Changes In Testosterone Levels Research Articles

(094) Safety and Efficacy of Enclomiphene Compared to Clomiphene for Hypogonadal Men

Abstract Introduction Clomiphene, and its trans isomer enclomiphene, have been used off-label in recent years for hypogonadal men seeking to maintain fertility. Both drugs have become increasingly widespread within andrology clinics; thus, understanding the comparative benefits and risks of these medications are crucial for optimizing treatment decisions and providing improved therapeutic options. Objective To investigate the longitudinal benefits and risks associated with enclomiphene compared to clomiphene to provide valuable insights for clinicians when making treatment decisions in the management of hypogonadism and male fertility preservation. Methods We retrospectively studied patients who had been prescribed clomiphene, and later enclomiphene, at a university hospital within the observation range of 1/1/2021-12/31/2022, encompassing 66 patients. All included patients were prescribed clomiphene prior to switching to enclomiphene. Baseline laboratory values for each patient prior to being prescribed clomiphene were documented, followed by subsequent values for each of these variables in the most recent visit prior to stopping clomiphene as well as any noted adverse effects experienced during this time. Laboratory values and adverse effects were noted for the same patients in their most recent visit while taking enclomiphene. Adverse events were defined by 1) depressive thoughts; 2) weak muscle strength; 3) gynecomastia; 4) mood changes; or 5) agitation as well as changes in estradiol and hematocrit laboratory values. Two-tailed T-Tests were employed using SPSS to analyze the longitudinal impacts of clomiphene and enclomiphene on serum hormone values. Results In our cohort, men on clomiphene experienced any adverse events 18.18% of the time, whereas men on enclomiphene experienced any adverse events 3.45% of the time. From our data, men on enclomiphene had statistically lower rates of documented adverse events than the same men on clomiphene, indicating no increased risk on the newer drug; neither treatment yielded any serious adverse events. In looking specifically at hormone-related adverse events, estradiol increased significantly on clomiphene but not on enclomiphene (17.25 versus -0.29 pg/mL; t=4.271, p=.00005). However, there was no difference in change in hematocrit between the two medications (0.10% versus 0.79% increase; t=-1.103, p=.314). On average, testosterone increased 149.33 ng/dL from their baseline scores while on clomiphene and increased 108.55 ng/dL from their clomiphene values while on enclomiphene. When comparing the improvement of testosterone values attributed to clomiphene versus enclomiphene, the change of testosterone levels over time attributed to either medication are not statistically different (t-value = .883; p-value = .379). Lastly, men stayed on clomiphene for an average of 32.92 months before switching to enclomiphene. Conclusions Our findings show that enclomiphene provides the same magnitude of improvement in testosterone but through safer means, as noted by its lower rate of documented adverse events. These findings support the use of enclomiphene as a comparable treatment option for hypogonadal men while minimizing the risk of adverse effects. Further research and larger studies are warranted to validate these conclusions and explore additional long-term effects of enclomiphene. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Larry Lipshultz: AbbVie (Consultant) American Medical Systems/Boston Scientific (Speaker) Augmenta LLC (Stockholder) Aytu BioScience (Consultant) Contraline, Inc. (Consultant) Endo Pharmaceuticals (Consultant/Speaker) Inherent Biosciences (Advisor) Lipocine (Consultant); Mohit Khera: Consultant- AbbVie, Halozyme, Clarus, Metuchen, Acerus, Boston Scientific, Coloplast, Endo.

Bilateral Subcapsular Orchidectomy as Surgical Castration: A Reasonable Aesthetic Alternative to Bilateral Total Orchidectomy in Patients with Metastatic Hormone-sensitive Prostate Cancer

Background: The study highlights the historical significance of bilateral orchidectomy as the traditional 'gold standard' for surgical androgen deprivation in treating advanced prostate cancer. The study presented aims to compare total orchidectomy and subcapsular orchidectomy, considering factors such as androgen ablation, disease progression control, and patient satisfaction. Objective: This study aims to compare the effectiveness and patient satisfaction of bilateral subcapsular orchidectomy and bilateral total orchidectomy treatment in managing hormone-sensitive metastatic prostate cancer. Methods and materials: In this prospective study of 18 months at North East Medical College Hospital, 40 participants with Metastatic Carcinoma of Prostate underwent bilateral orchidectomy, among them 20 subcapsular and 20 total orchidectomy. The research focused on evaluating the impact of these treatments on serum testosterone levels, serum PSA levels, employing as outpatient procedures and a 3-month follow-up, utilizing a satisfaction scoring scale. Data, including age, Gleason Grade Group, PSA, and testosterone levels at diagnosis & at 3-month follow-up were recorded and analyzed using IBM SPSS-21 software. Result: The study compared Bilateral Subcapsular Orchidectomy and Bilateral Simple Orchidectomy for Hormone-Sensitive Metastatic Carcinoma of Prostate in 40 patients. The highest frequency was in the 71-75 age group (30%), with a mean age of 66.67 ± 2.21 years. Gleason grade group 3 dominated (40%), followed by 2 (25%). Pre-operative PSA levels were 31.14±1.27 ng/ml for Subcapsular and 35.21±1.70 ng/ml for Total Orchidectomy, decreasing post-operatively to 8.25±0.41 ng/ml and 7.32±0.80 ng/ml, respectively. Pre-operative testosterone levels were 513.21±3.01 ng/dl for Subcapsular and 498.40±2.10 ng/dl for Total Orchidectomy, decreasing post-operatively to 21.14±2.84 ng/dl and 16.90±1.08 ng/dl, respectively, with non-significant p-values. Surgery related Satisfaction scores in the Follow-Up phase were significantly higher for Subcapsular Orchidectomy, 2.91±0.31 comparing with Total Orchidectomy, 2.05±0.45. The results emphasize better patient satisfaction after subcapsular orchidectomy, while maintaining similar cancer control in the form of PSA and testosterone level changes. Conclusion: In conclusion, our study advocates for the reconsideration of bilateral subcapsular orchidectomy as a preferred method for surgical androgen ablation in metastatic prostatic carcinoma, offering comparable efficacy to traditional total orchidectomy approach while prioritizing patient satisfaction and psychological well-being. This suggests a potential paradigm shift in the landscape of cost-effective androgen deprivation therapy within the urological field.

