Symptoms Of Testosterone Deficiency Research Articles

Castration Levels of Testosterone Results in Atrophy of Androgen-Sensitive Perineal Muscles: A Potential Biomarker for Male Hypogonadism

ObjectivesTo evaluate MRI-based measurements of androgen-sensitive perineal/pelvic muscles in men with prostate cancer before and after androgen deprivation therapy (ADT) as a novel imaging marker for end-organ effects of hypogonadism. Diagnosing hypogonadism or testosterone deficiency (TD) requires both low serum testosterone and clinical symptoms, such as erectile dysfunction and reduced libido. However, the non-specific nature of many TD symptoms makes it challenging to initiate therapy. Objective markers of TD help to better identify patients who may benefit from testosterone supplementation; however, current markers, such as low bone mineral density, lack sensitivity. Previous studies suggest that decreased bulbocavernosus-muscle (BCM) thickness may be associated with TD, although it remains unclear if this is a correlative relationship. MethodsData was prospectively collected for patients with intermediate/high-risk localized prostate cancer enrolled in a phase II trial (NCT02430480). Patients received ADT before prostatectomy and underwent prostate MRI pre-/post-ADT. BCM, ischiocavernosus-muscle (ICM), and levator-ani-muscle (LAM) measurements were made using T2W-MRI. Paired t-tests evaluated changes in BCM/ICM/LAM width, and linear regression analyses evaluated relationships between changes in testosterone and muscle width. ResultsThirty-eight consecutive patients with pre-/post-ADT MRIs were analyzed. Baseline testosterone was 286.5ng/dl, and 36/38 patients had post-ADT testosterone <50ng/dL. Pre-ADT and post-ADT measurements of the bilateral BCM/ICM/LAM width were 7.16mm/7.95mm/5.53mm and 5.68mm/6.71mm/4.89mm, respectively (p<0.001). Decreases in testosterone predicted reduction in combined perineal muscle (BCM+ICM) width (p=0.032). ConclusionsAndrogen deprivation led to significant and relatively rapid decreases in BCM/ICM/LAM thickness. This objective biomarker of low testosterone states may help identify patients who will potentially benefit from testosterone replacement.

Increase in Testosterone Levels and Improvement of Clinical Symptoms in Eugonadic men With a Prolactin-secreting Adenoma.

Testosterone concentrations, albeit rarely, may be in the normal range (>3.0 ng/mL) in men with a prolactin-secreting pituitary adenoma (PSPA-nt). The evolution of total, bioavailable testosterone, gonadotropin levels, and that of graded symptoms of testosterone deficiency (TD) are uncertain in these patients. Retrospective case-control longitudinal study at a tertiary referral center. From 287 men, we selected 25 PSPA-nt men undergoing prolactin normalization (<20.0 ng/mL) during the follow-up. Graded symptoms of TD were investigated by structured interviews. Biochemical changes and TD symptoms were compared to those of a matched cohort of 61 men with pituitary neoplasms and normal testosterone levels (PA-nt). Baseline testosterone levels were similar between PSPA-nt and PA-nt subjects. The prevalence of specific and suggestive symptoms of TD was higher in PSPA-nt (20% and 68%) than in PAnt (3.3 and 29.5%; P = .02 and P = .0015, respectively). At the follow-up, total and bioavailable testosterone levels increased in PSPA-nt but not in PA-nt patients (Δ change: 1.28 ± 2.1 vs0.03 ± 1.5 ng/mL, + 0.33 ± 0.55 vs-0.26 ± 0.60 ng/mL; P = .0028 and P = .0088, respectively). LH and FSH levels also increased in PSPA-nt men (P < .05). Specific and suggestive, but not nonspecific symptoms of TD, improved only in PSPA-nt men (P < .05 for both). Baseline testosterone and LH were the strongest predictors of testosterone improvement in PSPA-nt patients. Despite having normal testosterone levels at baseline, patients with PSPA-nt experience a relief of TD symptoms and an improvement of their pituitary-gonadal axis function following prolactin normalization, especially when baseline TT and LH levels are in the low-normal range.

