- Email: [email protected]
PD50-06 LONG-TERM SAFETY AND TOLERABILITY OF ORAL TESTOSTERONE (LPCN 1021) IN HYPOGONADAL MEN: RESULTS FROM THE 52-WEEK PHASE 3 STUDY
THE JOURNAL OF UROLOGYâ
Vol. 195, No. 4S, Supplement, Tuesday, May 10, 2016
statistically significant trend for decreasing risk with increasing cumulative dose exposure to testosterone (p-value for trend from <0.0001 to 0.03). CONCLUSIONS: Testosterone replacement therapy appears to decrease the risk of cardiovascular events, prostate cancer diagnoses and overall mortality in a dose-responsive manner. Due to the observational nature of the data, selection bias and the health user effect must be considered. Source of Funding: This work was funded by a peer-reviewed grant from The Physicians’ Services Inc. Foundation awarded to C.J.D.W.
PD50-04 EFFICACY AND TOLERABILITY OF DAPOXETINE AND SERTRALINE FOR THE TREATMENT OF CHINESE PATIENTS WITH PREMATURE EJACULATION Lin Yang*, Dalin He, Xian, China, People’s Republic of INTRODUCTION AND OBJECTIVES: Premature ejaculation (PE) is one of the most prevalent male sexual dysfunction, and can have a detrimental effect on self-confidence and on interpersonal relationships. Pharmacotherapy with selective serotonin reuptake inhibitor (SSRI) represents the most efficacious treatment option for PE. In this paper we compared the efficacy and tolerability of dapoxetine and sertraline pharmacotherapy for the treatment of PE. METHODS: From January 2015 to June 2015, a total of 117 patients with PE seeking treatment in our hospital were randomly assigned (2:1) to receive either dapoxetine 30 mg 1-3 h before planned sexual intercourse (n¼78) or sertraline 50 mg once daily for 1 month (n¼39). Intravaginal ejaculatory latency time (IELT), clinical global impression of change (CGIC) score, Premature Ejaculation Pro?le (PEP) and treatment-emergent adverse events (TEAEs) were recorded as outcomes. RESULTS: Both groups experienced significantly increased IELT after pharmacotherapy (dapoxetine-treated group: from 0.87 min to 2.84 min; sertraline-treated group: from 0.84 min to 2.71 min). The CGIC rating regarding PE was reported to be much better or better in 36.5% and 37.5% of dapoxetine and sertraline-treated patients, respectively. At least a slightly better CGIC rating was reported by 63.6% and 71.9%, respectively, of dapoxetine-treated and sertraline-treated groups. The incidence of adverse events that include dizziness (12.5% vs. 9.5%), nausea (9.4% vs. 6.3%), headache (6.3% vs. 3.2%), and diarrhea (6.3% vs. 3.2%) after sertraline therapy showed a slightly higher trend than that after dapoxetine therapy (P>0.05); while the incidence of fatigue (3.2% vs. 18.8%), somnolence (1.6% vs. 15.6%) and dry mouth (0% vs. 12.5%) was significantly lower after dapoxetine therapy compared with sertraline treatment (P<0.05). Although similar improvements in IELT, CGIC and PEP were observed between the two groups, dapoxetine therapy has the advantage of an on-demand dosing regimen, as well as possessing a better tolerability profile, especially for special populations such as those whose profession requires driving, pilots, and delicate handling skills. CONCLUSIONS: Dapoxetine is the only pharmacological therapy approved by the SFDA for PE treatment in China. The findings of this study suggest that on-demand oral dapoxetine therapy is effective and well tolerated. Dapoxetine should therefore be recommended as the first-line treatment option for Chinese patients with PE. Source of Funding: none
