The majority of patients with pubertal delay, can be classified as having primary pubertal delay (constitutional delay of growth and puberty, CDGP), although any child with a chronic disease could present with delayed puberty. In contrast, children with hypogonadism, either hyper- or hypogonadotropic, exhibit a total absence of pubertal development. Hence, early evaluation of these patients should be performed. Delay of puberty leads to psychological problems, secondary to short stature and/or delay in the acquisition of secondary sex characteristics and the reduction of bone mass. Although the final height in patients with CDGP is usually normal, some of these patients do not reach the third percentile or remain in the lowest part of the growth chart according to familial height. The most common reason for treating CDGP patients, usually with sex steroids, is for psychological difficulties and for loss of bone mineralization. Treatment must be individualized. Therapeutic options and new drugs will be discussed. Appropriate treatment and adequate nutritional intake are indicated in patients with delayed puberty due to chronic illness. In patients with hypo- or hypergonadotropic hypogonadism, puberty must be induced or completed. Different treatments (GnRH analogues, gonadotropins and sex steroids), and the main objectives are discussed.

1.
Teresawa EI, Fernández DL: Neurobiological mechanisms of the onset of puberty in primates. Endocr Rev 2001;22:111–151.
2.
Grumbach MM: The neuroendocrinology of human puberty. Horm Res 2002;57(suppl 2):2–14.
3.
Karlberg J: Secular trends in pubertal development. Horm Res 2002;57(suppl 2):19–30.
4.
Delemarre-van de Waal HA: Regulation of puberty. Best Pract Res Clin Endocrinol Metab 2002;16:1–12.
5.
Herman-Giddens ME, Slora EJ, Wasserman RC, Bourdony CJ, Bhapkar MV, Koch GG, Hasemeier CM: Secondary sexual characteristics and menses in young girls seen in office practice: A study from pediatric research in office settings network. Pediatrics 1997;99:505–512.
6.
Herman-Giddens ME, Wang L, Koch G: Secondary sexual characteristics in boys: Estimates from the National Health and Nutrition Examination Survey III, 1998–1994. Arch Pediatr Adolesc Med 2001;155:1022–1028.
7.
de Muinck Keizer-Schrama SM, Mul D: Trends in pubertal development in Europe. Hum Reprod Update 2001;7:287–291.
8.
Hauspie RC, Vercauteren M, Susanne C: Secular changes in growth. Horm Res 1996;45:8–17.
9.
Mul D, Fredriks AM, van Buuren S, Oostdijk W, Verloove-Vanhorick SP, Wit JM: Pubertal development in The Netherlands, 1965–1997. Pediatr Res 2001;50:479–486.
10.
Tanner JM: Growth at Adolescence. Oxford, Blackwell, 1962.
11.
Marshall WA, Tanner JM: Variations in the pattern of pubertal changes in boys. Arch Dis Child 1970;45:13–23.
12.
Marshall WA, Tanner JM: Variations in the pattern of pubertal changes in girls. Arch Dis Child 1969;44:291–303.
13.
Wheeler MD: Physical changes of puberty. Endocrinol Metab Clin North Am 1991;20:1–14.
14.
Argente J: Diagnosis of late puberty. Horm Res 1999;51(suppl 3):95–100.
15.
Reindollar RH, Byrd JR, McDonough PG: Delayed sexual development: A study of 252 patients. Am J Obstet Gynecol 1981;140:371–380.
16.
Toublanc JE, Roger M, Chaussain JL: Etiologies of late puberty. Horm Res 1991;36:136–140.
17.
Sedlmeyer IL, Palmert MR: Delayed puberty: Analysis of a large case series from an academic center. J Clin Endocrinol Metab 2002;87:1613–1620.
18.
Rosenfield RL: Diagnosis and management of delayed puberty. J Clin Endocrinol Metab 1990;70:559–562.
19.
Albanese A, Stanhope R: Investigation of delayed puberty. Clin Endocrinol 1995;43:105–110.
20.
Kulin HE: Delayed puberty. J Clin Endocrinol Metab 1996;81:3460–3464.
21.
Traggiai C, Stanhope R: Investigation of delayed puberty. Clin Endocrinol 1995;43:105–110.
