AndroGel (Testosterone Topical) and Erythrocytosis: When to Call the Doctor

Which label covers what

AndroGel is a brand of testosterone gel, and TRAVERSE used 1.62% gel [3]. The hematocrit schedule and stop instruction below are from the AndroGel 1.62% label [11], and the generic testosterone gel 1% label has the same wording [1]. The clot-symptom wording below is from the generic gel 1% label, which states that its dosage and administration differ from testosterone gel 1.62% and that topical testosterone products may have different doses, strengths or application instructions [1].

The AndroGel 1.62% label calls for hematocrit to be checked before starting treatment, re-evaluated 3 to 6 months after starting, and then checked annually. If hematocrit becomes elevated, it says to stop therapy until hematocrit decreases to an acceptable concentration, and it notes that an increase in red blood cell mass may increase the risk of thromboembolic events [11].

What the label attaches to a lab value and to symptoms

An elevated hematocrit result is the trigger the label attaches to an action: stop therapy until hematocrit falls to an acceptable concentration [11]. The polycythemia section gives no number that counts as elevated [11][1], and the generic gel 1% label does not describe a symptom set for erythrocytosis itself [1].

Clot symptoms are a separate matter. The generic gel 1% label warns that venous thromboembolic events, including deep vein thrombosis and pulmonary embolism, have been reported in patients using testosterone products. It says to evaluate leg pain, edema, warmth and erythema for deep vein thrombosis, and acute shortness of breath for pulmonary embolism, and to discontinue testosterone gel and begin appropriate workup and management if a venous thromboembolic event is suspected [1]. In the label's structure a high hematocrit leads to stopping therapy and rechecking, while a suspected clot leads to discontinuation plus workup and management [1][11].

How common is erythrocytosis on testosterone gel?

Erythrocytosis is a well-established effect of testosterone therapy. A 2015 review found that men on testosterone replacement had a 315% greater risk of erythrocytosis, defined there as hematocrit above 0.52, than controls; all formulations raised hemoglobin and hematocrit, with injectables raising them most [4]. A 2018 review reached the same broad conclusion and reported that short-acting injectable formulations have the highest incidence [5].

For gel specifically, a 2022 network meta-analysis of 29 placebo-controlled randomized trials with 3,393 men found that mean hematocrit rose 3.0% with gel, 4.0% with intramuscular enanthate or cypionate, 1.4% with patch, 4.3% with oral testosterone undecanoate and 1.6% with intramuscular testosterone undecanoate, all compared with placebo [2]. The analysis reported a significant difference between intramuscular enanthate or cypionate and patch, but not between the other pairs, so the smaller mean rise with gel than with short-acting injections was not a statistically significant separation [2].

A retrospective review of 178 hypogonadal men found erythrocytosis, defined as hematocrit above 50%, in 66.7% of men on injectable testosterone, 12.8% on gels and 35.1% on pellets [6]. The injection group was younger, with a mean age of 42.5 years versus about 54 years in the gel group, and had higher baseline hematocrit, so the comparison is not a clean estimate of route effect [6].

The generic gel 1% label's 180-day trial does not give a standalone erythrocytosis rate. It lists lab test abnormal as a composite that included elevated hemoglobin or hematocrit, reported in 6% of men at 50 mg, 5% at 75 mg and 3% at 100 mg; the composite also included hyperlipidemia, elevated triglycerides, low potassium, low HDL, high glucose, high creatinine and high bilirubin [1].

What does TRAVERSE add?

The generic gel 1% label gives TRAVERSE clot rates: venous thromboembolism 1.7% with testosterone gel versus 1.2% with placebo, including deep vein thrombosis 0.6% versus 0.5% and pulmonary embolism 0.9% versus 0.5% [1]. TRAVERSE enrolled 5,246 men and used daily 1.62% testosterone gel; the primary cardiovascular endpoint occurred in 7.0% with testosterone versus 7.3% with placebo, hazard ratio 0.96, noninferiority met [7]. Reviews describe the link between testosterone-related erythrocytosis and thromboembolic events as limited or inconclusive [4][5].

Does switching from gel to injections change hematocrit?

In the 2022 network meta-analysis, intramuscular enanthate or cypionate produced a larger mean hematocrit rise than gel, and reviews report the highest erythrocytosis incidence with short-acting injectables [2][5]. The retrospective review also found far more erythrocytosis in the injection group, though that group started with higher hematocrit and was younger [6]. A 2025 review of testosterone adverse effects says therapeutic phlebotomy is indicated when hematocrit exceeds 52% [8].

Who is more likely to reach a high hematocrit?

A 2024 retrospective single-center study of 247 men on testosterone replacement found that 23% reached a hematocrit above 0.50 and 5% above 0.54 [9]. Higher body mass index was associated with reaching a hematocrit of at least 0.50, and higher baseline hematocrit with reaching at least 0.46 [9]. Among men who reached a hematocrit above 0.46, 46% had their highest value within the first year of treatment [9].

The Endocrine Society's 2018 guideline recommends against starting testosterone therapy in men with elevated hematocrit, among other conditions, and recommends monitoring hematocrit in the first year [10].