Intramuscular Testosterone Cypionate Research Articles

Clonal hematopoiesis of indeterminate potential (CHIP) and association with response to bipolar androgen therapy (BAT).

e17048 Background: CHIP, the expansion of hematopoietic cells carrying acquired somatic alterations associated with hematologic malignancies, is associated with increased inflammation, risk of heart disease, and poor outcomes. BAT, where testosterone levels are therapeutically manipulated between castrate levels to supraphysiologic levels, has been shown to be an effective therapy for some men with castration resistant prostate cancer. Clinical predictors of response are not established. We hypothesized that CHIP, would be negatively associated with clinical outcomes. Methods: Baseline peripheral blood from participants on the RESTORE Cohort C (NCT02090114) were analyzed for the presence of CHIP. Patients in this cohort had castration resistant prostate cancer with progressive disease after treatment with ADT alone. All participants were treated with 400mg of intramuscular testosterone cypionate every 28 days. Peripheral blood mononuclear cells were analyzed for the presence of CHIP using targeted next generation sequencing focused on 49 genes most commonly mutated in CHIP and myeloid malignancies. Given patients had metastatic and non-metastatic CRPC, progression free survival was determined based on the time to the start of the next therapy. Results: CHIP was present in 6 of 29 patients at baseline (21%) with one patient having 2 clones (Table). Median age of patients CHIP+ was 73 compared to age of 68 in the CHIP- group (p = 0.16). Median PSA was higher in the CHIP+ group (median 15, IQR 1-56) compared to the CHIP- group (median 3.5, IQR 1-57). 67% of the CHIP+ group and 57% of the CHIP- group had baseline Gleason scores of > = 8. The CHIP+ group had a median PFS of 8.8 months compared to 13.3 months in the CHIP- group (HR 3.3 95%CI 1.2, 9.1; p = 0.02). This remained significant after adjusting for age. There was no difference in overall survival (HR = 2.5 95% CI 0.5,2.9; p = 0.3). Conclusions: Among men treated with BAT as first line treatment for CRPC after ADT alone, CHIP was associated with a decreased progression free survival. Larger studies are needed to understand the impact of CHIP in larger cohorts of men treated with BAT and other therapies for prostate cancer.[Table: see text]

MP79-03 COMPARISON OF HEMATOCRIT CHANGE IN TESTOSTERONE-DEFICIENT MEN TREATED WITH INTRANASAL TESTOSTERONE GEL VERSUS INTRAMUSCULAR TESTOSTERONE CYPIONATE: A SINGLE-CENTER RANDOMIZED CLINICAL TRIAL

You have accessJournal of UrologyCME1 Apr 2023MP79-03 COMPARISON OF HEMATOCRIT CHANGE IN TESTOSTERONE-DEFICIENT MEN TREATED WITH INTRANASAL TESTOSTERONE GEL VERSUS INTRAMUSCULAR TESTOSTERONE CYPIONATE: A SINGLE-CENTER RANDOMIZED CLINICAL TRIAL Marco-Jose Rivero, Jesse Ory, Halifax Canada, Parris Diaz, Raul Clavijo, Nannan Thirumavalavan, Ruben Blachman-Braun, Justin Loloi, Ari Bernstein, and Ranjith Ramasamy Marco-Jose RiveroMarco-Jose Rivero More articles by this author , Jesse OryJesse Ory More articles by this author , Halifax CanadaHalifax Canada More articles by this author , Parris DiazParris Diaz More articles by this author , Raul ClavijoRaul Clavijo More articles by this author , Nannan ThirumavalavanNannan Thirumavalavan More articles by this author , Ruben Blachman-BraunRuben Blachman-Braun More articles by this author , Justin LoloiJustin Loloi More articles by this author , Ari BernsteinAri Bernstein More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003356.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Testosterone therapy is associated with rise in hematocrit (HCT) and subsequent risk of polycythemia and thrombotic events. Incidence of these side effects may vary depending on the route of administration of testosterone therapy formulation. In this study, we compared the effects of intranasal testosterone gel (NT) and intramuscular testosterone cypionate (TC) on HCT and serum total testosterone (T) levels in testosterone-deficient men over 4 months. METHODS: Patients between 18 and 75 years of age with a diagnosis of testosterone deficiency were recruited. Testosterone deficiency (TD) was defined as two measurements of serum total testosterone below 300 ng/dL combined with one or more characteristic clinical symptoms. Men were randomized (1:1) to receive either NT (5.5 mg per nostril) three times a day or TC (200 mg intramuscularly) once every two weeks. The primary outcomes were changes in HCT and serum T before and after 4 months of treatment. Secondary outcomes were changes in estradiol, prostate-specific antigen, and 17-hydroxyprogesterone. RESULTS: 49 men were randomized to receive either NT (n=20) or TC (n=29). The median participant age was 47 years with a mean serum T of 236.6 ng/dL and mean HCT of 43.3%. The prevalence of participants who screened positive for obstructive sleep apnea on STOP-BANG questionnaire was 70% for the NT group and 72% for the TC group. Men in both groups experienced significantly increased serum T levels throughout the study period (p<0.001), although a larger increase was seen in the TC group. There was an increase in the mean HCT of the TC group from 42.6% to 46.0% at 4-month follow-up (p=0.006), while the NT group experienced no significant changes in mean HCT (p=0.903). The TC group experienced significant increases in estradiol (p<0.001) and decreases in 17-hydroxyprogesterone (p<0.001) at 4-month follow-up, while the NT group experienced no such changes. CONCLUSIONS: Although both NT and TC regimens are effective in treating men with TD, NT does not appear to significantly affect HCT levels. Patients who are at increased risk of developing polycythemia or those who wish to avoid changes in estradiol or 17-hydroxyprogesterone levels may benefit from short-acting testosterone therapy formulations such as NT. Source of Funding: This project was funded by an investigator-initiated grant provided by Acerus Pharmaceuticals © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1142 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Marco-Jose Rivero More articles by this author Jesse Ory More articles by this author Halifax Canada More articles by this author Parris Diaz More articles by this author Raul Clavijo More articles by this author Nannan Thirumavalavan More articles by this author Ruben Blachman-Braun More articles by this author Justin Loloi More articles by this author Ari Bernstein More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF downloadLoading ...

