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Geburtshilfe Frauenheilkd 2004; 64(8): R157-R196
DOI: 10.1055/s-2004-821260
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Georg Thieme Verlag KG Stuttgart · New York

Hyperandrogenämie - Teil 1

Adrenale, ovarielle und kutane HyperandrogenämieMichael Ludwig1 , Helge Binder2 , Matthias W. Beckmann2 , Heinrich M. Schulte1
  • 1Endokrinologikum Hamburg, Zentrum für Hormon- und Stoffwechselerkrankungen, Gynäkologische Endokrinologie und Reproduktionsmedizin
  • 2Frauenklinik, Universitätsklinikum Erlangen
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Publication History

Publication Date:
12 August 2004 (online)

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Unter Hyperandrogenämie versteht man die vermehrte Produktion und Ausschüttung männlicher Geschlechtshormone. Sie ist ein klinisches Problem, das in der Praxis aufgrund der kosmetischen Folgen oder einer reproduktionsmedizinischen Fragestellung täglich ein Thema ist.

In Abhängigkeit vom Schweregrad der Hyperandrogenämie kann sie in verschiedenen Erscheinungsformen

Erscheinungsformen der Hyperandrogenämie: Akne, Hirsutismus, diffuse Alopezie, Zyklusstörungen, unerfüllter Kinderwunsch, Stimmveränderungen, Klitomegalie, Maskulinisierung.
auftreten:

Akne, Hirsutismus, diffuse Alopezie, Zyklusstörungen (Oligo-/Amenorrhö), unerfüllter Kinderwunsch, Stimmveränderungen, Klitoromegalie, Maskulinisierung.

Dabei ist zu bedenken, dass bei erhöhter Empfindlichkeit der Zielzellen milde Veränderungen an Haut und Haaren auch bei normalen Hormonspiegeln auftreten können.

Zur gezielten Therapie der Hyperandrogenämie ist die differenzialdiagnostische Abgrenzung der Ursachen von wesentlicher Bedeutung. Ferner ist die im Vordergrund stehende Beschwerdesymptomatik bei der Wahl der Therapie

Die Wahl der Therapie richtet sich nach den Ursachen und der Beschwerdesymptomatik.
zu bedenken. So wird eine Patientin mit kutanen Erscheinungsformen der Hyperandrogenämie anders behandelt als die Kinderwunschpatientin.

