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.
Patients are girls aged 1-8 years (on entry to the study) with gonadotropin-independent
precocious puberty. All ethnic groups are included.
Males are excluded, as are patients with clinically-significant hepatic and/or renal
impairment (testolactone is metabolized via the liver and kidneys).