Role of sex steroid hormone on hand grip strength and cognitive function in the elderly

The aging process is associated with changes in hormone levels. There is a noticeable change in estrogen levels in women, while in men, there is a change in testosterone levels. In the elderly, as a result of the aging process, changes in these hormone levels affect handgrip strength, and cognitive function. In both women and men, the function of several organs is influenced by sex steroid hormones, namely Oestrogen and androgens. There are two theories of steroid action mechanism on target cells, namely steroid hormone action mechanism genomically and non-genomically. The function and action mechanism of steroid hormone is important because it is the basis of the hormonal aspect for muscle mass, handgrip strength, and cognitive function. Due to the aging process, hormonal changes in the elderly are different compared to the previous period. This has consequences for changes in metabolic processes that affect the body’s condition, including changes in the composition of bones, muscles, and other tissues, such as the brain. In the aging process, it is important to pay attention to nutritional factors because they contribute to hormone levels that help maintain muscle mass, body mass index, hand grip strength, and cognitive function. In the brain, the sex steroid hormone has activating and organizational effects mediated by intracellular or transmembrane G-protein-coupled receptors. Articles published in English in the last 9 years (from 2014 to 2023) were retrieved from Science Direct, PubMed, Springer link, Oxford and Nature using relevant searching terms. The fact that testosterone bioavailability is predominated in the brain in relation to its activity and significant positive association with processing speed, sustained attention, and working memory in older men. To obtain a better quality of life for the elderly, nutritional factors must be considered to maintain optimal sex steroid hormone levels, hand grip strength, and cognitive function.

OR25-01 Longitudinal Changes in the Hypothalamic-Pituitary-Testicular (HPT) Axis in Men with Longevity

Abstract Disclosure: D. He: None. T. Gao: None. N. Barzilai: None. S. Milman: None. S. Aleksic: None. Background: Aging in men is associated with a reduction in testosterone (T) levels. In men aged 50 - 80, the decline in T mainly occurs due to hypothalamic-pituitary dysfunction, which results from unhealthy aging characterized by obesity and metabolic disorders. The changes in the HPT axis in men with longevity are less understood. Our recent cross-sectional study in men aged 90 and older showed high prevalence of testicular dysfunction which was not associated with metabolic health. We now explore the longitudinal changes in the HPT axis in men with longevity to better understand their relationship with metabolic health and survival. Methods: In an observational study of community-dwelling Ashkenazi Jewish men (n = 68, mean age (SD) at baseline sample 84 ± 4 years), levels of total T (TT, LC/MS), LH, and SHBG were measured in longitudinal serum samples (a median of 3 measures per subject, age at final sample 89 ± 3 years). Men were followed for survival after the final sample. Free T (FT) was calculated per Vermeulen et al. Men treated with T or GnRH agonists were excluded. Metabolic measures included BMI, A1c, and serum lipids. Individual longitudinal trajectories of TT, FT, LH, and SHBG were estimated with linear regression. Biochemical gonadal phenotypes were determined based on the levels of TT and LH. Results: Baseline and final levels of TT, FT, LH, and SHBG were, respectively: 417 ± 173 and 346 ± 187 ng/dL (TT), 6.0 ± 2.4 and 4.7 ± 2.5 ng/dL (FT), 8.0 [5.1, 14.4] and 10.0 [5.9, 20.4] mIU/mL (LH), and 58 ± 20 and 63 ± 23 nmol/L (SHBG), with average change rate/year of −17 ± 47 ng/dL (TT), −0.3 ± 0.5 ng/dL (FT), 0.7 ± 2.2 mIU/mL (LH) and 0.9 ± 4.1 nmol/L (SHBG). At baseline, the most prevalent biochemical gonadal phenotype was eugonadism (54%), followed by compensated testicular dysfunction (24%), testicular dysfunction (10%), and hypothalamic-pituitary dysfunction (12%), while respective prevalence rates at the final sample were 40%, 24%, 29%, and 7%. Baseline TT (p=0.002), age (p=0.02), and history of cancer (p=0.01) predicted more negative trajectory, while the history of cardiovascular disease (p=0.02) predicted more positive trajectory of TT. Neither TT, FT, LH nor SHBG trajectories were significant predictors of final BMI, A1c, or serum lipid levels. Positive TT trajectory was associated with shorter survival, after adjustment for SHBG, age, and comorbidities (HR 6.61 [1.46, 29.8], p=0.01). Conclusions: This is one of the first longitudinal studies of the HPT axis in community-dwelling men with longevity. As men survive into the late 80s, they increasingly develop testicular dysfunction while hypothalamic-pituitary dysfunction is rare. Changes in testosterone levels do not seem to predict metabolic dysfunction; however, an increase in total testosterone with aging may be associated with reduced survival. These findings need to be explored further in larger and ethnically diverse cohorts. Presentation Date: Saturday, June 17, 2023

