Effects Of Testosterone Treatment Research Articles

(207) THE LANDSCAPE OF TESTOSTERONE REPLACEMENT THERAPY RESEARCH: A BIBLIOMETRIC AND PUBLIC ATTENTION ANALYSIS

Abstract Introduction Testosterone Replacement Therapy (TRT) is a pivotal treatment for men with hypogonadism, aiming to alleviate symptoms of testosterone deficiency. Given the debates over TRT’s safety, particularly concerning prostate cancer and cardiovascular risks, it is crucial to understand the most influential research at both the academic setting as well as what lay audiences are being exposed to. Objective This bibliometric analysis aims to identify and analyze the most cited and impactful literature on TRT using two distinct metrics: Web of Science (WoS) citations and Altmetric Attention Scores (AAS), a metric that captures the online visibility of academic work. Methods A comprehensive literature search was performed using WoS and Altmetric Explorer with the keyword "testosterone replacement therapy." Two urology researchers screened the top 1000 papers from both databases to identify the top 100 relevant papers. Data extraction included citations, authorship, publication journals, language, study design, country, year of publication, and specific TRT topics. Altmetric scores were calculated based on a weighted algorithm considering various types of attention, such as news and social media mentions. Results From WoS, the highest cited paper was “The Decline of Androgen Levels in Elderly Men and its Clinical and Therapeutic Implications” (Kaufman and Vermeulen, 2005), with 786 citations. The median and mean citations for the top 100 papers were 145.5 and 195.2, respectively. The most frequent journal was the Journal of Clinical Endocrinology & Metabolism (JCEM), contributing 17 papers and 4350 citations. Most papers were in English and affiliated with institutions in the United States (47%), followed by Europe (29%). Studies focused on treatment dominated (61%), with evaluation (34%) and comorbidities (5%) following. From Altmetric Explorer, the median and mean Dimension citations were 52 and 94.96, respectively. The most frequent journal was also JCEM, and all papers were in English, primarily from the United States. The paper “Effects of Testosterone Treatment in Older Men” by Synder et al. (2016) possessed the highest Altmetric Score of 1691, with 660 Dimension citations. The most recent top paper, “Cardiovascular Safety of Testosterone-Replacement Therapy” (Lincoff et al., 2023), ranked second with Altmetric Score of 1217 and 61 Dimension citations. Conclusions While WoS citations reveal the historical foundations and established research trends for evaluation and management of testosterone deficiency, Altmetric scores offer insights into current public and academic interest, particularly around cardiovascular concerns. This dual bibliometric approach provides a detailed understanding of influential TRT literature which shaped its history and current clinical concerns across specialties – from urology to endocrinology and primary care. Disclosure No.

Testosterone in prevention and treatment of type 2 diabetes in men: Focus on recent randomized controlled trials.

In epidemiological studies, lowered serum testosterone concentrations are common in men with obesity, prediabetes, and established type 2 diabetes (T2D). In men with prediabetes, lowered serum testosterone also predicts a future risk of T2D in men. Administration of testosterone consistently reduces fat mass and increases skeletal muscle mass-body compositional changes expected to be metabolically favorable. In men with established T2D, the effects of testosterone treatment on glycemic measures are inconsistent. Irrespective of baseline serum testosterone concentration in men with prediabetes or newly diagnosed early-onset T2D, testosterone treatment prescribed in conjunction with a lifestyle program has been reported to reduce the risk of T2D by 40% after 2 years, suggesting that either a lifestyle program is required to facilitate the glycemic benefit of testosterone treatment and/or that testosterone treatment has more favorable effects on glycemia in men early in the evolution or onset of the disease. The durability of the benefit and longer-term safety of testosterone treatment have not been established. Therefore, more studies are required before testosterone treatment can be recommended for the prevention and/or treatment of men with or at elevated risk of T2D who do not have hypogonadism due to an established disease of the hypothalamic-pituitary-testicular axis.