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PD50-05 IS THERE A PROTECTIVE ROLE OF TESTOSTERONE AGAINST HIGH-GRADE PROSTATE CANCER? INCIDENCE AND SEVERITY OF PROSTATE CANCER IN 553 PATIENTS UNDERGOING PROSTATE BIOPSY IN A PROSPECTIVE DATA REGISTER Aksam Yassin*, Dresden, Germany; Mahmoud Salman, Yousef Almehmadi, Norderstedt-Hamburg, Germany INTRODUCTION AND OBJECTIVES: Major concern regarding testosterone therapy (TRT) in middle-aged and elderly men is still prostate safety or cancer. METHODS: 553 prostate biopsies (2008-2013) were performed at our institute. 22 patients refused biopsy. We investigated incidence and severity of PCa in three groups: hypogonadal (T350 ng/dl) men receiving TRT, hypogonadal untreated, and eugonadal men. All groups underwent similar screening intensity of at least once per year. Biopsies were performed when indicated according to EAU guidelines. RESULTS: In 42 hypogonadal men receiving TRT, 7 (16.7%) had a positive biopsy. Of these, 5 had a Gleason score 6 (71.4%) and 2 subjects a Gleason score >6 (28.6%). Predominant Gleason score was 3 in all 7 men (100%). Tumor grade was II in 6 (85.7%) and II-III in 1 (14.3%) men. 162 untreated hypogonadal men, 84 (51.9%) had a positive biopsy. Of these, 34 had a Gleason score 6 (40.5%) and 50 a Gleason score >6 (59.5%). Predominant Gleason score was 3 in 65 (77.4%), 4 in 17 (20.2%) and 5 in 2 (2.4%) men. Tumor grade was II in 35 (41.7%), II-III in 10 (11.9%), III in 34 (40.5%) and IV in 5 (6.0%) men. In 349 eugonadal men, 132 (37.8%) had a positive biopsy. Of these, 56 had a Gleason score 6 (42.4%) and 76 a Gleason score >6 (57.6%). Predominant Gleason score was 3 in 109 (82.6%), 4 in 22 (16.7%) and 5 in 1 (0.1%) men. Tumor grade was II in 59 (44.7%), II-III in 6 (4.5%), III in 63 (47.7%) and IV in 4 (3.0%) men. CONCLUSIONS: The incidence of positive prostate biopsies was lowest in hypogonadal men receiving TRT. The severity of PCa in terms of Staging and Grading was significantly lower in hypogonadal patients receiving TRT. TRT may protect against high-grade PCa. Protective role of TRT against PCa must be confirmed in larger studies. Source of Funding: none
PD50-06 LONG-TERM SAFETY AND TOLERABILITY OF ORAL TESTOSTERONE (LPCN 1021) IN HYPOGONADAL MEN: RESULTS FROM THE 52-WEEK PHASE 3 STUDY Mohit Khera*, Houston, TX; Christina Wang, Torance, CA; Jed Kaminetsky, New York, NY; Martin Miner, Providence, RI; Adrian Dobs, Baltimore, MD; Anthony Delconte, Nachiappan Chidambaram, Satish Nachaegari, Mahesh Patel, Salt Lake City, UT INTRODUCTION AND OBJECTIVES: LPCN 1021 is a novel oral testosterone undecanoate (TU) formulation, absorbed primarily via lymphatics bypassing the liver. LPCN 1021 has been shown to be safe and efficacious after 13 weeks in a randomized, active-controlled Phase 3 study.1 We report long-term safety and tolerability of LPCN 1021 in hypogonadal subjects who continued receiving treatment for up to 52 weeks. METHODS: Hypogonadal patients (serum T levels < 300 ng/ dL) were randomized in a 2:1 ratio to LPCN 1021 or T gel 1.62% (active control) and titrated to a successful dose of the assigned treatment. Following a 13-week efficacy phase, subjects continued receiving their assigned study drug for up to 52 weeks. Subjects returned to the clinic at Weeks 26, 39, and 52 for safety assessments and to provide a 3 to 6 hour post dose blood sample. Safety assessments included an evaluation of adverse events (AEs), clinical laboratory tests, and physical examinations.
