Simvastatin is a very effective hypocholesterolemic drug which, reducing cholesterol biosynthesis, can affect normal steroid hormone production. Testes require a continuous cholesterol supply for testosterone synthesis and this can be derived from low density lipoprotein receptor-mediated uptake or from de novo local synthesis. The aim of the study was to see if prolonged simvastatin treatment compromised endocrine testicular function both in basal conditions and after stimulation by human Chorionic Gonadotropin (hCG) (Profasi 5,000 Ul, i.m. at 8 a.m.). Free testosterone (FT) levels were determined at baseline and after 3, 6 and 12 months of simvastatin treatment (20 mg/day) in eight hypercholesterolemic patients. At the same time we performed a hCG stimulation test to evaluate testicular reserve. A significant reduction of FT, both basal and hCG-stimulated, was observed in the 6th and the 12th month of the study. However, FT levels remained in the normal range and no patient complained of gonadal function related symptoms. No significant change was observed in estradiol response to hCG test. Lastly, there was no variation in LH, FSH, progesterone, 17-OH-progesterone, androstenedione or dehydroepiandrosterone-sulphate levels. Our study concluded that the drug causes a mild decline in FT secretion without any clinical sign of testicular dysfunction.
In order to investigate the role of melatonin on the neuroregulation of GH secretion, eight healthy male volunteers each underwent four separate tests in random order separated by at least 1 week. Following oral administration of melatonin (500 mg at -60 min and at -30 min) plasma GH levels were higher than after placebo at 45 min (mean +/- SEM 2.9 +/- 0.8 vs 0.9 +/- 0.4 ng/ml, P less than 0.01) and 60 min (mean +/- SEM 2.9 +/- 0.4 vs 0.8 +/- 0.1 ng/ml, P less than 0.05). Likewise, after prior administration of melatonin, GH responses to GRF 1-44 (1 micrograms/kg i.v. at 0 min) were greater than placebo plus GRF at 15 min (mean +/- SEM 22.4 +/- 6.1 ng/ml vs 11.3 +/- 2.3 ng/ml, P less than 0.05), 45 min (mean +/- SEM 26.2 +/- 5.3 ng/ml vs 13.3 +/- 2.5 ng/ml, P less than 0.01) and 60 min (mean +/- SEM, 24.7 +/- 7.4 ng/ml vs 11.1 +/- 2.5 ng/ml, P less than 0.05). In contrast we did not observe any effect of either 10(-9)M, 10(-7)M melatonin on in-vitro basal GH release and GH responses to 10(-8)M GRF by rat anterior pituitary cells in monolayer culture. These data suggest that melatonin plays a facilitatory role in the neuroregulation of GH secretion, probably by acting at the hypothalamic level.
Since recombinant growth hormone (GH) has been available, its use has been extended to treating not only children with growth hormone deficiency, but also short-statured children without GH deficiency. It is interesting, therefore, to determine whether GH therapy given in conventional doses causes metabolic side effects in these patients. In the present study we have examined the effect of recombinant human GH on eleven short normal children. Patients received 12 U/m2/week for 1 year. Before beginning treatment, the children had a mean annual growth velocity of 5.1 +/- 0.9 cm/yr; during the year of treatment, the therapy was effective and improved the mean growth velocity to 7.1 +/- 1.7 cm/yr, p < 0.05. We evaluated the subacute short-term effects during the first 15 days of treatment and the long-term effects for one year of GH treatment on lipid and lipoprotein levels. We found a significant increase in total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) at the 6th month. Triglycerides (TG) increased significantly at the 3rd and 6th month. Both TC and TG returned to baseline at the 12th month. In no case however did the levels of TC, LDL-C and TG go above normal nor were there any changes in the following tests: high density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) A-I, Apo B, Apo C-II, Apo C-III and Apo E. In conclusion, conventional doses of GH given to short normal children are effective in ameliorating growth velocity and do not cause serious metabolic side effects.
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