(062) Testosterone Therapy Improves Mortality after Solid Organ Transplant

Abstract Introduction Low testosterone has been suggested as a contributor to mortality and rejection after solid organ transplant. Whether testosterone therapy specifically improves these outcomes is unknown. Objective To determine whether treatment of low testosterone with testosterone therapy is associated with improved rejection or mortality after solid organ transplant using TriNetX, a large deidentified, multi-institutional database. Methods We compiled all clinical data from the TriNetX research network, a globally federated health research network (with waiver from Western IRB) that provides de-identified clinical information from 58 heath care organizations, and over 80 million patients located within the United States. We selected male patients (aged ≥ 18) with a history of lung, kidney, liver, heart, or pancreas transplant. We categorized patients into two groups, based on prescription for testosterone therapy. For all patients, we collected clinical information including demographics, comorbidities, laboratory findings, and medication use. Our outcomes of interest were 1-year, 3-year, and all-time mortality, as well as allograft rejection. We evaluated differences in baseline characteristics between testosterone level (Normal T, or Low T), using chi-square or Fisher’s exact test for categorical data (presented as frequencies and percentages), and independent t-test for continuous data. To address potential confounders that could bias our results, we used a propensity score weighted regression (inverse probability of treatment weighting), matched on age, race/ethnicity, comorbid conditions, multiple transplant status, and immunosuppressant use. Multivariable logistic regression was used to model outcome of transplant rejection, on the predictors of testosterone level, testosterone therapy, and their interaction, while a cox regression model was used to determine probability of mortality. Results A total of 1,762 men were identified with solid organ transplants. 262 (14.9 %) met criteria for low testosterone and had a history a prescription of testosterone therapy. Baseline characteristics were similar between the two groups (Table 1). After matching for existing patient characteristics, outcomes showed that a prescription for testosterone therapy was associated with improved mortality after organ transplant. The risk of mortality was reduced at 1 year (HR 0.33), 3 years (HR0.57) and for all time mortality (HR 0.61) among patients treated with testosterone therapy. No effect of testosterone treatment was seen with regards to allograft rejection (data not shown). Conclusions Testosterone therapy may improve mortality in men with low serum testosterone following solid organ transplant. Further studies are required to determine when and what patients derive most benefit from testosterone therapies, particularly as the result does not appear to be driven by reduced allograft rejection. Disclosure No

The effect of testosterone treatment on bone mineral density in Klinefelter syndrome: A retrospective cohort study.

Although Klinefelter syndrome (KS) is the most frequent sex-hormone disorder, there is ongoing uncertainty about the often associated sex-hormone deficiency, its impact on common comorbidities, and therefore about prevention and treatment. In this study, we focus on bone loss, reported to occur in over 40% of KS patients, and the impact of testosterone replacement therapy (TRT) on this comorbidity. This single-center retrospective cohort study in a tertiary hospital compared the effect of treatment with TRT to no TRT on evolution of bone mineral density (BMD) in KS patients. After a medical chart review, a total of 52 KS subjects were included in this study. BMD was measured by dual-energy X-ray absorptiometry (DXA) and expressed as T-scores. The subjects were divided into three groups, according to TRT. In the subgroup that only started TRT after baseline measurements (mean age 31 years), we observed significant gain in BMD T-score at the lumbar spine (0.58 ± 0.60, p = 0.003; mean gain of 0.62% areal BMD per year) and total femur T-score (0.24 ± 0.39, p = 0.041; mean gain of 0.25% areal BMD per year) after a mean follow-up period of 7.5 years. Compared to untreated subjects, a significant difference in evolution was demonstrated at the lumbar level (+0.58 ± 0.60 vs. -0.14 ± 0.42, p = 0.007). In untreated subjects with normal testosterone levels, a loss of BMD (-0.27 ± 0.37, p = 0.029; mean loss of 0.49% areal BMD per year) at the femoral neck was measured. This decline was equal to the predicted loss seen in the general male population. TRT results in BMD gain in patients with KS with testosterone deficiency, mainly at the lumbar spine. However, this effect is limited (0.62% per year). Patients who were not treated with TRT because of sufficient endogenous testosterone levels, showed only the predicted age-related bone loss during follow-up. The need for TRT in maintaining bone health in KS should be evaluated on an individual basis according to the degree of sex steroid deficiency.

P-475 Similar fertilization rates and preimplantation embryo development among testosterone-treated transgender men and cisgender women

