Contraception for Men: A Breakthrough New Approach

There has not been a new reversible contraceptive for men since the development of the condom, centuries ago. Matzuk et al. describe a new molecular approach using administration of a small molecule to directly and reversibly inhibit spermatogenesis in mice by blocking the function of a testicular bromodomain without apparent adverse effect on the organism or offspring

Association Between Ideal Cardiovascular Health and Carotid Intima-Media Thickness: A Twin Study

Background The American Heart Association (AHA) recently developed the Cardiovascular Health Index (CVHI), a health metric consisting of 7 modifiable risk factors. The relationship of the CVHI with preclinical markers, such as carotid intima-media thickness (CIMT) has not been assessed. Methods We examined 490 male monozygotic and dizygotic twins without overt cardiovascular disease. CIMT was measured using B-mode ultrasonography. Each of the 7 CVHI components (blood pressure, fasting glucose, total cholesterol, body mass index, physical activity, healthy diet, and smoking) was given a point score of 0, 1, or 2 to represent poor, intermediate, or ideal health, respectively. A CVHI summation score was computed (range 0 to 14) and categorized as inadequate (0 to 4), average (5 to 9), or optimum (10 to 14) cardiovascular health. Mixed-model regression was used to examine the association of the CVHI with CIMT. Results The mean age of the twins was 55.4 years, and 61% were monozygotic. The mean CIMT was 0.75 (±0.11) mm and the mean CVHI score was 7.7 (±2.1). There was an inverse correlation between CVHI and CIMT (Spearman r=−0.22, P\u3c0.01). For every 5-unit increase in overall CVHI score (indicating better cardiovascular health category), CIMT decreased by 0.045 mm (P\u3c0.001) after adjusting for demographic variables and other confounders. Within monozygotic twin pairs, a 5-unit increment in CVHI score was associated with a 0.05 mm lower CIMT (P\u3c0.001). Conclusions The CVHI is independently associated with CIMT and the association is not confounded by shared genetic and other familial factors

Association of childhood trauma with cognitive function in healthy adults: a pilot study

BACKGROUND: Animal and human studies suggest that stress experienced early in life has detrimental consequences on brain development, including brain regions involved in cognitive function. Cognitive changes are cardinal features of depression and posttraumatic stress disorder. Early-life trauma is a major risk factor for these disorders. Only few studies have measured the long-term consequences of childhood trauma on cognitive function in healthy adults. METHODS: In this pilot study, we investigated the relationship between childhood trauma exposure and cognitive function in 47 healthy adults, who were identified as part of a larger study from the general population in Wichita, KS. We used the Cambridge Neuropsychological Test Automated Battery (CANTAB) and the Wide-Range-Achievement-Test (WRAT-3) to examine cognitive function and individual achievement. Type and severity of childhood trauma was assessed by the Childhood Trauma Questionnaire (CTQ). Data were analyzed using multiple linear regression on CANTAB measures with primary predictors (CTQ scales) and potential confounders (age, sex, education, income). RESULTS: Specific CTQ scales were significantly associated with measures of cognitive function. Emotional abuse was associated with impaired spatial working memory performance. Physical neglect correlated with impaired spatial working memory and pattern recognition memory. Sexual abuse and physical neglect were negatively associated with WRAT-3 scores. However, the association did not reach the significance level of p < 0.01. CONCLUSIONS: Our results suggest that physical neglect and emotional abuse might be associated with memory deficits in adulthood, which in turn might pose a risk factor for the development of psychopathology

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Sperm counts and reproductive hormones in male marathoners and lean controls

In women, chronic and intense endurance exercise is frequently associated with menstrual cycle alterations. In men, the effects of similar amounts of exercise are less well-studied. We tested the hypothesis that endurance exercise in men is also associated with alterations in reproductive function. We studied 12 marathon runners and 12 age-matched, lean controls; serum and semen samples were collected every 2 weeks for 12 weeks. Sperm counts, sperm morphologies, and mean levels of testosterone (T), free T, sex hormone binding globulin, cortisol, follicle-stimulating hormone, and biologically active luteinizing hormone (LH) were similar in the two groups. Mean levels of immunologically active LH were somewhat higher in the marathoners. We conclude that this level of strenuous, long-term endurance exercise does not have major adverse effects on reproductive function in men

Treatment of stage D2 prostatic carcinoma with combined gonadal and adrenal suppression in a 60-year-old man

A 60-year-old man with stage D2 prostatic carcinoma received treatment with a new luteinizing hormone-releasing hormone superagonist. After a seven-month remission; relapse of the disease occurred and an adrenal-suppressing dose of dexamethasone was added. The resulting combined gonadal and adrenal suppression led to another remission that lasted five months. This case supports other observations of the importance of adrenal androgen production in the pathobiology of prostatic carcinoma.

Regulation of testicular function in men: implications for male hormonal contraceptive development

In the adult male, the testes produce both sperm and testosterone. The function of the testicles is directed by the central nervous system and pituitary gland. Precise regulation of testicular function is conferred by an elegant feedback loop in which the secretion of pituitary gonadotropins is stimulated by gonadotropin hormone-releasing hormone (GnRH) from the hypothalamus and modulated by testicular hormones. Testosterone and its metabolites estradiol and dihydrotestosterone (DHT) as well as inhibin B inhibit the secretion of the gonadotropins both directly at the pituitary and centrally at the level of the hypothalamus. In the testes, LH stimulates testosterone synthesis and FSH promotes spermatogenesis, but the exact details of gonadotropin action are incompletely understood. A primary goal of research into understanding the hormonal regulation of testicular function is the development of reversible, safe and effective male hormonal contraceptives. The administration of exogenous testosterone suppresses pituitary gonadotropins and hence spermatogenesis in most, but not all, men. The addition of a second agent such as a progestin or a GnRH antagonist yields more complete gonadotropin suppression; such combination regimens effectively suppress spermatogenesis in almost all men and may soon bring the promise of hormonal male contraception to fruition

Inhibition of fetal growth and survival by testosterone administration to pregnant sheep

Testosterone (as testosterone enanthate, 250 mg i.m. every 2 wk) was administered to pregnant ewes (n = 16), and injections of vehicle were used in 10 control pregnant ewes between days 75 of gestation and term (day 147). Fetal survival (7 of 16 in the treated group versus 10 of 10 in the controls) and growth (birth weights 4.00 +- 0.51 kg in the treated group versus 5.79 +- 0.93, mean +- SD, in the controls) were markedly impaired by testosterone administration. The mechanism of the testosterone effect is unknown, but could be through metabolism to estrogens by the feto-placental unit. These results imply that alterations in the production or metabolism of androgens by the mother or the feto-placement unit may exert important effects on fetal growth and survival