A Detailed Investigation of Hirsutism in a Turkish Population: Idiopathic Hyperandrogenemia as a Perplexing Issue[*]

Abstract

Hirsutism is a common clinical problem in women and the treatment depends on the cause of hirsutism. The study was designed to determine the various causes of hirsutism and their prevalences in a Turkish population. 168 women with hirsutism attending to Endocrinology Outpatient Clinic of Erciyes University Hospital were investigated in detail. Medical history, physical examination, and basal levels of free testosterone (fT), androstenedione, follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone-sulphate (DHEAS), 17 hydroxyprogesterone (17-OHP), 11-deoxycortisol (11-S), thyroid hormones, thyroid stimulating hormone (TSH), and prolactin were determined. ACTH stimulation test was performed for the diagnosis of non-classic congenital adrenal hyperplasia (NCAH). Pelvic/vaginal and adrenal ultrasonographies were performed for the detection of tumors and polycystic ovarian changes. Polycystic ovary syndrome (PCOS) was diagnosed in 96 (57.1 %) patients, idiopathic hirsutism in 27 (16 %), NCAH in 12 (7.1 %), adrenal carcinoma in 3 (1.8 %), and Cushing's disease in 1 (0.6 %) patient. Among patients with NCAH, 11 (91.7 %) patients had 11-β hydroxylase (11-β OH) deficiency, and 1 (8.3 %) had 21-hydroxylase deficiency. The etiology of hyperandrogenemia was not clear in 29 (17.4 %) patients and these patients were named as idiopathic hyperandrogenemia. The clinical presentation of 11-β OH deficiency is indistinguishable from that of other hyperandrogenic states and ACTH stimulation test is the only way to diagnose this entity. Although PCOS is the most common cause of hirsutism, it is notable that nearly one fifth of hirsute women have no apparent cause of hyperandrogenemia.

Key words

Polycystic ovary syndrome - idiopathic hirsutism - idiopathic hyperandrogenemia - late-onset adrenal hyperplasia