RF25 | PMON76 Kissing carotid arteries: An unusual cause of male hypogonadotropic hypogonadism.

Abstract Background Aneurysms of the internal carotid arteries are a rare cause of pituitary dysfunction1. While there are reports of primary amenorrhea in females due to ectatic internal carotid arteries2, hypogonadism in a male due to "kissing internal carotid arteries" causing compression of the pituitary gland has not previously been reported. Clinical Case A 27-year-old male with history of Crohn's disease, obesity, depression and sleep apnea on CPAP presented to endocrinology clinic for evaluation of low testosterone levels diagnosed 9 months prior to his initial visit. At the time of initial evaluation patient was using intramuscular testosterone cypionate 120mg weekly with total testosterone of 2.43 ng/mL (2.50-9.50 ng/mL). Testosterone replacement therapy was discontinued at that time to assess the hypothalamic-pituitary-gonadal (HPG) axis. After 9 months without testosterone treatment, repeat labs demonstrated total testosterone 0.91 ng/mL, bioavailable testosterone 0.69 ng/mL (1.10-4.0 ng/mL), SHBG 8 nmol/L (10-89 nmol/L), LH 3.1 mIU/mL (2-12 mIU/mL), FSH 2.7 mIU/mL (1.5-10 mIU/mL), estradiol 23 pg/mL (6-44 pg/mL), IGF-1 193 ng/mL (85-310 ng/mL), prolactin 10 ng/mL (3-23 ng/mL), TSH 1.03 mIU/L (0.3-5.5 mIU/L), FT4 1.15 ng/dL (0.76-1.70 ng/dL), 8 AM cortisol 13.5 ug/dL (5.3-22.5 ug/dL) and ACTH 37 pg/mL (5-52 pg/mL). Semen analysis was also performed which was unremarkable. Pituitary MRI revealed symmetric ectatic cavernous portions of the internal carotid arteries compressing and distorting the normal anatomy of the anterior pituitary gland consistent with "kissing carotid arteries." MRA was performed which did not demonstrate aneurysm or malformation of the cavernous internal carotid arteries. Patient was started on subcutaneous semaglutide 0.25mg weekly which was titrated to 1mg weekly for treatment of obesity. Testosterone replacement therapy was not re-initiated given future fertility goals and normal semen analysis. Conclusion To our knowledge, this is the first reported case of kissing internal carotid arteries causing isolated hypogonadotropic hypogonadism in a male patient. References 1) Heshmati HM, Fatourechi V, Dagam SA, Piepgras DG. Hypopituitarism caused by intrasellar aneurysms. Mayo Clin Proc. 2001 Aug;76(8): 789-93. doi: 10.1016/S0025-6196(11)63222-9. PMID: 11499817 2) Sahin M, Dilli A, Karbek B, Unsal IO, Gungunes A, Colak N, Uçan B, Cakal E, Ozbek M, Delibasi T. Unusual cause of primary amenorrhea due to kissing internal carotid arteries. Pituitary. 2012 Jun;15(2): 258-9. doi: 10.1007/s11102-012-0393-9. PMID: 22492265. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:44 p.m. - 12:49 p.m.

Comparing Rates of Polycythemia in Hypogonadal Men Using Nasal Testosterone Gel Versus Intramuscular Testosterone: Update of a Randomized Clinical Trial

Men with hypogonadism who use intranasal testosterone are less likely to develop polycythemia than men using intramuscular testosterone cypionate.

MP34-05 IMPACT OF NASAL, INTRAMUSCULAR, AND SUBCUTANEOUS TESTOSTERONE PELLETS ON INTRATESTICULAR TESTOSTERONE: EVALUATION OF DATA FROM TWO RANDOMIZED CLINICAL TRIALS

