From the Guidelines
Testosterone therapy should not be allowed to increase hematocrit levels above 54%, and intervention such as dose reduction or temporary discontinuation is warranted at this level. According to the American Urological Association guideline 1, prior to commencing testosterone therapy, all patients should undergo a baseline measurement of hemoglobin/hematocrit, and if the Hct exceeds 50%, clinicians should consider withholding testosterone therapy until the etiology is formally investigated. Some key points to consider when managing hematocrit levels during testosterone therapy include:
- Monitoring hematocrit levels regularly, ideally every 3-6 months during the first year of treatment and then annually thereafter
- Considering dose adjustment or temporary discontinuation of testosterone therapy if hematocrit levels reach 52-54%
- Recommending therapeutic phlebotomy (blood removal) if elevated hematocrit becomes a persistent issue, typically removing 1 unit (about 500 mL) of blood to quickly reduce levels
- Encouraging patients to stay well-hydrated before blood tests to prevent artificially elevated readings The increase in hematocrit occurs because testosterone stimulates erythropoiesis (red blood cell production) in the bone marrow, which is actually one of testosterone's normal physiological effects and explains why men typically have higher hematocrit levels than women 1.
From the Research
Hematocrit Levels with Testosterone Therapy
- The ideal hematocrit level for patients undergoing testosterone therapy is not clearly defined, with different studies suggesting various cutoffs 2, 3, 4, 5, 6.
- Some guidelines recommend decreasing or discontinuing testosterone therapy if the patient's hematocrit exceeds 54% until the hematocrit normalizes 4.
- Other studies suggest that the evidence for secondary polycythemia causing harm during testosterone therapy is scarce, and the hematocrit-based cutoffs present in multiple guidelines appear to be arbitrarily chosen 2.
- The association between hematocrit and morbidity and mortality appears likely but not proven and may be evident only in patient subgroups 3.
Factors Influencing Hematocrit Levels
- Testosterone therapy can effect an increased hematocrit via poorly understood mechanisms and may have harmful effects on blood flow that differ in patient subgroups 3.
- Patient-specific factors should be considered when choosing an appropriate testosterone therapy dosage and modality, as they can influence hematocrit levels 4.
- The route of delivery and formulation of testosterone therapy can also impact hematocrit levels, with injectables tend to produce the greatest effect 6.
Management of Erythrocytosis
- Therapeutic phlebotomy or venesection is mentioned as a means of reducing hematocrit in patients with testosterone therapy-induced erythrocytosis, but evidence supporting its efficacy or safety is lacking 5.
- The potential pros and cons of therapeutic phlebotomy should be carefully weighed against each other, and shared decision-making is recommended for initiating this treatment 5.
- Clinicians may consider adjusting testosterone therapy dosing, stopping therapy, or ordering a phlebotomy, or recommending a combination of these, upon encountering secondary erythrocytosis 2.