Safety and efficacy of Testosterone in woman

Introduction: The aim of this study is to evaluate the benefits and risks associated with testosterone treatment for postmenopausal women. Menopause is a natural phase in a woman's life marked by a decline in the production of female hormones like estrogen and progesterone. However, testosterone is also a hormone naturally produced by women, and it should be replenished when its production decreases. Although testosterone is not yet available for women due to lack of approval from the FDA (United States Food and Drug Administration), both research and clinical work have indicated its efficacy in addressing various symptoms of testosterone deficiency, including a diminished interest in sexual activity and weight gain. The objective of this article is to assess the benefits and risks of testosterone therapy in postmenopausal women by reviewing research and clinical studies that explore its use, as well as the associated side effects and risks. Materials and Methods: A systematic review was conducted, involving searches in databases such as PubMed and Google Scholar, using filters related to the topic. Initially, 42 published works were identified. Additional criteria, such as "prospective cohort studies" and "randomized clinical trials," were then applied to refine the results. The search had no language restrictions or time limitations, yielding 9 potentially relevant articles for the review. Results: However, this analysis utilized eight articles of the clinical trial or randomized trial type, retrieved from PUBMED and Google Scholar databases, highlighting the safety and effectiveness of testosterone in women. Conclusions: Following the conducted search, it was concluded that testosterone proves to be an effective treatment for postmenopausal women experiencing decreased sexual activity. Nevertheless, it is acknowledged that further research is imperative to validate its effectiveness in treating premenopausal women, as well as ensuring its safety in long-term treatment

Cardiovascular safety of testosterone replacement therapy (TRAVERSE trial)

Despite some confusing conclusions among recent findings from the TRAVERSE trial, the results should provide physicians with reassuring evidence to enable them to manage men with symptomatic testosterone deficiency with greater confidence.

Analysis of diurnal variation in serum testosterone levels in men with symptoms of testosterone deficiency.

Testosterone (T) plays a crucial role in various physiological functions in men, and understanding the variations in T levels during the day is essential for diagnosing and treating testosterone deficiency (TD). We sought to evaluate the reduction in serum total T (TT) levels throughout the day in men with symptoms of testosterone deficiency and to determine the variables having an impact on the extent of this decline. The study population consisted of a group of men who within 3months of each other had all undergone both early morning and afternoon TT level measurements. We did not include patients with a history of a prior orchiectomy, testosterone levels below 100ng/dL or above 1000ng/dL, a history of androgen deprivation therapy, or patients on T therapy. Statistical analyses were conducted using descriptive statistics, t-tests, chi-square tests, and correlation calculations. Liquid chromatography-tandem mass spectrometry was used to measure TT, and a change in TT levels greater than 100ng/dL was considered significant. Using multivariable and univariable analysis, we attempted to define predictors of a decrease in afternoon TT levels. The majority of men showed no significant difference in T levels between morning and afternoon. In total, 506 men with a median age of 65years were analyzed. The most common comorbidities were hypertension and hyperlipidemia. Levels of TT were measured in the morning and afternoon, and no significant differences in mean T levels based on the time of the test were found. Age was not significantly associated with T levels. There was a weak negative correlation between age and the difference between morning and afternoon T levels, with younger men showing more significant variations in T levels. The most considerable differences in T levels were observed in men younger than 30 years. There were no predictors of the magnitude of the T decrease in the afternoon. Strengths of the study include the number of subjects and the use of liquid chromatography-tandem mass spectrometry for T measurement. Limitations include failure to measure morning and afternoon T levels on the same day, the retrospective nature of the study, and a smaller sample size of patients younger than 30years. In this study we found no strong link between age and daily T fluctuation, but we observed a decrease in the magnitude of variation with aging. The group experiencing the most significant decline in daily T had higher morning and consistently normal afternoon T levels.

(082) Integrated Urology and Primary Care Model Improves Outcomes for Men with Testosterone Deficiency

Abstract Introduction Testosterone deficiency affects approximately 4-5 million men in the United States. The bidirectional association between testosterone deficiency and metabolic syndrome has been well-established. The diagnosis of testosterone deficiency should serve as a trigger for medical evaluation of other comorbidities. Furthermore, male sex is an independent predictor of decreased routine health maintenance; men are 40% less likely to have a primary care provider (PCP) compared to women in the United States. Thus, many patients who present to the urologist for symptomatic testosterone deficiency might have undiagnosed or poorly managed comorbidities coupled with a lack of a PCP. Objective We sought to investigate the impact of offering primary care access within an integrated Men’s Health Center to men presenting for initial evaluation of symptomatic testosterone deficiency. Methods This is a retrospective single institution study. All new patients presenting with testosterone deficiency between October 2019 and October 2022 were offered evaluation by a PCP within a university-based Men’s Health Center. Patients who were seen by the PCP underwent standard health screening and blood work including a lipid profile, liver function testing, and diabetes screening with hemoglobin (Hgb) A1c. All data were collected from the electronic medical record and deidentified. Institutional review board (IRB) exemption was obtained. Variables collected for analysis included age, race, body mass index (BMI), testosterone level on presentation, prior access to a pre-existing PCP, and number of visits attended with our PCP. Outcomes measured include new diagnoses made by the PCP and referral patterns to other specialties. All statistical analysis was conducted utilizing SPSS version 28. Results 81 men were evaluated over the 3-year study period. Median age was 49.0 (range: 21.2-93.7 years). 48 men (59%) established continuity of care and were seen by our PCP for more than 1 visit. 33 men (41%) did not have a pre-existing PCP. Older men were significantly more likely to have a pre-existing PCP (OR 1.06 [95% CI: 1.02-1.10], p&amp;lt;0.001). Hispanic men were significantly less likely to have an existing PCP (OR 0.16 [95% CI: 0.03-0.84], p=0.01). Newly diagnosed comorbidities included hypertension (41%), obesity (37%), hyperlipidemia (27%), obstructive sleep apnea (OSA; 25%), depression (23%), and diabetes (14%). 41 patients (51%) were prescribed a new medication. 21 patients (26%) were referred to nutrition, with mean BMI decrease of 1.75. 26 patients (32%) underwent sleep medicine evaluation for OSA. 27 (33%) and 37 patients (46%) received a flu vaccination and immunization updates. 11 patients (14%) were referred for screening colonoscopy. Patients who established continuity of care were significantly more likely to be treated for a new diagnosis (p&amp;lt;0.001) and receive a flu vaccination (p=0.007; Table 1). Conclusions This is the first report of integrated primary care and urology evaluation for testosterone deficiency. This comprehensive model results in improved outcomes including increased access to subspecialty referrals, objective weight loss, treatment of new diagnoses, updated immunizations, and cancer screening. Further studies are needed to assess reproducibility across other institutions, cost-effectiveness of this model, and patient satisfaction. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific, Endo Pharmaceuticals.

Testosterone Deficiency in Hypertensive Men: Prevalence and Associated Factors.

Testosterone deficiency (TD) is a prevalent condition in our midst and still very neglected. Arterial hypertension (AH) is one of the possible associated factors. To determine the prevalence of TD in a hypertensive male population and the factors associated with its occurrence, such as age, time since hypertension diagnosis, number of antihypertensive classes, body mass index (BMI), diabetes, dyslipidemia, chronic kidney disease (CKD), positive symptoms of TD (positive ADAM questionnaire) and use of spironolactone. Cross-sectional study with administration of the ADAM questionnaire, assessment of biochemical, clinical, and anthropometric data. Patients were stratified into DT and normal testosterone groups. Categorical variables were compared using the chi-squared test and continuous variables using the Mann-Witney test; variables with significance (p<0,05) were analyzed by multivariable linear regression. The prevalence of TD was 26.36%. There was an association between TD and body mass index (BMI) (p=0.0007) but there was no association with age (p=0.0520), time of hypertension diagnosis (p=0.1418), number of classes of antihypertensive drugs (p=0.732), diabetes (p=0.1112); dyslipidemia (p=0.3888); CKD (p=0.3321); use of spironolactone (p=0.3546) or positive ADAM questionnaire (p=0.2483). TD was highly prevalent and positively associated with BMI. Total testosterone (TT) declined by 8.44ng/dL with a one unit increase in BMI and dropped by 3.79ng/dL with a one-year increase in age.

Deficiência de Testosterona em Homens Hipertensos: Prevalência e Fatores Associados

Abstract Background: Testosterone deficiency (TD) is a prevalent condition in our midst and still very neglected. Arterial hypertension (AH) is one of the possible associated factors. Objectives: To determine the prevalence of TD in a hypertensive male population and the factors associated with its occurrence, such as age, time since hypertension diagnosis, number of antihypertensive classes, body mass index (BMI), diabetes, dyslipidemia, chronic kidney disease (CKD), positive symptoms of TD (positive ADAM questionnaire) and use of spironolactone. Methods: Cross-sectional study with administration of the ADAM questionnaire, assessment of biochemical, clinical, and anthropometric data. Patients were stratified into DT and normal testosterone groups. Categorical variables were compared using the chi-squared test and continuous variables using the Mann-Witney test; variables with significance (p&lt;0,05) were analyzed by multivariable linear regression. Results: The prevalence of TD was 26.36%. There was an association between TD and body mass index (BMI) (p=0.0007) but there was no association with age (p=0.0520), time of hypertension diagnosis (p=0.1418), number of classes of antihypertensive drugs (p=0.732), diabetes (p=0.1112); dyslipidemia (p=0.3888); CKD (p=0.3321); use of spironolactone (p=0.3546) or positive ADAM questionnaire (p=0.2483). Conclusions: TD was highly prevalent and positively associated with BMI. Total testosterone (TT) declined by 8.44ng/dL with a one unit increase in BMI and dropped by 3.79ng/dL with a one-year increase in age.

Male-specific consequences of obesity - functional hypogonadism and fertility disorders.

