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European Consensus on the evaluation of women presenting with excessive hair growth |
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European Journal of Dermatology. Volume 19, Number 6, 597-602, November-December 2009, Clinical report |
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DOI : 10.1684/ejd.2009.0786 |
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 Summary
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Author(s) : Ulrike Blume-Peytavi, Stephen Atkin, Jerry Shapiro, Stuart Lavery, Ramon Grimalt, Rolf Hoffmann, Uwe Gieler, Andrew Messenger , Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Charitéplatz1, D-10117 Berlin, Germany, Hull York Medical School, Hull, UK, Department of Dermatology and Skin Science, University of British Columbia, Vancouver, Canada, Department of Reproductive Medicine and Science, Hammersmith Hospital, Imperial College School of Medicine, London, UK, Department of Dermatology, University of Barcelona, Barcelona, Spain, Privatpraxis für Dermatologie, Freiburg, Germany, Department of Dermatology, University of Giessen and Marburg, Germany, Department of Dermatology, Royal Hallamshire Hospital, Sheffield, UK. | |||||
Summary : Our objective was to develop clinical practice guidance for the evaluation of hirsutism in premenopausal women. The Skin Academy is led by an international interdisciplinary team of experts, and aims to use the latest scientific and clinical data in selected dermatological diseases, to promote awareness, education and best clinical practice, thus improving patient care. The Skin Academy is an international platform designed to drive and develop education and awareness programmes, and to transfer scientific knowledge in dermatology across Europe and wider geographical areas. Consensus was guided by systematic review and discussion of current clinical practice across Europe during several group meetings of The Skin Academy, supported by conference calls, and e-mail communications. The outcome of the discussions was an evaluation form to be used by the clinician to help evaluate a patient presenting with excessive hair growth. This round-table expert opinion consensus paper, and the Diagnostic Evaluation Form it contains, is presented for discussion by the wider dermatology community. | |||||
Keywords : diagnosis, evaluation, hirsutism, unwanted facial hair | |||||
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ARTICLE
Auteur(s) : Ulrike Blume-Peytavi1, Stephen Atkin2, Jerry Shapiro3, Stuart Lavery4, Ramon Grimalt5, Rolf Hoffmann6, Uwe Gieler7, Andrew Messenger8 1Department of Dermatology and Allergy,
Charité-Universitätsmedizin Berlin, Charitéplatz1, D-10117 Berlin,
Germany accepté le 8 Juillet 2009 Hirsutism is defined medically as excessive terminal hair that appears in a male pattern in women [1]. The causes of hirsutism can be divided into non androgenic factors (i.e. not caused by excessive androgen action), hirsutism caused by androgen excess, and idiopathic hirsutism. Non androgenic causes of hirsutism are relatively rare. Non androgenic anabolic drugs cause a generalised growth of many tissues, particularly hair, generally leading to vellus hypertrichosis and not hirsutism [2]. Androgenic causes are responsible in up to 80% of patients, and include polycystic ovary syndrome (PCOS), which affects about 70-80% of hirsute women [3-5]; hyperandrogenic insulin-resistant acanthosis nigricans syndrome, affecting about 3% [6]; 21-OH-deficient non classic adrenal hyperplasia in 2-8% of patients; and, very rarely, ovarian or adrenal androgen-secreting neoplasms [4, 5, 7]. It is challenging to find a consensus for the diagnosis of women with excessive hair growth because they may present to the practising clinician in a myriad of different ways. Additionally, different countries have slightly different routes to appropriate care, and slightly different strategies for the care of these patients. They may be seen initially in primary care, or directly by a dermatologist, endocrinologist or gynaecologist depending on the country [1, 8-11]. The first step is to clarify the problem: hirsutism must be distinguished from hypertrichosis, which is androgen independent and presents with generalized or localized