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Body mass index (BMI) is an important factor when selecting dosage of subcutaneous testosterone enanthate (TE; Xysoted), investigators report.

By the end of a 12-week period, total testosterone C-trough, C-avg (0 to 168 hours), and C-max were inversely related to BMI, according to findings presented at the 2021 Sexual Medicine Society of North America Fall Scientific Meeting.

“[This is] an intuitive assumption that never has been found to be the case before,” said co-author Martin M. Miner, MD, in an interview with 

Because there is little knowledge about how BMI affects the pharmacokinetic (PK) profile or dosing of testosterone therapies in men with testosterone deficiency, even though obesity or high BMI (≥30 kg/m2) is typically associated with low levels of testosterone, Miner and co-authors sought to understand the potential relationship.

“My question was: in men with a larger BMI, would they have data to support the use of a larger dose of their weekly testosterone injection? This is part of men receiving testosterone therapy for hypogonadism, or low testosterone levels associated with clinical signs and symptoms of testosterone deficiency,” Miner said.

In this post-hoc analysis, a single-arm phase 3 trial of subcutaneous TE was examined to determine PK parameters of weekly subcutaneous TE treatment among men with testosterone deficiency and varying BMIs. The primary end point was the percentage of patients who received at least 1 dose of subcutaneous TE and achieved an average serum total testosterone concentration of 300 ng/dL to 1100 ng/dL over a 7-day dosing of TE (C-avg [0 to 168 hours]) at week 12.

The PK population consisted of 142 patients, all of whom were patients in the safety population (received 1 or more doses of subcutaneous TE) with at least 1 blood sample drawn after the dose was administered. Of this population, 137 patients finished the study to completion (12 weeks) and were categorized into tertiles based on baseline BMI. Tertile 1 had a BMI ≤29 kg/m2 (n=45). Tertile 2 had a BMI > 29-32 kg/m2 (n=33). Tertile 3 had a BMI > 32 kg/m2 (n=59).

PK parameters included total testosterone trough concentration (C-trough), AUC-(0 to 168 hours), C-avg (0 to 168 hours), and C-max. At weeks 6 and 12, BMI tertiles were used to assess C-trough and C-avg (0 to 168 hours). At week 12, C-trough and C-avg (0 to 168 hours) were calculated according to their treatment doses and an overall dose-normalized linear regression model was utilized.

At baseline, the mean (SD) serum total testosterone levels for patients in tertiles 1-3 were 250.7 (101.3) ng/dL, 235.3 (91.2) ng/dL, and 226.4 (81.1) ng/dL, respectively. Prior to dosing adjustments at week 6, tertiles 2 and 3 mean (SD) C-trough (459.2 [157.0] ng/dL and 453.2 [133.0] ng/dL) were lower than tertile 1 (616.9 [181.6] ng/dL). At week 6, 21.2% of the total variance in C-trough levels could be predicted from BMI (

At the completion of this study, results showed that tertiles 2 and 3 had lower serum total testosterone C-trough compared with tertile 1 (494.8 [137.6] ng/dL and 469.0 [146.2] ng/dL, respectively, vs 517.7 (153.5) ng/dL). For tertiles 1-3, the mean (SD) C-avg (0 to 168 hours) values were 585.2 (148.1) ng/dL, 554.2 (104.5) ng/dL, and 528.5 (118.0) ng/dL, respectively. And at week 12, the mean doses were 65.0 (13.48) ng/dL, 78.0 (12.12) ng/dL, and 78.4 (12.68) mg, respectively. So, patients in Tertiles 2 and 3 required higher final doses of subcutaneous TE vs those in tertile 1, demonstrating an inverse relationship related to BMI.

In addition, the regression model found that 9.36% (

 < .001) of the total variance in C-trough and C-avg (0 to 168 hours) could be predicted from independent BMI and dose variables at the completion of this study (12 weeks), respectively.

Overall, 98.5% of men with testosterone deficiency who made it to the end of this study (12 weeks) achieved a C-avg (0 to 168 hours) of 300 ng/dL to 1100 ng/dL.

Reflecting on these findings, Miner explained, “The initial levels were inversely related to body mass index, so…men who are the largest…or had the largest BMI have the lowest testosterone levels. And that's what you would expect with obese men, that the greater the amount of obesity, the lower their endogenous levels would be, and that men would require the largest dose adjustment if they had a larger BMI.”

