Hyperandrogenism? Increased 17, 20-Lyase Activity? A Metanalysis and Systematic Review of Altered Androgens in Boys and Girls with Autism

Introduction: There is increasing evidence that steroid hormone levels and, especially, androgen levels are elevated in autism. An overactivity of 17, 20-lyase with a higher production of the testosterone precursors dehydroepiandrosterone (DHEA) and androstenedione/androstenediol seems especially present in autism. Methods: An encompassing literature analysis was performed, searching for altered androgens in children with autism and using preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Included were all studies published before 31 March 2021 found using the following electronic databases: PubMed, Google Scholar, Cochrane Library, Scopus, and TRIP. Eight studies with boys and three studies with girls where steroid hormone measurements were performed from either plasma, urine, or saliva were found and analyzed. Analyses were performed for DHEA(-S/-C), androstenedione/androstenediol, and testosterone. Effect sizes were calculated for each parameter between mean concentrations for children with autism versus healthy controls. Results: Higher levels of androgens in autism were detected, with the majority of calculated effect sizes being larger than one. Conclusions: We found higher levels of the main testosterone precursors DHEA, androstenedione, and androstenediol, likely causing an additionally higher level of testosterone, and an increased 17, 20-lyase activity is therefore implied. Medications already used in PCOS such as metformin might be considered to treat hyperandrogenism in autism following further research.

Modeling the Contribution of Male Testosterone Levels to the Duration of Positive COVID Testing among Hospitalized Male COVID-19 Patients

Background: A growing body of evidence is emerging suggesting testosterone can affect all cells involved in the immune response to both bacterial and viral infections, and the testosterone effect on the immune response could explain the greater susceptibility of men to infections including COVID-19. We aimed to explore the predictive role of male serum total testosterone (TT) levels on the time till viral negativity testing among hospitalized COVID-19 patients. Methods: The univariate effect of risk factors for the duration of COVID-19 viral positivity was evaluated using the log-rank test and Kaplan–Meier estimates. A multivariable Cox regression model was developed to test the role of TT levels and the subsequent odds for shorter viral positivity intervals. Results: Increasing serum TT levels and the need for an oxygen administration strategy were independently predictive for respectively reduced and increased days to negativization (Hazard Ratio [HR]: 1.39, 95% CI: 0.95–2.03 and HR: 0.19, 95% CI: 0.03–1.18). Conclusion: Baseline higher TT levels for male COVID-19 patients at hospital admission are associated with shorter durations of positive COVID-19 testing and thus viral clearance. Our preliminary findings might play a relevant to help pandemic control strategies if these will be verified in future larger multicentric and possibly randomized trials.

The role of testosterone in the respiratory and thermal responses to hypoxia and hypercapnia in rats

Many diseases of the respiratory system occur differently in males and females, indicating a possible role of gonadal hormones in respiratory control. We hypothesized that testosterone (T) is important for the ventilatory chemosensitivity responses in males. To test this hypothesis, we evaluated ventilation (V̇E), metabolic rate and body temperature (Tb) under normoxia/normocapnia, hypercapnia and hypoxia in orchiectomized (ORX), ORX with testosterone replacement (ORX+T) or flutamide (FL, androgen receptor blocker)-treated rats. We also performed immunohistochemistry to evaluate the presence of androgen receptor (AR) in the carotid body (CB) of intact males. Orchiectomy promoted a reduction V̇E and ventilatory equivalent (V̇E/V̇O2) under room-air conditions, which was restored with testosterone treatment. Moreover, during hypoxia or hypercapnia, animals that received testosterone replacement had a higher V̇E and V̇E/V̇O2 than control and ORX, without changes in metabolic and thermal variables. Flutamide decreased the hypoxic ventilatory response without changing the CO2-drive to breathe, suggesting that the testosterone effect on hypercapnic hyperventilation does not appear to involve the AR. We also determined the presence of AR in the CB of intact animals. Our findings demonstrate that testosterone seems to be important for maintaining resting V̇E in males. In addition, the influence of testosterone on V̇E, either during resting conditions or under hypoxia and hypercapnia, seems to be a direct and specific effect, as no changes in metabolic rate or Tb were observed during any treatment. Finally, a putative site of testosterone action during hypoxia is the CB, since we detected the presence of AR in this structure.

Biomarkers and Noncalcified Coronary Artery Plaque Progression in Older Men Treated With Testosterone

Objective Recent results from the Cardiovascular Trial of the Testosterone Trials showed that testosterone treatment of older men with low testosterone was associated with greater progression of noncalcified plaque (NCP). We evaluated the effect of anthropometric measures and cardiovascular biomarkers on plaque progression in individuals in the Testosterone Trial. Methods The Cardiovascular part of the trial included 170 men aged 65 years or older with low testosterone. Participants received testosterone gel or placebo gel for 12 months. The primary outcome was change in NCP volume from baseline to 12 months, as determined by coronary computed tomography angiography (CCTA). We assayed several markers of cardiovascular risk and analyzed each marker individually in a model as predictive variables and change in NCP as the dependent variable. Results Of 170 enrollees, 138 (73 testosterone, 65 placebo) completed the study and were available for the primary analysis. Of 10 markers evaluated, none showed a significant association with the change in NCP volume, but a significant interaction between treatment assignment and waist-hip ratio (WHR) (P = 0.0014) indicated that this variable impacted the testosterone effect on NCP volume. The statistical model indicated that for every 0.1 change in the WHR, the testosterone-induced 12-month change in NCP volume increased by 26.96 mm3 (95% confidence interval, 7.72-46.20). Conclusion Among older men with low testosterone treated for 1 year, greater WHR was associated with greater NCP progression, as measured by CCTA. Other biomarkers and anthropometric measures did not show statistically significant association with plaque progression.

