Polycystic ovary syndrome in adolescents: Current and future treatment options

Pediatric Drugs

Volumn 8, Issue 5, 2006, Pages 311-318

  Mastorakos, George ^a,b   Lambrinoudaki, Irene ^a   Creatsas, George ^a  

^a UNIVERSITY OF ATHENS   (Greece)

^b NONE   (Greece)

Author keywords

[No Author keywords available]

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; AMINOTRANSFERASE; ANTIHYPERTENSIVE AGENT; ANTIOBESITY AGENT; BIGUANIDE DERIVATIVE; CYPROTERONE; DESOGESTREL; DESOGESTREL PLUS ETHINYLESTRADIOL; DIANE; DROSPIRENONE PLUS ETHINYLESTRADIOL; DYDROGESTERONE; EFLORNITHINE; ESTROGEN; ETHINYLESTRADIOL; ETHINYLESTRADIOL PLUS GESTODENE; FINASTERIDE; FLUTAMIDE; GONADORELIN DERIVATIVE; INSULIN SENSITIZING AGENT; LIPID; MEDROXYPROGESTERONE; METFORMIN; NORETHISTERONE; ORAL CONTRACEPTIVE AGENT; PROGESTERONE DERIVATIVE; SEX HORMONE; SEX HORMONE BINDING GLOBULIN; SPIRONOLACTONE; TESTOSTERONE; UNINDEXED DRUG;

ABNORMALLY HIGH SUBSTRATE CONCENTRATION IN BLOOD; ABSENCE OF SIDE EFFECTS; AMINOTRANSFERASE BLOOD LEVEL; BREAST TENDERNESS; CARBOHYDRATE METABOLISM; CARDIOVASCULAR DISEASE; CLINICAL FEATURE; CLINICAL TRIAL; DIABETES MELLITUS; DIARRHEA; DIET THERAPY; DISEASE ASSOCIATION; ECHOGRAPHY; ENDOMETRIUM CANCER; ESTROGEN DEFICIENCY; GASTROINTESTINAL SYMPTOM; HIRSUTISM; HORMONAL REGULATION; HUMAN; INCIDENCE; INSULIN RESISTANCE; LACTIC ACIDOSIS; LIPID BLOOD LEVEL; LIVER TOXICITY; LOW BIRTH WEIGHT; MENSTRUAL IRREGULARITY; MOOD CHANGE; NAUSEA; OBESITY; OLIGOMENORRHEA; OVARY POLYCYSTIC DISEASE; PRECOCIOUS PUBERTY; PRIORITY JOURNAL; REVIEW; RISK ASSESSMENT; SIDE EFFECT; TERATOGENICITY; TESTOSTERONE BLOOD LEVEL; VENOUS THROMBOEMBOLISM; WEIGHT GAIN; WITHDRAWAL BLEEDING;

ADOLESCENT; ANTI-OBESITY AGENTS; FEMALE; HORMONES; HUMANS; HYPOGLYCEMIC AGENTS; METFORMIN; POLYCYSTIC OVARY SYNDROME;

EID: 33750212347     PISSN: 11745878     EISSN: 11745878     Source Type: Journal    
DOI: 10.2165/00148581-200608050-00004     Document Type: Review

References (86)

1. Nestler JE, Stovall D, Akhter N, et al. Strategies for the use of insulin: sensitizing drugs to treat infertility in women with polycystic ovary syndrome. Fertil Steril 2002; 77: 209-15
2. Diamanti-Kandarakis E, Kouli CR, Bergiele AT, et al. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab 1999; 84: 4006-11
3. Goudas VT, Dumesic DA. Polycystic ovary syndrome. Endocrinol Metab Clin N Am 1997; 26: 893-912
4. Ehrmann DA. Obesity and glucose intolerance in androgen excess. In: Azziz R, Nestler JE, Dewailley D, editors. Androgen excess disorders in women. Philadelphia (PA): Lipincott-Raven, 1997: 12
5. Gambineri A, Pelusi C, Vicennati V, et al. Obesity and the polycystic ovary syndrome. Int J Obes Relat Metab Disord 2002; 26: 883-96
6. ESHRE/ASRM PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81: 19-25
7. Homburg R, Lambalk CB. Polycystic ovary syndrome in adolescence: a therapeutic conundrum. Hum Reprod 2004; 19: 1-4
8. van Hooff MH, Voorhorst FJ, Kaptein MB, et al. Polycystic ovaries in adolescents and the relationship with menstrual cycle patterns, luteinizing hormone, androgens, and insulin. Fertil Steril 2000; 74: 49-58
9. van Hooff MH, Voorhorst FJ, Kaptein MB, et al. Endocrine features of polycystic ovary syndrome in a random population sample of 14-16 year old adolescents. Hum Reprod 1999; 14: 2223-9
10. Avvad CK, Holeuwerger R, Silva VCG, et al. Menstrual irregularity in the first postmenarchal years: an early clinical sign of polycystic ovary syndrome in adolescence. Gynecol Endocrinol 2001; 15: 170-7
11. Kent SC, Legro RS. Polycystic ovary syndrome in adolescents. Adolesc Med 2002; 13: 73-88
12. Ibanez L, Vall C, Potau N, et al. Sensitization to insulin in adolescent girls to normalize hirsutism, hyperandrogenism, oligomenorrhea and hyperinsulinism after precocious pubarche. J Clin Endocrinol Metab 2000; 85: 3526-30
13. Colilla S, Cox NJ, Ehrmann DA. Heretability of insulin secretion and insulin action in women with polycystic ovary syndrome and their first degree relatives. J Clin Endocrinol Metab 2001; 86: 2027-31
14. Kahsar-Miller MD, Nixon C, Boots LR, et al. Prevalence of polycystic ovary syndrome (PCOS) in first-degree relatives of patients with PCOS. Fertil Steril 2001; 75: 53-8
15. Apter D, Butzow T, Laughlin GA, et al. Metabolic features of polycystic ovary syndrome are found in adolescent girls with hyperandrogenism. J Clin Endocrinol Metab 1995; 80: 2966-73
16. Silfen ME, Denburg MR, Manibo AM. Early endocrine, metabolic, and sonographic characteristics of polycystic ovary syndrome (PCOS): comparison between nonobese and obese adolescents. J Clin Endocrinol Metab 2003; 88: 4682-8
17. Koivunen RM, Morin-Papunen LC, Ruokonen A, et al. Ovarian steroidogenic response to human chorionic gonadotrophin in obese women with polycystic ovary syndrome. Hum Reprod 2001; 16: 2546-51
18. Nestler JE, Jakubowicz DJ. Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17α activity and serum androgens. J Clin Endocrinol Metab 1997; 82: 4075-9
19. Arslanian SA, Lewy V, Danadian K, et al. Metformin therapy in obese adolescents with polycystic ovary syndrome and impaired glucose tolerance: amelioration of exaggerated adrenal response to adrenocorticotropin with reduction of insulinemia/insulin resistance. J Clin Endocrinol Metab 2002; 87: 1555-9
20. Adams J, Polson DW, Abdulwahid N. Multifollicular ovaries: clinical and endocrine features and response to gonadotropin releasing hormone. Lancet 1985; II: 1375-8
21. Polson DW, Wadsworth J, Adams J. Polycystic ovaries: a common finding in normal women. Lancet 1988; I: 870-2
22. Conway GS, Agrawal R, Betteridge DJ, et al. Risk factors for coronary artery disease in lean and obese women with the polycystic ovary syndrome. Clin Endocrinol (Oxf) 1992; 37: 119-25
