Low Testosterone Concentrations Research Articles

The chronic alcohol consumption influences the gonadal axis in men: Results from a meta-analysis.

Low testosterone concentrations affect 2-13% of adult males, with a direct association between reduction in testosterone (T) concentrations and cardiovascular events. Lifestyle habits have been linked to visceral fat accumulation and endocrine disorders like secondary hypogonadism. Alcohol intake has also been a topic of debate, with studies showing a detrimental effect on sperm production and underlying mechanisms. This meta-analysis aims to comprehensively evaluate the effect of alcohol consumption on T serum concentrations in adult men. The literature search included only controlled clinical trials comparing men who drink alcohol to men who do not, or who assumed placebo or nonalcoholic beverages. The primary outcome was the comparison of total testosterone serum concentrations between the study and control groups. The publications were examined for publication bias using Egger's test. Twenty-one studies were included in the analysis for a total of 30 trials that examined the effects of alcohol consumption on testosterone level in 10,199 subjects. The meta-analysis showed that alcohol consumption overall is related to significant reduction in circulating concentrations of total testosterone (mean difference [MD]=-4.02; 95% CI -6.30, -1.73), free T (MD=-0.17; 95% CI -0.23, -0.12), sex hormone binding globulin (SHBG) (MD=-1.94; 95% CI -3.37, -0.48), an increase in estradiol (E2) (MD=7.65; 95% CI 1.06, 14.23) and neutral effect on luteinizing hormone (LH) (MD=-0.15; 95% CI -0.36, 0.06), independently by age, body mass index (BMI), E2, and LH serum concentrations and alcohol intake. However, these results are evident only in healthy men exposed to chronic alcohol consumption and not in those with a recognized diagnosis of alcohol use disorder or after acute alcohol intake. This study suggests how chronic alcohol consumption may inhibit the gonadal axis in healthy men, although the exact pathophysiological mechanisms connecting alcohol exposure and steroidogenesis are still not completely clarified.

Men, testosterone and Covid-19.

Men have more severe Coronavirus disease 2019 (Covid-19) outcomes and higher mortality rates than women, and it was suggested that testosterone levels might promote severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and Covid-19 severity. However, clinical studies have not supported this theory. Studies have consistently shown that serum testosterone concentrations during acute Covid-19 in men are inversely proportional to the inflammatory cytokines and severity of illness. It is likely that lower testosterone concentrations in this setting are a result of acute Covid-19 illness on the hypothalamic-pituitary-testicular axis. Clinical trials that attempted to lower testosterone concentrations further or block androgen signaling acutely during Covid-19 in men did not result in improved Covid-19 outcomes. Additionally, pre-existing male hypogonadism, diagnosed before Covid-19 pandemic, was found to be a risk factor for hospitalization from Covid-19. In this review, we also discuss the preclinical and mechanistic studies that have evaluated the role of androgens in SARS-CoV-2 infection and illness. Finally, long-term consequences of Covid-19 on male reproductive health are reviewed. SARS-CoV-2 virus is known to infiltrate testis and induce orchitis in men, but it is unclear if Covid-19 leads to an increase in incidence of male hypogonadism.

Effects of postnatal exposure to cadmium on male sexual incentive motivation and copulatory behavior: Estrogen and androgen receptors expression in adult brain rat

There are numerous evidence showing that cadmium (Cd) is an endocrine disruptor that exerts multiple toxic effects at different reproductive levels, including male sexual behavior (MSB). The effect of early exposure to Cd on sexual incentive motivation (SIM) and MSB in adult stage, and the immunoreactivity of receptors for hormones such as estrogens and androgens in brain regions that are relevant for the SIM and MSB display, have not been studied until now. The present study evaluated the effects of 0.5 and 1 mg/kg CdCl2 from day 1–56 of postnatal life on SIM and MSB in adults rats, as well as serum testosterone concentrations, Cd concentration in blood, testis, and brain areas, and the immunoreactivity in estrogen receptors (ER-α and -β), and androgen receptor (AR) in the olfactory bulbs (OB), medial preoptic area (mPOA), and medial amygdala (MeA). Our results showed that both doses of Cd decreased SIM and MSB, accompanied by low serum concentrations of testosterone. Also, there was a significant reduction in immunoreactivity of ER-α and AR in mPOA, and a significant reduction in AR in MeA on male rats treated with Cd 1 mg/kg. These results show that exposure to high doses of Cd in early postnatal life could alter the correct integration of hormonal signals in the brain areas that regulate and display SIM and MSB in adult male rats.

