Total T Levels Research Articles

Analysis of diurnal variation in serum testosterone levels in men with symptoms of testosterone deficiency.

Testosterone (T) plays a crucial role in various physiological functions in men, and understanding the variations in T levels during the day is essential for diagnosing and treating testosterone deficiency (TD). We sought to evaluate the reduction in serum total T (TT) levels throughout the day in men with symptoms of testosterone deficiency and to determine the variables having an impact on the extent of this decline. The study population consisted of a group of men who within 3months of each other had all undergone both early morning and afternoon TT level measurements. We did not include patients with a history of a prior orchiectomy, testosterone levels below 100ng/dL or above 1000ng/dL, a history of androgen deprivation therapy, or patients on T therapy. Statistical analyses were conducted using descriptive statistics, t-tests, chi-square tests, and correlation calculations. Liquid chromatography-tandem mass spectrometry was used to measure TT, and a change in TT levels greater than 100ng/dL was considered significant. Using multivariable and univariable analysis, we attempted to define predictors of a decrease in afternoon TT levels. The majority of men showed no significant difference in T levels between morning and afternoon. In total, 506 men with a median age of 65years were analyzed. The most common comorbidities were hypertension and hyperlipidemia. Levels of TT were measured in the morning and afternoon, and no significant differences in mean T levels based on the time of the test were found. Age was not significantly associated with T levels. There was a weak negative correlation between age and the difference between morning and afternoon T levels, with younger men showing more significant variations in T levels. The most considerable differences in T levels were observed in men younger than 30 years. There were no predictors of the magnitude of the T decrease in the afternoon. Strengths of the study include the number of subjects and the use of liquid chromatography-tandem mass spectrometry for T measurement. Limitations include failure to measure morning and afternoon T levels on the same day, the retrospective nature of the study, and a smaller sample size of patients younger than 30years. In this study we found no strong link between age and daily T fluctuation, but we observed a decrease in the magnitude of variation with aging. The group experiencing the most significant decline in daily T had higher morning and consistently normal afternoon T levels.

(327) Adverse Event Reporting in Testosterone Therapy Randomized Controlled Trials (RCT)

Abstract Introduction Testosterone (T) therapy (TTH) is associated with well recognized adverse events (AEs) such as: polycythemia (PCT), major adverse cardiac events (MACE), gynecomastia (GYN), worsening obstructive sleep apnea (OSA). Objective We aimed to critically analyze published TTH RCTs with regard to how well TTH AEs were reported. Methods A literature review was performed of all TTH RCTs listed on PUBMED that had been published between 1997-2021. We describe sample size, trial duration, industry funding, T assay used, baseline and on-treatment total and free T, TTH modality, and mean follow-up during the RCTs. We also describe the reporting of PCT, GYN, MACE, OSA and the definitions used in these RCTs. Results 29 trials were reviewed (Table 1), 55% reported on transdermal T, 41% intramuscular T, 7% enclomiphene, 7% human chorionic gonadotropin and 7% other oral treatments (aromatase inhibitor, tamoxifen). 17% compared two TTH modalities. Median sample size was 73 [41, 189]. Median age was 63 [58, 67] years. Median follow-up in the RCT reported was 8 [6, 12] months. 55% had the support of pharmaceutical companies. The total T (TT) assay used was immunoassay (IA 59%), LCMS (24%), other (10%), while 7% did not report on the assay type, and only 55% reported free T level (79% calculate by Vermeulen formula, and 21% equilibrium dialysis). Median baseline TT level was 248 [227, 320] ng/dL; on TTH it was 528 [460, 621] ng/dL. Median baseline free T level was 5.4 [5, 6.3] ng/dL, on TTH it was 11.1 [9.3, 15.5] ng/dL. 83% measured HCT levels at any point, only 21% reported baseline levels, 24% reported post treatment. Median baseline HCT 43 [42, 46]%, post-TTH median HCT increase of 2.4[-2.5, +3]%. 52% reported on PCT rates (45% defined HCT >52%, 7% HB >17 g/dL). Median PCT rate was 2%, none mentioned phlebotomy. 17% of RCTs reported on GYN, with a median rate of 1.5%, while none mentioned GYN grade or if mammography had been performed. 17% of trials mentioned MACE, but only 2 defined MACE. Median MACE rate was 2%. 10% reported OSA, but none mentioned the type of assessment; the median rate was OSA 2%. Conclusions This analysis showed that the majority TTH RCTs have sub-optimal reporting of TTH safety. Disclosure No.

(392) The Impact of Radical Prostatectomy (RP) On Testosterone (T) Levels

Abstract Introduction Severe illness is associated with a decrease in T levels and in particular, radical cystectomy has previously been shown to result in a decrease in T levels. There is a lack of data on the impact of RP on T levels. This analysis aimed to address this question. Objective To evaluate the impact of RP on T levels. Methods The study population included (i) men who underwent RP (ii) with morning total T (TT) levels pre and post-RP (iii) measured using LCMS. We considered men who had TT levels measured ≤ 12 months before and after RP. Patients with radiation therapy, androgen deprivation therapy, or T therapy pre or post-RP were excluded. Differences in TT level pre and post-RP were measured. Low total T was defined as total T levels < 300 ng/dL. Difference ≥ 100 ng/dL between pre and post-RP was considered clinically significant. Multivariable analysis was performed to define predictive factors associated with low T after RP. A p-value <0.05 was considered statistically significant. Results 569 patients were analyzed. Mean age was 62 ± 7 years, median pre-RP PSA level was 6.1 (4.3, 8.9) ng/mL, mean pre-RP TT level 402 ± 172 ng/dL. Median Gleason score (GS) was 7 (6,7). Post-RP, the mean TT levels were 425 ± 169 ng/dL. 30% of men had low T pre-RP, 27% post-RP. No significant difference was observed between the rate of low T pre and post-RP. 13% of the men had a significant decrease and 23% a significant increase in total T levels between pre and post-RP. After multivariable logistic regression assessments, lower baseline T was a predictor associated with low T post-RP (Pre-RP Testosterone (per 100 ng/dL decrease) OR = 3.96, 95% CI = 3.03-5.18). Conclusions Approximately 1 in 4 men with prostate cancer and RP had low T before and after surgery in our cohort. One tenth of men had a significant drop in TT level and about a quarter had a significant increase. Only lower pre-RP TT levels were a significant predictor of low T post-RP. Disclosure No

(372) Does Age Predict the Difference in Morning vs Afternoon Testosterone Levels?

