Steroidal aromatase inhibitor side effects

AB - The choice of treatment for elderly breast cancer patients needs particular care because the presence of physiological functional impairments can modify the drug bioavailability in an unpredictable manner. Hormonal treatment remains one of the choices and, although tamoxifen has proved to be effective in any setting, the use of selective aromatase inhibitors is arousing. Depending on their chemical structure, aromatase inhibitors are either steroidal (such as exemestane and formestane) or non-steroidal (such as letrozole, vorozole and anastrozole). Formestane has been studied in elderly patients with breast cancer and has been found to induce an overall response rate of 51% (95% CI, 35-67%). The drug suppresses estradiol (E2) levels, and changes in other hormones (FSH, LH and SHBG) are observed, but with poor clinical significance, thus confirming its selectivity and potency. Formestane has also been demonstrated to be as effective as tamoxifen. Exemestane and non-steroidal aromatase inhibitors appear to be very promising drugs. Copyright (C) 2000 Elsevier Science Ireland Ltd.

Abstract: Aromatase inhibition is an effective and rate-limiting step in estrogen production and in the treatment of advanced postmenopausal breast cancer. More than 3 decades of active research have already been put in its design, development and evaluation. The aromatase inhibitors can be classified either based on their mechanism of action, . competitive aromatase inhibitors, which compete with the substrate androstenedione for non-covalent binding to the active site of the enzyme, irreversible inhibitors that bind to the active site of the enzyme covalently and mechanism-based or suicide inhibitors, which mimic the substrate and require catalytic amounts of the enzyme to be converted to the reactive intermediate resulting in inactivation of the enzyme. Aromatase inhibitors can also be classified as non-steroidal and steroidal types. The prototype nonsteroidal inhibitor aminoglutethimide provided the impetus for the development of related compounds while the steroidal inhibitors function as false substrates for aromatase with expected high selectivity. This review article focuses mainly on the steroidal aromatase inhibitors that have been developed to date, and which are classified on the basis of various modifications in the different rings (A,B,C,D) and position C-19 in the basic androstene nucleus. The second-generation drug 4-hydroxyandrostenedione (formestane), which is an excellent example of success achieved by carrying out modification in ring A, was introduced to clinical practice in 1990. Among the latest example is the orally active, third generation drug exemestane which is an irreversible inhibitor. The full potential of the new steroidal aromatase inhibitors is currently being investigated by many workers to evaluate their use in the management of breast cancer either directly or as an adjuvant to surgery in postmenopausal patients with early diagnosis.

It is also suggested that there is an interaction between hormone levels and eating at different points in the female menstrual cycle . Research has predicted increased emotional eating during hormonal flux, which is characterized by high progesterone and estradiol levels that occur during the mid- luteal phase . It is hypothesized that these changes occur due to brain changes across the menstrual cycle that are likely a genomic effect of hormones. These effects produce menstrual cycle changes, which result in hormone release leading to behavioral changes, notably binge and emotional eating. These occur especially prominently among women who are genetically vulnerable to binge eating phenotypes. [51]

Steroidal aromatase inhibitor side effects

steroidal aromatase inhibitor side effects


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