Methods for Evaluating the Efficacy of Medical Castration: A Systematic Review.

Measuring serum testosterone determination during medical castration is recommended by prostate cancer (PCa) guidelines to assess its efficacy and define castration resistance. It has been suggested that other biochemical compounds, such as free testosterone or luteinising hormone (LH), could also assess castration efficacy. We aimed to analyse the current evidence for serum biochemical compounds that could be appropriate candidates for evaluating medical castration efficacy. A systematic review was conducted after two investigators independently searched the literature in the PubMed, Cochrane Library, and EMBASE databases published between January 1980 and February 2023. Their searches used the medical subject headings 'prostatic neoplasms', 'testosterone and androgen antagonists', 'gonadotropin-releasing hormone/analogues and derivatives', 'free testosterone', and 'luteinising hormone'. Studies were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria, and their eligibility was based on the Participants, Intervention, Comparator, and Outcome strategy. The search was limited to original articles published in English. Among the 6599 initially identified titles, 15 original studies analysing the clinical impact of serum testosterone levels in PCa patients undergoing androgen deprivation therapy (ADT) were selected for evidence acquisition. The risk of bias in individual studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. All selected studies used immunoassays to measure serum testosterone, although only methods based on liquid or gas chromatography and mass spectrometry are recommended to measure low testosterone concentrations. The reported series were not uniform in clinical stage, ADT types, and the time or number of serum testosterone measurements. Only some studies found low serum testosterone levels (<20 or <32 ng/dL) associated with greater survival free of biochemical progression and castration resistance. We conclude that little current evidence justifies the measurement of serum testosterone during ADT using no appropriate methods. No reported longitudinal studies have examined the clinical impact of serum testosterone measured using liquid chromatography with tandem mass spectrometry (LC-MSMS), free testosterone, or LH in PCa patients undergoing medical castration. We conclude that well-designed longitudinal studies examining the clinical impact of serum testosterone measured with LC-MSMS, serum-free testosterone, and LH on biochemical progression and castration resistance in PCa patients undergoing neo-adjuvant castration in radiation therapy or continuous castration are needed.

Testosterone treatment and change of categories of the International prostate symptom score (IPSS) in hypogonadal patients: 12 years prospective controlled registry study

Functional hypogonadism is a condition characterized by low testosterone concentrations, occurring more commonly in men as they age. The International Prostate Symptom Score (IPSS) is used to categorize the severity of lower urinary tract symptoms (LUTS) and related symptoms in hypogonadal men. Testosterone therapy (TTh) has previously shown potential in improving total IPSS in men with hypogonadism. However, concerns regarding the effects of urinary function following TTh often prevent treatment in hypogonadal men. To explore this further, two population-based single-center, prospective, cumulative registry studies were combined to contribute to a total population of 1176 men with symptoms of hypogonadism. The total population was separated into a TTh group receiving testosterone undecanoate (TU) for up to 12 years and a control group that did not receive treatment. IPSS was recorded at both baseline and at final recorded visit for each patient. Long-term TTh with TU in hypogonadal men resulted in significant improvements in IPSS categories, even in patients with severe symptoms at baseline. In the control group, untreated hypogonadal men experienced a worsening of IPSS categories. These data indicate that TTh improves LUTS in men with hypogonadism and suggest that previous concerns regarding urinary function may have been overstated.