Literatur

  • 1 Geisthövel F. Funktioneller Hyperandrogenismus (sog. „Syndrom polyzystischer Ovarien“).  Gynäkologe. 2002;  35 48-63
    PubMedGoogle Scholar
  • 2 Fassnacht M, Schlenz N, Schneider S B, Wudy S A, Allolio B, Arlt W. Beyond adrenal and ovarian androgen generation: Increased peripheral 5 alpha-reductase activity in women with polycystic ovary syndrome.  J Clin Endocrinol Metab. 2003;  88 2760-2766
    CrossrefPubMedGoogle Scholar
  • 3 Speiser P W, White P C. Congenital adrenal hyperplasia.  N Engl J Med. 2003;  349 776-788
    CrossrefPubMedGoogle Scholar
  • 4 Dörr H G, Sippell W G. Prenatal dexamethasone treatment in pregnancies at risk for congenital adrenal hyperplasia due to 21-hydroxylase deficiency: effect on midgestational amniotic fluid steroid levels.  J Clin Endocrinol Metab. 1993;  76 117-120
    CrossrefPubMedGoogle Scholar
  • 5 Joint Working Group L WPES/ESPECAH. Consensus Statement on 21-Hydroxylase Deficiency from The Lawson Wilkins Pediatric Endocrine Society and The European Society for Paediatric Endocrinology.  J Clin Endocrinol Metab. 2002;  87 4048-4053
    CrossrefPubMedGoogle Scholar
  • 6 New M I, Carlson A, Obeid J. et al . Prenatal diagnosis for congenital adrenal hyperplasia in 532 pregnancies.  J Clin Endocrinol Metab. 2001;  86 5661-5667
    PubMedGoogle Scholar
  • 7 Meyer-Bahlburg H F, Dolezahl C, Baker S W, Carlson D, New M I. Cognitive and motor development of children with and without congenital adrenal hyperplasia after early-prenatal dexamethasone.  J Clin Endocrinol Metab. 2004;  89 610-614
    CrossrefPubMedGoogle Scholar
  • 8 Zawadski J K, Dunaif A. Diagnostic criteria for polycystic ovarian syndrome: towards a rationale approach. Dunaif A, Givens JR, Haseltine F Polycystic Ovary Syndrome. (1st ed). Boston; Blackwell Scientific 1992: 377-384
    Google Scholar
  • 9 Pierroz D D, Aebi A C, Huhtaniemi I T, Aubert M L. Many LH peaks are needed to physiologically stimulate testosterone secretion: modulation by fasting and NPY.  Am J Physiol. 1999;  276 E603-E610
    PubMedGoogle Scholar
  • 10 Hileman S M, Lubbers L S, Kuehl D E, Schaeffer D J, Rhodes L, Jackson G L. Effect of inhibiting 5 alpha-reductase activity on the ability of testosterone to inhibit luteinizing hormone release in male sheep.  Biol Reprod. 1994;  50 1244-1250
    PubMedGoogle Scholar
  • 11 Belgorosky A, Chahin S, Rivarola M A. Elevation of serum luteinizing hormone levels during hydrocortisone treatment in infant girls with 21-hydroxylase deficiency. Acta Paediatr.  . 1996;  85 1172-1175
    PubMedGoogle Scholar
  • 12 Patel K, Coffler M S, Dahan M H. et al . Increased luteinizing hormone secretion in women with polycystic ovary syndrome is unaltered by prolonged insulin infusion.  J Clin Endocrinol Metab. 2003;  88 5456-5461
    CrossrefPubMedGoogle Scholar
  • 13 Weiss J M, Polack S, Diedrich K, Ortmann O. Effects of insulin on luteinizing hormone and prolactin secretion and calcium signaling in female rat pituitary cells.  Arch Gynecol Obstet. 2003;  269 45-50
    CrossrefPubMedGoogle Scholar
  • 14 Adams J, Frank S, Polson D W, Abdulwahid N. et al . Multifollicular ovaries: clinical and endocrine features and response to pulsatile gonadotropin releasing hormone.  Lancet. 1985;  2 1375-1379
    PubMedGoogle Scholar
  • 15 Revised consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.  Fertil Steril. 2004;  81 19-25
    PubMedGoogle Scholar
  • 16 Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS).  Hum Reprod. 2004;  19 41-47
    CrossrefPubMedGoogle Scholar
  • 17 Nahum R, Thong K J, Hillier S G. Metabolic regulation of androgen production by human thecal cells in vitro.  Hum Reprod. 1995;  10 75-81
    PubMedGoogle Scholar
  • 18 Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis.  Endocr Rev. 1997;  18 774-800
    CrossrefPubMedGoogle Scholar
