Serum Concentrations of Sex Hormone-binding Globulin Vary Widely in Younger and Older Men: Clinical Data from a Men's Health Practice.

BACKGROUND: The testosterone (T) status of a man is influenced by serum concentrations of sex hormone-binding globulin (SHBG). Specifically, tight binding of T to SHBG is believed to render the SHBG-bound T fraction biologically unavailable, meaning that interpretation of T levels in the clinical setting depends in part on knowledge of SHBG concentrations. Although SHBG levels have been reported in population studies, there is scant information for men presenting with clinical symptoms. OBJECTIVE: To report SHBG values for a large cohort of men presenting to a men's health center. DESIGN, SETTING, AND PARTICIPANTS: Medical records were reviewed for 1000 consecutive patients seen at our center with a reported SHBG value. SHBG concentrations were measured by a national clinical laboratory using an immunoassay run on a Beckman Coulter DXi system. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were age-stratified and data were plotted in the form of comparative histograms. RESULTS AND LIMITATIONS: The mean age (±standard deviation) of the total cohort was 53.5±13.5 yr (range 17-91). The mean SHBG was 31.8±15.2nmol/l (range 6-109), with a nearly 20-fold difference from the lowest to the highest values. SHBG was >60nmol/l in 5.6% of the men. Patients were stratified according to age. A total of 535 patients were ≤54 yr old. In this younger cohort, the mean age was 40.52±7.9 yr (range 17-54) and mean SHBG was 27.7±13.3nmol/l (range 6-88), and 2.2% of patients had SHBG >60nmol/l. A total of 465 patients were ≥55 yr old. In this older cohort, the mean age was 64.8±7.23 yr (range 55-91) and mean SHBG was 36.6±15.8 nmol/l (range 11-109), and 9% of patients had SHBG >60 nmol/l. Mean SHBG was significantly higher in the older group (p<0.001). CONCLUSIONS: A remarkably wide distribution of SHBG concentrations was observed in a clinical population of men presenting to a men's health center, among both younger and older men. Since SHBG concentrations greatly influence test results for hormones that bind to SHBG, recognition of this large interindividual variability should be considered in the clinical interpretation of these hormone results, particularly for T. Routine SHBG testing should be considered for men suspected of T deficiency. PATIENT SUMMARY: Sex hormone-binding globulin (SHBG) levels vary widely among both older and younger men. This may impact the interpretation of test results for hormones that bind to SHBG, such as testosterone, since the portion that binds to SHBG is believed to not be biologically available.

Initial Clinical Experience With Testosterone Undecanoate Therapy (AVEED) in Men With Testosterone Deficiency in the United States.

OBJECTIVE: To report our initial experiences with testosterone undecanoate (TU 750) mg (AVEED) in men with testosterone deficiency. METHODS: All patients receiving TU 750 mg at our center between July 1, 2014, and August 1, 2016, were identified. Clinical response was assessed through structured interviews and laboratory evaluations. Adverse events were documented, including increase in prostate specific antigen (PSA), increase in hematocrit (Hct), and the development of postinjection cough. RESULTS: More than 2 injections were received by 147 men, with mean age 63.2 years. Mean baseline total testosterone (T) and free T were 305 ng/dL and 0.69 ng/dL, respectively. Nadir mean results during treatment were higher for total and free T, at 413.2 ng/dL and 0.81 ng/dL, respectively (P < .001 for each). Symptomatic improvement was reported by 97 of 147 patients (66.0%). Thirty patients (20.4%) discontinued therapy. Return of symptoms before the next injection was noted by 34%, managed by reduced interval between injections and/or supplemental injections of T cypionate. Three patients (2%) experienced transient cough immediately after TU injection, none requiring intervention. Mean Hct rose from 45.6% to 47.2%. Mean PSA rose from 1.7 ng/mL to 2.0 ng/mL. There were no strokes, myocardial infarctions, or deaths, and no new cases of prostate cancer. CONCLUSION: This initial clinical experience with TU 750 mg provides evidence for good patient satisfaction and persistence with treatment, together with a favorable safety profile. Optimal dosing may be less than 10 weeks for some individuals.

Multicenter Investigation of the Micro-Organisms Involved in Penile Prosthesis Infection: An Analysis of the Efficacy of the AUA and EAU Guidelines for Penile Prosthesis Prophylaxis.

