I'm trying to decide what anti-e to use and here's some of what I found. I hope this can help others also.
Drug and hormone interactions of aromatase inhibitors
Abstract
The clinical development of aromatase inhibitors has been largely confined to postmenopausal breast cancer patients and strongly guided by pharmacological data. Comparative oestrogen suppression has been helpful in circumstances where at least one of the comparitors has caused substantially non-maximal aromatase inhibition. However, the triazole inhibitors, letrozole and anastrozole, and the steroidal inhibitor, exemestane, all cause >95% inhibition. Comparisons between these drugs therefore require more sensitive approaches such as the direct measurement of enzyme activity by isotopic means. None of these 3 agents have significant effects on other endocrine pathways at their clinically applied doses. Pharmacokinetic analyses of the combination of tamoxifen and letrozole have revealed that these drugs interact resulting in letrozole concentrations c. 35 to 40% lower than when letrozole is used alone.
Aromatase inhibitors in men
The effect of aromatase inhibition on male gonadotrophin and sex steroid concentrations is illustrated in the paper by Trunet et al. (1993): 2.5 mg letrozole suppressed plasma oestradiol concentrations to less than 50% of pretreatment after 2 days, with recovery to approximately pretreatment values after 6 days. These decreases were accompanied by increased gonadotrophin concentrations, with resultant increases of approximately 50% in plasma testosterone. These results, and those previously published (Bhatnagar et al. 1992) on the effects of fadrozole in men, indicate that the aromatization pathway is of major importance in the regulation of gonodotrophin secretion by aromatically androgens.
Full text of this article can be downloaded in PDF format.
http://journals.endocrinology.org/er...erc0060181.pdf
Endocrinological and clinical evaluation of exemestane, a new steroidal aromatase inhibitor.
The androstenedione derivative, exemestane (FCE 24304), is a new orally active irreversible aromatase inhibitor. Fifty-six post-menopausal advanced breast cancer patients entered this study to evaluate the activity of four low exemestane doses in reducing oestrogen levels. The drug's tolerability and clinical efficacy were also assessed. Exemestane was orally administered to four consecutive groups at daily doses of 25, 12.5, 5 and 2.5 mg, and the changes in oestrogen, gonadotrophins, sex-hormone binding globulin and dehydroepiandrosterone sulphate levels were evaluated. Drug selectivity was studied by measuring 17-hydroxycorticosteroid urinary levels. After 7 days of treatment, mean oestrone and oestradiol levels had decreased by respectively 64% and 65% (a decrease which was maintained over time); in the 2.5 mg group, oestrone sulphate levels also decreased by 74%. Gonadotrophin levels were significantly higher, whereas no changes in the other serum hormone levels or any interference with adrenal synthesis were detected. Treatment tolerability was satisfactory: nausea and dyspepsia were reported in 16% of patients. The overall objective response rate was 18%. In conclusion, exemestane is effective in reducing oestrogen levels at all of the tested doses and shows interesting clinical activity.
Aromatase inhibitors: a dose response effect?
Introduction
Aminoglutethimide, the first aromatase inhibitor, was established in the 1970s as an active treatment for patients with advanced breast cancer, but its lack of specificity was associated with side effects. Since that time, a series of much more specific non-steroidal aromatase inhibitors have been developed which are up to 10 000 times as potent as aminoglutethimide in vivo with no evidence of inhibition of other steroid pathways at doses required to inhibit oestrogen. Two of these, letrozole (Femara; Novartis) and anastrozole (Arimidex; Zeneca) are now well established in the treatment of advanced breast cancer and are under investigation as adjuvant therapy. These agents achieve 98-99% aromatase inhibition in patients, and reduce serum levels of oestrone and oestradiol beyond the limit of detection in many patients (Iveson et al. 1993). Until recently, it had been assumed that no clinical dose response effect could exist beyond levels of maximum serum oestrogen suppression but recent data have suggested this may not be the case. If a dose response effect does indeed exist for modern aromatase inhibitors, then it has important implications for their future development.
Full text of this article can be downloaded in PDF format. At http://journals.endocrinology.org/er...erc0060245.pdf
Hope this helps.
JohnnyB
Reply With Quote