  • 19 Poretsky L, Kalin M F. The gonadotropic function of insulin.  Endocr Rev. 1987;  8 132-141
    PubMedGoogle Scholar
  • 20 Xia Y X, Weiss J M, Polack S, Diedrich K, Ortmann O. Interactions of insulin-like growth factor-I, insulin and estradiol with GnRH-stimulated luteinizing hormone release from female rat gonadotrophs.  Eur J Endocrinol. 2001;  144 73-79
    CrossrefPubMedGoogle Scholar
  • 21 King H, Rewers M. Global estimates for prevalence of diabetes mellitus and impaired glucose tolerance in adults. WHO Ad Hoc Diabetes Reporting Group.  Diabetes Care. 1993;  16 157-177
    CrossrefPubMedGoogle Scholar
  • 22 Ehrmann D A, Barnes R B, Rosenfield R L, Cavaghan M K, Imperial J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome.  Diabetes Care. 1999;  22 141-146
    CrossrefPubMedGoogle Scholar
  • 23 Legro R S, Kunselman A R, Dodson W C, Dunaif A. 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;  84 165-169
    CrossrefPubMedGoogle Scholar
  • 24 Norman R J, Masters L, Milner C R, Wang J X, Davies M J. Relative risk of conversion from normoglycaemia to impaired glucose tolerance or non-insulin dependent diabetes mellitus in polycystic ovarian syndrome.  Hum Reprod. 2001;  16 1995-1998
    CrossrefPubMedGoogle Scholar
  • 25 Peppard H R, Marfori J, Iuorno M J, Nestler J E. Prevalence of polycystic ovary syndrome among premenopausal women with type 2 diabetes.  Diabetes Care. 2001;  24 1050-1052
    PubMedGoogle Scholar
  • 26 Conn J J, Jacobs H S, Conway G S. The prevalence of polycystic ovaries in women with type 2 diabetes mellitus.  Clin Endocrinol (Oxf). 2000;  52 81-86
    CrossrefPubMedGoogle Scholar
  • 27 Solomon C G, Hu F B, Dunaif A. et al . Long or highly irregular menstrual cycles as a marker for risk of type 2 diabetes mellitus.  Jama. 2001;  286 2421-2426
    CrossrefPubMedGoogle Scholar
  • 28 Colilla S, Cox N J, Ehrmann D A. Heritability of insulin secretion and insulin action in women with polycystic ovary syndrome and their first degree relatives.  J Clin Endocrinol Metab. 2001;  86 2027-2031
    CrossrefPubMedGoogle Scholar
  • 29 Dunaif A, Segal K R, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome.  Diabetes. 1989;  38 1165-1174
    CrossrefPubMedGoogle Scholar
  • 30 Dunaif A, Segal K R, Shelley D R, Green G, Dobrjansky A, Licholai T. Evidence for distinctive and intrinsic defects in insulin action in polycystic ovary syndrome.  Diabetes. 1992;  41 1257-1266
    CrossrefPubMedGoogle Scholar
  • 31 Dunaif A, Xia J, Book C B, Schenker E, Tang Z. Excessive insulin receptor serine phosphorylation in cultured fibroblasts and in skeletal muscle. A potential mechanism for insulin resistance in the polycystic ovary syndrome.  J Clin Invest. 1995;  96 801-810
    CrossrefPubMedGoogle Scholar
  • 32 Dunaif A, Finegood D T. Beta-cell dysfunction independent of obesity and glucose intolerance in the polycystic ovary syndrome.  J Clin Endocrinol Metab. 1996;  81 942-947
    CrossrefPubMedGoogle Scholar
  • 33 Ehrmann D A, Sturis J, Byrne M M, Karrison T, Rosenfield R L, Polonsky K S. Insulin secretory defects in polycystic ovary syndrome. Relationship to insulin sensitivity and family history of non-insulin-dependent diabetes mellitus.  J Clin Invest. 1995;  96 520-527
    CrossrefPubMedGoogle Scholar
  • 34 O'Meara N M, Blackman J D, Ehrmann D A. et al . Defects in beta-cell function in functional ovarian hyperandrogenism.  J Clin Endocrinol Metab. 1993;  76 1241-1247
    CrossrefPubMedGoogle Scholar
  • 35 Book C B, Dunaif A. Selective insulin resistance in the polycystic ovary syndrome.  J Clin Endocrinol Metab. 1999;  84 3110-3116
    CrossrefPubMedGoogle Scholar
  • 36 Bjercke S, Dale P O, Tanbo T, Storeng R, Ertzeid G, Abyholm T. Impact of insulin resistance on pregnancy complications and outcome in women with polycystic ovary syndrome.  Gynecol Obstet Invest. 2002;  54 94-98