INTRODUCTION: Penile prosthesis infections remain challenging despite advancements in surgical technique, device improvements, and adoption of antibiotic prophylaxis guidelines. AIM: To investigate penile prosthesis infection microbiology to consider which changes in practice could decrease infection rates, to evaluate current antibiotic prophylaxis guidelines, and to develop a proposed algorithm for penile prosthesis infections. METHODS: This retrospective institutional review board-exempt multi-institutional study from 25 centers reviewed intraoperative cultures obtained at explantation or Mulcahy salvage of infected three-piece inflatable penile prostheses (IPPs). Antibiotic usage was recorded at implantation, admission for infection, and explantation or salvage surgery. Cultures were obtained from purulent material in the implant space and from the biofilm on the device. MAIN OUTCOME MEASURES: Intraoperative culture data from infected IPPs. RESULTS: Two hundred twenty-seven intraoperative cultures (2002-2016) were obtained at salvage or explantation. No culture growth occurred in 33% of cases and gram-positive and gram-negative organisms were found in 73% and 39% of positive cultures, respectively. Candida species (11.1%), anaerobes (10.5%) and methicillin-resistant Staphylococcus aureus (9.2%) constituted nearly one third of 153 positive cultures. Multi-organism infections occurred in 25% of positive cultures. Antibiotic regimens at initial implantation were generally consistent with American Urological Association (AUA) and European Association of Urology (EAU) guidelines. However, the micro-organisms identified in this study were covered by these guidelines in only 62% to 86% of cases. Antibiotic selection at admissions for infection and salvage or explantation varied widely compared with those at IPP implantation. CONCLUSION: This study documents a high incidence of anaerobic, Candida, and methicillin-resistant S aureus infections. In addition, approximately one third of infected penile prosthesis cases had negative cultures. Micro-organisms identified in this study were not covered by the AUA and EAU antibiotic guidelines in at least 14% to 38% of cases. These findings suggest broadening antibiotic prophylaxis guidelines and creating a management algorithm for IPP infections might lower infection rates and improve salvage success. Gross MS, Phillips EA, Carrasquillo RJ, et al. Multicenter Investigation of the Micro-Organisms Involved in Penile Prosthesis Infection: An Analysis of the Efficacy of the AUA and EAU Guidelines for Penile Prosthesis Prophylaxis. J Sex Med 2017;14:455-463.

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.

Testosterone Therapy after Radiation Therapy for Low, Intermediate and High Risk Prostate Cancer.

PURPOSE: Limited literature exists regarding the safety of testosterone therapy in men treated for prostate cancer. We present multi-institutional data on testosterone therapy in hypogonadal men with prostate cancer treated with radiation therapy. MATERIALS AND METHODS: We retrospectively reviewed the records of hypogonadal men treated with testosterone therapy after radiation therapy for prostate cancer at 4 institutions. Serum testosterone, free testosterone, estradiol, sex hormone-binding globulin, prostate specific antigen, prostate specific antigen velocity and prostate biopsy findings were analyzed. RESULTS: A total of 98 men were treated with radiation therapy. Median age was 70.0 years (range 63.0 to 74.3) at initiation of testosterone therapy. Median baseline testosterone was 209 ng/dl (range 152 to 263) and median baseline prostate specific antigen was 0.08 ng/ml (range 0.00 to 0.33). In the cohort the tumor Gleason score was 5 in 3 men (3.1%), 6 in 44 (44.9%), 7 in 28 (28.6%), 8 in 7 (7.1%) and 9 in 4 (4.1%). Median followup was 40.8 months (range 1.5 to 147). Serum testosterone increased to a median of 420 ng/dl (range 231 to 711) during followup (p <0.001). Overall a nonsignificant increase in mean prostate specific antigen was observed from 0.08 ng/ml at baseline to 0.09 ng/ml (p = 0.05). Among patients at high risk prostate specific antigen increased from 0.10 to 0.36 ng/ml (p = 0.018). Six men (6.1%) met criteria for biochemical recurrence. CONCLUSIONS: Testosterone therapy in men following radiation therapy for prostate cancer was associated with a minor increase in serum prostate specific antigen and a low rate of biochemical recurrence.

