What is a safe hematocrit level for a person on testosterone (testosterone) therapy?

From the Guidelines

A safe hematocrit level for a person on testosterone therapy should generally be maintained below 54%. This is based on the guidelines from the American Urological Association, as stated in the 2018 study 1, which recommends that a hematocrit level above 54% warrants intervention, such as dose reduction or temporary discontinuation of testosterone therapy.

Key Considerations

• Prior to starting testosterone therapy, a baseline measurement of hemoglobin/hematocrit should be taken, and if the hematocrit exceeds 50%, the etiology should be formally investigated before commencing treatment 1.
• While on testosterone therapy, regular monitoring of hematocrit levels is crucial, and levels between 45-50% are generally considered normal and safe.
• Testosterone therapy can increase red blood cell production, leading to secondary polycythemia, which can increase blood viscosity and potentially raise the risk of blood clots, stroke, or cardiovascular events.

Management Strategies

• To manage hematocrit levels while on testosterone therapy, it is essential to stay well-hydrated, avoid smoking, consider regular exercise, and attend all follow-up appointments for blood work as scheduled by the healthcare provider.
• If the hematocrit level rises above 54%, the healthcare provider may recommend temporarily stopping testosterone, reducing the dose, or performing a therapeutic phlebotomy (blood removal) 1.

From the FDA Drug Label

Monitor serum testosterone, prostate specific antigen (PSA), hemoglobin, hematocrit, liver function tests and lipid concentrations periodically. (5.1,5.3,5.9,5.13)

The FDA drug label does not provide a specific safe hematocrit level for a person on testosterone. 2

From the Research

Safe Hematocrit Levels on Testosterone Therapy

• The safe hematocrit level for a person on testosterone therapy is a topic of ongoing research and debate 3, 4, 5, 6, 7.
• Current guidelines recommend monitoring hemoglobin or hematocrit routinely in the first year of testosterone therapy, with some guidelines suggesting action be taken if hematocrit exceeds 54% 4, 5, 7.
• Studies have shown that severe erythrocytosis (hematocrit >54%) is a rare outcome of gender-affirming testosterone therapy, occurring in approximately 0.6% of patients 3.
• However, other studies have found that hemoglobin concentrations above 180 g/L (calculated hematocrit, ≥54%) were measured at 25% of appointments in patients on testosterone replacement therapy 4.
• The clinical consequences of changes in hematocrit and blood flow characteristics due to testosterone therapy are not fully understood, and the validity of the current hematocrit cutoff value at which therapy may be modified is being questioned 5.
• Some guidelines recommend decreasing or discontinuing testosterone therapy if the patient's hematocrit exceeds 54% until the hematocrit normalizes 7.
• Phlebotomy or venesection is sometimes recommended as a means of reducing hematocrit in patients with testosterone therapy-induced erythrocytosis, but evidence supporting its efficacy and safety is lacking 6.

Key Findings

• Cumulative incidence of hematocrit >50.4% was 12.6%, hematocrit >52% was 1.0%, and hematocrit >54% was 0.6% in patients receiving gender-affirming testosterone therapy 3.
• Mean hemoglobin level at all clinic visits was 173 g/L (range, 134-205 g/L) in patients on testosterone replacement therapy 4.
• Analysis of data from the BLAST RCT showed a significant increase in mean hematocrit of 0.01 after 30 weeks of testosterone therapy 5.
• Evidence shows an increased thrombotic risk associated with testosterone therapy-induced erythrocytosis 6.