22.
Pozo J, Argente J: Retraso constitucional del crecimiento y de la adolescencia. Endocrinología 1994;41:60–68.
23.
Stanhope R, Preece MA: Management of constitutional delay of growth and puberty. Arch Dis Child 1988;63:1104–1110.
24.
Sedlmeyer IL, Hirschhorn JN, Palmert MR: Pedigree analysis of constitutional delay of growth and maturation: Determination of familial aggregation and inheritance patterns. J Clin Endocrinol Metab 2002;87:5581–5586.
25.
Ranke MB, Aronson S: Adult height in children with constitutional short stature. Acta Pædiatr Scand 1989;362(suppl):27–31.
26.
Volta C, Guizzoni L, Buono T, Ferrari F, Virdis R, Bernasconi S: Final height in a group of untreated children with constitutional growth delay. Helv Pædiatr Acta 1988;43:171–176.
27.
Arrigo T, Cisternino M, De Luca F, Saggese G, Messina MF, Pasquino AM, De Sanctis V: Final height outcome in both untreated and testosterone treated boys with constitutional delay of growth and puberty. J Pediatr Endocrinol Metab 1996;9:511–517.
28.
Mazur T, Clopper RR: Pubertal disorders. Psychology and clinical management. Endocrinol Metab Clin North Am 1991;20:211–230.
29.
La Franchi SH, Hanna CE, Mandel SH: Constitutional delay of growth: expected versus final adult height. Pediatrics 1991;87:82–87.
30.
Crowne EC, Shalet SM, Wallace WHB, Eminson DM, Price DA: Final height in boys with untreated constitutional delay in growth and puberty. Arch Dis Child 1990;65:1109–1112.
31.
Crowne EC, Shalet SM, Wallace WHB, Eminson DM, Price DA: Final height in girls with untreated constitutional delay in growth and puberty. Eur J Pediatr 1991;150:708–712.
32.
Albanese A, Stanhope R: Predictive factors in the determination of final height in boys with constitutional delay of growth of puberty. J Pediatr 1995;126:545–550.
33.
Ferrández A, Mayayo E, Valle A, Soria J, Labarta JI: Constitutional delay in growth and puberty: A comparison of final height achieved between treated and untreated children. J Pediatr Endocrinol Metab 1996;9:345–357.
34.
Ranke MB, Grauer ML, Kistner K, Blum WF, Wollmann HA: Spontaneous adult height in idiopathic short stature. Horm Res 1995;44:152–157.
35.
Finkelstein JS, Neer RM, Biller BMK, Crawford JD, Klibanski A: Osteopenia in men with a history of delayed puberty. N Engl J Med 1992;326:600–604.
36.
Moreira-Andres MN, Canizo FJ, de la Cruz FJ, Gomez-de la Camara A, Hawkins FG: Bone mineral status in prepubertal children with constitutional delay of growth and puberty. Eur J Endocrinol 1998;139:271–275.
37.
Moreira-Andres MN, Canizo FJ, de la Cruz FJ, Gomez-de la Camara A, Hawkins FG: Evaluation of radial bone mineral content in prepubertal children with constitutional delay of growth. J Pediatr Endocrinol Metab 2000;13:591–597.
38.
Bertelloni S, Baroncelli GI, Ferdeghini M, Perri G, Saggese G: Normal volumetric bone mineral density and bone turnover in young men with histories of constitutional delay of puberty. J Clin Endocrinol Metab 1998;83:4280–4283.
39.
Finkelstein JS, Klibanski A, Neer RM, Doppelt SH, Rosenthal DI, Segre GV, Crowley WF Jr: Increases in bone density during treatment of men with idiopathic hypogonadotrophic hypogonadism. J Clin Endocrinol Metab 1989;69:776–783.
40.
Stanhope R, Albanese A, Shalet S: Delayed puberty. Many good arguments to treat. Br Med J 1992;305:790.
41.
Houchin LD, Rogol AD: Androgen replacement in children with constitutional delay of puberty: The case for aggressive therapy. Baillière’s Clin Endocrinol Metab 1998;12:427–440.
42.