Testosterone therapy in men with prostate cancer: literature review, clinical experience, and recommendations.

For several decades any diagnosis of prostate cancer (PCa) has been considered an absolute contraindication to the use of testosterone (T) therapy in men. Yet this prohibition against T therapy has undergone recent re-examination with refinement of our understanding of the biology of androgens and PCa, and increased appreciation of the benefits of T therapy. A reassuringly low rate of negative outcomes has been reported with T therapy after radical prostatectomy (RP), radiation treatments, and in men on active surveillance. Although the number of these published reports are few and the total number of treated men is low, these experiences do provide a basis for consideration of T therapy in selected men with PCa. For clinicians considering offering this treatment, we recommend first selecting patients with low grade cancers and undetectable prostate-specific antigen following RP. Further research is required to define the safety of T therapy in men with PCa. However, many patients symptomatic from T deficiency are willing to accept the potential risk of PCa progression or recurrence in return for the opportunity to live a fuller and happier life with T therapy.

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.

The evaluation and management of testosterone deficiency: the new frontier in urology and men's health.

Testosterone deficiency (TD) is a common clinical condition that causes sexual and non-sexual symptoms. Low serum concentrations of testosterone also predict significant health outcomes, such as diabetes, metabolic syndrome, and increased mortality. Treatment with testosterone therapy (TTh) effectively improves symptoms, and also has a positive impact on body composition and bone density. Since there is no serum testosterone value that reliably identifies men who will respond to treatment from those who will not, healthcare providers must exercise clinical judgment in making the diagnosis of TD. Multiple formulations of TTh are available, each with advantages and disadvantages. Overall, TTh is relatively safe but the risks, such as erythrocytosis, makes long-term monitoring mandatory. The evidence does not support concerns regarding cardiovascular and prostate cancer risks.

An outcomes analysis of over 200 revision surgeries for penile prosthesis implantation: a multicenter study.

INTRODUCTION: Inflatable penile prosthesis (IPP) implantation is a well-established treatment for medically refractory erectile dysfunction, with long-term reliability. Overall survival is 96% at 5 years and 60% at 15 years for primary (virgin) implantation. AIM: The aim of this study was to explore factors associated with success and complications of IPP revision surgery in a multicenter study. MAIN OUTCOME MEASURES: Reasons for revision including mechanical issues, patient dissatisfaction, corporal deformity, and supersonic transport (SST) deformity were recorded. METHODS: At four institutions, 214 clinically uninfected IPP revisions were performed between November 2000 and November 2007. Data were incomplete for 28 cases (14%). Failure-free survival was estimated using Kaplan-Meier's Meier product limit method. RESULTS: The majority of revisions were secondary to mechanical failure (N = 109; 65%) and combined erosion or infection (N = 17 + 15 = 32; 19%). Sixteen percent (N = 26) were carried out on functional uninfected prostheses secondary to patient dissatisfaction (N = 9), SST deformity (N = 10), scrotal hematoma (N = 2), or upsize revision because of corporal fibrosis (N = 5). Average age at revision was 66 years. Mean follow-up time was 55.7 months. In this study, 12 individuals required a secondary revision procedure or suffered a complication. Despite prior reports of high infection rates with revision surgery, only 5.7% of clinically uninfected and noneroded prostheses were complicated by infection or impending extrusion/erosion, following a revision washout protocol. Overall, 93% of cases were successfully revised, providing functioning IPPs. CONCLUSIONS: For this study population, component exchange followed by revision washout showed a low incidence of infection and subsequent mechanical failure.

Influence of baseline serum testosterone on changes in body composition in response to testosterone therapy.