SAT397 A Low Dose Cyproterone Acetate In Feminizing Hormone Treatment

Abstract Disclosure: S. Korpaisarn: None. J. Arunakul: None. K. Chaisuksombat: None. T. Rattananukrom: None. Background: A feminizing hormone therapy (FHT) for transgender women (TW) who have not undergone gonadectomy consists of estrogens and antiandrogens. Cyproterone acetate (CPA) is the most common antiandrogen used in Thailand. A standard dose of CPA is 25-50 mg/day. Recent data showed that a low-dose CPA might be effective in testosterone suppression. However, the result was limited due to the small number of subjects. Our recent survey showed that CPA 12.5 mg/day was commonly used among Thai TW. This study aimed to evaluate the effectiveness of CPA 12.5 mg/day in testosterone suppression. Methods: The retrospective cohort chart review was done on all TW receiving FHT in a transgender clinic at Ramathibodi Hospital between January 2014-July 2022. Among the TW who initiated FHT during the study period, the effectiveness and safety of CPA 12.5 mg/day were compared with the standard dose of CPA. Only TW with information at 3-month follow-up were analyzed for a median time of achieving the T level at the goal (<50 ng/dL) using a Cox regression analysis and a proportion of TW achieving T level at goal at 3 months using risk ratio regression model. All TW who initiated CPA were analyzed for changes in laboratory measurements using a generalized estimating equation (GEE). Results: A total of 89 transwomen were initially reviewed. Forty-one TW initiated CPA, and 37 TW had information at the 3-month follow-up visit. Among the latter, 22 TW (59.5%) started with CPA 12.5 mg. The median age of FHT initiation were 19 years (IQR 15-23) in CPA 12.5 mg group and 20 years (IQR 17-27) in the standard CPA dose group (p-value=0.504). Median follow-up time was 7.5 months (IQR 3-12) and 9 months (IQR 6-12), respectively (p-value=0.402). Baseline T levels were not different, with the median level at 518 ng/dL (IQR 173-787) in CPA 12.5 mg and 752 ng/dL (IQR 56-957) in control (p-value =0.653). In terms of effectiveness, the median time when T levels were suppressed at goal (<50 ng/dL) was 3 months in both groups. The proportion of TW who achieved targeted testosterone level within 3 months was 72.7% in CPA 12.5 mg and 86.7% in control with the risk ratio (RR) of 0.84 (95%CI 0.60-1.17, p-value= 0.295) for univariable analysis. The multivariable analysis showed an adjusted RR of 0.85 (95% CI 0.46-1.57, p-value=0.606). The multivariable GEE showed no difference between testosterone level changes. Only the LDL levels was significantly lower in the CPA 12.5 mg dose group with the difference of -13.72 mg/dL (95%CI (-25.86) – (-1.58), p-value=0.027). Other laboratories were not different among the 2 groups. There was no report of cardiovascular disease or new-onset depression in both groups.Conclusion: A CPA of 12.5 mg/day is effective in testosterone suppression as the standard dose of CPA in a FHT for TW with a comparable safety profile. This low-dose CPA regimen could be used as a FHT since it has a 50% cost reduction with equivalent effectiveness. Presentation: Saturday, June 17, 2023

Impact of Prostate Cancer Treatment with Low Dose Rate Brachytherapy on Testosterone: A Retrospective Analysis

Decrease in serum testosterone counts have been reported in the literature following external beam radiotherapy (EBRT), with a suggested association to low dose irradiation of the testes occurring with historical and modern external techniques. Low dose rate (LDR) brachytherapy has been described as exposing the testes to between 2 and 19 cGy compared with 196-220 cGy with EBRT. This decrease in excess dose is hypothesized to spare post-treatment testosterone decrease and subsequent change in patient-perceived quality of life. Here, we retrospectively evaluate LDR-treated prostate cancer patient testosterone change in a single-institution patient cohort. Patients with prostate cancer who had previously received LDR brachytherapy were identified, and patients with prior baseline total testosterone lab values as well as a lab value within one year post-treatment were identified. Patients receiving concurrent androgen deprivation therapy or EBRT were excluded. The closest baseline values prior to and after LDR treatment were used for before/after comparison. Samples were compared using the paired t-test. A total of 1,463 patients receiving LDR were identified with data available for analysis between 1998 and 2023; of these, 139 patients met the above criteria for analysis. Mean age was 66 (median 67; range: 47 - 79). 5 patients received 110 Gy, 2 received 120 Gy, and the remainder 145 Gy, all conducted with I-125. Total mCi delivered ranged from 20.3 mCi to 56.7 mCi (median 37.6 mCi). Approximately 57% were GS6, 42% G7, and < 1% G8. Approximately 80% of patients had T1c disease, with 19% T2 and < 1% T3a. All patients were cN0M0. Mean pre- and post-treatment testosterone were 385.5 ng/dL and 382.9 (SD: 170.9, 150.9; mean difference 2.65 [95% CI: -15.6, 20.9]), respectively, with no statistical change noted (p = 0.774). Testosterone levels have been reported to drop following definitive EBRT owing to excess dose delivery to the testes. On review of our institutional experience in definitive LDR brachytherapy for patients treated without ADT administration, no change in testosterone levels were noted.

Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal death

We have recently demonstrated a causal link between loss of gonadotropin-releasing hormone (GnRH), the master molecule regulating reproduction, and cognitive deficits during pathological aging, including Down syndrome and Alzheimer's disease. Olfactory and cognitive alterations, which persist in some COVID-19 patients, and long-term hypotestosteronaemia in SARS-CoV-2-infected men are also reminiscent of the consequences of deficient GnRH, suggesting that GnRH system neuroinvasion could underlie certain post-COVID symptoms and thus lead to accelerated or exacerbated cognitive decline. We explored the hormonal profile of COVID-19 patients and targets of SARS-CoV-2 infection in post-mortem patient brains and human fetal tissue. We found that persistent hypotestosteronaemia in some men could indeed be of hypothalamic origin, favouring post-COVID cognitive or neurological symptoms, and that changes in testosterone levels and body weight over time were inversely correlated. Infection of olfactory sensory neurons and multifunctional hypothalamic glia called tanycytes highlighted at least two viable neuroinvasion routes. Furthermore, GnRH neurons themselves were dying in all patient brains studied, dramatically reducing GnRH expression. Human fetal olfactory and vomeronasal epithelia, from which GnRH neurons arise, and fetal GnRH neurons also appeared susceptible to infection. Putative GnRH neuron and tanycyte dysfunction following SARS-CoV-2 neuroinvasion could be responsible for serious reproductive, metabolic, and mental health consequences in long-COVID and lead to an increased risk of neurodevelopmental and neurodegenerative pathologies over time in all age groups. European Research Council (ERC) grant agreements No 810331, No 725149, No 804236, the European Union Horizon 2020 research and innovation program No 847941, the Fondation pour la Recherche Médicale (FRM) and the Agence Nationale de la Recherche en Santé (ANRS) No ECTZ200878 Long Covid 2021 ANRS0167 SIGNAL, Agence Nationale de la recherche (ANR) grant agreements No ANR-19-CE16-0021-02, No ANR-11-LABEX-0009, No. ANR-10-LABEX-0046, No. ANR-16-IDEX-0004, Inserm Cross-Cutting Scientific Program HuDeCA, the CHU Lille Bonus H, the UK Medical Research Council (MRC) and National Institute of Health and care Research (NIHR).

Pioglitazone ameliorates cisplatin-induced testicular toxicity by attenuating oxidative stress and inflammation via TLR4/MyD88/NF-κB signaling pathway

BackgroundCisplatin (CIS) is a chemotherapeutic agent widely used to cure several cancers. It exerts detrimental cellular effects that restrain its clinical application as an antineoplastic agent, as testicular damage. Pioglitazone (PIO), a peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist, is used to treat type-2 diabetes mellitus. PIO has been reported to exert anti-inflammatory and antioxidant effects in different tissues. The present study aimed to investigate the effect of PIO in a rat model of cisplatin-induced testicular toxicity and address the possible role of the Toll-like receptors (TLR4) / myeloid differentiation factor 88 (MyD88) / nuclear factor-kappa B (NF-kB) signal pathway. MethodsRats received a single dose of cisplatin (7 mg/kg, IP) on the first day and PIO (10 mg/kg, P.O.) for 7 days. At the end of the treatment period, rats were killed. Testicular weights, histopathological alterations, and serum testosterone levels were determined. Moreover, tissue samples were collected for the estimation of oxidative stress parameters, inflammatory markers, and the determination of TLR4 /MyD88/NF-kB signaling. ResultsConcurrent PIO administration with CIS markedly improved testicular weights, histopathological alteration, and serum testosterone level changes. Moreover, Concurrent PIO administration abrogated oxidative stress status and inflammatory markers caused by CIS administration. Furthermore, PIO inhibited the expression levels of TLR4, MyD88, and NF-κBp65, proteins that are activated by CIS administration. Conclusion: These findings suggested that PIO can protect against cisplatin-induced testicular toxicity in rats through inhibition of the TLR4 /MyD88/NF-kB signal pathway.

The male patient with obesity undergoing metabolic and bariatric surgery: changes in testosterone levels correlate with weight loss after one-anastomosis gastric bypass and Roux-en-Y gastric bypass.

Male obesity secondary hypogonadism (MOSH) is a common disease among men with obesity and can be associated with metabolic syndrome and a variety of metabolic problems ultimately leading to androgen deficiency. Metabolic and bariatric surgery is a well-established treatment option associated with significant weight loss and reduction in metabolic co-morbidities. To evaluate the impact of surgery on plasma levels of sexual hormones and their effect on weight loss comparing 2 surgical methods (one-anastomosis gastric bypass [OAGB] and Roux-en-Y gastric bypass [RYGB]) in male patients with obesity. University hospital, Austria. Patients undergoing OAGB and RYGB between 2012 and 2017 were analyzed retrospectively. Follow-up in this study was up to 24 months. Systemic levels of sexual hormones (luteinizing hormone [LH]), follicle stimulating hormone [FSH], total testosterone [TT], sexual hormone binding globin [SHBG], 17 beta-estradiol [17bE], androstenedione [AS]) were retrieved at each visit. A linear mixed model was used to assess the correlation between changes in testosterone levels and percent excess weight loss (%EWL). In 30.8% of all patients, MOSH was present preoperatively. A significant increase of TT was observed postoperatively that led to a complete resolution of hypogonadism within the period observed. Bioavailable testosterone (bTT) and FSH levels significantly increased each month of follow-up after surgery (all P < .01). Levels of 17bE did not change significantly after surgery. The overall change of TT, comparing preoperative and 1-year postoperative TT levels (ΔTT), significantly correlated with %EWL. Changes in TT levels were not affected by the choice of surgical method. Serum plasma testosterone levels rise significantly after metabolic and bariatric surgery in male patients. The change of testosterone levels seems to play a role in continued weight loss after surgery. This is true irrespective of the surgical method used.