1. Miner M, Amy T, Gollen R, et al. Subcutaneous testosterone enanthate and the effect of body mass index on serum testosterone in men with testosterone deficiency. Paper presented at 2021 Sexual Medicine Society of North America Fall Scientific Meeting; October 21-24, 2021. Abstract 002.

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By the end of a 12-week period, total testosterone C-trough, C-avg (0 to 168 hours), and C-max were inversely related to BMI.

Body mass index is key when selecting dosage of testosterone enanthate

, discusses the background and findings of the study, “Finasteride-Associated Suicide and Depression in Men Treated for Hypogonadism and Impotence,” presented recently at the 2021 Sexual Medicine Society of North America Fall Scientific Meeting. Campbell is an assistant professor in the department of urology at the University of Florida, Gainesville.

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“What we wanted to do was to substantiate any difference between BPH and alopecia with finasteride and also people who are concomitantly taking testosterone for hypogonadism,” says Kevin J. Campbell, MD, MS.

Study examines association between finasteride and suicidality, depression, and anxiety

Benjamin P. Saylor is associate editor of Urology Times, an Advanstar Communications publication.

Long-term testosterone therapy appears to improve erectile function and reduce mortality in men with hypogonadism and type 2 diabetes mellitus, according to a recent study presented at the 2021 Sexual Medicine Society of North America Fall Scientific Meeting.

A total 361 men with hypogonadism (defined as total testosterone ≤350 ng/mL and at least moderate symptoms as assessed by the Aging Males’ Symptoms scale) in a single urology office had type 2 diabetes mellitus. Of these men, 183 received testosterone undecanoate injections of 1000 mg/12 weeks following an initial 6-week interval, with 178 patients opting to not receive TU injections serving as controls. International Index of Erectile Function-Erectile Function (IIEF-EF) domain score was assessed at each visit. Mortality was recorded based on reports from the patients’ general practitioners.

“Changes over time between groups were compared by a mixed effects model for repeated measures with a random effect for intercept and fixed effects for time, group and their interaction and adjusted for age, weight, waist circumference, blood pressure, fasting glucose, lipids and quality of life to account for baseline differences between groups,” wrote the authors, led by Farid Saad, MD, of Bayer AG and Gulf Medical University School of Medicine, Ajman, United Arab Emirates.

Mean follow-up was 8.2±3.2 years (median, 8 years) in the treatment group and 9.2±2.8 years (median, 10 years) in the control group. Total observation time was 1508 years in the treatment group vs 1641 years in the control group. Age at baseline was 60.7±5.5 years in the treatment group and 63.0±4.9 years for the controls (

< .0001). Phosphodiesterase 5 inhibitor usage at baseline was 27.3% in the treatment group vs 34.3% of the control group (

= .1527). At first visit, erectile dysfunction (ED) was reported by 64.5% of the treatment group vs 54.5% in the control group. In patients who did not report ED, the condition was diagnosed using the IIEF-EF in 30.6% of patients in the treatment group vs 44.4% in the control group, and 4.9% of patients in the treatment group and 1.1% in the control group had no ED.

Regarding erectile function, in year 12 for the treatment group, IIEF-EF increased by 12.1±0.4 (least squares means ± standard errors), whereas IIEF-EF decreased by 14.2±0.4 in the control group. Estimated adjusted difference between the 2 groups was 26.3.

Over the observation period, 15 patients (8.2%) in the treatment group died compared with 61 patients (34.3%) in the control group (

“Our mortality data confirm the results by Hackett et al

…,who observed the lowest mortality in a subgroup of men receiving continuous long-term [testosterone therapy],” the investigators concluded.

1. Saad F, Haider A, Haider KS, Doros G, Traish A. Long-term testosterone therapy improves erectile function and reduces mortality in men with hypogonadism and type 2 diabetes – updated results from a registry study. Paper presented at 2021 Sexual Medicine Society of North America Fall Scientific Meeting; October 21-24, 2021; Scottsdale, Arizona. Abstract 001

2. Hackett G, Cole N, Mulay A, Strange RC, Ramachandran S. Long-term testosterone therapy in type 2 diabetes is associated with reduced mortality without improvement in conventional cardiovascular risk factors. 

2019;123(3):519-529. doi:10.1111/bju.14536

Over the observation period, 15 patients (8.2%) in the treatment group died compared with 61 patients (34.3%) in the control group.

Long-term testosterone improves erectile function, reduces mortality in men with hypogonadism and diabetes

Among patients with Peyronie’s disease who respond to collagenase clostridium histolyticum (CCH, Xiaflex) injections, there does not appear to be a significant regain of penile length.