Abstract A012: Adaptive and non-adaptive gene expression responses in prostate cancer during androgen deprivation

Abstract Development of novel and efficient treatments for advanced prostate cancer (PCa) requires better understanding of the cellular mechanisms behind the transition to castration resistant prostate cancer (CRPC). We created long-term cell cultures to model the development of castration resistance. Using a low passage VCaP cells as an initial model, we first created a highly testosterone-dependent PCa cell line (VCaP-T) and then a subclone cell line developing the ability to grow at low testosterone concentration (VCaP-CT). Adaptation to low testosterone was solely due to long term culturing and experimental work confirmed for example higher AR expression and antiandrogen resistance in VCaP-CT compared to VCaP-T. With the developed models we aimed to uncover persistent and adaptive responses to testosterone level and to identify genes that potentially contribute to transition and proliferation of the castration resistant cells through androgen receptor (AR) regulation. Expression levels were measured using RNA-seq. We defined AR-associated genes as the ones with changes due to testosterone depletion in VCaP-T (418 genes) and further adaptive genes as the ones that restored expression level in VCaP-CT (134 genes). Interestingly, we identified 151 genes that were non-AR-associated in VCaP-T but gained the association in VCaP-CT cells. Genes gaining the AR-association were also hypothesized to be important for CRPC progression and castration resistant cells. We validated and assessed the clinical significance of the model and the findings using The Cancer Genome Atlas Prostate Adenocarcinoma data and multivariate Cox regression analysis. Expressions of 47 AR-associated or association gaining genes were statistically significant markers for progression-free survival. These included genes related to immune response, adhesion and transport. Genes ABCC5, SPRED3, TMPRSS11F, SPARC, SLC1A1, SATB1, PDGFRB and C1QTNF6 showed strong evidence being associated with tumor stage and aggressiveness in addition to progression-free survival. Taken together, we identified and validated multiple genes being linked with progression of prostate cancer and proposed several novel risk genes. These findings increase knowledge on mechanisms of castration resistance and may open new possibilities for treatments. Identified genes have potential to be used as biomarkers or therapeutic targets after further studies. Citation Format: Reetta Nätkin, Pasi Pennanen, Heimo Syvälä, Merja Bläuer, Juha Kesseli, Teuvo L.J. Tammela, Matti Nykter, Teemu J. Murtola. Adaptive and non-adaptive gene expression responses in prostate cancer during androgen deprivation [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A012.

Genetically proxied impaired GIPR signaling and risk of 6 cancers

Preclinical and genetic studies suggest that impaired glucose-dependent insulinotropic polypeptide receptor (GIPR) signaling worsens glycemic control. The relationship between GIPR signaling and the risk of cancers influenced by impaired glucose homeostasis is unclear. We examined the association of a variant in GIPR, rs1800437 (E354Q), shown to impair long-term GIPR signaling and lower circulating glucose-dependent insulinotropic peptide concentrations, with risk of 6 cancers influenced by impaired glucose homeostasis (breast, colorectal, endometrial, lung, pancreatic, and renal) in up to 235,698 cases and 333,932 controls. Each copy of E354Q was associated with a higher risk of overall and luminal A-like breast cancer and this association was consistent in replication and colocalization analyses. E354Q was also associated with higher postprandial glucose concentrations but diminished insulin secretion and lower testosterone concentrations. Our human genetics analysis suggests an adverse effect of the GIPR E354Q variant on breast cancer risk, supporting further evaluation of GIPR signaling in breast cancer prevention.

Does Intense Endurance Workout Have an Impact on Serum Levels of Sex Hormones in Males?

