Testosterone is a ubiquitous molecule among vertebrates, leading to tens of thousands of research studies exploring its effects in animals. The effects of castration on muscle, fat, and sexual behaviour have been recognised in humans and domesticated animal species for millennia.
The androgen receptor, a key molecule that mediates the effects of androgens in most human tissues, has been identified in a remarkably broad range of tissues, including but not limited to muscle, bone, bone marrow, the peripheral and central nervous system, adipocytes, liver, kidney, skin, and testis.
It is no wonder that a deficiency of testosterone has been shown to have numerous negative effects in men, which may be improved or reversed with normalisation of serum testosterone through TTh.
Although healthcare providers may have a general awareness that testosterone is important for male sexual desire and muscle mass, it is not widely appreciated that TD is associated with several of the most important general medical conditions facing our society, including type 2 diabetes (T2DM), obesity, osteoporosis, and cardiovascular (CV) disease, and TTh has shown compelling health benefits for those conditions, among others.
Testosterone levels have been associated with the most urgent global medical issue of the past several years, namely Covid-19 infection, and TTh has even been shown to reduce the rate of severe infection.
Mortality has been shown to be associated with low levels of testosterone, and observational studies have shown a two-fold decrease in mortality among men with TD that received TTh.
Referring to the ‘most misunderstood molecule in medicine’, Morgentaler et al (2022) emphasise that there has been little recognition within the medical community of the health impact of T, TD, and the substantial benefits of TTh on health and quality of life despite high-level clinical evidence.
“TD negatively impacts human health and quality of life and is associated with increased mortality. Several studies have demonstrated that TTh in men with TD reduced all-cause and CV mortality. The longstanding belief that TTh is associated with increased prostate cancer risk is contradicted by recent evidence, including multiple studies showing that TTh is associated with reduced risk. Similarly, the weight of current evidence indicates the purported concern that TTh is associated with increased CV risk is incorrect,” the authors stated.
Lines of evidence argue strongly for the need for greater awareness in the medical community of the impact of TD on health, and of the health benefits of TTh.
Testosterone deficiency and its impact
Testosterone plays a crucial role in various aspects of male health, including metabolism, sexual function, and vascular health. A deficiency in testosterone can have negative effects on physical, psychological, and cognitive well-being.
Numerous studies have demonstrated the therapeutic value of TTh, showing improvements in sexual function, mood, bone density, and prevention of prediabetes progression to T2DM. Additionally, low testosterone levels have been linked to increased incidences of dementia and Alzheimer’s disease.
Challenges with FDA and age-related TD
In terms of ‘age-related’ hypogonadism, there is no scientific basis for distinguishing between known causes of TD and age-related TD, as the problem in both cases is a deficiency of testosterone. The safety profile of TTh is considered acceptable, and since classical TD cases are rare, most research studies involve men with age-related TD.
TTh may be protective and therapeutic for prostate cancer
Morgentaler et al highlight studies that suggest TTh may have protective and therapeutic effects on prostate cancer. Research shows reduced recurrence rates and delayed recurrence in men receiving TTh after radical prostatectomy.
A study on the combination of TTh and metformin shows a reduction in prostate cancer incidence. These findings challenge the historical belief that TTh increases the risk of prostate cancer.
TTh in diabetes and obesity
A significant portion of men with T2DM have TD, and obesity is a common cause of TD in the community. Studies indicate that body weight strongly influences testosterone levels. Therefore, healthcare practitioners should measure testosterone in all T2DM and obese patients and consider TTh not only for sexual function but also for its metabolic benefits.
Long-term benefits of TTh
Long-term studies to understand the lasting effects of TTh are important. A 13-year follow-up study showed substantial weight loss, improved glycaemic control, and remission of T2DM in the TTh group. Adverse CV events were less frequent in this group, indicating a potential cardioprotective effect of TTh.
A meta-analysis of TTh trials found no significantly increased risk of CV events. It also points out that active smoking can nullify the beneficial effects of TTh.
CV benefits of TTh
There is a link between low testosterone levels and increased mortality and CV events. Normalisation of serum testosterone with TTh is associated with reduced mortality, heart attacks, strokes, and atrial fibrillation, particularly in men without prior CV events. However, the protective effect of TTh is diminished in men with a history of myocardial infarction.
Morgentaler A, Traish A, Barua RS, et al. Recognizing the True Value of Testosterone Therapy in Health Care. Androg Clin Res Ther, 2022 Dec 28;3(1):217-223. doi: 10.1089/andro.2022.0021. PMID: 36643964; PMCID: PMC9814113.