Association between weight-adjusted waist index and testosterone deficiency in adult American men: findings from the national health and nutrition examination survey 2013-2016.

BACKGROUND: Testosterone deficiency (TD) and obesity are globally recognized health concerns, with a bidirectional causal relationship between them. And a newly discovered obesity indicator, the Weight-Adjusted-Waist Index (WWI), has been proposed, demonstrating superior adiposity identification capability compared to traditional body mass index (BMI) and waist circumference (WC) indicators. Therefore, we present the inaugural investigation into the associations of WWI with total testosterone levels and the risk of TD. METHODS: Data restricted to the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2016 were analyzed. Only males aged > 20 years who completed body measures and underwent serum sex hormone testing were potentially eligible for analysis. Weighted multivariable linear regression and logistic regression analyses were employed to investigate the relationships between WWI and total testosterone levels, and the risk of TD, respectively. Smooth curve fittings and weighted generalized additive model (GAM) regression were conducted to examine the linear relationship among them. Additionally, subgroup analyses with interaction tests were performed to assess the stability of the results. RESULTS: Finally, a total of 4099 participants with complete data on testosterone and WWI were included in the formal analysis. The mean age of study participants was 46.74 ± 0.35 years with a TD prevalence of 25.54%. After adjusting all potential confounders, the continuous WWI displayed a negative linear relationship with total testosterone levels (ß=-61.41, 95%CI: -72.53, -50.29, P < 0.0001) and a positive linear relationship with risk of TD (OR = 1.88, 95%CI: 1.47, 2.39, P < 0.0001). When WWI was transformed into quartiles as a categorical variable, participants in Q4 exhibited lower total testosterone levels (ß=-115.4, 95%CI: -142.34, -88.45, P < 0.0001) and a higher risk of TD (OR = 3.38, 95% CI: 2.10, 5.44, P < 0.001). These associations remained stable in subgroup analyses without significant interaction (all P for interaction > 0.05). CONCLUSIONS: This investigation firstly unveiled a negative linear association between WWI and total testosterone levels, coupled with a positive linear relationship with the prevalence of TD in U.S. male adults aged 20 years and older. Further studies are needed to validate the potential utility of WWI for the early identification and timely intervention of TD.

Associations between brain network, puberty, and behaviors in boys with Klinefelter syndrome.

BACKGROUND: Klinefelter syndrome (KS), also referred to as XXY syndrome, is a significant but inadequately studied risk factor for neuropsychiatric disability. Whether alterations in functional brain connectivity or pubertal delays are associated with aberrant cognitive-behavioral outcomes in individuals with KS is largely unknown. In this observational study, we investigated KS-related alterations in the resting-state brain network, testosterone level, and cognitive-behavioral impairment in adolescents with Klinefelter syndrome. METHODS: We recruited 46 boys with KS, ages 8 to 17 years, and 51 age-matched typically developing (TD) boys. All participants underwent resting-state functional magnetic resonance imaging scans, pubertal, and cognitive-behavioral assessments. Resting-state functional connectivity and regional brain activity of the participants were assessed. RESULTS: We found widespread alterations in global functional connectivity among the inferior frontal gyrus, temporal-parietal area, and hippocampus in boys with KS. Aberrant regional activities, including enhanced fALFF in the motor area and reduced ReHo in the caudate, were also found in the KS group compared to the TD children. Further, using machine learning methods, brain network alterations in these regions accurately differentiated boys with KS from TD controls. Finally, we showed that the alterations of brain network properties not only effectively predict cognitive-behavioral impairment in boys with KS, but also appear to mediate the association between total testosterone level and language ability, a cognitive domain at particular risk for dysfunction in this condition. CONCLUSION: Our results offer an informatic neurobiological foundation for understanding cognitive-behavioral impairments in individuals with KS and contribute to our understanding of the interplay between pubertal status, brain function, and cognitive-behavioral outcome in this population.

Exposure to zinc oxide nanoparticles induced reproductive toxicities in male Sprague Dawley rats.

