Two-Year Analysis of a New Oral Testosterone Undecanoate (TU) Formulation in Hypogonadal Men: Efficacy, Impact on Psychosexual Function, and Safety.

BACKGROUND: Long-term data evaluating the efficacy and safety of oral testosterone undecanoate (oral TU; JATENZO) in adult hypogonadal men provides important information for healthcare professionals who prescribe testosterone replacement therapy (TRT). AIM: To determine the efficacy and safety of long-term oral TU therapy, including its impact on total testosterone (T) levels and psychosexual functioning. METHODS: Hypogonadal men, between 18 and 75 years old, (mean age 56.2; 87.2% white) who completed a 12-month, open-label, multicenter, randomized, active-controlled trial were given the opportunity to enroll in a 12-month extension study. Among the 129 eligible TU-treated subjects, 86 chose this option, and 69 completed 24 months of uninterrupted oral TU therapy. OUTCOMES: The efficacy of oral TU was documented by measuring total serum T concentrations; sexual function was measured using the Psychosexual Daily Questionnaire (PDQ). For safety, liver function tests, cardiovascular endpoints, and prostate health were measured. RESULTS: Over 2 years, total serum T concentrations for patients treated with oral TU were in the eugonadal range (300-1,000 ng/dL [10-35 nmol/L]; mean ± SD: 617 ± 427 ng/dL [21 ± 15 nmol/L]) and increased significantly from baseline (P < .0001). For sexual function, mean score changes versus baseline for all PDQ domains at all time points were significantly improved (P < .0011 for all). For the sexual activity and sexual desire components, patient scores were consistently greater than validated thresholds for clinically meaningful change. Typical T-induced safety changes were observed, including a 3-6 mm Hg increase in systolic blood pressure (P < .05); a slight increase in hematocrit (P < .0001) that stayed <48% throughout the study; no clinically significant changes in prostate-specific antigen levels; and decreased high-density lipoprotein cholesterol (-9.8 ± 0.9 mg/dL from baseline; P < .0001). There were no clinically significant changes from baseline in liver function tests. CLINICAL IMPLICATIONS: Over 2 years of treatment, this novel oral TU formulation maintained total T concentrations in mideugonadal ranges, with improvements in sexual function and no clinically significant changes in liver function or other safety concerns previously associated with oral TRT. STRENGTHS & LIMITATIONS: These are the first long-term data to evaluate the efficacy and safety of a novel formulation of oral TU; the comparative long-term safety of oral TU would be strengthened by confirmatory studies versus other TRT formulations. CONCLUSION: Oral TU offers a safe and effective long-term treatment option for men with hypogonadism. Honig S, Gittelman M, Kaminetsky J, et al. Two-Year Analysis of a New Oral Testosterone Undecanoate (TU) Formulation in Hypogonadal Men: Efficacy, Impact on Psychosexual Function, and Safety. J Sex Med 2022;19:1750-1758.

Pharmacokinetics of testosterone therapies in relation to diurnal variation of serum testosterone levels as men age.

BACKGROUND: To improve symptoms associated with testosterone deficiency, many testosterone therapies are available that aim to restore serum testosterone (T) levels to the normal physiologic range. The magnitude, frequency, and duration between peak and trough T concentrations vary with route of administration, and none reflect normal endogenous daily diurnal T variations. OBJECTIVE: To compare pharmacokinetic profiles of serum T from approved T formulations with endogenous diurnal T variations in young and older men, and to consider whether there may be value in mimicking the diurnal T rhythmicity with exogenous testosterone therapies as men age. MATERIALS AND METHODS: A literature search of studies examining the diurnal variation of endogenous T in healthy men and men with testosterone deficiency was performed using PubMed in January 2020. Additional searches for serum T pharmacokinetic profiles of various testosterone therapy formulations were also conducted. Prescribing information for various T formulations was also reviewed. DISCUSSION AND CONCLUSION: Endogenous diurnal T variation is well described and appears to be blunted naturally as men age. Men with testosterone deficiency lack diurnal T variation and exhibit a flatter T profile compared with eugonadal men. Some T replacement options provide intraday T level variations similar to normal circadian secretion, and others provide a flatter exposure profile reflective of depot release. Others provide profiles that exceed the frequency and physiologic range of the natural diurnal variation of T. All exogenous T replacement dosing targets an increase in average T levels to within the normal physiologic range and improves symptoms associated with low T, but no single testosterone therapy can exactly mimic the normal diurnal T patterns seen in younger men and the blunted circadian T secretion of older men.