The benefits of physical activity and sports are widely known and proved to be crucial for overall health and well-being. In this research, the authors decided to measure the impact of endurance training in a professional male rowing team on the serum concentration levels of testosterone, estradiol, sex hormone binding globulin (SHBG) and nitric oxide (NO) and apolipoprotein A1 (Apo-A1). Proper levels of the serum concentration are necessary in order to maintain physical effectiveness. Authors analyzed the data and reviewed the former conterminous articles to find the possible mechanisms leading to changes of serum concentration of certain hormones and molecules. The direct effect of physical activity was a decrease in testosterone serum concentration (from 7.12 ± 0.4 to 6.59 ± 0.35 (ng/mL)), sex hormone binding globulin serum concentration (from 39.50 ± 2.48 to 34.27 ± 2.33 (nmol/L)), nitric oxide serum concentration (from 440.21 ± 88.64 to 432 ± 91.89 (ng/mL)), increase in estradiol serum concentration (from 78.2 ± 11.21 to 83.01 ± 13.21 (pg/mL)) and no significant increase in Apo-A1 serum concentration (from 2.63 ± 0.2 to 2.69 ± 0.21 (mg/mL)). Low testosterone concentration in OTS may be a consequence of increased conversion to estradiol, because gonadotropic stimulation is maintained. Apo-A1 serum concentration was measured due to a strong connection with testosterone level and its possible impact of decreasing cardiovascular risk.

Approach to the Patient: The Evaluation and Management of Men ≥50 Years With Low Serum Testosterone Concentration.

Although testosterone replacement in men with classic hypogonadism due to an identified pathology of the hypothalamic-pituitary-testicular axis is uncontroversial, the role of testosterone treatment for men with age-related declines in circulating testosterone is unclear. This is due to the lack of large, long-term testosterone therapy trials assessing definitive clinical endpoints. However, men ≥50 years of age, particularly those who have a body mass index >25 kg/m2 and multiple comorbidities, commonly present with clinical features of androgen deficiency and low serum testosterone concentrations. Clinicians are faced with the question whether to initiate testosterone therapy, a difficult dilemma that entails a benefit-risk analysis with limited evidence from clinical trials. Using a case scenario, we present a practical approach to the clinical assessment and management of such men.

New Horizons: Testosterone or Exercise for Cardiometabolic Health in Older Men.

Middle-aged and older men have typically accumulated comorbidities, are increasingly sedentary, and have lower testosterone concentrations (T) compared to younger men. Reduced physical activity (PA) and lower T both are associated with, and may predispose to, metabolically adverse changes in body composition, which contribute to higher risks of cardiometabolic disease. Exercise improves cardiometabolic health, but sustained participation is problematic. By contrast, rates of T prescription have increased, particularly in middle-aged and older men without organic diseases of the hypothalamus, pituitary, or testes, reflecting the unproven concept of a restorative hormone that preserves health. Two recent large randomized trials of T, and meta-analyses of randomized trials, did not show a signal for adverse cardiovascular (CV) events, and T treatment on a background of lifestyle intervention reduced type 2 diabetes by 40% in men at high risk. Men with both higher endogenous T and higher PA levels have lower CV risk, but causality remains unproven. Exercise training interventions improve blood pressure and endothelial function in middle-aged and older men, without comparable benefits or additive effects of T treatment. Therefore, exercise training improves cardiometabolic health in middle-aged and older men when effectively applied as a supervised regimen incorporating aerobic and resistance modalities. Treatment with T may have indirect cardiometabolic benefits, mediated via favorable changes in body composition. Further evaluation of T as a pharmacological intervention to improve cardiometabolic health in aging men could consider longer treatment durations and combination with targeted exercise programs.

Testosterone therapy increases the anticoagulant potential in men with opioid-induced hypogonadism: a randomized, placebo-controlled study.

