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A. CORBIN Investigations on LHRH and its analogs have just
completed their first decade. We have witnessed a veritable
explosion of chemical, physiologic and pharmacologic data on this
hypothalamic peptide and the approximately 1500 agonist and
antagonist analogs that have been synthesized. In order to track
this expanding field, I was asked to organize an international
symposium on basic and clinical aspects of LHRH analogs as part of
the Reproductive Health Care: CDS Symposium held in Maui, Hawaii,
in October 1982. This meeting brought together a number of the
leading investigators in the field. Much new state-of-the-art
information was presented which I and my colleagues felt deserved a
wider audience. Drs Vickery, Nestor, and Hafez consented to
undertake this task. Upon review of the literature, it was apparent
that there was no recent text which fully covered the breadth of
developments in the field. Accordingly, the editors decided to use
the symposium as a nucleus on which to build a singular,
comprehensive state-of-the-art analysis of this rapidly growing
discipline, and the application of such knowledge to reproductive
medicine. As exemplified by the various areas of expertise provided
by the individual contributors, it becomes obvious that the scope
of the subject matter, while relating solely to a well-defined
chemical class (LHRH analogs) and a circumscribed physiologic and
pharmacologic entity (reproduction), has expanded enormously.
Since the discovery of LHRH in 1971, research into the physiology
and therapeutics of this compound can be divided into three dis
tinctly different phases. In the first phase, attention was paid
chiefly to the natural sequence hormone; efforts were channeled to
explore its diagnostic use; and nearly all the clinical
investigations were coordinated by a single pharmaceutical company.
The successes in this area were quite limited and the interest in
the promise of this agent as a diagnostic test has long since
waned. This phase of research con sumed roughly the first seven
years of clinical testing after the isolation and characterization
of the compound by the two groups involved in the Nobel effort.
With the appearance of long-acting LHRH agonists, the second phase
of research on LHRH began in the late '70's. LHRH agonists were the
only compounds available during this period of research and
paradoxical desensitization was the predominant therapeutic basis
for the discoveries. An ever-widening number of therapeutic
applications using this approach were unearthed. A second theme
which emerged during this second 5-7 year period was that the
pulsatile administration of the natural sequence LHRH could be used
to treat LHRH deficiency in men and women."
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