BACKGROUND: This research delves into the reproductive toxicology of zinc oxide nanoparticles (ZnO-NPs) in male Sprague Dawley rats. It specifically examines the repercussions of Zn accumulation in the testes, alterations in testosterone levels, and histopathological changes in the gonadal tissues. AIMS: The primary objective of this study is to elucidate the extent of reproductive toxicity induced by ZnO-NPs in male Sprague Dawley rats. The investigation aims to contribute to a deeper understanding of the potential endocrine and reproductive disruptions caused by ZnO-NPs exposure. METHODS: Characterization techniques including SEM-EDX and XRD affirmed the characteristic nature of ZnO-NPs. Twenty-five healthy post weaning rats (200-250 g) were intraperitoneally exposed to different concentrations of ZnO-NPs @ 10 or 20 or 30 mg/kg BW for 28 days on alternate days. RESULTS: Results showed significant dose dependent decline in the body weight and testicular somatic index of rats. It also showed significant dose dependent accumulation of Zn in testis with increasing dose of ZnO-NPs. Conversely, serum testosterone level and sperm count were reduced with increasing dose of ZnO-NPs. Histological results showed dose dependent abnormalities i.e., vacuolization, edema, hemorrhage, destruction of seminiferous tubules, loss of germ cells and necrosis in rat testis. CONCLUSION: The findings of this study clearly indicate that high doses of zinc oxide nanoparticles (ZnO-NPs) can adversely affect the structural integrity and functional efficacy of the male reproductive system. Given these results, it becomes crucial to implement stringent precautionary measures in the utilization of ZnO-NPs, particularly in cosmetics and other relevant sectors. Such measures are imperative to mitigate the toxicological impact of ZnO-NPs on the male reproductive system and potentially on other related physiological functions. This study underscores the need for regulatory vigilance and safety assessments in the application of nanotechnology to safeguard human health.

Breed Differences in Serum Testosterone Levels of Male Pigs Are Highly Correlated with Differences in Testicular mRNA Levels of Enzymes and Proteins Involved in Testosterone Biosynthesis Process.

To clarify the causes of breed differences in serum testosterone levels of male pigs, which affect the mRNA expression of drug metabolizing enzymes and drug transporters in the liver and kidney, we focused on testicular enzymes and proteins involved in testosterone biosynthesis process and comparatively examined their mRNA levels by real time RT-PCR among low serum testosterone-type Landrace pigs and high serum testosterone-type Meishan and Landrace/Meishan-crossbreed (LM and ML) pigs. Testicular mRNA levels of the enzymes (3-hydroxy-3-methylglutaryl-CoA synthase 1 and 3-hydroxy-3-methylglutaryl-CoA reductase) and proteins (low density lipoprotein receptor and scavenger receptor class B member 1) affecting intracellular levels of cholesterol, a precursor of testosterone, were 2-5-fold higher in Meishan, LM and ML pigs than in Landrace pigs. Likewise, the mRNA levels of steroidogenic acute regulatory protein, which imports cholesterol to the inner mitochondrial membrane, and of testosterone biosynthesis enzymes (CYP11A1 and CYP17A1) were over 10-fold and approximately 3-fold higher, respectively, in Meishan, LM and ML pigs than in Landrace pigs. Furthermore, positive correlations between those mRNA levels and serum testosterone levels were observed. Despite large breed differences in testicular mRNA levels described above, no significant breed differences in intratesticular testosterone levels were observed. The present findings strongly suggest that breed differences in serum testosterone levels of male pigs are probably, at least in part, caused by differences in testicular mRNA levels of enzymes and proteins involved in testosterone biosynthesis process and by differences in the levels of testosterone released from testes.

The association between serum testosterone level and congestive heart failure in US male adults: data from National Health and Nutrition Examination Survey (NHANES) 2011-2016.

BACKGROUND: This study aimed to investigate the relationship between serum testosterone levels and the risk of congestive heart failure (CHF) in adult males. Previous research has suggested a potential link between serum testosterone and cardiovascular health, but the findings have been inconclusive. METHODS: This study was cross-sectional, and the data were obtained from the 2011-2016 cycle of the National Health and Nutrition Examination Survey (NHANES), which included a sample of 6,841 male participants. Serum testosterone levels were measured using a standardized assay, and CHF status was assessed through self-reporting. Covariates such as age, ethnicity, lifestyle factors, and health conditions were considered in the analysis. RESULTS: Among the participants, 242 individuals had a documented history of CHF. We observed a linear correlation between serum testosterone levels and CHF occurrence, with higher serum testosterone levels associated with a decreased risk of CHF (Q4 vs. Q1, OR = 0.29, 95% CI: 0.19-0.47, P < 0.001). After adjusting for confounding variables, multivariate analysis revealed that high serum testosterone levels remained significantly associated with a lower risk of CHF (OR: 0.47, 95% CI: 0.27-0.80, P = 0.01). Subgroup analysis indicated a significant association between high serum testosterone levels and reduced CHF risk in individuals over 50 years old. CONCLUSION: Our findings suggest that the serum testosterone level was positively associated with CHF in adult males. This study highlights the potential role of serum testosterone in cardiovascular health, particularly in older individuals. Further research is needed to elucidate the underlying mechanisms and explore the clinical implications of these findings.

