THE EFFECTS OF CLONIDINE ON BLOOD-PRESSURE, CATECHOLAMINE AND GROWTH-HORMONE RELEASE IN HYPOGONADAL MEN IS PRESERVED AND NOT INFLUENCED BY TESTOSTERONE REPLACEMENT THERAPY

It has been demonstrated that castration impairs the hypotensive effec t of clonidine in rat as well as its OH-releasing activity while testo sterone replacement restores to normal the effects of alpha-2 adrenoce ptor activation. Thus, these data point to main role of the gonadal st eroid testosterone in modulating the effects of alpha-2 adrenergic act ivation on blood pressure, catecholamine and GH release in animal. Aim of the present study was to verify the activity of clonidine on blood pressure, catecholamine and GH release in human male hypogonadism bef ore and after testosterone replacement. To this goal, 14 hypogonadal m en (HP, age 33.8+/-2.9 yr; BMI<25 kg/m(2); 8 with hypergonadotropic an d 6 with hypogonadotropic hypogonadism) received clonidine administrat ion (CLON, 300 mu g po at 0 min) before and after 3 months of testoste rone replacement (testosterone propionate depot, 250 mg i.m. every 21 days). Ten normal adult volunteers (NS, age 31.5+/-1.9 yr; BMI<25 kg/m (2)) were studied as control group. in all subjects, before and after clonidine administration, systolic and diastolic blood pressure (SEP a nd DBP), pulse rate (PR), norepinephrine (NE), epinephrine (Ef and GH levels were recorded. In HP basal testosterone levels were lower than those in NS (1.25+/-0.3 vs 7.34+/-1.5 ng/ml, p<0.05) and were restored to normal by hormonal replacement (6.91+/-1.3 ng/ml) In HP, both SSP and DBP as well as PR were normal in basal conditions and were not mod ified by testosterone replacement. Both before and during testosterone CLON lowered SEP, DBP and PR in HP to the same extent observed in NS, In HP, basal NE levels were lower than those in NS (0.85+/-0.15 vs 1. 28+/-0.19 nmol/l, p<0.05) and were restored to normal during testoster one replacement (1.25+/-0.13 nmol/l). On the other hand, basal E level s in HP were similar to those in NS (179+/-42 vs 197+/-38 pmol/l) and were not modified by testosterone therapy (167+/-28 pmol/l). in HP, bo th before and during testosterone replacement, CLON reduced NE (0.44+/ -0.10 and 0.58+/-0.07 nmol/l) levels to the same levels recorded in NS (0.68+/-0.08 nmol/l). Basal GH and IGF-I levels in HP (1.15+/-0.5 and 234+/-42 mu g/l, respectively) were similar to those in NS (1.18+/-0. 4 and 221+/-38 mu g/l, respectively) and were not modified by testoste rone (1.35+/-0.6 and 256+/-32 mu g/l, respectively). CLON administrati on induced a clear GH response in HP (F=37; p<0.001) which overlapped with that recorded in NS and was not modified by testosterone (F=1.7; P=NS). Our present findings demonstrate that, differently from in anim al, in man testosterone has no role in modulating the effects of alpha -2 adrenergic activation by clonidine on blood pressure, catecholamine and GH release, On the other hand, our data suggest the existence in male hypogonadism of a reduced basal noradrenergic activity which is r estored by testosterone replacement. (C) 1996, Editrice Kurtis