THE JOURNAL OF UROLOGYâ
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RESULTS: 210 subjects were randomized to LPCN 1021 and 105 to active control. Eugonadal T levels were restored with LPCN 1021 (Week 13 mean [SD] Cavg of 446 [171] ng/dL) and were reliably maintained throughout 52 weeks. AEs occurred in 67% of LPCN 1021 subjects and 65% of T gel 1.62% subjects. No hepatic, cardiac, or drug-related serious AEs occurred. The most common drug-related AEs (adverse drug reactions, ADRs) for LPCN 1021 and T gel 1.62% were acne (2.9% vs 2.9%, respectively), headache (0.5% vs 3.8%, respectively), weight increase (2.4% vs 0%, respectively), hematocrit increase (1.9% vs 0%, respectively), liver enzyme level increase (1.4% vs 0%, respectively), fatigue (0.5% vs 1.9%, respectively), and hypertension (0.5% vs 1.9%, respectively). All ADRs were mild or moderate in severity. Subjects receiving LPCN 1021 reported few androgenic ADRs with no reports of sleep apnea or oily skin and 1% or fewer subjects reporting peripheral edema and polycythemia. Most lipid parameters (cholesterol, LDL, HDL, and TG) were comparable between treatment groups at Week 52. Other androgenic parameters including hematocrit, hemoglobin, platelet, prothrombin, and PSA showed no significant differences in change from baseline to end of study between treatments. CONCLUSIONS: LPCN 1021 was well tolerated and had a favorable safety profile in the long-term management of hypogonadal subjects. Notably, no hepatic safety concerns were identified and gastrointestinal AEs with oral LPCN 1021 were generally comparable to active control. 1Wang C, et al. Endo Rev. 2015;36(2) Suppl. Abstract OR34-5. Source of Funding: None
PD50-07 SAFETY OF TESTOSTERONE THERAPY IN PATIENTS ON ACTIVE SURVEILLANCE FOR PROSTATE CANCER Lawrence C. Jenkins*, Rahul Krishnan, Boback M. Berookhim, Jonathan Coleman, James A. Eastham, Behfar Ehdaie, Vincent P. Laudone, Christian J. Nelson, John P. Mulhall, New York, NY INTRODUCTION AND OBJECTIVES: Testosterone (T) therapy (TTH) has a contraindication on product labeling for use in men with prostate cancer. Over the past decade, with promotion of the saturation model, men who have been treated for prostate cancer, especially men with low-risk disease (clinically and pathologically) are being increasingly offered TTH. A small number of reports have presented data on the use of TTH in men on active surveillance (AS) for prostate cancer. We present here our data on TTH use in this population. METHODS: We prospectively kept data on AS patients on TTH. Study population consisted of men who (i) were on AS for PCa (low volume cancer, Gleason sum 7, PSA 10) (ii) had two early morning total T levels (iii) were symptomatic or had abnormal bone densitometry (iv) elected to use TTH (v) had at least 6 months follow-up and (vi) agreed to intensive follow-up - total T (TT) and PSA levels every 3 months in year one after commencement of TTH. RESULTS: 24 patients met all inclusion criteria. Mean age ¼ 64.58.5 years. 22/24 (83%) patients had G6 cancer, 2/24 (17%) G7. Mean number of cores positive was 1.20.5 and mean core % positive was 11.7%12.4. Comorbidities included hypertension 29%, diabetes 21%, hyperlipidemia 63%, CAD 13%, tobacco 13%. Mean duration in the AS program before commencing TTH ¼ 17.619.6 months. Mean duration of follow-up while on TTH as an AS patient ¼ 29.227.5 months. TTH was administered as follows: 17 (71%) transdermal, 2 (8%) intramuscular, 2 (8%) subcutaneous pellets, and 3 (13%) clomiphene citrate. Mean baseline TT level ¼ 234102 ng/dL and mean treatment TT level ¼ 573228 ng/dL. Mean pre-treatment PSA ¼ 3.792.65 ng/mL and mean PSA (most recent) on treatment ¼ 4.232.42 ng/mL. 8 (33%) had 1 point increase in PSA level. One patient stopped
Vol. 195, No. 4S, Supplement, Tuesday, May 10, 2016
due to anxiety while 2 patients were upstaged (G6 to G7) while on TTH and proceeded to RP at 10.2 and 37.1 months after TTH commencement (0.11 and 1.56 point increases in PSA respectively). CONCLUSIONS: Testosterone therapy in patients on active surveillance for prostate cancer is safe in a monitored treatment program and the conversion-to-intervention rate appears to be no higher than expected in the AS population not treated with TTH. Source of Funding: none