Preoperative and postoperative blood testosterone levels in patients with acromegaly: a prospective study.

Purpose: To investigate the prevalence of low blood testosterone level (LTL) and its determinant factors among active male acromegaly patients, as well as the effect of surgery on LTL in male acromegaly patients. Methods: A retrospective, single-center study focused on 252 male acromegaly patients aged 18 years-60 years diagnosed in the Peking Union Medical College Hospital from January 2015 to December 2018 was carried out. The measurements of preoperative and postoperative testosterone levels, serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), and other clinical data were analyzed. Results: Forty per cent of subjects included were diagnosed with LTL pre surgery. Patients were divided into normal testosterone level (NTL) and LTL groups based on their testosterone level. There were significant differences (p < 0.01) between groups in the presence of macroadenomas, invasion of the cavernous sinus, compression of the optic chiasm, and serum GH and prolactin levels pre surgery. Invasion of the cavernous sinus [odds ratio (OR) = 4.299; p = 0.000] and serum prolactin level (OR = 1.023, p = 0.001) were independent predictors of LTLs in male patients before surgical intervention. A total of 67.9% of LTL patients recovered during the follow-up, with a new-onset rate of 3.4%. Body mass index, invasion of the cavernous sinus, GH, IGF-1, and prolactin levels, the presence of a prolactin-secreting tumor, and recovery from acromegaly were significantly different (p < 0.05) in the NTL group and in the LTL group during the follow-up. The presence of a prolactin-secreting tumor (OR = 0.224; p = 0.001) and recovery from acromegaly (OR = 0.168; p = 0.006) were independent predictors of LTLs in male acromegaly patients during the follow-up. Conclusion: The invasiveness of tumor and levels of blood prolactin are independent factors for LTLs before surgery, whereas GH and IGF-1 levels are not. Most male patients can recover from LTL after tumor restriction surgery: those who recover from acromegaly have a better chance of recovering from LTL.

The Fatty Liver Index, the Strongest Risk Factor for Low Testosterone Level.

INTRODUCTION: The study aimed to determine if hepatic steatosis assessed by fatty liver index (FLI) was an independent risk factor for male low testosterone level and whether the FLI was the strongest risk factor for low testosterone level in two different age groups. METHODS: Two cross-sectional studies were performed. A total of 3,443 male participants (aged 46-75) were recruited into study A (part of lONgitudinal study (REACTION)). Then a total of 267 male participants (aged 25-45) were recruited into study B. Serum total testosterone (TT) and sex hormone-binding globulin (SHBG) levels, indicators for assessing hepatic steatosis were measured. The Pearson correlation and regression analysis were performed to investigate the risk factors for low testosterone level. RESULTS: The FLI had the strongest negative correlation with serum testosterone in the study A (r = -0.436) and B (r = -0.542). Compared with patients with a FLI lower than 30, the risk for low testosterone level increased by 3.48-fold in subjects with a FLI higher than 60 adjusted for potential risk factors in study A. In study B, the odds ratio of low testosterone level in patients with potential hepatic steatosis was 4.26 (1.57-11.60) after adjusted for age and homeostasis model assessment of insulin resistance (HOMA-IR) and 0.59 (0.14-2.60) after adjusted for age, HOMA-IR, waist circumference, body mass index, and SHBG. CONCLUSIONS: FLI was the strongest risk factor for male low testosterone level independent of insulin resistance in male populations of different ages; however, the association can be modulated by SHBG levels in the young. SIGNIFICANCE STATEMENT: In the study, FLI was the strongest negative risk factor for low testosterone level in the Chinese adult male population. The results suggested that hepatic steatosis assessed by the FLI was the main risk factor for male low testosterone level, independent of age, insulin resistance, smoking, and drinking status; however, the association of FLI and TT levels can be modulated by SHBG levels. Taken together these findings indicate that clinical physicians should pay more attention to the FLI index and hepatic steatosis, so that they can take advantage of them for assessing the risk of developing of low testosterone level in the male population.

Early Postnatal Experience Modifies Activation of the Pituitary Testicular Complex in Male House Mice (Mus Musculus) Exposed to the Odor of Receptive Con- and Heterospecific Females.

For the first time, it was shown that activation of the pituitary-testicular complex in male house mice exposed to the odor of receptive females of their own and closely related species was modified under the influence of early postnatal experience and the maternal environment. We have confirmed associated formation of behavioral and physiological mechanisms of precopulatory isolation in early ontogenesis. The serum levels of free testosterone in males of closely related species M. spicilegus and M. m. wagneri differ, it is significantly lower in mound-building mice. In males fostered by a conspecific female, the level of free testosterone was significantly lower when exposed to a heterospecific female odor in comparison with a conspecific odor. The rearing of M. m. wagneri males by females of a closely related species led to a decrease in the testosterone response caused by exposure to female chemosignals (both con- and heterospecific) and to the absence of differences in the serum level of free testosterone when exposed to the odor of a female of their own or closely related species. These results indicate that the rearing conditions had a significant influence on the formation of hormonal mechanisms of reproductive isolation.

Genetically elevated bioavailable testosterone level was associated with the occurrence of benign prostatic hyperplasia.

BACKGROUND: Recent studies identified several risk factors of benign prostatic hyperplasia (BPH), including dyslipidemia, type 2 diabetes mellitus, hypertension, and obesity. But they were not so reliable and some studies contradicted with one another. Hence, a reliable method is urgently needed to explore exact factors that facilitated BPH development. METHODS: The study was based on Mendelian randomization (MR) design. All participants were from the most recent genome-wide association studies (GWAS) with large sample size. The causal associations between nine phenotypes (total testosterone level, bioavailable testosterone level, sex hormone-binding globulin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, type 2 diabetes mellitus, hyper-tension, and body mass index) and BPH outcome were estimated. Two sample MR, bidirectional MR, and multivariate MR (MVMR) were performed. RESULTS: Increase in bioavailable testosterone level was able to induce BPH based on nearly all combination methods [beta (95% confidence interval (CI)): 0.20 (0.06-0.34) for inverse variance weighted (IVW)]. The other traits seemed to interact with testosterone level and did not cause BPH generally. Higher triglycerides level was likely to raise bioavailable testosterone level [beta (95% CI): 0.04 (0.01-0.06) for IVW]. In MVMR model, bioavailable testosterone level was still associated with BPH occurrence [beta (95% CI) 0.27 (0.03-0.50) for IVW]. CONCLUSIONS: We for the first time validated the central role of bioavailable testosterone level in the pathogenesis of BPH. The complex associations between other traits and BPH should be further investigated.

Viabilidad de la varicocelectomía subinguinal con gafas de aumento en el tratamiento de la infertilidad masculina / Feasibility of loupe assisted subinguinal varicocelectomy in treatment of male infertility

Objetivos: Evaluar el impacto de la varicocelectomía subinguinal con gafas de aumento sobre la calidad del semen, el nivel de testosterona sérica y las tasas de embarazo espontáneo.MétodosSe recogieron datos de forma prospectiva de 102 hombres infértiles con varicocele clínico. Se compararon los valores preoperatorios de los parámetros de análisis de semen y el nivel de testosterona sérica con los valores postoperatorios a los 6 meses. Se evaluó la tasa de embarazo espontáneo a los 6 meses.ResultadosLa edad media de los pacientes era de 31,56±4,31 años. Se registró infertilidad primaria en 86 pacientes e infertilidad secundaria en 16. Se observó varicocele bilateral en 79 pacientes y varicocele unilateral en 23. La concentración total de espermatozoides (×106/ml) antes y después de la varicocelectomía fue de 12,82±3,91 y 20,06±2,13, respectivamente (p<0,0001). La motilidad espermática total (%) pre y posvaricocelectomía fue de 37,67±7,23 y 55,46±4,51 respectivamente (p<0,0001). La morfología espermática (criterios estrictos de morfología Kruger, %) antes y después de la varicocelectomía fue de 3,11±0,80 y 3,70±0,78, respectivamente (p<0,0001). El nivel de testosterona sérica (ng/dl) antes y después de la varicocelectomía fue de 323,90±67,81 y 396,74±40,88 respectivamente (p<0,0001). La tasa de embarazo espontáneo en las parejas con infertilidad primaria y secundaria fue de 18,60% y 31,25%, respectivamente. La diferencia de tasas no fue significativa (p=0,251). La tasa global de embarazo espontáneo fue del 20,5%.ConclusiónLa varicocelectomía subinguinal con gafas de aumento es una modalidad segura y eficaz para el tratamiento de varones infértiles, especialmente cuando no se dispone de medios para la cirugía microscópica. Sin embargo, solo los estudios comparativos de gran tamaño o los ensayos multicéntricos pueden confirmarlo. (AU)

