TRT improves components of MetS

madman

Super Moderator
Purpose of review The prevalence of metabolic syndrome and hypogonadism continues to rise in the United States and around the world. These two conditions are inexorably linked, and understanding their relationship with each other is key to treating men with either of these conditions.

Recent findings Testosterone has been shown to be a key regulator in the maintenance of metabolic homeostasis. A large volume of research has found that testosterone deficiency is closely linked to metabolic syndrome through complex physiologic mechanisms of endothelial dysfunction, inflammation, and glucose metabolism.

Summary Interventions through lifestyle modification and testosterone replacement in hypogonadal men may reduce the morbidity and mortality risks associated with metabolic syndrome.





INTRODUCTION

In the United States, almost 70% of men aged 20 years and older can be classified as overweight [1]. Additionally, the overall prevalence of metabolic syndrome (MetS) in the United States is almost 35%, with greater than 40% of men older than 60 being classified as having MetS [2]. Hypogonadism, also known as testosterone deficiency, similarly impacts a large number of men with approximately 30% of men ages 40–79 years affected [3]. Testosterone has been shown to be a key regulator in the maintenance of metabolic homeostasis. Insight from studies of hypogonadal men undergoing treatment with testosterone replacement therapy (TRT), and additional studies with androgen-deprivation therapy in prostate cancer patients, suggests that testosterone deficiency is closely linked to metabolic syndrome (MetS) through several complex pathways. These pathways include changes in insulin resistance, hyperglycemia, visceral fat accumulation, increases in waist circumference, dyslipidemia, increased synthesis of inflammatory cytokines, and endothelial dysfunction; all ultimately leading to cardiovascular disease [4–10]. Hypogonadism itself has been shown to result in significant changes in body composition with decreased lean body mass, increased fat mass (especially visceral fat mass), and decreased bone mineral density. It is through this lens we review the association between hypogonadism and metabolic syndrome [4].





*DEFINING METABOLIC SYNDROME

*DEFINING HYPOGONADISM

*ASSOCIATIONS BETWEEN HYPOGONADISM AND METABOLIC SYNDROME

*DIABETES AND HYPOGONADISM

*TESTOSTERONE DEFICIENCY AND METABOLIC SYNDROME: INFLUENCE MORBIDITY AND MORTALITY

*LIFESTYLE MODIFICATION IN THE TREATMENT OF METABOLIC SYNDROME AND TESTOSTERONE DEFICIENCY

*TESTOSTERONE THERAPY IMPACT ON METABOLIC SYNDROME





CONCLUSION

The associations of hypogonadism and metabolic syndrome are strong, though bidirectional causality has not been clearly established. The abundance of evidence suggests that hypogonadism and concurrent Mets put men at significant risk for morbidity, specifically diabetes, and also a significant risk of mortality. The impact of both hypogonadism and MetS crosses many medical specialties and is ripe for collaborative treatment and future research endeavors.
Most evidence points to testosterone therapy as safe and potentially helpful in reducing morbidity and mortality risks in men with MetS. This is most effective when combined with lifestyle modifications, most importantly regular aerobic exercise. Although testosterone replacement is clearly not a panacea, it can be a helpful adjunct to help enhance a patient’s path to a healthier lifestyle and improved cardiovascular risk.
 

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KEY POINTS

Metabolic syndrome and hypogonadism impact 30– 40% of Americans, and are increasing in prevalence in the United States and around the world.

Metabolic syndrome and hypogonadism have been shown to be closely linked and may have bidirectional causation. Lifestyle modification has been shown to resolve metabolic syndrome and improve testosterone levels.

Testosterone replacement in hypogonadal men has resulted in improvements in the components of metabolic syndrome and may prevent the development of metabolic syndrome in certain populations.
 
*Although testosterone replacement is clearly not a panacea, it can be a helpful adjunct to help enhance a patient’s path to a healthier lifestyle and improved cardiovascular risk.
 

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Understanding Your Hormones

Estradiol (E2)

A form of estrogen produced from testosterone. Important for bone health, mood, and libido. Too high can cause side effects; too low can affect well-being.

DHT

Dihydrotestosterone is a potent androgen derived from testosterone. Affects hair growth, prostate health, and masculinization effects.

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The biologically active form of testosterone not bound to proteins. Directly available for cellular uptake and biological effects.

Scientific Reference

Lakshman KM, Kaplan B, Travison TG, Basaria S, Knapp PE, Singh AB, LaValley MP, Mazer NA, Bhasin S. The effects of injected testosterone dose and age on the conversion of testosterone to estradiol and dihydrotestosterone in young and older men. J Clin Endocrinol Metab. 2010 Aug;95(8):3955-64.

DOI: 10.1210/jc.2010-0102 | PMID: 20534765 | PMCID: PMC2913038

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