Abstract Introduction It is recommended that serum testosterone (T) level measurement be conducted in the early morning (AM) as T levels decrease in the afternoon (PM) due to the circadian rhythm in T secretion. This rhythm is reported to be blunted in older men. Objective This study aimed to define the magnitude and direction of the changes between morning and afternoon T levels across age groups. Methods The study population included men who had both AM (before 10 am) and PM (after 2 pm) total T (TT) levels within 3 months of each other. All TT measurements were performed using LCMS. We excluded patients with a prior orchiectomy, with T levels 1000 ng/dL, those with a history of androgen deprivation therapy, and patients on T therapy. Differences in AM and PM TT levels were quantified and stratified by age continuously. We reported the directionality of the changes based on increases or the decreases in T levels between AM vs PM. No difference was defined as a delta T levels between -100 to + 100 ng/dL, changes increasing or decreasing as >100 ng/dL. Correlation of TT difference between AM vs PM levels and age was calculated. Results 506 men were analyzed. Mean age = 63 ± 12 years. Mean of AM and PM TT levels were 425 ± 164 ng/dL and 397 ± 155 ng/dL, respectively (p < 0.001). While 63% of men had no significant difference (-100 to +100) between AM and PM levels, 24% had a > 100 ng/dl decrease, 13% > 100 ng/dl increase. Overall, 13% had higher PM and 24% lower PM TT levels. Neither AM nor PM TT levels were significantly associated with age. Age was weakly negatively correlated with the change between AM and PM levels (r = 0.10, p = 0.03). That is, the mean difference between AM and PM levels was more pronounced for lower ages and approached zero as age increased. Conclusions While age was not associated with mean AM or PM total T levels, this study did find differences in the magnitude of the difference by age. Disclosure No

(060) Chronology of Endogenous Testosterone Recovery Following Androgen Deprivation Therapy Cessation – Results From a Prospective Analysis

Abstract Introduction Testosterone (T) recovery after androgen deprivation therapy (ADT) is reported in the literature from 7 to 96%, with data mainly from retrospective studies using variable definitions for this event. Age, Diabetes and ADT duration may affect the timing and completeness of recovery Objective Prospectively evaluate the chronology of T recovery following ADT cessation Methods This is a secondary analysis of a prospective oncological study designed to evaluate the impact of neoadjuvant use of ADT in combination with abiraterone acetate and prednisone with or without apalutamide in patients with high-risk prostate cancer. Both regimens were administered for 3 months before radical prostatectomy (RP). Early morning Total T (TT) levels were collected (immunoassay) at baseline and periodically (3, 6 and 12 months) after ADT cessation. 3 outcomes for T recovery were evaluated: return to non-castrate level (TT >50 ng/dL), to normal T (TT ≥ 300 ng/dL) and back to baseline level (BTB –TT≥ baseline level). We performed a time-to-event analysis and reported the cumulative incidence of each outcome. Multivariable analysis was conducted to investigate predictors of recovery Results In this preliminary report, from 64 initially enrolled patients, 1 year follow-up T data from 50 pts were available. Mean age was 64.6 ± 5.89 years, 28% had type 2 diabetes (DM) and 61% hypertension (HTN). Mean TT levels were 450 ± 170ng/dl at baseline, 112. 7± 96.9 at 3m, 208.5 ±197 at 6m, 337.7 ± 170 at 9m and 378.2 ± 166 at 12 m. Figure 1 shows the cumulative incidence of each outcome according to time. Median time to achieve T>50 was 5 m, to achieve T>300 was 9.1m and BTB 13.13 m. At 1 year, 98% had returned back from castrate-level, 76% had TT normalized and 42% had return BTB. In a multivariable analysis including DM, HTN, age and baseline T, only baseline T was associated with a greater chance of recovery, with 88.5% of those with baseline T > 450 ng/dl achieving normal T at 1y vs 46.9% for patients with baseline T < 450 ng/dl (HR: 3.56, p< 0.001) Conclusions In this prospective analysis of a population exposed to neoadjuvant short-term ADT, T recovery rates after 1 year showed that the vast majority (98%) had returned back from castrate level (median time 5m), about 2/3 recovered back to normal levels (median time 9,1m) and less than half returned to BTB level. Baseline TT was the only predictor of T recovery Disclosure Yes, this is sponsored by industry/sponsor: Source of Funding: Janssen-Cilag Farmacêutica Ltda Clarification Industry funding only - investigator initiated and executed study

RF03 | PMON300 Sex Hormones, Sex Hormone Binding Globulin, and Gonadotropins in Men with Inguinal Hernias

