Adverse Effects of Transdermal Testosterone 1.6% Gel

Hematologic Effects

Erythrocytosis is the most common and clinically significant adverse effect, occurring in up to 43.8% of patients on testosterone therapy, with most elevations occurring within the first three months of therapy 1
Hematocrit increases of 15-20% are typical as testosterone stimulates erythropoiesis 2
When hematocrit exceeds 54%, immediate intervention is mandatory: dose reduction, temporary discontinuation, therapeutic phlebotomy, or blood donation 1
Higher body mass can increase baseline hematocrit, compounding the risk in obese patients 2

Prostate volume increases significantly during the first six months to levels equivalent to eugonadal men 1
The American Urological Association states there is no evidence linking testosterone therapy to prostate cancer development, but monitoring remains essential 1

The 2024 American Heart Association/American Stroke Association guideline states that testosterone therapy in men 45-80 years with confirmed hypogonadism does not increase stroke risk based on the TRAVERSE trial 3
The American Urological Association cannot definitively state whether testosterone increases or decreases cardiovascular event risk, though recent data suggest a neutral or possibly beneficial effect 1
Fluid retention is uncommon and generally mild, but use cautiously given potential underlying cardiovascular risk 1

Transdermal gels cause skin reactions in only 5% of users, significantly lower than the 66% seen with patches 1

Exogenous testosterone will further suppress gonadotropin secretion in patients with low-normal FSH and LH 1
Down-regulation of gonadotropins causes testicular atrophy and infertility through suppression of FSH and LH 1
If fertility is desired, testosterone therapy is contraindicated and alternative treatments should be used 4

Testosterone can be aromatized to estradiol, potentially worsening or persisting gynecomastia 5, 6

Sleep apnea risk is highest in men receiving higher doses who have other identifiable risk factors, and assessment for sleep apnea history should be performed at baseline 1

Transdermal testosterone appears to have minimal effects on lipid profiles, with no significant changes in HDL, LDL, or total cholesterol in most studies 2
Obesity may independently affect lipid metabolism 2

Baseline and follow-up hematocrit/hemoglobin monitoring is mandatory, with first assessment at 1-2 months, then every 3-6 months for the first year 1
PSA and digital rectal examination must be performed at baseline and monitored regularly 1
Prostate biopsy should be performed for PSA increases ≥1.0 ng/mL in one year 1
Assessment for sleep apnea and voiding symptoms should be performed at baseline 1
More frequent monitoring may be warranted in high-risk patients 1