Initiation Of Testosterone Replacement Therapy Research Articles

(O-13) TESTOSTERONE REPLACEMENT THERAPY AND PROSTATE CANCER PROGRESSION IN HYPOGONADAL MEN ON ACTIVE SURVEILLANCE: A RETROSPECTIVE ANALYSIS

Abstract Introduction The use of testosterone replacement therapy (TRT) in hypogonadal men with prostate cancer (PC) on active surveillance (AS) has been controversial. However, recent studies have challenged this notion, warranting further investigation. We aim to assess the impact of TRT on PC progression in hypogonadal men on AS. Methods We conducted a retrospective chart review using data from a single hospital system between 2009 and 2022. The database included hypogonadal men with PC on AS who underwent TRT. Patients with prior PC treatment were excluded. PSA and total testosterone (TT) levels were recorded at various time points, including before and after TRT initiation. One-way ANOVA was used to analyze mean PSA and TT levels, and PC treatment progression was documented. Results A total of 25 men met the inclusion criteria. Mean PSA and TT levels at each time interval showed no significant difference in PSA (P = 0.283), while TT exhibited significant variation (P = 0.0052) throughout the 2-year study period. Mean TT before TRT initiation was 311.39 ng/dL, and after TRT, it increased to 773.04 ng/dL (P = 0.00011). Only one patient (4%) underwent radiation therapy for PC five years after starting TRT. Conclusions Initiating TRT in hypogonadal men on AS for PC did not result in a significant change in PSA levels, despite an increase in testosterone. As our database expands, we aim to strengthen the study's statistical power. These findings contribute to the growing evidence supporting the potential viability of TRT in hypogonadal men on AS. Financing No conflict.

(087) Testosterone Replacement Therapy in Men on Active Surveillance for Prostate Cancer: Using a Novel Database to Examine Disease Progression

Abstract Introduction Traditionally, the use of testosterone replacement therapy (TRT) in hypogonadal men on active surveillance (AS) with prostate cancer (PC) has been controversial, and for many providers, contraindicated. However, studies suggesting a need to revisit the association between TRT and prostate cancer progression have contributed to a recent paradigm shift in this approach. More studies are needed to analyze this relationship, especially due to the psychosocial and biological consequences of testosterone deficiency. Objective We aim to examine the effects of TRT on PC progression in hypogonadal men on active surveillance. Methods In this retrospective chart review, data from men diagnosed with hypogonadism and PC at a single hospital system between 2009 to 2022 were compiled into a database. Inclusion criteria for this specific study included men who underwent TRT while being on AS protocol for PC. Men receiving prior treatment for PC such as prostatectomy or radiation therapy were excluded. For each patient, PSA and total testosterone (TT) levels were recorded at 12 and 6 months prior to TRT, at the onset of TRT, and 3, 6, and 12 months following TRT initiation. One-way ANOVA was used to analyze variance in mean PSA and TT. Mean TT levels pre-TRT and post-TRT were calculated and analyzed for a significant difference. Progression to PC treatment was noted for each patient. Results 30 men meet the study criteria. The table below demonstrates the mean PSA and TT levels at each time interval. There was a significant variation in mean TT (P=0.0031) while there was no significant difference in mean PSA levels (P=0.3003) throughout the 2-year study period. Mean TT before initiation of TRT was 297.97 ng/dL, and mean TT after TRT was 716.15 ng/dL. There was an increase in mean TT after starting TRT (P=0.00072). One patient (3.3%) eventually underwent radiation therapy for PC five years after initiating TRT. Conclusions In hypogonadal men on AS for PC, no significant change in PSA level was observed after initiating TRT, despite an increase in testosterone. As we grow the database, we aim to increase the power of this study. Our findings contribute to the mounting evidence demonstrating TRT may be a viable option for hypogonadal men on AS. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Disclosures: Consultant for AbbVie, Marius, Tolmar, Endo, Petros, Boston Scientific, Coloplast Investor: Sprout.

EMAS position statement: Testosterone replacement therapy in older men.