You have accessJournal of UrologyCME1 May 2022MP34-05 IMPACT OF NASAL, INTRAMUSCULAR, AND SUBCUTANEOUS TESTOSTERONE PELLETS ON INTRATESTICULAR TESTOSTERONE: EVALUATION OF DATA FROM TWO RANDOMIZED CLINICAL TRIALS Parris Diaz, Rohit Reddy, Ruben Blachman-Braun, Alexandra Dullea, Isaac J. Zucker, Daniel C. Gonzalez, Eliyahu Kresch, and Ranjith Ramasamy Parris DiazParris Diaz More articles by this author , Rohit ReddyRohit Reddy More articles by this author , Ruben Blachman-BraunRuben Blachman-Braun More articles by this author , Alexandra DulleaAlexandra Dullea More articles by this author , Isaac J. ZuckerIsaac J. Zucker More articles by this author , Daniel C. GonzalezDaniel C. Gonzalez More articles by this author , Eliyahu KreschEliyahu Kresch More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002588.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Testosterone replacement therapy (TRT) can potentially cause decreased spermatogenesis and subsequent infertility due to decrease in intratesticular testosterone (ITT) production. Serum 17-hydroxyprogesterone (17-OHP) is a reliable surrogate for ITT that is critical for preserving male fertility. We hypothesized that long-acting T formulations will decrease ITT compared to short-acting formulations. We evaluated data from two open-label, randomized, two-arm clinical trials amongst different testosterone therapies with subcutaneous T pellets (TP), Intranasal Testosterone (NT) or Intramuscular Testosterone cypionate (TC). METHODS: A total of 75 symptomatic hypogonadal men (2 serum T <300 ng/dL drawn before 10AM) were randomized into open-label randomized clinical trials. Eligible subjects received 800mg TP, 11mg TID NT or 200 mg×2 weeks TC. Lab values were evaluated at baseline and follow-up. The primary outcome was changes in serum 17-OHP. Secondary outcome was changes in serum T. Data analyzed via Kruskal Wallis and Chi square test.Trials: NCT04439799 (June 19,2020) & NCT04523480 (August 21,2020). RESULTS: Median participant age was 45 years old, with overall baseline 17-OHP of 46 and serum testosterone of 223.5 ng/dL. Serum 17-OHP significantly decreased in all three TRT regimens (Table 1). The 4-month change in 17-OHP in the NT group (−33.3% from baseline) was less than the change seen in TC (−65.3% from baseline) or TP (−44% from baseline) (p=0.005). All T formulations increased serum testosterone levels at follow-up, with the largest increase seen in TC (+157.6%), followed by NT (+114.3%), and TP (+79.6%) (p=0.005). CONCLUSIONS: Short-acting nasal testosterone appears to decrease 17-OHP less than long-acting T formulations. All modalities saw significant increases in serum T levels at follow-up. Intranasal T and other short acting T formulations may better preserve ITT and be beneficial for hypogonadal men seeking to maintain fertility potential while on TRT. Source of Funding: Investigator Initiated Grant funded by Acerus Pharmaceuticals and Empower Pharmacy (RR). This work was also supported by National Institutes of Health Grant R01 DK130991 and Clinician Scientist Development Grant from the American Cancer Society to RR © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e580 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Parris Diaz More articles by this author Rohit Reddy More articles by this author Ruben Blachman-Braun More articles by this author Alexandra Dullea More articles by this author Isaac J. Zucker More articles by this author Daniel C. Gonzalez More articles by this author Eliyahu Kresch More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF DownloadLoading ...

Intramuscular testosterone cypionate vs subcutaneous testosterone enanthate: Comparing the outcomes in hypogonadal men

ABSTRACT Introduction Intramuscular testosterone cypionate (IM-TC) is the conventional treatment option for hypogonadal men with baseline serum total testosterone (TT) less than 300 ng/dL; however, significant peaks in testosterone cause adverse effects including polycythemia and rise in estradiol (E2). Subcutaneous testosterone enanthate-autoinjectors (SCTE-AI) were designed with a lower testosterone peak-to-trough ratio of 1.8. Objective This dual-institutional study compared the TT, hematocrit (HCT), E2, and prostate-specific antigen (PSA) response to treatment with IM-TC versus SCTE-AI. Methods 263 hypogonadal men were treated with testosterone replacement therapy (TRT) via IM-TC or SCTE-AI. TT, HCT, E2, and PSA levels were obtained at baseline and 6- to 12-weeks post-treatment. Significant differences in baseline and post-treatment levels were identified by univariate analysis. Linear regression models determined whether treatment modality was independently associated with post-TRT levels of TT, HCT, E2, and PSA. Results Patients treated with SCTE-AI were significantly younger, had higher baseline TT levels, and lower baseline E2 levels (Table 1). Post-TRT, the SCTE-AI cohort had significantly lower HCT and E2, while TT and PSA levels were not significantly different between the treatment arms. After adjusting for significant differences with linear regression, SCTE-AI was associated with a 14% greater increase in trough TT levels compared to IM-TC (p=0.027) (Table 2a). Furthermore, SCTE-AI was independently associated with 41% and 26.5% lower post-therapy HCT (p&amp;lt;0.001) and E2 (p&amp;lt;0.001) levels, respectively, when compared to IM-TC (Table 2b-c). Neither TRT modality was associated with post-therapy elevation of PSA (p=0.691). TT: Total Testosterone; HCT: Hematocrit; E2: Estradiol; PSA: prostate-specific antigen Conclusions While IM-TC and SCTE-AI provide a significant increase in testosterone, SCTE-AI is associated with lower levels of post-therapy HCT and E2 compared to IM-TC after adjusting for significant covariates. SCTE-AI is an effective testosterone delivery system with a preferable safety profile over IM-TC. Disclosure Work supported by industry: no. A consultant, employee (part time or full time) or shareholder is among the authors (Antares Pharma, Clarus Therapeutics, Coloplast, Promescent, Viome).

Comparison of Prevalence of Polycythemia between Nasal Testosterone Gel vs Intramuscular Testosterone Cypionate: Evaluation of Data from an Ongoing Phase IV, Open-Label, Randomized Clinical Trial

