Low Testosterone Concentrations Research Articles

Predictive value of low testosterone concentrations during and prior to enzalutamide treatment in metastatic castration-resistant prostate cancer

BackgroundEnzalutamide is an effective treatment for metastatic castration-resistant prostate cancer (mCRPC) patients. However, variances in responses are observed and there is a need for biomarkers predicting treatment outcome and selection. In this study, we aimed to explore the predictive value of testosterone for first-line enzalutamide treatment of mCRPC. MethodsA retrospective analysis of 72 mCRPC patients with no prior abiraterone or docetaxel treatment was performed. Serum testosterone was measured using a liquid chromatography tandem-mass spectrometry method. Association of pre- and during-enzalutimide treatment testosterone levels with progression-free survival (PFS) and failure-free survival (FFS) was investigated using univariate and multivariate Cox models. Testosterone levels were dichotomized into a low (Q1) and high (interquartile range-Q4) group. ResultsMedian PFS (7.4 v. 20.8 months, P<0.0001) and FFS (6.6 v. 17.7 months, P<0.0001) were shorter for patients with low testosterone levels (<0.217 nmol/L) during enzalutamide treatment. Furthermore, univariate Cox proportional hazards models revealed that low testosterone levels were associated with shorter PFS (HR 3.5, 95%CI 1.9-6.3; P<0.001) and FFS (HR 3.1, 95%CI 1.7–5.5; P<0.001). Pre-treatment testosterone levels were lower than during-treatment levels (P<0.0001) and low pre-treatment testosterone levels (<0.143 nmol/L) were associated with shorter median PFS (12.6 v. 20.5 months, P<0.01) and FFS (12.6 v. 22.5 months, P<0.01). ConclusionThe results of this study suggest that low serum testosterone levels during and prior to enzalutamide treatment can predict progression in mCRPC patients and identifies tumors resistant to next-in-line enzalutamide treatment. Validation in a prospective cohort is warranted.

Associations between salivary testosterone levels and cognitive function among 70-year-old Japanese elderly: A cross-sectional analysis of the SONIC study.

This cross-sectional study aimed to investigate the associations between salivary testosterone concentrations and cognitive function in 70-year-old Japanese elderly people without dementia and stroke. Participants were 197 Japanese community-dwelling people aged 69-71 years. Their salivary samples were collected, and their cognitive function was assessed using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Participants were also administered a 10-item recall and a 24-item recognition test. The data for 179 (106 men and 73 women) individuals were analyzed, excluding individuals with a past history of stroke and dementia. Multivariate logistic regression analyses were performed after adjusting for lifestyle factors and analyzing data separately for men and women. MoCA-J scores showed that men with low testosterone concentrations had a significantly greater risk of low cognitive performance than those with high testosterone concentrations (adjusted odds ratio: 4.72, 95% confidence interval: 1.06-21.00), while no significant association was found in women. The 10-item recall test scores showed that higher testosterone concentrations were significantly associated with greater recall in the second trial in women (standardized beta=0.24, P=0.040), whereas no significant association was found in men. Salivary testosterone concentrations were positively associated with better cognitive performance in older men and women. The associations between salivary testosterone concentrations and cognitive function were shown by different tasks for men and women. Geriatr Gerontol Int 2022; 22: 1040-1046.

Associations between Repeated Measures of Urinary Phthalate Metabolites with Hormones and Timing of Natural Menopause: The Study of Women&amp;#x27;s Health Across the Nation

Background and Aim: Studies on phthalate metabolites and sex hormones during the menopausal transition are limited and have yielded conflicting results. We aimed to examine the associations of phthalate metabolites with hormones including estradiol, testosterone, follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), anti-Müllerian hormone (AMH), and the timing of natural menopause. Methods: We examined 1,189 midlife women from the Study of Women’s Health Across the Nation aged 45-56 years in 1999-2000 who had complete information on phthalate metabolites and hormones while not receiving hormone therapy. Urinary concentrations of 12 phthalate metabolites were repeatedly measured in 1999-2000 and 2002-2003. Hormones were measured at the same time points. Linear mixed-effect models were used to calculate percent differences (%D) and 95% confidence intervals (CIs) in serum concentrations of estradiol, testosterone, FSH, SHBG, and AMH per doubling in urinary phthalate metabolites. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs of natural menopause per doubling increase in urinary phthalate metabolites. Results: We observed significant associations of phthalate metabolites with lower testosterone concentrations: mono (7-carboxy-2-methyloctyl) phthalate (MCOP) (%D: -2.08%, 95% CI: -3.66, -0.47), and mono-n-butyl phthalate (MnBP) (%D: -1.99%, 95% CI: -3.82, -0.13), after adjusting for multiple comparisons with false discovery rates &amp;#x3c; 5%. Lower AMH concentrations were also found with higher MECPP (%D: -14.26%, 95% CI: -24.10, -3.14), MEHHP (%D: -15.58%, 95% CI: -24.59, -5.50), and MEOHP (%D: -13.50%, 95% CI: -22.93, -2.90). No associations were observed for other hormones or timing of natural menopause. Conclusions: These results suggest that exposure to phthalates may affect circulating levels of testosterone in midlife women. Exposure to phthalates may also dimmish the ovarian reserve. Given the endocrine-disrupting role of phthalates, future studies are warranted to evaluate their impact on health outcomes among midlife women. Keywords: Phthalates; endocrine-disrupting chemicals; hormones; midlife women; menopause

Associations of testosterone and cortisol concentrations with sleep quality in Japanese male workers

Low testosterone concentrations are associated with disrupted sleep, and high levels of cortisol, which is elevated in response to stress, lead to insomnia. This study aimed to investigate the associations of testosterone and cortisol concentrations with sleep quality and to examine potential interactions between them in Japanese working men. This study was a cross-sectional design, and testosterone and cortisol concentrations in blood were the exposure variables and sleep parameters were the outcome variables. The Japanese version of the Pittsburgh Sleep Quality Index was used to measure sleep quality, and it included the total duration of sleep, time in bed (TIB), and sleep efficacy. We included 178 men (mean age = 49.1 years, standard deviation = 9.0) who completed all components in the questionnaire related to sleep and provided blood samples. Testosterone and cortisol concentrations were negatively associated with TIB (standardized beta = −0.15 and −0.24, p < 0.05, respectively), while only testosterone concentrations were positively associated with sleep efficacy (standardized beta = 0.15, p < 0.05). An interaction effect of testosterone and cortisol was significant for TIB and sleep efficacy (standardized beta for interaction term = 0.40, p < 0.001 and −0.22, p = 0.012, respectively). When stratified by cortisol concentrations, the associations between testosterone concentrations and sleep parameters were modified. Our findings suggest that associations between testosterone concentrations and sleep parameters are stronger at low cortisol concentrations, but not at high cortisol concentrations. High cortisol concentrations may diminish associations between low testosterone concentrations and diminished sleep efficacy.

Clinical Usefulness of Ultraperformance Liquid Chromatography-Tandem Mass Spectrometry Method for Low Serum Testosterone Measurement.

Mass spectrometry methods exhibit higher accuracy and lower variability than immunoassays at low testosterone concentrations. We developed and validated an ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay for quantifying serum total testosterone. We used an ExionLC UPLC (Sciex, Framingham, MA, USA) system and a Sciex Triple Quad 6500+ (Sciex) MS/MS system in electrospray ionization and positive ion modes with multiple reaction monitoring transitions to evaluate precision, accuracy, linearity, lower limit of quantitation (LLOQ), carryover, ion suppression, stability, and reference intervals. For method comparison, we measured serum testosterone concentrations using this method in 40 subjects whose testosterone concentrations ranged from 0.14 to 55.48 nmol/L as determined using the Architect i2000 immunoassay (Abbott Diagnostics, Abbott Park, IL, USA) and in an additional 160 sera with testosterone concentrations <1.67 nmol/L. The intra- and inter-run precision CVs were <2.81%, and the accuracy bias values were <3.85%, which were all acceptable. The verified linear interval was 0.03-180.84 nmol/L; the LLOQ was 0.03 nmol/L. No significant carryover and ion suppression were observed. The testosterone in serum was stable at 4°C, at -20°C, and after three freeze-thaw cycles. The reference intervals were successfully verified. The correlation was good at testosterone concentrations of 0.14-55.48 nmol/L; however, the Architect assay showed positive percent bias at concentrations <1.67 nmol/L. The UPLC-MS/MS assay shows acceptable performance, with a lower LLOQ than the immunoassay. This method will enable the quantitation of low testosterone concentrations.

Testosterone Deficiency as One of the Major Endocrine Disorders in Chronic Kidney Disease.

Reduced testosterone concentration is nowadays thought to be one of the main endocrine disorders in chronic kidney disease (CKD). It is caused by the dysfunction of the hypothalamic-pituitary-gonadal axis. The role of testosterone is multifactorial. Testosterone is responsible not only for reproductive processes, but it is a hormone which increases bone and muscle mass, improves lipid profile, insulin sensitivity, erythropoiesis, reduces blood pressure, and ameliorates mood and perception. The implications of hypogonadism in CKD are infertility and loss of libido, reduction of muscle mass and strength, disorders in bone mineralization, the development of sarcopenia and protein energy wasting (PEW), progression of atherosclerosis, increased visceral adiposity, insulin resistance, and anaemia. Reduced testosterone serum concentrations in CKD are associated with increased mortality rate. Testosterone supplementation improves sexual functions, reduces the level of inflammatory markers and blood pressure, stimulates muscle protein synthesis, improves insulin sensitivity and lipid profile, and increases muscle mass, bone mineral density, and haemoglobin concentration. It positively affects mood and well-being. The modes of testosterone supplementation are intramuscular injections, subcutaneous pellets, and percutaneous methods—patches and gels. Successful kidney transplantation may improve gonadal function and testosterone production, however, half of men with low testosterone concentrations before kidney transplantation do not restore hormonal function.

Metformin, testosterone, or both in men with obesity and low testosterone: A double-blind, parallel-group, randomized controlled trial

BackgroundMen with obesity tend to be insulin resistant and often have low-normal testosterone concentrations. We conducted a clinical trial aimed to evaluate potential therapeutic strategies for low testosterone in men with obesity. MethodsWe did a 1-year, parallel, randomized, double-blind, placebo-controlled trial, where we evaluated the independent and combined effects of metformin and testosterone in 106 men with obesity, aged 18–50 years, who had low levels of testosterone and no diabetes mellitus. The primary outcome was change in insulin resistance, measured as Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index. Secondary outcomes included changes in total and free serum testosterone, body composition, metabolic variables, erectile function, and health-related quality of life (HRQoL). ResultsIn the intention-to-treat analysis, the HOMA-IR index decreased significantly in all active groups compared to placebo (metformin −2.4, 95 % CI −4.1 to −0.8, p = 0.004; testosterone −2.7, 95 % CI −4.3 to −1.1, p = 0.001; combination −3.4, 95 % CI −5.0 to −1.8, p < 0.001). Combination therapy was not superior to testosterone alone in decreasing insulin resistance (−0.7, 95 % CI −2.3 to 0.9, p = 0.383). Only the combination of metformin plus testosterone significantly increased total and free testosterone concentrations, compared to placebo. No significant changes in body composition (except for a higher decrease in fat mass in the metformin and combination group), metabolic variables, erectile function, or HRQoL were found with any treatment. ConclusionsAmong men with obesity and low testosterone concentrations, the combination of metformin plus testosterone, metformin only, and testosterone only, compared to placebo, reduced insulin resistance with no evidence of additive benefit.

Correlations between behavior and hormone concentrations or gut microbiome imply that domestic cats (Felis silvestris catus) living in a group are not like 'groupmates'.

Domestic cats (Felis silvestris catus) can live in high densities, although most feline species are solitary and exclusively territorial animals; it is possible that certain behavioral strategies enable this phenomenon. These behaviors are regulated by hormones and the gut microbiome, which, in turn, is influenced by domestication. Therefore, we investigated the relationships between the sociality, hormone concentrations, and gut microbiome of domestic cats by conducting three sets of experiments for each group of five cats and analyzing their behavior, hormone concentrations (cortisol, oxytocin, and testosterone), and their gut microbiomes. We observed that individuals with high cortisol and testosterone concentrations established less contact with others, and individuals with high oxytocin concentrations did not exhibit affiliative behaviors as much as expected. Additionally, the higher the frequency of contact among the individuals, the greater the similarity in gut microbiome; gut microbial composition was also related to behavioral patterns and cortisol secretion. Notably, individuals with low cortisol and testosterone concentrations were highly tolerant, making high-density living easy. Oxytocin usually functions in an affiliative manner within groups, but our results suggest that even if typically solitary and territorial animals live in high densities, their oxytocin functions are opposite to those of typically group-living animals.

Pubertal Emergence of Testosterone Effects on Depressive Symptoms in Boys.

Puberty-driven increases in the secretion of testosterone may be a biological factor that protects males against the development of depression. Although all males produce testosterone, there are substantial between-person differences that could contribute to differential vulnerability to depression among pre-adolescent and adolescent boys, particularly after pubertal onset. Indeed, experimental animal and human data have shown that low testosterone increases risk for depressive-like symptoms in males, whereas higher levels of testosterone may be protective; however, prior studies have primarily investigated these effects in adulthood. This study investigated whether lower circulating levels of testosterone predict depressive symptoms in pre-adolescent and adolescent boys, and in particular, whether the testosterone-depression association becomes prominent with advancing pubertal maturation. Male twins (N = 213; ages 10-15 years) from the Michigan State University Twin Registry self-reported their depressive symptoms and pubertal status using the Children's Depression Inventory and the Pubertal Development Scale, respectively. Salivary testosterone was assayed using high-sensitivity enzyme immunoassays. Mixed Linear Models (MLMs), which could account for the non-independence of twin data, were used for analyses. As expected, lower testosterone concentrations were associated with higher depressive symptoms, and the magnitude of this effect increased with advancing pubertal status. In contrast, boys with higher levels of testosterone showed low levels of depressive symptomatology at all stages of pubertal maturation. Overall, these findings enhance understanding of within-sex variability in risk for depression in boys - average-to-high testosterone levels may underlie the general male resilience to depression after pubertal onset, whereas lower levels may increase vulnerability during/after puberty.

Higher premorbid serum testosterone predicts COVID-19-related mortality risk in men.

ObjectiveMen are at greater risk from COVID-19 than women. Older, overweight men, and those with type 2 diabetes, have lower testosterone concentrations and poorer COVID-19-related outcomes. We analysed the associations of premorbid serum testosterone concentrations, not confounded by the effects of acute SARS-CoV-2 infection, with COVID-19-related mortality risk in men.DesignThis study is a United Kingdom Biobank prospective cohort study of community-dwelling men aged 40–69 years.MethodsSerum total testosterone and sex hormone-binding globulin (SHBG) were measured at baseline (2006–2010). Free testosterone values were calculated (cFT). the incidence of SARS-CoV-2 infections and deaths related to COVID-19 were ascertained from 16 March 2020 to 31 January 2021 and modelled using time-stratified Cox regression.ResultsIn 159 964 men, there were 5558 SARS-CoV-2 infections and 438 COVID-19 deaths. Younger age, higher BMI, non-White ethnicity, lower educational attainment, and socioeconomic deprivation were associated with incidence of SARS-CoV-2 infections but total testosterone, SHBG, and cFT were not. Adjusting for potential confounders, higher total testosterone was associated with COVID-19-related mortality risk (overall trend P = 0.008; hazard ratios (95% CIs) quintile 1, Q1 vs Q5 (reference), 0.84 (0.65–1.12) Q2:Q5, 0.82 (0.63–1.10); Q3:Q5, 0.80 (0.66–1.00); Q4:Q5, 0.82 (0.75–0.93)). Higher SHBG was also associated with COVID-19 mortality risk (P = 0.008), but cFT was not (P = 0.248).ConclusionsMiddle-aged to older men with the highest premorbid serum total testosterone and SHBG concentrations are at greater risk of COVID-19-related mortality. Men could be advised that having relatively high serum testosterone concentrations does not protect against future COVID-19-related mortality. Further investigation of causality and potential underlying mechanisms is warranted.

