What are the implications of hypogonadism (low testosterone) in males?

From the Guidelines

Testosterone replacement therapy (TRT) may be considered for men with low testosterone levels, typically below 300 ng/dL, and symptoms such as fatigue, decreased libido, erectile dysfunction, reduced muscle mass, or depression, as it may provide small improvements in sexual functioning and quality of life, as seen in a recent study by the American College of Physicians 1. When considering TRT, it's essential to weigh the potential benefits against the unknown long-term efficacy and safety, as well as the potential risks, such as increased cardiovascular risk, as suggested by several epidemiologic studies 1. Some key points to consider when evaluating low testosterone in men include:

• Measuring testosterone levels routinely, especially in men with erectile dysfunction (ED) 1
• Assessing cardiovascular risk in all men with ED 1
• Considering lifestyle modifications, such as weight loss, regular exercise, adequate sleep, and stress reduction, to naturally support testosterone levels and reduce cardiovascular risk 1
• Avoiding TRT in men with prostate or breast cancer, untreated sleep apnea, or those trying to conceive, as it can reduce sperm production Treatment options for low testosterone include:
• Testosterone injections (typically 50-100mg weekly or 200mg every 2 weeks)
• Daily transdermal gels (AndroGel, Testim, 5-10g applied to shoulders, upper arms, or abdomen)
• Patches (Androderm, 2-6mg applied nightly)
• Pellets implanted subcutaneously every 3-6 months Regular monitoring of testosterone levels, hematocrit, PSA, and liver function is necessary during TRT, as seen in the study by the American College of Physicians 1.

From the FDA Drug Label

Testosterone Cypionate Injection is indicated for replacement therapy in the male in conditions associated with symptoms of deficiency or absence of endogenous testosterone. Primary hypogonadism (congenital or acquired)-testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome; or orchidectomy. Hypogonadotropic hypogonadism (congenital or acquired)-idiopathic gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation.

The main indications for testosterone cypionate (IM) are:

• Primary hypogonadism: testicular failure due to various conditions
• Hypogonadotropic hypogonadism: idiopathic gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury Testosterone cypionate (IM) is used for replacement therapy in males with conditions associated with low testosterone levels 2.

From the Research

Causes and Effects of Low Testosterone in Men

• Low testosterone in men, also known as hypogonadism, can be treated with various methods, including testosterone replacement therapy (TRT) 3.
• TRT can restore normal serum testosterone concentrations and relieve symptoms in most hypogonadal men, but the selection of the method depends on the patient's preference and advice from the physician 3.
• Testosterone treatment can induce reversible suppression of spermatogenesis, and alternative therapies such as human chorionic gonadotropin, selective estrogen receptor modulator, estrogen antagonist, or an aromatase inhibitor may be used if fertility is desired in the near future 3.

Alternative Therapies to Testosterone Replacement

• Alternative therapies to TRT, such as lifestyle modifications (diet and exercise, improvements in sleep, decreasing stress, and varicocele repair), medical therapies (human chorionic gonadotropins, aromatase inhibitors, and selective estrogen receptor modulators), can increase testosterone levels and should be considered before TRT 4.
• Daily subcutaneous testosterone therapy in combination with human chorionic gonadotropin and an aromatase inhibitor can be an effective treatment for testosterone deficiency, increasing total and free testosterone levels 5.

Exercise and Testosterone Treatment

• Exercise training can generate superior outcomes to testosterone treatment for improving aerobic fitness, muscular strength, and total and visceral fat mass in men with low-normal serum testosterone concentrations 6.
• Testosterone treatment at therapeutic doses can increase lean mass, but it confers limited additional benefit when combined with exercise, and exercise should be evaluated as an anti-aging intervention in preference to testosterone treatment in men 6.

Non-Testosterone-Based Treatment

• Non-testosterone-based treatments, such as selective estrogen receptor modulator, aromatase inhibitor, and human chorionic gonadotropin, can be efficacious in hypogonadal men, showing statistically significant improvement in total testosterone levels and hypogonadism symptoms 7.
• These alternative therapies can be considered for men who cannot use TRT due to safety concerns or fertility preservation, and future studies are warranted to elucidate the relationship between improved hypogonadism and erectile function in the setting of non-testosterone-based treatment 7.