Aromatase inhibitors: Possible future applications
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2004
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Abstract
In premenopausal women ovaries are the major sites of estrogen production, while in postmenopausal women estrogen is produced by aromatization of ovarian and adrenal androgens in extragonadal sites, mostly in adipose tissue. Aromatase is a cytochrome P450 hemoprotein-containing enzyme complex that catalyzes the rate-limiting step in the conversion of androstenedione and testosterone to estrone and estradiol (E2). Aromatase inhibitors (AIs) have been developed primarily for use in either natural or surgical postmenopausal patients. In premenopausal women, the ovary can overcome the estrogen blockade by reflex increments of luteinizing hormone (LH) and follicle stimulating hormone (FSH), so AIs must be combined with a gonadotropin releasing hormone (GnRH) agonist to prevent the reflex LH and FSH increments. In advanced hormone-dependent breast cancer treatment, AIs have been shown to be superior to tamoxifen. Preliminary evidence also suggests superiority in the adjuvant, neoadjuvant settings and also for breast cancer prevention. AIs have been used in infertility and can increase ovulation rate. Reducing FSH dose, estrogen levels, improving response to FSH, implantation rates, and developing multiple follicles that can be used in in vitro maturation procedures are potential areas that AIs might be used in in assisted reproductive technologies (ART), besides simple ovulation induction. AIs are reported to be successful in treatment of endometriosis, an estrogen-dependent process. The use of AIs in gynecomastia, puberte precox, leiomyoma uteri, some estrogen-dependent cancers (ovarian), endometrial cancer and male infertility are reported; some of the results are promising but more clinical trials are needed. AIs are predicted to become the gold standard in the treatment of estrogen-dependent diseases in reproductive medicine in the near future. © Acta Obstet Gynecol Scand 83 2004.
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Aromatase Inhibitors , Breast Neoplasms , Enzyme Inhibitors , Female , Humans , Neoplasms, Hormone-Dependent , aminoglutethimide , anastrozole , androstenedione , apolipoprotein B , aromatase , aromatase inhibitor , clomifene citrate , estradiol , estrogen , estrone , exemestane , fadrozole , follitropin , formestane , gonadorelin agonist , gonadorelin derivative , letrozole , low density lipoprotein cholesterol , luteinizing hormone , megestrol acetate , raloxifene , selective estrogen receptor modulator , tamoxifen , testolactone , testosterone , vorozole , zoledronic acid , Albright syndrome , aromatization , atherosclerosis , breast cancer , cancer adjuvant therapy , cancer hormone therapy , cancer prevention , clinical trial , diarrhea , drug classification , drug dose reduction , drug eruption , drug indication , drug mechanism , drug megadose , drug response , drug structure , dyspnea , endometriosis , endometrium cancer , enzyme activity , estrogen blood level , estrogen synthesis , estrogen therapy , female infertility , fertilization in vitro , fever , first pass effect , gynecomastia , headache , hormone release , hot flush , human , hyperlipoproteinemia , infertility therapy , injection site , lethargy , male infertility , menopausal syndrome , nausea , nidation , nonhuman , ovary cancer , ovary cyst , ovulation induction , postmenopause , precocious puberty , priority journal , review , secondary osteoporosis , side effect , thromboembolism , uterus myoma , vagina bleeding , weight gain