growth of vellus type (non-terminal) hair over the body distributed in a nonsexual pattern. This may be familial, drug related or caused by metabolic or other non-endocrine disorders such as seen in anorexia nervosa. The diagnostic evaluation of hirsutism involves two stages. Firstly, hirsutism should be established by a clinical history, which takes into account ethnic differences and a physical examination, to confirm the presence of excess hair in a male pattern. Secondly, associated or contributing disorders should be excluded (e.g. ovulatory dysfunction, adrenal hyperplasia, diabetes, thyroid hormone abnormalities [12]). However, whilst some women may not fulfill the criteria of hirsutism, the excess hair growth that they complain of may still cause them considerable distress. Martin et al. have elegantly proposed guidance for the treatment of women with excessive facial hair [13]. However, the evaluation and diagnosis of these patients is a common challenge to all physicians. Hirsutism leads mostly to psychosocial complaints, including depression, social phobia or body dysmorphic disorders [14, 15]. Also, in most cases the patient’s quality of life is affected [16]. Patients are often reluctant to present with all of their symptoms, unless they are asked directly about them (NICE guidelines [17]). With this in mind, an interdisciplinary group of leading experts (working under the umbrella of The Skin Academy) met to discuss and address this challenge. The result is a series of questions aimed at helping the clinician to evaluate women complaining of excessive hair growth. This evaluation form is presented in this manuscript as the basis for ongoing discussion and refinement by the wider medical community. This discussion process was expert opinion based and supported by a thorough literature research. Method of European ConsensusThe hirsutism subgroup of the Skin Academy met several times over the course of a year to contrast and compare best practice in the evaluation of women with excessive hair growth. The outcome of these meetings was an initial draft of the Diagnostic Evaluation Form. This draft was circulated for review, and conference calls conducted to clarify and gain consensus where appropriate. All members of the hirsutism subgroup of the Skin Academy were consulted for their opinion on the drafts, and all comments were addressed until consensus was reached. The final draft of the Diagnostic Evaluation Form was then submitted for practical evaluation by dermatologists and is currently being used in several different European countries (the UK, Germany and Switzerland).ResultsThe Evaluation Form is comprised of three sections: History, Clinical Examination, and Investigations. Each section is split into sub-sections, allowing the clinician to address each factor in turn (figure 1).HistoryAgeThe patient’s age should be taken into consideration because non-neoplastic forms of hirsutism usually manifest around puberty (when androgen secretion increases), or following a period of weight gain, or when oral contraceptives have been stopped [18, 19].Speed of onsetAfter the menopause, there is a slow physiological depilation in most women, with the exception of facial hair, which tends to increase. Some women experience a rapid development or worsening of hirsutism at puberty, especially if they have an androgen production disorder. Hirsutism becoming rapidly worse or starting at other times of life may be caused by androgen excess from neoplasia.MedicationSome drugs can cause hirsutism, e.g. danazol, valproic acid (the only anticonvulsant drug that raises blood testosterone levels), anabolic or androgenic steroids (these drugs are often taken by athletes and patients with endometriosis or sexual dysfunction). Standard assays do not detect some of these drugs, and so clinicians should obtain a history of use of androgenic drugs in particular, including anabolic and androgenic steroids [1, 2, 20]. Additionally, combined oestrogen-androgen hormone replacement therapy in postmenopausal women should be considered.EthnicityA patient’s racial background affects what is “normal” compared with “excessive” hair growth. Although 70-80% of patients with androgen excess demonstrate hirsutism, this sign may be less prevalent among Asian