Late-onset hypogonadism is the clinical entity characterised by low testosterone concentrations associated with clinical symptoms in the absence of organic disease in ageing men. It has been associated with metabolic syndrome, reduced bone mineral density, and increased cardiovascular morbidity and mortality risk. Although testosterone replacement therapy (TRT) reverses most of these conditions in young hypogonadal men, the risk/benefit ratio of TRT in older men is debatable. To update the 2015 EMAS statement on TRT in older men with new research on late-onset hypogonadism and TRT. Literature review and consensus of expert opinion. TRT should be offered only to symptomatic older men with confirmed low testosterone concentrations after explaining the uncertainties regarding the long-term safety of this treatment. TRT may be offered to men with severe hypogonadism and erectile dysfunction to improve sexual desire, erectile, and orgasmic function. It should also be considered in hypogonadal men with severe insulin resistance or pre-diabetes mellitus. TRT may also be considered, in combination with proven treatment strategies, for osteoporosis, or for selected patients with persistent mild depressive symptoms and/or low self-perceived quality of life, combined with standard medical care for each condition. TRT is contraindicated in hypogonadal men actively seeking fertility treatment. Due to a lack of data, TRT should not be routinely used in older men to improve exercise capacity/physical function, improve cognitive function, or prevent cognitive decline. TRT must be avoided in older, frail men with known breast cancer or untreated prostate cancer and all men who have had myocardial infarction or stroke within the last four months, and those with severe or decompensated heart failure. The quality of evidence regarding patients with previous prostate cancer or cardiovascular disease is too low to draw definitive conclusions. Any limits on duration of use are arbitrary, and treatment should continue for as long as the man feels the benefits outweigh the risks for him, and decisions must be made on an individual basis. Withdrawal should be considered when hypogonadism is reversed after the resolution of underlying disorder. Short-acting transdermal preparations should be preferred for TRT initiation in older men, but injectable forms may be considered subsequently. Older men on TRT should be monitored at 3, 6, and 12months after initiation and at least yearly thereafter, or earlier and more frequently if indicated. Evaluation should include assessment of the clinical response, and measurement of total testosterone, haematocrit, and prostate-specific antigen (PSA) concentrations. Bone density and/or quality should also be assessed. Obese and overweight patients should be encouraged to undergo lifestyle modifications, including exercise and weight loss, to increase endogenous testosterone.

FRI428 VTE And Testosterone Therapy: What Is The Risk?

Abstract Disclosure: C. Cheatham: None. J. Colburn: None. M. Kemm: None. Testosterone replacement therapy (TRT) to treat hypogonadism from a variety of underlying etiologies remains increasingly prevalent within the United States. While VTE is a known potential risk, the prevalence, underlying mechanism, and associated risk factors remain incompletely understood. Men initiating TRT for hypogonadism often do not receive adequate pre-treatment evaluation or have therapy initiated despite normal testosterone levels. While a 2021 meta-analysis 1 did not demonstrate significantly increased VTE risk associated with TRT, the wide confidence interval, reported low quality of evidence, and lack of studies examining VTE as a primary outcome with data obtained via adverse event reporting demonstrates the importance of further investigation. Case 1: 55-year-old male with unilateral orchiectomy and associated primary hypogonadism started on TRT 10years prior presented to the hospital with acute onset chest pain and shortness of breath. CT angiography demonstrated right lower lobe segmental pulmonary emboli with parenchymal infarction. At the time of presentation, he was on IM testosterone cypionate 200mg weekly and anastrozole with total testosterone970 ng/dL, free testosterone 298 pg/mL, undetectable estradiol, and hematocrit 41.5%. His testosterone and anastrozole were discontinued at discharge, and he had a negative hypercoagulability workup by a hematologist. Case 2: 61-year-old male with history of OSA, obesity, and TRT initiated 8 months prior for erectile dysfunction presented to the hospital with dyspnea. CT angiography demonstrated large bilateral pulmonary artery emboli with right heart strain consistent with submassive PE. Review of clinical records preceding TRT initiation indicate normal testosterone values of 533 ng/dL with free testosterone 60.6 pg/dL. At the timeof presentation, his total testosterone was 685 ng/dL, free testosterone 139 pg/mL, and hematocrit of 54%with history of polycythemia since TRT initiation and no documented intervention. He was treated withIR thrombectomy and anticoagulation, and TRT was discontinued at discharge. His hematocrit normalized at follow-up and, after negative hypercoagulability evaluation by a hematologist, TRT was felt to be the most likely etiology of his VTE. These reported cases of VTE in men of different ages, underlying pathology, testosterone levels at time of event, presence of polycythemia, and time since testosterone initiation highlights the importance of further investigation on the true risk of thrombotic events in TRT patients and necessity of increased patient counseling of potential adverse outcomes. 1. Ayele HT, Brunetti VC, Renoux C, Tagalakis V, Filion KB. Testosterone replacement therapy and the risk of venous thromboembolism: A systematic review and meta-analysis of randomized controlled trials. Thromb Res. 2021;199:123-131. doi:10.1016/j.thromres.2020.12.029 Presentation: Friday, June 16, 2023

Use of testosterone replacement therapy in the rehabilitation of patients with intensive care unit-associated weakness and hospital-associated deconditioning: the Singapore General Hospital rehabilitation experience.