Abstract Background More than 1 in 4 men will undergo inguinal hernia repair during their lifetime. Age is a significant risk factor for inguinal hernias in men with increased incidence in older age. Sex steroid hormone changes are observed with a higher ratio of serum estradiol (E2) to testosterone (T) as men age. We previously demonstrated that a shift from androgen to estrogen action caused inguinal hernia formation in a transgenic male mouse model with increased estrogen action in lower abdominal muscle tissues. However, age-related changes in serum E2 levels in men are conflicting, as some studies have reported increases but others have noted unchanged or even decreased E2 levels with advancing age. Method: This study was performed on 212 men with inguinal hernias, aged 20 to 90 years, stratified at 10-year intervals of age (20-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90 years). We assessed total T (TT), total E2 (TE2), dehydroepiandrosterone (DHEA), sex hormone-binding globulin (SHBG), and gonadotropins (FSH and LH). Body mass index (BMI) was calculated using height and weight. Results The BMI distribution was balanced for men with inguinal hernias among all age groups. TE2 was low in 23.7%, normal in 65.8%, and high in 10.5% of men 50 years or younger. In contrast, the percentage of patients with high TE2 was increased 2.6-fold in men over the age of 50 (20.1% in low, 52.3% in normal, and 27.6% in high). TT was normal in all men 50 years and younger but was low in 3.5% and normal in 96.5% of men over the age of 50. We found that serum TE2 levels and the ratio of TE2/TT positively correlated with age (p=0.001). In addition, serum TE2 levels were significantly higher in the advanced age groups (71-80 and 81-90 years) than in the young age group (20-40 years). Serum TT levels decreased but did not reach significance in the advanced age groups compared to the young age group. Remarkably the ratio of E2/T was higher in the advanced age groups than in the young age group (20-30 years). Serum DHEA levels in men over the age of 50 were significantly higher than in men 50 years or younger. SHBG levels were higher in men over 70 years than men 50 years or younger (p< 0.01). Serum levels of FSH and LH in men over 60 years were 3-fold greater than in men 50 or younger (p<0.01). Conclusions Our findings suggest a correlation of increased estrogen action in the formation of inguinal hernias at an advanced age. This points to a potential utilization of inhibitors of estrogen synthetase or estrogen antagonists in a subset of elderly inguinal hernia patients with increased circulating estrogen as a non-surgical intervention. Presentation: Saturday, June 11, 2022 1:42 p.m. - 1:47 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

SAT-050 Low Serum Testosterone (T) Is Associated with Poor Health Status in Young to Middle-Aged Human Immunodeficiency Virus (HIV)-Infected Men

BACKGROUND: The relationship between health status, defined by frailty and comorbidities, and serum T levels has been widely demonstrated in general population, while only one previous retrospective study has explored it in HIV-infected men1. AIM: To investigate the association between frailty and gonadal status by assessing serum total T (TT) with Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS) in a cohort of HIV-infected men. METHODS: Prospective, cross-sectional, observational study on HIV-infected men (age <50 years) with ongoing Highly Active Antiretroviral Therapy. Serum TT was assessed by the gold standard ID-LC-MS/MS. Sex hormone-binding globulin (SHBG) was measured by chemiluminescent immunoassay. Calculated free T (cFT) was obtained by Vermeulen equation. Multimorbidity was defined as at least 3 comorbid conditions, including: hypertension, diabetes, cardiovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, osteoporosis, chronic viral hepatitis and cancers. Frailty was calculated through the validated 37-item frailty index (FI)2. Patients with FI>0.21 were considered frail. Statistical analysis: Mann-Whitney U test was used to compare continuous variables. Correlations were performed using linear regression models. RESULTS: 315 consecutive HIV-infected men were enrolled (mean age 45.3±5.3 years; average duration of HIV-infection 16.3±8.8 years). 128 patients (40.5%) were comorbid and 207 (64.9%) were frail. Either cFT (p=0.001) or TT (p<0.001) were lower in comorbid patients than others. FT was inversely related to the number of comorbidities (p<0.001, R2=0.045). Accordingly, cFT (p=0.003) and TT (p<0.001) were significantly lower in frail patients. Frailty score was inversely correlated with cFT (p<0.001, R2=0.058), TT (p=0.041, R2=0.014) and SHBG (p=0.003, R2=0.029). However, after adjustment for age and duration of HIV-infection, cFT, TT and SHBG were excluded from the regression model. CONCLUSIONS: Low cFT and TT levels are associated with multimorbidity and poor health status in HIV infected men. The bidirectional nature of this relationship leads to the figuration of an intriguing vicious circle where T deficiency triggers the onset of comorbidities or, vice versa, poor health status induces hypogonadism. At the same time, notwithstanding the inverse relation between FT and frailty, it seems that other stronger predictive factors, and in particular the duration of infection, are involved in determining the health outcome in this clinical setting.REFERENCES 1Rochira V et al. Low testosterone is associated with poor health status in men with human immunodeficiency virus infection: a retrospective study. Andrology. 2015 Mar;3(2):298-308. 2Guaraldi et al. A frailty index predicts survival and incident multimorbidity independent of markers of HIV disease severity. AIDS. 2015 Aug 24;29(13):1633-41.

OR02-06 Sexual Symptoms Predict All-Cause Mortality Independently of Sex Steroids in Ageing Men