Obesity is currently one of the most serious public health problems which affects up to 30-40% of the population, and its prevalence is higher in men than in women. Complications of obesity include atherosclerosis, cardiovascular diseases, and type 2 diabetes mellitus, but it also has a negative impact on the hormonal system and fertility. The hormonal consequences of excess body fat in men are functional hypogonadism, which not only causes clinical symptoms of testosterone deficiency, but is also a risk factor for obesity (a vicious circle mechanism). Reduced fertility in obese men may be a consequence of functional hypogonadotropic hypogonadism (decreased gonadotropins and testosterone secretion, reduced libido, and erectile dysfunction), but other mechanisms associated with excess adipose tissue, like hyperinsulinaemia, hyperleptinaemia, chronic inflammation, and oxidative stress also play an important role. Therefore, in obese men deterioration of semen parameters (sperm concentration, motility, and morphology) and reduced fertility are observed, also concerning the effectiveness of assisted reproductive techniques. Reducing the mass of adipose tissue causes an increase in testosterone concentrations and has a beneficial effect on semen parameters. Functional hypogonadism in obese men should be diagnosed only after exclusion of organic causes of hypogonadism. Lifestyle changes, including physical exercise and low-caloric diet, and optimization of comorbidities, are still first line of treatment. In some patients, if such treatment is ineffective, pharmacotherapy or bariatric surgery may be considered. Testosterone replacement therapy is contraindicated in obese men with functional hypogonadism, especially in those who desire fertility. Selective oestrogen receptor modulators and aromatase inhibitors improve sperm quality but are not recommended for the treatment of hypogonadism in obese men. GLP-1 analogues appear to be effective and safe in the treatment of low testosterone and infertility in obese men and may be the main method of pharmacotherapy in the future.

Metabolic dysfunction-associated fatty liver disease is an early predictor for testosterone deficiency in aging men without metabolic syndrome.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as a valuable marker for identifying individuals at increased risk of metabolic dysfunction, liver-related complications, and cardiovascular disease. However, the association between MAFLD and testosterone deficiency (TD) in aging men remains poorly understood. This study aimed to investigate the association between MAFLD and the risk of TD in aging Taiwanese men, with a specific focus on those without metabolic syndrome (MetS). A free health screening program was conducted for Taiwanese men aged over 40 years in Kaohsiung, Taiwan. Participants underwent physical examinations, completed questionnaires regarding demographics, medical history, and clinical symptoms of TD, and provided 20-mL whole blood samples for biochemical, adipocytokine, and hormonal evaluations. Fatty liver index was used to evaluate the risk of fatty liver. Diagnostic criteria for MAFLD included fatty liver along with overweight/obesity, type 2 diabetes, or evidence of metabolic dysregulation. A total of 631 men (mean age: 54.4 ± 8.4 years) were enrolled. The prevalence rates of TD and MetS were significantly higher in men with MAFLD compared to those without (both p < 0.001). Additionally, the presence of MAFLD showed a significant correlation with adipocytokines associated with insulin resistance, such as adiponectin, leptin, and retinol-binding protein-4 (RBP-4) levels (all p < 0.001). Among men without MetS, those with MAFLD had a 3.89- and 4.74-fold higher risk of total testosterone < 300 ng/dL and TD, respectively, after adjusting for potential covariates. MAFLD is associated with an elevated risk of TD in aging Taiwanese men, particularly in the absence of MetS. This finding suggests that MAFLD could serve as an early predictor of TD, facilitating the identification of high-risk individuals and enabling timely interventions. Further research is needed to validate these findings and explore the underlying mechanisms linking MAFLD, TD, and MetS in diverse populations.

(303) Patient Satisfaction with Oral Testosterone Undecanoate (Jatenzo) in Men with Previous Testosterone Therapy: An Open-Label Single-Center Phase IV Clinical Trial