The finding was reported at the 2021 Sexual Medicine Society of North America Fall Scientific Meeting by investigators led by Jacob W. Greenberg of Tulane University School of Medicine, New Orleans, Louisiana, who worked on the study with Wayne J.G. Hellstrom, MD, FACS, and colleagues.

In the study, investigators conducted a post-marketing analysis to determine whether there was significant improvement of stretched penile length, erect penile length, and erect circumference in patients who respond to CCH compared with those who do not. The study included consecutive patients who received treatment with CCH for dorsal plaque and penile curvature above 30°in the absence of hourglass deformity.

A total of 148 patients were analyzed, completing 4 cycles of non-surgical intervention. To assess penile curvature, a goniometer was used after induction of artificial erection using alprostadil. This occurred before treatment and 8 weeks after the end of the fourth cycle. Stretched length, erectile length, and erectile circumference were also measured in the same setting.

“Based on the results of the IMPRESS trial, we decided that any improvement over 15 degrees was deemed a positive response (given our initial measurements were in increments of 5 degrees),” wrote the authors.

Of the 148 patients in the study, 129 (87%) had an improvement over 15° after completing 8 injections of CCH. The average penile curvature, stretched penile length, erected penile length, and erected circumference prior to the treatment were 61.4°, 13.9 cm, 13.3 cm, and 11.8 cm respectively.

Although there was no significant change in the erect or the stretched penile length in patients who responded to the injections, results showed that there was a significant decrease in the erect circumference among the majority of patients (11.8 cm decreasing to 9.3 cm).

The authors concluded, “There appears to be no significant regain of the penile length in which patients often complain about losing due to Peyronie's disease in those who respond to Xiaflex injections. The study finding suggests that the erect circumference might decrease, not necessarily due to the injection itself but due to the disease or recovery process.”

1. Greenberg JW, Soubra A, Kim J, et al. Xiaflex treatment for Peyronie’s disease may improve penile curvature degree with no effect on the loss on penile length in post-marketing analysis. Paper presented at 2021 Sexual Medicine Society of North America Annual Meeting; October 21-24, 2021. Abstract 069.

Although there was no significant change in the erect or the stretched penile length in patients who responded to the injections, results showed that there was a significant decrease in the erect circumference among the majority of patients.

Regain of penile length not seen with collagenase clostridium histolyticum treatment

 discusses the important findings from the study, “Subcutaneous Testosterone Enanthate and the Effect of Body Mass Index on Serum Testosterone in Men with Testosterone Deficiency,” presented recently at the 2021 Sexual Medicine Society of North America Fall Scientific Meeting. Mills is an associate clinical professor of urology at the David Geffen School of Medicine, the director of the UCLA division of Andrology, the director of the Men’s Clinic and the chief of UCLA Santa Monica Urology, University of California, Los Angeles

“There's 3 different levels of dosing…so this does provide you with a mechanism for titration if you're going to be using that in your patients,” says Jesse N. Mills, MD.

Dr. Mills weighs in on the benefits of testosterone enanthate

A novel oral formulation of testosterone undecanoate (TU; trade name: Jatenzo) displayed a safety profile that is consistent with other approved testosterone products, according to a recent study.

Investigators reporting their findings at the 2021 Sexual Medicine Society of North America Fall Scientific Meeting noted that no evidence of liver toxicity was observed with the treatment at 2 years.

For the study, the investigators conducted 2 open-label, multicenter, dose titration trials in men with hypogonadism (defined as serum testosterone of ≤ 300 ng/dL) aged 18 to 75 years. Trial 1 was a randomized, active-controlled, 2-arm, 12-month study, and Trial 2 was a long-term extension of those patients who completed Trial 1. “Statistical analyses were only conducted with the subjects who completed Trial 1 and continued treatment in Trial 2, thus providing up to 2 full years of data,” noted the authors.

Physical exam, adverse event reporting, and routine clinical laboratory measurements were used to evaluate safety.

A total of 86 patients participated in both trials. Testosterone concentration increased from 193.75 ± 9.44 ng/dL (mean ± SEM) at baseline to 475.5 ± 49.7 ng/dL after 24 months of therapy with oral TU. In addition, 84% of men achieved testosterone in the eugonadal range (300 ng/dL to 1000 ng/dL) after 90 days of therapy.