Abstract Study question What are the effects of testosterone treatment on fertilization rates and preimplantation embryo development among transgender men who underwent fertility preservation? Summary answer Testosterone exposure among transgender men has no adverse impacts on fertilization rates and preimplantation embryo development and quality. What is known already Transmen are assigned female sex at birth but identify as men. This mismatch might induce distress that is termed gender dysphoria. Testosterone therapy induces “masculine” physical traits, suppresses “feminine” ones, and relieves gender dysphoria. More transmen present for testosterone therapy, their average age is decreasing, and many express the desire to have biological children. Therefore, understanding the effects of testosterone on fertility is crucial. Previous data suggest that despite testosterone treatment, the ovarian reserve and the in-vitro oocyte maturation are preserved among transmen. However, the fertility potential in terms of fertilization rate and early embryo development was not explored. Study design, size, duration This retrospective cohort study included 7 testosterone-treated transgender men and 34 cisgender women between April 2016 and November 2021. Participants/materials, setting, methods Testosterone-treated transgender men who cryopreserved embryos were compared to 10 fertile women who cryopreserved embryos and to 24 women who underwent IVF treatment due to unexplained or mechanical infertility. Statistical analyses compared assisted reproductive technology data and outcomes between the transgender men group and the two cisgender women groups. Morphokinetic and morphological parameters were compared between 210 embryos of transgender men and 411 embryos of cisgender women. Main results and the role of chance The transgender men (30.2±3.59 years) were significantly younger than the cisgender women who cryopreserved embryos (35.1±1.85 years; P = 0.005) and the cisgender women who underwent fertility treatment (33.8±3.23 years; P = 0.017). Among the transgender men, the mean length of testosterone exposure was 99.7±49.24 months (range 14-156 months) and the mean time of discontinuation of testosterone prior to stimulation was 6.57±2.14 months (range 4-10 months). After adjusting for the patient’s age, the fertilization rate was comparable between the transgender men and both cisgender women groups (P = 0.391 and 0.659). No significant differences in the number of cryopreserved embryos (7.2±5.09 and 3.5±2.66; P = 0.473) and the days on which they were frozen (P = 0.576) were observed between the transgender men and the fertile cisgender women. All morphokinetic parameters that were evaluated using time-lapse imaging, as well as the morphological characteristics, were comparable between transgender men and both groups of cisgender women. Limitations, reasons for caution All transgender men in our study discontinued the testosterone treatment before starting ovarian stimulation. Stopping hormonal therapy might cause considerable anguish and gender dysphoria. Therefore, further studies that include subjects who did not stop testosterone before fertility preservation are needed. Wider implications of the findings Transgender men have acceptable fertilization rates and normal preimplantation embryo development and quality after long-term testosterone treatment. Embryo cryopreservation is, therefore, a feasible and effective way for them to preserve their fertility for future biological parenting. Trial registration number Not applicable

Similar fertilization rates and preimplantation embryo development among testosterone-treated transgender men and cisgender women

What are the effects of testosterone treatment on oocyte fertilization and preimplantation embryo development among transgender men who have undergone fertility preservation? A retrospective study was undertaken in a university-affiliated tertiary hospital between April 2016 and November 2021. Embryos were divided into three groups by source: 210 embryos from 7 testosterone-exposed transgender men, 135 from 10 cisgender women who cryopreserved embryos, and 276 from 24 cisgender women who underwent fertility treatment. Statistical analyses compared assisted reproductive technology outcomes between the group of transgender men and both groups of cisgender women. Morphokinetic and morphological parameters were compared between the embryos derived from these three groups. The transgender men (30.2±3.5 years of age) were significantly younger than the cisgender women who cryopreserved embryos (35.1±1.8 years; P=0.005) and the cisgender women who underwent fertility treatment (33.8±3.2 years; P=0.017). After adjusting for participant age, the fertilization rate was comparable between the transgender men and both groups of cisgender women (P=0.391 and 0.659). There were no significant differences between the transgender men and the cisgender women who preserved fertility in terms of number of cryopreserved embryos (7.2±5.1 and 3.5±2.6; P=0.473) or the distribution of embryo age at cryopreservation (P=0.576). All morphokinetic parameters evaluated by time-lapse imaging, as well as the morphological characteristics, were comparable for the embryos in all three groups. Testosterone exposure among transgender men has no adverse impact upon fertilization rates or preimplantation embryo development and quality.

Effects of testosterone treatment on clitoral haemodynamics in women with sexual dysfunction