Rehabilitation medicine in a tertiary care hospital involves attending to many patients affected by intensive care unit (ICU)-associated weakness (ICU-AW) and hospital-associated deconditioning (HAD). These conditions contribute to poor long-term functional outcomes and increased mortality. We explored the role of short-term adjunctive androgen therapy in this group of patients in improving the rehabilitative outcomes. This was a retrospective analysis of five patients with either ICU-AW or HAD who were given testosterone replacement therapy (TRT) or oxandrolone for a total of 2 weeks during the period from April to November 2020 was undertaken. During the 2-week trial period, the subjects underwent standard rehabilitation therapy. Grip strength was used as the primary outcome measure, and the mean improvement was 4.2 kg (+24.9%), which is encouraging in a 2-week timeframe. This was matched with good functional recovery in terms of distance ambulated and less assistance needed for ambulation. Sex hormone analysis was also done before initiation of TRT, and it showed that four out of five of the subjects were biochemically hypogonadal. None of the subjects dropped out or experienced any significant adverse events over the 2-week trial period. All the subjects except one improved to full independence at 3 months post-discharge. TRT has the potential to be used as a useful adjunct to standard rehabilitation in enhancing functional recovery in critically ill patients. A multidisciplinary approach would ensure that suitable patients benefit from optimal nutrition, optimal rehabilitation and synergistic testosterone therapy in a clinically sound and resource-efficient fashion.

PD36-04 AROMATIZATION OF ENDOGENOUS TESTOSTERONE OCCURS PRIMARILY IN TESTICULAR LEYDIG CELLS

You have accessJournal of UrologyCME1 May 2022PD36-04 AROMATIZATION OF ENDOGENOUS TESTOSTERONE OCCURS PRIMARILY IN TESTICULAR LEYDIG CELLS Caroline Kang, Nahid Punjani, Jessica Marinaro, and Peter Schlegel Caroline KangCaroline Kang More articles by this author , Nahid PunjaniNahid Punjani More articles by this author , Jessica MarinaroJessica Marinaro More articles by this author , and Peter SchlegelPeter Schlegel More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002594.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Endogenous testosterone (T) is produced by testicular Leydig cells that are rich in aromatase activity. Aromatization to estradiol (E2) can negatively regulate the hypothalamic-pituitary-testis (HPT) axis, thereby diminishing gonadotropin and T production as well as spermatogenesis. Exogenous T is exposed primarily to fat, muscle, and other peripheral tissues with limited exposure to testicular Leydig cells. We investigated the source of aromatization by comparing serum T:E2 ratios, as a surrogate for aromatase activity, in men with Klinefelter syndrome (KS) who have endogenous or exogenous testosterone production, that is, before and after the initiation of testosterone replacement therapy (TRT). METHODS: We performed a retrospective study of all adult men (> 20 years of age) with a diagnosis of KS undergoing sperm retrieval by microdissection testicular sperm extraction (mTESE) performed by a single surgeon at a tertiary infertility referral center between 1995-2020. Demographic data, along with hormone data (serum T and E2 levels) pre- and post-TRT were obtained from the electronic medical record. Patients not treated with TRT or with incomplete hormone data were excluded. Paired statistical analyses were completed to determine differences between hormone levels pre- and post-TRT initiation. RESULTS: A total of 35 men with KS were included in our final analysis. Median age was 32 years (interquartile range (IQR), 28 - 36), and median BMI was 25.9 kg/m2 (IQR, 24.6 - 30.8). The majority of our cohort was initiated on topical TRT (e.g., cream or gel; 26/35, 74.3%), while the remaining were treated with injectable or implanted TRT (9/35, 25.7%). Mean serum T increased from 239±134 ng/dL to 519±361 ng/dL (p=0.0003), while mean serum E2 increased from 30±22 pg/ml to 36±28 pg/ml (p=0.55) after initiation of TRT. Mean T:E2 ratio increased from 9.4±6.3 to 17.4±14.5 (p=0.0005) after initiation of TRT. CONCLUSIONS: Aromatization of T to E2 can result in suppression of the HPT axis and diminish both T production and spermatogenesis. After initiation of TRT, T:E2 ratios rose significantly due to an increase in T with relatively stable E2, suggesting that exogenous and endogenous T are not subject to the same cellular milieu and therefore differential aromatization. This finding has important implications in the treatment and counseling of men with infertility and abnormal hormone levels. Source of Funding: CK and JS are supported in part by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e634 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Caroline Kang More articles by this author Nahid Punjani More articles by this author Jessica Marinaro More articles by this author Peter Schlegel More articles by this author Expand All Advertisement PDF DownloadLoading ...