Final 5-Year Outcomes of the Multicenter Randomized Sham-Controlled Trial of a Water Vapor Thermal Therapy for Treatment of Moderate to Severe Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

PURPOSE: We present final 5-year outcomes of the multicenter randomized sham-controlled trial of a water vapor therapy (Rezum™) for treatment of moderate to severe lower urinary tract symptoms due to benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 197 subjects >50 years of age with International Prostate Symptom Score ≥13, maximum flow rate ≤15 ml/second and prostate volume 30 to 80 cc were randomized and followed for 5 years. From the control arm of 61 subjects, a subset of 53 subjects requalified and after 3 months received treatment as part of the crossover group and were also followed for 5 years. The total number of vapor treatments to each lobe of the prostate was determined by length of prostatic urethra and included middle lobe treatment per physician discretion. RESULTS: Significant improvement of lower urinary tract symptoms was observed at <3 months post-thermal therapy, remaining durable through 5 years in the treatment group (International Prostate Symptom Score reduced 48%, quality of life increased 45%, maximum flow rate improved 44%, Benign Prostatic Hyperplasia Impact Index decreased 48%). Surgical re-treatment rate was 4.4% with no reports of device or procedure related sexual dysfunction or sustained de novo erectile dysfunction. Results within the crossover group were similar through 5 years. CONCLUSIONS: Minimally invasive treatment with water vapor thermal therapy provides significant and durable symptom relief as well as flow rate improvements through 5 years, with low surgical re-treatment rates and without impacting sexual function. It is a versatile therapy, providing successful treatment to obstructive lateral and middle lobes.

A New Oral Testosterone Undecanoate Formulation Restores Testosterone to Normal Concentrations in Hypogonadal Men.

CONTEXT: A novel formulation of oral testosterone (T) undecanoate (TU) was evaluated in a phase 3 clinical trial. OBJECTIVE: Determine efficacy, short-term safety, and alignment of new oral TU formulation with current US approval standards for T replacement therapy. DESIGN: Randomized, active-controlled, open-label study. SETTING AND PATIENTS: Academic and private clinical practice sites; enrolled patients were clinically hypogonadal men 18 to 65 years old. METHODS: Patients were randomized 3:1 to oral TU, as prescribed (JATENZO®; n = 166) or a topical T product once daily (Axiron®; n = 56) for 3 to 4 months. Dose titration was based on average T levels (Cavg) calculated from serial pharmacokinetic (PK) samples. T was assayed by liquid chromatography-mass spectrometry/mass spectrometry. Patients had 2 dose adjustment opportunities prior to final PK visit. Safety was assessed by standard clinical measures, including ambulatory blood pressure (BP). RESULTS: 87% of patients in both groups achieved mean T Cavg in the eugonadal range. Sodium fluoride-ethylenediamine tetra-acetate plasma T Cavg (mean ± standard deviation) for the oral TU group was 403 ± 128 ng/dL (~14 ± 4 nmol/L); serum T equivalent, ~489 ± 155 ng/dL (17 ± 5 nmol/L); and topical T, 391 ± 140 ng/dL (~14 ± 5 nmol/L). Modeling/simulation of T PK data demonstrated that dose titration based on a single blood sample 4 to 6 h after oral TU dose yielded efficacy (93%) equivalent to Cavg-based titration (87%). Safety profiles were similar in both groups, but oral TU was associated with a mean increase in systolic BP of 3 to 5 mm Hg. CONCLUSION: A new oral TU formulation effectively restored T to mid-eugonadal levels in hypogonadal patients.

An Actual Use Study of Tamsulosin in Men with Bothersome Urinary Symptoms in a Simulated Over-the-Counter Setting.

INTRODUCTION: We assessed the ability of men with bothersome urinary symptoms to use an over-the-counter tamsulosin (0.4 mg) product concordant with the information in the proposed drug facts label in a simulated over-the-counter setting. METHODS: Eligibility for this 24-week study was determined by a phone interview. Men who reported not using (nonprescription users) or using (prescription users) a prescription medicine for benign prostatic hyperplasia at screening/baseline reviewed the proposed over-the-counter tamsulosin product. They could then choose to purchase this product and enter the actual use phase. The primary objective was to assess the proportion of nonprescription users compliant with "stop use" directions (performance threshold upper bound of 95% CI 10% or less). Secondary objectives included assessing the proportion of nonRx users compliant with other prespecified instructions on the proposed drug facts label and evaluating adverse events. Analyses were based on outcomes mitigated by a panel of urologists. RESULTS: Of the 4,508 men screened 3,929 were eligible for product review and 1,117 entered the home use phase. Overall 1,074 men (nonprescription users 924, prescription users 150) purchased and used tamsulosin. Mean±SD age was 62.6±10.7 and 66.5±8.8 years, respectively. The primary end point was met, as only 2 of 924 nonprescription users (0.2%, 95% CI 0.0-0.8) reported a "stop use" condition within the first 12 weeks and did not appropriately stop use or initiate contact with a doctor. No unexpected safety concerns were observed. CONCLUSIONS: Results indicate that self-directed use by men interested in using an over-the-counter tamsulosin product was in line with the drug facts label instructions implemented in this study and no unexpected safety concerns were identified.

