Andrianne Mini-Jupette Graft at the Time of Inflatable Penile Prosthesis Placement for the Management of Post-Prostatectomy Climacturia and Minimal Urinary Incontinence.

BACKGROUND: After radical prostatectomy (RP), erectile dysfunction, often necessitating the need for inflatable penile prosthesis (IPP) insertion, and urinary incontinence and climacturia can ensue. AIM: To assess the efficacy and safety of the mini-jupette, a mesh used to approximate the medial aspects of the 2 corporotomies at the time of IPP insertion, for the management of climacturia and urine leakage in patients with minimal incontinence. METHODS: We conducted a pilot multicenter study of patients with post-RP erectile dysfunction and climacturia and/or mild urinary incontinence (≤2 pads/day [ppd]) undergoing IPP insertion with concomitant placement of a mini-jupette graft. OUTCOMES: Pre- and postoperative erectile function, continence and climacturia, and overall surgical outcomes were assessed. RESULTS: 38 patients underwent the mini-jupette procedure. The mean age of the population was 65.3 years (SD = 7.7). 30 had post-RP climacturia and 32 patients had post-RP incontinence (mean = 1.3 ppd, SD = 0.8). 31 patients received Coloplast Titan, 4 received AMS 700 LGX, and 3 received AMS 700 CX IPPs. Mean corporotomy size was 2.9 cm (SD = 1.0). Mean graft measurements were 3.2 cm (SD = 0.9) for width, 3.3 cm (SD = 1.3) for length, and 11.0 cm2 (SD = 5.1) for surface area. At a mean follow-up of 5.1 months (SD = 6.9), there were 5 postoperative complications (13.2%) of which 4 required explantation. Climacturia and incontinence were subjectively improved in 92.8% and 85.7%, respectively. Mean ppd decreased by 1.3 postoperatively. CLINICAL IMPLICATIONS: The Andrianne mini-jupette is a feasible adjunct to IPP placement that can be used for subsets of patients with post-RP climacturia and/or minimal incontinence. STRENGTHS AND LIMITATIONS: Strengths of this study include the novel nature of this intervention, the multi-institutional nature of the study, and the promising results demonstrated. Limitations include the retrospective nature of the study and the heterogeneity of the techniques and grafts used by different surgeons involved. CONCLUSION: Longer follow-up and larger patient cohorts are needed to confirm the long-term safety and benefits of this intervention. Yafi FA, Andrianne R, Alzweri L, et al. Andrianne Mini-Jupette Graft at the Time of Inflatable Penile Prosthesis Placement for the Management of Post-Prostatectomy Climacturia and Minimal Urinary Incontinence. J Sex Med 2018;15:789-796.

Device Survival after Primary Implantation of an Artificial Urinary Sphincter for Male Stress Urinary Incontinence.

PURPOSE: The AMS 800™ artificial urinary sphincter remains the gold standard for the surgical management of male stress urinary incontinence. We reviewed artificial urinary sphincter device survival after primary implantation. MATERIALS AND METHODS: Retrospective data were collected from the AMS 800 patient information form database. Since 1972, 77,512 patient information forms for primary artificial urinary sphincter implantation have been completed in the United States. Following exclusion of procedures performed in children and females, and those labeled with an unknown surgical technique, 27,096 artificial urinary sphincter cases were included in the analysis. Collected variables included patient age, surgical approach, number of cuffs and surgeon volume. Measured outcomes included device explantation, device revision, component revision and time to each event. RESULTS: Artificial urinary sphincter insertion was performed by low volume implanters in 22,165 (82.6%) cases. The approach was perineal in 18,373 cases (67.8%) and a tandem cuff was used in 2,224 cases (8.2%). Overall 5,723 cases required revision or explantation (21.1%). Younger age and penoscrotal approach were associated with higher device explantation and revision rates, while the use of a tandem cuff was associated with higher explantation rates. On multivariate analysis younger age, penoscrotal approach and use of a tandem cuff but not surgeon volume were significant factors associated with device explantation and component revision. CONCLUSIONS: These data provide a general overview of artificial urinary sphincter device survival and may serve urologists when counseling patients. Younger age, penoscrotal approach and use of a tandem cuff may be associated with inferior outcomes.

Safety and Efficacy of Collagenase Clostridium histolyticum in the Treatment of Acute-Phase Peyronie's Disease.

