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Cardiovascular Safety and Testosterone Replacement Therapy in Male Hypogonadism

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by , 03-07-2013 at 06:34 PM (4761 Views)

Cardiovascular Safety and Testosterone Replacement Therapy in Male Hypogonadism Including Men with Type 2 Diabetes and Cardiovascular Disease

Jonathan C Brooke, BMedSci1,2, David S McLaren1,2, Deborah J Walter, BMedSci1,2, Vakkat Muraleedharan, MB, BS, MRCP1,2 and Thomas H Jones, MD, FRCP1,2

1 Centre for Diabetes and Endocrinology, Barnsley Hopsital, NHSFT Barnsley, UK
2 Human Metabolism, University of Sheffield Sheffield, UK
Testosterone replacement therapy (TRT) has recently been shown to have beneficial effects on CVD risk factors including insulin resistance, dyslipidaemia, obesity, hypertension and pro-atherogenic states. Nevertheless, the use of TRT remains controversial in men with cardiovascular disease.

A long-term retrospective audit of 401 (47.4% Type 2 diabetes (T2D), 34.0% CVD) hypogonadal men (age 58.714.3 years; mean baseline testosterone 7.162.59 nmol/l) receiving physiological TRT (84% testosterone gels) for up to 27 years (mean 5.41 years) in normal clinical practice was carried out to evaluate TRT's safety. BMI, waist circumference, blood pressure (BP), hemoglobin (Hb), hematocrit (HCT), lipid profile, liver function, testosterone, estradiol and PSA levels were monitored at 3, 6 and 12 months and yearly thereafter. Data from the most recent visits represent the primary endpoint. Hospital admissions, major adverse cardiovascular events (MACEs), mortalities and prostate-related outcomes were recorded.

TRT was associated with a reduction in total cholesterol (-0.28 mmol/l, p=0.004), non- fasting triglycerides (-0.244 mmol/l, p=0.04) and liver transaminases (ALT and AST) at the primary endpoint. HDL cholesterol fell by 0. /l (p=0.044). Hb increased by 0.72g/dl (p=0.002), HCT by 0.035 (p=0.011), PSA by 0.26g/l (p=0.008) and estradiol 128.4544.58 at baseline vs 15766.89 pmol/l. At the end of the study PSA levels were comparable to those of eugonadal males and were not grossly elevated. No significant changes in BMI, waist circumference or BP were observed.

Safety outcomes: Polycythaemia (HCT >0.52) developed in 22 patients. 3 new cases of BPH and 2 prostate carcinomas were diagnosed, but this is no more than expected in this population which included aging males. 4 patients were diagnosed with T2D during the study, and 24 MACEs (4 MI, 8 angina, 5 TIAs, 2 CVAs, 4 CABG, 1 CCF) were identified. Over the course of the study there were 54 hospital admissions and 2 deaths which are no higher than expected in this morbid population.

This audit confirms the cardioprotective role of physiological doses of testosterone and demonstrates that in clinical practice TRT has beneficial effects on cardiovascular risk factors including circulating lipid and cholesterol levels. This is the largest and most comprehensive study of TRT safety to date, representing over 1642 patient years of TRT. TRT was not associated with an increase in prostate carcinoma, MACEs or mortality.