23. Robinson S, Henderson AD, Gelding SV, et al. Dyslipidemia is associated with insulin resistance in women with polycystic ovaries. Clin Endocrinol (Oxf) 1996; 44: 277-84
24. Mastorakos G, Koliopoulos K, Creatsas G. Androgen and lipid profiles in adolescents with polycystic ovary syndrome who were treated with two forms of combined oral contraceptives. Fertil Steril 2002; 77: 919-27
25. Norman RJ, Masters SC, Hague W, et al. Metabolic approaches to the subclassification of the polycystic ovary syndrome. Fertil Steril 1995; 63: 329-35
26. Wild RA. Obesity, lipids, cardiovascular risk and androgen excess. Am J Med 1995; 98: 27S-32S
27. Burghen GA, Givens JR, Kitabchi AE. Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease. J Clin Endocrinol Metab 1980; 50: 113-6
28. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanisms and implications for the pathogenesis. Endocr Rev 1997; 18: 774-800
29. Book CB, Dunaif A. Selective insulin resistance in the polycystic ovary syndrome. J Clin Endocrinol Metab 1999; 84: 3110-6
30. Dunaif A, Segal KR, Futterweit W, et al. Profound peripheral insulin resistance, independent of obesity in polycystic ovary syndrome. Diabetes 1989; 38: 1165-74
31. Nestler JE, Jacubowitcz DJ, DeVargas AF, et al. Insulin stimulates testosterone biosynthesis by human theca cells from women with polycystic ovary syndrome by activating its own receptor and using inositoglycan mediators as the signal transductor system. J Clin Endocrinol Metab 1998; 83: 2001-5
32. Barbieri RL, Makris A, Randall RW, et al. Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism. J Clin Endocrinol Metab 1986; 62: 904-10
33. Ehrmann DA, Barnes RB, Rosenfield RL, et al. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care 1999; 22: 141-6
34. Legro RS, Kunselman AR, Dodson WC, et al. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab 1999; 84: 165-9
35. Palmert MR, Gordon CM, Kartashov AI, et al. Screening for abnormal glucose tolerance in adolescents with polycystic ovary syndrome. J Clin Endocrinol Metab 2001; 87: 1017-23
36. Arslanian SA, Lewy VD, Danadian K. Glucose intolerance in obese adolescents with polycystic ovary syndrome: roles of insulin resistance and β-cell dysfunction and risk of cardiovascular disease. J Clin Endocrinol Metab 2001; 86: 66-71
37. Balfour JA, McClellan K. Topical eflornithine. Am J Clin Dermatol 2001; 2: 197-201
38. Falsetti L, Dordoni D, Gastaldi C, et al. A new association of ethinylestradiol (0.035mg) cyproterone acetate (2mg) in the therapy of polycystic ovary syndrome. Acta Eur Fertil 1986; 17: 19-25
39. Falsetti L, Gambera A, Tisi G. Efficacy of the combination ethinyl oestradiol and cyproterone acetate on endocrine, clinical and ultrasonographic profile in polycystic ovarian syndrome. Hum Reprod 2001; 16: 36-42
40. Prelevic GM, Wurzburger MI, Balint-Peric L, et al. Effects of a low-dose estrogen-antiandrogen combination (Diane-35) on clinical signs of androgenization, hormone profile and ovarian size in patients with polycystic ovary syndrome. Gynecol Endocrinol 1989; 3: 269-80
41. Creatsas G, Koliopoulos C, Mastorakos G. Combined oral contraceptive treatment of adolescent girls with polycystic ovary syndrome: lipid profile. Ann N Y Acad Sci 2000; 900: 245-52
42. Cibula D, Hill M, Fanta M, et al. Does obesity diminish the positive effect of oral contraceptive treatment on hyperandrogenism in women with polycystic ovarian syndrome? Hum Reprod 2001; 16: 940-4
43. Morin-Papunen L, Vauhkonen I, Koivunen R, et al. Metformin versus ethinyl estradiol-cyproterone acetate in the treatment of nonobese women with polycystic ovary syndrome: a randomized study. J Clin Endocrinol Metab 2003; 88: 148-56
44. Falsetti L, Pasinetti E. Effects of long-term administration of an oral contraceptive containing ethinylestrdiol and cyproterone acetate on lipid metabolism in women with polycystic ovary syndrome. Acta Obstet Gynecol Scand 1995; 74: 56-60
