Testosterone and male rejuvenation


Testosterone and male rejuvenation
Sevann HELO, Peyton THOMAS, Nicholas N. TADROS


Testosterone has long been touted as the panacea for men wishing to restore their vitality, sexuality, and masculinity to that of their youth. While the benefits of testosterone are not mythical, they are definite. In this article, we will review the various benefits of testosterone as it pertains to men’s health and male infertility.

Metabolic syndrome (MetS) is a worldwide public health issue, which in the past has been largely confined to developed countries, yet now involves a growing number of developing countries undergoing industrialization as well. The industrialization has in turn led to the adoption of a Western diet, sedentary lifestyles, and increased obesity. This growing epidemic has garnered increased interest in the clinical application of testosterone therapy (TTh) for the improvement of MetS, weight loss, and muscle mass.

The relationship between testosterone, lean body mass, and athletic performance has long since been recognized. In 1935, Charles D. Kochakian, a pioneer in synthetic hormone research, reported that androgens stimulated the protein anabolic processes, leading to the belief that androgen therapy may restore protein tissue and stimulate muscle growth.1 Clinical literature from the early 1940s comments on the correlation between androgens and enhanced muscularity, including speculation that the use of exogenous androgens may improve athletic performance.1 In his 1945 publication of The Male Hormone, Paul De Kruif described the powers of TTh as “magical,” with the potential to cure a variety of ailments, and is credited for popularizing the use of synthetic testosterone among bodybuilders.2

While such claims about testosterone have not ceased, there is now a strong body of contemporary evidence supporting the clinical use of TTh to improve anthropometric parameters. Cross-sectional studies demonstrate a proportional decrease in total serum testosterone concentration with age,3, 4 a finding later corroborated by longitudinal studies.5 Similarly, lean body mass decreases, while fat mass increases with age.6 One consequence of these body composition changes that occur with aging is decreased muscle strength.7 Bhasin et al. were among the first to report an improvement in lean body mass, body weight, and cross-sectional size of muscle in their observational study of seven hypogonadal men treated with 10 weeks of intramuscular testosterone enanthate.8

In 1999, Snyder et al. published the first randomized placebo-controlled double-blind study of men over age 65 who were randomized to transdermal testosterone or placebo for 3 years.9 Authors selected for hypogonadal men, although admitted that mean baseline testosterone was 367 ng/dL, which is above the lower limit used by most modern studies to define hypogonadism. Subjects treated with placebo experienced no changes, while those in the treatment group benefited from a 3.8% improvement in lean body mass (P<0.001), 13.5% reduction in fat mass (P=0.001), and 6.3% reduction in insulin growth factor-1 (P=0.004). While the magnitude of improvement in lean body mass and insulin growth factor-1 is admittedly small, few would argue that a 13.5% reduction in fat mass is not clinically significant. With regard to muscle strength, the authors of this study chose to measure this parameter using knee extension angular velocity and handgrip as surrogates. Interestingly, they noted decreases in both groups, although not statistically significant compared to baseline or when compared between groups. Potential confounding factors included nutritional intake, physical activity level, exercise regimen, and precision of the tests used to assess muscle strength. Follow-up studies have reported similar improvements in physical performance and lean body mass.10, 11

Insulin sensitivity

Weight loss

Bone mineral density

Lower urinary tract symptoms

Cardiovascular disease

Sexual function

Cognitive aging and psychologic health

Impact on fertility


Men turning to TTh as the elusive fountain of youth need to adjust their expectations to avoid disappointment. While the benefits of TTh are not infinite, they are well defined by a strong body of evidence supporting the use of TTh for the treatment of testosterone deficiency.
Users may unlock improvements in anthropometric parameters, bone mineral density, cardiovascular health, sexual function, and urinary function. Prior to initiating TTh, clinicians should engage their patients in an informed conversation about the risks and benefits of therapy to ensure that they are the proper candidates with realistic expectations.


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