INTRODUCTION: The prognostic value of serum total testosterone (TT) prior to treatment has not been investigated. AIM: This study was performed to determine how baseline TT influences changes in body composition in men undergoing testosterone therapy (TTh). MAIN OUTCOME MEASURES: Response to TTh in a clinical population of men with symptomatic testosterone deficiency (TD). METHODS: Retrospective case series of 58 men with TD were treated with TTh. All were naïve to previous TTh. Men were stratified into two groups: group 1 (N = 38) consisted of men with baseline TT > 300 ng/dL (10.4 nmol/L) and group 2 (N = 20) consisted of men with total TT < 300 ng/dL. Men in group 1 were diagnosed with TD on the basis of low values of free testosterone (FT) < 1.5 ng/dL (19.3 pmol/L). Dual-energy X-ray absorptiometry was performed at baseline and follow-up (6.9 ± 4 months) to assess regional and whole body. RESULTS: At baseline, both groups had similar lean mass (LM) and fat mass (FM), but percentage of trunk FM and percentage of total FM were significantly higher in group 2. Both groups demonstrated similar increases in LM for arms, legs, and total body. Percentage of total FM significantly decreased in both groups. CONCLUSIONS: Baseline severity of symptomatic TD influences body composition. Similar changes in LM and FM were seen with TTh regardless of baseline severity in TD. Men with TT > 300 ng/dL demonstrated significant positive changes in body composition. The similarity in objective response to TTh in these two groups provides support for the value of FT in the assessment of men with symptoms suggestive of TD.

Outcomes with the "V" implantation technique vs. standard technique for testosterone pellet therapy.

INTRODUCTION: Standard technique (ST) for implantation of testosterone pellets involves making a single linear track in the subcutaneous tissue of the buttock from the incision. After our initial experience with this modality, we modified this surgical technique to our current "V" technique (VT). This involves two tracks both caudally directed and emanating from the same skin incision but angulated approximately 10-15 degrees apart. While this allows additional pellets to be inserted more easily, and increased space to place those pellets further from the skin incision, it minimally increases the surgical procedure. AIM: We sought to examine the impact of this technical modification on therapeutic efficacy and surgical complication rates. METHODS: Retrospective chart review of all patients treated with testosterone pellets at our institution. MAIN OUTCOME MEASURE: Complication rates for infection, extrusion, hematoma, and pain. RESULTS: One hundred sixty-eight patients underwent 281 implantation procedures (40 via ST and 241 via VT). The mode number of pellets used with ST was 8 (range 6-8) and with VT was 10 (range 10-13). Incidence of pellet extrusion was 7.5% with ST and 0.8% with VT. Infection complicated ST in 5% of cases but only 1.2% with VT. No cases of hematoma were seen with ST but 1.2% of VT cases. Pain prompting discontinuation of therapy was seen in 7.5% with ST and 1.7% with VT. Significant pain without discontinuation was seen in 5% with ST and 1.2% with VT. Only in 1 of the 3 cases of hematoma was the individual on blood thinners. Fifty-eight other insertions were performed on blood thinners without significant hematoma. None of the individuals who developed infection or bleeding required additional surgical therapy. CONCLUSIONS: VT allows successful placement of larger number of pellets, with low rates of complications, especially extrusion, even in men on anticoagulants.

L-NAME, a nitric oxide synthase inhibitor, diminishes oxidative damage in urinary bladder partial outlet obstruction.

Partial bladder outlet obstruction (PBOO) results in cellular damage due to ischemia and reperfusion injury. Our study seeks to establish how early this damage can occur and the role that nitric oxide may play in its pathophysiology. Surgical PBOO (1, 3, and 7 days) were performed on male New Zealand White rabbits. Half of the animals were premedicated for 3 days with N(G)-nitro-l-arginine methyl ester(l-NAME), an inhibitor of nitric oxide synthase before obstruction. Bladder weight increased with duration of PBOO but was significantly lower at 3 and 7 days in animals treated with l-NAME compared with their untreated counterparts. Contractile function decreased progressively with PBOO duration. At 1 day postobstruction, bladder contractility was significantly lower in the l-NAME rabbits than in the untreated rabbits. At 3 and 7 days, contractility of the l-NAME bladders was equal or higher than the untreated bladders. The level of hypoxia at 1 day after obstruction was significantly higher in the l-NAME-treated animals than in the untreated controls but equal at 3 and 7 days obstruction. Increased nitrotyrosine was seen by Western blot in all obstructed animals. However, the amount was significantly less in the l-NAME-treated animals at 3 and especially at 7 days. Nerve density decreased progressively after obstruction; however, it decreased to a significantly lesser degree in the l-NAME-treated bladders than in the untreated groups. These results suggest that l-NAME pretreatment enhanced ischemic damage at 1 day after obstruction but protected the bladder from nitric oxide-generated free radical damage at the later time periods by inhibiting the generation of nitrotyrosine.