Gonadotropin-releasing hormone (Gn-RH), a hypothalamic decapeptide, mediates the synthesis and release of pituitary luteinizing hormone (LH). Synthetic Gn-RH analogues with prolonged duration of action are therapeutically administered with ‘pro-fertility’ intention to overcome endogenous Gn-RH deficiency, i.e. hypogonadotropic hypogonadism and related disorders. When Gn-RH analogues are chronically administered in high supraphysiological dosages, however, a paradoxical effect of pituitary overstimulation becomes evident: gonadotropin release is reduced, Leydig cell responsiveness is impaired, and testosterone secretion is blocked to castrate levels. Metabolic mechanisms involved include desensitization of the pituitary to Gn-RH, down-regulation of Gn-RH receptors, the depletion of the releasable LH pool, the breakdown of physiological feedback mechanisms, as well as direct interactions of the Gn-RH analogue with the Leydig cell. It is tempting to assume that, on the basis of this untoward side effect, high dose Gn-RH analogues will acquire a therapeutical dimension in the palliative treatment of prostate cancer. The therapeutical effect of castrate levels of testosterone is achieved without orchiectomy, cardiovascular side effects of estrogens are avoided, and the drug is conveniently applicable via the pemasal route. From the data available today Gn-RH analogues in overstimulatory dosage can be expected to be safe and effective in the palliative treatment of prostate cancer and would thus prove a true alternative to conventional contrasexual measures.

Keywords:
Gonadotropin-releasing hormone, Gn-RH analogues, Prostate cancer
This content is only available via PDF.
1982
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.