Testolactone for the Treatment of Girls With LHRH Resistant Precocious Puberty
Testolactone for the Treatment of Girls With LHRH Resistant Precocious Puberty
The normal changes of puberty, such as breast enlargement, pubic hair and menstrual periods,
 usually begin between the ages of 9 and 15 in response to hormones produced in the body. Some
 children's bodies produce these hormones before the normal age and start puberty too early.
 This condition is known as precocious puberty.

 The hormones responsible for the onset of puberty come from the pituitary gland and the
 ovaries. The hormones from the pituitary gland act on the ovaries to produce different
 hormones that cause the breasts to grow, pubic hair to develop, and menstruation.

 Many children with precocious puberty can be treated with a medication known as lutenizing
 hormone-releasing hormone analog (Lupron, Histerelin, Deslorelin). This drug is made in a
 laboratory and is designed to act like the natural hormone LHRH, which is made in the
 pituitary gland. The drug causes the pituitary gland to decrease the amount of hormones it is
 releasing and thereby decrease the amount of hormones released by the ovaries. However, some
 girls already have low levels of pituitary hormones and yet their ovaries still produce
 hormones. Researchers do not believe that LHRH analog therapy will work for these children.

 Testolactone is a drug that acts directly on the ovary. It works by preventing the last step
 of estrogen production in the ovary. The goal of this treatment is to stop estrogen
 production and delay the onset of puberty until the normal age.

 Researchers will give patients with LHRHa resistant precocious puberty Testolactone for six
 months. If the initial treatment is successful and patients do not experience very bad side
 effects, they will continue to receive the medication until puberty is desired. Throughout
 the therapy patients will receive frequent monitoring of their general state of health,
 hormone levels, and medication levels.
Females with precocious puberty who have low levels of serum gonadotropins and high levels of
 serum estrogen, or those who have demonstrated an inadequate clinical response to therapy
 with the luteinizing hormone releasing hormone analog (Lupron, Histerelin, Deslorelin), will
 be treated with testolactone. Testolactone inhibits aromatase, the last enzyme of estrogen
 biosynthesis. The goal of treatment is to inhibit estrogen secretion and thus delay secondary
 sexual maturation and epiphyseal closure until the normal age. The intent is to alleviate the
 psychological problems and short stature frequently associated with this disorder. Throughout
 therapy, patients will receive frequent clinical, hormonal, and toxicological monitoring. The
 initial treatment period will be six months. If patients respond to the treatment and
 tolerate it well, testolactone will be given until puberty is desired. Patients who exhibit
 pubertal levels of serum gonadotropins during testolactone therapy, indicating the onset of
 secondary, gonadotropin-dependent puberty, will receive an LHRH analog in addition to
 testolactone.
INCLUSION CRITERIA:

 Patients are girls aged 1-8 years (on entry to the study) with gonadotropin-independent
 precocious puberty. All ethnic groups are included.

 EXCLUSION CRITERIA:

 Males are excluded, as are patients with clinically-significant hepatic and/or renal
 impairment (testolactone is metabolized via the liver and kidneys).