Objectives: To study the impact of loupe assisted subinguinal varicocelectomy on semen quality, serum testosterone level, and spontaneous pregnancy rate.MethodsThe data were prospectively collected for 102 infertile men with clinical varicocele. The preoperative values of semen analysis parameters and serum testosterone level were compared with postoperative values at 6 months. Spontaneous pregnancy was assessed at 6 months.ResultsThe mean age of patients was 31.56±4.31 years. Primary infertility was reported in 86 patients, while 16 had secondary infertility. Bilateral varicocele was seen in 79 patients while 23 had a unilateral varicocele. The total sperm concentration (x106/ml) before and after varicocelectomy was 12.82±3.91 and 20.06±2.13 respectively (P<.0001). The total sperm motility (%) before and after varicocelectomy was 37.67±7.23 and 55.46±4.51 respectively (P<.0001). The sperm morphology (Kruger/Strict morphology criteria, %) before and after varicocelectomy was 3.11±0.80 and 3.70±0.78 respectively (P<.0001). The serum testosterone level (ng/dl) before and after varicocelectomy was 323.90±67.81 and 396.74±40.88 respectively (p<0.0001). The Spontaneous pregnancy rate in couples with primary and secondary infertility was 18.60% and 31.25% respectively. The difference in their rates was not significant (P=.251). The overall spontaneous pregnancy rate was 20.5%.ConclusionLoupe-assisted sub-inguinal varicocelectomy is a safe and effective modality for treating infertile men, particularly when provision for microscopic surgery is unavailable. However, only large size comparative studies or multi-centric trials can confirm this. (AU)

Testosterone Replacement Therapy in Chronic Kidney Disease Patients.

(Background) The aim of our study was to evaluate the efficacy and safety of testosterone replacement therapy (TRT) in men with chronic kidney disease and hypogonadism on conservative and hemodialysis treatment. (Methods) The studied population consisted of 38 men on hemodialysis (HD), 46 men with CKD stages II-IV (predialysis group, PreD) and 35 men without kidney disease who were similar in age to others (control group). Serum total testosterone level (TT) was measured, and free testosterone level (fT) was calculated. Hypogonadism criteria according to the EAU definition were fulfilled by 26 men on HD (68.4%) and by 24 men from the PreD group (52%). Testosterone replacement therapy (TRT) with testosterone enanthate in intramuscular injections every 3 weeks was applied in 15 men from HD and in 14 men from PreD. The safety of TRT was monitored by measuring PSA and overhydration. (Results) A significant rise of TT and fT was observed after 3 months of TRT, but no significant changes were observed after 6 and 12 months in the HD and PreD group. An intensity of clinical symptoms of hypogonadism measured by ADAM (androgen deficiency in the ageing male) questionnaire gradually decreased, and the intensity of erectile dysfunction measured by the IIEF-5 (international index of erectile functioning) questionnaire also decreased after 3, 6 and 12 months of TRT in the HD and PreD group. (Conclusions) The applied model of TRT is effective in the correction of clinical signs of hypogonadism without a significant risk of overhydration or PSA changes.

Effect of Testosterone Replacement Therapy on Quality of Life and Sexual Function in Testicular Cancer Survivors With Mild Leydig Cell Insufficiency: Results From a Randomized Double-blind Trial.

