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Androgen therapy in men with testosterone deficiency: can testosterone reduce the risk of cardiovascular disease?
1Global Medical Affairs Men's Healthcare, Bayer Pharma AG, Muellerstrasse 178, Berlin, Germany. farid.saad@bayer.com
Abstract:
Obesity, hypertension, insulin resistance (IR), dyslipidaemia, impaired coagulation profile and chronic inflammation characterize cardiovascular risk factors in men. Adipose tissue is an active endocrine organ producing substances that suppress testosterone (T) production and visceral fat plays a key role in this process. Low T leads to further accumulation of fat mass, thus perpetuating a vicious circle. In this review, we discuss reduced levels of T and increased cardiovascular disease (CVD) risk factors by focusing on evidence derived from three different approaches. (i) epidemiological/ observational studies (without intervention); (ii) androgen deprivation therapy (ADT) studies (standard treatment in advanced prostate cancer); and (iii) T replacement therapy (TRT) in men with T deficiency (TD). In epidemiological studies, low T is associated with obesity, inflammation, atherosclerosis and the progression of atherosclerosis. Longitudinal epidemiological studies showed that low T is associated with an increased cardiovascular mortality. ADT brings about unfavourable changes in body composition, IR and dyslipidaemia. Increases in fibrinogen, plasminogen activator inhibitor 1 and C-reactive protein have also been observed. TRT in men with TD has consistently shown a decrease in fat mass and simultaneous increase in lean mass. T is a vasodilator and in long-term studies, it was shown to reduce blood pressure. There is increasing evidence that T treatment improves insulin sensitivity and lipid profiles. T may possess anti-inflammatory and anti-coagulatory properties and therefore TRT contributes to reduction of carotid intima media thickness. We suggest that T may have the potential to decrease CVD risk in men with androgen deficiency.
Insights
Low testosterone levels in men are linked to increased cardiovascular disease risk factors like obesity and inflammation. Testosterone replacement therapy may improve body composition, insulin sensitivity, and reduce cardiovascular risk in men with testosterone deficiency.
Area of Science:
- Endocrinology
- Cardiovascular Medicine
- Andrology
Background:
- Cardiovascular risk factors in men include obesity, hypertension, insulin resistance (IR), dyslipidaemia, and chronic inflammation.
- Adipose tissue, particularly visceral fat, actively suppresses testosterone (T) production, creating a cycle where low T promotes further fat accumulation.
- Reduced T levels are increasingly recognized as a significant factor in the development and progression of cardiovascular disease (CVD).
Purpose of the Study:
- To review the association between reduced testosterone levels and increased cardiovascular disease risk factors.
- To examine evidence from epidemiological studies, androgen deprivation therapy (ADT) studies, and testosterone replacement therapy (TRT) studies.
- To explore the potential of TRT in mitigating CVD risk in men with testosterone deficiency (TD).
Main Methods:
- Review of epidemiological/observational studies examining low T and CVD risk factors.
- Analysis of studies involving androgen deprivation therapy (ADT) in prostate cancer patients.
- Evaluation of studies on testosterone replacement therapy (TRT) in men with diagnosed testosterone deficiency (TD).
Main Results:
- Epidemiological studies link low T to obesity, inflammation, and atherosclerosis progression, with longitudinal data suggesting increased cardiovascular mortality.
- ADT is associated with adverse changes in body composition, IR, dyslipidaemia, and elevated inflammatory markers.
- TRT in men with TD consistently demonstrates reduced fat mass, increased lean mass, improved insulin sensitivity, better lipid profiles, and potential reductions in blood pressure and carotid intima-media thickness.
Conclusions:
- Low testosterone is associated with multiple cardiovascular risk factors and potentially increased cardiovascular mortality.
- While ADT exacerbates cardiovascular risk factors, TRT in men with TD shows promising benefits for body composition and metabolic health.
- Testosterone replacement therapy may offer a potential strategy to decrease cardiovascular disease risk in men with androgen deficiency.
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