Over-the-Counter Tamsulosin for Men with Urinary Symptoms: A Simulated Self-Selection Study.

INTRODUCTION: We determined whether consumers who self-select to use tamsulosin for urinary symptoms can make appropriate decisions without health care provider guidance in a simulated over-the-counter setting. METHODS: In a simulated retail setting eligible participants (18 years old or older) reviewed a mock-up of Flomax® over-the-counter packaging and determined whether it was right for them to use tamsulosin capsules (0.4 mg). Per an a priori mitigation procedure 3 urologists reviewed self-reported data, dipstick urinalysis results and AUA-SI (American Urological Association symptom index) scores of men who self-selected tamsulosin as appropriate to use despite information on the drug facts label instructing otherwise. Seemingly incorrect decisions were revised to "appropriate" if deemed well-informed and medically acceptable by 2 or 3 urologists. RESULTS: Overall 619 men and 38 women (mean age 60.9 and 51.6 years, respectively) were enrolled. Of the 470 (75.9%) men who self-selected to use tamsulosin 82 (17.4%) had low health literacy per the REALM (Rapid Estimate of Adult Literacy in Medicine) test and 365 (77.7%) reported seeing a physician at least once a year. Mean AUA-SI total score was 16.5 and 380 (80.9%) men reported urinary symptoms for 1 year or more. The proportions of men who made appropriate self-selection decisions in unmitigated and mitigated analyses were 92.8% (95% CI 90.0-94.9) and 97.9% (95% CI 96.1-99.0), respectively, and findings were similar regardless of health literacy level. Overall 36 of the 38 women (94.7%) made an appropriate decision not to use tamsulosin. CONCLUSIONS: These findings support the potential use of over-the-counter tamsulosin for male urinary symptoms.

Safety of a New Subcutaneous Testosterone Enanthate Auto-Injector: Results of a 26-Week Study.

INTRODUCTION: Patients with testosterone deficiency (TD) can be treated with exogenous testosterone (T) to achieve and maintain physiologic T levels and prevent negative clinical symptoms; with many testosterone replacement therapies currently available, this registration safety study was conducted to further characterize the clinical profile of chronically administered, concentration-guided subcutaneous testosterone enanthate (TE) dosing. AIM: The purpose of this study was to confirm the safety and characterize the pharmacokinetic (PK) profile of the subcutaneous TE auto-injector (SCTE-AI) in adult men with TD. METHODS: In this phase III, 26-week study, 133 men 18-75 years of age with symptomatic TD self-administered SCTE-AI 75 mg once weekly for 6 weeks from July 2015 to June 2016. Dosing was adjusted when indicated to 50 mg or 100 mg to maintain T trough levels between 350 and 650 ng/dL (12.1-22.5 nmol/L). PK data were collected from a subgroup of patients receiving 75 mg SCTE-AI through week 12. Safety, including ambulatory blood pressure monitoring (ABPM), lipid levels, and adverse drug reactions, and PK were assessed. MAIN OUTCOME MEASURES: The main outcomes were the documentation of the reproducibility of trough concentration-guided exposure to SCTE, 6-month safety profile, and PK data for the 75 mg dose SCTE. RESULTS: In total, 34 patients (25.6%) experienced adverse drug reactions; the most frequently reported were increased hematocrit (≥52%) in 10 patients (7.5%), injection-site hemorrhage in 6 patients (4.5%), injection-site bruising in 4 patients (3.0%), and increased prostate-specific antigen in 4 patients (3.0%). By week 26, mean systolic and diastolic blood pressure (BP) measured in the clinic increased by 3.4 mmHg (125.6-129.0 mmHg) and 1.8 mmHg (78.2-80.0 mmHg), respectively, from baseline. At week 12, ABPM showed 24-hour mean systolic and diastolic BP increases of 3.7 mmHg and 1.3 mmHg, respectively. All measured lipid fractions were below baseline levels at week 26. T, TE, dihydrotestosterone, and estradiol increased from weeks 1-12. T trough levels ranged from 300-650 ng/dL (10.4-22.5 nmol/L) in 82.4% and 83.2% of patients at weeks 12 and 26, respectively. Of the 965 assessed injections, mild pain was reported by 1 patient. CLINICAL IMPLICATIONS: Dosing with SCTE is well-tolerated overall, yet associated with a numerically small mean systolic BP increase. STRENGTHS & IMPLICATIONS: This study used a standardized ABPM protocol, confirming a numerically small systolic BP increase may be associated with reintroducing therapeutic T exposure in hypogonadal men. It is unknown at this time whether this applies with all routes of T supplementation. CONCLUSION: SCTE-AI has a favorable safety profile and is well-tolerated, with a stable PK profile. Gittelman M, Jaffe JS, Kaminetsky JC. Safety of a New Subcutaneous Testosterone Enanthate Auto-Injector: Results of a 26-Week Study. J Sex Med 2019;16:1741-1748. Clinicaltrials.gov Identifier: NCT02504541.

