Effect of Testosterone on Endothelial Function and Microcirculation in Type 2 Diabetic Patients With Hypogonadism
Effect of Testosterone on Endothelial Function and Microcirculation in Type 2 Diabetic Patients With Hypogonadism
Diabetes mellitus is associated with long-term complications affecting mainly the eyes,
 nerves and kidneys. One of the main underlying causes for this is damage to the lining of the
 small blood vessels supplying these organs with dysfunction of the endothelium (lining of the
 small blood vessels). Testosterone has been shown to have an effect macro (large) blood
 vessels with limited data available on the micro (small) blood vessels. Testosterone is
 recognised to have important effects on metabolism and vascular behaviour beyond the accepted
 effects on secondary sexual characteristics. Physiological testosterone therapy is associated
 with some beneficial effects on the cardiovascular system and has been used with some success
 to treat patients with stable angina and chronic heart failure. The investigators therefore
 propose to study the effects of testosterone replacement therapy in patients with
 hypogonadism (low testosterone levels) on the endothelium in males with type 2 diabetes. 40
 diabetic patients with type 2 diabetes and low testosterone levels and erectile dysfunction
 (impotence) will be recruited into the study. All patients will receive testosterone
 replacement therapy and 10 patients will also receive Vardenafil (a drug used to treat
 impotence). The investigators hope to demonstrate an improvement in endothelial dysfunction
 by assessing biochemical markers such as nitric oxide (a chemical that causes relaxation for
 the blood vessels) and C-reactive protein (a chemical that can increase in patients with
 diabetes) as well as the effect on weight, blood pressure, diabetes control and cholesterol.
Inclusion Criteria:

 -  40 male patients with type 2 diabetes mellitus.

 -  T2DM as judged by WHO criteria:

 -  onset of diabetes mellitus after the age of 30 years

 -  blood glucose controlled by diet or drugs other than insulin, or insulin
 initiated after 2 years diagnosis of diabetes

 -  no history of diabetic ketoacidosis.

 -  Symptomatic Hypogonadism as defined by:

 -  Total testosterone below 10 nmol/l

 -  Aging males' symptom score (AMS) above 36.

 -  Hypogonadic men with erectile dysfunction

 -  Age range- 50-80 years

 Exclusion Criteria:

 -  Patients with uncontrolled hypertension (BP>145/95 on treatment) or significant
 hypotension. (BP<100 systolic)

 -  Current smokers

 -  Recent myocardial infarction (<6 months), unstable angina or ongoing chest pain,
 recent (within 6 months) cardiac intervention (e.g. angioplasty, stenting or CABG) or
 stroke.

 -  Patients with clinical nephropathy (24 hr protein >0.5 g or urine protein +) or
 moderate renal failure (serum creatinine >150 micromol/l).

 -  History of prostate cancer or suspicion of prostate cancer on clinical examination

 -  Androgen dependent carcinoma of the male mammary gland

 -  Liver tumours

 -  Hypersensitivity to NEBIDO or LEVITRA

 -  Polycythaemia

 -  General systemic illness, including cardiac, renal or hepatic insufficiency

 -  Patients on nitrates will not be included in the Levitra arm.

 -  History of loss of vision in one eye because of non arteritic ischaemic optic
 neuropathy (NAION), regardless of whether this episode was in connection or not with
 previous PDE5 inhibitor exposure.

 -  Hereditary degenerative retinal disorders such as retinitis pigmentosa.

 -  Clinically significant chronic haematological disease which may lead to priapism

 -  Bleeding disorders

 -  Significant active peptic ulceration.

 -  Concomitant use of vardenafil with HIV protease inhibitors such as ritonavir and
 indinavir is contraindicated, as they are potent inhibitors of CYP 3A4

 -  Concomitant use of vardenafil with potent CYP 3A4 inhibitors ketoconazole and
 itraconazole (oral form) is contra-indicated in men older than 75 years.

 -  Patients deemed unable to comply with the requirements of the protocol.