Abstract Introduction Testosterone therapy is available in multiple delivery systems such as gels and injections; however, oral formulations have been unavailable in the United States due to hepatotoxicity and variable bioavailability. Oral formulations of testosterone are convenient, easy to use, and avoid the problems of other forms of testosterone therapy. Jatenzo (testosterone undecanoate) is a novel US FDA-approved oral testosterone capsule that provides a uniform response in patients with testosterone deficiency. Objective This study evaluates patient satisfaction with Jatenzo in men with a recent history of alternative testosterone therapy. Methods Patients between 18 and 65 years of age with a diagnosis of testosterone deficiency were recruited. Testosterone deficiency was defined as two measurements of serum total testosterone below 300 ng/dL combined with clinical symptoms in accordance with American Urological Association guidelines. Patients were required to have received previous testosterone therapy and completed an adequate washout period prior to starting Jatenzo. The primary outcomes were patient satisfaction, measured by the Treatment Satisfaction Questionnaire for Medication (TSQM-9); and changes in testosterone deficiency symptoms, measured by the quantitative Androgen Deficiency in Aging Males (qADAM) questionnaire at the 3- and 6-month intervals relative to baseline. Serum testosterone, PSA, hematocrit, and estradiol were also evaluated at each time point. Results Of the 41 patients recruited into the study, 46% had previously received subdermal pellets, 41% intramuscular injections, 6% transdermal gels, and 7% intranasal gels. Total testosterone levels increased from a baseline after appropriate washout from a mean of 187 ng/dL to 773 ng/dL at 1 month, 434 ng/dL at 3 months, and 397 at 6 months of treatment with Jatenzo. Patient satisfaction with Jatenzo as measured by TSQM-9 improved to 52 and 59.3 at the 3-month and 6-month time points, respectively, relative to 38.5 with previous testosterone therapy. Testosterone deficiency symptoms as measured by qADAM were 34 with Jatenzo and 33.5 with previous testosterone therapy. No significant difference was noted in side effects such as polycythemia or changes in estradiol or PSA. Conclusions Jatenzo appears to provide similar patient satisfaction and similar improvement in testosterone deficiency symptoms relative to other forms of testosterone therapy. In addition, Jatenzo increases serum total serum testosterone to reference range (300 – 1000 ng/dL) in &amp;gt;90% of men without a difference in side effect profile. Disclosure Yes, this is sponsored by industry/sponsor: Clarus Therapeutics Clarification Industry funding only - investigator initiated and executed study

(064) Pharmacokinetics and Safety Outcomes of Compounded Versus Branded Testosterone Pellets in Men with Testosterone Deficiency: A Single-Center, Open-Label, Randomized Trial

Abstract Introduction Testosterone deficiency (TD) is a prevalent condition, especially in men ≥ 45 years old, and testosterone therapy (TTh) can improve quality of life in these patients. Objective In this abstract, we aim to evaluate the safety profile of compounded subcutaneous testosterone pellets and to compare the pharmacokinetics between compounded and FDA approved testosterone pellets (Testopel®) for TTh. Methods This was a prospective, Phase 3, randomized, non-inferiority clinical trial. We enrolled 75 men diagnosed with TD and randomized them 1:1 ratio to Testopel® and a 100mg compounded pellet group. The patients were implanted with their respective treatment: Testopel® (10 pellets of 75mg) or compounded testosterone pellets (8 pellets of 100mg). Results After randomization, there were 35 participants enrolled in the Testopel® 75mg arm and 40 participants in E100 arm. Serum T levels were similar between the groups at 2, 4 and 6 months, with most men (82%) dropping below 300 ng/dL by the end of the trial. Adverse events such as elevations in prostate specific antigen, estrogen and hematocrit in each group were similar. Most dropouts were related to persistent TD symptoms and serum T &amp;lt; 300ng/dL, with similar rates between the two groups in the study. Conclusions Men treated with Testopel® and compounded pellets had comparable serum testosterone levels and similar adverse events rates. Compounded testosterone pellets can provide an effective choice of long term TTh among men with TD comparable to Testopel®. Disclosure Yes, this is sponsored by industry/sponsor: Empower Pharmaceuticals. Clarification Industry funding only - investigator initiated and executed study. Any of the authors act as a consultant, employee or shareholder of an industry for: Empower Pharmacy.

Prevalence of secondary erythrocytosis in men receiving testosterone therapy: A matched-cohort analysis of intranasal gel, injections, and pellets.

Increased hematocrit (HCT) is a common adverse effect in men on testosterone therapy (TTh). We aimed to uncover differences in HCT changes among men receiving different forms of TTh, namely intranasal gels, intramuscular injections, and subcutaneous pellets. We conducted a single-center, retrospective, matched-cohort study of patients treated for testosterone deficiency (TD) to investigate the effect of three TTh regimens on HCT. We included men who received intranasal testosterone (NT), intramuscular testosterone (TC), or subcutaneous testosterone pellet (TP) regimens between January 2011 and December 2020. We matched treatment cohorts 1:1:1 for age, body mass index (BMI), and history of obstructive sleep apnea. Those taking TTh for less than 16 weeks were excluded. Comparison between groups was performed with U-Mann Whitney test, Student t-test, ANOVA, or Kruskal Wallis test as appropriate. Seventy-eight matched-cohort individuals with testosterone deficiency (TD) received either NT, TC, or TP. The most common TD symptoms prior to initiation of TTh were erectile dysfunction (38%), low libido (22%), and lack of energy (17%). Baseline serum testosterone and HCT were higher in NT (p<0.05) recipients. As expected, all men receiving TTh were found to have increased serum testosterone levels at followup (p<0.001). Relative to their respective baselines, men receiving TC experienced the greatest increase in serum testosterone (240.8 ng/dL to 585.5 ng/dL), followed by NT (230.3 ng/dL to 493.5 ng/dL) and TP (210.8 ng/dL to 360.5 ng/dL) (all p<0.001). TC and TP were associated with significant increases in HCT (4.4% and 1.7%), while NT was associated with a decrease in HCT (-0.8%) at 16-week followup. When controlled for age, BMI, and OSA, men receiving NT experienced decreased HCT compared to TC or TP at 16-week followup. Intranasal testosterone, while able to increase serum testosterone levels to reference range, does not appear to have a significant impact on HCT compared to the longer-acting forms of TTh.