The Testosterone Effect on Metabolic and Urologic Outcomes in Patients with Nonfunctioning Pituitary Macroadenomas and Hypogonadotropic Hypogonadism

Objective. To evaluate cardiovascular risk, metabolic profile, low urinary tract symptoms (LUTS), and sexual function in patients with nonfunctional pituitary macroadenoma (NFPMA) and hypogonadotropic hypogonadism with testosterone therapy (TTh). Methods. A retrospective clinical study at a tertiary care center was performed in 101 men with NFPMA, HH, and TTh; metabolic profile, cardiovascular risk, International Prostate Symptoms Score (IPSS), and International Index of Erectile Function 5 (IIEF-5) scores were evaluated before initiation of TTh and at the last checkup with TTh. Results. Age was 49.3 ± 8.8 years; T before TTh was 195 ng/mL (101–259) vs. 574 (423–774) at the last checkup. The time of TTh administration was 34 months (12–72). An increase in triglyceride levels (200 (153–294) vs. 174 (134–233) mg/dL; p=0.03), dyslipidemia (40% vs. 52%; p=0.03), and MetS (25% vs. 34%; p=0.05) was corroborated. A statistical difference in the Globorisk score and cardiovascular (CV) risk stratification was not found. IIEF-5 score was 15.5 ± 6.5 vs. 17.8 ± 5.3 (p=0.11). An improvement in penetration quality (2.0 ± 1.5 vs. 2.6 ± 1.3; p=0.05), erection after penetration (1.8 ± 1.2 vs. 2.5 ± 1.6; p=0.02), completion of intercourse (1.8 ± 1.2 vs. 2.4 ± 1.3; p=0.03), and satisfaction of sexual intercourse (1.8 ± 1.3 vs. 2.5 ± 1.5; p=0.01) was evidenced. IPSS score was 6 (IQR 2–10) vs. 7 (IQR 4–12); p=0.30. A lower rate of intermittency (14% vs. 3%; p=0.02), urgency (39% vs. 16%; p=0.01), and episodes of nocturia (18% vs. 4%; p=0.02) was found. An increase of hematocrit (44.1 ± 4.4 vs. 47.3 ± 4.4%; p=0.001), hemoglobin (14.9 ± 1.4 vs. 15.9 ± 1.4 g/dL; p=0.001), and prostatic specific antigen (0.59 (0.43–1.19) vs. 0.82 (0.45–1.4) ng/mL; p=0.02) was evidenced during TTh. Conclusion. TTh in young men with NFPMA improves LUTS, sexual function, and some metabolic parameters, and it is relatively safe in the prostatic context.

Effect of inhibition of estrogen synthesis or blocking its receptors on male rabbit reproduction

Purpose: The present aimed to study the effects of tamoxifen and fadrozole on semen characteristics and fertility, besides we emphasized the relationship between brain estrogen and sexual behavior in male rabbits. Methods: Eighty rabbits allocated into four equal groups. The control injected with sesame oil; the second injected with estradiol; the third injected with tamoxifen and the fourth injected with fadrozole. Treatments done daily for 60 days. Ten rabbits from each group served artificial vagina for evaluation of semen and sexual behavior. The other ten served female rabbits for fertility test. Reproductive organ and brain weights recorded. Serum and testicular testosterone, serum and brain estradiol and testicular zinc and cholesterol levels assayed. Results: Tamoxifen caused decrease in all estimated parameters except it increased both sperm ab normalities percentage; testicular cholesterol content; time of reaction and time between two consecutive ejaculations. Fadrozole results were opposite to that of tamoxifen except it increased the time between two consecutive ejaculations and decreased brain estradiol level. Conclusion: Fadrozole may be improve male rabbits performance along with elevated testosterone evident highlighting the important played by testosterone in regulating male rabbit fertility and advocacy the postulate that testosterone effect is mediated in part by its aromatization to estradiol.

Low testosterone levels may be associated with suicidal behavior in older men while high testosterone levels may be related to suicidal behavior in adolescents and young adults: a hypothesis

Several lines of evidence suggest that there is an association between testosterone and suicidal behavior. A link between testosterone and the neurobiology of suicidal behavior may be related to: a) a direct effect of testosterone on suicidality via certain brain mechanisms; and/or b) a testosterone influence on aggression and, consequently, suicidality; and/or c) a testosterone effect on mood and, consequently, suicidality; and/or d) a testosterone effect on cognition and, consequently, suicidality. At least one study has demonstrated a relation between high levels of testosterone and suicide in young people. A significant number of studies suggest that high testosterone levels are associated with aggression in adolescents and adults. Multiple lines of evidence indicate that aggression is associated with suicidal behavior. The effect of high testosterone levels on suicidality in adolescents and young adults may be mediated by testosterone-related elevated aggression. It is also possible that, in young people, high testosterone levels are directly linked to suicidality via certain brain mechanisms. In older men, decreased testosterone levels are associated with depressive symptoms and reduced cognitive function, whereas higher blood levels of testosterone are associated with better mood and cognitive functioning. Depression and reduced cognition are associated with suicidal behavior and may mediate the effect of decreased testosterone levels on suicidality. Therefore, it is reasonable to propose that suicidal behavior in adolescents and young adults is associated with high testosterone levels, whereas suicidality in older men is associated with decreased testosterone secretion.