Screening of approved drugs identifies 3rd generation retinoids as in vitro therapeutic agents in multiple sulfatase deficiency

Molecular Genetics and Metabolism(2023)

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摘要
By reducing LDL cholesterol levels, statins may decrease androgen production. This study was aimed at investigating whether testosterone treatment has an impact on cardiometabolic risk factors in statin-treated men with late-onset hypogonadism (LOH).The study included 31 men with LOH who had been treated for at least 6 months with atorvastatin (20–40 mg daily). On the basis of patient preference, atorvastatin-treated patients were divided into two matched groups of patients: receiving intramuscular testosterone enanthate (100 mg weekly, n = 16) and not treated with this hormone (n = 15). Plasma lipids, glucose homeostasis markers, as well as plasma levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, and fibrinogen were assessed before and after 4 months of therapy.Compared with the control age-, weight, and lipid-matched statin-naïve subjects with LOH (n = 12), atorvastatin-treated patients were characterized by decreased levels of testosterone, hsCRP, and homocysteine. In patients not receiving testosterone therapy, plasma lipids, glucose homeostasis markers, as well as plasma levels of the investigated risk factors remained at the similar levels throughout the whole period of atorvastatin treatment. In atorvastatin-naïve patients, testosterone increased its plasma levels and decreased HDL cholesterol. Apart from an increase in testosterone levels, if administered to atorvastatin-treated subjects with LOH, testosterone reduced plasma levels of LDL cholesterol, uric acid, hsCRP, homocysteine, and fibrinogen, as well as improved insulin sensitivity.Our study may suggest the clinical benefits associated with combination therapy with a statin and testosterone in elderly men with LOH.
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关键词
multiple sulfatase deficiency,generation retinoids,therapeutic agents
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