MP79-02 PHARMACOKINETICS AND SAFETY OUTCOMES OF COMPOUNDED VERSUS BRANDED TESTOSTERONE PELLETS IN MEN WITH TESTOSTERONE DEFICIENCY: A SINGLE-CENTER, OPEN-LABEL, RANDOMIZED TRIAL

You have accessJournal of UrologyCME1 Apr 2023MP79-02 PHARMACOKINETICS AND SAFETY OUTCOMES OF COMPOUNDED VERSUS BRANDED TESTOSTERONE PELLETS IN MEN WITH TESTOSTERONE DEFICIENCY: A SINGLE-CENTER, OPEN-LABEL, RANDOMIZED TRIAL Nicholas Deebel, Eliyahu Kresch, Thiago Fernandes Negris Lima, Manuel Molina, Rohit Reddy, Mehul Patel, Justin Loloi, Chase Carto, Daniel Gonzalez, Jesse Ory, Halifax Canada, and Ranjith Ramasamy Nicholas DeebelNicholas Deebel More articles by this author , Eliyahu KreschEliyahu Kresch More articles by this author , Thiago Fernandes Negris LimaThiago Fernandes Negris Lima More articles by this author , Manuel MolinaManuel Molina More articles by this author , Rohit ReddyRohit Reddy More articles by this author , Mehul PatelMehul Patel More articles by this author , Justin LoloiJustin Loloi More articles by this author , Chase CartoChase Carto More articles by this author , Daniel GonzalezDaniel Gonzalez More articles by this author , Jesse OryJesse Ory More articles by this author , Halifax CanadaHalifax Canada More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003356.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Testosterone deficiency (TD) is a prevalent condition, especially in men ≥45 years old. Treatment of TD with testosterone therapy (TTh) carries numerous metabolic benefits. Subcutaneous Testopel® pellets are FDA approved for the treatment of TD however can impose a significant financial burden to the patient. The objective was to evaluate the safety profile of compounded subcutaneous testosterone pellets and compare the pharmacokinetics between compounded and FDA approved testosterone pellets (Testopel®) for TTh. METHODS: This was a prospective, randomized, non-inferiority clinical trial. We enrolled 75 men diagnosed with TD and randomized them 1:1 ratio to Testopel® and a 100mg compounded pellet group from Empower Pharmaceuticals, an FDA-registered-facility. The patients were implanted with their respective treatment: Testopel® (10 pellets of 75mg) or compounded testosterone pellets (8 pellets of 100mg). Patients were monitored for adverse events with morning laboratory assessment (serum Testosterone, estradiol, 17-hydroxyprogesterone (17-OHP), hematocrit & prostate specific antigen) at 2, 4 and 6 months. RESULTS: After randomization, 34 participants enrolled in the Testopel® 75mg arm and 42 participants in E100 arm. Serum T levels were similar between the groups at 2, 4 and 6 months, with most men (82%) dropping below 300 ng/dL by the end of the trial. The only adverse event was pellet extrusion (n=1). Most dropouts were related to persistent TD symptoms and serum T < 300ng/dL, with similar rates between the two groups in the study. The mean E levels for Testopel® and E100 at 2 months were 29.1 (IQR: 21.3-35.4) and 42.7±17.3 (IQR: 42.1-48.4) pg/mL respectively (p=0.0006). However, levels were not statistically different at the 4 (p=0.53) and 6-month (p=0.17) time points. Other lab values were similar (Figure 1). CONCLUSIONS: Compounded testosterone pellets are clinically efficacious and safe in the treatment of TD. Compounded pellets may represent an economic alternative to Testopel®. This pilot study may provide the practicing urologist with the support to offer compounded testosterone pellets as TTh. Source of Funding: Investigator-initiated grant by Empower Pharmaceuticals SupportNIH Grant R01 DK130991 and Clinician Scientist Development Grant from the ACS to RR © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1141 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nicholas Deebel More articles by this author Eliyahu Kresch More articles by this author Thiago Fernandes Negris Lima More articles by this author Manuel Molina More articles by this author Rohit Reddy More articles by this author Mehul Patel More articles by this author Justin Loloi More articles by this author Chase Carto More articles by this author Daniel Gonzalez More articles by this author Jesse Ory More articles by this author Halifax Canada More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF downloadLoading ...