ABSTRACT Introduction Men taking testosterone therapy (TT) have potential side effects such as polycythemia, testicular atrophy, and decreased spermatogenesis. Recent evidence has shown that the modality of delivery may affect the prevalence of these side effects. We hypothesized that intranasal short-acting testosterone will have a lower rate of polycythemia than injectable long-acting testosterone because shorter-acting formulations can more closely mimic normal physiology. Objective To compare the effects of Natesto and Testosterone Cypionate (TC) on hematocrit and serum testosterone levels in testosterone deficient men over 4 months. Methods This Phase IV, randomized, open-label clinical trial was performed on 30 symptomatic, testosterone deficient men with at least two serum testosterone levels below 300 ng/dL drawn before 10AM. Men were randomized (1:1) to receive either Natesto three times per day (5.5mg per nostril) and intramuscular TC (200mg) once every two weeks. Hematocrit and serum testosterone were evaluated before and after four months. The primary outcome was changes in hematocrit. Secondary outcomes were changes in E, DHT, PSA and 17-OHP. Data analysis was performed using two-sample and single-sample T tests, and determination of equal or unequal variances was computed using F tests. Results The median participant age was 45 years old. At baseline, serum T of all participants was 239.6 ng/dL and hematocrit of 43.1. Prevalence of participants who screened positive for OSA on STOP-BANG questionnaire for Natesto and TC group were 75% and 78%, respectively. The 4-month change in hematocrit in the Natesto group (-1.1 from baseline) was significantly less than the change in hematocrit seen in the TC group (+5.1 from baseline), (p &amp;lt; 0.001, t = -7.6). Prevalence of polycythemia (HCT &amp;gt; 52%) after 4 months was 0% in Natesto group and 5.5% in TC. Both groups increased testosterone levels above baseline at 1 and 4 months, with a larger increase seen in the TC group compared to Natesto (p = 0.029, t = 1.71), (Figure 1B). In the Natesto group, secondary outcomes E, DHT, PSA, and 17-OHP changed -2.9 (p = 0.54), +4.3 (p = 0.64), +0.34 (p = 0.52), and +1.6 (p = 0.88) from baseline, respectively (Figure 1C). In the TC group, secondary outcomes E, DHT, PSA, and 17-OHP changed +21.2 (p= 0.019), +4.3 (p = 0.64), -0.34 (p = 0.52), and -42.9 (p &amp;gt; 0.001) from baseline, respectively (Figure 1C). Conclusions Short-acting nasal testosterone does not appear to increase serum hematocrit when compared to intramuscular testosterone cypionate, while both modalities returned men to a eugonadal serum testosterone level (&amp;gt;300 ng/dL) in 83% of men. In men who are at risk of developing polycythemia (obstructive sleep apnea, high baseline hematocrit), nasal testosterone gel or other short acting formulations should be strongly considered. Disclosure Yes, this is sponsored by industry/sponsor: Acerus Pharmaceuticals Clarification Industry funding only - investigator initiated and executed study

Comparison of Intratesticular Testosterone between Men Receiving Nasal, Intramuscular, and Subcutaneous Pellet Testosterone Therapy: Evaluation of Data from Two Single-Center Randomized Clinical Trials.

Testosterone replacement therapy (TRT) can potentially cause decreased spermatogenesis and subsequent infertility. Recent studies have suggested that 17-hydroxyprogesterone (17-OHP) is a reliable surrogate for intratesticular testosterone (ITT) that is essential for spermatogenesis. We evaluated data from two ongoing open-label, randomized, two-arm clinical trials amongst different treatment preparations (Trial I) subcutaneous testosterone pellets (TP) and (Trial II) intranasal testosterone (NT) or intramuscular testosterone cypionate (TC). Seventy-five symptomatic hypogonadal men (2 serum testosterone <300 ng/dL) were randomized into open label randomized clinical trials. Eligible subjects received 800 mg TP, 11 mg TID NT or 200 mg ×2 weeks TC. 17-OHP and Serum testosterone were evaluated at baseline and follow-up. The primary outcome was changes in 17-OHP. Secondary outcome was changes in serum testosterone. Data was analyzed by two-sample and single-sample t-tests, and determination of equal or unequal variances was computed using F-tests. Median participant age was 45 years old, with overall baseline 17-OHP of 46 and serum testosterone of 223.5 ng/dL. 17-OHP significantly decreased in subjects prescribed long-acting TP or TC. The 4-month change in 17-OHP in the NT group (-33.3% from baseline) was less than the change seen in TC (-65.3% from baseline) or TP (-44% from baseline) (p=0.005). All testosterone formulations increased serum testosterone levels at follow-up, with the largest increase seen in TC (+157.6%), followed by NT (+114.3%) and TP (+79.6%) (p=0.005). Short-acting nasal testosterone appear to have no impact on serum 17-OHP especially in comparison to long-acting testosterone formulations. All modalities saw significant increases in serum testosterone levels at follow-up. NT and other short acting testosterone formulations may better preserve ITT and be beneficial for hypogonadal men seeking to maintain fertility potential while on TRT.

MP36-20 INTRAMUSCULAR TESTOSTERONE CYPIONATE VS SUBCUTANEOUS TESTOSTERONE ENANTHATE: COMPARING THE OUTCOMES IN HYPOGONADAL MEN