Determination of testosterone in serum by magnetic molecularly imprinted polymer-coupled nano-ESI-MS

Monitoring clinical biomarkers, such as testosterone in serum, is important for disease assessment. Due to the very low concentration of testosterone in serum, we have developed a new strategy for its enrichment in serum samples by magnetic molecularly imprinted polymers (MMIPs) technology and detection by nano-electrospray ionization mass spectrometry (Nano-ESI-MS). Testosterone was selectively extracted and enriched by the imprinted polymers on the surface of magnetic particles and the complex matrix was eliminated from the serum. The linear calibration curve was in the range of 0.1–10 μg/L and the limit of detection was 11.4 ng/L. The recovery and repeatability of the spiked serum were satisfactory. These results demonstrate that the proposed method is a promising approach for quantitative analysis of testosterone in serum.

Testosterone therapy reduces hepatic steatosis in men with type 2 diabetes and low serum testosterone concentrations.

BACKGROUNDNon-alcoholic fatty liver disease (NAFLD) is highly prevalent in people with diabetes with no available treatment. AIMTo explore the effect of testosterone treatment on liver. Testosterone therapy improves insulin resistance and reduces total body fat, but its impact on the liver remains poorly studied.METHODSThis secondary analysis of a 40 wk, randomised, double-blinded, placebo-controlled trial of intramuscular testosterone undecanoate in men with type 2 diabetes and lowered serum testosterone concentrations evaluated the change in hepatic steatosis as measured by liver fat fraction on magnetic resonance imaging (MRI).RESULTSOf 88 patients enrolled in the index study, 39 had liver MRIs of whom 20 received testosterone therapy and 19 received placebo. All patients had > 5% hepatic steatosis at baseline and 38 of 39 patients met diagnostic criteria for NAFLD. Median liver fat at baseline was 15.0% (IQR 11.5%-21.1%) in the testosterone and 18.4% (15.0%-28.9%) in the placebo group. Median ALT was 34units/L (26-38) in the testosterone and 32units/L (25-52) in the placebo group. At week 40, patients receiving testosterone had a median reduction in absolute liver fat of 3.5% (IQR 2.9%-6.4%) compared with an increase of 1.2% in the placebo arm (between-group difference 4.7% P < 0.001). After controlling for baseline liver fat, testosterone therapy was associated with a relative reduction in liver fat of 38.3% (95% confidence interval 25.4%-49.0%, P < 0.001). CONCLUSIONTestosterone therapy was associated with a reduction in hepatic steatosis in men with diabetes and low serum testosterone. Future randomised studies of testosterone therapy in men with NAFLD focusing on liver-related endpoints are therefore justified.

Definition of Castrate Resistant Prostate Cancer: New Insights.

The term castrate resistant prostate cancer (CRPC) was initially proposed by the Prostate Cancer Working Group 2 in 2008 to define the state of clinical and/or biochemical progression of prostate cancer (PCa) in an environment with very low serum testosterone concentration. Clinical progression is based on the radiological imaging proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) adapted to PCa. Biochemical progression is defined as an over 25% increase in serum prostate-specific antigen within two consecutive measurements separated by at least one week, and an absolute value above 2.0 ng/mL. Finally, the castrate environment is usually defined as a serum testosterone concentration maintained below 50 ng/dL or 1.7 nmol/dL. This definition does not incorporate the new and more accurate imaging modalities to assess clinical progression and the capability of the new biochemical measurements to assess the true castration environment. Ga-68-PSMA-11 PET CT/MRI and whole-body MRI are the new imaging modalities that should replace the classic thoracic CT scan, abdomino-pelvic CT scan, and technetium 99-m bone scintigraphy. In addition, Ga-68-PSMA-11 PET is the current basis for the new therapies targeting metastatic sites. Moreover, the current methods for measuring the very low serum testosterone concentrations in clinical laboratories are the widespread chemiluminescent assays, which are inappropriate, while LC-MSMS is the only method recommended to assess the castrate environment. In addition, recent research shows that serum luteinising hormone concentration associates better than serum testosterone with the castration environment, even when it is measured with LC-MSMS. In summary, the current definition of CRPC seems outdated. An extensive update to diagnose true CRPC is also needed to differentiate CRPC men with M0 (non-metastatic) from those with M1 (metastatic) CRPC. WC: 277.

