Endogenous Testosterone Levels Research Articles

Clomiphene citrate and optional human chorionic gonadotropin for treating male hypogonadism arising from long-term anabolic-androgenic steroid use—A pilot study

IntroductionLong-term anabolic-androgenic steroid (AAS) use poses several health risks, including secondary hypogonadism. There is a knowledge gap on treatment targeting the hypothalamic-pituitary-gonadal (HPG) axis among men with anabolic steroid-induced hypogonadism (ASIH). This study aims to gain insights into the potential utility of endocrine therapy to restore endogenous testosterone levels and alleviate ASIH symptoms in AAS dependent men. MethodsIn this proof-of-concept, single-site, open longitudinal pilot study, AAS dependent men with continuous AAS use and a desire to permanently discontinue use, were given endocrine therapy. The treatment included 25 mg clomiphene citrate (CC) every second day for 16 weeks, transdermal testosterone daily during the first four weeks, and if indicated, human chorionic gonadotropin (hCG) injections for a maximum of eight weeks. Physical exams including blood collection and online questionnaires were completed every four and two weeks, respectively. ResultsTen participants, with median age 32 years (interquartile range 30–45), with mean ± standard deviation AAS use of 11 ± 4 years, completed the CC intervention. Seven participants received hCG as part of their treatment protocol. Mild adverse events included headaches, dizziness, and mood swings, and no serious adverse events occurred. During the intervention, there was a decrease in levels of hematocrit, hemoglobin and ALT (alanine aminotransferase), as well as an increase in serum FSH (follicle stimulating hormone), LH (luteinizing hormone) and SHBG (sex hormone binding globulin). Five of ten participants reached a total testosterone level within normal range (9–30 nmol/l). The HPG axis response varied greatly among participants, and was not aligned with the severity of ASIH related withdrawal symptoms. ConclusionsThe findings from this proof-of-concept study may guide future randomized controlled trials aiming to investigate potential endocrine therapeutic approaches to ASIH.

Effects of testosterone enanthate on aggression, risk-taking, competition, mood, and other cognitive domains during 28 days of severe energy deprivation

RationaleBehavioral effects of testosterone depend on dose, acute versus sustained formulation, duration of administration, personality, genetics, and endogenous levels of testosterone. There are also considerable differences between effects of endogenous and exogenous testosterone.ObjectivesThis study was the secondary behavioral arm of a registered clinical trial designed to determine if testosterone protects against loss of lean body mass and lower-body muscle function induced by a severe energy deficit typical of sustained military operations.MethodsBehavioral effects of repeated doses of testosterone on healthy young men whose testosterone was reduced by severe energy deficit were examined. This was a double-blind, placebo-controlled, between-group study. Effects of four weekly intramuscular injections of testosterone enanthate (200 mg/week, N = 24) or matching placebo (N = 26) were evaluated. Determination of sample size was based on changes in lean body mass. Tasks assessing aggression, risk-taking, competition, social cognition, vigilance, memory, executive function, and mood were repeatedly administered.ResultsDuring a period of artificially induced, low testosterone levels, consistent behavioral effects of administration of exogenous testosterone were not observed.ConclusionsExogeneous testosterone enanthate (200 mg/week) during severe energy restriction did not reliably alter the measures of cognition. Study limitations include the relatively small sample size compared to many studies of acute testosterone administration. The findings are specific to healthy males experiencing severe energy deficit and should not be generalized to effects of other doses, formulations, or acute administration of endogenous testosterone or studies conducted with larger samples using tests of cognitive function designed to detect specific effects of testosterone.

FRI441 Antiestrogens To Treat Hypogonadotropic Hypogonadism In Male Users Of Anabolic-androgenic Steroids - A Clinical Pilot Study