Bergada I, Bergada C: Long-term treatment with low dose testosterone in constitutional delay of growth and puberty: Effect on bone age maturation and pubertal progression. J Pediatr Endocrinol Metab 1995;8:117–122.
43.
Kulin HE, Finkelstein JW, D’Arcangelo MR, Susman EJ, Chinchilli V, Kunselman S, Schwab J, Demers L, Lookingbill G: Diversity of pubertal testosterone changes in boys with constitutional delay in growth and/or adolescence. J Pediatr Endocrinol Metab 1997;10:395–400.
44.
Gupta MK, Brown DC, Faiman C, Kelnar CJ, Wu FC: Effect of low-dose testosterone treatment on androgen regulated proteins prostate specific antigen and sex hormone binding globulin in short prepubertal boys: Lack of initiation of puberty. J Pediatr Endocrinol Metab 2003;16:55–62.
45.
Zachmann M: Therapeutic indications for delayed puberty and hypogonadism in adolescent boys. Horm Res 1991;36:141–146.
46.
De Luca F, Argente J, Cavallo L, Crowne E, Delemarre-van de Waal HA, De Sanctis C, Di Maio S, Norjavaara E, Oostdijk W, Severi F, Tonini G, Trifiro G, Voorhoeve PG, Wu F: Management of puberty in constitutional delay of growth and puberty. J Pediatr Endocrinol Metab 2001;14(suppl 2):953–957.
47.
Zachmann M, Studer S, Prader A: Short-term testosterone treatment at bone age of 12 to 13 years does not reduce adult height in boys with constitutional delay of growth and adolescence. Helv Pædiatr Acta 1987;42:21–28.
48.
Rosenfeld RG, Northcraft GB, Hintz RL: A prospective, randomized study of testosterone treatment of constitutional delay of growth and development in male adolescents. Pediatrics 1982;69:681–687.
49.
Richman RA, Kirsch LR: Testosterone treatment in adolescent boys with constitutional delay in growth and development. N Engl J Med 1988;319:1563–1567.
50.
Uruena M, Pantsiotou S, Preece MA, Stanhope R: Is testosterone therapy for boys with constitutional delay of growth and puberty associated with impaired final height and suppression of the hypothalamo-pituitary-gonadal axis? Eur J Pediatr 1992;151:15–18.
51.
Kaplowitz PB. Diagnostic value of testosterone therapy in boys with delayed puberty. Am J Dis Child 1989;143:116–120.
52.
Crowne EC, Shalet SM: Constitutional delay in growth and puberty; in Prader A, Rappaport R (eds): Clinical Issues in Growth Disorders: Evaluation, Diagnosis and Therapy. London, Freund, 1994, pp 71–96.
53.
Butler GE, Sellar RE, Walker RF, Hendry M, Kelnar CJ, Wu FC: Oral testosterone undecanoate in the management of delayed puberty in boys: Pharmacokinetics and effects on sexual maturation and growth. J Clin Endocrinol Metab 1992;75:37–44.
54.
Brown DC, Butler GE, Kelnar CJ, Wu FC: A double blind, placebo controlled study of the effects of low dose testosterone undecanoate on the growth of small for age, prepubertal boys. Arch Dis Child 1995;73:131–135.
55.
Albanese A, Kewley GD, Long A, Pearl KN, Robins DG, Stanhope R: Oral treatment for constitutional delay of growth and puberty in boys: A randomised trial of an anabolic steroid or testosterone undecanoate. Arch Dis Child 1994;71:315–317.
56.
Blizzard RM, Hindmarsh PC, Stanhope R: Oxandrolone therapy: 25 years’ experience. Growth Genet Horm 1991;7:1–6.
57.
Marti-Henneberg C, Niirianen AK, Rappaport R: Oxandrolone treatment of constitutional short stature in boys during adolescence: Effect on linear growth, bone age, pubic hair, and testicular development. J Pediatr 1975;86:783–788.
58.
Stanhope R, Brook CGD: Oxandrolone in low dose for constitutional delay of growth and puberty in boys. Arch Dis Child 1985;60:379–381.
59.
Stanhope R, Buchanan CR, Fenn GC, Preece MA: Double blind placebo controlled trial of low dose oxandrolone in the treatment of boys with constitutional delay of growth and puberty. Arch Dis Child 1988;63:501–505.