PD50-08 IMPROVEMENT OF ARTERIAL ENDOTHELIAL FUNCTION FOLLOWING INITIATION OF TESTOSTERONE REPLACEMENT THERAPY Daniel Shoskes*, Kathryn Dunlap, Barbara Tucky, Cleveland, OH INTRODUCTION AND OBJECTIVES: Isolated recent studies have suggested an increased risk of heart attack as early as 3 months following testosterone replacement therapy (TRT) initiation. Such a rapid risk increase would likely require rapid deterioration of arterial endothelial function since atherosclerosis would be unlikely to develop so quickly de novo. Our goal was to assess arterial endothelial function in hypogonadal men prior to and at least 3 months after initiation of TRT METHODS: Adult men were consented for the study if they had symptoms of hypogonadism, a total testosterone < 350 ng/dl, and planned to begin TRT. Endothelial function was non-invasively assessed using the Endo-PAT2000 machine, an FDA approved test of cardiac risk. We measured the Augmentation Index (AI) (normal < 3%), a measure of arterial stiffness and Reactive Hyperemia Index (RHI), a measure of endothelial vasodilation (normal > 1.69). Prior studies suggest that a 10% level of day to day test variability is expected. Topical gels or Testopel were used for TRT and target testosterone confirmed post therapy. Endothelial function was reassessed at the next clinic visit, between 3 and 6 months after treatment started if the patients were compliant with therapy. Changes in continuous variables were assessed with the paired t test and significance set at p<0.05 RESULTS: 23 patients were consented with a mean age of 52.7 (range 34-68) and starting testosterone 196.9 ng/dl (range 35-339). There was a history of diabetes in 4, hypertension in 10 and coronary artery disease in 5 men. Mean RHI was 1.67+/-0.37 (70% were abnormal) and mean AI was 2.57%+/-14.0 (39% were abnormal). No patient subsequently developed a clinical cardiac event. At follow up 20 patients were compliant with therapy and retested. Mean total testosterone increased from 203 to 511 (p<0.0001). Mean RHI improved from 1.70 to 2.14 (p¼0.01). Mean AI improved from 2.9% to -1.75% (p¼0.01). In 4 men RHI was unchanged and any lower values were within the 10% error of the test (1.3-6.3%). No man had worsening of AI. CONCLUSIONS: Men with symptomatic hypogonadism often have abnormal arterial endothelial function. Following TRT, this endothelial function either remains unchanged or improves. This improvement would be expected to reduce the risk of subsequent cardiac events. Source of Funding: None
PD50-09 HEAVY TESTOSTERONE USE AMONG BODYBUILDERS: AN UNCOMMON COHORT OF ILLICIT SUBSTANCE USERS Mary E. Westerman*, Cameron M. Charchenko, Matthew J. Ziegelmann, George C. Bailey, Todd B. Nippoldt, Landon Trost, Rochester, MN INTRODUCTION AND OBJECTIVES: Pharmacologic agents have long been used for performance enhancement in high level
Vol. 195, No. 4S, Supplement, Tuesday, May 10, 2016
statistically significant trend for decreasing risk with increasing cumulative dose exposure to testosterone (p-value for trend from <0.0001 to 0.03). CONCLUSIONS: Testosterone replacement therapy appears to decrease the risk of cardiovascular events, prostate cancer diagnoses and overall mortality in a dose-responsive manner. Due to the observational nature of the data, selection bias and the health user effect must be considered. Source of Funding: This work was funded by a peer-reviewed grant from The Physicians’ Services Inc. Foundation awarded to C.J.D.W.
PD50-04 EFFICACY AND TOLERABILITY OF DAPOXETINE AND SERTRALINE FOR THE TREATMENT OF CHINESE PATIENTS WITH PREMATURE EJACULATION Lin Yang*, Dalin He, Xian, China, People’s Republic of INTRODUCTION AND OBJECTIVES: Premature ejaculation (PE) is one of the most prevalent male sexual dysfunction, and can have a detrimental effect on self-confidence and on interpersonal relationships. Pharmacotherapy with selective serotonin reuptake inhibitor (SSRI) represents the most efficacious treatment option for PE. In this paper we compared the efficacy and tolerability of dapoxetine and sertraline pharmacotherapy for the treatment of PE. METHODS: From January 2015 to June 2015, a total of 117 patients with PE seeking treatment in our hospital were randomly assigned (2:1) to receive either dapoxetine 30 mg 1-3 h before planned sexual intercourse (n¼78) or sertraline 50 mg once daily for 1 month (n¼39). Intravaginal ejaculatory latency time (IELT), clinical global impression of change (CGIC) score, Premature Ejaculation Pro?le (PEP) and treatment-emergent adverse events (TEAEs) were recorded as outcomes. RESULTS: Both groups experienced significantly increased IELT after pharmacotherapy (dapoxetine-treated group: from 0.87 min to 2.84 min; sertraline-treated group: from 0.84 min to 2.71 min). The CGIC rating regarding PE was reported to be much better or better in 36.5% and 37.5% of dapoxetine and sertraline-treated patients, respectively. At least a slightly better CGIC rating was reported by 63.6% and 71.9%, respectively, of dapoxetine-treated