women [21].Family historyHirsutism may have occurred in both female and male members of the patient’s family, and a genetic element of the disorder should be examined [22-24].Menstrual cycleExcess androgen production is usually caused by PCOS [1, 25]. The diagnosis of PCOS is based on at least two of the three diagnostic criteria of the Rotterdam consensus [26] being present for each patient, namely clinical and biochemical evidence of hyperandrogenemia, oligomenorrhoea or amenorrhea and polycystic ovaries on transvaginal ultrasound. A diagnosis of PCOS is normally often made when there is hyperandrogenism and oligoanovulation. Some of the features associated with PCOS (menstrual irregularity, polycystic ovaries, or central obesity) may not be present. Therefore, the absence of such features in a patient presenting with hirsutism does not rule out a diagnosis of PCOS. The associated medical risks of PCOS warrant examination of the patient for the following: subtle ovarian dysfunction that may present as infertility [27], abnormal carbohydrate and lipid metabolism, or a family history of type 2 diabetes mellitus. When irregular menstruation or amenorrhoea is present in women with rapidly progressive hirsutism or signs of virilisation, an androgen-secreting neoplasm should also be considered.HyperandrogenismHirsutism results from an interaction between the androgens in the blood, and the sensitivity of the hair follicle to androgen, which is determined partly by the local metabolism of androgens, and by the binding of these molecules to the androgen receptor. Most women with a 2-fold or greater increase in their androgen levels have some degree of hirsutism or correlating symptoms such as acne vulgaris, seborrhoea, or pattern alopecia. When features such as menstrual irregularity are present, even normal degrees of hirsutism are usually associated with hyperandrogenemia. Hirsutism without hyperandrogenemia is termed idiopathic hirsutism [28].Clinical examinationDistribution of hairThe growth of sexual hair is dependent on the presence of androgen and growth hormones. The amount and distribution of hair is an index of androgen effect. Hair on the upper back, shoulders, and upper abdomen suggests a marked increase in androgen production. However, any variation in the pattern and degree of hirsutism may be seen in women with idiopathic hirsutism, PCOS, or any other cause of androgen excess [29].If the hirsutism is mild (i.e. with a Ferriman-Gallwey score of 8 to 15 (depending on ethnic group) and the patient’s periods are regular, with nothing to suggest a secondary cause, it is highly likely that the hirsutism is idiopathic [30-34]. Between 5% and 15% of hirsute women have idiopathic hirsutism [35, 36]. In some of these women the 5α-reductase activity in the skin and hair follicle is overactive, leading to hirsutism despite their normal circulating androgen levels. The investigating doctor may ask the patient to complete the form to reach the score as often the patient has epilated, and so it is not possible for the clinician to judge the extent of excessive hair growth [30]. Dermatological examinationAn increase in androgen levels (2-fold or greater) usually leads to some degree of hirsutism, but may also lead to pilosebaceous responses such as acne, excessive sebum secretion, or diffuse or localized loss of hair from the head or other regions.Thickening and darkening of the skinThickening and darkening of the skin of the neck and/or inguinal region is an indication of acanthosis nigricans, which is related to high levels of insulin in the blood or a symptom of obese patients. The hyperandrogenic insulin-resistant acanthosis nigricans syndrome is a genetic disorder including many different genetic syndromes [37]. Approximately 3% of hyperandrogenic women suffer from these disorders, which are characterized by extremely high circulating levels of insulin leading to severe insulin resistance. Clinically these patients are very difficult to distinguish from other hyperandrogenic patients.PCOS is one of the most common causes of hirsutism, and insulin resistance is also common in PCOS and can lead to symptoms such as hyperglycaemia and dyslipidaemia. These require consideration and treatments in their own right, and are distinct from