ABSTRACT Introduction Preclinical studies show that, in the clitoris, testosterone (T) is necessary to maintain a functional contractile and relaxant machinery, which represents the underlying mechanism of the peripheral arousal response. Although there is clinical evidence suggesting that T treatment significantly improves multiple domains of sexual functioning, the vascularization of clitoral tissue and its regulation by sex steroids are still under-investigated. Objective To explore the effects of 6-month systemic T administration on clitoral color Doppler ultrasound (CDU) parameters in women with female sexual dysfunction (FSD). Methods 81 women with FSD were retrospectively recruited. Data on CDU parameters at baseline and after 6 months with four different treatments were available and thus further longitudinally analyzed: local non-hormonal moisturizers (NH group), n=37; transdermal 2% T gel 300 mcg/day (T group), n=23; local estrogens (E group), n=12; combined therapy (T+E group), n=9. Patients underwent physical, laboratory, and genital CDU examinations at both visits and completed different validated questionnaires, including the Female Sexual Function Index (FSFI). Results At 6-month visit, T therapy significantly increased clitoral artery peak systolic velocity (PSV) when compared to both NH (p < 0.0001) and E (p < 0.0001) groups. A similar increase was found in the T + E group (p = 0.039 vs. E) (Fig.1). In addition, T treatment was associated with significantly higher FSFI desire, pain, arousal, lubrication, orgasm and total scores at 6-month visit vs. baseline. Similar findings were observed in the T + E group. No significant differences in the variations of total and high-density lipoprotein-cholesterol, triglycerides, fasting glycemia, insulin and glycated hemoglobin levels were found among the four groups. No adverse events were observed. Conclusions In women complaining for FSD, systemic T administration, either alone or combined with local estrogens, was associated with a positive effect on clitoral blood flow and a clinical improvement in sexual function, showing a good safety profile. Disclosure Work supported by industry: no.

Elevated corticosterone levels are associated with increased immunocompetence in male toads, both when calling and under experimental conditions

Circulating androgens can influence immune responses and sexual traits in male vertebrates. However, in the last 20 years, glucocorticoids have also been implicated as a possible source of variation in male sexual traits and immunocompetence. In this context, we studied the relations between male vocal mating display, immunity, androgens, and glucocorticoids in the explosive breeding toad Rhinella granulosa. In the field, males with high calling effort display either high- or low-corticosterone (CORT) plasma levels, but only males with both high calling effort and high CORT plasma levels showed high bacterial killing ability (BKA), suggesting that the acute CORT elevation can be immunostimulatory. CORT treatments increased BKA in laboratory experiments, confirming the functional relationship observed in the field. However, toads treated with a low dose of CORT increased BKA for 10 h after the treatment, while toads that received a high dose increased BKA for only 1 h after the treatment. These results indicate that different CORT doses can result in temporal differences in the immune response. We did not find any relationship between calling effort, immune response (BKA and PHA swelling response), and testosterone plasma levels in the field, or any effects of testosterone treatment on immunocompetence. Our results suggest a complex relationship between calling effort and immunity, mediated by CORT plasma levels.

Effects of testosterone treatment on clitoral haemodynamics in women with sexual dysfunction

PurposeTo explore the effects of 6-month systemic testosterone (T) administration on clitoral color Doppler ultrasound (CDU) parameters in women with female sexual dysfunction (FSD).Methods81 women with FSD were retrospectively recruited. Data on CDU parameters at baseline and after 6 months with four different treatments were available and thus further longitudinally analyzed: local non-hormonal moisturizers (NH group), n = 37; transdermal 2% T gel 300 mcg/day (T group), n = 23; local estrogens (E group), n = 12; combined therapy (T + E group), n = 9. Patients underwent physical, laboratory, and genital CDU examinations at both visits and completed different validated questionnaires, including the Female Sexual Function Index (FSFI).ResultsAt 6-month visit, T therapy significantly increased clitoral artery peak systolic velocity (PSV) when compared to both NH (p < 0.0001) and E (p < 0.0001) groups. A similar increase was found in the T + E group (p = 0.039 vs. E). In addition, T treatment was associated with significantly higher FSFI desire, pain, arousal, lubrication, orgasm, and total scores at 6-month visit vs. baseline. Similar findings were observed in the T + E group. No significant differences in the variations of total and high-density lipoprotein-cholesterol, triglycerides, fasting glycemia, insulin and glycated hemoglobin levels were found among the four groups. No adverse events were observed.ConclusionIn women complaining for FSD, systemic T administration, either alone or combined with local estrogens, was associated with a positive effect on clitoral blood flow and a clinical improvement in sexual function, showing a good safety profile.Trial registration numberNCT04336891; date of registration: April 7, 2020.

Effects of testosterone treatment, with and without exercise training, on ambulatory blood pressure in middle-aged and older men.