1 This study has been partially presented in 6th European Congress of Endocrinology in 26 - 30 April 2003, Lyon, France

References

• 1 Adams J, Polson D W, Franks S. Prevalence of polycystic ovaries in women with anovulation and idiopathic hirsutism.  Br Med J. 1986;  293 355-359
• 2 Azziz D, Dewailly D, Owerbach D. Nonclassic adrenal hyperplasia: current concepts.  J Clin Endocrinol Metab. 1994;  78 810-815
• 3 Azziz R, Waggoner W T, Ochoa T, Knochenhauer E S, Boots L R. Idiopathic hirsutism: an uncommon cause of hirsutism in Alabama.  Fertil Steril. 1998;  70 274-278
• 4 Azziz R, Hincapie L A, Knochenhauer E S, Dewailly D, Fox L, Boots L R. Screening for 21-hydroxylase-deficient nonclassic adrenal hyperplasia among hyperandrogenic women: a prospective study.  Fertil Steril. 1999;  72 915-925
• 5 Azziz R. The time has come to simplify the evaluation of the hirsute patient.  Fertil Steril. 2000;  74 870-872
• 6 Azziz R, Carmina E, Sawaya M E. Idiopathic hirsutism.  Endocr Rev. 2000;  21 347-362
• 7 Azziz R. The evaluation and management of hirsutism.  Obstet Gynecol. 2003;  101 995-1007
• 8 Bidzinska B, Tworowska U, Demissie M, Milewicz. A modified dexamethasone and gonadotropin-releasing hormone agonist (dx-GnRHa) test in the evaluation of androgen source(s) in hirsute women.  Przegl Lek. 2000;  57 393-396
• 9 Carmina E. Prevalance of idiopathic hirsutism (Abstract # P286). Proceedings of the 53rd annual meeting of the American Society for Reproductive Medicine. Cincinnati; Elsevier Science 1997
• 10 Carmina E. Prevalance of idiopathic hirsutism.  Eur J Endocrinol. 1998;  139 421-423
• 11 Carmina E, Lobo R A. The addition of dexamethasone to antiandrogen therapy for hisutism prolongs the duration of remission.  Fertil Steril. 1998;  69 1075-1079
• 12 Carmina E, Lobo R A. Polycystic ovaries in hirsute women with normal menses.  Am J Med. 2000;  111 602-606
• 13 Carmina E, Malizia G, Pagano M, Janni A. Prevalence of late-onset 11 beta-hydroxylase deficiency in hirsute patients.  J Endocrinol Invest. 1988;  11 595-598
• 14 Conn J J, Jacobs H S. The clinical management of hirsutism.  Eur J Endocrinol. 1997;  136 339-348
• 15 Ehrmann D A, Barnes R B, Rosenfield R L. Polycystic ovary syndrome as a form of functional ovarian hyperandrogenism due to dysregulation of androgen secretion.  Endocrine Reviews. 1995;  16 322-353
• 16 Falsetti L, Rosina B, De Fusco D. Serum levels of 3α-androstanediol glucuronide in hirsute and non-hirsute women.  Eur J Endocrinol. 1998;  138 421-424
• 17 Frank-Raue K, Junga G, Raue F, Vescei P, Ziegler R. Therapy of hirsutism in females with adrenal enzyme defects of steroid hormone biosynthesis: comparison of dexamethasone with cyproterone acetate (Article in German).  Klin Wochenschr. 1990;  68 597-601
• 18 Hatch R, Rosenfield R L, Kim M H, Tredway D. Hirsutism: implications, etiology, and management.  Am J Obstet Gynecol. 1981;  140 815-830
• 19 Kelestimur F, Sahin Y, Ayata D, Tutus A. The prevalence of non-classic adrenal hyperplasia due to 11β-hydroxylase deficiency among hirsute women in a Turkish population.  Clin Endocrinol. 1996;  45 381-384
• 20 Kelestimur F. Hirsutism of adrenal origin in adolescents: consequences in adults.  J Ped Endocrinol Metabol. 2001;  14 1309-1315
• 21 Moran C, Tapia M C, Hernandez E, Vazquez G, Garcia-Hernandez E, Bermudez J A. Etiological review of hirsutism in 250 patients.  Arch Med Res. 1994;  25 311-314
• 22 New M I, Lorenzen F, Lerner A J, Kohn B, Oberfield S E, Pollack M S, Dupont B, Stoner E, Levy D J, Pang S, Levine U. Genotyping steroid 21-hydroxylase deficiency: hormonal reference data.  J Clin Endocrinol Metab. 1983;  57 320-326
• 23 O'Driscoll J B, Mamtora H, Higginson J, Pollock A, Kane J, Anderson D C. A prospective study of the prevalance of clear-cut endocrine disorders and polycystic ovaries in 350 patients presenting with hirsutism and androgenic alopecia.  Clin Endocrinol. 1994;  41 231-236
• 24 Rosler A, Leiberman E, Cohen T. High frequency of congenital adrenal hyperplasia (classic 11 beta-hydroxylase deficiency) among Jews from Morocco.  Am J Med Genet. 1992;  42 827-834
• 25 Rossi R, Tauchmanova L, Luciano A, Valentino R, Savastana S, Battista C, Di Martino M, Lombardi G. Functional hyperandrogenism detected by corticotropin and GnRH-analogue stimulation tests in women affected by apparently idiopathic hirsutism.  J Endocrinol Invest. 2001;  24 491-498
• 26 Sahin Y, Kelestimur F. The frequency of late-onset 21-hydroxylase and 11β-hydroxylase deficiency in women with polycystic ovary syndrome.  Eur J Endocrinol. 1997;  137 670-674
• 27 Schteingart D E, Valderrama R. Identifying an adrenal disorder in the hirsute women.  Curr Opin Endocrinol Diab. 1997;  4 225-230
• 28 Unal A, Sahin Y, Kelestimur F. Acromegaly with polycystic ovaries, hyperandrogenemia, hirsutism, insulin resistance and acanthosis nigricans: a case report.  Endocrine J. 1993;  40 207-211
• 29 Unluhizarci K, Kelestimur F, Guven M, Bayram F, Colak R. The value of low dose (1 µg) ACTH stimulation test in the investigation of non-classic adrenal hyperplasia due to 11-β hydroxylase deficiency.  Exp Clin Endocrinol Diabetes. 2002;  110 381-385
• 30 Valentino R, Tommaselli A P, Savastano S, Dorato M, Rossi R, Lombardi G. Different dysregulations in adrenal steroid biosynthesis as a prevalent cause of hyperandrogenism in women from southern Italy.  Fertil Steril. 1997;  68 236-241
• 31 White P C, Speiser P W. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency.  Endocrine Reviews. 2000;  21 245-291
• 32 Zargar A H, Wani A I, Masoodi S R, Laway B A, Bashir M I, Salahuddin M. Epidemiologic and etiologic aspects of hirsutism in Kashmiri women in the Indian subcontinent.  Fertil Steril. 2002;  77 674-678
• 33 Zawadki J K, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. Dunaif A, Givens JR, Haseltine F, Merriam GR Polycystic Ovary Syndrome. Boston; Blackwell 1992: 377-384

1 This study has been partially presented in 6th European Congress of Endocrinology in 26 - 30 April 2003, Lyon, France