- Aromatase inhibitor
Type I and II
AIs are categorized into two types: [cite journal |author=Mokbel K |title=The evolving role of aromatase inhibitors in breast cancer |journal=Int J Clin Oncol |volume=7 |issue=5 |pages=279–83 |year=2002 |pmid=12402060 |doi=10.1007/s101470200040]
* Irreversible steroidal inhibitors such as
exemestaneform 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.
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 glandfrom the conversion of androgens. The other main source of estrogen post-menopausally is adipose tissueFact|date=February 2007. 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. [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. Lancet2005 Jan 1-7;365(9453):60-2. PMID 15639680]
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.
Tamoxifenhas 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 receptorpositive. Further studies of various AIs are ongoing.
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. [Attar E, Bulun SE. Aromatase inhibitors: the next generation of therapeutics for endometriosis? Fertil Steril 2006;85:1307-18. PMID 16647373]
AIs have also been used experimentally in the treatment of adolescents whose predicted adult height is low. [cite journal |author=Hero M, Wickman S, Dunkel L |title=Treatment with the aromatase inhibitor letrozole during adolescence increases near-final height in boys with constitutional delay of puberty |journal=Clin Endocrinol (Oxf) |volume=64 |issue=5 |pages=510–3 |year=2006 |pmid=16649968 |doi=10.1111/j.1365-2265.2006.02499.x]
Bodybuilders who take
anabolic steroidsmay 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 [http://dmd.aspetjournals.org/cgi/content/full/31/4/384] has itself been inhibited.4-OHAD is a metaboliteof testosterone, which can mean 4-OHAD remains inhibited whilst aromataselevels are allowed high.
In one recent study, aromatase inhibitors were found to be no more successful at treating pubertal gynecomastia than a placebo. [cite journal |author=Plourde PV, Reiter EO, Jou HC, Desrochers PE, Rubin SD, Bercu BB, Diamond FB Jr, Backeljauw PF |title=Safety and efficacy of anastrozole for the treatment of pubertal gynecomastia: a randomized, double-blind, placebo-controlled trial |journal=Clin Endocrinol (Oxf)|pmid=15356042]
Aromatase inhibitors have also been shown to reverse age-related declines in testosterone, as well as primary hypogonadism. [cite journal |author=Leder BZ, Rohrer JL, Rubin SD, Gallo J, Longcope C. |title= Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels|journal=Clin Endocrinol (Oxf)|pmid=15001605 ]
Some of the aromatase inhibitors in use include:
4-androstene-3,6,17-trione("6-OXO", marketed as a nutritional supplementfor athletes and weight lifters)
Wikimedia Foundation. 2010.
Look at other dictionaries:
Aromatase inhibitor — A drug that inhibits the enzyme aromatase and thus lowers the level of the estrogen, estradiol. Aromatase inhibitors are a class of antiestrogens. Aromatase catalyzes the conversion of testosterone (an androgen) to estradiol (an estrogen) in… … Medical dictionary
aromatase inhibitor — any one of a class of drugs used in the treatment of early and advanced oestrogen dependent breast cancer in postmenopausal women. These drugs act by inhibiting the action of aromatase, an enzyme that promotes the conversion of testosterone to… … The new mediacal dictionary
aromatase inhibitor — A drug that prevents the formation of estradiol, a female hormone, by interfering with an aromatase enzyme. Aromatase inhibitors are used as a type of hormone therapy for postmenopausal women who have hormone dependent breast cancer … English dictionary of cancer terms
nonsteroidal aromatase inhibitor — A drug that decreases the production of sex hormones (estrogen or testosterone) and slows the growth of tumors that need sex hormones to grow … English dictionary of cancer terms
Aromatase — Bändermodell nach PDB … Deutsch Wikipedia
Aromatase — Cytochrome P450, family 19, subfamily A, polypeptide 1 Crystallographic structure of the human aromatase cytochrome P450 (rainbow colored cartoon, N terminus = blue, C terminus = red) in complex with the cofactor protoporphyrin IX (top) and the… … Wikipedia
inhibitor — 1. An agent that restrains or retards physiologic, chemical, or enzymatic action. 2. A nerve, stimulation of which represses activity. SEE ALSO: inhibition. α glucosidase i. an oral agent that aids in th … Medical dictionary
Monoamine oxidase inhibitor — MAOI redirects here. For the Easter Island statues, see Moai. Monoamine oxidase Monoamine oxidase inhibitors (MAOIs) are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating… … Wikipedia
Phosphodiesterase inhibitor — A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), therefore preventing the inactivation of the intracellular second messengers cyclic adenosine monophosphate (cAMP) and… … Wikipedia
Dihydrofolate reductase inhibitor — A dihydrofolate reductase inhibitor is a molecule that inhibits the function of dihydrofolate reductase, and is a type of antifolate. Since folate is needed by rapidly dividing cells to make thymine, this effect may be used to therapeutic… … Wikipedia