The daily dose of testosterone-replacement therapy dependence from the body mass index in FtM transgender PATIENTS

The basis for the management of transgender patients is the use of various hormonal correction schemes necessary for changing the hormonal sex and, possibly, further preparation for surgical correction. Currently, the choice of the starting dose and the scheme is carried out empirically, which lengthens the period of selection of therapy and increases the risk of its complications. Taking into account the individual characteristics of the patient can help in optimizing therapy. Investigate Factors Affecting the Daily Demand for Testosterone Ester Blends in Transgender MenMATERIALS AND METHODS:This study is a case-control observational study. Patients included prior to initiation of testosterone replacement therapy. The analysis of factors interrelated with the daily requirement of testosterone preparations was carried out. Among the factors of interest, the body mass index (BMI), the results of blood tests for total testosterone and the functional state of the liver and kidneys are considered. Testosterone replacement therapy (TRT) regimens were evaluated in transgender men. For thecalculation, we used the formulas for BMI and the average daily dose of testosterone. Based on the data obtained, conclusions were drawn that allow determining the necessary TRT scheme in different trans-gender men at an early stage of hormonal correction. Our study included 58 transgender FtM patients who were prescribed testosterone preparations with an identical composition. We found a positive correlation between BMI and testosterone dose in patients of group II (p = 0.04). In the conclusion, the obtained schemes of hormonal sex reassignment with a minimum risk of possible complications are presented. Our results demonstrated a relationship between BMI in overweight and obese patients and the need for TRT. For patients with a BMI of 25 to 29 kg / m2, the interval between injections of a mixture of testosterone esters does not differ significantly from that in the group with a BMI below 25 kg / m2and averages once every 18 days, and in thegroup with a BMI ≥ 30 kg / m2tested testosterone ester preparations should be prescribed once every 2 weeks (14 days).

Oncological safety and functional outcomes of testosterone replacement therapy in symptomatic adult-onset hypogonadal prostate cancer patients following robot-assisted radical prostatectomy.

Testosterone replacement therapy (TRT) remains controversial in men with treated prostate cancer. We assessed its safety and functional impacts in patients after definitive surgical treatment with robotic-assisted radical prostatectomy (RARP). We performed a retrospective analysis of 1303 patients who underwent RARP during the years 2006-2019. We identified men with symptoms of andropause and low serum testosterone who received TRT post-RARP; then we divided the cohort into two groups accordingly for comparison. Biochemical recurrence (BCR) was the primary endpoint. Secondary endpoints included functional outcomes. Predictors of BCR, including the effect of TRT on BCR, were evaluated using univariable and multivariable logistic regression. Among the forty-seven men who received TRT, the mean age was 60.83years with a median follow-up of 48months. Three (6.4%) and 157 (12.56%) patients experienced BCR in TRT and non-TRT groups, respectively. Baseline characteristics were similar between both groups except for higher mean BMI in the TRT group (p = 0.03). In the multivariate analysis (MVA), higher pre-RARP prostate-specific antigen (PSA) (p = 0.043), higher International Society of Urological Pathology score (p < 0.001), seminal vesical invasion (p = 0.018) and positive surgical margin (p < 0.001) were predictors of BCR. However, TRT was not (p = 0.389). In addition, there was a significant change in the Sexual Health Inventory for Men (p = 0.022), and serum testosterone level (p < 0.001) before and 6months after initiation of TRT. Our findings suggest that TRT, in well-selected, closely followed, symptomatic men post-RARP is an oncologically safe and functionally effective treatment in prostate cancer patients post-RARP.

European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males: Endorsing organization: European Society of Endocrinology.

Evidence regarding functional hypogonadism, previously referred to as 'late-onset' hypogonadism, has increased substantially during the last 10year. To update the European Academy of Andrology (EAA) guidelines on functional hypogonadism. Expert group of academicians appointed by the EAA generated a series of consensus recommendations according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system. The diagnosis of functional hypogonadism should be based on both the presence of clinical symptoms supported by repeatedly low morning fasting serum total testosterone (T) measured with a well-validated assay, after exclusion of organic causes of hypogonadism. Lifestyle changes and weight reduction should be the first approach in all overweight and obese men. Whenever possible, withdrawal/modification of drugs potentially interfering with T production should be advised. Testosterone replacement therapy (TRT) is contraindicated in men with untreated prostate or breast cancer, as well as severe heart failure. Severe low urinary tract symptoms and haematocrit >48%-50% represent relative contraindications for TRT. Prostate-specific antigen and digital rectal examination of the prostate should be undertaken in men >40years of age before initiating TRT to exclude occult prostate cancer. Transdermal T should be preferred for initiation of TRT, whereas gonadotrophin therapy is only recommended when fertility is desired in men with secondary hypogonadism. TRT is able to improve sexual function in hypogonadal men. Other potential positive outcomes of TRT remain uncertain and controversial. TRT can reliably improve global sexual function in men with hypogonadism in the short term. Long-term clinical benefits, and safety of TRT in functional hypogonadism, remain to be fully documented. Clinicians should therefore explicitly discuss the uncertainties and benefits of TRT and engage them in shared management decision-making.