Abstract Disclosure: H.C. Henriksen: None. A.P. Jørgensen: None. A. Bjørnebekk: None. S.P. Neupane: None. I.A. Havnes: None. Background: Anabolic-androgenic steroids (AAS) used recreationally in supra-physiological doses is a growing public health concern. The use is associated with cardiovascular, metabolic and endocrine disturbances including AAS induced hypogonadism (ASIH). ASIH is a form of hypogonadotropic hypogonadism caused by AAS’ long-term negative feedback on the hypothalamic-pituitary-gonadal (HPG) axis, promoting fatigue, depression and sexual dysfunction. Aims: The primary objective of the study is to explore the safety and efficacy of clomiphene citrate (CC) in treating ASIH. Secondary aims are to detect AAS associated health risks and assess whether these risks are reversed 12 months after cessation. Methods: In this open longitudinal pilot study at Oslo University Hospital in Norway, men with AAS dependence, continuous use and a desire to quit are treated for 16 weeks with an antiestrogen (CC). The CC is given to stimulate endogenous secretion of gonadotropin-releasing hormone (GnRH), gonadotropins (luteinizing hormone (LH)) and testosterone by blocking the estrogenic negative feedback on the HPG-axis. Transdermal testosterone is administered daily during the first four weeks to prevent a sudden drop in androgen levels. If HPG response is subpar, human chorionic gonadotropin (hCG), a synthetic LH analog, is added. The participants are monitored every 4th week during intervention, and at follow-up at 6 and 12 months. Physical health is assessed through clinical examinations, blood and fat tissue sampling, cardiovascular examination, dual-energy x-ray absorptiometry, testicular ultrasound and semen analysis. Results: Preliminary results are available from 11 men that were eligible for endocrine intervention with median age of 33 (range 26-57) and median cumulative lifetime AAS use of 11 years (1-20). Cardiovascular findings were recurrent and included hypertension, myocardial hypertrophy, increased arterial stiffness, reduced flow-mediated dilation and lower carotid artery reactivity. Polycythemia, testicular atrophy and oligozoospermia were other common findings at inclusion. Intervention with CC showed varying HPG response: While some participants responded poorly to treatment, others developed normalized endogenous levels of gonadotropins and testosterone after only 4-8 weeks of therapy. No serious adverse events from CC use were reported. Among the few reported less severe adverse effects were headache, nausea and mood swings. Conclusion: Preliminary results of this ongoing study indicate that treatment with CC and hCG is safe and effective in treating ASIH from long-term continuous AAS use. Insufficient HPG response after 16 weeks of intervention might indicate persisting hypogonadotropic hypogonadism, but further monitoring is needed. Presentation: Friday, June 16, 2023

Where sports performance meets reproductive rights: hormonal contraception

Rational To discuss the use of hormonal contraception (HC) in elite women’s competitive sports from an anti-doping perspective because 1) it changes the natural female hormonal milieu; 2) is used to manipulate the menstrual cycle with performance enhancement intent; 3) even though lowering endogenous testosterone levels, some HCs contain testosterone-like androgenic compounds with potential performance-enhancing effects. Results A complex interaction between rapidly advancing sports-relevant biomedical scientific discoveries, societal changes concerning sex and gender, and a zero-tolerance anti-doping ideology, leads to contentious results, jeopardizing the premises defining and protecting contemporary elite sport in general and that of women in particular. Discussion and conclusions This is in part because of the two out of three criteria for inclusion on the World Anti-Doping Agency’s List of forbidden substances and methods: i) actual or potential for performance enhancement, ii) actual or potential for health risk, and iii) counter to the Spirit of Sport concept. These criteria would suffice for the inclusion of HC on the List, especially in their androgenic form. The fact that they are not is good for women’s reproductive rights but also illustrates the arbitrariness of the administration of WADA’s Prohibited List of substances and methods in elite sports.

Testosterone deficiency impairs cardiac interfibrillar mitochondrial function and myocardial contractility while inducing oxidative stress.

Clinical studies have shown that low levels of endogenous testosterone are associated with cardiovascular diseases. Considering the intimate connection between oxidative metabolism and myocardial contractility, we determined the effects of testosterone deficiency on the two spatially distinct subpopulations of cardiac mitochondria, subsarcolemmal (SSM) and interfibrillar (IFM). We assessed cardiac function and cardiac mitochondria structure of SSM and IFM after 12 weeks of testosterone deficiency in male Wistar rats. Results show that low testosterone reduced myocardial contractility. Orchidectomy increased total left ventricular mitochondrial protein in the SSM, but not in IFM. The membrane potential, size and internal complexity in the IFM after orchidectomy were higher compared to the SHAM group. However, the rate of oxidative phosphorylation with all substrates in the IFM after orchidectomy was lower compared to the SHAM group. Testosterone replacement restored these changes. In the testosterone-deficient SSM group, oxidative phosphorylation was decreased with palmitoyl-L-carnitine as substrate; however, the mitochondrial calcium retention capacity in IFM was increased. There was no difference in swelling of the mitochondria in either group. These changes in IFM were followed by a reduction in phosphorylated form of AMP-activated protein kinase (p-AMPK-α), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) translocation to mitochondria and decreased mitochondrial transcription factor A (TFAM). Testosterone deficiency increased NADPH oxidase (NOX), angiotensin converting enzyme (ACE) protein expression and reduced mitochondrial antioxidant proteins such as manganese superoxide dismutase (Mn-SOD) and catalase in the IFM. Treatment with apocynin (1.5 mM in drinking water) normalized myocardial contractility and interfibrillar mitochondrial function in the testosterone depleted animals. In conclusion, our findings demonstrate that testosterone deficiency leads to reduced myocardial contractility and impaired cardiac interfibrillar mitochondrial function. Our data suggest the involvement of reactive oxygen species, with a possibility of NOX as an enzymatic source.