BACKGROUND: Peyronie's disease (PD), defined as the abnormal formation of fibrous plaque(s) in the tunica albuginea of the penis, is a chronic condition that afflicts 3% to 13% of the US male population; there is no current research on the efficacy and safety of collagenase Clostridium histolyticum (CCH) in the treatment of acute phase PD. AIM: To examine the efficacy and safety of CCH in the treatment of acute-phase PD. METHODS: We retrospectively reviewed the records for all patients treated with CCH for PD from April 2014 through April 2017. Patients who reported penile pain and duration of PD no longer than 12 months at presentation qualified as being in the acute phase of PD. The primary outcomes of interest were final changes in curvature after CCH treatment regardless of the number of CCH cycles received and frequency of treatment-related adverse events. OUTCOMES: Parameters of efficacy and safety were compared between acute- and stable-phase PD. RESULTS: A total of 162 patients were included in the study, of which 36 (22%) qualified as having acute-phase PD (group 1) and the remaining 126 (78%) qualified as having stable-phase PD (group 2). Median duration of PD was 8.5 months (range = 1-12) for group 1 and 18 months (range = 1-492) for group 2. There was no significant difference in final change in curvature between the acute and stable phases of PD (16.7° vs 15.6°; P = .654). There was no statistically significant difference in frequency of treatment-related adverse events between the acute phase (4 patients, 11%) and the stable phase (12 patients, 10%; P = .778). CLINICAL IMPLICATIONS: CCH therapy is as safe and efficacious in acute-phase PD as it is in stable-phase PD. STRENGTHS AND LIMITATIONS: This is the first report that assesses the safety and efficacy of CCH therapy focusing on acute-phase PD. This study was composed of a large cohort of patients receiving CCH therapy in acute- and stable-phase PD. Limitations include bias associated with retrospective studies, a small sample, and a single-center setting. CONCLUSIONS: Although CCH is not clearly indicated for treatment during the acute phase of PD, these results suggest that CCH use during this phase can be effective and safe. There was no statistically significant difference in final change in curvature or treatment-related adverse events after CCH therapy delivered between the acute and stable phases of PD. Nguyen HMT, Anaissie J, DeLay KJ, et al. Safety and Efficacy of Collagenase Clostridium histolyticum in the Treatment of Acute-Phase Peyronie's Disease. J Sex Med 2017;14:1220-1225.

Pioglitazone's beneficial effects on erectile function preservation after cavernosal nerve injury in the rat are negated by inhibition of the insulin-like growth factor-1 receptor: a preclinical study.

To determine if the insulin-like growth factor-1 (IGF-1) pathway is involved in the improvement in erectile function recovery in rats after nerve crush injury treated with pioglitazone (Pio). Sprague-Dawley rats were divided into four groups. The first group received sham operation (n = 5). The second group underwent bilateral cavernous nerve injury (BCNI, n = 7). The third group received BCNI and Pio treatment (BCNI + Pio, n = 7), whereas the fourth group underwent BCNI with Pio treatment and IGF-1 inhibition (BCNI + Pio + JB-1, n = 7). The IGF-1 receptor (IGF-1R) was inhibited by JB-1, a small molecular antagonist of the receptor. After 14 days of treatment, erectile function was measured via intracorporal pressure normalized to mean arterial pressure (ICP/MAP) and the major pelvic ganglion and cavernous nerve harvested for western blot and immunohistochemistry (IHC) of phosphorylated-IGF-1Rß (p-IGF-1Rß), phosphorylated-ERK1/2 (p-ERK1/2), and neuronal NOS (nNOS). BCNI + Pio animals exhibited improvements in ICP/MAP, similar to Sham animals, and BCNI + Pio + JB-1 rats demonstrated a reduced ICP/MAP similar to BCNI-only rats at all measured voltages. Western blot results showed upregulation of p-IGF-1Rß was observed in the BCNI + Pio group. Low levels of p-ERK1/2 were seen in the JB-1-treated animals. The immunoblot results were supported by IHC findings. Intense IHC staining of nNOS was detected in the BCNI + Pio group. The group treated with JB-1 showed minimal protein expression of p-ERK1/2, nNOS, and p-IGF-1Rß. Pio improves erectile function in rats undergoing BCNI via an IGF-1-mediated pathway.

Multi-institutional Prospective Analysis of Intralesional Injection of Collagenase Clostridium Histolyticum, Tunical Plication, and Partial Plaque Excision and Grafting for the Management of Peyronie's Disease.

