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  • Title: Effects of hydroxyflutamide on female reproductive function.
    Author: Chandrasekhar Y.
    Journal: Adv Contracept Deliv Syst; 1991; 7(2):157-66. PubMed ID: 12284218.
    Abstract:
    Among the observed effects of hydroxyflutamide (HF), a nonsteroidal anti-androgenic drug, are blockade of ovulation and the preovulatory luteinizing hormone (LH) surge and delay in implantation and suppressed decidualization of the uterus. HF binds to the androgen receptor and competitively inhibits the binding of testosterone and dihydrotestosterone. As a nonsteroidal compound, HF is devoid of other hormonal or anti-hormonal activities and thus can be used for the investigation of the role of androgens in various reproductive processes. In female rats, HF has been demonstrated to overcome the ovulation inhibitory effect of a high LH: follicle stimulating hormone (FSH) ratio and to block the LH surge. Since HF is not anti-estrogenic, the suppressed HF surge in HF-treated rates is not due to interference with estradiol-mediated positive feedback. There are indications, however, that HF does interfere with progesterone action in induction of the LH surge and thus may have an anti-progestagenic activity. In prepubertal rats, HF exhibits anti-progestagenic action at the level of the uterus and cervix as well as the hypothalamus. This function appears related to HF's ability to bind to progesterone receptors and reduce receptor levels. Injection of HF significantly enhances the estradiol-induced elevation in rat's uterine progesterone binding sites yet does not affect uterine growth response. It is hypothesized that HF interferes with the ability of estrogen to induce progesterone receptors at a post-receptor site, but further research is needed to identify the mechanisms involved.
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