What we know about testosterone and aging

A recent Scientific Statement from the (US-based) Endocrine Society, focuses on the endocrine effects of ageing, provides useful summaries of contemporary knowledge about the effects of age on major hormonal axes (adrenal, ovarian, testicular, thyroid, hypothalamic-pituitary-adrenal), osteoporosis and type 2 diabetes, and therapies targeting endocrine function in ageing.

The section of the article that deals with the testicular axis begins by pointing out that age-related declines in testosterone production and spermatogenesis are the consequence of the “accumulation of ageing comorbidities rather than ageing itself”.

Unreliable measurement of serum testosterone by immunoassay methods and inaccurate calculations of ‘free’ testosterone levels are suggested as contributors to the misconception that testosterone naturally declines with age. Recent measures of testosterone using liquid chromatography-mass spectrometry (LC-MS) “highlight lifestyle confounders of the age-related reduction in blood testosterone, notably overweight/obesity, insulin resistance or diabetes, smoking, cardiovascular disease or depression, which explain most or all apparent age-related reductions in serum testosterone”.

The recent T2DM and TRAVERSE randomised controlled trials have increased knowledge about the efficacy and safety of testosterone to treat at least some of these age-related diseases but available research remains “inadequate” to guide such use. A lack of certainty about efficacy and concerns about safety, especially related to long-term cardiovascular effects and prostate disease in older men.

The article is critical of past regulations that were relatively permissive of testosterone prescribing, and which led to large increases in androgen misuse. However, it suggests it will be difficult to ascertain from this period whether rates of cardiovascular or prostate disease have been affected.

The article emphasises that phosphodiesterase type 5 inhibitors are “highly effective and well tolerated for improving erectile dysfunction” in ageing men without contraindications (e.g., nitrates) and that androgen deficiency is rarely the cause of erectile dysfunction.

The Endocrine Society Scientific Statement does not rule out the potential of testosterone therapy to treat the comorbidities or underlying mechanisms of ageing, suggesting that more targeted and specific modulation of androgen signalling might be able to achieve potential benefits of testosterone without its detrimental side effects.