Testosterone replacement therapy is associated with an
increased risk of over-production of red blood cells (polycythaemia) in HIV-positive men, US investigators report in
the online edition of AIDS.
None of their patients developed health problems because of
the condition. However, polycythaemia can cause blood clots and cardiovascular
events. The investigators stress
that that patients taking testosterone replacement therapy should be regularly
monitored for polycythemia, and if appropriate have their testosterone dose
Polycythemia is an increase in the number of red blood cells
circulating in the blood. It is well known that the condition can be caused by
testosterone replacement therapy, but there is little information on its risk
factors in patients with HIV.
The risk of blood clots due to polycythaemia is greatest in people with other risks for blood vessel diseases such as diabetes or high blood pressure. In other patients the only symptoms may be headache, blurry vision or confusion.
Doctors in New York conducted a case controlled
study involving patients who received HIV care between 1988 and 2008.
Patients were diagnosed as having polycythaemia if they had a
sustained (eight weeks or longer) increase in their haemoglobin. The value for
men was a haemoglobin level above 18.5 g/dl, and the level for women was 16.5
Each patient with polycythaemia was matched with two patients
of the same age and sex who received HIV care at the clinic at the same time
and for a similar duration.
The investigators hypothesised that as in the general
population, testosterone replacement therapy would be a risk factor
for polycythaemia in their HIV-positive patients.
The total clinic population comprised 6005 patients, and 25
individuals (21 men and four women) met the criteria for polycythaemia. The investigators therefore calculated
that the overall prevalence of the condition was 0.42%.
Mean haemoglobin at the time of diagnosis with polycythaemia
was 18.9 g/dl for men and 17 g/dl for women.
Because only four women met the criteria for polycythaemia
and as the study’s primary hypothesis was that testosterone replacement therapy
caused the condition, the investigators focused their analysis on the 21 male
These individuals had a mean age of 46 years at the time
polycythaemia was diagnosed. All the cases occurred between 2002 and 2007. CD4
cell counts and viral load were comparable between the cases and controls.
Testosterone was used within two months of polycythemia
diagnosis by 67% of patients and by 21% of controls (p = 0.004). Administration
of testosterone replacement therapy via intramuscular injections (p = 0.15) was
more strongly associated with polycythaemia than the use of testosterone patches
(p = 0.09).
After controlling for potentially confounding factors, any
use of testosterone was shown to significantly increase the risk of
polycythaemia (OR = 7.65; 95% CI, 1.99-29.4; p = 0.003).
“Testosterone use was the leading explanation for elevated
haemoglobin in our patients,” comment the investigators.
Approximately a quarter of patients with polycythaemia did
not use testosterone. There were other explanations for the condition for three
of these individuals. These included pulmonary hypertension, chronic
obstructive pulmonary disease, and plasma volume contraction. However, for two
patients no documented cause for elevations in haemoglobin could be found.
None of the patients developed cardiovascular complications
or blood costs, possible consequences of polycythaemia.
“We did not observe any adverse clinical events attributable
to polycythaemia,” write the authors. However, they add “we cannot exclude the
possibility that polycythaemia is clinically important given our small sample
size, limited duration of follow-up, and predisposition of HIV-infected
patients to atherosclerotic and thrombotic disease.”
They therefore recommend that HIV-infected patients taking
testosterone replacement therapy should have regular tests to monitor their red
blood cell count with “adjustment of testosterone dose or cessation of therapy
as appropriate…patients with polycythaemia should be queried about prescription
or non-prescription use of testosterone.”