With age, testosterone (T) and physical activity levels often decline in parallel. The effect of combining T treatment and exercise training on ambulatory blood pressure (ABP) is unclear. To assess T and exercise effects, alone and in combination, on ABP in men aged 50-70years, waist circumference≥95cm and low-normal serum T (6-14nmol/L), without organic hypogonadism. A 2 × 2 factorial randomised, placebo-controlled study. Randomization to daily transdermal AndroForte5® (Testosterone 5.0%w/v, 100mg in 2ml) cream (T), or matching placebo (P) (double-blind), and to supervised exercise (Ex) or no additional exercise (NEx), for 12weeks. Average 24-h systolic blood pressure (SBP) increased with T treatment (testosterone*time, p=.035). Average 24-h SBP increased in T+Ex (T+Ex:+3.0 vs. P+NEx: -3.0mmHg, p=.026) driven by day-time changes (T+Ex:+3.5 vs. P+NEx: -3.0mmHg, p=.026). There was an effect of T for 24-h average diastolic blood pressure (DBP, testosterone*time, p=.044) driven by the decrease in P+Ex (P+Ex: -3.9 vs. T+NEx: -0.5mmHg, p=.015). Night-time DBP was lower with exercise (P+Ex: -4.0 vs. P+NEx: +0.7mmHg, p=.032). The effect of exercise to lower night-time DBP was not apparent in the presence of T (T+Ex: -0.4 vs. P+NEx: +0.7mmHg, p>.05). Ex increased average 24-h pulse pressure (PP, exercise*time, p=.022), largely during daytime hours (exercise*time, p=.013). There was a main effect of T to increase 24-h SBP, primarily seen when T was combined with Ex. Exercise alone decreased 24-h and night-time DBP; an effect attenuated by T. BP should be carefully assessed and monitored, when prescribing T treatment to middle-aged and older men, especially when combined with exercise training.

Effects of testosterone treatment on transgender males: A single-institution study.

Objectives:Data regarding gender-affirming hormone therapy in the Asian population are sparse. We aimed to evaluate the efficacy and safety of testosterone therapy in transgender men.Methods:A retrospective study chart review was conducted in a single university-based transgender clinic. Transgender men aged >18 years who newly started testosterone therapy during January 2015 to October 2019 were recruited. Physical changes, laboratory results, and adverse events, including cancer, thromboembolism, cardiovascular events, and death after masculinizing hormone therapy, were evaluated.Results:A total of 39 transgender men (mean age: 27.8 ± 6.0 years) were included. All individuals were treated with intramuscular testosterone injection with a mean follow-up of 25.2 ± 12.9 months. The most common maintenance regimen was testosterone enanthate 250 mg every 4 weeks. Masculinizing effects developed in all transgender men. There were no changes in body weight, and systolic and diastolic blood pressure. Hematocrit levels were 12% significantly increased from 39.9 ± 3.3% to 48.9 ± 2% (p < 0.001). Ten individuals (25.6%) had hematocrit >50%. Significant changes were found in decreased fasting plasma glucose, increased creatinine, and increased uric acid levels. A non-significantly increased alanine aminotransferase, increased low-density lipoprotein cholesterol, and decreased high-density lipoprotein cholesterol were observed. No thromboembolism, cancer, stroke, or coronary artery disease occurred.Conclusions:Gender-affirming hormone therapy is an effective and safe short-term treatment in Thai transgender men. Apart from the standard recommendation, uric acid, plasma glucose, and creatinine level evaluation before and during masculinizing hormone therapy are rational practices. An intramuscular testosterone enanthate 250 mg every 4 weeks is an alternative masculinizing regimen with decent efficacy and safety profile.

Effect of Testosterone Treatment on Cardiovascular Events in Men: Protocol for a Systematic Literature Review and Meta-Analysis.

BackgroundTestosterone prescriptions have increased dramatically in recent decades, with increasing usage in men. Despite epidemiological associations reported high circulating concentrations of endogenous androgens and low risk of cardiovascular events and mortality, the effects of exogenous androgens in the form of testosterone therapy for maintaining physiological circulating androgen concentrations on the cardiovascular system remain uncertain with no published meta-analysis on this topic.ObjectiveThe aim of this study was to investigate the effects of prescribed testosterone treatment, in all forms and durations, from well-developed randomized controlled trials, on cardiovascular events in men aged 18 years or older.MethodsPeer-reviewed journal articles published from 1980 to 2019 will be searched from databases (ie CINAHL [Cumulated Index to Nursing and Allied Health Literature], Embase, Medline, Scopus, Cochrane Controlled Register of Trials as well as the Clinical Trial Registry). Randomized controlled trials or cluster randomized controlled trials with at least one intervention arm of testosterone and a control group of usual care or no testosterone treatment will be included in this review and meta-analysis. Studies on men with previous cardiovascular events or cardiac vascularization (coronary bypass surgery or percutaneous coronary intervention) will be excluded. Data related to primary outcomes such as clinical events of any type of stroke or transient ischemic attack, nonfatal myocardial infarction or acute coronary syndrome, emergency coronary artery revascularization, carotid surgery, cardiac mortality, and all-cause mortality will be extracted for analysis. The criteria for PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) will be followed in the evaluation of evidence.ResultsSearch terms have been piloted and finalized. This study will be completed by the end of 2020.ConclusionsThis protocol will guide a systematic literature review of the evidence around prescribed testosterone and its effect on cardiovascular events in men aged 18 years or older. The findings will inform clinical management of hypogonadal men.Trial RegistrationPROSPERO International Prospective Register of Systematic Reviews CRD42019134278; https://tinyurl.com/y6t7gggeInternational Registered Report Identifier (IRRID)PRR1-10.2196/15163