those for the hirsutism itself. Approximately 50% of PCOS patients demonstrate insulin resistance and secondary hyperinsulinemia [38]. Body mass index (BMI)Central obesity is a common feature often associated with PCOS and may exacerbate the phenotype. The central adiposity is often associated with other features of the metabolic syndrome. Thus calculating the BMI (BMI = weight/height2) should be part of the investigation.Ferriman-Gallwey scoreThe Ferriman-Gallwey score is a method for quantifying a patient’s hirsutism. Hirsutism is indicated by a Ferriman-Gallwey score of at least 8 [39]. The Ferriman-Gallwey score is well known, but does have limitations; not least its subjective nature. It is generally perceived as time consuming but if the clinician is trained or has at least some experience of the technique and uses a scoring sheet it can give rather rapid documentary evidence and be a valuable task. The F-G-score is the most widely accepted scoring system available for hirsute patients (figure 2).Psychosomatic AspectsThe patients should be asked about changes in their quality of life since they became conscious of their excessive hair growth. They should also be investigated for symptoms of depression, e.g. sleeping difficulties, and lost energy. Feelings of disgust, sexual activity changes, signs of body dysmorphic disorder and changes in life-behaviour or life-events should also be investigated to evaluate if additional counselling or psychotherapy is necessary.InvestigationsThe initial laboratory investigations include free androgen index (FAI) to assess biochemical hyperandrogenemia and thyroid function tests, prolactin, 17 hydroxyprogesterone (17OHP) as well as a 24 hour urine cortisol to rule out Cushing’s syndrome, if there is a clinical suspicion. Pregnancy should be ruled out in any woman with “irregular” or absent menstrual cycles.Thyroid functionThyroid dysfunction is often considered as a cause of hirsutism, though in reality hypothyroidism is more associated with coarsening of the hair rather than true hirsutism through androgen excess.Testosterone evaluation and Free Androgen IndexThe decision to test for androgen excess depends on how likely this abnormality is in the patient with hirsutism. A normal total testosterone level supports the diagnosis of idiopathic hirsutism, although it does not rule out androgen excess, and approximately half of isolated mild hirsutism (F-G score 8-15) cases, especially in women with no evidence to suggest a secondary cause, are not caused by hyperandrogenemia.Serum analysis fails to detect the biochemical hyperandrogenism of PCOS in about 20-40% of patients [40]. Total testosterone measurement by modern immunoassay has a low sensitivity when used to diagnose polycystic ovary syndrome [41]. Sex hormone binding globulin (SHBG) levels may influence total testosterone levels when increased (e.g., with the use of oral contraceptive pills) or decreased (e.g., in insulin resistance [42]), or in obesity. Measurement of the SHBG level enables calculation of the FAI (FAI = total testosterone divided by SHBG × 100 [43]). In practice, total testosterone is often not elevated in PCOS, and FAI, as a measure of bioavailable testosterone, is elevated by virtue of a suppressed SHBG. However, in the remainder of cases of mild hirsutism and in most cases of moderate or severe hirsutism, or in patients with symptoms suggesting an underlying disorder, plasma total and free testosterone levels are likely to be raised [1, 31, 44, 45]. If hirsutism is moderate or severe (with a F-G score of more than 15) or there are features to suggest a secondary cause, assessment of androgen levels is prudent [13, 46]. Very high testosterone levels more than 1.5-2 times the upper limit of normal or a history of rapid development of virilisation are more likely to be associated with tumour associated hyperandrogenism. This would then trigger measurement of dehydroepiandrosterone sulfate (DHEAS) and androstenedione to identify an adrenal or ovarian source of the hyperandrogenaemia, respectively [47]. Prolactin levelDespite the fact that PCOS is the most likely explanation for women presenting with moderate to severe hirsutism, clinicians should also examine to exclude other likely causes. Typically, this evaluation includes