Hypogonadism is prevalent during opioid treatment, and low testosterone concentrations are associated with cardiovascular disease. The effect of testosterone replacement therapy (TRT) on the coagulation system in men with hypogonadism is not clarified. We investigate the effects of TRT on the tissue factor (TF) and contact activation pathways of coagulation in opioid-treated men. This was a double-blinded, placebo-controlled study in 37 men with total testosterone < 12 nmol/L randomized to 24 weeks of testosterone injections (n = 17) or placebo (n = 20). Variables of the coagulation system were analysed at baseline and after 24 weeks. Measurements included the TF pathway (endogenous thrombin potential (ETP) and peak thrombin), the contact activation pathway (endogenous kallikrein potential (EKP) and peak kallikrein), coagulation factors (FVII, FX, prothrombin, and FXII), and inhibitors (tissue factor pathway inhibitor (TFPI), protein C, protein S, antithrombin, and C1 esterase inhibitor (C1inh)). Between-group differences at 24 weeks were determined with analysis of covariance. Within-group changes in TRT and placebo were analysed with paired t-test. Between-group differences at 24 weeks were observed for ETP (P = 0.036), FVII (P = 0.044), FX (P = 0.015), prothrombin (P = 0.003), protein C (P = 0.004), and protein S (P = 0.038). Within the TRT group, ETP, peak thrombin, FVII, FX, prothrombin, TFPI, protein C, FXII, and C1inh decreased and protein S increased (all P < 0.05). Within the placebo group, coagulation outcomes were unchanged. TRT affects the coagulation system in an anticoagulant direction through suppressed TF pathway in men with opioid-induced hypogonadism.

Serum testosterone and sex hormone-binding globulin are inversely associated with leucocyte telomere length in men: a cross-sectional analysis of the UK Biobank study.

Older men on an average have lower testosterone concentrations, compared with younger men, and more age-related comorbidities. Whether lower testosterone concentrations contribute to biological ageing remains unclear. Shorter telomeres are a marker for biological age. We tested the hypothesis that testosterone concentrations are associated with leucocyte telomere length (LTL), in middle- to older-aged men. Cross-sectional analysis of the UK Biobank study, involving community-dwelling men aged 40-69 years. Serum testosterone and sex hormone-binding globulin (SHBG) were assayed. Free testosterone was calculated (cFT). Leucocyte telomere length was measured using polymerase chain reaction. Multivariable models were used to assess associations of hormones with standardised LTL. In 167 706 men, median age 58 years, adjusting for sociodemographic, lifestyle, and medical factors, total testosterone was inversely associated with standardised LTL, which was 0.09 longer (95% confidence interval [CI], 0.08-0.10, P < .001) in men with total testosterone at median of lowest quintile [Q1] vs highest [Q5]. This relationship was attenuated after additional adjustment for SHBG (0.03 longer, CI = 0.02-0.05, P = .003). The association between cFT and LTL was similar in direction but lower in magnitude. In multivariable analysis, SHBG was inversely associated with standardised LTL, which was 0.12 longer (CI = 0.10-0.13, P < .001) for SHBG at median Q1 vs Q5. Results were similar with testosterone included in the model (0.10 longer, CI = 0.08-0.12, P < .001). Total testosterone and SHBG were independently and inversely associated with LTL. Men with higher testosterone or SHBG had shorter telomeres, arguing against a role for testosterone to slow biological ageing in men.

Associations Between Repeated Measures of Urinary Phthalate Metabolites With Hormones and Timing of Natural Menopause.

