What are the potential side effects and management strategies for testosterone replacement therapy using pellets?

From the Guidelines

Testosterone replacement therapy using pellets can cause several side effects, including pain, bruising, bleeding, or infection at the insertion site, and patients should be aware of these potential risks. According to the study by 1, the disadvantages of subcutaneous implants (pellets) include incision required for insertion, pellet extrusion, and infection at the site of pellet insertion. Common side effects include:

• Pain, bruising, bleeding, or infection at the insertion site
• Extrusion of the pellets through the skin, particularly if patients engage in vigorous physical activity soon after insertion
• Systemic side effects such as acne, hair loss, mood changes, increased red blood cell production (polycythemia), sleep apnea, breast enlargement (gynecomastia), testicular shrinkage, reduced sperm production, and potential worsening of benign prostatic hyperplasia symptoms.

To manage these side effects, patients should:

• Keep the insertion site clean and dry for 24-48 hours
• Avoid strenuous activity for 5-7 days post-insertion
• Attend regular follow-up appointments for blood tests to monitor testosterone levels, complete blood count, prostate-specific antigen, and lipid profiles, which should occur at 1,3, and 6 months after insertion, then annually
• Undergo therapeutic phlebotomy if polycythemia develops (hematocrit >54%)
• Receive pellets typically lasting 3-6 months before requiring replacement, with dosing usually ranging from 600-1200mg depending on the patient's needs. Patients with a history of prostate cancer, breast cancer, severe heart failure, or untreated sleep apnea should avoid testosterone therapy. The pellet delivery system provides more stable testosterone levels compared to injections or topical applications, which explains why some patients prefer this method despite the need for a minor surgical procedure for insertion, as seen in the study by 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY ... Use over long periods may result in fusion of the epiphyseal growth centers and termination of the growth process.

Androgens have been reported to stimulate production of red blood cells by enhancing production of erythropoietic stimulation factor

During exogenous administration of androgens, endogenous testosterone release is inhibited through feedback inhibition of pituitary luteinizing hormone (LH).

At large doses of exogenous androgens, spermatogenesis may also be suppressed through feedback inhibition of pituitary follicle stimulating hormone (FSH)

The potential side effects of testosterone replacement therapy using pellets include:

• Suppression of endogenous testosterone release through feedback inhibition of pituitary luteinizing hormone (LH) 2
• Suppression of spermatogenesis through feedback inhibition of pituitary follicle stimulating hormone (FSH) at large doses of exogenous androgens 2
• Stimulation of red blood cell production, which may be a concern in certain individuals 2
• Premature termination of linear growth in children due to fusion of the epiphyseal growth centers 2 Management strategies for these side effects are not explicitly stated in the provided drug labels.

From the Research

Potential Side Effects of Testosterone Pellet Therapy

• Dermatitis, characterized by erythematous plaques and patches, has been reported as a rare adverse cutaneous event associated with testosterone pellet insertion 3
• Other cutaneous adverse events include acne, hirsutism, and male pattern alopecia 3
• Localized reactions at the injection site, such as bleeding, bruising, fibrosis, infections, pellet extrusion, scarring, and subcutaneous nodules, may also occur 3

Management Strategies for Testosterone Replacement Therapy Using Pellets

• Topical corticosteroid application can be effective in resolving skin lesions associated with testosterone pellet-induced dermatitis 3
• Careful patient selection and monitoring of testosterone levels during treatment can contribute to the safe and effective use of testosterone replacement therapy 4
• Consideration should be given to deferring treatment pending resolution or stabilization of cardiovascular disease or risk factors 4

Cardiovascular Risk Associated with Testosterone Replacement Therapy

• The relationship between testosterone replacement therapy and cardiovascular risk is unclear, with some studies suggesting an increased risk and others finding no association 5, 4
• Low endogenous testosterone levels have been associated with an increased cardiovascular risk and mortality, while exogenous testosterone therapy may influence cardiovascular risk factors in patients with adult-onset hypogonadism 4
• A critical analysis of studies reporting increased cardiovascular risk associated with testosterone therapy found methodological flaws and debatable conclusions in many of the studies 4