What are the side effects of testosterone injections in young adult transgender men?

Side Effects of Testosterone Injections in Young Adult Transgender Men

Testosterone therapy for young adult transgender men carries well-defined side effects including erythrocytosis (occurring in approximately 44% of injectable users), cardiovascular metabolic changes, androgenic effects, and injection site reactions, though serious adverse events remain uncommon and the therapy significantly improves quality of life. 1, 2

Hematologic Side Effects

Erythrocytosis/Polycythemia (Most Common Serious Effect)

• Erythrocytosis occurs in approximately 44% of transgender men using injectable testosterone, making it the most frequent clinically significant adverse effect. 2
• Hemoglobin increases to the male reference range within 3 months of starting therapy. 2
• Monitor hematocrit at baseline, 3 months, then every 6–12 months. 2
• If hematocrit exceeds 54% or rises above the male reference range, consider dose reduction, switching to transdermal formulation (which has only ~15% erythrocytosis incidence), or therapeutic phlebotomy. 1, 2
• Dose reduction to 100 mg biweekly can stabilize hematocrit in patients with moderate elevations while maintaining therapeutic testosterone levels. 3

Cardiovascular and Metabolic Effects

Lipid Profile Changes

• Testosterone increases triglycerides and LDL cholesterol while decreasing HDL cholesterol. 1, 2
• Regular lipid panel monitoring is advised, especially for patients with pre-existing cardiovascular risk factors. 2

Blood Pressure

• Testosterone may increase blood pressure, requiring regular monitoring. 1, 2
• One study showed diastolic blood pressure reduction with dose adjustment (117 mmHg to 113 mmHg), suggesting dose optimization may help manage this effect. 3

Overall Cardiovascular Risk

• Despite multiple metabolic risk factors, large cohort studies have not demonstrated a significant rise in cardiovascular mortality among transgender men on testosterone. 1, 2
• Data remain contradictory, with no significant difference in cardiovascular mortality outcomes relative to the general population when studies are viewed together. 1

Androgenic Side Effects

Common Androgenic Effects

• Acne and oily skin are common, particularly in the first year of therapy. 2, 4, 5
• Mild acne was common in adolescent cohorts; severe acne was uncommon. 5
• Androgenic alopecia (male-pattern baldness) may develop, though acceleration rates in testosterone-replacement therapy have not been carefully studied. 1, 2
• Hirsutism (increased facial and body hair growth) is an expected masculinizing effect. 4

Dermatologic Reactions

• Seborrhea (increased sebum production) occurs as an androgenic effect. 4

Injection Site Reactions

Local Effects

• Intramuscular injections can cause local pain, soreness, bruising, erythema, swelling, nodules, or furuncles. 1
• Subcutaneous administration (increasingly preferred) results in minor and transient local reactions in approximately 14% of patients (9 out of 63 in one cohort). 6
• Significant injection site reactions are uncommon with subcutaneous delivery. 5
• Inflammation and pain at the site of intramuscular injection are listed as adverse reactions in FDA labeling. 4

Reproductive and Gynecologic Effects

Fertility and Menstrual Changes

• Menstrual suppression typically occurs within 2.9 to 4.7 months, with 85-97% achieving amenorrhea within 6 months depending on dose. 7, 5
• Fertility will be greatly compromised during testosterone therapy due to down-regulation of gonadotropins, though this effect may be reversible. 1
• Testicular tissue (ovarian) function: more than 1 year of androgen treatment did not reduce primordial follicles in ovarian cortex in one study of 40 transgender men. 1

Gynecologic Symptoms

• Pelvic pain and genital dryness may occur as gynecological effects. 2
• Clitoral growth is an expected physical change. 2

Hepatic Effects

Liver Function

• Intramuscular injections and transdermal preparations do not appear to be associated with hepatic dysfunction, and routine monitoring with liver-function tests is unnecessary for these formulations. 1
• Oral testosterone preparations (strongly discouraged in the United States) are associated with hepatotoxicity and neoplasia. 1
• Sustained transaminitis (elevated liver enzymes) was infrequent in adolescent cohorts on subcutaneous testosterone. 5

Neuropsychiatric Effects

Mental Health and Libido

• Increased libido is an expected effect. 1, 2, 4
• Headache, anxiety, depression, and generalized paresthesia are listed as potential nervous system adverse reactions in FDA labeling. 4
• One study showed reduction in anxiety scores (HADS) from 7.90 to 5.19 with dose optimization. 3
• Gender-affirming hormone therapy is associated with significant improvements in quality of life, reduced gender dysphoria, and lower rates of anxiety and depression overall. 2

Fluid and Electrolyte Effects

Fluid Retention

• Retention of sodium, chloride, water, potassium, calcium, and inorganic phosphates can occur. 4
• Fluid retention is uncommon and generally mild, but testosterone should be used cautiously in patients with congestive heart failure or renal insufficiency. 1

Gastrointestinal Effects

• Nausea may occur. 4
• Cholestatic jaundice and alterations in liver function tests are possible but rare with injectable formulations. 4

Endocrine Effects

Breast and Body Composition

• Breast tenderness and swelling may occur in a small number of patients. 1
• Increased lean muscle mass, muscle cross-sectional area, and grip strength are expected masculinizing effects. 1
• Body mass index Z-scores did not change significantly in adolescent cohorts. 5

Hematologic Coagulation Effects

• Suppression of clotting factors II, V, VII, and X may occur. 4
• Bleeding in patients on concomitant anticoagulant therapy is a risk due to clotting factor suppression. 4

Allergic Reactions

• Hypersensitivity reactions, including skin manifestations and anaphylactoid reactions, are possible but rare. 4
• Testosterone undecanoate (long-acting injectable) carries rare but serious risks of pulmonary oil microembolism and anaphylaxis and should generally be avoided. 1, 2

Sleep-Related Effects

• Testosterone therapy has been associated with exacerbation or development of sleep apnea, generally in patients treated with higher doses who have other identifiable risk factors. 1
• Upper-airway dimensions are unaffected, suggesting testosterone contributes to sleep-disordered breathing by central mechanisms rather than anatomical airway changes. 1

Bone Health Considerations

• Inadequate testosterone dosing can negatively impact bone density, making appropriate dosing and monitoring essential. 2, 8
• Testosterone levels below 300 ng/dL can impair bone density and limit desired masculinization. 2

Critical Pitfalls to Avoid

• Supraphysiologic dosing (levels consistently >1,000 ng/dL) increases adverse effects—particularly erythrocytosis—without additional masculinization benefit. 2
• Mild hematocrit elevations (50-52%) should trigger closer surveillance and possible dose adjustment, especially in patients with cardiovascular risk factors. 2
• Do not measure peak levels (2-5 days post-injection) as this can misrepresent average exposure and lead to inappropriate dose reductions; trough levels are preferred. 2
• Sustained hypertension and dyslipidemia were infrequent in large cohorts but require monitoring. 5