RELATION BETWEEN LOW SERUM TESTOSTERONE AND PROSTATE CANCER BEHAVIOR

Objectives: Prostate cancer is intensifying globally, including Asian countries also. There are a numerous arguments is still going on in concerning the connection among endogenous testosterone levels and prostate ailments. The present research was performed to recognize the assessment of serum testosterone in identifying the threat and prostate cancer incidences. Methods: Hundred cases were registered in the research, among that, the cases showing low testosterone value (<250 ng/dL) was considered A Group and cases with normal testosterone value (>250 ng/dL) was considered B Group. All cases those went radical prostatectomy were followed for post-operatively with histopathological analysis and variables, namely, Post-operative Gleason grade, pathological tumor status, pathological node status, surgical margin status, extracapsular extension of tumor, seminal vesicle invasion, and matched among groups. Variables were completed with the Student’s t-test; p<0.05 was considered statistically significant. Results: Serum testosterone levels as found to be reduced among 74% and regular among 34% prostate cancer cases. Patients in Group A showed greater complete tumor stage, advanced nodal stage, and widespread metastases on scientific assessment associated with Group B. Conclusion: All the elderly men aged 60 and more should be screened of for serum testosterone levels for timely prostate carcinoma diagnosis and for better prognosis in the management.

The effects of hydrocortisone and yohimbine on human behavior in approach-avoidance conflicts

RationaleBalancing approach of positive and avoidance of negative stimuli is essential when faced with approach-avoidance conflicts, e.g., situations with both positive and negative outcomes. This balance is disturbed in several mental disorders, e.g., excessive avoidance in anxiety disorders, and heightened approach in substance use disorders. Since stress is assumed to impact these disorders’ etiology and maintenance, it seems crucial to understand how stress influences behavior in approach-avoidance conflicts. Indeed, some studies suggested altered approach-avoidance behavior under acute stress, but the mechanism underlying these effects is unknown.ObjectivesInvestigate how the pharmacological manipulation of major stress mediators (cortisol and noradrenaline) influences task-based approach-avoidance conflict behavior in healthy individuals.MethodsNinety-six participants (48 women, 48 men) received either 20mg hydrocortisone, 20mg yohimbine, both, or placebo before performing a task targeting foraging under predation in a fully crossed double-blind between-subject design. Moreover, we investigated effects of gender and endogenous testosterone and estradiol levels on approach-avoidance behavior.ResultsWhile biological stress markers (cortisol concentration, alpha amylase activity) indicated successful pharmacological manipulation, behavior in approach-avoidance conflicts was not affected as expected. Although yohimbine administration affected risky foraging latency under predation, we found no main effect of hydrocortisone or their interaction on behavior. In contrast, we found gender differences for almost all behavioral outcome measures, which might be explained by differences in endogenous testosterone levels.ConclusionsThe investigated major stress mediators were not sufficient to imitate previously shown stress effects on approach-avoidance conflict behavior. We discuss potential reasons for our findings and implications for future research.

Baseline endogenous serum testosterone levels and all-cause mortality in men with prostate cancer treated by radical radiotherapy: 11-year follow-up data.