OBJECTIVE: To compare in a prospective nonrandomized fashion, the outcomes of collagenase clostridium histolyticum (CCH) and surgical interventions (tunical plication [TP] and partial plaque excision and grafting [PEG]) in patients with Peyronie's disease (PD). Intralesional injection of CCH is the only Food and Drug Administration-approved nonsurgical intervention for PD. MATERIALS AND METHODS: Between June 2015 and January 2017, 57 patients with PD and dorsal, dorsolateral, and/or lateral penile curvatures 30°-90° were included in this study. Patients with ventral curvature, hourglass deformity, and previous surgery for PD were excluded. All patients completed questionnaires and underwent penile measurements and penile vascular studies prior to and after completion of treatment, and were followed for at least 6 months. RESULTS: CCH was administered to 18 patients, TP performed in 14, and PEG in 25. The median follow-up for the whole cohort was 12 months (6-28). Mean changes in curvature after treatment were 23.3° (34.4%) for CCH, 72.0° (92.2%) for TP, and 71.8 ° (94.9%) for PEG, P<.001. Mean changes in International Index of Erectile Function-5 scores were +5.7 for CCH, +4.9 for TP, and +2.2 for PEG, P = .395. Mean penile length changes were -0.2 cm for CCH, -1.0 cm for TP, and +0.9 cm for PEG, P<.001. Three patients in the CCH group had bothersome residual curvature and underwent uneventful TP. CONCLUSION: Surgical options are associated with superior curvature correction. CCH is an effective and safe option for motivated patients who prefer to avoid surgery. PEG is associated with a small stretched penile length gain.

Comparison of Adjuvant Radiation Therapy Before or After Artificial Urinary Sphincter Placement: A Multi-Institutional, Retrospective Analysis.

OBJECTIVE: To determine if the timing of radiation therapy on artificial urinary sphincter (AUS) impacts complication rates, revision rates, and number of pads per day after placement. METHODS: A retrospective review was conducted of men with prostate cancer who underwent AUS placement and radiation therapy between 1987 and 2016. RESULTS: Of 306 men, 292 (95.4%) received radiation before AUS placement (group 1) and 14 (4.6%) received radiation after AUS placement (group 2). Median follow-up was 30 months after AUS placement. Group 1 had 32 of 292 (11.0%) patients suffer from erosion, compared with 0 of 14 (0.0%) patients in group 2 (P = .191). None of the patients in group 2 had infection or mechanical failure. The number of patients who received revision in group 1 was 91 of 292 (31.2%) and in group 2 was 2 of 14 (14.3%) (P = .180). The number of pads used per day in group 1 before and after AUS placement was 5.24 ± 3.12 and 1.13 ± 1.31, respectively (P <.001). In group 2, the number of pads used per day before and after AUS placement was 6.09 ± 1.97 and 1.53 ± 0.99, respectively (P <.001). There was no significant difference in the average number of postoperative pads used per day between group 1 and group 2 (P = .907). CONCLUSION: The timing of radiation therapy does not appear to significantly affect complication rates or urinary continence, as measured in pads used after AUS placement. This multi-institutional retrospective analysis showed similar erosion and revision rates when radiation occurred after AUS placement and demonstrates preliminary safety and feasibility of the administration of radiation after AUS placement.

The Conception and Evaluation of Sexual Health Literature.

INTRODUCTION: Understanding the appropriate evaluation and development methods for studying the literature as it pertains to sexual health is important for those practicing within the subspecialty. AIM: To further understand the methodology that is necessary to evaluate and design optimal studies in sexual health. METHODS: A PubMed search was performed using the terms urologic study design, urologic validated questionnaires, clinical trials, and study bias. Articles with current and relevant topics in sexual health were selected for evaluation. MAIN OUTCOME MEASURE: Summary of the current state of sexual medicine literature with insights into the evaluation and development of this literature. RESULTS: Most of the urologic and sexual medicine literature consists of retrospective studies that have resulted in low levels of evidence. Case series, case-control studies, cohort studies, and experimental studies are designs commonly used in sexual health. There are numerous types of bias that decrease the validity of the results within the literature. There are multiple validated questionnaires that can decrease bias when collecting data. These instruments are preferred over non-validated questionnaires and can help discern whether an intervention improves a patient's quality of life. The quality of the literature varies and often reflects the incidence of the condition being studied. CONCLUSION: Those caring for patients with sexual dysfunction need to recognize the quality of the literature they read and understand the means of developing the highest quality studies, recommendations, and published literature. DeLay KJ, Voznesensky I, Hellstrom WJG. The Conception and Evaluation of Sexual Health Literature. Sex Med Rev 2017;5:135-145.