Testosterone treatment of late-onset hypogonadism - benefits and risks.

As men age, their serum testosterone concentration falls, the total testosterone concentration barely but the free testosterone concentration more so. Testosterone treatment of older men who have low testosterone concentrations can ameliorate several consequences of this fall, including libido and sexual activity, distance walked, hemoglobin and volumetric bone mineral density and strength, but not vitality and cognitive function. The possibility that testosterone treatment of late-onset hypogonadism increases the risks of benign prostatic hyperplasia, prostate cancer or heart disease has been suggested but will not be determined until larger and longer trials are conducted.

Comparison of Patterns of Use and Clinical Outcomes Between Injections of Testosterone Undecanoate and Testosterone Cypionate: An Electronic Health Record Cohort Study

Background: Hypogonadism is characterized by low serum testosterone concentrations and the associated clinical manifestations (e.g., reduced libido, erectile dysfunction, and fatigue); testosterone therapy (TTh) is the primary treatment. This study compared treatment patterns and health outcomes in men using injection TTh with long-acting testosterone undecanoate (TU) injection versus short-acting testosterone cypionate (TC) injection. Methods: A U.S. electronic health records (EHR) database was retrospectively reviewed to identify adult men who had TTh of TU or TC (index treatment) between January 1, 2014, and December 31, 2018, and ≥1 EHR within the 12 months before and 6 months after index treatment. Results: There were 948 patients in the TU cohort and 121,852 in the TC cohort, of whom 419 and 86,219, respectively, were TTh-naive at index treatment. Hypogonadism diagnosis was documented in 81.1% and 58.8% of patients in the overall TU and TC cohorts, respectively. During the 1-year postindex period, higher adherence rates were observed in the TU versus TC cohort during months 7 through 12 (82.0% vs. 40.8%; p < 0.001), and a greater percentage of patients continued to receive TU (41.9%) versus TC (8.2%) for 12 months (p < 0.001). Variability in total testosterone levels was lower for TU versus TC in the TTh-naive population. Conclusions: In this retrospective EHR study, men who received TU demonstrated a two-fold higher adherence, a five-fold improved maintenance on index TTh, and more stable testosterone levels at 1-year follow-up versus men who received TC. More consistent TTh use observed with TU may result in improved health outcomes for men with hypogonadism.

Ethnic differences in serum testosterone concentration among Malay, Chinese and Indian men: A cross-sectional study.

To investigate non-urological patients with multiple comorbidities for factors contributing towards differences in testosterone concentration in multiethnic Malaysian men. An observational study. Sexually active men, ≥40 years, with no known urological problems, were recruited at the phlebotomy clinic at our centre. A brief history along with latest fasting lipid profile and plasma glucose levels were obtained. An Aging Male Symptoms questionnaire was administered; waist circumference (WC) and serum testosterone concentration were measured. Analysis of testosterone concentration between Malay, Indian and Chinese men was performed. Statistical tests such as analysis of variance, χ2 test, univariate and multivariable regression were performed. Any p < .05 was noted as statistically significant. Among the 604 participants analysed, mean testosterone concentration was significantly lower in Malays (15.1 ± 5.9 nmol/L) compared to the Chinese (17.0 ± 5.9 nmol/L) and Indian (16.1 ± 6.5 nmol/L) participants. The mean WC was also found to be higher among the Malays (96.1 ± 10.9 cm) compared to Chinese (92.6 ± 9.6 cm) and Indians (95.6 ± 9.9 cm). Testosterone concentration tended to be lower with higher age, but this was not statistically significant (p > .05). In the multivariable analysis only Malay ethnicity, WC ≥ 90 cm and low high-density lipoprotein (HDL) were associated with lower testosterone concentration. In this study, Malaysian men of Malay origin had lower testosterone concentration compared with Indian and Chinese men. WC and low HDL were also associated with lower testosterone concentrations.