188 Comparative Assessment of Outcomes Using Two Different Intramuscular Testosterone Replacement Therapy Regimens

Hypogonadism is defined as serum total testosterone level < 300 ng/dL in combination with clinical signs or symptoms. Testosterone replacement therapy (TRT) aims to restore testosterone levels and reverse the signs and symptoms of hypogonadism. Several testosterone delivery systems, including intramuscular (IM) injections, are currently available. Nevertheless, side effect profile for the different dosing regimens of IM testosterone injections has not been investigated. We sought to compare outcomes using two different commonly used IM TRT regimens. We conducted a multi-institutional retrospective review of charts of men who presented to 4 different clinics between 2015 and 2019. Patients were included if they were 18 years or older and received one of the following TRT regimens: 100mg IM once weekly or 200mg IM once every other week. Patients were excluded if they received any additional non-TRT hormone replacement therapies in the last 6 months or had a diagnosis of prostate cancer. Primary outcomes were absolute and relative changes in Total Testosterone (TT), Free Testosterone (FT), Estradiol (E), Prostate Specific Antigen (PSA) and Hematocrit (Hct) at 3, 6 and 12 months after initiation of TRT. Secondary outcomes were any significant rises in E, Hct, PSA, and any other treatment related adverse events requiring cessation of TRT.

Misuse of testosterone replacement therapy in men in infertile couples and its influence on infertility treatment.

ObjectiveWe investigated the clinical characteristics of men with testosterone replacement therapy (TRT)-induced hypogonadism and its effect on assisted reproductive technology (ART) in infertile couples.MethodsThis study examined the records of 20 consecutive male patients diagnosed with azoospermia or severe oligozoospermia (<5×106/mL) who visited a single infertility center from January 2008 to July 2018. All patients were treated at a primary clinic for erectile dysfunction or androgen deficiency symptoms combined with low serum testosterone. All men received a phosphodiesterase 5 inhibitor and TRT with testosterone undecanoate (Nebido®) or testosterone enanthate (Jenasteron®). Patients older than 50 years or with a chronic medical disease such as diabetes were excluded.ResultsThe mean age of patients was 37 years and the mean duration of infertility was 16.3±11.6 months. At the initial presentation, eight patients had azoospermia, nine had cryptozoospermia, and three had severe oligozoospermia. Serum follicle-stimulating hormone levels were below 1.0 mIU/mL in most patients. Three ongoing ART programs with female factor infertility were cancelled due to male spermatogenic dysfunction; two of these men had normal semen parameters in the previous cycle. After withholding TRT, serum hormone levels and sperm concentrations returned to normal range after a median duration of 8 months.ConclusionTRT with high-dose testosterone can cause spermatogenic dysfunction due to suppression of the hypothalamic-pituitary-testicular axis, with adverse effects on infertility treatment programs. TRT is therefore contraindicated for infertile couples attempting to conceive, and the patient’s desire for fertility must be considered before initiation of TRT in a hypogonadal man.

Fertility in Adolescents With Klinefelter Syndrome: A Survey of Current Clinical Practice.

Progress has been made in determining the fertility timeline and potential in adolescents with Klinefelter syndrome; however, medical professionals are currently without protocols to guide treatment. To evaluate the current practices regarding fertility and andrology care in adolescent males with Klinefelter syndrome. A 24-question survey was developed to elicit practitioner background/expertise and management practices. This was distributed to members of the Society for the Study of Male Reproduction, the Pediatric Endocrine Society, and the Endocrine Society. N/A. Adolescent males with Klinefelter syndrome. None. Current practices regarding fertility and andrology care. 232 responses were received from 133 (57%) adult endocrinologists, 60 (26%) pediatric endocrinologists, and 39 (17%) urologists. Among these, 69% of respondents were in academics, 62% practiced for > 10 years, and 65% received formal training in Klinefelter syndrome. All specialties encouraged sperm banking in late puberty, however most disagreed with the practice in early puberty. Seventy-eight percent agreed that testicular biopsy should be offered if no sperm was found in the ejaculate. The perceived optimal age for testicular biopsy varied among specialists. Clinical symptoms of hypogonadism (28%), rising gonadotropin levels (15%), and testosterone levels (15%) were the most commonly cited reasons for initiation of testosterone replacement therapy. Fertility preservation practices in adolescents with Klinefelter syndrome vary greatly within and among the specialties caring for these patients. These findings should guide future research and highlight the importance of establishing clinical practice guidelines.