e17003 Background: Low levels of serum testosterone are associated with higher all-cause mortality and cardiovascular mortality in some studies.(PMID: 18040028). But men with low levels of serum testosterone at reduced risk of developing prostate cancer. (PMID: 30077399). In middle-aged and elderly men, single point testosterone measurements have been shown to reliably reflect long term androgen exposure. [PMID: 1548361]. We assessed the interaction of pre-treatment serum testosterone levels and long term all-cause mortality in men with newly diagnosed prostate cancer. Methods: Prostate cancer pts enrolled in an ethics approved, prospective study evaluating a rating scale. Baseline serum testosterone levels were measured before the pts were commenced on androgen deprivation therapy and radical radiotherapy. Patient characteristics: Mean age 68.2yrs (median 69yrs); Age range category < 60yrs:14.9% , 61-70yrs:47.3% and > 71 yrs: 37.8%. Charlson Comorbidity Index (CCI) prevalence at baseline as follows CCI- Low risk : 39.9%; CCI-medium risk : 51.4%; CCI-high risk: 8.8%. PSA median level was 10.85 ug/L. Tumour was localised in a majority of pts- stage T1/T2 in 72% . Pts with M1 disease were not enrolled. Histology grade: Gleeson grade 6 in 7.4% and Gleeson grade 7 in 53.4% . Serum testosterone: Median 11.9 nmol/l; Mean 12.4 (Min-Max 2.6 to 26.7). Cox proportional hazards regression used to analyze the effect of baseline Serum Testosterone on long term overall survival, while controlling for covariates (age, cancer T stage, PSA category, Gleeson Category and Charlson Comorbidity index). Results: Lower levels of serum testosterone at baseline were associated with decreased all-cause mortality. There was no significant correlation between testosterone levels and age in our study sample of relatively elderly population (Pearson Correlation p = 0.362); There was no correlation testosterone levels and PSA levels(P = 0.821); no association between serum Testosterone levels and Gleeson Grade as well as T stage. (F = 0.78 ; P = 0.46 and F = 1.34 ; P = 0.26 respectively). There was also no significant variation in testosterone levels according to Comorbidity categorised by Charlson Comorbidity Index. (F = 1.31 P = 0 .26). Conclusions: Lower Serum testosterone levels were associated with decreased all-cause mortality in this prospectively collected survival data of non-metastatic Prostate cancer patients. [Table: see text]

MP77-18 THE IMPACT OF TESTOSTERONE ON URINARY INCONTINENCE FOLLOWING ROBOT-ASSISTED LAPAROSCOPIC PROSTATECTOMY

You have accessJournal of UrologyCME1 Apr 2023MP77-18 THE IMPACT OF TESTOSTERONE ON URINARY INCONTINENCE FOLLOWING ROBOT-ASSISTED LAPAROSCOPIC PROSTATECTOMY Jordan Kassab, John Lindsey Ii, Juan Torres-Anguiano, and Larry Lipshultz Jordan KassabJordan Kassab More articles by this author , John Lindsey IiJohn Lindsey Ii More articles by this author , Juan Torres-AnguianoJuan Torres-Anguiano More articles by this author , and Larry LipshultzLarry Lipshultz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003351.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urinary incontinence following robot-assisted laparoscopic prostatectomy (RALP) affects one in five men. Further, low testosterone has been associated with lower urinary tract symptoms and incontinence in both men and women. The aim of this study is to determine whether endogenous testosterone (T) levels (low or normal) or testosterone therapy (TTh) have an impact on the incidence of incontinence following RALP. METHODS: Utilizing diagnoses codes associated with RALP, 5129 patients were identified. We then retrospectively documented testosterone levels and continence status for each of these patients throughout the 10/1/2017 - 10/1/2022 observation period. The patient cohort was stratified into three groups: 1) eugonadal 2) hypogonadal and 3) patients on T therapy. Chi-squared analyses were used to determine associations between hypogonadism, eugonadism, TTh, and incontinence in patients who have undergone RALP. This work was completed on SPSS. RESULTS: Of the men with normal serum T (n=3972) who underwent RALP, 628 were found to have urinary incontinence (15.8 %) after one year. Of those men with hypogonadism who underwent RALP (n=656), 164 patients faced urinary incontinence (25.0%) after one year. Lastly, among the patients receiving TTh who had prostatectomies (n=501), 24 encountered incontinence (4.8%). There was a statistically significant difference of incontinence rates between the three patient populations (p<.00001). CONCLUSIONS: This study suggests that hypogonadal men undergoing RALP have an increased risk of urinary incontinence. These findings expand previously demonstrated associations between hypogonadism and less successful outcomes following oncologic genitourinary surgery. Further investigation of testosterone’s role in urinary continence following RALP may improve pre-operative evaluation and counseling as well as warrant new treatment paradigms for hypogonadal men with prostate cancer. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1109 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jordan Kassab More articles by this author John Lindsey Ii More articles by this author Juan Torres-Anguiano More articles by this author Larry Lipshultz More articles by this author Expand All Advertisement PDF downloadLoading ...

