Abstract
Aromatase is a cytochrome P450 enzyme (CYP19A1 isoform) able to catalyze the conversion of androgens to estrogens. The aromatase gene mutations highlighted the action of estrogen as one of the main regulators of bone maturation and closure of bone plate. The use of aromatase inhibitors (AI) in boys with short stature has showed its capability to improve the predicted final height. Anastrozole (ANZ) and letrozole (LTZ) are nonsteroidal inhibitors able to bind reversibly to the heme group of cytochrome P450. In this review, we describe the pharmacokinetic profile of both drugs, discussing possible drug interactions between ANZ and LTZ with other drugs. AIs are triazolic compounds that can induce or suppress cytochrome P450 enzymes, interfering with metabolism of other compounds. Hydroxilation, N-dealkylation and glucoronidation are involved in the metabolism of AIs. Drug interactions can occur with azole antifungals, such as ketoconazole, by inhibiting CYP3A4 and by reducing the clearance of AIs. Antiepileptic drugs (lamotrigine, phenobarbital, and phenytoin) also inhibit aromatase. Concomitant use of phenobarbital or valproate has a synergistic effect on aromatase inhibition. Therefore, it is important to understand the pharmacokinetics of AIs, recognizing and avoiding possible drug interactions and offering a safer prescription profile of this class of aromatase inhibitors. Arch Endocrinol Metab. 2017;61(3):391-7.
Highlights
Aromatase is a cytochrome P450 enzyme, identified as the CYP19A1 isoform, which catalyzes the conversion of androstenedione and testosterone to estrone and estradiol, respectively
The enzyme is a complex formed by two proteins: CYP19 and nicotinamide-adenine dinucleotide phosphate reductase (NADPH) [1]
Adipose tissue is the primary site of aromatization, but aromatase can be found at other sites such as the brain, breast, placenta, liver, muscle, bone, testes (Leydig cell and germ cell), vasculature, and skin [4,5]
Summary
Aromatase is a cytochrome P450 enzyme, identified as the CYP19A1 isoform, which catalyzes the conversion of androstenedione and testosterone to estrone and estradiol, respectively. Androgens are produced both by the adrenal glands and the testes, whereas estrogen is mostly synthesized locally in peripheral tissues from the local aromatization of circulating androgens [2,3]. Adipose tissue is the primary site of aromatization, but aromatase can be found at other sites such as the brain (hypothalamus, limbic system, and cerebral cortex), breast, placenta, liver, muscle, bone (osteoblast and chondrocyte), testes (Leydig cell and germ cell), vasculature (smooth muscle cell), and skin (fibroblast and hair follicle) [4,5]. Synthesized estrogen seems to have predominantly local effects [2,3,6]. The clinical presentation includes gynecomastia and bone age advancement with potential reduction of final height [10]
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