60.
Tse WY, Buyukgebiz A, Hindmarsh PC, Stanhope R, Preece MA, Brook CG: Long-term outcome of oxandrolone treatment in boys with constitutional delay of growth and puberty. J Pediatr 1990;117:588–591.
61.
Wilson DM, McCauley E, Brown DR, Dudley R: Oxandrolone therapy in constitutionally delayed growth and puberty. Bio-Technology General Corporation Cooperative Study Group. Pediatrics 1995;96:1095–1100.
62.
Bagatell CJ, Bremner WJ: Androgens in men – uses and abuses. N Engl J Med 1996;334:707–714.
63.
Kiess W, Conway G, Ritzén M, Rosenfield R, Bernasconi S, Juul A, van Pareren Y, de Muinck Keizer-Schrama SM, Bourguignon JP: Induction of puberty in the hypogonadal girl – practices and attitudes of pediatric endocrinologists in Europe. Horm Res 2002;57:66–71.
64.
Heinrichs C, Bourguignon JP: Treatment of delayed puberty and hypogonadism in girls. Horm Res 1991;36:147–152.
65.
Grumbach MM, Auchus RJ: Estrogen: Consequences and implications of human mutations in synthesis and action. J Clin Endocrinol Metab 1999;84:4677–4694.
66.
MacGillivray MH, Morishima A, Conte F, Grumbach M, Smith EP: Pediatric endocrinology update: An overview. The essential roles of estrogens in pubertal growth, epiphyseal fusion and bone turnover: Lessons from mutations in the genes for aromatase and the estrogen receptor. Horm Res 1998;49(suppl 1):2–8.
67.
Thomas MA, Rebar RW: Delayed puberty in girls and primary amenorrhea; in Bardin CW (ed): Current Therapy in Endocrinology and Metabolism, ed 6. St Louis, Mo., Mosby, 1997, pp 223–227.
68.
Burger HG: Physiological principles of endocrine replacement: Estrogen. Horm Res 2001;56(suppl 1):82–85.
69.
Illig R, DeCampo C, Lang-Muritano MR, Prader A, Torresani T, Werder EA, Willi U, Schenkel L: A physiological mode of puberty induction in hypogonadal girls by low dose transdermal 17 beta-oestradiol. Eur J Pediatr 1990;150:86–91.
70.
Cisternino M, Nahoul K, Bozzola M, Grignani G, Perani G, Sampaolo P, Roger M, Severi F: Transdermal estradiol substitution therapy for the induction of puberty in female hypogonadism. J Endocrinol Invest 1991;14:481–488.
71.
Ankarberg-Lindgren C, Elfving M, Wikland KA, Norjavaara E: Nocturnal application of transdermal estradiol patches produces levels of estradiol that mimic those seen at the onset of spontaneous puberty in girls. J Clin Endocrinol Metab 2001;86:3039–3044.
72.
Lanes R, Bohorquez L, Leal V, Hernández G, Borges M, Hurtado E, Moncada G: Growth hormone secretion in patients with constitutional delay of growth and pubertal development. J Pediatr 1986;109:781–783.
73.
Pozo J, Argente J, Barrios V, González-Parra S, Muñoz MT, Hernández H: Growth hormone secretion in children with normal variants of short stature. Horm Res 1994;41:185–192.
74.
Gourmelen M, Pham-Huu-Trung MT, Girard F: Transient partial hGH deficiency in prepubertal children with delay of growth. Pediatr Res 1979;13:221–224.
75.
Bierich JR: Serum growth hormone levels in provocation tests and during nocturnal spontaneous secretion: a comparative study. Acta Pædiatr Scand 1987;337(suppl):48–59.
76.
Kerrigan JR, Martha PM Jr, Veldhuis JD, Blizzard RM, Rogol AD: Altered growth hormone secretory dynamics in prepubertal males with constitutional delay of growth. Pediatr Res 1993;33:278–283.
77.
Bierich JR, Nolte K, Drews K, Brugmann G: Constitutional delay of growth and adolescence. Results of short-term and long-term treatment with GH. Acta Endocrinol (Copenh) 1992;127:392–396.
78.