Phthalates, ubiquitous endocrine-disrupting chemicals, may affect ovarian folliculogenesis and steroidogenesis. We examined the associations of urinary phthalate metabolites with hormones including estradiol, testosterone, follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), and anti-Müllerian hormone (AMH), and timing of natural menopause in midlife women. Data were from 1189 multiracial/multiethnic women aged 45 to 56 years without hormone therapy from the Study of Women's Health Across the Nation (SWAN). Urinary concentrations of 12 phthalate metabolites and hormones were repeatedly measured in 1999 to 2000 and 2002 to 2003, resulting in a total of 2111 observations. Linear mixed-effect models were used to calculate percentage differences (%D) and 95% CIs in serum concentrations of estradiol, testosterone, FSH, SHBG, and AMH. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and 95% CIs of natural menopause. We observed statistically significant associations of phthalate metabolites with lower testosterone concentrations: MCOP with testosterone (%D: -2.08%; 95% CI, -3.66 to -0.47) and MnBP with testosterone (%D: -1.99%; 95% CI, -3.82 to -0.13), after adjusting for multiple comparisons with false discovery rates less than 5%. Lower AMH concentrations were also found with higher MECPP (%D: -14.26%; 95% CI, -24.10 to -3.14), MEHHP (%D: -15.58%; 95% CI, -24.59 to -5.50), and MEOHP (%D: -13.50%; 95% CI, -22.93 to -2.90). No associations were observed for other hormones or timing of natural menopause. These results suggest that exposure to phthalates may affect circulating levels of testosterone and diminish the ovarian reserve in midlife women. Given the widespread exposure, reduced exposure to phthalates may be a key step to prevent reproductive effects of phthalates.

Low Free Triiodothyronine as a More Sensitive Predictor of Survival Than Total Testosterone among Dialysis Men.

Some endocrine disorders, previously considered benign, may be related to a poorer prognosis for patients with renal failure. Both low serum free triiodothyronine (fT3) and low total testosterone (TT) concentrations have been considered as predictors of death in dialysis patients, but the results of studies are inconsistent. In our study, we evaluated the relationships of the serum thyroid hormone levels and the total testosterone levels with survival in male dialysis patients. Forty-eight male dialysis patients, 31 on hemodialysis (HD) and 17 on peritoneal dialysis (PD), aged 61.4 ± 10.0, 59.2 ± 12.2 years, respectively, were included in the study. Serum thyroid hormones and total testosterone were measured. During the 12-month follow-up, nine all-cause deaths were recorded. The concentrations of fT3 were significantly lower in those who died than in the survivors (p = 0.001). We did not observe any statistically considerable differences between the group of men who died and the rest of the participants in terms of the total serum testosterone concentration (p = 0.350). Total testosterone positively correlated with fT3 (r = 0.463, p = 0.009) in the HD group. In the group of male dialysis patients, the serum concentration of fT3 had a better prognostic value in terms of survival than the total testosterone. A linear relationship between the fT3 levels and testosterone levels in men undergoing hemodialysis may confirm the hypothesis that some of the hormonal changes observed in chronic kidney disease (CKD) may have a common cause.

Connection of Low Serum Testosterone Levels in Cardiovascular Disease in Metabolic Syndrome Patients with Diagnosis of Critic Iliac Artery Stenosis (TASC II A and B) and Can Exercise Improve those Levels and Primary Potency of Revascularization after Surgical and Endovascular Treatment? (Pilot Study)

Introduction: Low concentration of free testosterone and low serum testosterone levels are associated in males patients with metabolic syndrome and cardiovascular disease and in some cases in connection with critic iliac stenosis and also in most cases with lack of physical activity. Exercise can be also important factor to improve primary bypass and endovascular potency and general health benefits after surigal and endovascular treatment in patients with critical ishemia over 75% of lumen obstruction of short liiac artery segment have positive impact on improvemt of generely Testosterone Levels. Subjects and Methods: 72 selected Patients with Cardiovascular Disease with Metabolic Syndrome and Critic Iliac Artery Stenosis (TASC II A and B) were observed in period 3 years between ferbruary 2015 and ferbruary 2018. In focus was 1 year potency after invasive and minimalinvasive tertmant (45 patients treated with surgical dacron reconstruction and 25 patients with endovascular tretmant of short segment critical iliac artery stenosis (TASC II A and B). Results: In the total population no difference in changes of CIMT from baseline was observed between the standard exercise group and controls. However, there was no significant interaction between the effect of exercise training and primary bypass potency during 1 year. Conclusion: Primary potency of Endovascular procedure and Dacron bypass revascularization after 1 year in exercise training group significantly rise of testosterone levels higher but still not therapy adequate. With potential optimization testosterone therapy levels we can answer of the question. Is any major influence on primary bypass potency and are higher levels of free testosterone are preventing further progressing of cardiovascular disease and generel symptomatic and asymptomatic atherosclerosis?