BACKGROUND: Testicular cancer (TC) treatment leaves many patients with low levels of testosterone. While most TC patients with low testosterone (< - 2 SD) and hypogonadal symptoms will initiate testosterone replacement therapy (TRT), the role of TRT in patients with mild Leydig cell insufficiency, defined as elevated luteinizing hormone in combination with borderline low testosterone, is unknown. To clarify if TRT improves symptoms of depression and anxiety, sexual function, fatigue, and quality of life in TC survivors with mild Leydig cell insufficiency. MATERIALS AND METHODS: In total, 69 men aged between 18 and 65 years with mild Leydig cell insufficiency after TC treatment were randomized 1:1 to 12 months daily transdermal testosterone (maximum dose 40 mg/daily) vs. placebo. Patient reported anxiety, depression, sexual function, fatigue, and overall quality of life were assessed at baseline, after 6- and 12 months treatment, and 3 months post-treatment using validated questionnaires. RESULTS: After 12 months of treatment, median luteinizing hormone and median free testosterone were normalized in the testosterone group. Compared to placebo, TRT was not associated with statistically significant improvement of symptoms of anxiety and depression, sexual function, fatigue, and overall quality of life. Testosterone replacement therapy did not improve anxiety, depression, sexual function, fatigue, or overall quality of life in patients with mild Leydig cell insufficiency compared to placebo. CONCLUSION: Routine TRT in TC survivors with mild Leydig cell insufficiency to improve sexual function and quality of life cannot be generally recommended. The findings should preferably be validated in a larger cohort.

Feasibility of loupe assisted subinguinal varicocelectomy in treatment of male infertility.

OBJECTIVES: To study the impact of loupe assisted subinguinal varicocelectomy on semen quality, serum testosterone level, and spontaneous pregnancy rate. METHODS: The data were prospectively collected for 102 infertile men with clinical varicocele. The preoperative values of semen analysis parameters and serum testosterone level were compared with postoperative values at 6 months. Spontaneous pregnancy was assessed at 6 months. RESULTS: The mean age of patients was 31.56 ±â€¯4.31 years. Primary infertility was reported in 86 patients, while 16 had secondary infertility. Bilateral varicocele was seen in 79 patients while 23 had a unilateral varicocele. The total sperm concentration (×106/mL) before and after varicocelectomy was 12.82 ±â€¯3.91 and 20.06 ±â€¯2.13 respectively (P < .0001). The total sperm motility (%) before and after varicocelectomy was 37.67 ±â€¯7.23 and 55.46 ±â€¯4.51 respectively (P < .0001). The sperm morphology (Kruger/Strict morphology criteria, %) before and after varicocelectomy was 3.11 ±â€¯0.80 and 3.70 ±â€¯0.78 respectively (P < .0001). The serum testosterone level (ng/dL) before and after varicocelectomy was 323.90 ±â€¯67.81 and 396.74 ±â€¯40.88 respectively (P < .0001). The Spontaneous pregnancy rate in couples with primary and secondary infertility was 18.60% and 31.25% respectively. The difference in their rates was not significant (P = .251). The overall spontaneous pregnancy rate was 20.5%. CONCLUSION: Loupe-assisted sub-inguinal varicocelectomy is a safe and effective modality for treating infertile men, particularly when provision for microscopic surgery is unavailable. However, only large size comparative studies or multi-centric trials can confirm this.

Biochemical aspect of crime: a case study of testosterone levels among rapists in Enugu State

Testosterone concentration is a contributing factor to rape tendency. Our research aimed to determine the plasma testosterone concentrations in male rapists. Subjects (100) recruited from Enugu state prison grouped viz: Violent-rapist (VR), nonviolent-rapist (NVR), violent child-molester (VCM), nonviolent child-molester (NCM), and none rapist (NR). The blood sample was collected in the morning (8-9) for four months by veno-puncture and used in the determination. The testosterone levels determination was by the enzyme-linked immunosorbent assay method. The results indicated the mean age of 33 (VR), 34 (NVR), 46 (VCM), 47 (NCM), and 32 (NR). The age at first intercourse was highest in NCM (18) and lowest in VR (13). Heterosexuals were highest in VR (14) and lowest in NCM (6). Homosexuals were highest in NCM (4) and non in VM, NVR, and NR (0). In bisexuals, NVR and NCM were the highest (4), the NR (1) was the lowest. The concentrations of testosterone (in ng/100ml) were 8.65 (VR), 9.23 (NVR), 9.63 (VCM), 7.73 (NCM) and 7.95 (NR). The testosterone concentration of the VR, NVR, and VCM is higher than NR. The NCM was lower than the NR. This result suggests that VR, NVR, and VCM are associated with higher testosterone concentrations in males. The modest associations indicate that there might be other influencing factors. The relationship between testosterone levels in rapists and child molestation is, at best, tentative. In some people, hormonal factors might influence the likelihood of rape and child molestation.