a prolactin level test, to exclude hyperprolactinaemia [13].Ultrasound of the pelvisUltrasonographic examination of the ovaries, the adrenal glands, or both is a useful screening procedure if the symptoms suggest the presence of a neoplasm [48]. Pelvic ultrasound may also be useful if PCOS is suspected to fulfil the Rotterdam criteria for its diagnosis [26, 49].The transvaginal ultrasound is the preferred mode, but if the patient is a virgin or anatomically small, or slim, then transabdominal ultrasound may be sufficient. Routine ultrasonographic imaging of ovaries is not required to diagnose polycystic ovary syndrome in patients with oligo-/amenorrhea and clinical or biochemical evidence of hyperandrogenism. Psychosomatic/psychiatric diagnosisPsychosomatic/psychiatric investigations should be carried out if psychological symptoms are present.ConclusionThe Evaluation Form based on European interdisciplinary consensus presented here is intended to help the practising doctor in the diagnosis, treatment and follow-up of women presenting with excessive hair growth.This form can be individually modified according to the patient and to the main interest or discipline of the doctor. It is hoped that it will form a solid foundation to allow the clinician to consider the different aspects of excessive hair growth, such as endocrinological, gynaecological, dermatological and psychological. Based on this first screening and evaluation, hints can be found as to the underlying cause of the disorder and indicate the direction for a subtle and detailed work up. Thus this evaluation form can be regarded as a “door opener” and a checklist for clinicians in daily practice. AcknowledgementsThe authors gratefully acknowledge the assistance of Dr Lisa Chamberlain James in the preparation of this manuscript. The Skin Academy is supported by an unrestricted grant from Almirall Ltd, S.A., Spain.References1 Rosenfield RL. Clinical practice. Hirsutism. N Engl J Med 2005; 353: 2578-88.2 Trueb RM. Causes and management of hypertrichosis. Am J Clin Dermatol 2002; 3: 617-27. 3 Nikolaou D, Gilling-Smith C. Hirsutism. Curr Obstet Gynaecol 2005; 15: 174-83. 4 O’Driscoll JB, Mamtora H, Higginson J, Pollock A, Kane J, Anderson DC. A prospective study of the prevalence of clear-cut endocrine disorders and polycystic ovaries in 350 patients presenting with hirsutism or androgenic alopecia. Clin Endocrinol 1994; 41: 231-6. 5 Morán C, Tapia MC, Hernández E, Vázquez G, García-Hernández E, Bermúdez JA. Etiologic review of hirsutism in 250 patients. Arch Med Res 1994; 25: 311-4. 6 Sanchez LA, Knochenhauer ES, Gatlin R, et al. Differential diagnosis of clinically evident hyperandrogenism: Experience with over 1000 consecutive patients. Fertil Steril 2001; 76: S111; [abstract]. 7 Waggoner W, Boots LR, Azziz R. Total testosterone and DHEAS levels as predictors of androgen-secreting neoplasms: A populational study. Gynecol Endocrinol 1999; 13: 1-7. 8 Carmina E, Rosato F, Janni A, Rizzo M, Longo R. Extensive clinical experience: relative prevalence of different androgen excess disorders in 950 women referred because of clinical hyperandrogenism. J Clin Endocrinol Metab 2006; 91: 2-6. 9 ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician-Gynecologists: number 41, December 2002. Obstet Gynecol 2002; 100: 1389-402. 10 Buggs C, Rosenfield RL. Polycystic ovary syndrome in adolescence. Endocrinol Metab Clin North Am 2005; 34: 677-705. 11 Goodman NF, Bledsoe MB, Cobin RH, et al. American Association of Clinical Endocrinologists medical guidelines for the clinical practice for the diagnosis and treatment of hyperandrogenic disorders. Endocr Pract 2001; 7: 120-34. 12 Azziz R. The evaluation and management of hirsutism. Obstet Gynecol 2003; 101: 995-1007. 13 Martin KA, Chang RJ, Ehrmann DA, et al. Evaluation and Treatment of Hirsutism in Premenopausal Women: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2008; 93: 1105-20. 14 Barth JH, Catalan J, Cherry CA, Day A. Psychological morbidity in women referred for treatment of hirsutism. J Psychosom Res 1993; 37: 615-9. 15 Hahn S, Janssen OE, Tan S, et al. Clinical and psychological correlates of quality-of-life in polycystic ovary syndrome. Eur J Endocrino 2005; 153: 853-60. 