[Show abstract][Hide abstract] ABSTRACT: Acromegaly is associated with long-term adverse effects on cardiovascular mortality and morbidity. Reducing growth hormone secretion improves well-being and symptoms, but may not significantly improve the lipoprotein profile. An additional approach to cardiovascular risk reduction in acromegaly may therefore be to target lipoprotein metabolism directly. In this study we investigated the effect of statin treatment.
Double blind, placebo-controlled, crossover study of the effects on circulating lipoproteins of atorvastatin 10 mg daily vs. placebo. Each treatment was given for 3 months in random order.
Eleven patients with acromegaly.
Lipids, lipoproteins, apolipoproteins, enzyme activity and calculated cardiovascular risk.
Atorvastatin treatment compared to placebo resulted in a significant decrease in serum cholesterol (5.85 +/- 1.04 mmol/l vs. 4.22 +/- 0.69 mmol/l; mean +/- SD; P < 0.001), low-density lipoprotein (LDL) cholesterol (2.95 +/- 1.07 mmol/l vs. 1.82 +/- 0.92 mmol/l; P < 0.001), very low-density lipoprotein (VLDL) cholesterol (0.31 (0.21-0.47) mmol vs. 0.23 (0.13-0.30) mmol/l median (interquartile range); P < 0.05), apolipoprotein B (111 +/- 28 mg/dl vs. 80 +/- 18 mg/dl; P < 0.001), and calculated coronary heart disease risk (6.8 (3.3-17.9) vs. 2.8 (1.5-5.7)% over next 10 years; P < 0.01). Serum triglyceride was 1.34 (1.06-1.71) mmol/l on placebo and 1.14 (0.88-1.48) mmol/l on atorvastatin (ns). HDL cholesterol, apolipoprotein A1 and Lp(a) concentrations and cholesteryl ester transfer protein and lecithin: cholesterol acyl transferase activities were also not significantly altered.
Atorvastatin treatment was safe, well tolerated and effective in improving the atherogenic lipoprotein profile in acromegaly.
No preview · Article · Jul 2005 · Clinical Endocrinology
[Show abstract][Hide abstract] ABSTRACT: Hormone replacement therapy (HRT) in postmenopausal women is controversial, with an elevated cardiovascular event rate for combined estrogen-progestogen but no adverse cardiovascular effect and possible cumulative benefit for estrogen alone. Here we measured the effects of differing estrogen/progestogen combinations on the insulin-like growth factor (IGF)/IGF binding protein (IGFBP) system which has been implicated in the pathophysiological mechanisms underlying cardiovascular disease, higher IGFBP-1 levels having been linked with a reduced cardiovascular risk.
Oral conjugated equine estrogens (CEE) alone, or in combination with the increasingly androgenic progestogens medroxyprogesterone acetate, desogestrel or norethisterone, were given in a randomized triple crossover fashion to 35 healthy postmenopausal women. Serum concentrations of IGFs and the principal circulating IGFBPs were measured.
Circulating IGF-I, IGFBP-3 and IGF-I/IGFBP-3 molar ratio were significantly reduced by CEE. These effects were reversed by progestogens according to their androgenicity. Plasma IGFBP-1 concentration increased from baseline to CEE alone. This rise was opposed by progestogens of increasing androgenicity. IGFBP-2 levels fell and IGFBP-4 increased with CEE, with no further change with addition of progestogens. CEE increased the proportional contribution of IGFBP-1 and IGFBP-4 to total IGFBP binding and decreased the IGFBP-3 contribution. This was reversed by progestogens.
There are marked changes in molar ratios of the IGFBPs in relation to estrogen/progestogens in HRT. The effect of progestogens on IGF bioavailability could be an important determinant of the longer-term risks of specific HRT preparations by opposing the potentially beneficial effects of CEE alone on cardiovascular risk.
No preview · Article · Apr 2005 · Gynecological Endocrinology