MP33-10 INCREASED GENITOURINARY CANCER INCIDENCE AND LOWER TESTOSTERONE LEVELS ARE FOUND IN MEN PERFORMING NON-STANDARD SHIFT WORK

You have accessJournal of UrologyCME1 Apr 2023MP33-10 INCREASED GENITOURINARY CANCER INCIDENCE AND LOWER TESTOSTERONE LEVELS ARE FOUND IN MEN PERFORMING NON-STANDARD SHIFT WORK Jordan Kassab and Larry Lipshultz Jordan KassabJordan Kassab More articles by this author and Larry LipshultzLarry Lipshultz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003266.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Previous studies have documented hypogonadal serum hormone levels in men regularly involved in non-standard shift work (NSSW) schedules. This work schedule is defined as working outside of the normal 7am-6pm hours. Additionally, past literature have shown a marked correlation between sleep deprivation and cancer risk, prompting us to investigate the relationship between NSSW schedules and cancer. The objective of this study is to explore the impact of NSSW schedules on the incidence of cancer as well as its impact on urologic markers. METHODS: A retrospective chart review was conducted, having identified over 3000 patients from the electronic medical records of a university hospital. The accrued patient cohort included both those who were involved in NSSW schedules and those who were not. The database was then linked to the Texas Cancer Registry to identify which of these patients have had a documented cancer diagnosis since 1995. The data from the registry included the age of cancer diagnosis, primary site, histology type, and metastatic status. The statistical analyses were performed using SPSS software. RESULTS: The statistical analysis revealed that the average age of cancer diagnosis is more than six years younger in NSSW versus those with regular work schedules. Similarly, non-standard shift workers experienced higher levels of prostate-specific antigens (4.942 ng/mL vs. 1.204 ng/mL). As expected from previous studies, non-standard shift workers faced significantly lower levels of endogenous testosterone (358.6 ng/dL vs 618.6 ng/dL). Furthermore, the NSSW population’s incidence of cancer is roughly double the age-adjusted cancer incidence rate of men in Texas. Of the NSSW who had a cancer diagnosis (n=45), the most common cancer primary sites were the male genital organs (n=16), the urinary tract (n=5), and the hematopoietic and reticuloendothelial systems (n=5). CONCLUSIONS: Our study has demonstrated that NSSW are at higher risk of developing cancer than the general male population. NSSW who already represent a clinically vulnerable population, may be somewhat immunocompromised as evidenced by their increased cancer incidence. The increased incidence of urogenital cancers within the NSSW group emphasizes the greater need of urologic focus for these men in clinical practice. Source of Funding: None. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e453 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jordan Kassab More articles by this author Larry Lipshultz More articles by this author Expand All Advertisement PDF downloadLoading ...

Hypogonadism: cardiometabolism and gonadal function in men

Hypogonadism is a relatively rare condition in men, which increases in frequency as men age, but also as they become less active and gain weight. In the past 20 years, developing knowledge on the relationship between hypogonadism and cardiovascular and cerebrovascular health and on aspects of metabolic health has become clearer. The relationship between hypogonadism and specific endocrine abnormalities of spermatogenesis is much longer established. Long- and short-term testosterone replacement therapies have well-recognised effects on cardiovascular and cerebrovascular health and on aspects of metabolic health. This leads to a sense of safety when it comes to considering these options as ways of managing the recognised symptoms of hypogonadism and the hidden adverse findings. That confidence has yet to be proven by long-term randomised controlled studies. The use of exogenous gonadotrophins to raise endogenous testosterone levels is a cost-efficient method of achieving spermatogenesis but is not suitable for long-term testosterone maintenance therapy.

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.

Normal preoperative endogenous testosterone levels predict prostate cancer progression in elderly patients after radical prostatectomy.

The impact of senior age on prostate cancer (PCa) oncological outcomes following radical prostatectomy (RP) is controversial, and further clinical factors could help stratifying risk categories in these patients. We tested the association between endogenous testosterone (ET) and risk of PCa progression in elderly patients treated with RP. Data from PCa patients treated with RP at a single tertiary referral center, between November 2014 and December 2019 with available follow-up, were retrospectively evaluated. Preoperative ET (classified as normal if >350 ng/dl) was measured for each patient. Patients were divided according to a cut-off age of 70 years. Unfavorable pathology consisted of International Society of Urologic Pathology (ISUP) grade group >2, seminal vesicle, and pelvic lymph node invasion. Cox regression models tested the association between clinical/pathological tumor features and risk of PCa progression in each age subgroup. Of 651 included patients, 190 (29.2%) were elderly. Abnormal ET levels were detected in 195 (30.0%) cases. Compared with their younger counterparts, elderly patients were more likely to have pathological ISUP grade group >2 (49.0% versus 63.2%). Disease progression occurred in 108 (16.6%) cases with no statistically significant difference between age subgroups. Among the elderly, clinically progressing patients were more likely to have normal ET levels (77.4% versus 67.9%) and unfavorable tumor grades (90.3% versus 57.9%) than patients who did not progress. In multivariable Cox regression models, normal ET [hazard ratio (HR) = 3.29; 95% confidence interval (CI) = 1.27-8.55; p = 0.014] and pathological ISUP grade group >2 (HR = 5.62; 95% CI = 1.60-19.79; p = 0.007) were independent predictors of PCa progression. On clinical multivariable models, elderly patients were more likely to progress for normal ET levels (HR = 3.42; 95% CI = 1.34-8.70; p = 0.010), independently by belonging to high-risk category. Elderly patients with normal ET progressed more rapidly than those with abnormal ET. In elderly patients, normal preoperative ET independently predicted PCa progression. Elderly patients with normal ET progressed more rapidly than controls, suggesting that longer exposure time to high-grade tumors could adversely impact sequential cancer mutations, where normal ET is not anymore protective on disease progression.