(371) Testosterone Levels after Lung Transplant: An Analysis of the TriNetX Research Network

Abstract Introduction Men with end stage organ dysfunction or failure are more likely to have low testosterone. In the case of men with heart and kidney failure, improvement in testosterone levels are seen after successful transplantation. Limited data exists regarding the natural course of serum testosterone after lung transplant. Objective To report incidence of low testosterone in men prior to lung transplant and to determine changes in testosterone levels after transplantation. 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 transplant and testosterone levels recorded before and after transplantation. All men who had a recorded prescription for testosterone therapy were excluded. For all patients, we collected clinical information including demographics, comorbidities, laboratory findings, and medication use. Patients were stratified by testosterone levels and grouped into those who had low serum testosterone versus those with normal levels, with a cut-off point of 300 ng/dL. Patient characteristics were compared using descriptive statistics. Propensity score matching was performed between the two groups to normalize differences in pre-operative characteristics. Mean serum testosterone levels before and after transplantation was compared using a paired T test to determine change in serum testosterone levels after successful transplantation. Results A total of 37 men were identified with history of lung transplant, and testosterone levels recorded before and after transplant. Average serum testosterone level in the year prior to lung transplantation was 301.57 +/− 163.25. After transplantation, average serum testosterone was 332.37 +/− 200.92, for a mean difference of 30.80 (p = 0.4815). Prior to transplantation, 24 (65%) men met criteria for low serum testosterone. After transplantation 17 (46%) men demonstrated serum testosterone less than 300 ng/dl. Among men with low serum testosterone, average testosterone levels in the year prior to lung transplantation was 203.29 +/− 66.57, and was 332.37 +/− 200.92 after transplantation (p = 0.0057). Conclusions Among men with low serum testosterone receiving lung transplant, transplantation was associated with rescue of low testosterone levels. Further research incorporating a larger cohort is required to determine which patients recover endocrine function after lung transplant and whether etiology of chronic lung disease results in different outcomes after transplantation with regards to serum androgen level and function. Disclosure No

(523) Changes in Testosterone Levels in Patients with Erectile Function

Abstract Introduction Erectile dysfunction (ED) is a disease that affects approximately 20% of adult men. Androgen deficiency is one of the organic etiologies described for this sexual dysfunction. Objective To estimate the frequency of alterations in the sex hormone binding globuline (SHBG), total testosterone (TT), calculated free (FT) and bioavailable testosterone (BT) in Spanish men with a clinical diagnosis of erectile dysfunction in Madrid, Spain. Patients and methods Cross-sectional study. Men over 18 years of age with a clinical diagnosis of erectile dysfunction and a score in the international index of erectile function (IIEF-EF) &amp;lt; 26 were included. Serum levels of SHBG, TT, TL and TB were evaluated and the proportion of men was estimated. with hormonal alterations defined as: a) serum levels &amp;lt;2.49 ng/mL of TT in men under 50 years and &amp;lt;1.93 ng/mL in men of 50 years or older; b) TL for calculated value &amp;lt;2% of total testosterone; c) TB for calculated value &amp;lt;40% of total testosterone; d) serum SHBG levels &amp;gt;54.1 nmol/L in men younger than 50 years and &amp;gt;76.7 nmol/L in men 50 years and older. Results 30 subjects participated in the study. The mean age was 50.6 years (+/− 13.2), the median scores for IIEF-EF, Erection Hardness Score (EHS) and Aging Male Symptoms Score (AMS) were 15 (range 1-24), 2 (range 1-3) and 29.5 (range 11-62) respectively. 6 patients (20%) had severe erectile dysfunction, 13 (43.3%) moderate, 8 (26.7%) mild to moderate, and 3 (10%) mild erectile dysfunction. The mean TT was 4.94 ng/mL (+/− 1.91), FT 1.94% (+/− 0.605), BT 45.6% (+/− 14.2), and SHBG 33.3 nmol/L ( +/− 14.5). Only 6.7% of the patients (n=2) presented alterations of the TT, while in 60% (n=18) an alteration of the FT was found, in 36.7% (n=11) an alteration of the BT and in 3.3% (n=1) SHBG alterations, alterations being more frequent in men with moderate ED. Conclusions Our study found alterations in total testosterone in a small percentage of patients with ED, however the alterations in Free Testosterone calculated turned out to be much higher. This study suggests that future research should be carried out to identify a relationship between changes in calculated free testosterone levels and the presence of erectile dysfunction. Disclosure No

Testosterone levels mediate the dynamics of motor oscillatory coding and behavior in developing youth

Recent investigations have studied the development of motor-related oscillatory responses to delineate maturational changes from childhood to young adulthood. While these studies included youth during the pubertal transition period, none have probed the impact of testosterone levels on motor cortical dynamics and performance. We collected salivary testosterone samples and recorded magnetoencephalography during a complex motor sequencing task in 58 youth aged 9–15 years old. The relationships between testosterone, age, task behavior, and beta (15–23 Hz) oscillatory dynamics were examined using multiple mediation modeling. We found that testosterone mediated the effect of age on movement-related beta activity. We also found that the effect of age on movement duration was mediated by testosterone and reaction time. Interestingly, the relationships between testosterone and motor performance were not mediated by beta activity in the left primary motor cortex, which may indicate the importance of higher-order motor regions. Overall, our results suggest that testosterone has unique associations with neural and behavioral indices of complex motor performance, beyond those already characterized in the literature. These findings are the first to link developmental changes in testosterone levels to maturation of beta oscillatory dynamics serving complex motor planning and execution, and specific measures of motor performance.

MP79-16 ANALYSIS OF THE EFFECT OF TESTOSTERONE REPLACEMENT ON BODY COMPOSITION, PHYSICAL FITNESS AND THE CORRELATION WITH HYPOGONADAL SYMPTOMS IN THE TESTOSTERONE DEFICIENCY