    CrossrefPubMedGoogle Scholar
  • 37 Kannel W B, D'Agostino R B, Wilson P W, Belanger A J, Gagnon D R. Diabetes, fibrinogen, and risk of cardiovascular disease: the Framingham experience.  Am Heart J. 1990;  120 672-676
    CrossrefPubMedGoogle Scholar
  • 38 Wild R A. Obesity, lipids, cardiovascular risk, and androgen excess.  Am J Med. 1995;  98 27S-32S
    CrossrefPubMedGoogle Scholar
  • 39 Wild S, Pierpoint T, McKeigue P, Jacobs H. Cardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: a retrospective cohort study.  Clin Endocrinol (Oxf). 2000;  52 595-600
    Google Scholar
  • 40 Amowitz L L, Sobel B E. Cardiovascular consequences of polycystic ovary syndrome.  Endocrinol Metab Clin North Am. 1999;  28 439-458, viii
    CrossrefPubMedGoogle Scholar
  • 41 Birdsall M A, Farquhar C M, White H D. Association between polycystic ovaries and extent of coronary artery disease in women having cardiac catheterization.  Ann Intern Med. 1997;  126 32-35
    CrossrefPubMedGoogle Scholar
  • 42 Paradisi G, Steinberg H O, Hempfling A. et al . Polycystic ovary syndrome is associated with endothelial dysfunction.  Circulation. 2001;  103 1410-1415
    CrossrefPubMedGoogle Scholar
  • 43 Talbott E, Guzick D, Clerici A. et al . Coronary heart disease risk factors in women with polycystic ovary syndrome.  Arterioscler Thromb Vasc Biol. 1995;  15 821-826
    CrossrefPubMedGoogle Scholar
  • 44 Talbott E O, Guzick D S, Sutton-Tyrrell K. et al . Evidence for association between polycystic ovary syndrome and premature carotid atherosclerosis in middle-aged women.  Arterioscler Thromb Vasc Biol. 2000;  20 2414-2421
    PubMedGoogle Scholar
  • 45 Pierpoint T, McKeigue P M, Isaacs A J, Wild S H, Jacobs H S. Mortality of women with polycystic ovary syndrome at long-term follow-up.  J Clin Epidemiol. 1998;  51 581-586
    CrossrefPubMedGoogle Scholar
  • 46 Solomon C G, Hu F B, Dunaif A. et al . Menstrual cycle irregularity and risk for future cardiovascular disease.  J Clin Endocrinol Metab. 2002;  87 2013-2017
    CrossrefPubMedGoogle Scholar
  • 47 Hiort O, Holterhus P M, Nitsche E M. Physiology and pathophysiology of androgen action.  Baillieres Clin Endocrinol Metab. 1998;  12 115-132
    CrossrefPubMedGoogle Scholar
  • 48 Diamanti-Kandarakis E, Baillargeon J P, Iuorno M J, Jakubowicz D J, Nestler J E. A modern medical quandary: polycystic ovary syndrome, insulin resistance, and oral contraceptive pills.  J Clin Endocrinol Metab. 2003;  88 1927-1932
    CrossrefPubMedGoogle Scholar
  • 49 Hammerstein J, Meckies J, Leo-Rossberg I, Moltz L, Zielske F. Use of cyproterone acetate (CPA) in the treatment of acne, hirsutism and virilism.  J Steroid Biochem. 1975;  6 827-836
    CrossrefPubMedGoogle Scholar
  • 50 Leo-Rossberg I, Laur S, Zielske F, Hammerstein J. Reversed sequential therapy of hirsutism using cyproterone acetate. I. Further clinical observations.  Acta Endocrinol Suppl (Copenh). 1971;  152 14
    PubMedGoogle Scholar
  • 51 Zielske F, Dreykluft R, Magnus U, Hammerstein J. Reversed sequential therapy of hirsutism using cyproterone acetate. II. Hormonal analyses.  Acta Endocrinol Suppl (Copenh). 1971;  152 15
    PubMedGoogle Scholar
  • 52 Azziz R, Black V Y, Knochenhauer E S, Hines G A, Boots L R. Ovulation after glucocorticoid suppression of adrenal androgens in the polycystic ovary syndrome is not predicted by the basal dehydroepiandrosterone sulfate level.  J Clin Endocrinol Metab. 1999;  84 946-950
    CrossrefPubMedGoogle Scholar
  • 53 Imani B, Eijkemans M J, Te Velde E R, Habbema J D, Fauser B C. Predictors of chances to conceive in ovulatory patients during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility.  J Clin Endocrinol Metab. 1999;  84 1617-1622
    CrossrefPubMedGoogle Scholar
  • 54 Eijkemans M J, Imani B, Mulders A G, Habbema J D, Fauser B C. High singleton live birth rate following classical ovulation induction in normogonadotrophic anovulatory infertility (WHO 2).  Hum Reprod. 2003;  18 2357-2362