Interaction between Pelvic Bone Mineral Density and Sex Steroid Hormone on the Risk of Urinary Incontinence from National Health and Nutrition Examination Survey 2013–2014

Introduction: The correlation between sex hormone levels and pelvic bone mineral density in people with urinary incontinence (UI) has not been evaluated. This study explored the association between sex hormones, pelvic bone mineral density, and UI, and analyzed the association between pelvic bone mineral density-combined sex hormones and UI in women. Method: The data of the National Health and Nutrition Examination Survey (NHANES) 2013–2014 were used in this cross-sectional study. Women aged 20 years and older with complete sex steroid hormone and pelvic bone mineral density data were included. Outcomes were stress UI (SUI), urgency UI (UUI), and mixed UI (MUI). Sex steroid hormone included testosterone, estradiol, and sex hormone binding globulin (SHBG). Multivariate logistic regression analyses with the odds ratios (ORs) and 95% confidence intervals (CIs) were used. Results: Of 2,442 women, 579 had SUI, 202 had UUI, and 344 had MUI. The estimated multiplicative interactions were significantly between testosterone and pelvic bone mineral density, between SHBG and pelvic bone mineral density on UI (p = 0.002, p = 0.003), MUI (p = 0.036, p < 0.001), and SUI (p = 0.008, p = 0.044), respectively. High pelvic bone mineral density was associated with UI (p = 0.022) and MUI (p = 0.028) in the age <45-year-old subgroup. Multiplicative interactions were between testosterone and pelvic bone mineral density on all types of UI in the age <45-year-old subgroup, on SUI in women who did not have vaginal deliveries, and on UI in women who had more than one-time vaginal delivery. Conclusion: Our study found negatively multiplicative interactions between testosterone, SHBG, and pelvic bone mineral density on UI, MUI, and SUI. Similar results were found in women aged <45 years old and in women who had more than one-time vaginal delivery. Clinicians may consider testosterone or SHBG supplementation and pelvic density enhancement in women with SUI, MUI, and low endogenous testosterone levels.

Associations between cognitive function and endogenous levels of estradiol and testosterone in adults with Type 2 diabetes?

AbstractBackgroundType 2 diabetes mellitus (T2D) accelerates cognitive decline in women and men. Among older women, prior reports suggest that higher endogenous estradiol levels may further accelerate the cognitive decline associated with T2D and increase risks for cognitive impairment. Testosterone may interact directly with cognitive decline in T2D, or through its conversion to estradiol via the aromatase enzyme.MethodsEstradiol (E2) and total testosterone (TT) concentrations were determined using stored serum from 996 individuals, mean (±SD) age 69±6 and not receiving hormone therapies, collected at two times (averaging 4 years apart). Serum was collected during follow‐up years 8‐18 of the Look AHEAD cohort, a randomized controlled clinical trial of a 10‐year behavioral weight loss intervention in individuals with T2D and overweight or obesity at trial enrollment. One to four standardized assessments of attention, executive function, memory, and verbal fluency were collected during follow‐up years 8‐18. Mixed effects models were used to assess associations that E2 and TT concentrations had with current body mass index (BMI) and cognitive function.ResultsGreater current BMI was associated with higher E2 concentrations in women and men, and greater TT concentrations in women, but lower TT concentrations in men (all p&lt;0.001). The weight loss intervention did not leave a legacy of differences in E2 and TT concentrations. E2 concentrations were not associated with cognitive function in women or men. TT concentrations were not associated with cognitive function in women, but greater TT concentrations were associated with better verbal fluency in men (p&lt;0.001), most strongly among those carrying the APOE‐e4 allele (interaction p = 0.02). While the weight loss intervention left a legacy of relatively lower cognitive functioning among women, this was not mediated by current concentrations of E2 and TT.ConclusionsContrary to prior reports, we found no evidence that higher endogenous E2 concentrations were related to worse cognitive functioning in women with T2D. Higher TT concentrations were associated with better verbal fluency in men, but not women. The legacy of modestly lower cognitive function in women left by a 10‐year weight loss intervention was unrelated to any long‐term alterations in E2 or TT concentrations.