You have accessJournal of UrologySexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II (MP36)1 Sep 2021MP36-20 INTRAMUSCULAR TESTOSTERONE CYPIONATE VS SUBCUTANEOUS TESTOSTERONE ENANTHATE: COMPARING THE OUTCOMES IN HYPOGONADAL MEN Edward Choi, Perry Xu, Farouk El-Khatib, Faysal Yafi, and Parviz Kavoussi Edward ChoiEdward Choi More articles by this author , Perry XuPerry Xu More articles by this author , Farouk El-KhatibFarouk El-Khatib More articles by this author , Faysal YafiFaysal Yafi More articles by this author , and Parviz KavoussiParviz Kavoussi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002045.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Intramuscular testosterone cypionate (IM-TC) is the conventional treatment option for hypogonadal men with baseline serum total testosterone (TT) less than 300 ng/dL; however, significant peaks in testosterone cause adverse effects including polycythemia and rise in estradiol (E2). Subcutaneous testosterone enanthate-autoinjectors (SCTE-AI) were designed with a lower testosterone peak-to-trough ratio of 1.8. This dual-institutional study compared the TT, hematocrit (HCT), E2, and prostate-specific antigen (PSA) response to treatment with IM-TC versus SCTE-AI. METHODS: 263 hypogonadal men were treated with testosterone replacement therapy (TRT) via IM-TC 100 mg weekly or SCTE-AI 100 mg weekly. TT, HCT, E2, and PSA levels were obtained at baseline and 6- to 12-weeks post-treatment. Significant differences in baseline and post-treatment levels were identified by univariate analysis. Linear regression models determined whether treatment modality was independently associated with post-TRT levels of TT, HCT, E2, and PSA. RESULTS: Patients treated with SCTE-AI were significantly younger, had higher baseline TT levels, and lower baseline E2 levels. Post-TRT, both cohorts had significant increases in trough TT compared to their respective baseline levels (IM-TC: 313.6 ng/dL to 536.4 ng/dL, p<0.001; SCTE-AI: 249.6 ng/dL to 540.4 ng/dL, p<0.001). When comparing between cohorts, the SCTE-AI cohort group had significantly lower HCT and E2, while TT and PSA levels were not significantly different between the treatment arms. After adjusting for significant differences with linear regression, SCTE-AI was associated with a 14% greater increase in trough TT levels compared to IM-TC (p=0.027). Furthermore, SCTE-AI was independently associated with 41% and 27% lower post-therapy HCT (p<0.001) and E2 (p<0.001) levels, respectively, when compared to IM-TC (Table 2b-c). Neither TRT modality was associated with significant post-therapy elevation of PSA (p=0.691). CONCLUSIONS: While IM-TC and SCTE-AI provide a significant increase in TT levels, SCTE-AI is associated with lower levels of post-therapy HCT and E2 compared to IM-TC after adjusting for significant covariates. SCTE-AI is an effective testosterone delivery system with a potentially preferable safety profile over IM-TC. Source of Funding: n/a © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e643-e644 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Edward Choi More articles by this author Perry Xu More articles by this author Farouk El-Khatib More articles by this author Faysal Yafi More articles by this author Parviz Kavoussi More articles by this author Expand All Advertisement Loading ...

IMPACT OF TESTOSTERONE THERAPY ON POLYCYTHEMIA: EVALUATION OF DATA FROM TWO ONGOING OPEN-LABEL RANDOMIZED SINGLE-CENTER CLINICAL TRIALS

Testosterone (T) replacement therapy (TRT) is the mainstay treatment for male hypogonadism. The most commonly reported adverse event among men using TRT is polycythemia. What is unknown is whether the short-acting vs. long-acting testosterone preparations have different effects on hematocrit. We hypothesized that short-acting testosterone therapy will be physiologic and have lesser effect on hematocrit compared to long-acting TRT. We evaluated data from two simultaneous ongoing open-label, randomized, two-arm clinical trials to evaluate the impact of TRT on Hematocrit and compared prevalence rates of polycythemia among subcutaneous T pellets (long-acting) and Intranasal Testosterone or Intramuscular Testosterone cypionate (TC) (short-acting).

MP36-03 IMPACT OF TESTOSTERONE THERAPY ON INTRATESTICULAR TESTOSTERONE: EVALUATION OF TWO OPEN-LABEL RANDOMIZED CLINICAL TRIALS OF TESTOSTERONE PELLETS, INJECTIONS, AND INTRANASAL GEL IN HYPOGONADAL MEN

You have accessJournal of UrologySexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II (MP36)1 Sep 2021MP36-03 IMPACT OF TESTOSTERONE THERAPY ON INTRATESTICULAR TESTOSTERONE: EVALUATION OF TWO OPEN-LABEL RANDOMIZED CLINICAL TRIALS OF TESTOSTERONE PELLETS, INJECTIONS, AND INTRANASAL GEL IN HYPOGONADAL MEN Daniel Gonzalez, Eliyahu Kresch, Jesse Ory, Sirpi Nackeeran, Ruben Blachman-Braun, Manuel Molina, and Ranjith Ramasamy Daniel GonzalezDaniel Gonzalez More articles by this author , Eliyahu KreschEliyahu Kresch More articles by this author , Jesse OryJesse Ory More articles by this author , Sirpi NackeeranSirpi Nackeeran More articles by this author , Ruben Blachman-BraunRuben Blachman-Braun More articles by this author , Manuel MolinaManuel Molina More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002045.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Testosterone replacement therapy (TRT) can potentially cause infertility via suppression of HPG axis. Intratesticular testosterone (ITT) is vital for spermatogenesis and can be reliably evaluated with serum 17-hydroxyprogesterone (17-OHP) as a serum biomarker. We hypothesized that long-acting TRT will have a significant impact on suppressing ITT production as compared to short-acting TRT. We evaluated data from two simultaneous open-label, randomized, two-arm clinical trials amongst different treatment preparations (Trial I) subcutaneous T pellets and (Trial II) Intranasal Testosterone or Intramuscular Testosterone cypionate (TC). METHODS: Hypogonadal men (2 serum T <300 ng/dL by LC-MS/MS) were randomized into open-label randomized clinical trials. Eligible subjects received: 800mg subcutaneous T pellets or 11mg TID Intranasal T or 200mg x 2 weeks TC for 2 months. Serum T and 17-OHP were collected at baseline and follow-up. Data are presented as a post-hoc analysis of the two randomized clinical trials and reported as the mean percent change (SD). Paired sample analysis (baseline versus follow-up) was performed with Student's T-test to determine change within the different preparations. RESULTS: ITT via 17-OHP significantly decrease among men receiving all the different T preparations.(Fig. 1) Of note, longer acting TRT such as pellets and TC demonstrated the greatest % decrease in 17-OHP, -64 +29 ng/dL and -54 + 31 ng/dL, respectively (p<0.05) as compared to nasal T gel. Shorter acting T preparations such as nasal T gel demonstrated a mean % decrease in 17-OHP -38 +26 (p=0.008), but to a lesser extent as pellets. Changes in ITT paralleled with subjective changes in testis size, with men receiving nasal T gel reported maintenance of testis size whereas those with T pellets or TC reported decreased testis size. CONCLUSIONS: Intranasal T and other short acting forms of TRT may help hypogonadal men maintain ITT and testis size that is critical for maintaining spermatogenesis and fertility potential. The differential effects of TRT (based on half-life) on intratesticular T is novel and should be considered during the decision making for hypogonadal men who wish to preserve future fertility. Source of Funding: Investigator Initiated Grants from Acerus Pharmaceuticals, Canada and Empower Pharmacy © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e636-e637 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniel Gonzalez More articles by this author Eliyahu Kresch More articles by this author Jesse Ory More articles by this author Sirpi Nackeeran More articles by this author Ruben Blachman-Braun More articles by this author Manuel Molina More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement Loading ...