    CrossrefPubMedGoogle Scholar
  • 55 van Santbrink E J, Fauser B C. Urinary follicle-stimulating hormone for normogonadotropic clomiphene-resistant anovulatory infertility: prospective, randomized comparison between low dose step-up and step-down dose regimens.  J Clin Endocrinol Metab. 1997;  82 3597-3602
    CrossrefPubMedGoogle Scholar
  • 56 van Santbrink E J, Donderwinkel P F, van Dessel T J, Fauser B C. Gonadotrophin induction of ovulation using a step-down dose regimen: single-centre clinical experience in 82 patients.  Hum Reprod. 1995;  10 1048-1053
    PubMedGoogle Scholar
  • 57 Venturoli S, Marescalchi O, Colombo F M. et al . A prospective randomized trial comparing low dose flutamide, finasteride, ketoconazole, and cyproterone acetate-estrogen regimens in the treatment of hirsutism.  J Clin Endocrinol Metab. 1999;  84 1304-1310
    CrossrefPubMedGoogle Scholar
  • 58 Carmina E, Lobo R A. Treatment of hyperandrogenic alopecia in women.  Fertil Steril. 2003;  79 91-95
    CrossrefPubMedGoogle Scholar
  • 59 Carmina E, Lobo R A. A comparison of the relative efficacy of antiandrogens for the treatment of acne in hyperandrogenic women.  Clin Endocrinol (Oxf). 2002;  57 231-234
    CrossrefPubMedGoogle Scholar
  • 60 Muderris I I, Bayram F, Guven M. A prospective, randomized trial comparing flutamide (250 mg/d) and finasteride (5 mg/d) in the treatment of hirsutism.  Fertil Steril. 2000;  73 984-987
    CrossrefPubMedGoogle Scholar
  • 61 Fruzzetti F, Bersi C, Parrini D, Ricci C, Genazzani A R. Treatment of hirsutism: comparisons between different antiandrogens with central and peripheral effects.  Fertil Steril. 1999;  71 445-451
    CrossrefPubMedGoogle Scholar
  • 62 Salpeter S R, Greyber E, Pasternak G A, Salpeter E E. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus: systematic review and meta-analysis.  Arch Intern Med. 2003;  163 2594-2602
    CrossrefPubMedGoogle Scholar
  • 63 Haas D A, Carr B R, Attia G R. Effects of metformin on body mass index, menstrual cyclicity, and ovulation induction in women with polycystic ovary syndrome.  Fertil Steril. 2003;  79 469-481
    CrossrefPubMedGoogle Scholar
  • 64 Costello M F, Eden J A. A systematic review of the reproductive system effects of metformin in patients with polycystic ovary syndrome.  Fertil Steril. 2003;  79 1-13
    CrossrefPubMedGoogle Scholar
  • 65 Harborne L, Fleming R, Lyall H, Sattar N, Norman J. Metformin or antiandrogen in the treatment of hirsutism in polycystic ovary syndrome.  J Clin Endocrinol Metab. 2003;  88 4116-4123
    CrossrefPubMedGoogle Scholar
  • 66 Lord J M, Flight I H, Norman R J. Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome.  Cochrane Database Syst Rev. 2003;  CD003053
    PubMedGoogle Scholar
  • 67 Coetzee E J, Jackson W P. Pregnancy in established non-insulin-dependent diabetics. A five-and-a-half year study at Groote Schuur Hospital.  S Afr Med J. 1980;  58 795-802
    PubMedGoogle Scholar
  • 68 Coetzee E J, Jackson W P. Diabetes newly diagnosed during pregnancy: A 4-year study at Groote Schuur Hospital.  S Afr Med J. 1979;  56 467-475
    PubMedGoogle Scholar
  • 69 Jakubowicz D J, Iuorno M J, Jakubowicz S, Roberts K A, Nestler J E. Effects of metformin on early pregnancy loss in the polycystic ovary syndrome.  J Clin Endocrinol Metab. 2002;  87 524-529
    CrossrefPubMedGoogle Scholar
  • 70 Vandermolen D T, Ratts V S, Evans W S, Stovall D W, Kauma S W, Nestler J E. 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;  75 310-315
    CrossrefPubMedGoogle Scholar
  • 71 Glueck C J, Wang P, Goldenberg N, Sieve-Smith L. Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin.  Hum Reprod. 2002;  17 2858-2864
    CrossrefPubMedGoogle Scholar
