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Erectile dysfunction is not uncommon after radical prostatectomy and men who undergo ADT in addition to this are likely to show further decline in their ability to engage in penetrative intercourse, as well as their desire to do so. [13] A study looking at the differences of using GnRH-A (and androgen suppressant) or an orchiectomy report differences in sexual interest, the experience of erections, and the prevalence of participating in sexual activity. Men reporting no sexual interest increased from % to % after orchiectomy, and from % to % after GnRH-A; men who experienced no erections increased from % to %; and men who did not report engaging in sexual activity increased from % to % after orchiectomy and % to %. [14] This study suggests that the GnRH-A and orchiectomy had similar effects on sexual functioning. A vicious cycle whereby lowering testosterone levels leads to decreased sexual activity, which in turn cause both free and total testosterone levels to decline even further. [12] This demonstrates the importance of androgens for maintaining sexual structures and functions. [12] [15]

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Flutamide and 2-hydroxyflutamide have been found in vitro to inhibit CYP17A1 (17α-hydroxylase/17,20-lyase), an enzyme which is required for the biosynthesis of androgens. [53] In accordance, flutamide has been found to slightly but significantly lower androgen levels in GnRH analogue-treated male prostate cancer patients [54] and women with polycystic ovary syndrome . [23] As such, flutamide is a weak inhibitor of androgen biosynthesis. [50] However, the clinical significance of this action may be limited when flutamide is given without a GnRH analogue to non-castrated men, as the drug markedly elevates testosterone levels into the high normal male range via prevention of AR activation-mediated negative feedback on the hypothalamic–pituitary–gonadal axis in this context. [12]

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