Impact of Testosterone Therapy on Hematocrit and Polycythemia: Evaluation of Data From Two Ongoing Open-Label Randomized Single-Center Clinical Trials

Introduction & Objective: Testosterone (T) replacement therapy (TRT) is the mainstay treatment for male hypogonadism. The most commonly reported adverse event among men using TRT is polycythemia. What is unknown is whether the short-acting vs. long-acting testosterone preparations have different effects on hematocrit. We hypothesized that short-acting testosterone therapy will be physiologic and have lesser effect on hematocrit compared to long-acting TRT. We evaluated data from two simultaneous ongoing open-label, randomized, two-arm clinical trials to evaluate the impact of TRT on Hematocrit and compared prevalence rates of polycythemia among subcutaneous T pellets (long-acting) and Intranasal Testosterone (Natesto) or Intramuscular Testosterone cypionate (TC) (short-acting). Subject and Methods: Hypogonadal men (2 AM serum T < 300 ng/dL assayed by LC-MS/MS) aged 18-65 years were randomized into open-label randomized clinical trials. Eligible subjects received: Trial 1: 800mg subcutaneous Testopel T pellets; Trial 2: 11mg TID Intranasal testosterone (Natesto) or 200mg x 2 weeks TC for 2 months. Serum T, Hematocrit (HCT), and prevalence of polycythemia (as defined as HCT >50%) were collected at baseline and after 2 months of therapy. Data are presented as a post-hoc analysis of the two randomized clinical trials and reported as median and interquartile range [25th-75th], paired sample analysis (baseline versus follow-up) was performed with the Wilcoxon rank test to determine change during time within the different TRT modalities, with p<0.05 considered significant. Results: Median change for serum T between baseline and 2mo follow-up to subcutaneous T pellets was 542 [454-757] ng/dL, Intranasal Testosterone 706 [517-1010] ng/dL, and TC 525 [280-712]ng/dL. T pellets showed a statistically significant increase in HCT from 44.6 [42.0-46.6] to 46.7 [42.6-48.9] (p<0.001), with a prevalence of 7/47 (14%) men developing polycythemia. A safety trigger for HCT greater than 54% occurred in 2/47 (4%). The treatment effect was independent of baseline serum testosterone. TRT with Natesto decreased HCT, from 43.4 [41.6-46.1] to 43.4 [40.6-46.5], however not statistically significant (p=0.262). TC statistically increased HCT from 41.6 [40.3-43.1] to 43.8 [43.5-47.4] (p=0.018), with 0% of men developing polycythemia in both groups. Conclusions: Long acting TRT appears to increase hematocrit compared to short-acting testosterone therapies. Treatment of hypogonadal men with Intranasal T Natesto and testosterone cypionate successfully achieved target serum T level and maintained HCT levels. Longer-term durability and safety effects of the intervention remain to be further investigated.

Impact of Short-Acting vs Long-Acting Testosterone Therapy on Intratesticular Testosterone Using Data From Two Open-Label Randomized Clinical Trials of Testosterone Pellets, Injections, and Intranasal Gel in Hypogonadal Men

Introduction & Objective: Exogenous testosterone (T) replacement therapy (TRT) is typically long-acting and can potentially cause infertility in a majority of men due to suppression of HPG axis. Intratesticular testosterone is vital for spermatogenesis and can be reliably evaluated with serum 17-hydroxyprogesterone (17-OHP). Based on this observation, we hypothesized that we used serum 17-OHP as a serum biomarker for evaluating intratesticular T in men receiving TRT. We hypothesized that long-acting TRT will have a significant impact on suppressing HPG axis as compared to short-acting preparations. We evaluated data from two simultaneous open-label, randomized, two-arm clinical trials amongst different treatment preparations (Trial I) subcutaneous T pellets and (Trial II) Intranasal Testosterone (Natesto) or Intramuscular Testosterone cypionate (TC).Subject & Methods: Hypogonadal men (2 AM serum T < 300 ng/dL assayed by LC-MS/MS) aged 18-65 years were randomized into open-label randomized clinical trials. Eligible subjects received: 800mg subcutaneous Testopel T pellets (n=47); or 11mg TID Intranasal testosterone (Natesto) (n=10) or 200mg x 2 weeks TC (n=10) for 2 months. Serum T and 17-OHP were collected at baseline and after 2 months of therapy. Data are presented as a post-hoc analysis of the two randomized clinical trials and reported as the median and interquartile range [25th-75th], paired sample analysis (baseline versus follow-up) was performed with the Wilcoxon test to determine change during time within the different TRT modalities, with p<0.05 considered significant. Results: Median change for serum T between baseline and 2mo follow-up to subcutaneous T pellets was 542 [454-757] ng/dL, Intranasal Testosterone 706 [517-1010] ng/dL, and TC 525 [280-712]ng/dL.; 96% of subjects in each trial achieved mean T concentrations in the eugonadal range. We demonstrated that serum T levels were within normal range among men receiving the various therapies. As expected, we found a statistically significant decrease amongst the different T preparations in serum 17-OHP. Longer acting T preparations such as T pellets and TC demonstrated the greatest decrease in 17-OHP, from 41 [20.3-65.6] to 14 [10.3-20.8] ng/dL and 80 [48-121] ng/dL to 20 [17-36] ng/dL (p<0.001), respectively. Shorter acting T preparations such as Natesto demonstrated a statistically significant decrease in 17-OHP, from 52.5 [26-67] ng/dL to 26.5 [18-39.8]ng/dL (p=0.007), but to a lesser extent as compared to the longer-acting preparations.Conclusions: Natesto, and other short acting forms of TRT may help hyogonadal men maintain Intratesticular T that is critical for maintaining spermatogenesis. The differential effects of TRT on intratesticular T based on their half-lives is novel and should be considered during the decision making for hypogondal men who wish to preserve fertility and / or testis size.