Review of Management Options for Patients With Atypical Peyronie's Disease.

INTRODUCTION: Peyronie's disease (PD) is a wound-healing disorder of the tunica albuginea often associated with penile deformity. Less commonly, patients with PD might display atypical presentations such as ventral curvature, hourglass deformity, significantly shortened penis, and/or multiplanar curvature. AIM: To review the available literature on the prevalence of and management options for atypical PD. METHODS: A literature review was performed through PubMed from 1982 through 2016 regarding atypical PD. Keywords used for the search were Peyronie's disease, atypical Peyronie's disease, ventral Peyronie's disease, ventral plaque, hourglass deformity, penile indentation, penile notching, short penis, shortened penis, shrunken penis, biplanar curvature, and multiplanar curvature. MAIN OUTCOME MEASURES: To assess the various surgical and non-surgical techniques used for the management of atypical PD. RESULTS: Collagenase Clostridium histolyticum is contraindicated for patients with ventral plaques and/or hourglass deformities. Patients with maintained erectile function and ventral PD plaques are best treated with intralesional injections of interferon alpha-2b or tunica plication. Patients with maintained erectile function with PD associated with hourglass deformity and/or multiplanar curvature are best treated with plaque incision or partial excision and grafting. Patients with a shortened penis could attempt conservative measures such as penile traction therapy and medical management. When erectile function is compromised, insertion of an inflatable penile prosthesis with or without ancillary straightening procedures should be recommended. Lengthening procedures can be attempted in very special circumstances by expert surgeons. CONCLUSION: There is a paucity of data regarding atypical PD. Ventral plaques can be treated with intralesional injections or surgery, hourglass deformity and multiplanar curvatures are best managed surgically, and a shortened penis should be treated with non-invasive approaches. When concomitant erectile dysfunction is present, insertion of an inflatable penile prosthesis is recommended. Caution should be advised before undergoing ancillary penile lengthening maneuvers owing to the potential for serious complications. Yafi FA, Hatzichristodoulou G, DeLay KJ, Hellstrom WJG. Review of Management Options for Patients With Atypical Peyronie's Disease. Sex Med Rev 2017;5:211-221.

Impact of Number of Cycles of Collagenase Clostridium Histolyticum on Outcomes in Patients With Peyronie's Disease.

OBJECTIVE: To analyze the impact of the number of cycles of collagenase Clostridium histolyticum (CCH) intralesional injection therapy on outcomes to further characterize CCH therapy. METHODS: We conducted a retrospective review of the records of all patients treated with CCH for Peyronie disease between April 2014 and March 2016. Collected variables included demographics, pre- and posttreatment sexual function, penile curvature, penile vascular findings, and treatment outcomes. RESULTS: A total of 77 patients were included in the study, of which 41 (53%) completed 4 cycles of treatment, consisting of 8 total injections. For all-comers regardless of numbers of cycles, curvature improved from 58.2° (standard deviation = 17.9°, range = 30°-105°) pre-treatment to 41.0° (standard deviation = 17.0°, range = 0°-85°) posttreatment (P < .001). In a repeated measures model, penile curvature improved significantly following the first 3 cycles, but not the fourth. Patients who had a ≥20% final reduction in curvature had a significantly greater change in curvature following the first injection (-16.2° vs -5.8°, P < .001). CONCLUSION: Intralesional CCH therapy is an effective minimally invasive treatment for Peyronie disease, although the therapeutic benefit may decline after the third cycle of treatment. Patients with ≥20% reduction in curvature at the conclusion of treatment documented a greater curvature improvement after the first cycle and received more cycles of CCH.

Collagenase Clostridium histolyticum in the treatment of Peyronie's disease: patient selection and perspectives.