Двусторонний крипторхизм как клинический маркер ранней диагностики врожденного дефицита гонадотропных гормонов: клинические наблюдения

Bilateral cryptorchidism is a common symptom of congenital gonadotropin deficiency. Detection of congenital hypogonadotropic hypogonadism (CHH) at an early age is important for preventing the long delayed puberty and timely initiation of therapy. The purpose — to identify СHH in boys with bilateral cryptorchidism based on hormonal examinations during mini-puberty. Material and methods. We present five clinical cases of patients with bilateral cryptorchidism, with CHH diagnosed in mini-puberty. The examination of 1–6 months old boys included tests of serum LH, FSH, testosterone, anti-Müllerian hormone (AMH), and inhibin B. To assess the pituitary gonadotropic function, a test with a Gn-RH analogue was performed. Patients with established CHH underwent molecular genetic testing. Results. The basis for СHH identification were the low serum concentrations of gonadotropins, AMH, testosterone, and inhibin B in boys with bilateral cryptorchidism during mini-puberty. Mutations in the FGF8 and SPRY4 genes associated with CHH were detected in 2 patients. CHH as part of hypopituitarism was revealed in 2 boys. Conclusions. Hormonal examination of boys with bilateral cryptorchidism during mini-puberty allows establishing gonadotropin deficiency at an early age, to carry out a long-term control for patients, and to begin treatment timely. Hormonal examination during mini-puberty can be the basis for diagnosing both isolated CHH and congenital hypopituitarism.

Efficacy of testosterone replacement treatment for patients with symptoms of late-onset hypogonadism based on real-world patient satisfaction.

Late-onset hypogonadism is generally treated with testosterone replacement treatment. However, the efficacy rate of treatment for patients with low testosterone is not clear because patients without low testosterone are also treated in real-world clinical settings. This study comprised 110 men with low testosterone concentration of <3.0 ng/mL who underwent testosterone replacement treatment. Physical factors, laboratory and endocrinologic profiles, and scores of several questionnaires were assessed. Testosterone replacement treatment was performed with intramuscular injection of 250 mg of testosterone esters every 2-4 weeks, and efficacy was judged by patient satisfaction. After confirming efficacy, changes in several factors by the treatment were evaluated. Finally, the comparison between evaluation by patient satisfaction and by that with the questionnaires was assessed. Among the 110 patients, 77 (70.0%) were satisfied with the treatment, which was effective in 65.7%, 71.4%, and 73.1% of patients with mental, physical, and sexual dysfunction, respectively. The questionnaire scores including the Aging Males Symptoms rating scale were significantly improved in both the satisfaction and non-satisfaction group. However, no significant differences in the amount of change in questionnaire scores were found for all questionnaire scores improved by testosterone replacement treatment between the groups. Patient satisfaction was not associated with improvement of the Aging Males Symptoms score. Although testosterone replacement treatment was effective for 70.0% of the hypogonadal patients, patient satisfaction did not correlate with improvement of questionnaire scores. We concluded that not only questionnaire results but also patient satisfaction is important when evaluating efficacy in patients undergoing testosterone replacement treatment.

The influence of testosterone on the risk of cardiovascular events after percutaneous coronary intervention.