Background: The association between low testosterone (T) and higher mortality in men remains controversial. Most studies focus only on the association between total T (TT) and mortality. While TT declines with age, free T (FT) shows a greater fall, due to the rise in SHBG. Moreover, higher LH as well as sexual dysfunction, often co-existing with low T, have also been associated with mortality in ageing men. Objective: To study the interrelationships between sex steroids, gonadotrophins and sexual symptoms with all-cause mortality in a large prospective cohort of European men. Methods: 1913 community-dwelling men, aged 40-79, participated in the European Male Ageing Study (EMAS) between 2003-2005. Sexual symptoms were assessed via a validated questionnaire (EMAS-SFQ). Sex steroids were measured by mass spectrometry. In 5 of 8 EMAS centres, survival status was available until 1 April 2018. Cox proportional hazard models were used to study the association between hormones, sexual symptoms and mortality. Because of the wide age range at study entry, age was used as time-scale, instead of years since inclusion adjusting for age. Results were expressed as hazard ratios (HR) with 95% confidence intervals, adjusted for centre, BMI and smoking. Results: 483 (25.3%) men died during a mean follow-up of 12.4±3.3 years. Men who died had a higher BMI (p=0.002), but smoking status did not differ. TT levels were similar in both groups, but FT was lower in those who died (mean±SD: 312±86 pmol/L vs 270±84, p<0.001) and LH was higher (5.7±3.3 U/L vs 7.8±5.8, p<0.001). Men in the lowest FT quartile had higher mortality risk compared to men in the highest quartile (HR 1.43 (1.06-1.95); p=0.021). Also men in the highest FSH quartile had increased mortality risk (HR 1.38 (1.02-1.88); p=0.036). However, there was no association with TT, E2 or LH. Men with 3 sexual symptoms had a higher mortality risk compared to men with no sexual symptoms (HR 1.77 (1.28-2.41); p<0.001). In particular erectile dysfunction and poor morning erections, but not lower libido, were associated with increased mortality (HR 1.40 (1.15-1.73); p=0.001; HR 1.30 (1.06-1.60); p=0.012; HR 1.14 (0.93-1.40); p=0.203 respectively). Further adjusting for TT and FT did not influence the observed HRs. Also in men with normal TT (>12 nmol/L), the presence of sexual symptoms increased mortality risk (HR 1.51 (1.15-1.97); p=0.003). Finally, men with TT<8 nmol/L and sexual symptoms had a higher mortality risk compared to men with normal TT and no sexual symptoms (HR 1.92 (1.05-3.52); p=0.035). Conclusions: Men with the lowest FT and highest FSH levels have an increased mortality risk. Sexual symptoms, in particular erectile dysfunction, predict all-cause mortality independently of T levels. As both vascular disease and low T can influence erectile function, sexual symptoms can be an early sign for increased cardiovascular risk and mortality, as well as a sequela of low T.

MP78-03 TESTOSTERONE LEVELS FOLLOWING RADIATION THERAPY FOR PROSTATE CANCER

You have accessJournal of UrologySexual Function/Dysfunction: Evaluation II (MP78)1 Apr 2020MP78-03 TESTOSTERONE LEVELS FOLLOWING RADIATION THERAPY FOR PROSTATE CANCER Justin Haseltine*, Nicole Benfante, Michael Zelefsky, and John Mulhall Justin Haseltine*Justin Haseltine* More articles by this author , Nicole BenfanteNicole Benfante More articles by this author , Michael ZelefskyMichael Zelefsky More articles by this author , and John MulhallJohn Mulhall More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000964.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The impact of radiotherapy (RT) with androgen deprivation therapy (ADT) on testosterone (T) levels has been well documented. However, the data on the impact of RT monotherapy on T levels is less clear. We report our experience examining T profiles after RT without ADT for prostate cancer (PC). METHODS: The study population included patients who received RT for PC without ADT who had pre -RT (within 6 months of RT commencement) and post-RT total T (TT) levels collected before noon, measured using LCMS at a single lab. Patients with baseline castrate TT levels (TT<50) were excluded. Demographic, comorbidity, pathological and RT dosing data were recorded. Predictors of TT decreases were analyzed using logistic regression. Factors entered in to the model included: patient age, TT levels pre-RT, type of RT, and presence of hypertension (HTN), diabetes (DM), or cigarette smoking history. RESULTS: 168 patients have complete information and were included in the analysis. Median age was 68 (IQR 61, 71) and median pre-RT TT was 362 (IQR 299, 451). The majority of biopsy Gleason scores were 6 (30%) or 7 (61%). Comorbidities included HTN (46%), DM (13%), and smoking history (42%). RT was delivered as brachytherapy (BT) (11%), external beam RT (EBRT) alone (64%) or EBRT + BT (24%). Median time-point at the last TT measurement was 36 months (IQR 16, 70). Median number of TT levels was 3 (IQR 2, 5). Median TT at 6 and 24 months was 356 and 404, respectively. Pre-RT, TT was <300 ng/dL in 26% of patients. There was a decrease in TT from baseline of >100, >200, or >300 ng/dL post-RT in 43%, 17%, and 6%, respectively. No predictors of TT decreases were identified. CONCLUSIONS: Almost one quarter of men had a significant (≥200 point) decrease in total T levels within 3 years of RT completion. These data suggest that men after RT monotherapy should have their T levels monitored. Source of Funding: NIH grant P30 CA 008748 © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1174-e1174 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Justin Haseltine* More articles by this author Nicole Benfante More articles by this author Michael Zelefsky More articles by this author John Mulhall More articles by this author Expand All Advertisement PDF downloadLoading ...

189 Biochemical Recurrence Rates In Men With High Grade Prostate Cancer on Testosterone Therapy

Testosterone therapy (TTH) in men with prostate cancer is controversial especially in men with high risk prostate cancer, with little data exiting in he literature to guide clinicians. This study assessed biochemical recurrence rates (BCR) in men with high risk prostate cancer on TTH. Study Population: We included all men who underwent radical prostatectomy (RP) with high risk prostate cancer (HRPC), defined as a Gleason sum (GS) 6-7 with unfavorable pathology: positive surgical margins (SMS+), lymph node involvement (LNI+), seminal vesicle involvement (SVI+); or GS ≥8 with any pathology status. BCR was defined as a PSA level of ≥0.1ng/mL. Low T was defined as a total T (TT) level <300nd/dl on two occasions using LCMS collected prior to noon. Men were divided into 3 groups based on T levels and TTH: those with normal TT levels and no TTH (NT); men with low TT who did not receive TTH (LT); men with low TT who received TTH (LT+).

