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07-SEPTEMBER-2008 03:17:44 - Aromatase inhibitor Aromatase converts testosterone to estradiol Aromatase converts testosterone to estradiol Aromatase converts androstenedione to estrone Aromatase converts androstenedione to estrone Aromatase inhibitors AI are a class of drugs used in the treatment of breast cancer and ovarian cancer in postmenopausal women that block the aromatase enzyme. Contents 1 Type I and II 2 Mode of action 3 Indication 3.1 Cancer 3.2 Other 4 Members 5 References Type I and II AIs are categorized into two types: 1 Irreversible steroidal inhibitors such as exemestane form a permanent bond with the aromatase enzyme complex. Non-steroidal inhibitors such as anastrozole, letrozole inhibit the enzyme by reversible competition. Mode of action Aromatase inhibitors work by inhibiting the action of the enzyme aromatase, which converts androgens into estrogens by a process called aromatization. As breast tissue is stimulated by estrogens, decreasing their production is a way of suppressing recurrence of the breast tumor tissue. Indication Cancer In contrast to pre-menopausal women, in whom most of the estrogen is produced in the ovaries, in post-menopausal women most of the body's estrogen is produced in the adrenal gland from the conversion of androgens. The other main source of estrogen post-menopausally is adipose tissuecitation needed. Because some breast cancers respond to estrogen, lowering the estrogen level in post-menopausal women using aromatase inhibitors has been proven to be effective in breast cancer treatment.2 Aromatase inhibitors are generally not used to treat breast cancer in premenopausal women. Since most of the circulating estrogen is produced by the ovaries, not by conversion of androgens to estrogen, blocking the enzyme aromatase does not significantly decrease the production of estrogen. When aromatase inhibitors are used in premenopausal women, the decrease in estrogen activates the hypothalamus and pituitary axis to increase gonadotropin secretion, which in turn stimulates the ovary to increase androgen production. This counteracts the effect of the aromatase inhibitor. An ongoing area of clinical research is optimizing adjuvant hormonal therapy in postmenopausal women with breast cancer. Tamoxifen has been standard treatment, however the ATAC trial has shown that clinical results are superior with an AI in postmenopausal women with localized breast cancer that is estrogen receptor positive. Further studies of various AIs are ongoing. Other Investigations are ongoing to look for other applications. Researchers are studying aromatase inhibitors to stimulate ovulation in a manner similar to, but not exactly the same as, clomiphene citrate or suppress estrogen production, ie in endometriosis.3 AIs have also been used experimentally in the treatment of adolescents whose predicted adult height is low.4 Bodybuilders who take anabolic steroids may also take AIs to prevent the steroids from being converted to estrogen; an increase in estrogen levels has undesirable consequences for a bodybuilder, such as gynecomastia. This is often the case when a natural aromatase inhibitor 4-OHAD 1 has itself been inhibited. 4-OHAD is a metabolite of testosterone, which can mean it remains inhibited whilst aromatase levels are allowed high. In one recent study, aromatase inhibitors were found to be no more successful at treating pubertal gynecomastia than a placebo. 