If your testosterone is truly low and symptoms are affecting your quality of life, there are effective ways to take control, and it doesn’t always start with a prescription. There’s also concern about overuse; some men are prescribed TRT even when their testosterone is borderline or normal. If you’re dealing with symptoms that don’t feel like "just aging," and especially if you have sexual changes, don’t ignore them. That's why doctors look at both your symptoms and your bloodwork to make a diagnosis, not just one or the other. In older men, the testosterone output per LH stimulus is lower than in younger men, indicating impaired coupling between LH signalling and androgen production.
It is possible that low androgen levels masked the usual evidence of prostate cancer in this population (Morgentaler et al 1996). Treatment of prostate cancer with androgen deprivation is known to be successful and is widely practiced, indicating an important role for testosterone in modifying the behavior of prostate cancer. A prospective study also failed to demonstrate a correlation between testosterone and the development of BPH (Gann et al 1995). Testosterone also requires conversion to dihydrotestosterone in the prostate gland for full activity. Appropriately-powered randomized controlled trials, with cardiovascular disease primary endpoints, are needed to clarify the situation, but in the meantime the balance of evidence is that testosterone has either neutral or beneficial effects on the risk of cardiovascular disease in men.
One analysis of 13 studies (including over 10,000 males) found that the average male testosterone level peaks at age 19, falls only slightly until 40 years, and then remains relatively stable until death.4 These require daily application by patients and produce steady state physiological testosterone levels within a few days in most patients (Swerdloff et al 2000; Steidle et al 2003). This has a much longer half life and produces testosterone levels in the physiological range throughout each treatment cycle (Schubert et al 2004). Once treatment has been established, less frequent review is appropriate but the care of the patient should be the responsibility of an appropriately trained specialist with sufficient experience of managing patients treated with testosterone. This would seem appropriate because, in addition to benefits on sexual function, identification and treatment of hypogonadal men with testosterone could improve other symptoms of hypogonadism and protect against other conditions such as osteoporosis. Randomized controlled trials of testosterone treatment have found a low incidence of prostate cancer and they do not provide evidence of a link between testosterone treatment and the development of prostate cancer (Rhoden and Morgentaler 2004).
Most men focus on total testosterone levels when they’re trying to figure out if they have low testosterone, but free testosterone levels matter, too. The average male who reaches 70 years old will have testosterone production that’s 30 percent below his peak (5). McDevitt says she sees older men who live a healthy lifestyle in their fifties who have the testosterone levels of a man in his thirties. A combination of age, genetics, and pre-existing medical conditions determines your testosterone levels. Indeed, there is evidence that testosterone levels do not significantly differ in men above and below 40 years old if they are deemed in very good to excellent health.11
Most men begin experiencing testosterone decline around age 40, though it can vary considerably based on individual factors. These age-related changes naturally occur because the Leydig cells in the testicles (which make testosterone) produce less testosterone with advancing age. Monitoring your status with a comprehensive testosterone test can provide useful insights into your health. It plays a vital role in sexual development, muscle mass, bone density, red blood cell production, fat distribution and more. Testosterone is the primary male sex hormone.
How testosterone’s shifts impact men will help men, their partners, and clinicians choose the right next step. While hormones matter, they’re only part of a bigger picture. These drugs are still in the animal testing phase, and more research is needed to support their clinical application . Researchers have designed a VDAC1 peptide that binds to 14–3-3ε, blocking the interaction between 14–3-3ε and VDAC1, thereby limiting testosterone synthesis . 14–3-3 proteins bind to VDAC1, reducing cholesterol input and limiting testosterone synthesis .
Keeping those caveats in mind, in one study (2) of healthy adult males between the ages of 40 and 70, researchers observed these normal total testosterone levels. Regardless of the method of testosterone treatment chosen, patients will require regular monitoring during the first year of treatment in order to monitor clinical response to testosterone, testosterone levels and adverse effects, including prostate cancer (see Table 2). Late-onset male hypogonadism happens when the decline in testosterone levels is linked to general aging and/or age-related conditions, particularly obesity and Type 2 diabetes. Indeed, it is apparent that longer duration randomized controlled trials of testosterone treatment in large numbers of men are needed to confirm the effects of testosterone on many aspects of aging male health including cardiovascular health, psychiatric health, prostate cancer and functional capacity. Longitudinal studies in male aging studies have shown that serum testosterone levels decline with age (Harman et al 2001; Feldman et al 2002).
A recent 2023 study in male cynomolgus macaques demonstrated a significant age-related reduction in the number of LCs . Neaves et al. performed testicular biopsies on 30 men aged 20–76 who died from trauma or heart disease and found a 44% reduction in the total number of LCs in older males . Upon tissue injury, macrophages become activated, initiating chemotaxis, phagocytosis, and the production of reactive oxygen species (ROS) and pro-inflammatory factors, thereby suppressing testosterone production . Decreases in GnRH neuronal number and/or function underlie reduced GnRH outflow, but clinical studies elucidating age-related changes in human GnRH neurons are lacking due to their sparse distribution and low quantity. The study found that increasing age led to decreased GnRH outflow, while pituitary responsiveness to GnRH remained normal. Early biomathematical models predicted a 33–50% decline in GnRH secretion in males from ages 20 to 80 years 26, 27.
Truly physiological testosterone replacement would require replication of the diurnal rhythm of serum testosterone levels, but there is no current evidence that this is beneficial (Nieschlag et al 2005). The exact target testosterone level is a matter of debate, but current recommendations advocate levels in the mid-lower normal adult range (Nieschlag et al 2005). Evidence from placebo-controlled trials in this group of men shows that testosterone treatment added to PDE-5 inhibitors improves erectile function compared to PDE-5 inhibitors alone (Aversa et al 2003; Shabsigh et al 2004). Furthermore, the severity of erectile dysfunction positively correlates with lower testosterone levels in men with type 2 diabetes (Kapoor, Clarke et al 2007). This suggests that the men in this older age group are particularly likely to suffer sexual symptoms if their testosterone is low.

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