Buyukgebiz A, Hindmarsh PC, Brook CG: Treatment of constitutional delay of growth and puberty with oxandrolone compared with growth hormone. Arch Dis Child 1990;65:448–449.
79.
Van der Eerden BC, Karperien M, Wit JM: The estrogen receptor in the growth plate: Implications for pubertal growth. J Pediatr Endocrinol Metab 2001;14(suppl 6):1527–1533.
80.
Grumbach MM: Estrogen, bone, growth and sex: A sea change in conventional wisdom. J Pediatr Endocrinol Metab 2000;13:1439–1455.
81.
Wickman S, Sipila I, Ankarberg-Lindgren C, Norjavaara E, Dunkel L: A specific aromatase inhibitor and potential increase in adult height in boys with delayed puberty: A randomised controlled trial. Lancet 2001;357:1743–1748.
82.
Dunkel L, Wickman S: Novel treatment of delayed male puberty with aromatase inhibitors. Horm Res 2002;57(suppl 2):44–52
83.
Pozo J, Argente J: Delayed puberty in chronic illness. Best Pract Res Clin Endocrinol Metab 2002;16:73–90.
84.
Simon D: Puberty in chronically diseased patients. Horm Res 2002;57(suppl 2):53–56.
85.
Low LC: Growth, puberty and endocrine function in beta-thalassaemia major. J Pediatr Endocrinol Metab 1997;10:175–184.
86.
Zacharin M: Use of androgens and oestrogens in adolescents – a review of hormone replacement treatment. J Pediatr Endocrinol Metab 2000;13:3–11.
87.
Howell S, Shalet S: Testosterone deficiency and replacement. Horm Res 2001;56(suppl 1):86–92.
88.
Schmidt H, Knorr D, Schwarz HP: Oral testosterone undecanoate for the induction of puberty in anorchid boys. Arch Dis Child 1998;78:397.
89.
Gooren LJ: A ten-year safety study of the oral androgen testosterone undecanoate. J Androl 1994;15:212–215.
90.
Stanhope R, Brook CG, Pringle PJ, Adams J, Jacobs HS: Induction of puberty by pulsatile gonadotropin releasing hormone. Lancet 1987;2:552–555.
91.
Buchter D, Behre HM, Kliesch S, Nieschlag E: Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: A review of 42 cases. Eur J Endocrinol 1998;139:298–303.
92.
Barrio R, de Luis D, Alonso M, Lamas A, Moreno JC: Induction of puberty with human chorionic gonadotropin and follicle-stimulating hormone in adolescent males with hypogonadotropic hypogonadism. Fertil Steril 1999;71:244–248.
93.
Bouvattier C, Tauber M, Jouret B, Chaussain JL, Rochiccioli P: Gonadotropin treatment of hypogonadotropic hypogonadal adolescents. J Pediatr Endocrinol Metab 1999;12(suppl 1):339–344.
94.
Bistritzer T, Lunenfeld B, Passwell JH, Theodor R: Hormonal therapy and pubertal development in boys with selective hypogonadotropic hypogonadism. Fertil Steril 1989;52:302–306.
95.
Christiansen C, Skakkebæk NE: Pulsatile gonadotropin-releasing hormone treatment of men with idiopathic hypogonadotropic hypogonadism. Horm Res 2002;57:32–36.
96.
Bhasin S, Salehian B: Gonadotropin therapy of men with hypogonadotropic hypogonadism; in Bardin CW (ed): Current Therapy in Endocrinology and Metabolism, ed 6. St Louis, Mo., Mosby, 1997, pp 349–352.
97.
Burris AS, Rodbard HW, Winters SJ, Sherins RJ: Gonadotropin therapy in men with isolated hypogonadotropic hypogonadism: The response to human chorionic gonadotropin is predicted by initial testicular size. J Clin Endocrinol Metab 1988;66:1144–1151.
98.
Whitcomb RW, Crowley WF Jr: Hypogonadotropic hypogonadism: Gonadotropin-releasing hormone therapy; in Bardin CW (ed): Current Therapy in Endocrinology and Metabolism, ed 6. St Louis, Mo., Mosby, 1997, pp 353–355.
99.