37-Year-Old Man With Fatigue and Erectile Dysfunction

37-Year-Old Man With Fatigue and Erectile Dysfunction

SUN-LB039 Novel Use of Thromboelastography (TEG) to Investigate the Prothrombotic Effects of Testosterone Replacement Therapy (TRT) for Androgen Deficiency (AD) Established with Diagnostic Rigor (DR)

Background Endocrine Society recommends ≥2 low bioavailable (BAT) or free Testosterone (T) levels in the early AM by tandem mass spectroscopy to establish AD with DR. They also advise against TRT with a recent history of vascular events (VEs). Data from our center affirm these recommendations. TRT increased VE risk four-fold without DR versus with DR, and eight-fold with a history of recent VEs versus without, suggesting that inappropriate TRT might provoke VEs in the absence of AD, or with high vascular risk. The etiopathogenesis of VEs on TRT is not understood, nor is it known if TRT induces a prothrombotic state, but two putative mechanisms might be involved. First, T increases platelet receptors for thromboxane A2, a potent vasoconstrictor and platelet aggregant. Second, T is aromatized to estradiol (E2), a potent activator of the clotting cascade, inhibitor of antithrombin III, and platelet aggregant. Objective To determine (a) whether TEG, a clinically validated tool for assessing platelet function and clotting can be used to identify a prothrombotic state during TRT for AD proven with DR, and (b) if changes are related to estradiol levels. Methods Male veterans >18 years of age referred for suspected AD, and with no contraindications to TRT, were recruited for the study. After AD was established according to guidelines, blood samples were drawn for TEG and E2 before TRT initiation and after 3 months of TRT, and the following TEG parameters were assessed: Reaction Time for initial fibrin formation (R), reflecting the clotting cascade, Kinetic Time for fibrin cross linkage (K), reflecting fibrinogen and platelet number, Angle (α), reflecting the speed of clot strengthening, and Maximum Amplitude (MA), reflecting platelet function. Results In 7 subjects (median age 64 [IQR 38,68]), on TRT for 88±5d (Mean±SE), calculated BAT increased from 82±17ng/dl to 143±32ng/dl (p=0.046), but E2 did not change significantly (14.3±2.5 vs 19.6±4.2pg/ml, p=0.4). R increased 17% on TRT compared to before (∆=0.9±0.2min, p=0.012), showing that time to initial fibrin formation was prolonged, while remaining within the normal range. However, there was no significant change in K, α, or MA. ConclusionsOur data, based on the novel use of TEG to study a potentially prothrombotic effect of TRT, show for the first time that TRT inhibits, not activates the kinetics of the enzymatic process of coagulation. In other words, appropriate TRT had no prothrombotic effect in an admittedly small number of patients with AD established with DR. This accords with both the four-fold decrease in VEs we observed earlier on TRT prescribed appropriately with DR, as well as some prior reports of a lower risk of VEs on TRT. It is conceivable that TRT might induce a prothrombotic state when prescribed inappropriately in the absence of AD, given that many studies showing that TRT increases VE risk have not employed DR to establish AD conclusively. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

SUN-223 Impact of Testosterone Replacement Therapy (TRT) on Prostate Specific Antigen (PSA) in Patients with Clinical Evidence of Prostate Hyperplasia

Introduction/ Background Prostate cell growth is androgen dependent, so dogma holds that testosterone replacement therapy (TRT) can lead to the onset, progression, and unmasking of prostate problems. As a result, there continues to be a theoretical concern that TRT-induced proliferation of prostatic epithelial cells could result in benign prostatic hyperplasia (BPH), or prostate cancer. Although the intensity and frequency of monitoring prostate health during TRT remains controversial, a Prostate Specific Antigen (PSA) level >4 ng/ml is widely considered the cut-off at which urological evaluation should be sought. It is noteworthy that, despite a lack of conclusive evidence that TRT causes prostate cancer, Endocrine Society guidelines show an abundance of caution in recommending prostate cancer screening with PSA and DRE 3 to 12 months after treatment initiation followed by race- and age-appropriate monitoring after 1-year in patients who agree to prostate cancer monitoring after shared decision making. One unfortunate consequence of such vigilance is a reported increase in prostate biopsies for patients on TRT with PSA elevations. Although the merits of such vigilance might be debatable, the consensus appears to be that TRT does not cause prostate cancer, as much as unmask pre-existing subclinical prostate cancer, reflecting confirmation bias. An even more vexing issue is whether PSA monitoring might exaggerate the appearance of risk, given that it is more strongly associated with BPH than prostate cancer. Objective To compare the incidence of PSA >4 ng/ml during TRT in veterans with a pre-existing elevation in PSA or with a prior clinical diagnosis of BPH, versus those without elevated PSA or BPH. Design A retrospective cohort study of male veterans prescribed TRT between 2008 and 2014. Results Patients without a clinical diagnosis of BPH prior to initiating TRT were much less likely to develop PSA >4 ng/ml on TRT (16/746 [2.1%]) compared to those with prior BPH (19/222[8.5%], p=0.00007). Similarly, only 3% (22/879) of patients with PSA <4 ng/ml prior to TRT initiation developed a PSA >4 ng/ml on TRT, whereas ten of the fourteen patients (71.4%) who were prescribed TRT despite PSA >4 ng/ml continued to have a persistent elevation in PSA on TRT (P<0.00001). Surprisingly, PSA in four of the fourteen patients (28.6%) with PSA >4 ng/ml prior to TRT initiation declined to <4 ng/ml on TRT. Conclusions: Patients with PSA <4 ng/ml and no prior BPH are very unlikely to develop PSA >4 ng/ml on TRT. Even in patients with a prior PSA >4 ng/ml, further elevations were not seen on TRT, with a few even experiencing a decline in PSA to <4 ng/ml. We conclude, therefore, that the risk of developing PSA >4 ng/ml on TRT is small in the absence of either a prior diagnosis of BPH or PSA >4ng/ml. Urological outcomes remain uncertain, but need to be determined to better inform monitoring guidelines.