Serum testosterone levels and testosterone 'bounce' phenomenon predict response to novel anti-androgen therapies in castration-resistant prostate cancer.

BACKGROUND: The relevance of continuous testosterone (TT) monitoring in castration-resistant prostate cancer (CRPC) remains in question. OBJECTIVE: To determine if TT levels before and during novel anti-androgen therapies (NAAT), and the TT 'bounce' phenomenon may predict treatment response in CRPC. MATERIALS AND METHODS: From 2014 through 2018, we identified 92 CRPC patients treated with either Abiraterone or Enzalutamide from a prospectively maintained cancer registry. The TT levels measured before and during NAAT were correlated with the oncological outcomes, determined by PSA response (% change), PSA progression-free survival (PFS) and overall survival (OS). RESULTS AND LIMITATIONS: At CRPC, 58 (63.0%) and 34 (37.0%) patients opted for Abiraterone and Enzalutamide respectively. Median TT levels at CRPC status before and during NAAT were 10.37 ng/dl and 20.46 ng/dl respectively. PSA response was superior in patients with a higher TT before NAAT (P:0.048, median difference: 18.22%, 95% CI 0.70 - 40.37) and longer time to CRPC (P: 0.041, median difference: 15.31%, 95% CI 1.84 -34.84), with a trend towards lower TT during NAAT (P: 0.062). Over a follow up of 33.0 months, 65 patients (70.7%) developed PSA progression. PSA PFS was longer in patients with higher TT before NAAT (16.3 vs. 10.8 months; P: 0.023), lower TT during NAAT (17.0 vs. 9.1 months; P: 0.001), and longer time to CRPC (13.4 vs. 8.0 months; P: 0.032). Importantly, better OS was observed in lower TT during NAAT (45.0 vs. 33.0 months; P:0.029) and longer time to CRPC (43.0 vs. 31.0 months; P: 0.025). The TT 'bounce' phenomenon was observed in 28 patients (33.3%), and was associated with a poorer PSA response (P: 0.029, median difference: 18.90%, 95% CI 3.83 - 41.45), shorter PSA PFS (8.6 vs 15.2 months, P: 0.002) and shorter OS (29.0 vs. 45.0 months, P: 0.012). CONCLUSION: In CRPC patients, TT behaviors before and during NAAT, and the 'bounce' phenomenon continue to predict treatment response and could guide clinical decisions.

Prognostic value of testosterone castration levels following androgen deprivation and high-dose radiotherapy in localized prostate cancer: Results from a phase III trial.

BACKGROUND/OBJECTIVE: The optimal prognostic value of testosterone following androgen deprivation therapy (ADT) is controversial. We studied the effect of serum testosterone levels on clinical outcome in localized prostate cancer (PCa) treated with ADT and high-dose radiotherapy (HRT). PATIENTS AND METHODS: The DART01/05 trial randomized 355 men with intermediate and high-risk PCa to 4 months of ADT plus HRT (STADT, N = 178) or the same treatment followed by 24 months of ADT (LTADT, N = 177). This study included patients treated with LTADT who had at least 3 determinations of testosterone during ADT (N = 154). Patients were stratified into 3 subgroups by testosterone level: minimum <20 ng/dL; median 20-49 ng/dL; and maximum ≥50 ng/dL. Kaplan-Meyer and Cox regression analysis were used for overall survival (OS) and Fine & Gray regression model for metastasis free survival (MFS), biochemical disease-free survival (bDFS) and time to TT recovery. RESULTS: There were no statistically significant differences in 10-year bDFS, MFS, or OS between the <20 ng/mL and 20-49 ng/dL subgroups. Multivariate analysis showed that a median testosterone ≥50 ng/dL was significantly associated with a decrease in bDFS (HR: 6.58, 95%CI 1.28-33.76, p = 0.03). Time to testosterone recovery after ADT did not correlate with bDFS, MFS, or OS and was not significantly associated with any of the testosterone subgroups. CONCLUSIONS: Our results do not support the concept that additional serum testosterone suppression below 20 ng/dL is associated with better outcomes than 20-49 ng/dL. Time to testosterone recovery after ADT and HRT did not impact clinical failure.

Association of daily step count and serum testosterone among men in the United States.

