Keywords: testosterone, testosterone deficiency, testosterone therapy, hypogonadism in male
Testosterone deficiency is recognized as the deficiency of testosterone (T) production by the testes. This deficiency results in a pathologically low systemic testosterone concentration, as well as the concentrations of its bioactive metabolites dihydrotestosterone (DHT) and estradiol (E2).1 Testosterone deficiency may affect up to 10% of men worldwide and 40% of men over the age of 45.Signs and symptoms of testosterone deficiency include characteristic physical changes such as regression of secondary sex characteristics, decreased lean muscle mass, and cognitive changes. The restoration of serum testosterone to physiologic, or eugonadal, levels has been shown to alleviate some of the symptoms of testosterone deficiency and provide significant improvement in quality of life.Multiple treatment options for testosterone deficiency exist, most commonly consisting of testosterone therapy (TT) with exogenous testosterone. Specifically, testosterone undecanoate (TU) is an 11-carbon long androgen ester derivative of testosterone that comes in an injectable or oral formulation. Recently, we have seen a rapid increase in the available FDA-approved TU forms of T. Herein, we present a focused review on testosterone undecanoate and its various formulations, as well as a practical guide for prescribers.
What is Testosterone Deficiency
As per American Urologic Association guidelines, testosterone deficiency is diagnosed with a serum testosterone level below 300 ng/dL on two separate occasions, with both conducted in the early morning in combination with symptoms. Recent studies suggest that 300 ng/dL may not be an appropriate cutoff for diagnosis of testosterone deficiency, and thus the diagnosis should be made by a trained physician based on serum biochemical (testosterone and sex hormone binding globulin) and clinical symptoms given the specific patient’s concomitant medical conditions. Regardless of primary or secondary etiology, testosterone deficiency is associated with characteristic physical changes, including gynecomastia, regression of secondary sex characteristics, and sexual dysfunction.Testosterone deficiency is also associated with musculoskeletal changes such as decreased bone mineral density and muscle mass. In addition, obese or overweight men have been shown to have higher rates of secondary testosterone deficiency than their normal weight counterparts. Psychological disturbances such as low motivation, poor concentration, and diminished energy are also frequent concerns of men with low T., Of the symptoms, diminished energy is the most reported hypogonadal symptom in men younger than 40 years old.
Why Do We Treat Testosterone Deficiency?
Testosterone therapy can improve mood, libido, sexual function, as well as increase muscle mass and bone density, elevate hematocrit from anemic levels, and reduce body fat. Despite less conclusive evidence, many patients also report significant improvements in their energy level and cognitive function with TT.Currently, studies have shown conflicting results as to the reproducibility and mechanism of these improvements in energy and cognition, and, as such, the 2018 AUA Guidelines do not recognize improvements in energy and cognition as known benefits of TT.
Treating patients with testosterone deficiency not only improves immediate symptoms, but also minimizes long-term sequelae of T deficiency itself. T deficiency is a known risk for cardiovascular disease, and is associated with hypertension, dyslipidemia, obesity, and diabetes. A 2018 meta-analysis of seven observational studies indicated that men with testosterone deficiency have an increased risk of myocardial infarction and pooled analysis of 12 studies demonstrated an increased risk of cerebrovascular accidents compared to men with normal T levels.