Factors associated with the initiation of testosterone replacement therapy in men from the 45 and Up Study

There have been large increases in testosterone prescribing since 2000. The aim of this study was to identify factors associated with testosterone replacement therapy (TRT) initiation in men. Data were from the 45 and Up Study, an ongoing cohort study involving 266,942 participants from New South Wales aged ≥45 years. Baseline data (2006−09) were linked to administrative data on government-subsidised prescriptions and medical services. The study included 105,429 men. In two years following baseline, 2.9 per 1000 men (95% confidence interval: 2.6, 3.2) had initiated TRT. Men with self-rated poor health, those treated for osteoporosis; anxiety, depression or high blood cholesterol, and those who lived in major cities or were aged 55–74 years had greater odds of TRT initiation. In the six months before TRT initiation, 41% of men had a hormone test record. Discussion The high rate of TRT initiation and low rate of recommended investigations suggest TRT may have been prescribed outside recommended indications.

PD09-06 FERTILITY IN ADOLESCENTS WITH KLINEFELTER SYNDROME – A SURVEY OF CURRENT CLINICAL PRACTICE

You have accessJournal of UrologyInfertility: Epidemiology & Evaluation I1 Apr 2018PD09-06 FERTILITY IN ADOLESCENTS WITH KLINEFELTER SYNDROME – A SURVEY OF CURRENT CLINICAL PRACTICE Andrew Zganjar, Ajay Nangia, Rebecca Sokol, Anna Ryabets, Anthony Thomas, and Mary Samplaski Andrew ZganjarAndrew Zganjar More articles by this author , Ajay NangiaAjay Nangia More articles by this author , Rebecca SokolRebecca Sokol More articles by this author , Anna RyabetsAnna Ryabets More articles by this author , Anthony ThomasAnthony Thomas More articles by this author , and Mary SamplaskiMary Samplaski More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.603AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The optimal fertility preservation protocols in adolescents with Klinefelter Syndrome (KS) are still being determined. We sought to survey which specialties are treating these patients, and the currently executed practices regarding fertility and andrology care in these patients. METHODS A 24 question electronic survey was developed to elicit practitioner background/expertise and management practices regarding fertility preservation in adolescent males with KS. The survey was distributed to members of the Society for the Study of Male Reproduction, Pediatric Endocrine Society, and Endocrine Society. Survey responses were compiled for each question with additional analysis by individual medical specialties. RESULTS We received 232 responses: 60 (26%) pediatric endocrinologists (PE), 133 (57%) adult endocrinologists (AE), and 39 (17%) urologists. 68% of physicians were in the academic setting, 63% were in practice for >10 years, and 65% received formal training in KS. ″Past clinical experience″ and ″current literature″ guided management decisions for most providers. Table 1 summarizes responses regarding sperm banking and testicular biopsy. The majority of the respondents agreed that testicular biopsy should be offered if no sperm was found in the ejaculate; however, the optimal age for the procedure varied among specialists. Most agreed that sperm extraction shouldn′t be done in boys < 8 years of age. There was variation in responses regarding the need for psychotherapy care prior to undergoing invasive fertility treatments, as well as the optimal timing for starting testosterone replacement therapy (TRT). Rising gonadotropin levels (15%), testosterone levels (15%), and clinical symptoms of hypogonadism (28%) were commonly cited reasons for TRT initiation. Most AE (60%) and urologists (65%) did not agree with starting infants on TRT; however, most PE (65%) believed it was indicated if/when patients had a micropenis. CONCLUSIONS Clinical practices for fertility preservation in adolescents with KS vary greatly within and between the specialties caring for these patients. These findings may help guide future research and highlight the importance of establishing clinical practice guidelines. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e224 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Andrew Zganjar More articles by this author Ajay Nangia More articles by this author Rebecca Sokol More articles by this author Anna Ryabets More articles by this author Anthony Thomas More articles by this author Mary Samplaski More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Incidence of Prostate Cancer in Men on Testosterone Replacement Therapy after Resection of Pituitary Adenomas: No Increased Risk on Long-Term Follow-Up

