HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Hormonal effects of aromatase inhibitors: focus on premenopausal effects and interaction with tamoxifen.

Abstract
Third generation aromatase inhibitors have excellent specificity. Some reports indicate that letrozole may have a minor effect on cortisol synthesis but these were not confirmed: valid comparisons with other aromatase inhibitors requires randomised study. The putative use of a third generation inhibitor as a single agent in premenopausal women has been investigated using YM511. It was hypothesised that in this situation site-specific suppression of estrogens in breast carcinomas, without systemic effects, may lead to a down-regulation of tumour proliferation. Plasma levels of androstenedione and testosterone were significantly increased by 2 weeks treatment with YM511. Mean plasma estrone levels were suppressed, but some plasma estradiol levels were abnormally high and others abnormally low. These differential effects of YM511 on circulating estrogens supported the concept that peripheral synthesis of estrogens might be suppressed while ovarian production remained high. However, YM511 did not demonstrate anti-proliferative effects in hormone sensitive breast carcinomas. Consideration of the pharmacology of the estrogen receptor during tamoxifen therapy indicates that tamoxifen effectively saturates the receptor (>99.94% occupancy) in postmenopausal women. The addition of an aromatase inhibitor in this situation would be very unlikely to affect the biological activity of the estrogen receptor. This provides a possible explanation why the clinical efficacy of tamoxifen combined with an aromatase inhibitor appears to be equivalent to that of tamoxifen alone.
AuthorsM Dowsett, B P Haynes
JournalThe Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 86 Issue 3-5 Pg. 255-63 (Sep 2003) ISSN: 0960-0760 [Print] England
PMID14623519 (Publication Type: Journal Article, Review)
Chemical References
  • Aromatase Inhibitors
  • Enzyme Inhibitors
  • Estrogen Antagonists
  • Estrogens
  • Receptors, Estrogen
  • Tamoxifen
  • Adrenocorticotropic Hormone
Topics
  • Adrenocorticotropic Hormone (pharmacology)
  • Animals
  • Aromatase Inhibitors
  • Breast Neoplasms (drug therapy)
  • Clinical Trials as Topic
  • Drug Interactions
  • Enzyme Inhibitors (metabolism, pharmacology)
  • Estrogen Antagonists (pharmacology)
  • Estrogens (blood)
  • Female
  • Humans
  • Menstrual Cycle (blood, drug effects)
  • Premenopause (blood, drug effects)
  • Receptors, Estrogen (drug effects, metabolism)
  • Tamoxifen (analogs & derivatives, metabolism, pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: