (28%) were the most frequent indications for chronic anticoagulation. Bridging anticoagulation with unfractionated heparin was the most frequent management method (68% of cases). Patients with anticoagulation were older (p <0.001) and hospitalized longer (<0.001) than those without anticoagulation. Operative time, estimated blood loss and the conversion rate were not significantly different between the groups. However patients on chronic warfarin significantly more often required transfusion (24% vs 5.2%, p <0.005) and had more postoperative bleeding episodes (8% vs 0.9%, p <0.05) than patients not on chronic anticoagulation. No thromboembolic events occurred in the anticoagulated group, while 3 occurred in the nonanticoagulated group (p = 1). CONCLUSIONS: Laparoscopic renal/adrenal surgery in patients requiring chronic anticoagulation therapy can be performed safely. The risk of intraoperative bleeding is not increased, although the incidence of postoperative bleeding as well as transfusions is higher.

Safety of trazodone as a sleep agent for inpatients.

Trazodone, an atypical antidepressant with relatively low anticholinergic and cardiac conduction effects, offers useful augmentation to classic antidepressant drugs, notably selective serotonin reuptake inhibitors. One rare but serious side effect of the drug is priapism, the urological emergency in which the cavernosa of the penis become painfully engorged in the absence of sexual stimulation. The authors present what appears to be the first published case of priapism requiring urologic intervention after a single 100-mg dose of trazodone. In addition to a discussion of the history and physiology of trazodone and priapism, the authors present a profile of patients who present a safety risk in treatment.

Laparoscopic partial nephrectomy in patients with neoplasia in a solitary kidney.

OBJECTIVES: To assess the renal function and describe our operative experience with laparoscopic partial nephrectomy (LPN) in patients with solitary kidneys. METHODS: The medical records were analyzed to find patients with a solitary kidney and renal neoplasms who underwent LPN. Demographic, operative, pathologic, and follow-up data were obtained. RESULTS: Four patients were identified with solitary kidneys who had undergone LPN. The mean operative time was 251 minutes, mean warm ischemic time 15 minutes, mean estimated blood loss 395 mL, and mean hospitalization stay 3 days. The mean preoperative creatinine was 1.5 mg/dL and the mean peak creatinine 2.0 mg/dL. All patients returned to their baseline creatinine levels in the follow-up period. The final pathologic finding was Stage pT1 in 1, pT3a in 2, and angiomyolipoma in 1 patient. All surgical margins were negative. No cancer recurrence developed in the patients, with a mean follow-up of 17 months (range 3 to 35). CONCLUSIONS: LPN in patients with a solitary kidney is feasible and a reasonable treatment alternative to open partial nephrectomy.