Testosterone Recovery Profiles After Cessation of Androgen Deprivation Therapy for Prostate Cancer

IntroductionAndrogen deprivation therapy (ADT) is frequently used in the treatment of prostate cancer worldwide. Variable testosterone (T) recovery profiles after ADT cessation have been cited. AimTo evaluate T recovery after cessation of ADT. MethodsWe reviewed our institutional prospectively maintained database of patients with prostate cancer who received ADT. Serum early morning total T (TT) levels, collected at baseline and periodically after ADT cessation, were analyzed. Patient age, baseline T level, duration of ADT, and presence of diabetes and sleep apnea were selected as potential predictors of T recovery. 3 metrics of T recovery after 24 months of ADT cessation were analyzed: return to non-castrate level (TT > 50 ng/dL), return to normal (T > 300 ng/dL), and return back to baseline level (BTB). Multivariable time-to-event analysis (Cox proportional hazards), χ2 test, logistic regression model, and Kaplan-Meier curve were performed to define impact of the above predictors on time and chance of T recovery. Main Outcome MeasuresTime and chance of T recovery to non-castrate level (TT > 50 ng/dL), return to normal (T > 300 ng/dL), and return BTB. Results307 men with a mean age of 65 ± 8 years were included. Mean duration of ADT was 17 ± 25 months, and median follow-up was 31 ± 35 months. Mean TT values were 379 ng/dL at baseline and 321 ng/dL at >24 months. At 24 months after cessation of ADT, 8% of men remained at castrate level, 76% returned to TT >300 ng/dL, and 51% had returned BTB. Lower baseline T levels (TT < 400 ng/dL) and ADT duration >6 months were associated with a lower likelihood of recovery to normal TT at 24 months. Age >65 years and receiving ADT for >6 months were significantly associated with a slower T recovery. Clinical ImplicationsT recovery after ADT is not certain and may take longer than expected. Considering the range of side effects of low T, we believe that these findings must be discussed with patients before initiating such therapies. Strengths & LimitationsOur strengths consisted of a relatively large database, long follow-up, and clinically meaningful endpoints. Limitations included the retrospective design of the study. ConclusionT recovery rates after ADT cessation vary according to patient age, ADT duration, and baseline T levels. Approximately one-quarter of patients failed to normalize their TT level, and one-tenth of men remained at castrate levels 24 months after ADT cessation.Nascimento B, Miranda EP, Jenkins LC, et al. Testosterone Recovery Profiles After Cessation of Androgen Deprivation Therapy for Prostate Cancer. J Sex Med 2019;16:872–879.

OR18-3 Gonadal Function in Human Immunodeficiency Virus (HIV)-Infected Men Assessed by Isotopic Dilution-Liquid Chromatography-Tandem Mass Spectrometry (ID-LC-MS/MS) and Chemiluminescent Immunoassay

BACKGROUND: HIV-infection is associated to premature decline of serum T1,2. However, prevalence and biochemical characterization of hypogonadism in HIV-infected men are still to be well defined1,2. AIM: To evaluate the gonadal status in HIV-infected men by assessing circulating total T (TT) with either ID-LC-MS/MS or chemiluminescent immunoassay. METHODS: Prospective, cross-sectional, observational study on HIV-infected men with ongoing Highly Active Antiretroviral Therapy (HAART). Serum TT, gonadotropins and sex hormone-binding globulin (SHBG) were measured by chemiluminescent immunoassay. TT was also assessed by the gold standard ID-LC-MS/MS. Free T (FT) was calculated by Vermeulen equation. Hypogonadism was defined as serum TT levels below 320 ng/dL and/or free T levels below 64 pg/ml. Statistical analysis: Categorical variables were compared using Chi-Square test, while correlations were performed using linear regression models. RESULTS: 315 consecutive HIV-infected men were enrolled (mean age 45.56±5.61 years; average duration of HIV-infection 16.57±10.45 years). Considering serum TT levels assessed by LC-MS/MS and immunoassay, 11 patients out of 233 (4.8%) and 10 patients out of 315 (3.2%) had T deficiency, respectively. TT combined with luteinizing hormone (LH) levels was used to classify hypogonadism. No difference was found comparing the two methodologies used for TT measurement (p=0.914). 56 patients (17.8%) showed SHBG above the normal range (>71.4 nmol/L). Considering calculated FT, the incidence of hypogonadism raised to 6.9% using either immunoassay or LC-MS/MS, with no difference between methodologies (p=0.895). Including compensated form of hypogonadism, the prevalence raised to 13% for TT and to 15% for FT. FT showed an inverse relation with age (-0.340,p<0.0001,R2=0.116), years of infection (-0.339,p<0.0001,R2=0.120) and years of HAART (-0.346,p<0.0001,R2=0.117), but not with BMI of patients. CONCLUSIONS: To the best of our knowledge, this is the first properly-designed prospective study aiming to investigate the gonadal status of HIV-infected men with both LC-MS/MS and chemiluminescent assay, together with gonadotropins. In HIV-infected patients a) the two methodologies have equivalent reliability in TT measurement; b) SHBG for calculated FT is essential for the detection of T deficiency, revealing the real prevalence of hypogonadism in this context; c) duration of HIV-infection and HAART seem to be potent predictive factors for serum FT levels, suggesting a concomitant negative effect of virus per se and antiretroviral drugs on gonadal function. REFERENCES1Rochira V et al. Premature decline of serum total testosterone in HIV-infected men in the HAART-era. PLoS One. 2011;6(12):e28512. 2Rochira V & Guaraldi G. Hypogonadism in the HIV-infected man. Endocrinol Metab Clin North Am. 2014 Sep;43(3):709-30.