Tamsulosin dispensation patterns in the United States: a real-world, longitudinal, population claims database analysis.

BACKGROUND: Tamsulosin remains the single most popular uroselective alpha adrenoceptor antagonist approved for the treatment of lower urinary tract symptoms (LUTS) attributable to benign prostatic hyperplasia (BPH). Over the last 3 decades, the utilization of tamsulosin has extended to conditions beyond its original indication. To identify potential changes to prescribing patterns and the extent of tamsulosin use for conditions beyond its original indication, we evaluated tamsulosin dispensing patterns in the United States using a large, multi-payer claims database. METHODS: We conducted a retrospective analysis using IMS PharMetrics Plus™. Patients with a tamsulosin dispensation/BPH diagnosis code (index dates), identified during a 12-month selection period (October 2012-September 2013), were included if continuously enrolled in a health plan during the 18-month analysis period (12 months pre-index-6 months post-index). Patient and provider characteristics were evaluated using descriptive statistics and were contrasted with previously reported data from the literature. RESULTS: Of 133,977 patients dispensed tamsulosin during the analysis period, 72,583 (54.2%) were new users [59,197 (81.6%) men; 13,386 (18.4%) women]. Tamsulosin was newly initiated in men and women mostly by primary care physicians (PCPs; 31.6%) and emergency medicine physicians (21.6%). During the analysis period, 35,071 (59.2%) male new tamsulosin users did not receive a BPH diagnosis code during the analysis period. Of 199,468 men with a BPH diagnosis code, 143,444 (71.9%) were newly diagnosed, mostly [70,412 (49.1%)] by urologists. Few men received hypotension diagnosis: 252 (0.4%) new tamsulosin users within 1 month of starting tamsulosin and 640 (0.4%) within 1 month of a new BPH diagnosis. CONCLUSIONS: Tamsulosin was prescribed in patients without a recorded diagnosis of BPH and in women. Physicians were comfortable prescribing tamsulosin in the presence of comorbidity and polypharmacy, and PCPs and emergency medicine physicians were the primary prescribers. These results have important implications for future retrospective research for tamsulosin.

Characteristics of men with untreated LUTS interested in over-the-counter tamsulosin.

INTRODUCTION: Treatment for lower urinary tract symptoms (LUTS) is often delayed, as it is considered a natural progression of aging. We described baseline demographic and clinical characteristics of men currently not using prescription medications for benign prostatic hyperplasia (BPH) but interested in self-directed use of over-the-counter (OTC) tamsulosin and who had participated in OTC tamsulosin-simulated studies. MATERIALS AND METHODS: Pooled baseline data from four OTC tamsulosin-simulated studies were analyzed for men who were currently not using BPH prescription medication and who believed that OTC tamsulosin was appropriate for use or were interested in purchasing it. Data from the OTC-simulated studies for men using BPH prescription medication and from the BPH registry, which included men diagnosed with BPH, were used for comparison. RESULTS: Overall, 3285 non-prescription-using men (mean age +/- standard deviation [SD], 60.6 +/- 11.6 years) were included. Average American Urological Association Symptom Index (AUA-SI) total score was 17.6; 25.5% reported urinary symptoms for > 5 years. Overall, 46.7% of these men had > 1 visit/year with their physicians. Baseline characteristics of prescription users from the OTC-simulated studies (n = 364; mean age ± SD, 68.3 +/- 9.1 years; mean AUA-SI score, 18.5) and of men from the BPH registry (n = 5042; 64.8 +/- 10 years; 11.6) were similar to those of non-prescription users. CONCLUSIONS: Non-prescription users had long term moderate-to-severe male LUTS, yet remained untreated; self-management may be a viable alternative strategy for this population. Disease characteristics of men not using BPH prescription medication and interested in using OTC tamsulosin were similar to those using BPH medication or diagnosed with BPH.

