Polycythaemia in Athletes: Causes and Links to Performance Drugs

A routine blood test showing high haemoglobin or haematocrit is a common surprise for athletes. Sometimes the explanation is harmless, such as dehydration or altitude training. In other cases it reflects testosterone therapy, anabolic steroid use or blood doping, and carries a real risk of clots, heart attack and stroke. Our editorial team explains the causes, the link with pharmacology and what the numbers mean.

What polycythaemia means

Polycythaemia, also called erythrocytosis, means an abnormally high concentration of red blood cells. It is usually identified by a raised haematocrit — the proportion of blood volume made up of red cells — or a raised haemoglobin concentration on a full blood count.

British Society for Haematology guidelines suggest investigating erythrocytosis when haematocrit is persistently above 0.52 in men or 0.48 in women, while values above 0.60 in men or 0.56 in women are regarded as absolute erythrocytosis without further measurement. Results should be confirmed on a repeat sample.

There are three broad categories. Relative or apparent polycythaemia occurs when plasma volume falls, as in dehydration, so the red cell mass is normal but more concentrated. Primary polycythaemia, mainly polycythaemia vera, is a bone marrow disorder usually linked to a JAK2 gene mutation. Secondary polycythaemia is driven by increased erythropoietin (EPO) or by substances that stimulate red cell production.

The main danger is that thicker blood flows less easily, raising the risk of thrombosis. Symptoms can include headaches, dizziness, blurred vision, itching after a warm bath, flushing and fatigue, but many people have no symptoms at all.

Natural and non-drug causes in athletes

Not every high haematocrit in a sportsperson is a cause for alarm. Several physiological situations can raise it temporarily or modestly.

• Dehydration: testing after heavy sweating, a hard session or a weight cut can give a falsely high result.
• Altitude training: lower oxygen levels stimulate EPO release, increasing red cell mass over weeks. This is legal and widely used in endurance sport.
• Smoking: carbon monoxide reduces oxygen delivery and stimulates red cell production.
• Obstructive sleep apnoea: repeated overnight drops in oxygen, more common in heavier strength athletes.
• Kidney conditions and some tumours that produce EPO.
• SGLT2 inhibitor medicines for diabetes, which can modestly raise haematocrit.

Endurance athletes often have the opposite pattern — so-called sports anaemia — because training expands plasma volume more than red cell mass. A high value in such an athlete is therefore particularly noteworthy.

A doctor will typically repeat the test when you are well hydrated, review medicines and lifestyle, and if needed check EPO levels, oxygen saturation, kidney function and the JAK2 mutation.

Testosterone and anabolic steroids

Raised haematocrit is one of the most common side effects of testosterone therapy. Research by Bachman and colleagues showed that testosterone stimulates EPO and suppresses hepcidin, a hormone that limits iron availability, effectively resetting the body's haemoglobin 'set point' upwards.

A review by Ohlander and colleagues found that erythrocytosis is more frequent with injectable testosterone than with gels, particularly with short-acting injections that create high peaks. Older men, smokers and people with sleep apnoea are at greater risk.

The Endocrine Society guideline recommends checking haematocrit before and during testosterone therapy, and advises against starting treatment when haematocrit exceeds 0.50, and pausing it when it rises above 0.54 until the cause is evaluated.

Non-prescribed anabolic–androgenic steroids, often used at doses far above therapeutic levels and in combination, carry a greater risk. The Endocrine Society scientific statement by Pope and colleagues lists polycythaemia among the cardiovascular hazards of these drugs, alongside adverse lipid changes, raised blood pressure and cardiomyopathy.

EPO, blood doping and anti-doping

Erythropoietin and its analogues are licensed medicines for anaemia in chronic kidney disease and some cancers. In healthy athletes they raise haemoglobin and oxygen-carrying capacity, which is why they became notorious in endurance sport.

The dangers are substantial. EPO misuse can push haematocrit to levels at which blood viscosity rises steeply, especially combined with dehydration during competition. Deaths of young cyclists in the late 1980s and early 1990s were widely attributed to this, although individual cases are difficult to prove.

All erythropoiesis-stimulating agents, HIF activators and blood transfusions are prohibited at all times under the World Anti-Doping Code. The Athlete Biological Passport, described by Sottas and colleagues, tracks an athlete's haematological values over time to detect manipulation indirectly.

Altitude tents and natural altitude training are permitted, which is one reason passport results are interpreted by expert panels taking training history into account.

Risks and what to do

High haematocrit increases the risk of deep vein thrombosis, pulmonary embolism, heart attack and stroke. Risk rises with higher levels and with other factors such as smoking, high blood pressure, dehydration, long-haul travel and inherited clotting tendencies.

If a blood test shows a raised haematocrit, the first step is a repeat test when well hydrated, along with a full medical review. Be honest with your GP about any testosterone, steroids or other substances; this directly determines what investigations and treatment are appropriate.

Treatment depends on the cause. In polycythaemia vera, haematologists use therapeutic venesection and medicines to keep haematocrit below 0.45. In testosterone-related erythrocytosis, the usual approach is to review or pause therapy, change the formulation or adjust the dose under medical supervision. Self-arranged blood removal is not a safe alternative.

Seek urgent medical help for chest pain, sudden breathlessness, a painful swollen leg, sudden weakness, facial droop, speech difficulty or a severe sudden headache — these can be signs of a clot.

Editorial conclusions

Polycythaemia in athletes can result from harmless factors such as dehydration or altitude, but persistent elevation needs investigation.

Testosterone therapy, non-prescribed anabolic steroids and EPO are major pharmacological causes, and all increase the risk of blood clots, heart attack and stroke.

Repeat abnormal tests under standard conditions, disclose all substances to your doctor and seek urgent help for symptoms of thrombosis. Haematocrit management belongs in medical hands.

Further reading from our editorial team: what haematocrit and haemoglobin show on a blood count, cardiovascular effects of anabolic steroids and how the Athlete Biological Passport works.

References

1. McMullin MF, Harrison CN, Ali S, et al. A guideline for the diagnosis and management of polycythaemia vera. A British Society for Haematology Guideline. Br J Haematol. 2019;184(2):176–191.
2. McMullin MFF, Mead AJ, Ali S, et al. A guideline for the management of specific situations in polycythaemia vera and secondary erythrocytosis: a British Society for Haematology Guideline. Br J Haematol. 2019;184(2):161–175.
3. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715–1744.
4. Bachman E, Travison TG, Basaria S, et al. Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point. J Gerontol A Biol Sci Med Sci. 2014;69(6):725–735.
5. Ohlander SJ, Varghese B, Pastuszak AW. Erythrocytosis following testosterone therapy. Sex Med Rev. 2018;6(1):77–85.
6. Pope HG Jr, Wood RI, Rogol A, et al. Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement. Endocr Rev. 2014;35(3):341–375.
7. Sottas PE, Robinson N, Rabin O, Saugy M. The athlete biological passport. Clin Chem. 2011;57(7):969–976.