Pitteloud N, Hayes FJ, Dwyer A, Boepple PA, Lee H, Crowley WF Jr: Predictors of outcome of long-term GnRH therapy in men with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab 2002;87:4128–4136.
100.
Lippe BM, Saenger PH: Turner syndrome; in Sperling MA (ed): Pediatric Endocrinology, ed 2. Philadelphia, Pa., Saunders, 2002, pp 519–564.
101.
Minto CF, Howe C, Wishart S, Conway AJ, Handelsman DJ: Pharmacokinetics and pharmacodynamics of nandrolone esters in oil vehicle: Effects of ester, injection site and injection volume. J Pharmacol Exp Ther 1997;281:93–102.
102.
Behre HM, Nieschlag E: Testosterone buciclate (20 Aet-1) in hypogonadal men: Pharmacokinetics and pharmacodynamics of the new long-acting androgen ester. J Clin Endocrinol Metab 1992;75:1204–1210.
103.
von Eckardstein S, Nieschlag E: Treatment of male hypogonadism with testosterone undecanoate injected at extended intervals of 12 weeks: A phase II study. J Androl 2002;23:419–425.
104.
Handelsman DJ, Conway AJ, Boylan LM: Pharmacokinetics and pharmacodynamics of testosterone pellets in man. J Clin Endocrinol Metab 1990;71:216–222.
105.
Handelsman DJ, Mackey MA, Howe C, Turner L, Conway AJ: An analysis of testosterone implants for androgen replacement therapy. Clin Endocrinol (Oxf) 1997;47:311–316.
106.
Kelleher S, Turner L, Howe C, Conway AJ, Handelsman DJ: Extrusion of testosterone pellets: A randomized controlled clinical study. Clin Endocrinol (Oxf) 1999;51:469–471.
107.
Kelleher S, Conway AJ, Handelsman DJ: A randomised controlled clinical trial of antibiotic impregnation of testosterone pellet implants to reduce extrusion rate. Eur J Endocrinol 2002;146:513–518.
108.
Amory JK, Anawalt BD, Blaskovich PD, Gilchriest J, Nuwayser ES, Matsumoto AM: Testosterone release from a subcutaneous, biodegradable microcapsule formulation (Viatrel) in hypogonadal men. J Androl 2002;23:84–91.
109.
Bals-Pratsch M, Knuth UA, Yoon YD, Nieschlag E: Transdermal testosterone substitution therapy for male hypogonadism. Lancet 1986;2:943–946.
110.
Meikle AW, Mazer NA, Moellmer JF, Stringham JD, Tolman KG, Sanders SW, Odell WD: Enhanced transdermal delivery of testosterone across nonscrotal skin produces physiological concentrations of testosterone and its metabolites in hypogonadal men. J Clin Endocrinol Metab 1992;74:623–628.
111.
Jordan WP Jr, Atkinson LE, Lai C: Comparison of the skin irritation potential of two testosterone transdermal systems: An investigational system and a marketed product. Clin Ther 1998;20:80–87.
112.
Wilson DE, Kaidbey K, Boike SC, Jorkasky DK: Use of topical corticosteroid pretreatment to reduce the incidence and severity of skin reactions associated with testosterone transdermal therapy. Clin Ther 1998;20:299–306.
113.
Swerdloff RS, Wang C, Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ, Weber T, Longstreth J, Berman N: Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men. J Clin Endocrinol Metab 2000;85:4500–4510.
114.
Rolf C, Knie U, Lemmnitz G, Nieschlag E: Interpersonal testosterone transfer after topical application of a newly developed testosterone gel preparation. Clin Endocrinol (Oxf) 2002;56:637–641.
115.
Saenger P: Turner’s syndrome. N Engl J Med 1996;335:1749–1754.
116.
Guttmann H, Weiner Z, Nikolski E, Ish-Shalom S, Itskovitz-Eldor J, Aviram M, Reisner S, Hochberg Z: Choosing an oestrogen replacement therapy in young adult women with Turner syndrome. Clin Endocrinol (Oxf) 2001;54:159–164.
117.
Lufkin EG, Ory SJ: Relative value of transdermal and oral estrogen therapy in various clinical situations. Mayo Clin Proc 1994;69:131–135.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.