Management of Male Lower Urinary Tract Symptoms in a Simulated, Over-the-Counter Setting: An Exploratory Study of Tamsulosin.

BACKGROUND: Lower urinary tract symptoms (LUTS) attributed to benign prostatic hyperplasia (BPH) are common in men, considerably affecting quality of life. AIMS: The self-directed use of over-the-counter (OTC) tamsulosin (0.4 mg) and potential safety risks were evaluated in an open-label, uncontrolled, exploratory, 8-week OTC-simulated study. METHODS: Men (≥ 18 years) were recruited via mass advertising about bothersome LUTS. In a working retail environment, respondents reviewed the product and decided whether it was appropriate for them to use (self-selection phase). After purchasing the product, participants' ability to use it as directed by the proposed drug facts label (DFL) was assessed (home-use phase). RESULTS: Of 1446 eligible men, 679 completed the self-selection phase, and 73.9% (502/679) self-selected to use tamsulosin correctly according to the DFL. Of 369 participants who purchased tamsulosin and entered the home-use phase, 321 took one or more doses of tamsulosin and participated in at least one telephone interview. In total, 85.4% (274/321) of participants adhered to the 'Stop Use' and 'Directions' instructions in the DFL. Overall, 139 (39.6%) participants experienced one or more adverse events (AEs); 65 (18.5%) were deemed drug-related, including dizziness (11 [3.1%]), ejaculation disorder (6 [1.7%]), and semen volume decrease (6 [1.7%]). No unexpected AEs were reported. CONCLUSIONS: Of the men interested in self-managing their LUTS, a majority had moderate-to-severe LUTS of long duration. Most men were able to appropriately self-select and use tamsulosin in concordance with DFL instructions and directions. No unexpected AEs were reported during self-directed use. With further label refinement, an over-the-counter tamsulosin option might be feasible. TRIAL REGISTRATION: ClinicalTrials.gov NCT01726270.

EFFICACY AND SAFETY OF A NEW TOPICAL TESTOSTERONE REPLACEMENT GEL THERAPY FOR THE TREATMENT OF MALE HYPOGONADISM.

OBJECTIVE: Testosterone replacement therapy is indicated for male hypogonadism. This study aimed to evaluate the efficacy and safety of testosterone gel 2% (Tgel) over 90 days. METHODS: This phase 3, open-label, noncomparator study was conducted in adult hypogonadal men (2 consecutive fasting serum testosterone values <300 ng/dL and >86% subjects with symptoms consistent with testosterone deficiency). Subjects applied Tgel 23 mg/day (single pump-actuation using a hands-free cap applicator). The dose was uptitrated to 46 mg/day after 2 weeks if the 4-hour serum total testosterone level was <500 ng/dL. The dose could be further up- or downtitrated to 23, 46, and 69 mg on Days 21, 42, and 63. The primary endpoint included the percentage of subjects with average testosterone concentration (Cave (0-24)) between 300 and 1,050 ng/dL on Day 90. Safety endpoints were adverse events (AEs), laboratory parameters, and vital signs. RESULTS: Of the 159 who enrolled, 139 men completed the study. Approximately three-quarters (76.1%) of subjects met Cave criteria on Day 90. Most AEs were mild to moderate. There were 5 serious AEs, and 1 (myocardial infarction) was judged as possibly related to Tgel. Confirmed excessive increases in prostate-specific antigen or hematocrit levels were rare. Tgel had a favorable local skin tolerability profile. CONCLUSION: Overall, 76% of subjects achieved Cave between 300 and 1,050 ng/dL with Tgel. Symptoms of testosterone deficiency improved with few safety concerns. ABBREVIATIONS: AE = adverse event Cave(0-24) = average testosterone concentration CI = confidence interval Cmax = maximum concentration IIEF = International Index of Erectile Function MAF = Multidimensional Assessment of Fatigue PK = pharmacokinetic PSA = prostate-specific antigen SAE = serious adverse event SF-12 = Short Form 12 Health Survey Tgel = testosterone gel 2% Tmax = time to achieve maximum concentration TRT = testosterone replacement therapy.

