Aromatase inhibitors

Abstract

Aromatase inhibitors (AIs) are anti-estrogenic agents, which exert their action by inhibiting aromatase enzyme. AIs are a newer class of drugs that inhibit the function of the aromatase enzyme. In postmenopausal women, AIs can suppress most of the peripheral aromatase activity, leading to profound estrogen deprivation. AIs are classified as first, second or third generation according to their sequential development. Aromatization is the final step in steroid biosynthesis and, therefore, aromatase is a suitable target for selective inhibition. Aromatase is expressed primarily in the ovary and also in central and peripheral tissues, fat, muscle, liver, and breast. Normal and malignant breast tissue contributes to the peripheral synthesis of estrogens. Studies have consistently shown that lifetime exposure to estrogens increase the risk of breast cancer. The degree of risk is increased by persistently elevated blood concentrations of estrogen. AI can effectively reduce the estrogen level hence improves breast cancer including advanced stage. Aromatase enzyme is demonstrated locally in endometriotic implants, which indicates local production of estrogen by these implants. Thus, extraovarian aromatse is likely to cause a resistance to GnRHa treatment via persistence of local and peripheral estrogen production during such treatment. In this situation aromatase inhibitors are effective to reduce the synthesis of both ovarian and extraovarian estrogen. Anti-estrogens have lot of potential to be used as oral ovulation inducing agent. In the late 1990s, aromatase inhibitors, including letrozole, began to be used to induce ovulation by being administered in the early part of the menstrual cycle. Estrogen production from all sources is blocked by inhibiting aromatization, releasing the hypothalamic-pituitary axis from estrogenic negative feedback and resulting in increased gonadotropin secretion and ovarian follicular stimulation.There may be potential new applications for aromatase inhibitors including improving implantation and prevention of ovarian hyperstimulation syndrome during assisted reproductive technology by reducing supraphysiologic level of estrogen. Regarding safety concern different studies showed that there were no increased rates of major and minor malformations beyond what would be expected in the general population (1-3%). It is not far away that aromatase inhibitors will possibly emerge as first line ovulation inducing drug for anovulatory or ovulatory infertility following further largescale, multicentric, randomized controlled research and clinical trials. © 2009 Nova Science Publishers, Inc. All rights reserved.