You have accessJournal of UrologyCME1 Apr 2023MP79-16 ANALYSIS OF THE EFFECT OF TESTOSTERONE REPLACEMENT ON BODY COMPOSITION, PHYSICAL FITNESS AND THE CORRELATION WITH HYPOGONADAL SYMPTOMS IN THE TESTOSTERONE DEFICIENCY Tae Yong Park, Dong Su Kim, Jeong Kyun Yeo, and Min Gu Park Tae Yong ParkTae Yong Park More articles by this author , Dong Su KimDong Su Kim More articles by this author , Jeong Kyun YeoJeong Kyun Yeo More articles by this author , and Min Gu ParkMin Gu Park More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003356.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: This study aimed to investigate how testosterone replacement therapy (TRT) change body composition and physical fitness, and which those changes correlate with serum testosterone level and hypogonadal symptoms. METHODS: Seventy patients with testosterone deficiency (TD) were divided into group I (n: 23) and group II (n :47). Only group II was given testosterone enanthate intramuscularly for 6 months. Both groups were investigated following items at the beginning and end of the study: Baseline demographics and serologic test; questionnaires of aging male symptom (AMS) scale and international prostate symptom score (IPSS); BMI, waist circumference, body composition; and physical fitness. Body composition was assessed by bioelectrical impedance analysis. Seven types of basic exercise tests were used to measure physical fitness. RESULTS: No significant difference was observed in baseline measurements between the two groups before treatment. After 6 months, group I showed no significant change in all measurements. Group II showed significant improvement in IPSS and AMS scales. Hematocrit, and prostate specific antigen slightly increased, while total cholesterol significantly decreased after treatment. As to body composition parameters, TRT significantly decreased body fat mass, visceral fat mass and waist circumference. Skeletal muscle mass was significantly increased by TRT although upper body muscle appeared to be more responsive. Most parameters of physical fitness resulted in improvement except for flexibility and endurance. The decrease of waist circumference was significantly correlated with serum testosterone level changes. AMS scale improvement was correlated with the changes of IPSS, cardiorespiratory fitness and agility. CONCLUSIONS: TRT improved hypogonadal and lower urinary tract symptoms. TRT also resulted in overall improvement in metabolic syndrome components, body composition and physical fitness. Testosterone increment and hypogonadal symptom improvement are correlated with waist circumference, cardiorespiratory fitness, and agility, respectively. Combined adjunctive exercise program that improve those parameters, might maximize the effect of TRT. Source of Funding: No conflict of interests © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1147 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tae Yong Park More articles by this author Dong Su Kim More articles by this author Jeong Kyun Yeo More articles by this author Min Gu Park More articles by this author Expand All Advertisement PDF downloadLoading ...

Testosterone and psychophysiological aspects of personality in sports

Recent studies have shown that testosterone, in addition to its well-known anabolic effect, has a relationship with a number of psychological and psychophysiological characteristics. The purpose of the study is to generalize information about the relationship between psychophysiological aspects of personality and the level of testosterone in athletes. Methodology: analysis and generalization of data of modern scientific and methodological literature from scientometric bases and resources of Google Scholar, PubMed, Web of Science, Scopus. Research results and their discussion. Research by scientists has shown that high concentrations of basal testosterone are associated with a number of character traits and behavior. Competition, rivalry, competitions affect changes in testosterone levels and cause behavior modification. Scientists express the opinion that the basal level of testosterone before competitions can be an individual biopsychophysiological marker that interacts in the regulation of the hypothalamic-pituitary hormonal axis (HPA) under stress conditions and reflects the degree of dominance, the level of power motivation and obtaining a winning status. In separate studies, the positive effect of testosterone on cognitive functions and visual-spatial abilities was established, the relationship of this hormone with the propensity to take risks, reducing the feeling of fear, increasing attention in the face of threat, which can contribute to the combat readiness of the athlete and the desire to win, was established. Scientists have observed a connection between testosterone and such personality traits as fearless dominance, impulsiveness. Conclusions. According to literary sources, the level of testosterone is associated with a number of psychophysiological and psychological characteristics of an athlete, namely, it increases aggression, the motivation to dominate, which contributes to the motivation to achieve success in sports. High endogenous concentrations of testosterone can provide both a physiological and a psychological advantage in sports. The study of hormonal and psychophysiological parameters can provide an opportunity for a more complete assessment of human stress reactions in the conditions of sports competition.

8Spheres conformal microspheres as embolic agents for symptomatic uterine leiomyoma therapy in uterine artery embolization (UAE): A prospective clinical trial.

To evaluate the treatment efficacy of uterine artery embolization (UAE) using 8Spheres conformal microspheres for symptomatic uterine leiomyoma. In this prospective observational study, 15 patients were enrolled and underwent UAE by 2 experienced interventionalists from September 1, 2018, to September 1, 2019. All patients underwent menstrual bleeding scores, the symptom severity domain of the Uterine Fibroid Symptom and Quality of Life questionnaire scores (with lower scores indicating mild symptoms), pelvic contrast-enhanced magnetic resonance imaging, ovarian reserve tests (estradiol, prolactin, testosterone, follicle-stimulating, luteinizing, and progesterone), and other appropriate preoperative examinations within 1 week before UAE. During follow-up, menstrual bleeding scores and the symptom severity domain of the Uterine Fibroid Symptom and Quality of Life questionnaire scores were recorded at 1, 3, 6, and 12 months after UAE to assess the efficacy of symptomatic uterine leiomyoma. Pelvic contrast-enhanced magnetic resonance imaging was performed 6 months after the interventional therapy. Biomarkers of ovarian reserve function were reviewed at 6 and 12 months after treatment. All 15 patients successfully underwent UAE, without severe adverse effects. Six patients experienced abdominal pain, nausea, or vomiting, all of which improved significantly after symptomatic treatment. The menstrual bleeding scores declined from baseline (350.2 ± 61.9 mL) to (131.8 ± 42.7 mL), (140.3 ± 42.4 mL), (68.0 ± 22.8 mL), and (64.43 ± 17.0 mL) at 1, 3, 6, and 12 months, respectively. The symptom severity domain scores at 1, 3, 6, and 12 months postoperatively were significantly lower and statistically significant compared to the preoperative scores. The uterus and dominant leiomyoma volumes decreased from baseline (340.0 ± 35.8 cm3), (100.6 ± 24.3 cm3) to (266.6 ± 30.9 cm3), (56.1 ± 17.3 cm3) at 6 months after UAE, respectively. Moreover, the ratio of leiomyoma volumes and uterus decreased from (27.4 ± 4.5%) to (18.7 ± 3.9%). At the same time, there was no significant effect on changes in the biomarkers of ovarian reserve levels. Only the changes in testosterone levels before and after UAE were statistically significant (P < .05). 8Spheres conformal microspheres are ideal embolic agents for UAE therapy. This study showed that 8Spheres conformal microsphere embolization for symptomatic uterine leiomyoma could effectively relieve heavy menstrual bleeding, improve the symptom severity of patients, reduce the volume of leiomyoma, and have no significant effect on ovarian reserve function.

