Testosterone replacement therapy: a safety audit of clinical practice including men with Type 2 diabetes and cardiovascular disease
J. Brooke1,2, D. Walter1,2, V. Muraleedharan1,2 & T. Jones1,2
Hypogonadism is highly prevalent in men with type 2 diabetes (T2D) and/or cardiovascular disease (CVD). Low testosterone levels are associated with CVD risk factors including obesity, insulin resistance, dyslipidaemia and hypertension. Testosterone replacement therapy (TRT) has been shown to have beneficial effects on these parameters; however, safety needs to be verified. An audit of 308 (50% with T2D, 32.1% CVD, 82.8% ED) hypogonadal men (age 59.02±13.23 years; mean baseline testosterone 7.33±2.85 nmol/l) receiving physiological TRT (86.3% testosterone gels) for up to 27 (mean 4.6±0.10) years in normal clinical practice. BMI, waist circumference, BP, Hb, haematocrit (Hct), lipid profile, liver function, testosterone, estradiol and PSA levels were monitored at 3, 6 and 12 months and yearly thereafter. Hospital admissions, major adverse cardiovascular events (MACEs) and mortalities were recorded.
TRT was associated with a reduction in total cholesterol (−0.26±0.11 mmol/l, P=0.018), non-fasting triglycerides (−0.30±0.14 mmol/l, P=0.033), liver transaminases (ALT and AST), HbA1c (−0.32% in whole cohort, P=0.05) at the primary endpoint. In diabetics with HbA1c >7.0% at baseline; HbA1c sharply fell: 8.65% vs 7.65%, P<0.001, n=151 after 3 months and 8.65% vs 6.74%, P<0.001 after five years with few changes in diabetic medications. HDL-cholesterol fell by 0.06 mmol/l (P=0.04). Hb increased by 0.63 g/dl (P<0.001), hematocrit by 0.02 (P<0.001) and PSA by 0.24 g/l (P=0.038). No significant changes in BMI, waist circumference or BP were observed. Adverse events: Hct exceeded 0.52 in eight cases, two new prostate carcinomas, two deaths, 13 MACEs (2 MIs, 2 angina, 5 TIAs, 2 CVAs, 1 CABG and 1 CCF) and 34 hospital admissions. This audit demonstrates that in over 1033 patient years, physiological TRT had beneficial effects on cardiovascular risk factors including glycaemic control, lipids and total cholesterol levels. Importantly, long-term TRT was not associated with any increase in prostate carcinoma, MACEs or mortality over that expected in this morbid population.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.