Clinical Trial: Treatment of Boys With Precocious Puberty
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Spironolactone and Testolactone Treatment of Boys With Familial Isosexual Precocious Puberty
Brief Summary:
This study is a continuation of two previous studies conducted at the NIH. The first study , "Treatment of True Precocious Puberty with a Long-Acting Lutenizing Hormone Releasing Hormone Analog (D-Trp(6)-Pro(9)-Net-LHRH)" had less than optimal results. Some patients, all of whom were diagnosed with familial isosexual precocious puberty, had an inadequate response to the medication and were observed to have high levels of testosterone, advanced bone aging, and other complications of the disease. As a result these patients were enrolled in a second study
In the second study, "Spironolactone Treatment for Boys with Familial Isosexual Precocious Puberty", - the patients received another medication, spironolactone (Aldactone). The drug blocked the effects of testosterone, -but bone age advancement did not improve. Some patients began experiencing gynecomastia (an abnormal growth of the male breasts). Researchers believe these may be the effects of elevated levels of estrodiol (a form of the female hormone, estrogen).
In the present study, testolactone is added to the drug regimen to block the production of estrogen. The study therefore uses spironolactone to prevent the action of the male hormones (androgen) and testolactone to block the production of female hormones (estrogen). Deslorelin, an LHRH analog which works by turning off true (central) puberty, is added to the drug regimen once true puberty begins. This is because it is know that boys with familial male precocious puberty go into true puberty too early (despite treatment with spironolactone and testolactone), and when that happens, the spironolactone and testolactone are no longer as effective. The goal of the treatment is to delay sexual development until a more appropriate age and prevent short adult stature (height).
Detailed Summary:
Most males with precocious puberty who have been referred to NIH have been successfully treated under protocol 79-CH-0112 "Treatment of True Precocious Puberty with a Long-Acting Luteinizing Hormone Releasing Hormone Analog (D-Trp6-Pro9-Net-LHRH)." A subset of these patients, however, all of whom had familial male isosexual precocity, had an inadequate response to LHRH analog as demonstrated by high serum testosterone levels, rapid advancement in bone age, testicular growth, sperm production, and lack of regression of secondary sex characteristics. These patients had low baseline gonadotropin levels and lacked a pubertal response to LHRH, whereas the patients who had responded to LHRH analog all had clear evidence of central precocious puberty.
As an alternative approach to treatment, the patients with familial male precocious puberty were enrolled in protocol 83-CH-0028, "Spironolactone Treatment of Boys with Familial Isosexual Precocious Puberty". Spironolactone (Aldactone) is an antiandrogen that also reduced testosterone synthesis by inhibiting the enzyme 17-hydroxylase. This treatment decreased the plasma testosterone level and inhibited the peripheral effect of testosterone on target tissues. This was apparent through a decrease in acne and in the frequency of spontaneous erections.
Bone age advancement, however, was not slowed by spironolactone and gynecomastia had begun to occur in a number of patients. Both of these processes may be the result of persisting elevated estradiol levels. To attempt to reduce elevated estrogen levels in these patients to normal prepubertal levels, we plan to use testolactone (Teslac) to inhibit aromatase, the last step of estrogen biosynthesis. Testolactone has previously been used for a similar purpose in girls with gonadotropin-independent precocious puberty (McCu
Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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Original Secondary Outcome:
Information By: National Institutes of Health Clinical Center (CC)
Dates:
Date Received: November 3, 1999
Date Started: January 1985
Date Completion: January 2004
Last Updated: March 3, 2008
Last Verified: January 2004