PURPOSE: To describe the association between daily activity (i.e., daily step counts and accelerometer intensity measures) and serum TT levels in a representative sample of US adults aged 18 years or older. METHODS: A retrospective cohort study was carried out utilizing the NHANES (National Health and Nutrition Examination Survey) 2003-2004 cycle. Physical activity was measured with a waist-worn uniaxial accelerometer (AM-7164; ActiGraph) for up to 7 days using a standardized protocol. Using linear and multivariable logistic regression controlling for relevant social, demographic, lifestyle, and comorbidity characteristics, we assessed the association between daily step counts and TT. RESULTS: A total of 279 subjects with a median age 46 (IQR: 33-56) were included in the analysis. 23.3% of the cohort had a low serum TT level (TT < 350 ng/dl). Compared to men who took <4000 steps per day, men who took >4000 or >8000 steps/day had a lower odd of being hypogonadal (OR 0.14, 95% CI: 0.07-0.49 and 0.08, 95%CI: 0.02-0.44, respectively). While a threshold effect was noted on average, TT increased 7 ng/dL for each additional 1000 steps taken daily (ß-estimate: 0.007, 95% CI: 0.002-0.013). CONCLUSIONS: Patients with the lowest daily step counts had higher odds of being hypogonadal. The current work supports a possible association between daily steps, total testosterone, and hypogonadism for men in the US.

Hormonal Treatment of Men with Nonobstructive Azoospermia: What Does the Evidence Suggest?

Hormonal stimulation of spermatogenesis prior to surgery has been tested by some authors to maximize the sperm retrieval yield in patients with nonobstructive azoospermia. Although the rationale of such an approach is theoretically sound, studies have provided conflicting results, and there are unmet questions that need to be addressed. In the present narrative review, we reviewed the current knowledge about the hormonal control of spermatogenesis, the relationship between presurgical serum hormones levels and sperm retrieval rates, and the results of studies investigating the effect of hormonal treatments prior to microdissection testicular sperm extraction. We pooled the available data about sperm retrieval rate in patients with low vs. normal testosterone levels, and found that patients with normal testosterone levels had a significantly higher chance of successful sperm retrieval compared to those with subnormal T levels (OR 1.63, 95% CI 1.08-2.45, p = 0.02). These data suggest that hormonal treatment may be justified in patients with hypogonadism; on the other hand, the available evidence is insufficient to recommend hormonal therapy as standard clinical practice to improve the sperm retrieval rate in patients with nonobstructive azoospermia.

SERUM HORMONE CONCENTRATIONS IN TRANSGENDER INDIVIDUALS RECEIVING GENDER-AFFIRMING HORMONE THERAPY: A LONGITUDINAL RETROSPECTIVE COHORT STUDY.

OBJECTIVE: To examine the association of various gender-affirming hormone therapy regimens with blood sex hormone concentrations in transgender individuals. METHODS: This retrospective study included transgender people receiving gender-affirming hormone therapy between January 2000 and September 2018. Data on patient demographics, laboratory values, and hormone dose and frequency were collected. Nonparametric tests and linear regression analyses were used to identify factors associated with serum hormone concentrations. RESULTS: Overall, 196 subjects (134 transgender women and 62 transgender men), with a total of 941 clinical visits, were included in this study. Transgender men receiving transdermal testosterone had a significantly lower median concentration of serum total testosterone when compared with those receiving injectable preparations (326.0 ng/dL vs 524.5 ng/dL, respectively, P = .018). Serum total estradiol concentrations in the transgender women were higher in those receiving intramuscular estrogen compared with those receiving oral and transdermal estrogen (366.0 pg/mL vs 102.0 pg/mL vs 70.8 pg/mL, respectively, P < .001). A dose-dependent increase in the hormone levels was observed for oral estradiol (P < .001) and injectable testosterone (P = .018) but not for intramuscular and transdermal estradiol. Older age and a history of gonadectomy in both the transgender men and women were associated with significantly higher concentrations of serum gender-affirming sex hormones. CONCLUSION: In the transgender men, all routes and formulations of testosterone appeared to be equally effective in achieving concentrations in the male range. The intramuscular injections of estradiol resulted in the highest serum concentrations of estradiol, whereas transdermal estradiol resulted in the lowest concentration. There was positive relationship between both oral estradiol and injectable testosterone dose and serum sex hormone concentrations in transgender people receiving GAHT.