  • 72 Glueck C J, Wang P, Kobayashi S, Phillips H, Sieve-Smith L. Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome.  Fertil Steril. 2002;  77 520-525
    CrossrefPubMedGoogle Scholar
  • 73 Glueck C J, Phillips H, Cameron D, Sieve-Smith L, Wang P. 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
    CrossrefPubMedGoogle Scholar
  • 74 Cavaghan M K, Ehrmann D A, Byrne M M, Polonsky K S. Treatment with the oral antidiabetic agent troglitazone improves beta cell responses to glucose in subjects with impaired glucose tolerance.  J Clin Invest. 1997;  100 530-537
    PubMedGoogle Scholar
  • 75 Dunaif A, Scott D, Finegood D, Quintana B, Whitcomb R. The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome.  J Clin Endocrinol Metab. 1996;  81 3299-3306
    CrossrefPubMedGoogle Scholar
  • 76 Ehrmann D A, Schneider D J, Sobel B E. et al . Troglitazone improves defects in insulin action, insulin secretion, ovarian steroidogenesis, and fibrinolysis in women with polycystic ovary syndrome.  J Clin Endocrinol Metab. 1997;  82 2108-2116
    CrossrefPubMedGoogle Scholar
  • 77 Azziz R, Ehrmann D, Legro R S. 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 1626-1632
    CrossrefPubMedGoogle Scholar
  • 78 Cataldo N A, Abbasi F, McLaughlin T L, Lamendola C, Reaven G M. 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 1057-1059
    CrossrefPubMedGoogle Scholar
  • 79 Ghazeeri G, Kutteh W H, Bryer-Ash M, Haas D, Ke R W. Effect of rosiglitazone on spontaneous and clomiphene citrate-induced ovulation in women with polycystic ovary syndrome.  Fertil Steril. 2003;  79 562-566
    CrossrefPubMedGoogle Scholar
  • 80 Shobokshi A, Shaarawy M. Correction of insulin resistance and hyperandrogenism in polycystic ovary syndrome by combined rosiglitazone and clomiphene citrate therapy.  J Soc Gynecol Investig. 2003;  10 99-104
    PubMedGoogle Scholar
  • 81 Glueck C J, Moreira A, Goldenberg N, Sieve L, Wang P. Pioglitazone and metformin in obese women with polycystic ovary syndrome not optimally responsive to metformin.  Hum Reprod. 2003;  18 1618-1625
    CrossrefPubMedGoogle Scholar
  • 82 Nestler J E, Stovall D, Akhter N, Iuorno M J, Jakubowicz D J. Strategies for the use of insulin-sensitizing drugs to treat infertility in women with polycystic ovary syndrome.  Fertil Steril. 2002;  77 209-215
    CrossrefPubMedGoogle Scholar
  • 83 Crave J C, Fimbel S, LeJeune H, Cugnardey N, Dechaud H, Pugeat M. Effects of diet and metformin administration on sex hormone-binding globulin, androgens, and insulin in hirsute and obese women.  J Clin Endocrinol Metab. 1995;  80 2057-62
    CrossrefPubMedGoogle Scholar
  • 84 Nestler J E, Jakubowicz D J. Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome.  N Engl J Med. 1996;  335 617-623
    CrossrefPubMedGoogle Scholar
  • 85 Nestler J E, Jakubowicz D J. Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17 alpha activity and serum androgens.  J Clin Endocrinol Metab. 1997;  82 4075-4079
    PubMedGoogle Scholar
  • 86 Velazquez E, Acosta A, Mendoza S G. Menstrual cyclicity after metformin therapy in polycystic ovary syndrome.  Obstet Gynecol. 1997;  90 392-395
    PubMedGoogle Scholar
  • 87 Diamanti-Kandarakis E, Kouli C, Tsianateli T, Bergiele A. Therapeutic effects of metformin on insulin resistance and hyperandrogenism in polycystic ovary syndrome.  Eur J Endocrinol. 1998;  138 269-274
    CrossrefPubMedGoogle Scholar
  • 88 Morin-Papunen L C, Koivunen R M, Ruokonen A, Martikainen H K. Metformin therapy improves the menstrual pattern with minimal endocrine and metabolic effects in women with polycystic ovary syndrome.  Fertil Steril. 1998;  69 691-696
    CrossrefPubMedGoogle Scholar
  • 89 Nestler J E, Jakubowicz D J, Evans W S, Pasquali R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome.  N Engl J Med. 1998;  338 1876-1880
    PubMedGoogle Scholar