274-OR: Effect of Testosterone Treatment on Type 2 Diabetes Incidence in High-Risk Men Enrolled in a Lifestyle Program: A Two-Year Randomized Placebo-Controlled Trial

In men with obesity and IGT, serum testosterone (T) is inversely associated with incident T2D. Hypothesizing that T treatment prevents or reverses T2D beyond the effects of a lifestyle program alone, we conducted a multi-center, double-blinded placebo-controlled trial. Men (N=1007), aged 50-74 yrs., waist circumference (WC)&amp;gt;95cm, serum T≤14nmol/L (chemiluminescent assay), and IGT or newly diagnosed T2D, established by an OGTT, were randomized to receive, on a 1:1 basis, either IM T undecanoate (Reandron, Bayer) (1000mg/4ml) or vehicle (V) at baseline, 6 weeks and then 3-monthly for 2 yrs. All participants were enrolled in a lifestyle program (Weight Watchers® (WW)). Co-primary 2-yr outcomes: (1) OGTT 2-hr glucose ≥11 mmol/L: 55/443 (12.4%) in the T and 87/413 (21.1%) in V groups; RR (95% CI) 0.59 (0.43-0.80), P&amp;lt;0.001; and (2) mean change from baseline in 2-hr glucose: -1.70 mmol/L and -0.95 mmol/L in the T and V groups, respectively (mean difference -0.75 (95% CI -1.10 to -0.40) P&amp;lt;0.001). The treatment effect was independent of baseline serum T. Secondary 2-year outcomes: Greater decreases from baseline in fasting glucose by 0.17 mmol/L, WC by 2.1 cm, total fat mass by 2.7kg, and abdominal fat mass by 2.3%, and greater increases in total muscle mass by 1.7kg, arm muscle mass by 0.36kg and hand grip strength by 2.2kg, occurred in the T vs. V group (all P&amp;lt;0.004). Compliance with the WW program was similar in the T (30%) vs. V (28%) groups (P=0.89). Safety: Hematocrit ≥ 0.54: 106/491 (21.6%) vs. 6/484 (1.2%) in the T vs. V groups (P&amp;lt;0.001). SAEs in T vs. V groups (total events 55 vs. 42): Arrythmias (8 vs. 3), IHD (7 vs. 13), cerebrovascular disease (4 vs. 3), BPH (8 vs. 3), prostate cancer (4 vs. 5), other cancers (10 vs. 4), depression (1 vs. 3). There were 2 deaths in each group. Beyond a lifestyle program, T treatment reduced the RR of T2D by ∼40% at least partially mediated by favorable changes in body composition. Clinical Trial Registration: ACTRN12612000287831. Disclosure G.A. Wittert: Research Support; Self; Bayer Inc., Lawley Pharmaceuticals, Lilly, Weight Watchers International, Inc. Speaker’s Bureau; Self; Besins. K.P. Robledo: None. M. Grossmann: Research Support; Self; Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Novartis Pharmaceuticals Canada Inc., Otsuka Pharmaceutical Co., Ltd., Weight Watchers International, Inc. Speaker’s Bureau; Self; Besins Healthcare, Otsuka Pharmaceutical Co., Ltd. K. Bracken: None. B.B. Yeap: Advisory Panel; Self; Sanofi. Research Support; Self; Bayer AG, Lawley Pharmaceuticals. Speaker’s Bureau; Self; Besins, Sanofi. B.G.A. Stuckey: None. R.I. McLachlan: None. D.J. Handelsman: None. C. Allan: Advisory Panel; Self; Ferring Pharmaceuticals. Speaker’s Bureau; Self; Besins. W. Inder: Research Support; Self; Bayer Healthcare Pharmaceuticals Inc. Speaker’s Bureau; Self; Amgen, Novo Nordisk Inc., Pfizer Inc. D. Jesudason: Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company. A.C. Keech: Advisory Panel; Self; Amgen, Kowa Research Institute, Inc. Consultant; Self; Sanofi-Aventis. Speaker’s Bureau; Self; Abbott, Amgen. A. Jenkins: Advisory Panel; Self; Abbott, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Sanofi-Aventis. M. Ng Tang Fui: None. M. Daniel: None. Funding National Health and Medical Council of Australia (1030123); Eli Lilly and Company; Bayer AG; Weight Watchers; University of Adelaide

