NATIONAL LUPRON VICTIMS NETWORK - Precocious Puberty

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LUPRON: PRECOCIOUS PUBERTY

How Effective is Lupron for Precocious Puberty?

1. Dr. Bridges and Dr. Brook stated that "In precocious puberty, holding up puberty by using a GnRH analog has little impact on final height and does not restore the loss in height that occurs in this condition.

Although there may be an increase in height prediction during treatment, growth velocity is slow after stopping treatment and the increase in prediction is lost." (16)

2. Dr. Crudo and colleagues stated that Lupron "had variable, and in some cases, undesired effects on linear growth, bone maturation, and predicted adult height. If indeed a primary goal of therapy is increased adult height, based on our data, one cannot predict a favorable outcome using this GnRH analog." (3)

According to Dr. Mansfield and colleagues, LHRHa is "a therapeutic unique probe [a device used to get information] into the pubertal process, offering a novel approach to the study of the interrelations between gonadarche and other facets of puberty such as skeletal growth, bone maturation, and adrenarche." (10)

In 1979, Dr. Comite and colleagues, at the NIH (National Institute of Health) experimented with "five girls with idiopathic precocious puberty (ages 2 to 8) for 8 weeks with daily subcutaneous injections of LHRHa [a GnRH analogue; not Lupron]." (1)

In response to Dr. Comite's article, Dr. MacGillivray, in 1982, sent a letter to the editor, in which she stated the following:

• "The pharmacology of the analogue of luteinizing hormone-releasing hormone (LHRH) used by [Dr.] Comite and her colleagues to treat idiopathic precocious puberty is extremely complex, and the full range of its effects is still unknown." (2)

• "Marked degenerative changes in the gonads of male rats have been documented." (2)

• "Long-term studies in suitable animal models (chimpanzees and baboons) have not been completed." (2)

• "Furthermore, an antibody to administered LHRH has been documented in men. Pregnant rats given LHRH antibody have produced male offspring with a micropenis and hypoplastic testes, and neonatal rats treated with LHRH antibody have had permanent impairment of testicular development with bisexual behavior." (2)

• "Data are available from three centers that followed similar patients before any therapy became available. At least two thirds of untreated children reached adult heights of 1.5m (5 feet) or more. There is little justification for the use of a research drug in the two 7-year-old girls whose bone ages and height ages were not significantly discordant and whose chronologic ages were close to the physiologic limit of normal puberty. In general, the psychological adjustment to precocious puberty has been reported to be satisfactory, provided that the families and physicians give adequate support to the patients. The authors' research protocol, which required physical examinations, vaginal smears, and blood tests every 2 weeks in addition to daily injections, is itself physically and psychologically stressful." (2)

II. Predicted Height vs. Achieved Final Height

Predicted Height: The height that is expected.

Achieved Final Height: The final height that is achieved.

III. An Effect on Bone

1. Dr. Antoniazzi and colleagues tested only girls with central precocious puberty. (14)

a. "Trabecular and cortical bone mass variations, measured by dual x-ray absorptiometry [DEXAJ in the lumbar spine and by dual photon absorptiometry [DPA] in the radius, respectively were evaluated before the start and after 12 months" of Lupron 3.75 mg for 1 year.

(11)

b. In our patients, there was a "reduction of trabecular bone mass, which appears to be the primary consequence of GnRHa therapy." (14)

2. Dr. Saggese and colleagues stated that "GnRH-a treatment is also associated with bone loss in girls with central precocious puberty." (15)

a. Dr. Saggese "investigated bone mineralization by single photon

absorptiometry [SPA] in girls with central precocious puberty before
-*and during 1 year of treatment with GnRH-a." (14)
^ b. "During GnRH-a treatment, patient BMD [bone mineral density]

decreased significantly (6 months: -6.0%; 12 months: -8.0%). (15)

c. "GnRH-a treatment caused a significant decrease in BMD [bone mineral density]." (15)

3. According to Dr. Mann and colleagues, when male monkeys were given a GnRHa for the first four months of postnatal life, "Growth of the skeleton was diminished as evidenced by shorter adult crown-rump, tibia, and femur length and reduced bone mineral density of the humerus and lumbar spine." (17)

For further information see LUPRON: AN EFFECT ON BONE / BONE MARROW

More To Come

REFERENCES

1. Comite F, Cutler GB, River J, Vale WW, Loriaux DL, Crowley WF. Short-term treatment of idiopathic precocious puberty with a long-acting analogue of luteinizing hormone-releasing hormone. The New England Journal of Medicine. 305: 26: 1981; p. 1546-1550.

2. MacGillivray MH. Treatment of idiopathic precocious puberty. The New England Journal of Medicine. 306: 18: p. 1109.

3. Crudo DF, Wilson BE, Poth MA, (Spon. by Johnsonbaugh, RE). Failure of Leuprolide to Increase Predicted Adult Height in Some Patients with Precocious Puberty. Endocrinology.53: #446. p.275A

10. Mansfield MJ, Beardsworth DE, Loughlin JS, Crawford 3D, Bode HH, River J, Vale W, Kushner DC, Crigler JF, Crowley WF. Long-term treatment of central precocious puberty with a long-acting analogue of luteinizing hormone-releasing hormone. The New England Journal of Medicine. 309: 21: 1983; 1286-1290.

11. Crudo DF, Wilson BE, Poth MA. Failure of leuprolide to increase predicted adult height in some patients with precocious puberty. Endocrinology. 446. p.275A

14. Antoniazzi F, Bertoldo F, Zamboni G, Valenti R, Sirpresi S, Cavallo L, Adami S, Tato L Bone mineral metabolism in girls with precocious puberty during gonadotropin-releasing hormone agonist treatment. European Journal of Endocrinology. 133: 1995; p. 412-7

15. Saggese G, Bertelloni S, Bertelloni GI, Battini R, Franchi G. Reduction of bone density: an effect of gonadotropin releasing hormone analogue treatment in central precocious puberty. European Journal of Pediatrics. 152: 1993; p. 717-720.

16. Bridges NA, Brook CGD. Precocious puberty: combined treatment with GnRH analogs and growth hormone. In Treatment With GnRH Analogs: Controversies and Perspectives, M. Filicori, C. Flamigni (Eds.). The Parthenon Publishing Group. New York. 1996; p.240.

17. Mann DR, Akinbami MA, Gould KG, Tanner JM, Wallen K. Neonatal Treatment of Male Monkeys with a Gonadotropin-Releasing Hormone Agonist Alters Differentiation of Central Nervous System Centers that Regulate Sexual and Skeletal Development. Journal of Clinical Endocrinology and Metabolism. 1993; 76: 5: p. 1319-1324.

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