Between 2015 and 2018, 580 men undergoing PCI at a tertiary referral hospital were divided into low (<3.25 ng/mL) and normal (≥3.25 ng/mL) testosterone groups. Major adverse cardiovascular event (MACE) was defined as the composite outcome of CV death, myocardial infarction, and target lesion revascularization/target vessel revascularization (TLR/TVR) during up to 48 months follow-up after PCI. There were 111 and 469 patients in the low and normal testosterone groups, respectively, with the overall MACE rate of the former being higher than the latter (26.13% vs. 13.01%, p = 0.0006). Moreover, the overall TLR/TVR (20.72% vs. 11.73%, p = 0.0125) and myocardial infarction (3.6% vs. 0.85%, p = 0.0255) rates were significantly higher in those with low serum testosterone who also had a shorter average event-free survival analysis of MACE (25.22 ± 0.88 months) than those with normal testosterone levels (35.09 ± 0.47 months, log-rank p = 0.0004). Multiple logistic regression demonstrated an association between low serum testosterone (<3.25 ng/mL) and a higher MACE rate [odds ratio: 2.06, 95% confidence interval (CI) 1.21-3.51, p = 0.0081]. After adjusting for variables in a Cox regression model, hazard ratios (HRs) for MACE (HR: 1.88, 95% CI: 1.20-2.95, p = 0.0058) and TLR/TVR (HR: 1.73, 95% CI: 1.06-2.83, p = 0.0290) rates were higher in the low testosterone group than those in the normal testosterone group. Low serum testosterone concentrations were associated with a higher risk of MACE and TLR/TVR after PCI than those with normal testosterone levels.

New Insights into Testosterone Biosynthesis: Novel Observations from HSD17B3 Deficient Mice

Androgens such as testosterone and dihydrotestosterone (DHT) are essential for male sexual development, masculinisation, and fertility. Testosterone is produced via the canonical androgen production pathway and is essential for normal masculinisation and testis function. Disruption to androgen production can result in disorders of sexual development (DSD). In the canonical pathway, 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) is viewed as a critical enzyme in the production of testosterone, performing the final conversion required. HSD17B3 deficiency in humans is associated with DSD due to low testosterone concentration during development. Individuals with HSD17B3 mutations have poorly masculinised external genitalia that can appear as ambiguous or female, whilst having internal Wolffian structures and testes. Recent studies in mice deficient in HSD17B3 have made the surprising finding that testosterone production is maintained, male mice are masculinised and remain fertile, suggesting differences between mice and human testosterone production exist. We discuss the phenotypic differences observed and the possible other pathways and enzymes that could be contributing to testosterone production and male development. The identification of alternative testosterone synthesising enzymes could inform the development of novel therapies to endogenously regulate testosterone production in individuals with testosterone deficiency.

Aging and androgens: Physiology and clinical implications.

In men > ~35years, aging is associated with perturbations in the hypothalamus-pituitary-testicular axis and declining serum testosterone concentrations. The major changes are decreased gonadotropin-releasing hormone (GnRH) outflow and decreased Leydig cell responsivity to stimulation by luteinizing hormone (LH). These physiologic changes increase the prevalence of biochemical secondary hypogonadism-a low serum testosterone concentration without an elevated serum LH concentration. Obesity, medications such as opioids or corticosteroids, and systemic disease further reduce GnRH and LH secretion and might result in biochemical or clinical secondary hypogonadism. Biochemical secondary hypogonadism related to aging often remits with weight reduction and avoidance or treatment of other factors that suppress GnRH and LH secretion. Starting at age ~65-70, progressive Leydig cell dysfunction increases the prevalence of biochemical primary hypogonadism-a low serum testosterone concentration with an elevated serum LH concentration. Unlike biochemical secondary hypogonadism in older men, biochemical primary hypogonadism is generally irreversible. The evaluation of low serum testosterone concentrations in older men requires a careful assessment for symptoms, signs and causes of male hypogonadism. In older men with a body mass index (BMI) ≥ 30, biochemical secondary hypogonadism and without an identifiable cause of hypothalamus or pituitary pathology, weight reduction and improvement of overall health might reverse biochemical hypogonadism. For older men with biochemical primary hypogonadism, testosterone replacement therapy might be beneficial. Because aging is associated with decreased metabolism of testosterone and increased tissue-specific androgen sensitivity, lower dosages of testosterone replacement therapy are often effective and safer in older men.