The investigators reported that mean testosterone concentrations remained in the eugonadal range throughout Trial 2. In addition, there were no clinically significant changes in liver function tests throughout the 2 trials. At day 270, 1 patient had an ALT level of 227 U/L, which was more than 4 times the ULN. The patient’s ALT was measured again at day 290 after continued TU use, and the level had dropped to 87 U/L, or less than 2 times the ULN.

A modest initial increase in prostate-related growth end points (ie, prostate-specific antigen and prostate volume) was reported that stabilized over time. There were no significant changes in International Prostate Symptom Score total score observed.

“There were significant, yet modest, increases in mean HCT (44.3 ± 0.3 to 46.6 ± 0.5%, 

 < .001) and cuff systolic BP (127.1 ± 1.2 to 131.8 ± 1.67 mmHg vs BL, 

 = .006),” the authors wrote. Cardiovascular end points such as HDL-C, hematocrit, and blood pressure changed initially and then stabilized throughout the trials.

“The long-term efficacy and safety profile of oral TU may provide a treatment option that avoids issues associated with other [testosterone replacement therapies], such as injection site pain or transference to partners and children,” the authors concluded.

1. Swerdloff R, Honig S, Wang C, et al. Two-year administration data of an oral testosterone undecanoate (TU) formulation in hypogonadal men. Real-world experience with first FDA-approved oral testosterone undecanoate formulation. Paper presented at 2021 Sexual Medicine Society of North America Fall Scientific Meeting; October 21-24, 2021; Scottsdale, Arizona. Abstract 003.

There were no clinically significant changes in liver function tests throughout the 2 trials.

Oral formulation of testosterone displays safety at 2 years

 discusses the background and findings of the study, “Subcutaneous Testosterone Enanthate and the Effect of Body Mass Index on Serum Testosterone in Men with Testosterone Deficiency,” presented recently at the 2021 Sexual Medicine Society of North America Fall Scientific Meeting. Miner is the founder of the Men’s Health Center at Miriam Hospital and clinical professor of family medicine and urology in the Warren Alpert School of Medicine at Brown University, Providence, Rhode Island.

“The initial levels were inversely related to body mass index, so…men who are the largest…or had the largest BMI have the lowest testosterone levels,” says Martin M. Miner, MD.

Dr. Miner on the effect of BMI on dosing in patients with testosterone deficiency

Platelet-rich plasma (PRP) injections appear to be a safe and feasible approach to treating patients with Peyronie’s disease, according to early research shared in a poster during the 2021 Sexual Medicine Society of North America (SMSNA) Fall Scientific Meeting.

First author Kevin Chu, MD, a men’s health fellow at the University of Miami, and colleagues reported data at SMSNA for the first 6 patients enrolled in the study. The patients were randomized to PRP or placebo and completed 2 injections.

“The notable finding to be taken from this abstract is that there were no noted adverse effects for patients that received PRP injections. We had thought there would be some patients with mild ecchymosis or penile pain. This, of course, may change as we enroll more patients into the trial, and our sample size gets larger. But from a preliminary standpoint, it appears to be safe to use in patients with Peyronie’s disease,” Chu said in an interview with 

Explaining the rationale for their study, Chu et al wrote in their poster that 7.1% of the general population has Peyronie’s disease, with use of intralesional collagenase clostridium histolyticum injection being the only FDA-approved medical therapy. They noted that surgical interventions for the condition include tunica albuginea plication, plaque excision without grafting, or placement of penile prothesis.

“Intervention only occurs once the disease process has entered the chronic, stable phase,” wrote Chu et al, adding, “Additional Peyronie’s disease therapies are needed as current treatment modalities have limited efficacy and considerable side effects.”

The increased use of platelet-derived therapies in other healthcare specialties inspired Chu et al to examine the approach in patients with Peyronie’s disease. The investigators were particularly intrigued by the use of platelet-derived therapies in orthopedics for the potential of healing wounds and regenerating tissue. “As calcified scar plaques are frequently identified in Peyronie’s disease patients, autologous PRP may prove to be a viable treatment for this patient population,” wrote Chu et al.

Accordingly, a double-blind placebo-controlled, single-center, randomized clinical trial was launched at the University of Miami Miller School of Medicine to compare PRP with placebo in patients with Peyronie’s disease. Chu et al’s SMSNA poster shared the outcome from their safety and feasibility review of the initial series of patients recruited to the trial.
This study population included men enrolled at the University of Miami trial site between April and July 2021 and treated with PRP versus placebo. For their review, the investigators evaluated patients for complications and tolerability immediately following PRP injection and at follow-up. Patients’ International Index of Erectile Function (IIEF-5) scores were reviewed prior to and following injections where applicable.

