Age-Related Testosterone Deficiency Merits Testosterone Treatment
Guidelines published by most medical societies recommend that men with testosterone deficiency receive testosterone treatment, regardless of the underlying causes.1-5 In contrast, the US Food and Drug Administration (FDA), while acknowledging that testosterone deficiency merits treatment, has made an artificial distinction between testosterone deficiency caused by rare diseases and organ failure, and testosterone deficiency caused by aging or obesity, and proclaiming that only testosterone deficiency due to rare diseases merits testosterone treatment.
This had led to debate among scientists and confusion among physicians. Prominent scientists have pointed out that that there is no evidence to support the claim of differences in benefits or risks among men with different forms of testosterone deficiency. As explained below,6 there is no basis for this distinction, and men suffering from testosterone deficiency associated with aging, obesity, metabolic syndrome and type 2 diabetes merit receiving testosterone treatment as much as men suffering from testosterone deficiency caused, for example, by genetic abnormalities or testicular failure.
Testosterone deficiency caused by obesity or aging versus rare diseases
Testosterone deficiency, also known as low testosterone, is a medical condition characterized by low testosterone levels combined with characteristic signs/symptoms.7 Testosterone deficiency occurs as a result of reduced testosterone production by the body.
There are many causes of testosterone deficiency. When an underlying isolated disease cause has been identified, such as testicular failure, Klinefelter syndrome or chemotherapy, traumatic brain injury, pituitary gland cancer or radiation, the condition is called classical testosterone deficiency. Only a minority of men are affected by classical testosterone deficiency.
The most common causes of testosterone deficiency are obesity, type 2 diabetes and aging, as well as some medications, especially opioids and glucocorticoids.8, 9 With the rising prevalence of obesity and type 2 diabetes, and the aging demographic, the prevalence of testosterone deficiency is high.10-14
Does testosterone deficiency that is caused by obesity, type 2 diabetes and/or aging merit testosterone treatment?
In contrast to the European Medicines Agency (EMA), the United States FDA has taken the position – despite data to the contrary - that only classical testosterone deficiency merits treatment with testosterone treatment.15 This has ignited a debate among scientists and confusion among physicians. Below is a summary of the rationale as to why age-related testosterone deficiency should be treated as any other clinical condition.
Evidence for benefits of testosterone treatment in men with testosterone deficiency
The wide range of health consequences of testosterone deficiency are well documented, and include sexual problems (reduced libido, impotence etc.), impaired general health, reduced wellbeing, lack of energy and enthusiasm, obesity, type 2 diabetes, osteoporosis, anemia, as well as increased risk of premature death.16-20 These health consequences have been observed in all men with testosterone deficiency, regardless of what caused the testosterone deficiency.
Testosterone treatment has been used to successfully treat testosterone deficiency since the 1940s, and has become the first-line treatment for restoring testosterone levels.21 Long-term real-world evidence studies have shown that men with all forms of testosterone deficiency experience significant health benefits from testosterone treatment.22-27
The importance of treating testosterone deficiency has been demonstrated in long-term real-world evidence studies that compared health outcomes among men with testosterone deficiency who received testosterone treatment, with those of men with testosterone deficiency who did not receive testosterone treatment.24-27 These studies showed that men with testosterone deficiency who did not get testosterone treatment experienced a marked increase in body weight and waist size, along with worsening of impotence (also known as erectile dysfunction), wellbeing, cholesterol and blood sugar levels. Furthermore, men with untreated testosterone deficiency had a higher incidence of heart attack, stroke and premature death.24-27 The largest studies of testosterone treatment to date - the Testosterone Trials 28 and the T4DM trial 29 - have provided convincing evidence of health benefits in men with age-related or obesity/diabetes-related testosterone deficiency. These studies also provided reassurance regarding the safety of testosterone treatment.
Furthermore, studies have shown that older men over 65 years of age with age-related testosterone deficiency benefit as much from testosterone treatment as do younger men with testosterone deficiency, and that testosterone treatment is a safe treatment for men of all ages.30
Does it matter what the cause of testosterone deficiency is?
Whether testosterone deficiency is a result from classical causes or not is mostly an issue of scientific inquiry, with less clinical practice relevance.
In 2015, an international expert consensus panel convened to discuss the negative impact of testosterone deficiency on men’s health and quality of life, and evaluated the merits of testosterone treatment in men with testosterone deficiency.7 Experts included a broad range of medical specialties including urology, endocrinology, diabetology, internal medicine and basic science researchers, as well as a representative from the European Medicines Agency. It was concluded that:
- Symptoms and signs of testosterone deficiency occur as a result of low testosterone, and may benefit from testosterone treatment regardless of whether there is an identified underlying cause.
- Testosterone treatment confers a wide range of health benefits in men with testosterone deficiency, regardless of age.
Guidelines published by most medical societies recommend testosterone treatment for men with testosterone deficiency, regardless of whether it is caused by genetic abnormalities, testicular failure, aging, obesity or type 2 diabetes.
Clinical practice guidelines only require a diagnosis of testosterone deficiency, which is made in men who have symptoms/signs of testosterone deficiency combined with low testosterone levels.1-5 Depending on the clinical situation, additional testing may be recommended for individual patients. For more information, see “How to diagnose testosterone deficiency?”
As stated by the FDA itself, “Once the FDA approves a drug, a health care provider may prescribe the drug for an unapproved use when the health care provider judges that it is medically appropriate for the patient. FDA does not regulate this off-label use, which is considered the practice of medicine.”31
Therefore, physicians do not have to worry about getting charged for malpractice if they prescribe testosterone treatment to men who suffer from symptoms/signs of testosterone deficiency and have low testosterone levels, even if the actual cause of their testosterone deficiency has not been identified.