A phase 2 randomized open-label study of oral darolutamide monotherapy vs. androgen deprivation therapy in men with hormone-naive prostate cancer (EORTC-GUCG 1532).

160 Background: Darolutamide is androgen-receptor (AR) inhibitor with low blood–brain barrier penetration and limited potential for clinically relevant drug–drug interactions. Darolutamide has been shown to increase overall survival in combination with androgen deprivation therapy (ADT) in patients with newly diagnosed metastatic hormone sensitive prostate cancer (PC) and, in combination with docetaxel, in men with non-metastatic castration resistant PC. This phase 2 study assessed the efficacy and safety of DARO as a monotherapy without ADT in patients with non-castrate testosterone (T) levels (≥230 ng/dL). Methods: This was a 24-wk, open-label, randomized study of patients with hormone-naïve, histologically confirmed prostate cancer (all stages, with a max of 4 metastatic lesions) requiring hormonal treatment, an ECOG PS score of 0, and a life expectancy &gt;1 y. All patients received DARO 600 mg bid or commercially available LHRH analogue. The primary endpoint is PSA response defined as a ≥ 80% decline at week 24 relative to baseline, in the DARO study arm. The ADT arm is used as an internal control. Secondary endpoints included changes in T levels, safety/tolerability, and quality of life. Results: Among 61 men enrolled, the median (range) age was 72 y (53-86y); 49.2% had metastases; 14.8% and 62.3% had undergone prostatectomy or radiotherapy before study entry. The median (range) of PSA at baseline was 8.9 ng/mL (2.2-333.8). In the DARO arm, the evaluable population with available PSA values at baseline and week 24 consisted of 21 patients. The PSA response rate (&gt;80% PSA decline at wk 24) was 100%, with a median (range) decrease of -99.6% (-94.3, -100) at wk 24 in the DARO arm. Serum T levels increased by a median (range) of 43.4% (5.7-144.0) at wk 24, compared with baseline. In the DARO arm, 45.2% of men reported drug-related AEs (mostly Grade 1 or 2). Most frequent treatment-emergent AEs included gynaecomastia (19.4%), fatigue (12.9%), and hot flush (12.9%). 3.1% of men experienced SAEs, none of which were drug related. HR-QoL measures and ADT arm results will be presented as internal reference. Conclusions: DARO monotherapy (600 mg bid) was associated with significant PSA response in nearly all men with hormone-naïve prostate cancer. Testosterone level changes and most common AEs (gynecomastica, fatigue and hot flush) were consistent with potent AR inhibition. Clinical trial information: NCT02972060 .

Correlation Analysis between Hypogonadal Symptoms and Changes in Body Composition and Physical Fitness after Testosterone Treatment in Men with Testosterone Deficiency.

This study analyzed changes in body composition and physical fitness in men with testosterone deficiency (TD) after testosterone treatment (TT) and examined the correlations of body composition and physical fitness with serum testosterone levels and hypogonadal symptoms. Seventy patients with TD were divided into control (group I, n=23) and experimental (group II, n=47) groups. Patients in the experimental group were administered intramuscular testosterone enanthate (250 mg) for six months. The aging males symptom scale (AMS) score, international prostate symptom score (IPSS), body mass index, waist circumference, and serum laboratory values were measured at baseline and at the end of the study. Bioelectrical impedance analysis was used to assess the patients' body composition. Seven types of basic exercise tests were used to evaluate the patients' physical fitness. After six months, there were no significant differences in group I, while group II had significantly improved IPSS and AMS scores; increased hemoglobin, hematocrit, prostate-specific antigen, and testosterone levels and skeletal muscle mass; and waist circumference, and body fat mass. All elements of the physical fitness test were significantly improved in group II, with the exceptions of flexibility and endurance. Decreased waist circumference was correlated with changes in testosterone levels in group II, and the IPSS, cardiorespiratory fitness, and agility were correlated with improved hypogonadal symptoms. TT improved the hypogonadal and lower urinary tract symptoms in patients with TD and improved body composition, physical fitness, and metabolic syndrome parameters. Increased testosterone and improved hypogonadal symptoms were correlated with a decrease in waist circumference and an improvement in cardiorespiratory fitness and agility. As such, when implementing TT, we should consider whether these areas may be improved, as this can help to predict the effect.

Probiotic and prebiotic supplementation ameliorates chronic restraint stress-induced male reproductive dysfunction.