036 Testosterone Recovery Profiles after Cessation of Androgen Deprivation Therapy (ADT)

It has been demonstrated that the combination use of ADT improves overall and cancer-specific survival in men with unfavorable prostate cancer (PCa). After cessation of ADT, testosterone (T) levels are expected to recover from castrate to normal levels. However, very little is known about T recovery profiles in this population, and many patients remain on castrate levels indefinitely. The aim of this study was to evaluate T recovery after cessation of ADT in PCa patients. We reviewed our prospectively maintained database for PCa patients who received ADT therapy at our institution. Serum early morning total T (TT) levels were measured at baseline and periodically after ADT cessation. Multivariable time-to-event analysis (Cox proportional hazards) was performed to determine predictors of TT recovery after ADT cessation and included the following variables: patient age, baseline T level, and duration of ADT. 1641 men with a mean age of 66 (43-94) years were included. Primary treatment for PCa was RP in 36%, while the remainder had either RT or primary ADT. The majority received a GnRH agonist as mainstay for ADT. Mean duration of ADT was 28.8±39 months [0.5 to 324]. Distribution of ADT exposure was: <6 months (m) 33%, 6-12m 19%, 12-24m 16%, >24m 33%. Median follow-up was 47.5±45 months. Mean TT values were: baseline 358 ng/dl, 6-12m post ADT cessation 96 ng/dl, 12-18 174 ng/dl, 18-24m 228 ng/dl, >24m 273 ng/dl. At last follow-up: 77% men had TT level above castrate level, 45% had TT >300ng/dl and 39% returned to pre-treatment TT level. On multivariable analysis age over 65 years (HR 2.01, 95%CI 1.48-2.71, P<0.0001), ADT duration of 6 months or greater (HR 1.42, 95%CI 1.07-1.90, P=0.02), and baseline T of 400 ng/dl or more (HR 1.80, 95%CI 1.36-2.40, P<0.0001) were all significantly associated with a slower recovery time.

Testosterone and Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Propensity Score-Matched Analysis

IntroductionA recent study investigated the role of testosterone (T) in chronic prostatitis or chronic pelvic pain syndrome (CP/CPPS). However, only a small amount of data is available to date, and the results are inconsistent. AimsTo evaluate the relation between total T (TT) and CP/CPPS. MethodsWe conducted a propensity-matched study by identifying men with a TT level lower than 3.5 ng/mL among 8,336 men in their 40s and 50s. A control group of men with a TT level of at least 3.5 ng/mL matched for age, metabolic syndrome, and body mass index at a 5:1 ratio was selected for comparison. Using the same cohort and methods, another case group (TT < 3.0 ng/mL) and control group (TT ≥ 3.0 ng/mL) were selected. The National Institutes of Health—Chronic Prostatitis Symptom Index (NIH-CPSI) was administered. A χ2 test, a t-test and logistic regression analyses were used to evaluate the relation between TT and prostatitis-like symptoms. Main Outcome MeasuresAssociation of TT with NIH-CPSI score. ResultsAfter propensity score matching, 948 cases (TT < 3.5 ng/mL) and 4,740 controls (TT ≥ 3.5 ng/mL) were included. The ratio of mild and moderate to severe prostatitis-like symptoms was higher in the case group than in the control group (24.0% vs 27.4%, P = .001). The ratio of moderate to severe prostatitis-like symptoms also was higher in the case group than in the control group (6.2% vs 9.2%, P = .028). The pain domain of the NIH-CPSI, quality of life, and total NIH-CPSI scores also were higher in the case group. Ratios of severe lower urinary tract symptoms (12.6% vs 15.1%, P = .044) to maximal flow rate no higher than 10 mL/sec (3.8% vs 5.3%, P = .044) and postvoid residual urine volume of at least 100 mL (4.0% vs 5.6%, P = .035), which suggest high pressure in the prostate urethra, were higher in the case group. After adjusting for voided volume during uroflowmetry and total prostate volume, the relations of a TT level lower than 3.5 ng/mL to a maximal flow rate no higher than 10 mL/sec (odds ratio = 1.402, 95% CI = 1.017–1.934, P = .039) and to a postvoid residual urine volume of at least 100 mL (odds ratio = 1.410, 95% CI = 1.031–1.927, P = .031) were maintained. Using the cutoff TT value of 3.0 ng/mL, 437 cases (TT < 3.0 ng/mL) and 2,185 controls (TT ≥ 3.0 ng/mL) were included. The result of the 3.0-ng/mL cutoff value for TT showed a higher incidence of prostatitis-like symptoms in the group with a TT level lower than 3.0 ng/mL, but this was not statistically significant. ConclusionLow TT level (<3.5 ng/mL) was significantly correlated with prostatitis-like symptoms in this study.

Association of endogenous testosterone with subclinical atherosclerosis in men: the multi-ethnic study of atherosclerosis.

Whether endogenous sex hormones play a role in cardiovascular disease (CVD) risk in men is unclear. Few studies have examined associations of sex hormones with atherosclerosis measured by coronary artery calcium score (CACS) and carotid intima-media thickness (cIMT). We evaluated the association of testosterone (T) and other sex hormones with CACS and cIMT. Using the large multi-ethnic cohort of 3164 men without known CVD in the Multi-Ethnic Study of Atherosclerosis (MESA), cross-sectional associations of tertiles of endogenous sex hormones with CACS and cIMT were analysed. In regard to CAC, there was a significant negative trend (P-trend = 0·02) for CACS>0 over tertiles of free T (FT) with RRs (95% CI) for the lowest to highest tertiles. There was also a marginally significant positive trend (P-trend = 0·06) for CACS>0 over tertiles of sex hormone-binding globulin (SHBG) with RRs for the lowest to highest tertiles. There were no significant associations with CACS >0 for tertiles of TT (Total T), bioavailable T (BT), oestradiol (E2) and dehydroepiandrosterone (DHEA). There was significantly higher log CACS after adjustment for CVD risk factors for lower TT levels, compared to higher levels, using 9·54 and 10·4 nmol/l as cut-off points. In regard to cIMT, there was a significant positive trend (P = 0·003) in mean cIMT over the tertiles of BT, but not for TT, FT, E2, DHEA and SHBG. There was significantly lower cIMT after adjustment for CVD risk factors for lower TT levels compared to higher levels. In a population of male subjects with no known CVD, lower FT is associated with higher RR of CACS>0 and lower TT is associated with higher log CACS. Lower BT and TT are associated with lower cIMT. While these findings support the positive correlation between low T and coronary atherosclerosis, the opposite findings on cIMT warrant further evaluation.