The safety and efficacy of the use of collagenase Clostridium histolyticum (CCH) for the treatment of Peyronie's disease has been confirmed over the past several years. However, identification of the ideal patient population for use of this treatment is not well established. Multiple studies have attempted to delineate various patient-specific factors that may predict response to treatment with CCH, with the intent of enhancing patient selection. To date, these include baseline curvature severity, duration of disease, disease phase at presentation, plaque calcification, baseline erectile function, plaque size, age, comorbid diabetes, previous penile trauma, responsiveness to first treatment cycle, baseline penile shortening or pain, prior treatment with intralesional injection, compliance with plaque modeling, and atypical curvature. In addition, other studies have sought to explore various aspects of treatment with CCH that may affect patient perspective of treatment. They have focused on patient-reported outcomes, female partner considerations, cost of treatment, and potential confounders of patient satisfaction. This review provides a summary and analysis of currently available literature on topics of patient selection and perspectives in regard to treatment of Peyronie's disease with CCH.

Racial variations in response to intralesional collagenase clostridium histolyticum in men with Peyronie's disease.

BACKGROUND: An examination of potential racial variations between Caucasian American (CA) and African American (AA) men in the efficacy and safety of collagenase clostridium histolyticum (CCH) in the treatment of Peyronie's disease (PD). METHODS: We retrospectively reviewed the records for all patients treated with CCH for PD between 04/2014 and 05/2017. Patients were divided into two groups based on their self-reported race. The primary outcomes of interest were final change in curvature after CCH treatment regardless of number of CCH cycles received, and frequency of treatment-related adverse events (TRAEs). RESULTS: A total of 159 patients were included in the study, of which 146 (91.8%) were CA while 13 (8.2%) were AA. Mean duration of PD was 28.3 months for CA patients and 16.8 months for CA patients (P=0.436). There was no significant difference in final change in curvature CA and AA patients (15.9° vs. 13.1° respectively, P=0.445). There was no statistically significant difference in frequency of TRAEs between CA patients (17, 12%) and AA patients (0, 0%) (P=0.208). CONCLUSIONS: Although racial variations in efficacy and safety of CCH in patients with PD have not been addressed in the literature, preliminary results from our study suggest that CCH therapy may be equally efficacious and safe in both CA and AA men. There was no statistically significant difference in final change in curvature, International Index of Erectile Function (IIEF) scores, penile length, or TRAEs after CCH treatment between CA and AA patients.

Effect of collagenase Clostridium histolyticum on penile vascular and morphological parameters in patients with Peyronie's disease.

BACKGROUND: To examine the changes in penile vascular parameters after the administration of collagenase Clostridium histolyticum (CCH) in patients with Peyronie's disease (PD). METHODS: We retrospectively reviewed the records for all patients treated with CCH for PD between 04/2014 and 05/2017 who underwent penile duplex Doppler ultrasound (PDDU) after pharmacologically induced erection both before and after four cycles of CCH treatment. The primary outcomes measured were changes in peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI) after CCH treatment. Paired t-tests, chi-squared tests, and correlation coefficients were performed between functional and vascular parameters before and after four rounds of CCH to determine statistical significance (P<0.05). RESULTS: A total of 51 patients were included in the study. After four cycles of CCH therapy, there was no statistically significant change in PSV, EDV, RI, or International Index of Erectile Function score when compared to baseline. Similarly, there was no correlation between vascular parameters and change in curvature. There was a statistically significant change in penile curvature (60˚±16.9˚ to 40.8˚±14.9˚, P<0.001) and erect penile circumference (11.6±1.0 to 11.9±1.0 cm, P<0.05) after treatment. CONCLUSIONS: In spite of a significant change in penile curvature, this change did not correlate with changing penile vascular or morphological parameters. Overall, CCH therapy seems to have a negligible impact on penile vasculature, furthering evidence of its favorable safety profile.

Practice Patterns in the Diagnosis and Management of Hypogonadism: A Survey of Sexual Medicine Society of North America Members.