Restraint stress (RS) can induce male reproductive deficits by activating the hypothalamic-pituitary-adrenal (HPA) axis and causing oxidative stress. Previous studies have shown that probiotics can alleviate neurological and metabolic disorders induced by stress. However, the effects of probiotics on RS-induced reproductive deficits have not been fully elucidated. This study aimed to investigate whether Lactobacillus rhamnosus NCDC-610 (Probiotic-1) and Lactobacillus fermentum NCDC-400 (Probiotic-2) with prebiotic (fructooligosaccharides (FOS)) could prevent RS-induced reproductive deficits. C57BL6/J mice were subjected to RS for four hours daily before oral administration of probiotics (4 × 109 CFU per mice) either separately or concurrently with FOS. The results showed that oral administration of Probiotic-1 and Probiotic-2 protected against RS-induced sperm deficits, including sperm count, motility, morphology, and histopathology of testes, and improved intestinal health. Furthermore, Probiotic-1 and Probiotic-2 prevented RS-induced changes in testosterone levels by up-regulating the expressions of steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage enzyme (P450scc), and 17β-hydroxysteroid dehydrogenase (17βHSD) in the testes. Additionally, Probiotic-1 and Probiotic-2 increased the activities of catalase and superoxide dismutase and reduced the fold change of interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-α), indicating a protective effect against RS-induced oxidative stress. Oral administration of Probiotic-1 and Probiotic-2, either separately or concurrently with FOS (probiotic dose of 4 × 109 CFU per mice and prebiotic 5% w/v), prevented RS-induced activation of the HPA axis and improved male fertility. These findings suggest that L. rhamnosus NCDC-610 and L. fermentum NCDC-400 are safe and effective probiotics for mitigating stress-induced male reproductive deficits.

Association of lipid accumulation products with testosterone deficiency in adult American men: A cross-sectional study.

Testosterone deficiency and changes in testosterone levels are important in men's health and may be associated with fat accumulation. In order to investigate the connection between testosterone and fat accumulation in adult males, we employed lipid accumulation product and compared it to triglyceride-glucose and Homeostasis Model Assessment of Insulin Resistance. An intersecting surface research of participators from 2013 to 2014 was carried out using National Health and Nutrition Examination Survey, in addition, participants from 2015 to 2016 were selected. Using multivariate adjusted logistic regression, the connection between lipid accumulation product, testosterone levels, and testosterone insufficiency was investigated, smoothed curve fitting was calculated to integrate non-linear relationships, and subgroup analysis was performed to identify sensitive populations. After removing all potential confounders, testosterone levels in 1651 subjects tended to decrease with increasing continuous variable lipid accumulation product (β = -0.49, 95% confidence interval [-0.77, -0.22], p = 0.0005) and adding the chance of testosterone deficiency (odds ratio = 1.01, 95% confidence interval [1.01, 1.01], p < 0.0001). In the lipid accumulation product quartile, testosterone levels decreased the most (β = -77.65, 95% confidence interval [-110.99, -44.31], p < 0.0001) and the risk of testosterone deficiency was highest (odds ratio = 2.76, 95% confidence interval [1.47, 5.20], p = 0.0016). The area under the curve values were 0.718 (95% confidence interval: 0.688-0.750) for lipid accumulation product, 0.723 (95% confidence interval: 0.689-0.756) for Homeostasis Model Assessment of Insulin Resistance, and 0.673 (95% confidence interval: 0.640-0.708) for triglyceride-glucose, with no statistical difference between lipid accumulation product and Homeostasis Model Assessment of Insulin Resistance comparisons. The cut-off value of lipid accumulation product ≥52.408 predicted testosterone deficiency with good sensitivity and specificity. Higher lipid accumulation product was linked to a higher incidence of testosterone loss and inadequate, especially in hypertensive and non-smoker. Lipid accumulation product is a better predictor of testosterone deficiency than triglyceride-glucose and does not differ significantly from the Homeostasis Model Assessment of Insulin Resistance phase.

The effect of Nateglinide and Octreotide on follicular morphology and free radical scavenging system in letrazole-induced rat model of PCOS.

To investigate the effects of octreotide and nateglinide on ovarian follicle count, ovarian tissue damage, biochemical parameters and free radical scavenging system in letrazole-induced rat model of PCOS. Forty-two female Sprague-Dawley rats were divided into six groups. Group 1 (Control Group): after localizing the ovaries and the uterine horns, the abdominal wall was closed without any surgical procedure. Group 2 (PCOS Group): PCOS was induced by administrating Letrozole orally for 21 successive days. At the end of 21 days, rats underwent ovarian biopsies. The experimental PCOS model was considered successful in the presence of atretic follicles without granulosa cell stratification. Group 3 (PCOS + Nateglinide Group): Nateglinide was administered by oral dropper for 30 days to the rats in which PCOS model was created. Group 4 (Nateglinid only Group): 30 days of NG was applied to the rats without PCOS. Group 5 (PCOS+Octreotide Group): 0.1 mg/kg/day Octreotide was given intraperitoneally for 4 weeks to the rats in which PCOS model was created. Group 6 (Octreotide only Group): animals without PCOS given 0.1 mg/kg/day Octreotide at the end of the treatment, bilateral oophorectomy was performed and blood samples were collected from all groups. Ovarian tissue was stained immunohistochemically with TLR-4 in addition to conventional staining. In addition to follicle classification, ovarian damage was graded. Serum insulin, FSH and LH, TNF-α, IL-6, SHBG, SOD, IGF-1, MDA and GSH levels were also measured. The cystic and degenerated follicle density of PCOS group was high compared with the other groups. Both cystic and degenerated follicles were significantly reduced in PCOS+NG and PCOS+OC groups compared to PCOS group. There was no difference between the groups in terms of serum LH, FSH and insulin levels (p>0.05). Serum testosterone level was significantly higher in the PCOS group compared to the other groups (p<0.01). Adding OC or NG to PCOS groups did not cause significant changes in testosterone levels. TNF-α and IL-6 levels were high in PCOS group (p<0.03). IGF-1 and MDA levels were higher in PCOS than in other groups (p<0.03, p<0.01 respectively). Adding OC or NG to the treatment normalized IGF-1 and MDA levels. Serum GSH levels were significantly lower in the PCOS group (p<0.05). Adding NG to the treatment increased GSH levels. Both NG and OCT reverses atretic and degenerate follicle damage due to PCOS through TLR-4, antioxidant and anti-inflammatory pathways.