5 Aromatase inhibitors have also been shown to reverse age-related declines in testosterone, as well as primary hypogonadism.6 Members Some of the aromatase inhibitors in use include: Aminoglutethimide Anastrozole Arimidex Letrozole Femara Vorozole Rivizor Exemestane Aromasin 4-androstene-3,6,17-trione 6-OXO, marketed as a nutritional supplement for athletes and weight lifters 1,4,6-androstatrien-3,17-dione ATD Formestane Lentaron Testolactone Teslac Fadrozole Afema References ^ Mokbel K 2002. The evolving role of aromatase inhibitors in breast cancer. Int J Clin Oncol 7 5: 279-83. doi:10.1007/s101470200040. PMID 12402060. ^ Howell A, et al; ATAC Trialists Group. Results of the ATAC Arimidex, Tamoxifen, Alone or in Combination trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet 2005 Jan 1-7;3659453:60-2. PMID 15639680 ^ Attar E, Bulun SE. Aromatase inhibitors: the next generation of therapeutics for endometriosis? Fertil Steril 2006;85:1307-18. PMID 16647373 ^ Hero M, Wickman S, Dunkel L 2006. Treatment with the aromatase inhibitor letrozole during adolescence increases near-final height in boys with constitutional delay of puberty. Clin Endocrinol Oxf 64 5: 510-3. doi:10.1111/j.1365-2265.2006.02499.x. PMID 16649968. ^ Plourde PV, Reiter EO, Jou HC, Desrochers PE, Rubin SD, Bercu BB, Diamond FB Jr, Backeljauw PF. Safety and efficacy of anastrozole for the treatment of pubertal gynecomastia: a randomized, double-blind, placebo-controlled trial. Clin Endocrinol Oxf. PMID 15356042. ^ Leder BZ, Rohrer JL, Rubin SD, Gallo J, Longcope C.. Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels. Clin Endocrinol Oxf. PMID 15001605. v d e Sex hormones and related agents primarily G03, also L02, H01C - human endogenous in CAPS Progestogens: receptor Agonist PROGESTERONE, Dienogest, Desogestrel, Drospirenone, Dydrogesterone, Ethisterone, Etonogestrel, Ethynodiol diacetate, Gestodene, Gestonorone, Levonorgestrel, Lynestrenol, Medroxyprogesterone, Megestrol, Norelgestromin, Norethisterone, Norethynodrel, Norgestimate, Norgestrel, Norgestrienone, Tibolone SPRM Asoprisnil, CDB-4124 Antiprogestogen Mifepristone Androgens: receptor Agonist TESTOSTERONE, Androstanolone, Fluoxymesterone, Mesterolone, Methyltestosterone, see also anabolic steroids Antiandrogen Bicalutamide, Cyproterone, Dienogest, Flutamide, Nilutamide, Spironolactone Estrogens: receptor Agonist ESTRADIOL, ESTRIOL, ESTRONE, Chlorotrianisene, Dienestrol, Diethylstilbestrol, Ethinylestradiol, Fosfestrol, Mestranol, Polyestradiol phosphate SERM Afimoxifene, Arzoxifene, Bazedoxifene, Clomifene, Fulvestrant, Lasofoxifene, Raloxifene, Tamoxifen, Toremifene AI Aminoglutethimide, Anastrozole, Atamestane, Exemestane, Fadrozole, Formestane, Letrozole, Vorozole Antiestrogen Mepitiostane Gonadotropins: FSHR/LHCGR ovulation stim. Clomifene, Urofollitropin Antigonadotropin Danazol, Gestrinone GnRH: receptor Agonist Buserelin, Goserelin, Histrelin, Leuprorelin, Nafarelin, Triptorelin Antagonist Abarelix, Cetrorelix, Ganirelix v d e Pharmacology: enzyme inhibition Class Competitive inhibition - Uncompetitive inhibition - Non-competitive inhibition - Suicide inhibition - Mixed inhibition Substrate Oxidoreductase EC 1: Aromatase inhibitors - Lipoxygenase inhibitor - Monoamine oxidase inhibitors - COX-2 inhibitor Transferase EC 2: Integrase inhibitor - Protein kinase inhibitors - Reverse transcriptase inhibitors - COMT inhibitors Hydrolase EC 3: Acetylcholinesterase inhibitors - Phosphodiesterase inhibitors - Protease inhibitors ACE inhibitor, Trypsin inhibitor - Histone deacetylase inhibitor Lyase EC 4: Carbonic anhydrase inhibitors Retrieved from http://en..org/wiki/Aromatase_inhibitor Categories: Hormonal agentsHidden categories: All articles with statements | Articles with statements since February 2007 Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Português This page was last modified on 30 July 2008, at 12:35
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