OBJECTIVE: To describe practice patterns in the diagnosis and treatment of hypogonadism, as the optimal approaches are controversial. Multiple therapeutic options are currently available for hypogonadal men and treatment patterns vary considerably. The safety of testosterone therapy (TTh) remains understudied. MATERIALS AND METHODS: A 23-question survey regarding diagnosis and treatment of hypogonadism was sent to all members of the Sexual Medicine Society of North America. Subgroup analyses compared responses between sexual medicine fellows and non-fellows, as well as between academic and nonacademic physicians, using a chi-squared analysis. RESULTS: A total of 101 responses were included for analysis. The most common cutoff value used to diagnose hypogonadism was 300 ng/dL (55%, range = 200-400 ng/dL), and 31% felt comfortable giving TTh to a symptomatic patient with normal serum testosterone levels. No respondents felt that TTh increased a cardiovascular event risk. Of those surveyed, 68% would prescribe TTh to a hypogonadal man with severe lower urinary tract symptoms, and 64% would offer TTh to a man with low-risk prostate cancer on active surveillance. Fellowship-trained physicians were more likely to prescribe TTh to a man with hypogonadism but normal serum testosterone (P = .038), but they differed in the types of therapy they would use for men with hypogonadism who wish to preserve or regain fertility. CONCLUSION: Significant variety exists in the diagnosis and treatment of hypogonadism. The majority of physicians will only prescribe TTh in the setting of subnormal serum testosterone levels, despite the presence of symptoms. None of the surveyed physicians reported concern over the risk of cardiovascular events.

Advances in pharmacotherapy for erectile dysfunction and associated cardiac impact.

INTRODUCTION: Cardiovascular disease (CVD) and erectile dysfunction (ED) are two disease processes that affect millions of men. CVD and ED are increasingly recognized as sharing a common pathophysiologic origin. As the nature of this relationship continues to be elucidated, there is growing interest in developing a therapy to effectively target both processes. While researchers have largely focused on phosphodiesterase-5 inhibitors (PDE5Is), the established first-line therapy for ED, newer ED drugs, designed based on better understanding of the physiology of erection, may also show promise. Areas covered: This paper will review the relationship between ED and CVD, as well as the currently available and investigational pharmacologic treatments for ED. The particular focus will be on the role that these therapies play in managing CVD. Expert opinion: PDE5Is, along with the newer ED therapies, are promising candidates for managing ED and concurrently providing cardioprotection. Despite some in vitro success with PDE5Is, maxi-K channel activators, and guanylyl cyclase (GC) stimulators, in vivo studies have either been lacking, or shown conflicting results. More well designed clinical studies are needed in order to characterize an ED pharmacotherapy that offers proven cardioprotection.

Modifying Risk Factors in the Management of Erectile Dysfunction: A Review.

Erectile dysfunction (ED) is prevalent among men and its presence is often an indicator of systemic disease. Risk factors for ED include cardiovascular disease, hypertension, diabetes mellitus (DM), tobacco use, hyperlipidemia, hypogonadism, lower urinary tract symptoms, metabolic syndrome, and depression. Addressing the modifiable risk factors frequently improves a patient's overall health and increases lifespan. The literature suggests that smoking cessation, treatment of hyperlipidemia, and increasing physical activity will improve erectile function in many patients. How the treatment of DM, depression, and hypogonadism impacts erectile function is less clear. Clinicians need to be aware that certain antihypertensive agents can adversely impact erectile function. The treatment of men with ED needs to address the underlying risk factors to ameliorate the disease process.

Stem cell therapy for the treatment of Leydig cell dysfunction in primary hypogonadism.

The production of testosterone occurs within the Leydig cells of the testes. When production fails at this level from either congenital, acquired, or systemic disorders, the result is primary hypogonadism. While numerous testosterone formulations have been developed, none are yet fully capable of replicating the physiological patterns of testosterone secretion. Multiple stem cell therapies to restore androgenic function of the testes are under investigation. Leydig cells derived from bone marrow, adipose tissue, umbilical cord, and the testes have shown promise for future therapy for primary hypogonadism. In particular, the discovery and utilization of a group of progenitor stem cells within the testes, known as stem Leydig cells (SLCs), has led not only to a better understanding of testicular development, but of treatment as well. When combining this with an understanding of the mechanisms that lead to Leydig cell dysfunction, researchers and physicians will be able to develop stem cell therapies that target the specific step in the steroidogenic process that is deficient. The current preclinical studies highlight the complex nature of regenerating this steroidogenic process and the problems remain unresolved. In summary, there appears to be two current directions for stem cell therapy in male primary hypogonadism. The first method involves differentiating adult Leydig cells from stem cells of various origins from bone marrow, adipose, or embryonic sources. The second method involves isolating, identifying, and transplanting stem Leydig cells into testicular tissue. Theoretically, in-vivo re-activation of SLCs in men with primary hypogonadism due to age would be another alternative method to treat hypogonadism while eliminating the need for transplantation.