There is a common misconception that testosterone therapy is only limited to addressing low testosterone levels and male hypogonadism. However, ongoing research indicates that the benefits of testosterone therapy are beyond these conditions.
Extensive investigation reveals that testosterone therapy has preventive and therapeutic effects on various health conditions. Studies have explored its impact on diabetes, heart disease, infectious diseases, and prostate cancer.
Let’s follow the valuable findings by Morgentaler et al. to understand the broader scope of testosterone therapy in medicine and how this excellent therapy offers doctors and patients more applications for treatment than we ever know.
Beyond Hypogonadism: Testosterone Therapy to Gain More Applications in Medicine
Benefits of Testosterone Therapy in Prostate Cancer
In the past, testosterone therapy was thought to increase the risk of prostate cancer. “Adding fuel to the fire” – many believed the therapy would do just that.
However, a paradigm shift has occurred, with the belief evolving from seeing the therapy as dangerous to potentially therapeutic and protective against prostate cancer.
Studies have shown the protective effects of testosterone therapy in men with a history of prostate cancer. For example, one study found significantly fewer biochemical recurrences in men on testosterone than those who did not (15.3% vs. 53.3%). Another study observed a lower risk of aggressive prostate cancer in testosterone therapy patients.
In hypogonadal men after prostatectomy, cancer recurrence rates were lower for those treated with testosterone therapy than those who did not receive it (7.2% vs. 12.6%). Also, the therapy delays the time to recurrence in men destined to recur by 1.5 years.
A study on testosterone therapy combined with metformin found a reduction in prostate cancer incidence by over 50%. Studies involving bipolar androgen therapy (BAT) to treat metastatic castrate-resistant prostate cancer demonstrated promising results, including reduced prostate-specific antigen levels and improved radiographic response.
Benefits of Testosterone Therapy in Diabetes
It is not coincidental that doctors recommend measuring testosterone levels in diabetic and obese patients. If low testosterone is detected, testosterone therapy will be used not only for its sexual function benefits but also for its profound metabolic effects.
A study involving 103 men with diabetes found that 33% had testosterone deficiency. On top of being hypogonadal, these individuals had low levels of luteinizing and follicle-stimulating hormones, indicating hypogonadotropic hypogonadism (HH). Diabetes patients with HH have increased insulin resistance compared to those without HH.
Testosterone levels were also found to be low in men with obesity. The prevalence of HH in nondiabetic obese men is 25%, and in severely obese young males is 75%.
Although weight loss through surgery normalized testosterone levels in most severely obese males after 2 years and maintained them as long as the desired body weight remained, testosterone tended to diminish again once the patient regained weight.
Meanwhile, testosterone therapy can restore insulin sensitivity, enhance genes in the insulin signaling pathway, promote fat loss, and increase muscle mass. The therapy can thus prevent diabetes in obese men with impaired glucose tolerance or early diabetes.
In another two-year study, testosterone injections and lifestyle changes resulted in a 41% reduction in the incidence of diabetes. Among early diabetes patients, 45.2% experienced diabetes reversal in the testosterone group.
Benefits of Testosterone Therapy in Heart Disease
Testosterone therapy has also shown protective benefits in heart disease. At a physiological level, testosterone improves coronary vasodilatation, blood flow, and vascular reactivity. All of these effects are thought to contribute to reducing cardiovascular risk.
However, the role of testosterone therapy has been controversial due to conflicting findings, as the therapy has been linked to increased mortality and myocardial infarction (MI). Yet, negative studies on testosterone have been underpowered and do not accurately evaluate the magnitude of testosterone therapy’s impact on cardiovascular events.
A study involving over 83,000 men with testosterone deficiency and no history of MI or stroke found that normalization of testosterone levels was associated with reduced all-cause mortality, MI, and stroke compared to those with low testosterone levels.
Even in men with prior MI, testosterone therapy was linked to decreased all-cause mortality without an increased risk of recurrence. A meta-analysis also found no increased cardiovascular risk in over 5,600 men with low testosterone after 9.5 months.
Moreover, a study cohort of over 76,000 men with low testosterone showed a decreased incidence of atrial fibrillation (AF), a common cardiac dysrhythmia (heartbeat rhythm abnormality leading to morbidity and mortality), through testosterone therapy.
Benefits of Testosterone Therapy in Infectious Diseases
Since the beginning of the COVID-19 pandemic, it has been observed that hospitalized patients are predominantly men. This disproportion led to the hypothesis that testosterone may be a risk factor for severe COVID-19 infections and hospitalizations.
However, serum testosterone levels in men differ significantly from one another, depending on age and genetics. Also, low testosterone is associated with aging and comorbidities, increasing the risk of COVID-19 hospitalization.
These findings raise a disputable question – Is testosterone deficiency a risk factor for severe COVID-19 illness?
A recent study evaluated COVID-19 hospitalizations in men with and without testosterone deficiency. The study included 116 untreated hypogonadal men, 427 eugonadal men (having healthily functioning gonads), and 180 men receiving testosterone therapy.
Hypogonadal men had 2.4 times higher odds of hospitalization than eugonadal men, independent of other known risk factors. In contrast, men on testosterone therapy had similar hospitalization rates to eugonadal men, indicating a protective effect.
Importantly, this risk reduction was observed only in men who successfully achieved normalization of testosterone levels with testosterone therapy. Hypogonadal men who did not achieve normalized testosterone levels despite receiving the therapy had 3.5 times higher odds of hospitalization than those on adequate therapy.
The findings by Morgentaler et al. and other relevant research have challenged the prevailing belief that testosterone is only for hypogonadism and emphasized the broader scope of testosterone therapy. By recognizing its diverse applications, we can harness the potential of testosterone therapy in promoting overall health and well-being.
Morgentaler A. et al. (2022). Recognizing The True Value Of Testosterone Therapy In Health Care. Androgens: Clinical Research And Therapeutics.
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