Efficacy and safety outcomes of a compounded testosterone pellet versus a branded testosterone pellet in men with testosterone deficiency: a single-center, open-label, randomized trial.

Testosterone deficiency (TD) is a prevalent condition, especially in men ≥45years old, and testosterone therapy (TTh) can improve the quality of life in these patients. To evaluate the safety profile of compounded subcutaneous testosterone pellets and to compare the efficacy between compounded and market brand testosterone pellets for TTh: E100 (Empower Pharmacy) and Testopel (Food and Drug Administration approved), respectively. This was a prospective, phase 3, randomized, noninferiority clinical trial. We enrolled 75 men diagnosed with TD and randomized them 1:1 to a market brand group and a compounded pellet group. The patients were implanted with their respective testosterone pellets: Testopel (10 pellets of 75mg) and E100 (8 pellets of 100mg). We evaluated adverse events after implantation and followed men at 2, 4, and 6months for morning laboratory levels (prior to 10am): serum testosterone, estradiol, hematocrit, and prostate-specific antigen. After randomization, 33 participants were enrolled in the Testopel arm and 42 in the E100 arm. Serum testosterone levels were similar between the groups at 2, 4, and 6months, with most men (82%) dropping to <300ng/dL by the end of the trial. Adverse events were also similar, such as elevations in prostate-specific antigen, estradiol, and hematocrit. Most dropouts were related to persistent TD symptoms and serum testosterone <300ng/dL, with similar rates between the groups in the study. Men treated with Testopel and E100 pellets had comparable serum testosterone levels and similar adverse event rates, providing an effective choice of long-term TTh among men with TD. Strengths include the prospective, randomized, single-blinded study design and adequate follow-up. Limitations include the lack of external validity and the single-institution cohort. E100 compounded testosterone pellets are a noninferior option of TTh as compared with Testopel for men presenting with TD.

Pituitary-testis axis dysfunction following adjuvant androgen deprivation therapy.

Men with high-risk, non-metastatic prostate cancer receive adjuvant androgen deprivation therapy (ADT) for at least 2 years according to Danish guidelines. It remains unclarified if patients regain the function of the pituitary-testis axis after cessation of ADT. Thus, we aimed to investigate the function of the pituitary-testis axis following adjuvant ADT. In this study, we included men who underwent external beam radiation therapy and ADT for high-risk prostate cancer. All patients underwent assessment of testosterone deficiency (TD) symptoms, full biochemical assessment of the pituitary-testis axis, and dynamic stimulatory tests of gonadotropin (gonadotropin-releasing hormone (GnRH) test) and testosterone production (human chorionic gonadotrophin (hCG) test). Patients were diagnosed with TD based on a combination of TD symptoms and testosterone below age-specific reference ranges. TD was characterized as primary, secondary, or mixed based on serum gonadotropins and stimulatory tests. We found that among the 51 patients included in the study, the median time on ADT was 3.2 years and median time since ADT cessation was 3.8 years. Twenty-eight patients were diagnosed with TD; 10 had primary TD (testicular dysfunction), 11 secondary TD (pituitary dysfunction), and 7 mixed TD (combined pituitary and testicular dysfunction). An inadequate testosterone response to hCG stimulation was shown in 42 patients, whereas only 11 patients had a subnormal gonadotropin response to GnRH. We conclude that persistent TD is a common long-term consequence of adjuvant ADT in prostate cancer survivors, equally distributed between pituitary and testicular dysfunction. The study emphasizes the necessity for systematic follow-up of full pituitary-testis axis function in patients receiving adjuvant ADT.

Testosterone Deficiency in the Older Male

Testosterone deficiency (TD) in the older male is a difficult diagnosis to make with potentially life changing treatment. Awareness of the normal hormonal pathways, and an understanding of the corrective homeostatic mechanisms, can help in understanding the downstream effects of potential physiologic disturbances. Depending on age, the signs and symptoms of TD can vary from under developed external genitalia in the fetus, to lack of normal pubertal changes in the young adolescent up to an alteration in certain masculine physical characteristics present in the normal adult male. For the adult male, multiple treatment options are available, with newer ones being refined and developed. Monitoring for effective response to Testosterone Replacement Therapy (TRT) and screening for complications is not an onerous task and has the potential to improve the lives of many men.