Testosterone: An Unauthorized Biography

Among all the endogenous small molecules of our bodies, perhaps oxytocin and testosterone have garnered the most mystique, the supposed biochemical mediators of love and dominance, respectively.In the popular imagination, we know what these molecules do. But biology isn’t simple. A single compound can have myriad effects throughout a body—depending on the relative concentrations of receptors in different organ systems, the same molecule might affect two people’s bodies very differently.Testosterone unpacks dozens of studies on the role of testosterone in athleticism, psychology, and sexuality, attempting to separate the robust, significant findings from a swirl of hyperbolic summaries and news reports. (While reviewing the book, we chanced across conspiracy-theory-ish headlines bemoaning a drop in testosterone levels among young men, others touting testosterone as an anti-aging miracle drug. This sort of hype isn’t new: throughout the 1920s, celebrity doctor John Brinkley toured the country implanting goat testicles into the bodies of credulous patients as a cure for diminished vigor.)Testosterone is a potent molecule; high doses of exogenous testosterone can permanently change a person’s voice, face shape, distribution of body hair, and ability to build muscle mass, especially if that person was assigned female at birth. But numerous correlation studies also attribute personality traits to small differences in the interpersonal levels of endogenous testosterone, often in ways that are unintentionally classist or racist; for instance, dominance-seeking behavior is described as antisocial aggression when studied in prison populations and as prosocial leadership when studied in university settings. Jordan-Young and Karkazis deftly note these hidden biases in scientific research.Often, Jordan-Young and Karkazis are frustrated by the narrow scope of questions that have even been asked, reminding us of the book Invisible Women, in which Caroline Criado Perez explains how the paucity of data collected on the ways that medicines, buildings, and political structures affect women has perpetuated designs that actively harm women.The same gender-biased omissions in data collection appear throughout the scientific literature on testosterone. The design of our experiments determines the range of possible knowledge that we might gain from them; for instance, perhaps because we refer to testosterone as a “male sex hormone,” researchers have only recently begun to study the role of testosterone in ovulation and female fertility.At times, though, we felt that Jordan-Young and Karkazis were overly critical of studies they cited. In our experience attending journal clubs, undergraduates often seemed most trusting of research papers’ discussion and conclusion sections; midcareer graduate students, hypersensitive to imperfect data or overstatement; and postdocs and faculty, more understanding of the compromises inherent in any scientific study. Most scientists would conduct experiments differently if all the results could be predicted in advance, or if they were granted an infinite budget of time and money. (Memorably, at one of Kirstin’s first graduate journal clubs, the faculty advisor listened patiently for five minutes while the students denigrated the stray bands of a paper’s Western blot. Finally, the professor smiled and said, “You, too, will have such bands.”)Not that we’d wish for Jordan-Young and Karkazis to overlook the flaws of ill-designed studies, but they don’t always exhibit the sympathy that comes from undergoing one’s own trials and tribulations in the laboratory. And while we enjoyed the book, the stylistic conventions and jargon from gender theory might reduce its appeal to students and teachers of science. We found ourselves wishing it was written more accessibly, because the study of testosterone is fascinating: implicated in wound-healing, essential for gender-affirming medical care, interwoven with many men’s self-conceptions of masculinity, stubbornly debated in the context of competitive sports. While Jordan-Young and Karkazis don’t offer firm conclusions, their careful guidance and philosophical insights could help anyone think about and teach these subjects from a more nuanced, open-minded perspective.

097 Evidence of a female-specific causal relationship between endogenous testosterone levels and acne

To investigate a potential causal role of natural variation in endogenous testosterone levels in the development of acne, we performed a two-sample sex-stratified Mendelian randomisation (MR) study. Instrumental variables comprised genetic variants with genome-wide significant effects on total testosterone (TT), free testosterone (FT) and steroid hormone binding globulin (SHBG) levels in male and female participants in UK Biobank. The effects of these instrumental variables on acne were derived from sex-stratified genome-wide association studies of acne comprising 3,173 female cases and 2,426 male cases.

