Medical Bulletin 20/ May/ 2024

According to a study published in the journal Annals of Internal Medicine, a low baseline serum testosterone concentration in men is associated with an increased risk for all-cause mortality.

Low testosterone levels in men have been linked to a higher risk of death due to several health factors. Testosterone plays a crucial role in maintaining muscle mass, bone density, and red blood cell production, and it influences mood and cognitive function.

When testosterone levels are low, men are more susceptible to conditions like obesity, type 2 diabetes, cardiovascular disease, and metabolic syndrome, all of which can significantly increase mortality risk. Additionally, low testosterone can lead to decreased physical fitness and frailty, further exacerbating health risks. The combination of these factors contributes to an overall higher death risk in men with low testosterone levels.

In the study conducted by researchers from the University of Western Australia, 11 studies comprising over 24,000 participants were reviewed to clarify the associations of sex hormones with mortality and cardiovascular disease (CVD) risk in aging men. Individual patient data (IPD) was used to summarize relationships between baseline hormone concentrations and the relative risk for CVD events, CVD deaths, and all-cause mortality.

The results showed that only men with low total testosterone concentrations had higher risks for all-cause mortality. A key finding was that men with a testosterone concentration below 7.4 nmol/L faced a higher risk for all-cause mortality, regardless of LH concentration. Additionally, men with a testosterone concentration below 5.3 nmol/L had an increased risk of cardiovascular death.

“Our research underscores the importance of understanding the impact of sex hormones on health outcomes, particularly in ageing men. By obtaining raw data from nine of the included studies and re-analysing it collectively, the research team was able to conduct a more comprehensive analysis with robust testing for associations. This pioneering study marks a significant step forward in our understanding of the link between testosterone levels and mortality risks in men, offering valuable insights for future research and clinical practice,” said Lead author Professor Bu Yeap from UWA’s Medical School.

Reference: Bu B. Yeap, MBBS, PhD, et al.; Associations of Testosterone and Related Hormones With All-Cause and Cardiovascular Mortality and Incident Cardiovascular Disease in Men: Individual Participant Data Meta-analyses; Annals of Internal Medicine; https://doi.org/10.7326/M23-2781

Immunotherapy, which uses the immune system to fight cancer, benefits about one in five cancer patients, showing significant success in lung cancer and melanoma. Researchers are now working to enhance immunotherapy for cancers, aiming to help more patients.

Now, researchers at Washington University School of Medicine in St. Louis have found, in mice, that a strain of gut bacteria – Ruminococcus gnavus – can enhance the effects of cancer immunotherapy. The study, published in the journal Science Immunology, suggested a new strategy of using gut microbes to help unlock immunotherapy’s untapped cancer-fighting potential.

The findings are published in the journal Science Immunology.

Cancer immunotherapy employs the body’s immune cells to target and destroy tumors. One such treatment uses immune checkpoint inhibitor drugs to unleash the immune system by releasing the natural brakes that keep immune T cells quiet, a feature that prevents the body from harming itself. But some tumors fight back to suppress the attacking immune cells, damping the effectiveness of such inhibitors.

In the study, researchers eliminated sarcoma tumours in mice by inhibiting TREM2, a protein made by tumour macrophages that prevents T cells from attacking the tumour. Blocking the gene made cancer immunotherapy more effective, indicating TREM2 reduces immunotherapy's efficacy. Notably, TREM2 mice housed with TREM2-deficient mice showed the same beneficial response to the checkpoint inhibitor, revealing unexpected environmental effects on treatment outcomes.

Additionally, the researchers studied the microbes in the intestines of the mice that were treated successfully with immunotherapy and found an expansion of Ruminococcus gnavus, compared with a lack of such microbes in mice that didn’t respond to the therapy.

“The microbiome plays an important role in mobilizing the body’s immune system to attack cancer cells. Our findings shine a light on one bacterial species in the intestine that helps an immunotherapy drug eliminate tumors in mice. Identifying such microbial partners is an important step in developing probiotics to help improve the effectiveness of immunotherapy drugs and benefit more cancer patients,” explained the study’s senior author, Marco Colonna, Professor of Pathology.

Reference: Blanda Di Luccia et al. ,TREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti–PD-1 tumor immunotherapy. Science Immunology.(2024) .DOI:10.1126/sciimmunol.adi5374

In a study published in the Journal of Physiology, Researchers from the University of São Paulo’s School of Physical Education and Sports in Brazil concluded that evening exercise is better for blood pressure regulation owing to improved cardiovascular control by the autonomic nervous system via a mechanism known as baroreflex sensitivity.

Baroreflex sensitivity modulates each heartbeat interval and regulates autonomic activity throughout the body. It involves sensitive fibres and artery wall deformations, particularly in the aortic arch and carotid body. When blood pressure decreases, these regions alert the brain's autonomic control centre, prompting the heart to beat faster and arteries to contract more. Conversely, if blood pressure rises, the heart slows down, and arteries relax. Essentially, baroreflex sensitivity adjusts arterial pressure beat by beat.

In the study, 23 elderly hypertension patients were divided into morning and evening training groups. Both groups cycled at moderate intensity for ten weeks, with three 45-minute sessions weekly. Researchers analysed key cardiovascular parameters, including systolic and diastolic blood pressure and heart rate, before and after the training period. They also monitored autonomic nervous system mechanisms, such as muscle sympathetic nerve activity and sympathetic baroreflex sensitivity, to assess blood pressure control.

The results showed that in the evening training group, all four analysed parameters demonstrated improvement: systolic and diastolic blood pressure, sympathetic baroreflex sensitivity, and muscle sympathetic nerve activity. However, in the morning training group, no improvements were observed in muscle sympathetic nerve activity, systolic blood pressure, or sympathetic baroreflex sensitivity.

“There are multiple mechanisms to regulate blood pressure, and although morning training was beneficial, only evening training improved short-term control of blood pressure by enhancing baroreflex sensitivity. This is important because baroreflex control has a positive effect on blood pressure regulation, and there aren’t any medications to modulate the mechanism,” said Leandro Campos de Brito, first author of the article.

Reference: John R. M. Renwick, Stuart P. S. Mladen, Workin’ on our night moves: leveraging the timing of aerobic exercise to enhance cardiovascular autonomic control in hypertensive older adults, The Journal of Physiology, 10.1113/JP286458.