We also note that even if testosterone remains stable when you account for chronic diseases, it is important to remember that age and chronic diseases are closely tied. Experts agree that chronic diseases, which are more common with advancing age, are a main driver of low testosterone. If we also use mere intuition, it is simply unlikely that unknown factors increase testosterone in ageing men as much as known factors (such as chronic disease) decrease it. The data is at odds with the totality of evidence (we never expect all evidence to favour a truthful claim), and the studies tended to measure testosterone with less accurate and more variable tools (non-extraction immunoassays) compared to ‘gold-standard’ methods (mass spectrometry).6,7 With personalized care, the treatment is designed based on lab work, symptoms, health history, and the goals of the patient. Many conditions are similar to those that define low testosterone, including thyroid issues, poor sleep quality, or stress. TSPO is a protein located on the outer mitochondrial membrane and plays a crucial role in transporting cholesterol from the outer to the inner mitochondrial membrane . Additionally, melatonin exhibits anti-inflammatory effects, with exogenous melatonin reducing the levels of inflammatory markers in humans . SERMs prevent estrogen's negative feedback on the HPG axis, while AIs inhibit the aromatization of testosterone to estrogens. Antiestrogen agents are classified into selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). Moreover, TRT interferes with the feedback mechanism of endogenous testosterone on the HPG axis. Nonetheless, the incidence of atrial fibrillation, acute kidney injury, and pulmonary embolism is slightly higher in the testosterone treatment group . Given testosterone's importance for male reproductive health and overall well-being, this review investigates the primary mechanisms underlying age-induced testosterone decline, intervention strategies, and future research priorities. Not all men experience clinically meaningful effects; symptoms are not universal and depend on baseline testosterone levels, overall health, underlying conditions, medications, sleep, and other factors. Andropause refers to the gradual, age-related decline in testosterone levels in men. If you’re concerned about your health or testosterone levels, it’s best to talk to a healthcare provider. Low testosterone levels also go hand in hand with increased inflammatory levels, regardless of age and body size. Otherwise, be reassured that testosterone levels can gradually decline as you get older. Despite the growing trends in testosterone therapy, there’s no need to worry or obsess over your testosterone levels. A 2022 study looked at testosterone levels of 1,486 men between the ages of 20 and 44 . These values don’t take your symptoms, baseline levels, or age-related decline into account. To understand why testosterone levels decline, it’s useful to understand how testosterone levels are controlled. If you experience any of these symptoms, you might start addressing the issue by asking your doctor, "What is a good testosterone level for a man my age? Because the adequate level varies by age, doctors commonly get questions from patients, like "What should a 40-year-old male’s testosterone level be? What’s involved in the assessment of testosterone levels? Clinical trials have shown limited improvement in energy levels, cognitive function, or overall quality of life in these populations. But the evidence for its benefits in otherwise healthy men with age-related declines is far less convincing. TRT can be effective for men with documented hypogonadism – meaning a genuine medical condition where the testes aren’t producing enough testosterone – and are experiencing related symptoms. However, the clinical misuse of testosterone preparations remains a concern, with testosterone prescriptions increasing 11-fold between 2001 and 2011 . However, reliable animal studies and clinical trials are still needed to confirm its safety and efficacy. A meta-analysis involving 3,439,874 participants followed for a mean of 12.3 years found that 150 min of moderate-intensity aerobic exercise per week provides substantial health benefits for adults . Regular physical activity significantly reduces the risk of age-related diseases and mortality . HPG Hypothalamic-Pituitary–Gonadal, LIPUS Low-Intensity Pulsed Ultrasound, RCT Randomized Controlled Trial, StAR Steroidogenic Acute Regulatory protein, SLCs Stem Leydig Cells, TSPO Translocator Protein, VDAC1 Voltage-Dependent Anion Channel 1 These include drugs targeting the gonadal axis, stem cell therapies, physical interventions, and testosterone replacement formulations—the latter being the most common clinical approach (summarized in Table 1). Only a few studies in the last 10 years provide evidence against ageing reducing testosterone in men. ‘I want to feel like I did in my 20s’ is a common goal of older male patients with an interest in the potential treatments that might bring their levels back to normal. Without enough of this androgenic hormone, men risk impairing reproductive health, sexual function, bone health, fat metabolism, muscle mass, and strength, among other key functions.
