A review has recently been published to evaluate

A review has recently been published to evaluate the potential effects of food, alcohol and AM251 juices on the pharmacokinetics and pharmacodynamics of the drugs for BPH. The authors reviewed the PubMed database during the years 1991–2015. In addition, a digital version of Stockley on drug interactions and other electronic databases such as drugs.com and Medscape were also analyzed. The pharmacokinetics of the prolonged release forms of alfuzosin, doxazosin, tamsulosin and silodosin are known to be sensitive to food. Alfuzosin, tamsulosin and silodosin may interact with grapefruit juice and citrus fruits, which may intensify the adverse effects of these drugs. ABs are known to interact with alcohol, which can lead to orthostatic hypotension. For 5-ARI, the pharmacokinetic effect due to the foods consumed is not clinically relevant and, therefore, it can be taken regardless of the meals. summarizes the main interactions with meals and alcohol of these medicines used in BPH, and recommendations are given for their correct use.
Introduction Sex development disorders (DSD) are conditions characterized by genetic, hormonal and phenotypic alterations. Patients with 46,XY DSD are characterized by ambiguous or female external genitalia due to incomplete intrauterine masculinization. Steroid 5-α-reductase deficiency (OMIM number #264600) is a rare autosomal recessive form of 46,XY DSD, first described in 1974 by Imperato-McGinley in patients with pseudovaginal perineoscrotal hypospadias, microphallus, and cryptorchid testes (Imperato-McGinley et al., 1974). This under-virilization is due to an alteration in the 5-α-reductase type 2 gene (SRD5A2), which encodes for 5 α reductase activity that catalyzes the conversion of testosterone (T) to its more active metabolite, dihydrotestosterone (DHT). Presently, two 5-α-reductase isoenzymes, designed as type 1 and 2, have been identified in humans (Jenkins et al., 1992), but only type 2 is expressed in urogenital sinus and urogenital tubercle during gestation and in prostate, seminal vesicle and liver in adulthood and it has higher affinity for steroid substrates, especially T, than type 1. The 5-α-reductase isozyme 2 consists of 254 amino acids, a reduced (NADPH)-dependent isoenzyme, encoded by SRD5A2 gene. The gene is located in the short arm of chromosome 2 and it has five exons (Labrie et al., 1992). Many studies showed that point mutations or the complete deletion of SRD5A2 result in a variable entity of phenotypic expression, depending on the type of mutation and its effect on enzyme activity. In spite of male karyotype, patients with SRD5A2 mutations present pseudovagina and characteristics of dihydrotestosterone deficiency, like perineoscrotal hypospadias, micropenis, rudimentary prostate, clitoris-like phallus, bifid scrotum and cryptorchid testes. Since testosterone production is normal, Wolffian duct differentiation and regression of Müllerian structures are regular (Imperato-McGinley and Zhu, 2002). The extent of ambiguity of the genitalia has been reported to be quite variable and heterogeneous, varying from a female to a fully male phenotype with hypospadias or only microphallus (Hiort et al., 1996). The resulting phenotype is classified by Sinnecker et al. in 5 different categories: type 1 are completely male patients without overt signs of under-masculinization, type 2 are predominantly male with micropenis and hypospadias, type 3 are patients with ambiguous genitalia, type 4 with predominantly female phenotype and type 5 are completely female (Sinnecker et al., 1996). The percentage of patients raised as male is variable from 20% to 50% (Maimoun et al., 2011, Sinnecker et al., 1996, Wilson et al., 1993). Patients with predominantly normal external female structures are often raised as girls, however, at puberty, significant virilization occurs, and without any therapeutic intervention, masculinization is frequently accompanied by a gender identity change from female to male (Cohen-Kettenis, 2005).