  • 90 Glueck C J, Wang P, Fontaine R, Tracy T, Sieve-Smith L. Metformin-induced resumption of normal menses in 39 of 43 (91 %) previously amenorrheic women with the polycystic ovary syndrome.  Metabolism. 1999;  48 511-519
    CrossrefPubMedGoogle Scholar
  • 91 La Marca A, Morgante G, Paglia T, Ciotta L, Cianci A, De L V. Effects of metformin on adrenal steroidogenesis in women with polycystic ovary syndrome.  Fertil Steril. 1999;  72 985-989
    PubMedGoogle Scholar
  • 92 Pirwany I R, Yates R W, Cameron I T, Fleming R. Effects of the insulin sensitizing drug metformin on ovarian function, follicular growth and ovulation rate in obese women with oligomenorrhoea.  Hum Reprod. 1999;  14 2963-2968
    CrossrefPubMedGoogle Scholar
  • 93 Unluhizarci K, Kelestimur F, Bayram F, Sahin Y, Tutus A. The effects of metformin on insulin resistance and ovarian steroidogenesis in women with polycystic ovary syndrome.  Clin Endocrinol (Oxf). 1999;  51 231-236
    CrossrefPubMedGoogle Scholar
  • 94 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;  85 139-146
    CrossrefPubMedGoogle Scholar
  • 95 Kolodziejczyk B, Duleba A J, Spaczynski R Z, Pawelczyk L. Metformin therapy decreases hyperandrogenism and hyperinsulinemia in women with polycystic ovary syndrome.  Fertil Steril. 2000;  73 1149-1154
    Google Scholar
  • 96 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 2767-2774
    CrossrefPubMedGoogle Scholar
  • 97 Ibanez L, Valls C, Ferrer A, Marcos M V, Rodriguez-Hierro F, de Zegher F. Sensitization to insulin induces ovulation in nonobese adolescents with anovulatory hyperandrogenism.  J Clin Endocrinol Metab. 2001;  86 3595-3598
    CrossrefPubMedGoogle Scholar
  • 98 Baysal B, Batukan M, Batukan C. Biochemical and body weight changes with metformin in polycystic ovary syndrome.  Clin Exp Obstet Gynecol. 2001;  28 212-214
    PubMedGoogle Scholar
  • 99 Vrbikova J, Hill M, Starka L, Vondra K. Prediction of the effect of metformin treatment in patients with polycystic ovary syndrome.  Gynecol Obstet Invest. 2002;  53 100-104
    CrossrefPubMedGoogle Scholar
  • 100 Fleming R, Hopkinson Z E, Wallace A M, Greer I A, Sattar N. Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial.  J Clin Endocrinol Metab. 2002;  87 569-574
    CrossrefPubMedGoogle Scholar
  • 101 Karck U. Therapie der Hyperandrogenämie und ihrer Symptome Hirsutismus, Seborrhö und Akne.  Gynäkologe. 2002;  35 22-30
    PubMedGoogle Scholar
  • 102 Azziz R. The evaluation and management of hirsutism.  Obstetrics & Gynecology. 2003;  101 995-1007
    CrossrefPubMedGoogle Scholar
  • 103 Lucky A W, Piacquadio D J, Ditre C M. et al . A randomized, placebo-controlled trial of 5 % and 2 % topical minoxidil solutions in the treatment of female pattern hair loss.  J Am Acad Dermatol. 2004;  50 541-553
    CrossrefPubMedGoogle Scholar
  • 104 Bouhanna P. Androgenetic alopecia: Combining medical and surgical treatments.  Dermatol Surg. 2003;  29) 1130-1134
    PubMedGoogle Scholar
  • 105 Chen W C, Thiboutot D, Zouboulis C C. Cutaneous androgen metabolism: Basic research and clinical perspectives.  J Invest Dermatol. 2002;  119 992-1007
    CrossrefPubMedGoogle Scholar
  • 106 Hanneken S, Ritzmann A, Nöthen M M, Kruse R. Androgenetische Alopezie.  Hautarzt. 2003;  54 703-712
    CrossrefPubMedGoogle Scholar
  • 107 Hunter M H, Carek P J. Evaluation and treatment of hirsutism.  American Family Physician. 2003;  67 2565-2572
    PubMedGoogle Scholar
  • 108 Price V H. Androgenetic alopecia in women.  J Invest Dermatol Symposium Proceedings. 2003;  8 24-27
    PubMedGoogle Scholar
  • 109 Kaufmann K D. Androgens and alopecia.  Mol Cell Endocrinol. 2002;  198 89-95
    CrossrefPubMedGoogle Scholar
  • 110 Van der Spuy Z M, le Roux P A. Cyproterone acetate for hirsutism. (Cochrane Review). The Cochrane Library. Chichester, UK; John Wiley & Sons, Ltd. 2004 2: 1-53
    Google Scholar