Despite evidence to the contrary, concern exists regarding prostate cancer (PCa) in men managed with long-term testosterone replacement therapy (TRT). After pituitary resection, many men develop hypogonadism requiring replacement. We sought to determine the incidence of PCa diagnosed subsequent to TRT in men with long-term follow-up after pituitary surgery. Since 2000, all patients undergoing resection of pituitary adenoma have been entered into a prospective database. Cases from 2000 to 2016 were reviewed for demographics and clinical parameters. Male patients were categorized by receipt of TRT. One hundred twenty-two cases were identified. Nine men diagnosed with PCa prior to pituitary surgery were excluded. Of the remainder, 56 (49.6%) received TRT, and 57 (50.4%) did not (control group). There were no significant demographic differences between groups. Mean preoperative and postoperative testosterone values were 253 and 131, respectively (p = 0.013). Mean preoperative and postoperative prostate specific antigens (PSA) were 0.5 and 0.57, respectively (NS). Mean duration of TRT was 5 years, and mean follow-up was 11 years. After TRT, mean testosterone and PSA were 385 and 0.84, respectively (p = 0.00003 and NS). One patient was diagnosed with PCa subsequent to TRT and no cases were found among controls (NS). For the case identified, timing of diagnosis was felt to be too proximate to initiation of TRT to be attributable. This study is the first to examine rates of PCa among men treated with TRT for hypogonadism secondary to pituitary resection. This analysis suggests that TRT is not associated with an increased risk of PCa in this population.

Improvement of endothelial function following initiation of testosterone replacement therapy.

BackgroundIsolated recent studies have suggested an increased risk of heart attack as early as 3 months following testosterone replacement therapy (TRT). Such a rapid risk increase would likely require rapid deterioration of arterial endothelial function. Our goal was to assess arterial endothelial function in hypogonadal men prior to and at least 3 months after initiation of TRT.MethodsAdult men were consented 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 EndoPAT-2000 machine. 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. Endothelial function was reassessed at the next clinic visit, between 3 and 6 months if the patients were compliant with therapy. Changes in continuous variables were assessed with the paired t test.ResultsTwenty-three patients were consented with a mean age of 52.7 years (range, 34–68 years) and starting testosterone 196.9 ng/dL (range, 35–339 ng/dL). There was a history of diabetes in four, hypertension in ten and coronary artery disease in five. Mean RHI was 1.67±0.37 (70% were abnormal) and mean AI was 2.57%±14.0% (39% were abnormal). There were no cardiac events. At follow-up 20 patients were compliant with therapy and retested. Mean testosterone increased from 203 to 511 (P<0.0001). Mean RHI improved from 1.70 to 2.14 (P=0.01). Mean AI improved from 2.9% to −1.75% (P=0.01). In four men RHI worsened but in each case less than the 10% error of the test. No man had worsened AI.ConclusionsMen with symptomatic hypogonadism often have abnormal arterial endothelial function. Following TRT, endothelial function either remains unchanged or improves.

The appropriateness and persistence of testosterone replacement therapy in Ontario.

To examine the concordance between testosterone replacement therapy (TRT) use and established reimbursement criteria, as well as compare the persistence of use among available formulations (injectable, oral, topical gel, transdermal patch) among elderly men in Ontario, Canada. We conducted a retrospective cohort study of men aged 66 years or older in Ontario newly treated with testosterone between 1 January 2009 and 31 December 2012 using linked health administrative data. Continuous use was defined on the basis of prescription refills issued within 180 days of the preceding prescription. We studied men who received at least two consecutive TRT prescriptions. We estimated the prevalence of hypogonadism, human immunodeficiency virus, specialist visits and lab tests for serum testosterone prior to initiation of TRT to investigate concordance with prescribing criteria. We also performed a Kaplan-Meier analysis to test for differences in the median time to discontinuation among formulations. Among the 4797 men who received at least two TRT prescriptions, only 38.7% met the reimbursement criteria for use prior to initiating therapy. The median time to discontinuation differed significantly among formulations and was longest among recipients of oral TRT products (383 days), and lower for recipients of topical gels (319 days), injectable (283 days) and transdermal patches (160 days; Log-rank test p < 0.001). A large proportion of older men in Ontario do not appear to meet reimbursement criteria prior to commencing therapy, and many discontinue TRT within a year of initiation. Copyright © 2016 John Wiley & Sons, Ltd.