A Proposal of a New Nomogram to Predict the Need for Testosterone ReplACEment (TRACE): A Simple Tool for Everyday Clinical Practice.

International guidelines suggest to use testosterone therapy (TTh) in hypogonadal men presenting symptoms of testosterone deficiency (TD), even if there is no fixed threshold level of T at which TTh should be started. We aimed to develop and validate a nomogram named TRACE (Testosterone ReplACEment) for predicting the need of TTh in patients with “low–normal” total testosterone levels. The following nomogram variables were used: serum T level; serum LH level; BMI; state of nocturnal erections; metabolic comorbidities; and IPSS total score. The nomogram has been tested by calculating concordance probabilities, as well as assaying the calibration of predicted probability of clinical testosterone deficiency and need for TTh, together with the clinical outcome of the TTh. A cohort of 141 patients was used for the development of the nomogram, while a cohort of 123 patients attending another institution was used to externally validate and calibrate it. Sixty-four patients (45.3%) received TTh. Among them, sixty patients (93.7%) reported a significant clinical improvement after TTh. The nomogram had a concordance index of 0.83 [area under the ROC curve 0.81 (95% CI 0.71–0.83)]. In conclusion, the TRACE nomogram accurately predicted the probability of clinical impairment related to TD, and resulted in a simple and reliable method to use to select hypogonadal patients with not clearly pathological testosterone values who will benefit from TTh.

Prevalence and clinical associations with primary hypogonadism in male systemic sclerosis.

Systemic sclerosis may affect male and female fertility. Premature ovarian failure has been reported in female systemic sclerosis patients, but the effects on male fertility in systemic sclerosis have not been studied. We aimed to determine the prevalence and clinical associations with primary hypogonadism among male systemic sclerosis patients. This was a cross-sectional pilot study, including 30 adult male systemic sclerosis patients attending the Scleroderma Clinic, Khon Kaen University. Testosterone deficiency symptoms were assessed using the Aging Males' Symptoms Rating Scale, urological examination, and blood testing (for total testosterone, free testosterone, follicle-stimulating hormone, and luteinizing hormone). We excluded patients with congenital hypogonadism and any acquired disorders of the testes and genitalia. The definition of primary hypogonadism was based on the International Society for the Study of the Aging Male 2015 diagnostic criteria for hypogonadism. Seven patients met the definition of primary hypogonadism-a prevalence of 23.3% (95% confidence interval: 9.9-42.3). The respective mean age and mean systemic sclerosis duration was 59.4 ± 11.9 and 5.5 ± 4.7 years. Older age at onset, high triglyceride level, and older age starting corticosteroid treatment were significantly associated with primary hypogonadism (p = 0.02, 0.02, and 0.03, respectively). Systemic sclerosis subset, disease severity, and immunosuppressant use were not associated with primary hypogonadism among Thai male systemic sclerosis patients. Around one-quarter of male systemic sclerosis patients had primary hypogonadism. Elderly onset of systemic sclerosis, hypertriglyceridemia, and late corticosteroid treatment were risk factors for developing primary hypogonadism.

Testosterone, Hypogonadism, and Heart Failure

Male hypogonadism is defined as low circulating testosterone level associated with signs and symptoms of testosterone deficiency. Although the bidirectional link between hypogonadism and cardiovascular disease has been clarified, the association between testosterone and chronic heart failure (HF) is more controversial. Herein, we critically review published studies relating to testosterone, hypogonadism, and HF and provide practical clinical information on proper diagnosis and treatment of male hypogonadism in patients with HF. In general, published studies are extremely heterogeneous, frequently have not adhered to hypogonadism guidelines, and suffer from many intrinsic methodological inaccuracies; therefore, data provide only low-quality evidence. Nevertheless, by selecting the few methodologically robust studies, we show the prevalence of testosterone deficiency (30%-50%) and symptomatic hypogonadism (15%) in men with HF is significant. Low testosterone correlates with HF severity, New York Heart Association class, exercise functional capacity, and a worse clinical prognosis and mortality. Interventional studies on testosterone treatment in men with HF are inconclusive but do suggest beneficial effects on exercise capacity, New York Heart Association class, metabolic health, and cardiac prognosis. We suggest that clinicians should measure testosterone levels in men with HF who have symptoms of a testosterone deficiency and conditions that predispose to hypogonadism, such as obesity and diabetes. These patients-if diagnosed as hypogonadal-may benefit from the short- and long-term effects of testosterone replacement therapy, which include improvements in both cardiac prognosis and systemic outcomes. Further collaborative studies involving both cardiologists and endocrinologists are warranted.