and sertraline-treated groups. The incidence of adverse events that include dizziness (12.5% vs. 9.5%), nausea (9.4% vs. 6.3%), headache (6.3% vs. 3.2%), and diarrhea (6.3% vs. 3.2%) after sertraline therapy showed a slightly higher trend than that after dapoxetine therapy (P>0.05); while the incidence of fatigue (3.2% vs. 18.8%), somnolence (1.6% vs. 15.6%) and dry mouth (0% vs. 12.5%) was significantly lower after dapoxetine therapy compared with sertraline treatment (P<0.05). Although similar improvements in IELT, CGIC and PEP were observed between the two groups, dapoxetine therapy has the advantage of an on-demand dosing regimen, as well as possessing a better tolerability profile, especially for special populations such as those whose profession requires driving, pilots, and delicate handling skills. CONCLUSIONS: Dapoxetine is the only pharmacological therapy approved by the SFDA for PE treatment in China. The findings of this study suggest that on-demand oral dapoxetine therapy is effective and well tolerated. Dapoxetine should therefore be recommended as the first-line treatment option for Chinese patients with PE. Source of Funding: none
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PD50-05 IS THERE A PROTECTIVE ROLE OF TESTOSTERONE AGAINST HIGH-GRADE PROSTATE CANCER? INCIDENCE AND SEVERITY OF PROSTATE CANCER IN 553 PATIENTS UNDERGOING PROSTATE BIOPSY IN A PROSPECTIVE DATA REGISTER Aksam Yassin*, Dresden, Germany; Mahmoud Salman, Yousef Almehmadi, Norderstedt-Hamburg, Germany INTRODUCTION AND OBJECTIVES: Major concern regarding testosterone therapy (TRT) in middle-aged and elderly men is still prostate safety or cancer. METHODS: 553 prostate biopsies (2008-2013) were performed at our institute. 22 patients refused biopsy. We investigated incidence and severity of PCa in three groups: hypogonadal (T350 ng/dl) men receiving TRT, hypogonadal untreated, and eugonadal men. All groups underwent similar screening intensity of at least once per year. Biopsies were performed when indicated according to EAU guidelines. RESULTS: In 42 hypogonadal men receiving TRT, 7 (16.7%) had a positive biopsy. Of these, 5 had a Gleason score 6 (71.4%) and 2 subjects a Gleason score >6 (28.6%). Predominant Gleason score was 3 in all 7 men (100%). Tumor grade was II in 6 (85.7%) and II-III in 1 (14.3%) men. 162 untreated hypogonadal men, 84 (51.9%) had a positive biopsy. Of these, 34 had a Gleason score 6 (40.5%) and 50 a Gleason score >6 (59.5%). Predominant Gleason score was 3 in 65 (77.4%), 4 in 17 (20.2%) and 5 in 2 (2.4%) men. Tumor grade was II in 35 (41.7%), II-III in 10 (11.9%), III in 34 (40.5%) and IV in 5 (6.0%) men. In 349 eugonadal men, 132 (37.8%) had a positive biopsy. Of these, 56 had a Gleason score 6 (42.4%) and 76 a Gleason score >6 (57.6%). Predominant Gleason score was 3 in 109 (82.6%), 4 in 22 (16.7%) and 5 in 1 (0.1%) men. Tumor grade was II in 59 (44.7%), II-III in 6 (4.5%), III in 63 (47.7%) and IV in 4 (3.0%) men. CONCLUSIONS: The incidence of positive prostate biopsies was lowest in hypogonadal men receiving TRT. The severity of PCa in terms of Staging and Grading was significantly lower in hypogonadal patients receiving TRT. TRT may protect against high-grade PCa. Protective role of TRT against PCa must be confirmed in larger studies. Source of Funding: none
PD50-06 LONG-TERM SAFETY AND TOLERABILITY OF ORAL TESTOSTERONE (LPCN 1021) IN HYPOGONADAL MEN: RESULTS FROM THE 52-WEEK PHASE 3 STUDY Mohit Khera*, Houston, TX; Christina Wang, Torance, CA; Jed Kaminetsky, New York, NY; Martin Miner, Providence, RI; Adrian Dobs, Baltimore, MD; Anthony Delconte, Nachiappan Chidambaram, Satish Nachaegari, Mahesh Patel, Salt Lake City, UT INTRODUCTION AND OBJECTIVES: LPCN 1021 is a novel oral testosterone undecanoate (TU) formulation, absorbed primarily via lymphatics bypassing the liver. LPCN 1021 has been shown to be safe and efficacious after 13 weeks in a randomized, active-controlled Phase 3 study.1 We report long-term safety and tolerability of LPCN 1021 in hypogonadal subjects who continued receiving treatment for up to 52 weeks. METHODS: Hypogonadal patients (serum T levels < 300 ng/ dL) were randomized in a 2:1 ratio to LPCN 1021 or T gel 1.62% (active control) and titrated to a successful dose of the assigned treatment. Following a 13-week efficacy phase, subjects continued receiving their assigned study drug for up to 52 weeks. Subjects returned to the clinic at Weeks 26, 39, and 52 for safety assessments and to provide a 3 to 6 hour post dose blood sample. Safety assessments included an evaluation of adverse events (AEs), clinical laboratory tests, and physical examinations.