Are Over-the-Counter Alpha Blockers in the Best Interest of Men with Lower Urinary Tract Symptoms?

INTRODUCTION: Lower urinary tract symptoms have a multifactorial etiology, are common in men and increase with age. In view of the unprecedented growth of the aging population worldwide and in the United States, an increase in the number of men with lower urinary tract symptoms is expected in the near future. In contrast, a decline in the number of practicing urologists is projected. Many men do not discuss their lower urinary tract symptoms with health care practitioners or seek treatment. Thus, they remain undiagnosed, untreated or both. For such men, self-treatment with over-the-counter alpha blockers with proven efficacy and safety is an unsubstantiated option. However, use of over-the-counter alpha blockers for the treatment of lower urinary tract symptoms is controversial owing to the multifactorial nature of these symptoms and concerns associated with over-the-counter use of alpha blockers. METHODS: This review summarizes a debate held at the 2015 Annual Meeting of the American Urological Association (May 15-19, 2015, New Orleans, Louisiana) on whether over-the-counter alpha blockers are in the best interest of patients. RESULTS: Concerns about over-the-counter use of alpha blockers for the treatment of lower urinary tract symptoms, including inappropriate self-diagnosis and/or self-treatment by patients; potential for missing an important disease; and failure to adhere with guidelines on the assessment of lower urinary tract symptoms are reviewed, as are corresponding rebuttals supporting use of over-the-counter alpha blockers for the treatment of lower urinary tract symptoms. CONCLUSIONS: Over-the-counter alpha blockers are not yet available. Ongoing studies will determine whether appropriate safety and usage criteria can be achieved.

Convective Thermal Therapy: Durable 2-Year Results of Randomized Controlled and Prospective Crossover Studies for Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia.

PURPOSE: We report 2-year outcomes of a multicenter randomized controlled trial plus 1-year results of a crossover trial after treatment with convective radiofrequency water vapor thermal energy for lower urinary tract symptoms due to benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 197 men at least 50 years old with I-PSS (International Prostate Symptom Score) 13 or greater, maximum flow rate 15 ml per second or less and prostate size 30 to 80 cc were randomized 2:1 to thermal therapy with the Rezum® System or a control group. Rigid cystoscopy with simulated active treatment sounds served as the control procedure. After unblinding at 3 months control subjects could requalify for crossover study. Convectively delivered radiofrequency thermal energy was delivered into obstructive prostate tissue, including the median lobe as needed. The primary efficacy end point was a change in severity of symptom scores. RESULTS: Convective radiofrequency thermal therapy improved urinary symptoms significantly over controls at 3 months and provided a sustained 51% reduction from baseline at 24 months (p <0.0001). This produced a 5 and 8-point or greater score decrease in 84% and 74% of subjects, respectively, at 24 months. Crossover subject symptoms, flow rate and quality of life measures were markedly improved after thermal therapy compared to after the control procedure (p = 0.024 to <0.0001). No de novo erectile dysfunction was reported. CONCLUSIONS: Convective radiofrequency water vapor thermal therapy is a minimally invasive office or outpatient procedure that provides early effective symptom relief that remains durable for 2 years and is applicable to the median lobe.

Intramuscular depot formulations of leuprolide acetate suppress testosterone levels below a 20 ng/dL threshold: a retrospective analysis of two Phase III studies.

INTRODUCTION: Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) analogs is a standard treatment for advanced prostate cancer. GnRH analog therapy can reduce testosterone to "castrate" levels, historically defined as <50 ng/dL. With the advent of newer assays, a lower threshold of <20 ng/dL has recently been proposed. We report the results of a retrospective analysis of two Phase III trials of 4- and 6-month depot microsphere formulations of leuprolide acetate (LA), a GnRH agonist that has previously demonstrated efficacy in testosterone suppression to <50 ng/dL in patients on ADT. This analysis investigates the ability of these LA formulations to suppress to ≤20 ng/dL levels. METHODS: In two of five AbbVie/Abbott clinical trials of microsphere formulations of LA for ADT, analytic technology permitting testosterone detection as low as 3 ng/dL was used and thus was selected for this analysis. Both trials were open-label, fixed-dose studies in prostate cancer patients, naïve to ADT. Patients received either 30 mg (4-month formulation; n=49) or 45 mg (6-month formulation; n=151) depot injections of LA microspheres. Treatment duration was up to 32 weeks for the 4-month formulation and 48 weeks for the 6-month formulation. The proportion of patients achieving the 20 ng/dL threshold was determined every 4 weeks. RESULTS: Pooled analysis showed that 152 of 193 (79%) of patients achieved serum testosterone levels of ≤20 ng/dL at 4 weeks, and sustained the improvement at week 24 (169/189, 89%). Additionally, in the 6-month study, 127/135 (94.1%) patients were suppressed to ≤20 ng/dL at 48 weeks. CONCLUSION: Both 4- and 6-month intramuscular depot formulations of LA achieved and maintained mean serum testosterone levels ≤20 ng/dL in the vast majority of patients as early as 4 weeks following treatment initiation. Additional research on the clinical relevance of this lower testosterone threshold is warranted.