According to Chu, “The take-home message from our findings is that PRP appears to be safe for use in patients with Peyronie’s Disease. We are still very early on in our clinical trial, as we expect to enroll a total of 60 patients into the trial. As the trial is a double-blind, crossover trial, we do not have any current information on the actual efficacy of PRP in Peyronie’s Disease.”

Chu added, “It is important for [urologists] to know that the trial is currently ongoing. We hope to have a better idea of the efficacy of PRP for Peyronie’s Disease in 1 year. Restorative therapies for sexual medicine have hypothesized mechanisms for efficacy, but more robust clinical trials in humans are needed to show their true potential. At the University of Miami, we are running randomized clinical trials on PRP and combination (PRP + shockwave therapy) for sexual medicine ailments.”

1. Chu K, Masterson, T, Efimenko, I et al. Safety and feasibility of platelet-rich plasma injections for Peyronie’s disease: update from a single-center double-blind placebo-controlled randomized trial. Paper presented at 2021 Sexual Medicine Society of North America Fall Scientific Meeting; October 21-24, 2021; Scottsdale, Arizona. Abstract 179.

“Additional Peyronie’s disease therapies are needed as current treatment modalities have limited efficacy and considerable side effects," the authors wrote.

Platelet-rich plasma injections safe and feasible treatment for Peyronie’s disease

A recent assessment of the oral softgel formulation of testosterone undecanoate (TU, Jatenzo) indicates that dose titration is not required in most patients receiving the treatment.

The finding was part of a study presented at the 2021 Sexual Medicine Society of North America Fall Scientific Meeting by Robert E. Dudley, PhD, and co-authors.

For the study, the investigators performed pharmacokinetic (PK) simulations using a robust population PK model that was developed for testosterone in 474 men with hypogonadism who were treated with oral TU in previous PK studies. Average testosterone concentrations (Cavg) were derived from multiple serial blood samples collected over 24 hours for oral TU doses of 237 mg, 316 mg, and 396 mg twice daily. The investigators calculated the percent of subjects with T levels within the eugonadal range (serum Cavg between 304 ng/dL and 1030 ng/dL) at each of the TU dose levels. To assess the frequency of real-world dose titration, prescription data were accessed from the Symphony PatientSource Patient Transactional Dataset.

The investigators found that the percentage of subjects with steady state Cavg within the eugonadal range for 237 mg, 316 mg, and 396 mg twice daily were 61%, 74%, and 74%, respectively. These percentages corresponded to mean serum testosterone levels of 398 ng/dL, 560 ng/dL, and 728 ng/dL, respectively. In addition, wrote the authors, “Early assessment of real-world prescribing data for JATENZO indicated 35% of patients underwent dose titration by month 5.”

According to the investigators, their findings were consistent with initial real-world experience with oral TU indicating that dose titration is not required in most patients.

“However,” wrote the authors, “because the desired outcome of TRT therapy focuses on both T Cavg and symptomatic response, this oral TU formulation enables necessary dose adjustment when needed.”

1. Dudley R, Newmark J, Stark S, Pheng L, Beliveau M, Longstreth J. Real-world experience with first FDA-approved oral testosterone undecanoate formulation. Paper presented at 2021 Sexual Medicine Society of North America Fall Scientific Meeting; October 21-24, 2021; Scottsdale, Arizona. Abstract 028.

According to the investigators, their findings were consistent with initial real-world experience with oral testosterone undecanoate indicating that dose titration is not required in most patients.

Dose titration is not required in most patients receiving oral softgel testosterone

 discusses the background and findings of the study, “Two-Year Administration Data of an Oral Testosterone Undecanoate (TU) Formulation in Hypogonadal Men,” presented recently at the 2021 Sexual Medicine Society of North America Fall Scientific Meeting. Swerdloff is a professor of medicine and senior investigator at The Lundquist Institute, Harbor-UCLA Medical Center and David Geffen School of Medicine, University of California, Los Angeles.

“The difference between this compound and other compounds that were orally administered, is that this seems to go through the lymphatic system rather than going directly to the liver,” says Ronald Swerdloff, MD.

Platelet-rich plasma injections safe and feasible treatment for Peyronie’s disease

Dose titration is not required in most patients receiving oral softgel testosterone

Dr. Swerdloff on promising results with oral testosterone undecanoate