Puberty, an essential part of growing up, usually occurs between 9 to 13 years of age. Occasionally, however, puberty starts much too early, mandating that we transiently suppress its progression. Fortunately, we have an excellent drug for this purpose. Depot leuprolide, given by monthly injection, stops the most common forms of precocious puberty. This drug is safe, effective, and well tolerated when given in appropriate doses. Interestingly, children commonly require higher doses than adults do. While initial dose is generally based on body weight, some children require more or less than this average dose. Many children require higher doses at the beginning of therapy than they do in subsequent years. Depot leuprolide injections transiently stimulate pubertal hormones when therapy is first begun, making things worse for a week or so. If enough depot leuprolide is given often enough, the precocious puberty is suppressed. Conversely, if the dose is too low, each subsequent injection again stimulates the pubertal hormones. These recurrent periods of stimulation advance pubertal progression, exactly the opposite of the goal of therapy. Moreover, the high cost of this medication (currently $572 to $1,333 per month at Packard) mandates that we optimize the dose in each patient throughout the years of therapy. All of these factors mean that depot leuprolide therapy must be carefully monitored to assure that appropriate doses are used and recurrent stimulation of the pubertal hormones is avoided. The traditional method for monitoring this therapy is a GnRH stimulation test. This test involves securing IV access, giving an injection of a hormone, and then monitoring the response in the blood at multiple times points. This is an expensive and cumbersome test. In this proposal, we plan to test a much easier and cheaper method to monitor therapy. The basic concept of this proposal is that we can detect this transient stimulation of puberty that occurs after each injection IF the dose of depot leuprolide is too small. Data from adults demonstrate that after an injection of Depot Leuprolide is given, substantial amounts of the drug are immediately released into the circulation. If chronically treated patients are adequately suppressed; this bolus of drug will not stimulate hormones of puberty. Conversely, if suppression is not adequate, this bolus of drug should result in a detectable elevation in the hormones of puberty. We can thus measure these pubertal hormones after an injection of depot leuprolide and determine it the depot leuprolide dose is correct. If our theory were confirmed by this proposed trial, this procedure would be an inexpensive and easy method to monitor the adequacy of GnRH analog therapy.
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