Androgen Receptor Coregulator CTBP1-AS Is Associated With Polycystic Ovary Syndrome in Chinese Women: A Preliminary Study.

Polycystic ovary syndrome (PCOS) is currently considered a predominantly hyperandrogenic syndrome. In theory, hyperandrogenism can be caused by high level of testosterone (T) as well as by enhanced androgen receptor (AR) activity. C-Terminal binding protein 1 antisense (CTBP1-AS) was a novel long noncoding RNA (lncRNA) to regulate AR activity. In this study, we found that expression level of CTBP1-AS in peripheral blood leukocytes was significantly higher in women with PCOS than that in controls after adjustment for age and body mass index (BMI). Individuals having higher expression of CTBP1-AS had significantly greater disease risk than those having lower expression. We also identified expression of CTBP1-AS as an independent risk factor for PCOS. A positive correlation was observed between the CTBP1-AS expression and the total T (TT) concentration either unadjusted or after adjusting for age, BMI, and homeostatic model assessment insulin resistance. Taken together, our current study presented the first evidence that the lncRNA CTBP1-AS, a novel AR modulator, is associated with PCOS in Chinese population and established the possibility that abnormal CTBP1-AS expression is a risk factor for PCOS and it is a predictor of variability in serum TT level in Chinese women with PCOS.

MP51-05 DEFINING THE INCIDENCE OF POLYCYTHEMIA IN MEN USING INTRAMUSCULAR TESTOSTERONE SUPPLEMENTATION

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Evaluation II1 Apr 2015MP51-05 DEFINING THE INCIDENCE OF POLYCYTHEMIA IN MEN USING INTRAMUSCULAR TESTOSTERONE SUPPLEMENTATION Serkan Deveci, Patrick Teloken, Keith O'Brien, Patricia Guhring, Marilyn Parker, Joseph Narus, and John P. Mulhall Serkan DeveciSerkan Deveci More articles by this author , Patrick TelokenPatrick Teloken More articles by this author , Keith O'BrienKeith O'Brien More articles by this author , Patricia GuhringPatricia Guhring More articles by this author , Marilyn ParkerMarilyn Parker More articles by this author , Joseph NarusJoseph Narus More articles by this author , and John P. MulhallJohn P. Mulhall More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1742AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Polycythemia (PCT) is well-recognized adverse effect of testosterone supplementation. However, widely disparate rates exist in the literature (2-24%) based on varied definitions of PCT and modality of T supplementation. We attempted to determine the rate of PCT in patients in our intramuscular testosterone (IMT) program. METHODS Symptomatic men with two low total T (TT) levels (<350 ng/dl), using IMT for at least 6 months comprised the study cohort. Men used 200mg IM every 2 weeks and had peak (day 1-2) and trough T (day 13-14) levels checked after two cycles, and every 6 months. PCT was defined as hematocrit (HCT) ≥52%. Patients were excluded from IMT if they had baseline HCT >48%. A multivariate model was constructed to define predictors of PCT development. Factors assessed included: patient age, mean BMI, cigarette smoking history, baseline HCT, mean per patient peak TT level, mean per patient trough TT level, RESULTS 176 men were analyzed. 24% were diabetic, 48% prior or current cigarette smokers. At baseline, mean TT = 224±104 ng/dl. mean HCT = 38±6%, mean BMI = 32±6. Mean duration on IMT = 17±23 months. Mean peak TT level = 1164±240 ng/dl, mean trough TT level = 324±180 ng/dl. Mean HCT for entire cohort on IMT = 44±9 (39-57)%, representing a mean per patient change of 4.7±3.9 (2-11)%. 17% met the definition of HCT on IMT with a mean HCT = 54.2±1.8%. 23/30 patients with PCT developed it after 6 months on IMT. Factors found to be a predictor on multivariate analysis are listed in the Tables 1and 2, however cigarette smoking was not a predictor. CONCLUSIONS Almost one fifth of men on IMT experience PCT. Most men appear to develop it after 6 months of treatment. Predictors of PCT development are higher baseline HCT and higher peak TT levels. Categorical Variables Factor Odds Ratio 95% CI P value Baseline HCT >45% 2.8 1.6-5.9 <0.01 Baseline HCT per % point increase 1.4 1.1-3.4 <0.05 Any peak >1000 1.9 1.4-7.3 <0.01 Any trough >600 1.07 1.0-2.2 0.06 Continuous Variables Factor r P value Baseline HCT 0.58 <0.01 Mean peak 0.62 <0.01 © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e621 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Serkan Deveci More articles by this author Patrick Teloken More articles by this author Keith O'Brien More articles by this author Patricia Guhring More articles by this author Marilyn Parker More articles by this author Joseph Narus More articles by this author John P. Mulhall More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Is serum sex hormone-binding globulin a dominant risk factor for metabolic syndrome?

This multi-center, cross-sectional study investigated the association between serum testosterone (T) levels, serum sex hormone-binding globulin (SHBG) levels, and the risk of metabolic syndrome (MS) in 3332 adult Chinese men. The prevalence of MS was 34.7%, and men with MS had lower serum levels of total T (TT) and SHBG than those without MS (P < 0.001). There was no significant difference in serum free T (FT) levels between subjects with and without MS (P = 0.627). In logistic regression analysis, the association between MS and serum SHBG levels persisted after adjusting for age, body mass index (BMI), smoking and drinking status, and serum TT (odds ratio [OR] 0.962, 95% confidence interval [95% CI] 0.954−0.969, P< 0.01). However, the association between serum TT level and the risk of MS was weak after adjusting for age, BMI, SHBG level, and smoking and drinking status (OR 0.981, 95% CI 0.960−1.007). Our study reveals that both serum TT and SHBG levels, but not serum FT, are inversely associated with the prevalence of MS and that serum SHBG is an independent and dominant risk factor for MS.

Coadministration of Anastrozole Sustains Therapeutic Testosterone Levels in Hypogonadal Men Undergoing Testosterone Pellet Insertion

Current U.S. Food and Drug Administration-approved therapies for hypogonadism involve testosterone (T) replacement. Testosterone pellets (TP) require a minor office procedure every 3 to 4 months. The need for repeated insertions increases the likelihood of a complication. Anastrozole (AZ) is an aromatase inhibitor that has been used off-label for the treatment of male hypogonadism. AZ increases T levels by lowering serum estradiol (E2) levels and increasing gonadotropin (GTP) levels. We hypothesized that the concomitant use of AZ with TP insertions would sustain therapeutic T levels and increase the interval between TP insertions. Men treated with TP for hypogonadism at an academic center were offered AZ (1 mg/day) at the time of TP reinsertion as a way of potentially decreasing the frequency of TP insertions. Total T (TT), free T (FT), sex hormone binding globulin, E2, luteinizing hormone (LH), and follicle-stimulating hormone FSH levels were obtained prior to T replacement and at 6 and 15 weeks from TP insertion. Men were re-implanted at 16 weeks if their TT levels were less than 350 ng/dL and their symptoms recurred. We retrospectively reviewed our records of men who underwent TP, TP, and AZ from 2011 to 2012. Demographics, TT, FT, LH, FSH, and E2 levels were recorded. Data were analyzed with anova and a Tukey's test. TT level at 6, 15, or >15 weeks from TP insertion. Thirty-eight men with 65 insertions were analyzed. The TP AZ group had significantly higher TT and FT levels than the TP group at >120 days (P < 0.05). The TP group had significantly higher E2 levels at all time points (P < 0.01). GTP levels remained stable in the TP AZ group. Average time to reinsertion in TP AZ was 198 days vs. 128 days in the TP group. Men on TP AZ maintain therapeutic T levels longer than men on TP alone and have significantly less GTP suppression.

1901 DEFINING THE UTILITY OF A CLINICAL CARE PATHWAY FOR CLOMIPHENE CITRATE USE IN MEN WITH HYPOGONADISM

You have accessJournal of UrologyInfertility: Therapy1 Apr 20131901 DEFINING THE UTILITY OF A CLINICAL CARE PATHWAY FOR CLOMIPHENE CITRATE USE IN MEN WITH HYPOGONADISM Clarisse R. Mazzola, Darren J. Katz, and John P. Mulhall Clarisse R. MazzolaClarisse R. Mazzola New York City, NY More articles by this author , Darren J. KatzDarren J. Katz New York City, NY More articles by this author , and John P. MulhallJohn P. Mulhall New York City, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2320AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Clomiphene citrate (CC) is an effective treatment for men with hypogonadism (HG). For fear of tachyphylaxis, many clinicians commence CC at low dose and some dose every other day rather than daily. This analysis was undertaken to define if up-titrating dose in men failing to respond to low dose CC is an effective therapeutic approach. METHODS Men with a diagnosis of HG (defined by having 2 separate early morning total T (TT) levels <300 ng/dl) opting for CC therapy constituted the study population. Demographic, comorbidity data, physical and laboratory characteristics were recorded. All patients were started on CC 25 every other day (QOD) and were up-titrated to 50mgs QOD and then eventually 50 mgs daily (QD) if the original dose strategy failed. Laboratory testing was conducted 4 weeks after commencement, 4 weeks after a dose change and every six months thereafter. Response was defined as an increase of ≥200 ng/dl in TT and a TT level ≥400 ng/dl at ≥6 months after commencing CC. ANOVA was conducted comparing TT and LH levels among the three dosing groups. Multivariable analysis was performed on patients failing to respond to CC25 QOD to define predictors of successful response to higher doses. Parameters included in the multivariable model were: patient age, mean testicular volume, varicocele presence, baseline TT, free T and LH levels. RESULTS 112 patients were included with a mean age = 45±19 years. Mean pre-treatment testicular volume = 16±8 mls. Mean baseline T and LH levels were 222±98 ng/dl and 3.8±1.6 (0.1-5.8) IU/ml. On CC25 QOD, 71/112 (63%) patients met the responder definition (TT = 467±190 ng/dl, LH = 12.4±3.6). Of the 41 who were up-titrated to C50 QOD, 32% (13) met the responder definition (TT = 414±212 ng/dl, LH = 8.2±5.2). Of the 28 moving to CC50 QD, 18% (5) met responder definition (TT = 366±166 ng/dl, LH = 7.0±1.6; ANOVA p=0.033 for TT, p=0.025 for LH). On multivariable analysis, the only factors predictive of response to up-titrating CC were: pre-treatment LH level (r=0.51, p<0.01) and pre-treatment LH level ≤6 IU/ml (RR 2.1, p<0.01). CONCLUSIONS These data confirm that about two thirds of men with HG meet a robust responder definition using CC25mgs QOD. Up-titrating permitted 44% of patients not responding to CC25 QOD to meet the responder definition. We believe these data support starting CC at low dose and up-titrating when appropriate giving patients realistic expectations when the latter is necessary. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e779 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Clarisse R. Mazzola New York City, NY More articles by this author Darren J. Katz New York City, NY More articles by this author John P. Mulhall New York City, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...