Effects of Testosterone Treatment on Quality of Life in Patients With Chronic Kidney Disease.

Testosterone deficiency (TD) is common and impairs quality of life (QoL) in patients with chronic kidney disease (CKD). However, there are no studies about whether testosterone replacement therapy (TRT) can improve QoL in patients with CKD. Therefore, we investigated the effect of TRT on the QoL of patients with CKD and confirmed the safety of TRT. Twenty-five male patients with stages III–IV CKD whose serum testosterone levels were <350 ng/dl (TD) were enrolled and treated with testosterone gel for 3 months (group II). Age-matched controls with stages III–IV CKD and TD (group I) were recommended to exercise for the same period. Before and after the treatment, the BMI and handgrip strength were checked, serological tests were performed, and questionnaires were administered in both groups. Compared to baseline, there was no significant difference in serum testosterone levels, scores of the 36-Item Short Form Health Survey (SF-36), Aging Males’ Symptoms Scale (AMS), and International Prostate Symptom Score (IPSS), and grip strength in group I after 3 months. In group II, a significant increase in testosterone, hemoglobin (Hb), and hematocrit (Hct) was observed, and grip strength significantly increased after TRT. Significant improvement in scores of SF-36, AMS, and IPSS was also confirmed after TRT in group II. There was a significant difference in testosterone, Hb, Hct, grip strength, and scores of SF-36, AMS, and IPSS between the two groups after 3 months. The patients in group II showed positive results and continued with TRT. Therefore, we conclude that TRT safely improves the QoL and TD symptoms in patients with moderate-to-severe CKD.

50 Years Ago in TheJournal ofPediatrics: The Effects of Testosterone Treatment in Klinefelter's Syndrome

50 Years Ago in TheJournal ofPediatrics: The Effects of Testosterone Treatment in Klinefelter's Syndrome

The effects of testosterone treatment on fat tissue dysfunction and nonalcoholic fatty liver disease in obese men undergoing bariatric surgery

The effects of testosterone treatment on fat tissue dysfunction and nonalcoholic fatty liver disease in obese men undergoing bariatric surgery

PO-01-077 The effects of testosterone treatment on fat tissue dysfunction and nonalcoholic fatty liver disease in obese men undergoing bariatric surgery

Substitution treatment of hypogonadism in clinical and experimental models has shown beneficial effects on insulin sensitivity and accumulation of visceral and liver fat. Aim of the study was to analyze the effects of testosterone replacement therapy on benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS) clinical parameters, adipose tissue dysfunction and nonalcoholic fatty liver disease (NAFLD) in obese patients candidates for bariatric surgery. Patients were divided into three groups: eugonadal, untreated hypogonadal and symptomatic hypogonadal treated for 6-8 months with testosterone. BPH/LUTS parameters were assessed by IPSS (International Prostate Symptom Score) and prostate ultrasound. Preadipocyte cells (hPADs) isolated from adipose tissue biopsies were used to evaluate insulin sensitivity, adipogenic potential and mitochondrial function. NAFLD was evaluated by triglycerides (TG) assay and histological examination of liver biopsies. Clinically, notwithstanding a prostate volume increase, testosterone treatment improved the IPSS score and hyperemia. Liver TG levels correlated positively with both steatosis and NAS scores, and resulted significantly higher in hypogonadal patients when compared to eugonadal patients, with testosterone treatment significantly reducing TG levels. In the liver, testosterone treatment induced an increased mRNA expression of lipid metabolism markers, whereas in visceral adipose tissue it induced an increased mRNA expression of lipid catabolism and mitochondrial biofunctionality markers. In hPADs testosterone treatment induced an increased mRNA expression of brown adipogenesis and mitochondrial biofunctionality markers. Testosterone treatment normalized hPADs ability to respond to increasing concentrations of insulin. Accordingly, glucose uptake AUCs showed a positive correlation with testosterone levels. Hypogonadal hPADs mitochondria displayed a lower average length and a superoxide generation increase, compared to eugonadal, with testosterone treatment normalizing both parameters.

