What are the side effects of testosterone pellets?

Side Effects of Testosterone Pellets

Testosterone pellets carry a significantly elevated risk of polycythemia (46.67% incidence) compared to other testosterone formulations, along with notable risks of pellet extrusion (13.33%), local site reactions, and dermatologic complications. 1

Hematologic Side Effects

Polycythemia represents the most concerning adverse effect of testosterone pellets:

• Erythrocytosis occurs in 46.67% of patients using testosterone pellets, which is substantially higher than the 12.8% rate seen with gels and even exceeds the 35.1% rate with pellets in comparative studies 1, 2
• Injectable testosterone shows the highest erythrocytosis rate at 66.7%, but pellets remain a significant concern 2
• Hemoglobin increases to male reference range within 3 months of testosterone therapy initiation 3
• Suppression of clotting factors II, V, VII, and X can occur, with increased bleeding risk in patients on anticoagulants 4

Clinical Pitfall: The high polycythemia rate with pellets necessitates caution in patients with pre-existing elevated hematocrit or thromboembolic risk factors 1

Local Injection Site Complications

Pellet-specific local reactions occur with notable frequency:

• Pellet extrusion occurs in 13.33% of patients, representing a unique complication not seen with other formulations 1
• Pellet site hematoma develops in 6.67% of cases 1
• Cellulitis at the insertion site occurs in 3.33% of patients 1
• Bleeding, bruising, fibrosis, scarring, and subcutaneous nodules may develop at injection sites 5
• Inflammation and pain at intramuscular injection sites are common with injectable formulations 4

Dermatologic Adverse Effects

Testosterone pellets can cause both localized and systemic skin reactions:

• Testosterone pellet-induced dermatitis manifests as erythematous plaques and patches, typically appearing within 28 days of pellet insertion 5
• This dermatitis can occur on buttocks, thighs, and facial areas, recurring with each subsequent pellet insertion 5, 6
• Acne and seborrhea are common across all testosterone formulations 4, 5
• Hirsutism and male pattern baldness (androgenic alopecia) occur frequently 3, 4, 5
• Increased body and facial hair growth occurs in 96.3% of patients 1
• Oily skin is a frequent complaint 3

Treatment approach: High-potency topical corticosteroids rapidly resolve pellet-induced dermatitis, though switching to gel formulations (5% skin reaction rate) may be preferable for recurrent cases 6, 5

Cardiovascular and Metabolic Effects

Cardiovascular concerns exist, though data remain limited:

• Potentially increased risk of myocardial infarction with testosterone therapy 3
• Reduced HDL cholesterol levels occur with testosterone use 3
• Fluid retention can develop, though typically mild; use cautiously in congestive heart failure or renal insufficiency 3, 4
• Retention of sodium, chloride, water, potassium, calcium, and inorganic phosphates may occur 4
• No thromboembolic or cardiovascular events occurred in the transgender men pellet study, though follow-up was short-term 1

Prostate-Related Effects

Prostate monitoring remains essential despite unclear direct causation:

• Gynecomastia and excessive frequency/duration of penile erections can occur 4
• Routine PSA and digital rectal examination monitoring are required at baseline and throughout therapy 3
• No PSA increases were observed in comparative studies of pellets versus other formulations 2

Hepatic Effects

Hepatotoxicity risk is formulation-dependent:

• Oral testosterone preparations carry significant hepatotoxicity risk, including benign and malignant tumors 3
• Intramuscular injections and transdermal preparations (including pellets) do not appear associated with hepatic dysfunction 3
• Cholestatic jaundice and alterations in liver function tests can occur, though rarely with non-oral formulations 4

Neuropsychiatric and Sexual Effects

Testosterone pellets produce both desired and adverse neuropsychiatric effects:

• Improved libido occurs in 70% of patients using pellets 1
• Increased or decreased libido, headache, anxiety, depression, and generalized paresthesia may develop 4
• Improved mood and energy levels occur even in patients with normal baseline testosterone 7

Reproductive Effects

Fertility suppression is universal with testosterone therapy:

• Testicular size and consistency diminish with all testosterone formulations 3
• Oligospermia occurs at high dosages 4
• Fertility is greatly compromised during therapy due to gonadotropin down-regulation 3
• These effects are typically reversible upon cessation 3

Sleep-Related Effects

Sleep apnea can be exacerbated or newly developed:

• Testosterone therapy associates with sleep apnea development, particularly with higher parenteral doses in patients with pre-existing risk factors 3
• Central mechanisms rather than anatomical airway changes mediate this effect 3

Monitoring Requirements

Comprehensive monitoring is mandatory for pellet users:

• Measure testosterone levels 2-3 months after pellet insertion, targeting mid-normal values 6
• Monitor hematocrit/hemoglobin at baseline and regularly throughout therapy given the 46.67% polycythemia rate 1, 3
• PSA and digital rectal examination at baseline and periodically 3
• Once stable, monitor every 6-12 months 6