1.
Management of dyslipidemia in Cushing's syndrome.
Greenman, Y
Neuroendocrinology. 2010;:91-5
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Abstract
Cardiovascular risk factors such as hypertension, hyperlipidemia and glucose intolerance are highly prevalent in Cushing's syndrome. Lipid abnormalities have been reported in 40-70% of patients, including those with 'subclinical' disease. Surgical cure is associated with significant amelioration of lipid profile in the majority of patients. Treatment of persistent hyperlipidemia should be conducted according to the accepted general principles in use for other medical conditions. Nevertheless, patients requiring medical treatment for persistent hypercortisolism present specific challenges, according to the selected therapeutic agent. For example, treatment with the adrenolytic drug o,p'DDD is associated with a prominent increase in cholesterol levels that necessitates intensive use of lipid lowering agents. The use of ketoconazole, a potent inhibitor of cytochrome P450 3A4 (CYP3A4), may significantly increase plasma concentrations of certain statins (such as simvastatin and atorvastatin) that undergo metabolism by the same pathway, thus increasing the risk of complications and side effects. Therefore, preference should be given to HMG-CoA inhibitors that are metabolized by different pathways, such as pravastatin. In summary, hyperlipidemia should be aggressively treated in patients with Cushing's syndrome in view of the increased cardiovascular morbidity and mortality associated with this disorder.
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Improved responsiveness of PCOS patients to clomiphene after CYP17a inhibitor.
Ali Hassan, H, El-Gezeiry, D, Nafaa, TM, Baghdady, I
Journal of assisted reproduction and genetics. 2001;(11):608-11
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Abstract
PURPOSE To study the effect of CYP17a inhibitor, "ketoconazole," on clomiphene responsiveness in PCOS patients. METHODS Prospective analysis was employed with the setup at Alexandria IVF/ICSI center. Ninety-seven insulin-resistant PCOS patients undergoing ovulation induction using clomiphene citrate were randomly divided, by random number table, into two groups. The first group (n = 49) received ketoconazole (400 mg daily) till correction of metabolic syndrome followed by clomiphene (100 mg/day); the second group (n = 48) receiving clomiphene without ketoconazole pretreatment. Main outcome measures were incidence of clomiphene resistance, monofollicular response, fasting insulin/glucose ratio, serum testosterone, and pregnancy rates. RESULTS The ketoconazole group showed significantly (p < 0.05) higher incidence of monofollicular response (38%), higher pregnancy rates, and significantly less marked antiestrogenic manifestations than did the control group. They also had significantly lower incidence of clomiphene resistance (11.6%), lower serum testosterone levels, less hyperinsulinaemia, than did the control group. CONCLUSION Ketoconazole improved clomiphene responsivenss in PCOS patients and attenuated its untoward biological effects.