Predictive Factors of Efficacy Maintenance after Testosterone Treatment Cessation.

There is no conclusive evidence as to whether patients with testosterone deficiency (TD) who benefit from testosterone treatment (TRT) must continue the treatment for the rest of their lives. In some patients, the effect of TRT does not maintained after stopping TRT and, some patients show no significant TD symptoms, with normal testosterone levels after TRT cessation. Therefore, we investigated the predictive factors of response maintenance after TRT cessation. A total of 151 men with TD who responded to TRT were followed up for six months after TRT discontinuation. Ninety-two patients (Group I) failed to show response maintenance; 59 patients (Group II) had a maintained response. The groups did not differ in baseline characteristics or the type of TRT (oral, gel, short/long-acting injectables). However, TRT duration was significantly longer (10.7 vs. 5.2 months), and peak total testosterone (TT) level was significantly higher (713.7 vs. 546.1 ng/dL), in Group II than in Group I. More patients regularly exercised in Group II than in Group I (45.8% vs. 9.8%, p < 0.001). A multivariate logistic regression analysis revealed that exercise (B = 2.325, odds ratio = 10.231, p < 0.001) and TRT duration (B = 0.153, Exp(B) = 1.166, p < 0.001) were independent predictive factors of response maintenance. In men with TD who respond to TRT, longer treatment periods can improve the response durability after TRT cessation, regardless of the type of TRT. Additionally, regular exercise can increase the probability of maintaining the response after TRT cessation.

Association of high circulating testosterone with increased glycaemic variability in type 2 diabetes: A cross‐sectional study in China

Testosterone affects insulin resistance, but the effect of testosterone treatment on type 2 diabetes (T2D) remains controversial. We aimed to investigate the association between circulating total testosterone (TT) and glycaemic variability using continuous glucose monitoring (CGM) in patients with T2D. A total of 248 men with T2D were enrolled in the study. Clinical characteristics and plasma for glycated haemoglobin (HbA1c) and C-peptide assessment were collected. TT was measured using a chemiluminescent immunometric assay. All patients were subjected to a 3-day CGM before making adjustments for hypoglycaemic therapy. TT positively correlated with the standard deviation of mean blood glucose (SDBG) (P<0.05), especially in older patients. Linear regression analysis showed that SDBG was associated with HbA1c (β=0.354, P<0.001) and TT (β=0.164, P=0.008) after adjusting for age, duration of diabetes, body mass index, fasting/postprandial C-peptide, and use of different hypoglycaemic drugs. The cut-off value of TT for predicting glycaemic variability was 14.76mmol/L according to receiver operating characteristic (ROC) analysis. SDBG, the coefficient of variation, the incremental area under the curve of glucose (AUC)>10mmol/L, and AUC night were increased in the group with TT>14.76nmol/L (P<0.01 for all variables). Body mass index and fasting/postprandial C-peptide were lower in the group with TT>14.76nmol/L than in the group with TT≤14.76nmol/L (P<0.05). Circulating TT levels should be assessed in patients with T2D in addition to HbA1c for predicting glycaemic variability. More frequent blood glucose monitoring or CGM is suggested for patients with T2D and high testosterone levels. NCT03519529, ClinicalTrials.gov.

Effects of testosterone treatment on hypothalamic neuroplasticity in female-to-male transgender individuals

Diffusion-weighted imaging (DWI) is used to measure gray matter tissue density and white matter fiber organization/directionality. Recent studies show that DWI also allows for assessing neuroplastic adaptations in the human hypothalamus. To this end, we investigated a potential influence of testosterone replacement therapy on hypothalamic microstructure in female-to-male (FtM) transgender individuals. 25 FtMs were measured at baseline, 4 weeks, and 4 months past treatment start and compared to 25 female and male controls. Our results show androgenization-related reductions in mean diffusivity in the lateral hypothalamus. Significant reductions were observed unilaterally after 1 month and bilaterally after 4 months of testosterone treatment. Moreover, treatment induced increases in free androgen index and bioavailable testosterone were significantly associated with the magnitude of reductions in mean diffusivity. These findings imply microstructural plasticity and potentially related changes in neural activity by testosterone in the adult human hypothalamus and suggest that testosterone replacement therapy in FtMs changes hypothalamic microstructure towards male proportions.