  • 111 Farquar C, Lee O, Toomath R, Jepson R. Spironolactone versus placebo or in combination with steroids for Hirsutism and/or acne. (Cochrane Review).  The Cochrane Library. Chichester, UK; John Wiley & Sons, Ltd. 2004 2: 1-33
    Google Scholar
  • 112 Lumchi F, Rondinone R. Use of cyproterone acetate, finasteride and spironolactone to treat idiopathic hirsurtism.  Fertil Steril. 2003;  79 942-946
    CrossrefPubMedGoogle Scholar
  • 113 Birch M P, Lalla S C, Messenger A G. Female pattern hair loss.  Clin Dermatol. 2002;  27 283-388
    PubMedGoogle Scholar
  • 114 Fischer T W, Burmeister G, Schmidt H W, Elsner P. Melatonin increases anagen hair rate in women with androgenetic alopecia or diffuse alopecia: results of a pilot randomized controlled trial.  Br J Dermatol. 2004;  150 341-345
    CrossrefPubMedGoogle Scholar
  • 115 Raulin C, Greve B. Aktueller Stand der Photoepilation.  Hautarzt. 2000;  51 809-817
    CrossrefPubMedGoogle Scholar
  • 116 Trüeb R M. Neues und Bewährtes in der Therapie von Haarerkrankungen.  Hautarzt. 2003;  45 732-740
    PubMedGoogle Scholar
  • 117 McPhaul M J. Factors that mediate and modulate androgen action.  J Invest Dermatol Symposium Proceedings. 2003;  8 1-5
    PubMedGoogle Scholar
  • 118 Norwood O T. Incidence of female androgenetic alopecia (female pattern alopecia).  Dermatol Surg. 2001;  27 53-54
    CrossrefPubMedGoogle Scholar
  • 119 Javidnia K, Dastgheib L, Samani M S, Nasiri A. Antihirsutim activity of fennel (fruits of Foeniculum vulgare) extract. A double-blind placebo controlled study.  Phytomedicine. 2003;  10 455-458
    CrossrefPubMedGoogle Scholar
  • 120 Glueck C J, Goldenberg N, Wang P, Loftspring M, Sherman A. Metformin during pregnancy reduces insulin, insulin resistance, insulin secretion, weight, testosterone and development of gestational diabetes: prospective longitudinal assessment of women with polycystic ovary syndrome from preconception throughout pregnancy.  Hum Reprod. 2004;  19 510-521
    CrossrefPubMedGoogle Scholar
  • 121 Elder A T, Hague W M, Davoren P M, Oliver J. et al . Contraindications to use of metformin.  BMJ. 2003;  326 762
    CrossrefPubMedGoogle Scholar
  • 122 National Collaborating Centre for Women's and Children's Health .Clinical Guideline. London; RCOG Press 2004: 1-216
    Google Scholar
  • 123 Kunte C, Wolf H. Aktuelle Therapie der Hypertrichosen.  Hautarzt. 2001;  52 993-997
    CrossrefPubMedGoogle Scholar
  • 124 Wolf H. unveröffentlichte Daten. LMU München 2004
    Google Scholar
  • 125 Farquhar C, Vandekerckhove P, Lilford R. Laparoscopic “drilling” by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome.  The Cochrane Library, Update Software. Oxford; 2002 3
    Google Scholar
  • 126 El Saeed M, Ezzar M, Hasan M, Elhelw Aboumaaty B Z, Aboulghar M. High incidence of pelviv adhesions detected by secondary look laparoscopy after laparoscopic drilling.  Middle East Fert Soc J. 2000;  5 519-525
    PubMedGoogle Scholar
  • 127 Farquhar C M, Williamson K, Brown P M, Garland J. An economic evaluation of laparoscopic ovarian diathermy versus gonadotrophin therapy for women with clomiphene citrate resistant polycystic ovary syndrome.  Hum Reprod. 2004;  19 1110-1115
    CrossrefPubMedGoogle Scholar
  • 128 Shapiro L, Pastuszak A, Curto G, Koren G. Safety of first trimester exposure to topical tretinoin (Letter).  Lancet. 1997;  350 1134-1144
    PubMedGoogle Scholar
  • 129 Jick S S, Terris B Z, Jick H. First trimester topical tretinoin and congenital disorders.  Lancet. 1993;  341 1181-1182
    CrossrefPubMedGoogle Scholar
  • 130 Thomas L. Labor und Diagnose. 5. Aufl. Frankfurt/Main; TH-Books 1998
    Google Scholar

Priv. Doz. Dr. med. Michael Ludwig

Endokrinologikum Hamburg, Zentrum für Hormon- und Stoffwechselerkrankungen, Reproduktionsmedizin und gynäkologische Endokrinologie

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