Erectile and Ejaculatory Function Preserved With Convective Water Vapor Energy Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: Randomized Controlled Study.

INTRODUCTION: Most surgical treatments for male lower urinary tract symptoms and benign prostatic hyperplasia affect erectile and ejaculatory functions negatively, leading to patient dissatisfaction. AIM: To determine whether water vapor thermal therapy, when conducted in a randomized controlled trial, would significantly improve lower urinary tract symptoms secondary to benign prostatic hyperplasia and urinary flow rate while preserving erectile and ejaculatory functions. METHODS: Men at least 50 years old with International Prostate Symptom Scores of at least 13, a peak flow rate of at least 5 to no higher than 15 mL/s, and prostate volume of 30 to 80 cm(3) were randomized 2:1 between Rezum System thermal therapy and control. Thermal water vapor (103°C) was injected into lateral and median lobes as required for treatment of benign prostatic hyperplasia. The control procedure entailed rigid cystoscopy with simulated active treatment sounds. MAIN OUTCOME MEASURES: Blinded group (active = 136, control = 61) comparison occurred at 3 months and the active arm was followed to 12 months for International Prostate Symptom Score, peak flow rate, and sexual function using the International Index of Erectile Function and the Male Sexual Health Questionnaire for Ejaculatory Function. The minimal clinically important difference in erectile function perceived by subjects as beneficial was determined for each erectile function severity category. Subjects not sexually active were censored from sexual function analysis. RESULTS: No treatment- or device-related de novo erectile dysfunction occurred after thermal therapy. International Index of Erectile Function and Male Sexual Health Questionnaire for Ejaculatory Function scores were not different from the control group at 3 months or from baseline at 1 year. Ejaculatory bother score improved 31% over baseline (P = .0011). Also, 32% of subjects achieved minimal clinically important differences in erectile function scores at 3 months, and 27% at 1 year, including those with moderate to severe erectile dysfunction. International Prostate Symptom Score and peak flow rate were significantly superior to controls at 3 months and throughout 1 year (P < .0001). CONCLUSION: Convective water vapor thermal therapy provides sustainable improvements for 12 months to lower urinary tract symptoms and urinary flow while preserving erectile and ejaculatory functions.

Minimally Invasive Prostate Convective Water Vapor Energy Ablation: A Multicenter, Randomized, Controlled Study for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

PURPOSE: This report reveals the results of a multicenter, randomized, controlled study using transurethral prostate convective water vapor thermal energy to treat lower urinary tract symptoms associated with benign prostatic hyperplasia. MATERIALS AND METHODS: Men 50 years old or older with an International Prostate Symptom Score of 13 or greater, maximum flow rate of 15 ml per second or less and prostate size 30 to 80 cc were randomized 2:1 between thermal therapy with the Rezum® System and control. Thermal water vapor was injected into the transition zone and median lobe as needed. The control procedure was rigid cystoscopy with simulated active treatment sounds. The primary end point compared International Prostate Symptom Score reduction at 3 months. Treatment subjects were followed for 12 months. RESULTS: There were 197 men randomized (active 136, control 61). Thermal therapy and control International Prostate Symptom Score was reduced by 11.2 ± 7.6 and 4.3 ± 6.9 respectively (p <0.0001). Treatment subject baseline International Prostate Symptom Score of 22 decreased at 2 weeks (18.6, p=0.0006) and by 50% or greater at 3, 6 and 12 months, p <0.0001. The peak flow rate increased by 6.2 ml per second at 3 months and was sustained throughout 12 months (p <0.0001). No de novo erectile dysfunction was reported. Adverse events were mild to moderate and resolved quickly. CONCLUSIONS: Convective water vapor thermal therapy provides rapid and durable improvements in benign prostatic hyperplasia symptoms and preserves erectile and ejaculatory function. Treatment can be delivered in an office or hospital setting using oral pain medication and is applicable to all prostate zones including the median lobe.