Virilizing doses of testosterone decrease circulating insulin levels and differentially regulate insulin signaling in liver and adipose tissue of females.

Transgender men undergoing hormone therapy are at risk for insulin resistance. However, how virilizing testosterone therapy affects serum insulin and peripheral insulin sensitivity in transgender men is unknown. This study assessed the effect of acute, virilizing testosterone on serum insulin concentrations and insulin signaling in liver, skeletal muscle, and white adipose tissue (WAT) of female pigs as a translational model for transgender men. Females received three doses of intramuscular testosterone cypionate (TEST females; 50 mg/day/pig) or corn oil (control) spaced 6 days apart starting on the day of estrus (D0). Fasting blood was collected on D0, D3, D5, D11, and D13, and females were euthanized on D13. On D13, TEST females had virilizing concentrations of serum testosterone with normal concentrations of serum estradiol. Virilizing serum testosterone concentrations (D13) were associated with decreased serum insulin and C-peptide concentrations. Blood glucose and serum glycerol concentrations were not altered by testosterone. Virilizing concentrations of testosterone downregulated AR and ESR1 in subcutaneous (sc) WAT and upregulated transcript levels of insulin-signaling pathway components in WAT and liver. At the protein level, virilizing testosterone concentrations were associated with increased PI3K 110α in liver and increased insulin receptor (INSR) and phospho(Ser256)-FOXO1 in visceral (v) WAT but decreased phospho(Ser473)-AKT in vWAT and scWAT. These results suggest that acute exposure to virilizing concentrations of testosterone suppresses circulating insulin levels and results in increased abundance of proteins in the insulin-signaling pathway in liver and altered phosphorylation of key proteins in control of insulin sensitivity in WAT.NEW & NOTEWORTHY Acute virilizing doses of testosterone administered to females suppress circulating insulin levels, upregulate components of the insulin-signaling pathway in liver, and suppress insulin signaling in white adipose tissue. These results suggest that insulin resistance in transgender men may be due to suppression of the insulin-signaling pathway and decreased insulin sensitivity in white adipose tissue.

027 Comparison of Outcomes for Hypogonadal Men Treated with Intramuscular Testosterone Cypionate Versus Subcutaneous Testosterone Enanthate

027 Comparison of Outcomes for Hypogonadal Men Treated with Intramuscular Testosterone Cypionate Versus Subcutaneous Testosterone Enanthate

A cross-sectional comparison of secondary polycythemia in testosterone-deficient men treated with nasal testosterone gel vs. intramuscular testosterone cypionate.

Secondary polycythemia is a known adverse effect of testosterone replacement therapy (TRT). Different testosterone formulations are available, with significantly different half-lives, which have varying influences on the development of secondary polycythemia. Herein, we compared the prevalence of secondary polycythemia in testosterone-deficient men treated with intranasal testosterone gel (Natesto®) vs. intramuscular testosterone cypionate (TC) therapy. We performed a cross-sectional analysis of secondary polycythemia (hematocrit [Hct] ≥54%) in men who received TRT. We included a total of 60 men: 30 men who received Natesto (4.5% testosterone gel [tid, 5.5 mg/nostril, 11 mg/dose, 33 mg/day]), and 30 who received TC (between 0.5 and 1.0 mL or 100-200 mg intramuscularly weekly). A univariable and multiple regression analysis was performed considering last Hct measurement as the main outcome. The analyzed variables included were age, body mass index (BMI), smoking history, treatment group, and testosterone levels on followup. We identified polycythemia (Hct ≥54%) in 10% (3/30) of men who received TC. Additionally, in men treated with TC, 33.3% (10/30) had a Hct ≥50% during therapy. None of the men who received Natesto had a Hct ≥50% during therapy. On multivariable linear regression analysis, we demonstrated that the use of TC increased Hct by 3.24% (95% confidence interval [CI] 0.74-5.73%, p=0.012) compared to Natesto. The prevalence of polycythemia in men treated with Natesto was markedly lower compared to the men who received TC therapy.

MP07-07 SERUM TESTOSTERONE PROFILES IN MEN ON TESTOSTERONE THERAPY AFTER BILATERAL ORCHIECTOMY

You have accessJournal of UrologyInfertility: Therapy II1 Apr 2018MP07-07 SERUM TESTOSTERONE PROFILES IN MEN ON TESTOSTERONE THERAPY AFTER BILATERAL ORCHIECTOMY Jose Torremade, Coskun Kagacan, Yanira Ortega, and John P Mulhall Jose TorremadeJose Torremade More articles by this author , Coskun KagacanCoskun Kagacan More articles by this author , Yanira OrtegaYanira Ortega More articles by this author , and John P MulhallJohn P Mulhall More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.3070AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A low but well recognized incidence of bilateral testis cancer occurs. Such men, requiring bilateral orchiectomy, rely entirely on adrenal androgens, sustaining a testosterone (T) level not compatible with a healthy life and thus testosterone therapy (TT) is mandatory. The objective of this study was to define the outcomes of transdermal therapy in such men. METHODS Men who had undergone bilateral orchiectomy and presented for testosterone therapy were studied. All such patients received 200mg of intramuscular testosterone injection in the recovery room at the completion of their second orchiectomy prior to discharge. 2-4 weeks later they were commenced on transdermal TT at maximum dose. 2 weeks later they had a serum total testosterone (T) level checked. If less than 300 ng/dl switching to intramuscular (IM) TT was discussed with the patient. For those who opted to switch, 100mg IM testosterone cypionate was administered and was to be injected by the patient every 7 days. An attempt was made using multivariable analysis to find predictors of achievement of a total T level >300ng/dl on transdermal TT. RESULTS 47 patients were studied with a mean age of 26±11 (22-41) years. 4 had had synchronous, 43 metachronous bilateral orchiectomy. 19 of these men had been on transdermal TT between the 2 orchiectomies, all with good levels achieved. On transdermal TT, mean total T level was 246±196 (184-480 ng/dl), 20 men (42%) having levels above 300ng/dl. All 27 of the men failing to achieve a physiological T level opted to pursue IM T, as did 11/20 men who did achieve total T levels above 300. All 38 of these men achieved total T levels above 300 while injecting. On IM TT, mean total T was 711±140 (548-902) ng/dl. No predictors were found of achievement of physiological total T level on transdermal TT. CONCLUSIONS Many men who have undergone bilateral orchiectomy struggle to achieve physiological total T levels using transdermal testosterone administration. This information should be helpful to clinicians in their discussion with such patients. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e90 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Jose Torremade More articles by this author Coskun Kagacan More articles by this author Yanira Ortega More articles by this author John P Mulhall More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Transgender Man Being Evaluated for a Kidney Transplant.

A 33-year-old female-to-male transgender individual (height, 5′1″; weight, 135 lb) presented to emergency care with acute otitis media and hypertension (170/110). Currently prescribed medications include daily atorvastatin and intramuscular testosterone cypionate injections (100 mg/week). The patient refused admission because of discrimination concerns as a transgender man, but presented to his primary care physician the following morning. Laboratory results revealed a urine total protein concentration of 199.5 mg/dL (random collection, 0.0–10.0 mg/dL) and an estimated glomerular filtration rate (eGFR)3 of 31 mL/min/1.73m2 if assessed using the male equation or 23 mL/min/1.73m2 if assessed using the female equation. On the basis of male categorization, the patient was diagnosed with stage 3 chronic kidney disease (CKD3), prescribed carvedilol, and strongly encouraged to discontinue testosterone, to which he agreed. The patient transferred to an alternate institution; here testosterone administration was restarted, lisinopril was prescribed, and reduction in protein and sodium intake was encouraged. Incidentally, the patient had maintained a vegan diet for >10 years. Renal transplant evaluation was initiated several months later. Corresponding male eGFR was 24 mL/min/1.73m2, but the corresponding female eGFR was 18 mL/min/1.73m2. Urine protein excretion was 3 g/day. Because transplant candidates require a GFR <20 mL/min/1.73m2 (1) and because the patient's male-calculated eGFR was above the cutoff, he was not listed. An evaluation 4 months later documented an eGFR of 21 and 15 mL/min/1.73m2 for corresponding male and female levels, respectively. In the patient's medical chart, only the corresponding male eGFR was documented, and the medical care team did not consider that the sex-based equations will lead to a different interpretation. All eGFR values were calculated using the Modification of Diet in Renal Disease study equation. ### QUESTIONS TO CONSIDER 1. What genetic, biological, and environmental factors can influence creatinine concentration and lead to subsequent uncertainty …

Hormone Replacement Therapy in Children with Hypogonadotropic Hypogonadism: Where do we Stand?

ObjectiveTo characterize hormone replacement therapy in a cohort of adolescent males and females with hypo-gonadotropic hypogonadism (HH) with a focus on changes in management during the past 10 years. MethodsMedical records of patients followed for HH during the past 10 years were reviewed. ResultsA total of 45 patients (22 female: 23 male) with HH were identified. The average age at HH diagnosis was 14.48 ± 2.02 years in females and 14.89 ± 1.64 years in males (P = .53). In females, the average age of pubertal induction was 14.53 ± 1.86 years. Conjugated equine estrogen was used in 54.5%, transdermal estradiol in 41%, and oral estradiol in 4.5%. The average duration to cycling was 1.96 ± 0.78 years. A progressive increase in the use of transdermal estradiol was noted over time, with 100% of females being started on this regimen since 2008. In males, the average age of induction was 15.22 ± 1.41 years. All were started on intramuscular testosterone cypionate at various doses. The average duration to full adult replacement was 1.95 ± 0.51 years. ConclusionThere is no current standard of care to guide pubertal induction in adolescents with HH. However, a significant increase in the use of transdermal estrogen was noted in females during the past 10 years. While much less variability in pubertal induction was seen in males, wide disparities in doses and escalation schedules were found. Prospective studies aimed at elucidating optimal strategies for sex steroid replacement in this pediatric population are badly needed. (Endocr Pract. 2013;19:968-971)

The Use of Testosterone in the Treatment of Chronic Postvasectomy Pain Syndrome: Case Report and Review of the Literature

The purpose of this article is to describe a simple, intellectually reasonable, initial treatment for all subacute and chronic postvasectomy scrotal pains. The use of intramuscular testosterone cypionate in a dose of 400 mg monthly for 3 months is described for patients suffering from painful sperm granuloma at the vasectomy site or in the epididymis, circumventing the need for other medical or surgical approaches. Excellent results have been achieved in patients and a representative case is illustrated. The rationale for this approach based on endocrinological and immunological mechanisms is described.