Low testosterone concentrations and risk of ischaemic cardiovascular disease in ageing: not just a problem for older men

Coronary heart disease, myocardial infarction, and ischaemic stroke increase sharply in prevalence with age in both men and women.1 The understanding that such diseases are more likely to occur in women after the menopause has motivated research into the cardiovascular effects of low blood oestrogen concentrations. By contrast, it is less well appreciated that blood testosterone concentrations also decrease gradually with age in women, although these concentrations can rise again at the start of the seventh decade.

Annals for Educators - February 2022.

Annals for Educators - February 2022.

Hypogonadism: a neglected comorbidity in young and middle-aged HIV-positive men on effective combination antiretroviral therapy.

Male hypogonadism is poorly characterized in young-to-middle-aged people with HIV (PWH). We used a reliable free testosterone assay to assess the prevalence and predictive factors for male hypogonadism in PWH on effective combined antiretroviral therapy (cART). A French cross-sectional study from January 2013 to June 2016. We included HIV-1-infected men aged between 18 and 50years with HIV loads of 50 RNA copies/ml or less, on effective cART for at least 6 months. Hypogonadism was defined, according to guidelines, as a mean calculated serum free testosterone concentration less than 70pg/ml (Vermeulen equation). Sociodemographic, anthropo-metric, bone-densitometry, hormonal, immunovirological, metabolic, and therapeutic parameters were collected. The IIEF-5, HAM-D, and AMS scales, respectively, assessed erectile function, depression, and quality of life. Overall, 240 patients were enrolled, 231 were analyzed. Low free testosterone concentrations (<70pg/ml) were recorded in 20 patients (8.7%), and were exclusively of secondary origin. In multivariable analysis, the risk factors predictive of male hypogonadism were age more than 43 years [adjusted odds ratio (aOR) 3.17, 95% confidence interval (95% CI) 1.02-9.86; P = 0.04], total fat percentage more than 19% (aOR3.5, 95% CI 1.18-10.37; P = 0.02), and treatment including efavirenz (aOR3.77, 95% CI 1.29-10.98; P = 0.02). A nadir CD4+ T-cell count more than 200 cells / μl (aOR 0.22, 95% CI 0.07-0.65;P < 0.01) were protective. Male hypogonadism remains common in young-to-middle-aged PWH with stably suppressed viral replication. Treatment including efavirenz, being over 43 years old, and having a total body fat percentage greater than 19% could be used as criteria for identifying PWH at risk. Early screening for male hypogonadism might improve care by identifying patients requiring testosterone replacement.

Could Lower Testosterone in Older Men Explain Higher COVID-19 Morbidity and Mortalities?

The health scourge imposed on humanity by the COVID-19 pandemic seems not to recede. This fact warrants refined and novel ideas analyzing different aspects of the illness. One such aspect is related to the observation that most COVID-19 casualties were older males, a tendency also noticed in the epidemics of SARS-CoV in 2003 and the Middle East respiratory syndrome in 2012. This gender-related difference in the COVID-19 death toll might be directly involved with testosterone (TEST) and its plasmatic concentration in men. TEST has been demonstrated to provide men with anti-inflammatory and immunological advantages. As the plasmatic concentration of this androgen decreases with age, the health benefit it confers also diminishes. Low plasmatic levels of TEST can be determinant in the infection’s outcome and might be related to a dysfunctional cell Ca2+ homeostasis. Not only does TEST modulate the activity of diverse proteins that regulate cellular calcium concentrations, but these proteins have also been proven to be necessary for the replication of many viruses. Therefore, we discuss herein how TEST regulates different Ca2+-handling proteins in healthy tissues and propose how low TEST concentrations might facilitate the replication of the SARS-CoV-2 virus through the lack of modulation of the mechanisms that regulate intracellular Ca2+ concentrations.