Feasibility of an Alternative Option for the Management of Male Lower Urinary Tract Symptoms.

PURPOSE: We determine if men with self-reported lower urinary tract symptoms can make a correct decision to use an over-the-counter alpha-1 blocker. Furthermore, we assess the frequency of medically significant conditions presenting with urinary symptoms in these consumers. MATERIALS AND METHODS: Subjects reviewed a mock-up of an over-the-counter product for male lower urinary tract symptoms (part 1). Subjects who selected the product underwent urine dipstick testing and male subjects completed the AUA Symptom Index (part 2). Urological assessment was conducted in women; in men younger than 45 years; men 45 years old or older who reported "Do Not Use" symptoms listed on the over-the-counter label; who had glucose, leukocytes and/or blood in their urine; or had an AUA-SI score of 20 or greater. RESULTS: Of the 1,967 subjects enrolled 1,953 completed part 1 (men/women 1,697/256), 1,311 (1,294/17) entered part 2 and 1,289 (1,274/15) were evaluated. Frequently reported baseline medical conditions were hypertension (45.8%/46.7%) and dyslipidemia (36.4%/60.0%). Lower urinary tract symptoms were present for more than 3 years in 47.6% of men and 40% of women. Mean AUA-SI score was 18.9. Urine dipstick results were positive in 20.9% of men. Overall 729 men and 12 women underwent urological assessment, and 517 (70.9%) men had urologist confirmed lower urinary tract symptoms while 200 (27.4%) did not. Newly diagnosed medically significant conditions causing/contributing to lower urinary tract symptoms were identified in 21 (2.9%) men and 2 (16.7%) women. CONCLUSIONS: Most men correctly selected the over-the-counter product for the management of lower urinary tract symptoms/benign prostatic hyperplasia, while most women correctly deselected to use the product. Since few men had undiagnosed medically significant conditions causing/contributing to urinary symptoms, the risk of harm due to incorrect selection was low.

Selective estrogen receptor alpha agonist GTx-758 decreases testosterone with reduced side effects of androgen deprivation therapy in men with advanced prostate cancer.

BACKGROUND: A need remains for new therapeutic approaches for men with advanced prostate cancer, particularly earlier in the disease course. OBJECTIVE: To assess the ability of an oral selective estrogen receptor α agonist (GTx-758) to lower testosterone concentrations compared with leuprolide while minimizing estrogen deficiency-related side effects of androgen-deprivation therapy. DESIGN, SETTING, AND PARTICIPANTS: Hormone-naive advanced prostate cancer patients were randomized to oral GTx-758 1000 mg/d, 2000 mg/d, or leuprolide depot. INTERVENTION: GTx-758 and leuprolide. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was the proportion of patients achieving total testosterone ≤ 50 ng/dl by day 60. Secondary end points included serum free testosterone, prostate-specific antigen (PSA), sex hormone-binding globulin, hot flashes, bone turnover markers, and insulin-like growth factor (IGF)-1 levels. RESULTS AND LIMITATIONS: Of 159 randomized patients, leuprolide reduced total testosterone to ≤ 50 ng/dl in a greater proportion of patients than GTx-758 by day 60 (43.4%, 63.6%, and 88.2% of subjects receiving GTx-758 1000 mg [p<0.001], GTx-758 2000 mg [p=0.004], and leuprolide, respectively). GTx-758 reduced free testosterone and PSA earlier and to a greater degree than leuprolide. GTx-758 led to fewer hot flashes, decreases in bone turnover markers, and alterations in IGF-1 compared with leuprolide. A higher incidence of venous thromboembolic events (VTEs) was seen with GTx-758 (4.1%) compared with leuprolide (0.0%). CONCLUSIONS: Although leuprolide reduced total testosterone to ≤ 50 ng/dl in a greater proportion of patients compared with GTx-758, GTx-758 was superior in lowering free testosterone and PSA. GTx-758 reduced estrogen deficiency side effects of hot flashes, bone loss, and insulin resistance but with a higher incidence of VTEs. PATIENT SUMMARY: This paper reports findings that leuprolide lowered total testosterone more than GTx-758 but that GTx-758 lowered free testosterone and prostate-specific antigen more than leuprolide. GTx-758 also reduced estrogen deficiency side effects, albeit at a higher rate of vascular events. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01615120.