PMON266 The Effect of Testosterone Replacement Therapy on Cardiovascular Safety and Other Adverse Effects – a Randomised Double Blinded Placebo Controlled Trial (STRIDE Study)
Authors: Mohan Rao Preethi , Ranjan Nishant , Jones Thomas Hugh 
Published: November 2022

Background

Concerns about testosterone treatment and its safety ranging from cardiovascular risk to prostate cancer risk to polycythaemia and obstructive sleep apnoea has always been controversial especially cardiovascular safety. To tip the balance, there were 3 trials that were published in the recent past which induced more controversy by demonstrating that testosterone therapy increased cardiovascular disease and mortality. Our RCT evaluates the safety of testosterone Undecanoate in patients with type 2 diabetes and hypogonadism.

Research design and methods: This is a randomised double blinded placebo-controlled add-on trial of testosterone undecanoate (Nebido®) administered every 12 weeks in 65 hypogonadal men with poorly-controlled type 2 diabetes. Phase 1 patients were randomly assigned to either treatment or placebo arm for 6 months of TRT. Phase 2 was an open-labelled phase for 6 months and patients on placebo moved on to the treatment group wherein patients in the treatment group continued. Adverse events, hospitalizations and mortality were recorded and biochemical parameters were measured at baseline and every three months for a year.

Results

Mean age of the cohort was 59(42-77)years. Baseline characteristics were comparable between active/placebo groups apart from cardiovascular disease and hypertension which were significantly higher in the active group compared to placebo group (n=28 vs n=18, p=0.05), (n=23 vs n=13, p=0.008) respectively. There was no mortality during the period of the trial. There were no cardiovascular adverse effects in either of the phases of the trial in the active arm. One patient had TIA in the placebo arm. There were 3 prostrate related hospitalisations - 2 in those receiving TRT. One gentleman on TRT was diagnosed to have unmasked prostate cancer in the phase-2 of the trial.

There was non-significant increase in PSA between active and placebo group at 6 months (p=0.756). There was no significant increase in mean PSA between baseline, 3, 6, 9 and 12months post treatment in active group. There was no significant increase in number of patients with &gt;0.75 µg/l PSA rise between active and placebo group at 6 months (p=0.902).

An increase in mean haematocrit value at 6 months post treatment with testosterone (Active group- pre-treatment 00.42±0.033 l/l, post treatment 0.435±0.024 l/l Vs Placebo group – pre-treatment 0.42±0.027 l/l, post treatment 0.46±0.034 l/l, p=0.000) was noted. Similar rise was seen in mean RBC and haemoglobin levels (p=0.000, p=0.001 respectively). Such increase in haematocrit and haemoglobin was observed to persist at 12 months in the active arm of the trial. However, no participant had haematocrit value of more than 0.54l/l in both first and second phase of the trial.

Conclusions

Results from our study demonstrates that testosterone replacement therapy in physiological dose was not associated with any serious adverse effects. However, a close monitoring of adverse events is highly advisable.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.