45. Prelevic GM, Wurzburger MI, Trpkovic D, et al. Effects of a low-dose estrogen: antiandrogen combination (Diane-35) on lipid and carbohydrate metabolism in patients with polycystic ovary syndrome. Gynecol Endocrinol 1990; 4: 157-68
46. Escobar-Morreale HF, Lasuncion MA, Sancho J. Treatment of hirsutism with ethinyl estradiol-desogestrel contraceptive pills has beneficial effects on the lipid profile and improves insulin sensitivity. Fertil Steril 2000; 74 (4): 816-9
47. Guido M, Romualdi D, Giuliani M, et al. Drospirenone for the treatment of hirsute women with polycystic ovary syndrome: a clinical, endocrinological, metabolic pilot study. J Clin Endocrinol Metab 2004; 89: 2817-23
48. Thorneycroft H, Gollnick H, Schellschmidt I. Superiority of a combined contraceptive containing drospirenone to a triphasic preparation containing norgestimate in acne treatment. Cutis 2004; 74: 123-30
49. Thorneycroft IH. Evolution of progestins: focus on the novel progestin drospirenone. J Reprod Med 2002; 47 (11 Suppl.): 975-80
50. van Vloten WA, van Haselen CW, van Zuuren EJ, et al. The effect of 2 combined oral contraceptives containing either drospirenone or cyproterone acetate on acne and seborrhea. Cutis 2002; 69 (4 Suppl.): 2-15
51. Palep-Singh M, Mook K, Barth J, et al. An observational study of Yasmin in the management of women with polycystic ovary syndrome. J Fam Plann Reprod Health Care 2004; 30: 163-5
52. Godsland IF, Crook D, Simpson R, et al. The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism. N Engl J Med 1990; 323: 1375-81
53. Korytkowski MT, Mokan M, Horwitz MJ, et al. Metabolic effects of oral contraceptives in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1995; 80: 3327-34
54. Armstrong VL, Wiggam MI, Ennis CN, et al. Insulin action and insulin secretion in polycystic ovary syndrome treated with ethinyl oestradiol/ cyproterone acetate. QJM 2001; 94: 31-7
55. Gaspard U, Scheen A, Endrikat J, et al. A randomized study over 13 cycles to assess the influence of oral contraceptives containing ethinylestradiol combined with drospirenone or desogestrel on carbohydrate metabolism. Contraception 2003; 67: 423-9
56. Ludicke F, Gaspard UJ, Demeyer F, et al. Randomized controlled study of the influence of two low estrogen dose oral contraceptives containing gestodene or desogestrel on carbohydrate metabolism. Contraception 2002; 66: 411-5
57. Dawber RPR, Sinclair RD. Hirsuties. Clin Dermatol 2001; 19: 189-99
58. Barth JH, Cherry CA, Wojnarowska F, et al. Cyproterone acetate for severe hirsutism. J Clin Endocrinol Metab 1991; 35: 5-10
59. Venturoli S, Paradisi R, Bagnoli A, et al. Low-dose flutamide (125mg/day) as maintenance therapy in the treatment of hirsutism. Horm Res 2001; 56: 25-31
60. Spritzer PM, Lisboa KO, Mattielo S, et al. Spironolactone as a single agent for long-term therapy of hirsute patients. Clin Endocrinol (Oxf) 2000; 52: 587-94
61. Barth JH, Cherry CA, Wojnaroswka F, et al. Spironolactone is an effective and well tolerated systemic antiandrogen therapy for hirsute women. J Clin Endocrinol Metab 1989; 68: 966-70
62. Wong IL, Morris RS, Chang L, et al. A prospective randomized trial comparing finasteride to spironolactone in the treatment of hirsute women. J Clin Endocrinol Metab 1995; 80: 233-8
63. Tartagni M, Schonauer LM, De Salvia MA, et al. Comparison of Diane 35 and Diane 35 plus finasteride in the treatment of hirsutism. Fertil Steril 2000; 73: 718-23
64. De Leo V, Fulghesu AM, la Marca A, et al. Hormonal and clinical effects of GnRH agonist alone, or in combination with a combined oral contraceptive or flutamide in women with severe hirsutism. Gynecol Endocrinol 2000; 14: 411-6