THE JOURNAL OF UROLOGYâ
e1188
RESULTS: 210 subjects were randomized to LPCN 1021 and 105 to active control. Eugonadal T levels were restored with LPCN 1021 (Week 13 mean [SD] Cavg of 446 [171] ng/dL) and were reliably maintained throughout 52 weeks. AEs occurred in 67% of LPCN 1021 subjects and 65% of T gel 1.62% subjects. No hepatic, cardiac, or drug-related serious AEs occurred. The most common drug-related AEs (adverse drug reactions, ADRs) for LPCN 1021 and T gel 1.62% were acne (2.9% vs 2.9%, respectively), headache (0.5% vs 3.8%, respectively), weight increase (2.4% vs 0%, respectively), hematocrit increase (1.9% vs 0%, respectively), liver enzyme level increase (1.4% vs 0%, respectively), fatigue (0.5% vs 1.9%, respectively), and hypertension (0.5% vs 1.9%, respectively). All ADRs were mild or moderate in severity. Subjects receiving LPCN 1021 reported few androgenic ADRs with no reports of sleep apnea or oily skin and 1% or fewer subjects reporting peripheral edema and polycythemia. Most lipid parameters (cholesterol, LDL, HDL, and TG) were comparable between treatment groups at Week 52. Other androgenic parameters including hematocrit, hemoglobin, platelet, prothrombin, and PSA showed no significant differences in change from baseline to end of study between treatments. CONCLUSIONS: LPCN 1021 was well tolerated and had a favorable safety profile in the long-term management of hypogonadal subjects. Notably, no hepatic safety concerns were identified and gastrointestinal AEs with oral LPCN 1021 were generally comparable to active control. 1Wang C, et al. Endo Rev. 2015;36(2) Suppl. Abstract OR34-5. Source of Funding: None
PD50-07 SAFETY OF TESTOSTERONE THERAPY IN PATIENTS ON ACTIVE SURVEILLANCE FOR PROSTATE CANCER Lawrence C. Jenkins*, Rahul Krishnan, Boback M. Berookhim, Jonathan Coleman, James A. Eastham, Behfar Ehdaie, Vincent P. Laudone, Christian J. Nelson, John P. Mulhall, New York, NY INTRODUCTION AND OBJECTIVES: Testosterone (T) therapy (TTH) has a contraindication on product labeling for use in men with prostate cancer. Over the past decade, with promotion of the saturation model, men who have been treated for prostate cancer, especially men with low-risk disease (clinically and pathologically) are being increasingly offered TTH. A small number of reports have presented data on the use of TTH in men on active surveillance (AS) for prostate cancer. We present here our data on TTH use in this population. METHODS: We prospectively kept data on AS patients on TTH. Study population consisted of men who (i) were on AS for PCa (low volume cancer, Gleason sum 7, PSA 10) (ii) had two early morning total T levels (iii) were symptomatic or had abnormal bone densitometry (iv) elected to use TTH (v) had at least 6 months follow-up and (vi) agreed to intensive follow-up - total T (TT) and PSA levels every 3 months in year one after commencement of TTH. RESULTS: 24 patients met all inclusion criteria. Mean age ¼ 64.58.5 years. 22/24 (83%) patients had G6 cancer, 2/24 (17%) G7. Mean number of cores positive was 1.20.5 and mean core % positive was 11.7%12.4. Comorbidities included hypertension 29%, diabetes 21%, hyperlipidemia 63%, CAD 13%, tobacco 13%. Mean duration in the AS program before commencing TTH ¼ 17.619.6 months. Mean duration of follow-up while on TTH as an AS patient ¼ 29.227.5 months. TTH was administered as follows: 17 (71%) transdermal, 2 (8%) intramuscular, 2 (8%) subcutaneous pellets, and 3 (13%) clomiphene citrate. Mean baseline TT level ¼ 234102 ng/dL and mean treatment TT level ¼ 573228 ng/dL. Mean pre-treatment PSA ¼ 3.792.65 ng/mL and mean PSA (most recent) on treatment ¼ 4.232.42 ng/mL. 8 (33%) had 1 point increase in PSA level. One patient stopped