RF15 | PMON304 Utilizing LC-MS/MS for the clinical quantitation of testosterone using dried blood spot and how it compare to serum

Abstract Introduction Hormones are the chemical messengers of your body. Steroid hormones like testosterone are a specific class of hormone that are produced predominantly in the gonads (sex steroids) and less so in the adrenal glands (corticosteroids). When too little or too much of testosterone is produced, adverse symptoms and conditions can occur. In order to restore the vital balance of hormones, detailed and accurate measurement of hormones is needed. Serum currently represents the gold standard when it comes to hormone testing. However, there are other body fluids such as saliva, urine, and capillary blood (finger prick) where the hormone levels correlate well with serum. A significant advantage of these alternative fluids is that they are non-invasive, or semi-invasive, can be collected "on the go" by the patient at home, and don't have the strict requirements for cold-chain shipping. Objectives The primary objective of this work is to show that finger-prick dried blood spot blood is quantitatively equivalent to serum when compared by LC-MS/MS testing in patients only producing endogenous testosterone. We will also show that topically delivered testosterone increases in a dose-dependent fashion, whereas serum levels of testosterone increase very little regardless of topical testosterone dosing. Methods Serum samples were collected by a physician and sent into the lab and analyzed for testosterone on a Siemens Immulite 2000 autoanalyzer. Dried blood spots were collected by the patient and sent into the lab and analyzed on an AB Sciex 5500 triple quadrupole mass spectrometer. Results Patients who don't supplement with topical testosterone show a strong correlation between endogenous venipuncture serum and DBS testosterone levels. In sharp contrast, samples from topical testosterone users show remarkably different results with hormone levels 10-100×higher in the DBS than serum results. Conclusion These results are significant because it gives a glimpse into which forms of testing are most appropriate for different patients based on the mode of steroid hormone delivery. Without using the proper body fluid for testosterone detection, patients potentially could be overdosed if serum results are used to guide therapeutic dosing. Also, venipuncture serum will fail to show "sports-doping" with exogenous testosterone, which easily can be identified with capillary finger stick blood. This is also significant as the World Anti-doping Agency has finally begun accepting these data as fact and have listed dried blood spot as an appropriate form of collection and analysis for drug testing. This can help find athletes using performance enhancers that would normally have skirted by the system (1). WADA. (2021, May 21) WADA Executive Committee approves Technical Document for innovative dried blood spot testing method. https://www.wada-ama.org/en/media/news/wada-executive-committee-approves-technical-document-for-innovative-dried-blood-spot. Presentation: Sunday, June 12, 2022 12:36 p.m. - 12:41 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

The Role of Post-Radical Prostatectomy Testosterone Therapy in Erectile Function Recovery

The relationship between androgens and prostate cancer (PC) continues to be a source of much controversy within the urologic community. It is well established that low endogenous testosterone levels correlate with increased prevalence of erectile dysfunction and that exogenous testosterone therapy (TT) significantly decreases this risk. Although TT is often used for these purposes in the general patient population, the application of TT to patients with a history of PC is dismissed due to questions regarding oncologic safety and recurrence risk. However, for patients presenting with symptomatic hypogonadism and no evidence of PC after definitive treatment, the benefits of TT on surgical recovery, erectile function (EF), and quality of life are significant. In this regard, the review seeks to present published data regarding the oncologic safety and therapeutic efficacy of TT use for improved EF recovery in patients with post-radical prostatectomy.

Elevated Endogenous Testosterone Levels are not Associated With Significant Clinical Morbidity

ObjectiveTo investigate the association between elevated endogenous testosterone levels and deleterious effects associated with testosterone therapy. Elevated serum testosterone levels in men receiving testosterone therapy have been associated with side effects, though precise thresholds above which these occur are unknown. Data on the association between naturally elevated endogenous testosterone levels and their physiologic effects is sparse. MethodsWe examined National Health and Nutrition Examination Survey data between 2011 and 2016, analyzing men aged 18 and older not on testosterone or androgen ablation therapy, excluding men who had testosterone <300 ng/dL, to compare men with elevated testosterone (>800 ng/dL) to men with normal testosterone (300-800 ng/dL). We used multivariable logistic and linear regressions for comparison. ResultsAfter excluding men with testosterone levels <300 ng/dL, 3673 men met inclusion criterion. Only 146 (4%) of men had a testosterone >800 ng/dL. When compared to men with normal testosterone, men with high testosterone had similar rates of sleep disorders, urinary symptoms, and depression. Men with elevated testosterone had higher hematocrit regression coefficient (βi 1.30, 95% confidence interval [CI] 0.69-1.90 P < .01), AST (βi 8.48, 95% CI 0.31-16.66, P = .04) and ALT (βi 12.23, 95% CI 0.70-23.77, P = .04) compared to men with normal testosterone. ConclusionNo association was found between higher endogenous testosterone levels and adverse events associated with testosterone therapy. Men with higher testosterone had increased hematocrit, but this was not clinically significant. This challenges what is considered a safe target for testosterone therapy and prompts future prospective studies to delineate the safety of elevated endogenous and exogenous modulated levels of testosterone.