65. Castelo-Branco C, Martinez de Osaba MJ, Pons F, et al. Gonadotropin-releasing hormone analog plus an oral contraceptive containing desogestrel in women with severe hirsutism: effects on hair, bone, and hormone profile after 1-year use. Metabolism 1997; 46: 437-40
66. Kahn JA, Gordon CM. Polycystic ovary syndrome. Adolesc Med 1999; 10: 321-36
67. Diamanti-Kandarakis E, Zapanti E. Insulin sensitizers and antiandrogens in the treatment of polycystic ovary syndrome. Ann N Y Acad Sci 2000; 900: 203-12
68. Pasquali R, Gambineri A, Biscotti D, et al. Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. J Clin Endocrinol Metab 2000; 85: 2767-74
69. Moghetti P, Castello R, Negri C, et al. Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation. J Clin Endocrinol Metab 2000; 85: 139-46
70. Kelly CJ, Gordon D. The effect of metformin on hirsutism in polycystic ovary syndrome. Eur J Endocrinol 2002 Aug; 147: 217-21
71. Loverro G, Lorusso F, De Pergola G, et al. Clinical and endocrinological effects of 6 months of metformin treatment in young hyperinsulinemic patients affected by polycystic ovary syndrome. Gynecol Endocrinol 2002; 16: 217-24
72. Harborne L, Fleming R, Lyall H, et al. Metformin or antiandrogen in the treatment of hirsutism in polycystic ovary syndrome. J Clin Endocrinol Metab 2003; 88: 4116-23
73. Heard MJ, Pierce A, Carson SA, et al. Pregnancies following use of metformin for ovulation induction in patients with polycystic ovary syndrome. Fertil Steril 2002; 77: 669-73
74. Vandermolen DT, Ratts VS, Evans WS, et al. Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone. Fertil Steril 2001; 75: 310-5
75. Kocak M, Caliskan E, Simsir C, et al. Metformin therapy improves ovulatory rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome. Fertil Steril 2002 Jan; 77 (1): 101-6
76. Glueck CJ, Philips H, Cameron D, et al. Continuing metformin throughout pregnancy in women with polycystic ovary syndrome appears to safely reduce first-trimester spontaneous abortion: a pilot study. Fertil Steril 2001; 75: 46-52
77. Glueck CJ, Wang P, Kobayashi S, et al. Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome. Fertil Steril 2002; 77: 520-5
78. Glueck CCJ, Wang P, Fontaine R, et al. Metformin to restore normal menses in oligo-amenorrheic teenage girls with polycystic ovary syndrome (PCOS). J Adolesc Health 2001; 29: 160-9
79. Azziz R, Ehrman D, Legro R, et al. Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome: a multicenter, double blind, placebo-controlled trial. J Clin Endocrinol Metab 2001; 86: 1626-32
80. Cataldo NA, Abbasi F, McLaughlin TL, et al. Improvement in insulin sensitivity followed by ovulation and pregnancy in a woman with polycystic ovary syndrome who was treated with rosiglitazone. Fertil Steril 2001; 76: 1057-9
81. Belli SH, Graffigna MN, Oneto A, et al. Effect of rosiglitazone on insulin resistance, growth factors, and reproductive disturbances in women with polycystic ovary syndrome. Fertil Steril 2004; 81: 624-9
82. Sepilian V, Nagamani M. Effects of rosiglitazone in obese women with polycystic ovary syndrome and severe insulin resistance. J Clin Endocrinol Metab 2005 Jan; 90 (1): 60-5
83. Baillargeon JP, Jakubowicz DJ, Iuorno MJ, et al. Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity. Fertil Steril 2004; 82: 893-902
84. Brettenthaler N, De Geyter C, Huber PR, et al. Effect of the insulin sensitizer pioglitazone on insulin resistance, hyperandrogenism, and ovulatory dysfunction in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2004; 89: 3835-40
85. Padwal R, Li SK, Lau DC. Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials. Int J Obes Relat Metab Disord 2003; 27: 1437-46
86. Berkowitz RI, Wadden TA, Tershakovec AM, et al. Behavior therapy and sibutramine for the treatment of adolescent obesity. JAMA 2003; 289: 1805-12