Precocious puberty in children

Management of endometriosis or treatment of central precocious puberty (CPP) (gonadotropin-dependent precocious puberty) in children of both sexes... 

Patients with 11/1-hydroxylase deficiency present with features of androgen excess, including masculinization of female newborns and precocious puberty in male children. There are two human isozymes that are responsible for cortisol and aldosterone synthesis, respectively. The CYP11B1 enzyme (p45011B) converts DOC to corticosterone (B) and 11-deoxycortisol (S or 11-dihydrocortisol) to cortisol (F). It is also capable of 18-hydroxylating DOC but cannot convert to aldosterone. The latter transformation is carried out by CYP11B2 (also known as aldosterone synthase), which encompasses activity for 18-hydroxylation and subsequent 18-oxidation. When CAH is associated with hypertension, deficient lljS-hydroxylase (CYP11B1) is suspected at this time more than ten mutations have been defined in affected individuals [103]. 

Contamination of isoniazid tablets with diethylstilbestrol was the cause of several cases of precocious puberty in a children s tuberculosis ward (50). 

In leukemia, the intensified use of methotrexate and glucocorticoids is responsible for causing an increased frequency of neurotoxicity and, in older children and adults, avascular necrosis of bone. High cumulative doses of anthracyclines can cause cardiomyopathy. Cranial irradiation causes neuropsychologic deficits and endocrine abnormalities that lead to obesity, short stature, precocious puberty, and osteoporosis.3 As newer and more intensive treatments enter clinical trials, close observation for long-term side effects will assume even greater importance.24... 

B. Indications and use Lupron Injection, Lupron Depot, Lupron Depot-3 Month, and Lupron Depot-4 Month are indicated in the palliative treatment of advanced prostate cancer. These products offer an alternative treatment when orchiectomy or estrogen administration is either not indicated or unacceptable to the patient. Lupron Injection Pediatric and Lupron Depot-PED are indicated in the treatment of children with central precocious puberty. Lupron Depot and Lupron Depot-3 Month are indicated for the management of endometriosis, including pain relief and reduction of endometriotic lesions. 

G. Other applications Limited data show some beneficial effects of leuprolide in the treatment of breast cancer. According to Micromedex, there is good documentation that leuprolide is effective for bowel pain and nausea associated with irritable bowel syndrome. Leuprolide has been used for controlled ovarian hyperstimulation to enhance the in vitro fertilization-embryo transfer procedure. In endometriosis, the goal of treatment is pain relief and reduction of endometriotic lesions. In children with central precocious puberty, stimulated and basal gonadotropins are reduced to prepubertal levels. Testosterone and estradiol are reduced to prepubertal levels in males and females, respectively. 

Medroxyprogesterone acetate, 10-20 mg orally twice weekly—or intramuscularly in doses of 100 mg/m2 every 1-2 weeks—will prevent menstruation, but it will not arrest accelerated bone maturation in children with precocious puberty. 

Occasionally, children are exposed unknowingly to estrogens. Precocious puberty has been observed in young girls after contact with hair lotions and other products containing estrogenic compounds (SED-12,1032) (202,203). 

In Japanese children with precocious puberty treated with leuprolide the time between the last injection and the median onset of menarche was 15 (range 3.6-63) months (25). The age at menarche was higher than that of the healthy population (13 versus 12 years). 

In 47 children treated with depot leuprolide acetate for precocious puberty for 2 years, bone mineral density decreased significantly and markers of bone turnover increased significantly during treatment but were normal for age 2 years after treatment was withdrawn (54). 

GnRH analog (leuprolide, nafarelin) treatment of children is generally well tolerated. However, temporary exacerbation of precocious puberty may occur during the first few weeks of therapy. Injection site reactions occur in about 5%. Nafarelin nasal spray may cause or aggravate sinusitis. 

Lawson ML, Cohen N. A single sample subcutaneous luteinizing hormone (LH)-releasing hormone (LHRH) stimulation test for monitoring LH suppression in children with central precocious puberty receiving LHRH agonists. J Clin Endocrinol Metab 1999 84 4536-40. 

The goal of CNS prophylaxis is to eradicate undetectable leukemic cells from the CNS. Leukemic meningitis is more easily prevented than treated. Once CNS relapse has occnrred, patients are at increased risk of bone marrow relapse and death from refractory leukemia. Initial trials in childhood ALL in the 1960s established craniospinal irradiation as the standard for prevention of CNS relapse." However, this approach was associated with long-term seqnelae including neuropsychological deficits, precocious puberty, osteoporosis, thyroid dysfunction, an increased incidence of brain tumors, short stature, and obesity. Subseqnent trials have demonstrated that irradiation may be replaced by freqnent administration of intrathecal chemotherapy in most children with ALL."... 

D5. Degenhart, H. J., Visser, H. K. A., Wilmink, R., and Frankena, L., Production and excretion of testosterone in children with congenital adrenal hyperplasia and precocious puberty. Acta Endocrinol. Suppl. 100, 51 (1965). 

Nafarelin acetate also is used in children, male and female, for the treatment of central precocious puberty. By suppressing the release of LH, the estradiol or testosterone levels fall to prepubertal levels early secondary sexual development is arrested, linear growth and skeletal maturation are slowed, and in girls, menstruation stops. 

As indicated previously, adverse health outcomes from early exposures may become apparent at any point in the lifespan. In some instances, they may be apparent only after long latency periods. Chapter 6 addresses the various methodologies that can be used to assess health outcomes. Studies have shown that the effects of toxic exposures on developmental processes may result from different mechanisms of action, and the toxic exposures may produce different health outcomes compared with the same exposures in adults. Some examples of health effects resulting from developmental exposures include those observed prenatally and at birth (e.g. miscarriage, stillbirth, low birth weight, birth defects), in young children (e.g. asthma, neurobehavioural and immune impairment), in adolescents (e.g. precocious or delayed puberty), and in adults (e.g. diabetes and heart disease). 

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