help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

Journal of Clinical Endocrinology & Metabolism Vol. 68, No. 1 99-106
doi:10.1210/jcem-68-1-99
Copyright © 1989 by the Endocrine Society.
This Article
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by SANTEN, R. J.
Right arrow Articles by LIPTON, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by SANTEN, R. J.
Right arrow Articles by LIPTON, A.

Inhibition of Aromatase With CGS 16949A in Postmenopausal Women*

R. J. SANTEN, L. M. DEMERS, H. ADLERCREUTZ, H. HARVEY, S. SANTNER, S. SANDERS and A. LIPTON

Departments of Medicine and Pathology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey Pennsylvania 17033
the Department of Clinical Chemistry, University of Helsinki, Meilahati Hospital 00290 Helsinki, Finland

Address requests for reprints to: Dr. R. J. Santen, Department of Medicine, Milton S.Hershey Medical Center, Pennsylvania State University, P.O. Box 850, Hershey, Pennsylvania 17033.

Potent, specific, and nontoxic inhibitors of aromatase would be useful for experimental studies and for use in the treatment of breast cancer and other disorders. We evaluatedthe effects of CGS 16949A, a nonsteroidal inhibitor of aromatase activity, in 12 postmenopausal women with breast cancer by measuring plasma and/or urinary androgens and estrogens after oral administration of CGS 16949A at doses ranging from 0.6– 16 mg daily; each dose was given for 2 weeks. The 0.6-mg daily dose partially lowered estrogen levels, and maximum reduction occurred at doses of 2–16 mg daily. The fall in plasma and urinary estrogens without a concomitant fall in plasma androgens confirmed the blockade of aromatase activity. The degree of estrogen reduction was greatest for urinary estrone [to 27 ± 3± (±SE) of basal], followed in order by plasma estrone sulfate (30 ± 4%), plasma estrone (32 ± 6%), urine estradiol (45 ± 5%), andplasma estradiol (65 ± 5%). Use of gas liquid chromatography- mass spectrometry techniques revealed similar patterns of reduction in catechol estrogens, estriol, and total urinary estrogens,estrogens, suggesting that CGS 16949A does not alter the pathways of estrogen metabolism. The degree of estrogen reduction was remarkably similar to that caused with aminoglutethimide. At doses of 4–16 mg daily, CGS 16949A inhibited the C21-hydroxylase enzyme as well, based on concomitant rises in plasma androstenedione, testosterone, and 17{alpha}-hydroxyprogesterone. This effect was insufficient to lower urinary cortisol excretion during the study. However, a statistically significant blunting of plasma cortisol responsesto ACTH occurred with the 16-mg daily dose. No changes in plasma dehydroepiandrosterone sulfate levels or in thyroid, hematological, liver, or renal parameters were found. No significant side-effects of the medication were encountered.

CGS 16949A appears to be a specific inhibitor of aromatase at doses below 4 mg daily and tolack apparent side-effects or toxic actions at doses up to 16 mg daily. This agent showspromise as a potent aromatase inhibitor for physiological and clinical studies.

* This work was supported by the Ciba-Geigy Corp. (Summit, NJ).

Received April 25, 1988.




This article has been cited by other articles:


Home page
J. Clin. Endocrinol. Metab.Home page
S. B. Nunez, K. Calis, G. B. Cutler Jr., J. Jones, and P. P. Feuillan
Lack of Efficacy of Fadrozole in Treating Precocious Puberty in Girls with the McCune-Albright Syndrome
J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5730 - 5733.
[Abstract] [Full Text] [PDF]


Home page
LupusHome page
B. Greenstein
Hormonal Aspects of Lupus: Therapeutic Possibilities
Lupus, December 1, 1993; 2(6): 349 - 350.
[PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1989 by The Endocrine Society