Vol. 195, No. 4S, Supplement, Tuesday, May 10, 2016
due to anxiety while 2 patients were upstaged (G6 to G7) while on TTH and proceeded to RP at 10.2 and 37.1 months after TTH commencement (0.11 and 1.56 point increases in PSA respectively). CONCLUSIONS: Testosterone therapy in patients on active surveillance for prostate cancer is safe in a monitored treatment program and the conversion-to-intervention rate appears to be no higher than expected in the AS population not treated with TTH. Source of Funding: none
PD50-08 IMPROVEMENT OF ARTERIAL ENDOTHELIAL FUNCTION FOLLOWING INITIATION OF TESTOSTERONE REPLACEMENT THERAPY Daniel Shoskes*, Kathryn Dunlap, Barbara Tucky, Cleveland, OH INTRODUCTION AND OBJECTIVES: Isolated recent studies have suggested an increased risk of heart attack as early as 3 months following testosterone replacement therapy (TRT) initiation. Such a rapid risk increase would likely require rapid deterioration of arterial endothelial function since atherosclerosis would be unlikely to develop so quickly de novo. Our goal was to assess arterial endothelial function in hypogonadal men prior to and at least 3 months after initiation of TRT METHODS: Adult men were consented for the study if they had symptoms of hypogonadism, a total testosterone < 350 ng/dl, and planned to begin TRT. Endothelial function was non-invasively assessed using the Endo-PAT2000 machine, an FDA approved test of cardiac risk. We measured the Augmentation Index (AI) (normal < 3%), a measure of arterial stiffness and Reactive Hyperemia Index (RHI), a measure of endothelial vasodilation (normal > 1.69). Prior studies suggest that a 10% level of day to day test variability is expected. Topical gels or Testopel were used for TRT and target testosterone confirmed post therapy. Endothelial function was reassessed at the next clinic visit, between 3 and 6 months after treatment started if the patients were compliant with therapy. Changes in continuous variables were assessed with the paired t test and significance set at p<0.05 RESULTS: 23 patients were consented with a mean age of 52.7 (range 34-68) and starting testosterone 196.9 ng/dl (range 35-339). There was a history of diabetes in 4, hypertension in 10 and coronary artery disease in 5 men. Mean RHI was 1.67+/-0.37 (70% were abnormal) and mean AI was 2.57%+/-14.0 (39% were abnormal). No patient subsequently developed a clinical cardiac event. At follow up 20 patients were compliant with therapy and retested. Mean total testosterone increased from 203 to 511 (p<0.0001). Mean RHI improved from 1.70 to 2.14 (p¼0.01). Mean AI improved from 2.9% to -1.75% (p¼0.01). In 4 men RHI was unchanged and any lower values were within the 10% error of the test (1.3-6.3%). No man had worsening of AI. CONCLUSIONS: Men with symptomatic hypogonadism often have abnormal arterial endothelial function. Following TRT, this endothelial function either remains unchanged or improves. This improvement would be expected to reduce the risk of subsequent cardiac events. Source of Funding: None
PD50-09 HEAVY TESTOSTERONE USE AMONG BODYBUILDERS: AN UNCOMMON COHORT OF ILLICIT SUBSTANCE USERS Mary E. Westerman*, Cameron M. Charchenko, Matthew J. Ziegelmann, George C. Bailey, Todd B. Nippoldt, Landon Trost, Rochester, MN INTRODUCTION AND OBJECTIVES: Pharmacologic agents have long been used for performance enhancement in high level