Testosterone therapy in men with testosterone deficiency: Are we beyond the point of no return?

Abstract

Although testosterone therapy in men with testosterone deficiency was introduced in the early 1940s, utilization of this effective treatment approach in hypogonadal men is met with considerable skepticism and resistance. Indeed, for decades, the fear that testosterone may cause prostate cancer has hampered clinical progress in this field. Nevertheless, even after considerable knowledge was acquired that this fear is unsubstantiated, many in the medical community remain hesitant to utilize this therapeutic approach to treat men with hypogonadism. As the fears concerning prostate cancer have subsided, a new controversy regarding use of testosterone therapy and increase in cardiovascular disease was introduced. Although the new controversy was based on one ill-fated clinical trial, one meta-analysis with studies that utilized unapproved formulation in men with liver cirrhosis, and two retrospective studies with suspect or nonvalidated statistical methodologies and database contaminations, the flames of such controversy were fanned by the lay press and academics alike. In this review we discuss the adverse effect of testosterone deficiency and highlight the numerous proven benefits of testosterone therapy on men's health and debunk the myth that testosterone therapy increases cardiovascular risk. Ultimately, we believe that there is considerable scientific and clinical evidence to suggest that testosterone therapy is safe and effective with restoration of physiological levels in men with testosterone deficiency, irrespective of its etiology.

Keywords: Cardiovascular risk; Hypogonadism; Prostate cancer; Testosterone; Therapy.

Fig. 1. Testosterone therapy in men with testosterone deficiency and differing grade of obesity produces significant and sustained weight loss. Hypogonadal men (n=362) with obesity grade I (Gr. I: n=185; mean age, 58.39±8.04 years), grade II (Gr. II: n=131; mean age, 60.62±5.56 years) and grade III (Gr. III: n=46; mean age, 60.28±5.39 years) treated with testosterone undecanoate injections for up to 6 years. Weight expressed in kilogram. Adapted from Kenny AM, et al. J Am Geriatr Soc 2010;58:1134-43 [74].

Fig. 2. Testosterone therapy in men with testosterone deficiency and differing grade of obesity produces marked and sustained reductions in waist circumference. Waist circumference (WC) (cm) in 362 hypogonadal men with obesity grade I (Gr. I: n=185; mean age, 58.39±8.04 years), grade II (Gr. II: n=131; mean age, 60.62±5.56 years) and grade III (Gr. III: n=46; mean age, 60.28±5.39 years) Treated with testosterone undecanoate injections for up to 6 years. Adapted from Kenny AM, et al. J Am Geriatr Soc 2010;58:1134-43 [74].

Fig. 3. Total cholesterol (A) and low-density lipoprotein (LDL) cholesterol levels (B) and triglyceride levels (C) in men with testosterone (T) deficiency undergoing T therapy for 5 years. Adapted from Traish AM. Am J Physiol Regul Integr Comp Physiol 2016;311:R566-73 [5].

Fig. 4. Glucose concentration (A) and hemoglobin A1c (HbA1c) levels (B) in men with testosterone (T) deficiency undergoing T therapy for 5 years. Adapted from Traish AM. Am J Physiol Regul Integr Comp Physiol 2016;311:R566-73 [5].