16 Sonino N, Fava GA, Mani E, Belluardo P, Boscaro M. Quality of life of hirsute women. Postgrad Med J 1993; 69: 186-9. 17 NICE Guidelines: Core interventions in the treatment of obsessive-compulsive disorder and body dimorphic disorder. 2005; http://guidance.nice.org.uk/CG31/quickrefguide/pdf/English. 18 Fruzzetti F, Perini D, Lazzarini V, Parrini D, Genazzani AR. Adolescent girls with polycystic ovary syndrome showing different phenotypes have a different metabolic profile associated with increasing androgen levels. Fertil Steril 2008: 13. 19 Codner E, Cassoria F. Puberty and ovarian function in girls with type 1 diabetes mellitus. Horm Res 2009; 71: 12-21. 20 Camacho-Martinez FM. Hypertrichosis. In: Blume-Peytavi U, Tosti A, Whiting DA, Trüeb R, eds. Hair Growth and Disorders. Springer 1. Edition, 2008: 333-53. 21 Wijeyaratne CN, Balen AH, Barth JH. Clinical manifestations and insulin resistance (IR) in polycystic ovary syndrome (PCOS) among South Asians and Caucasians: is there a difference? Clin Endocrinol (Oxf) 2002; 57: 343-50. 22 Carey AH, Chan KL, Short F, White D, Williamson R, Franks S. Evidence for a single gene effect causing polycystic ovaries and male pattern baldness. Clin Endocrinol (Oxf) 1993; 38: 653-8. 23 Goodarzi MO, Shah NA, Antoine HJ, Pall M, Guo X, Azziz R. Variants in the 5alpha-reductase type 1 and type 2 genes are associated with polycystic ovary syndrome and the severity of hirsutism in affected women. J Clin Endocrinol Metab 2006; 91: 4085-91. 24 Hahn S, Fingerhut A, Khomtsiv U, et al. The peroxisome proliferator activated receptor gamma Pro12Ala polymorphism is associated with a lower hirsutism score and increased insulin sensitivity in women with poycystic ovary syndrome. Clin Endocrinol (Oxf) 2005; 62: 573-9. 25 Ehrmann DA. Polycystic ovary syndrome. N Engl J Med 2005; 352: 1223-36. 26 Rotterdam ESHRE/ASRM-Sponsored 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. 27 Joseph-Horne R, Mason H, Batty S, et al. Luteal phase progesterone excretion in ovulatory women with polycystic ovaries. Hum Reprod 2002; 17: 1459-63. 28 Souter I, Sanchez LA, Perez M, Bartolucci AA, Azziz R. The prevalence of androgen excess among patients with minimal unwanted hair growth. Am J Obstet Gynecol 2004; 191: 1914-20. 29 Rigopoulos D, Georgala S. Pathogenesis of hirsutism. In: Camacho FM, Randall VA, Price VH, eds. Hair and its disorders: biology, pathology and management. London: Martin Dunitz, 2000: 33-5. 30 Azziz R, Carmina E, Sawaya ME. Idiopathic hirsutism. Endocr Rev 2000; 21: 347-62. 31 Reingold SB, Rosenfield RL. The relationship of mild hirsutism or acne in women to androgens. Arch Dermatol 1987; 123: 209-12. 32 Ehrmann DA, Rosenfield RL, Barnes RB, Brigell DF, Sheikh Z. Detection of functional ovarian hyperandrogenism in women with androgen excess. N Engl J Med 1992; 327: 157-62. 33 Polson DW, Adams J, Wadsworth J, Franks S. Polycystic ovaries – a common finding in normal women. Lancet 1988; 1: 870-2. 34 Glintborg D, Hermann AP, Brusgaard K, Hangaard J, Hagen C, Andersen M. Significantly higher adrenocorticotropin-stimulated cortisol and 17-hydroxyprogesterone levels in 337 consecutive, premenopausal, caucasian, hirsute patients compared with healthy controls. J Clin Endocrinol Metab 2005; 90: 1347-53. 35 Azziz R, Waggoner WT, Ochoa T, Knochenhauer ES, Boots LR. Idiopathic hirsutism: An uncommon cause of hirsutism in Alabama. Fertil Steril 1998; 70: 274-8. 36 Carmina E. Prevalence of idiopathic hirsutism. Eur J Endocrinol 1998; 139: 421-3. 37 Barbieri RL, Ryan KJ. Hyperandrogenism, insulin resistance, and acanthosis nigricans syndrome: A common endocrinopathy with distinct pathophysiologic features. Am J Obstet Gynecol 1983; 147: 90-101. 38 Legro RS, Finegood D, Dunaif A. A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1998; 83: 2694-8. 39 Hatch R, Rosenfield RL, Kim MH, Tredway D. Hirsutism: implications, etiology, and management. Am J Obstet Gynecol 1981; 140: 815-30. 40 Chang WY, Knochenhauer ES, Bartolucci AA, Azziz R. Phenotypic spectrum of polycystic ovary syndrome: clinical and biochemical characterization of the three major clinical subgroups. Fertil Steril 2005; 83: 1717-23. 41 Hahn S, Kuehnel W, Tan S, et al. Diagnostic value of calculated testosterone indices in the assessment of polycystic ovary syndrome. Clin Chem Lab Med 2007; 45: 202-7. 42 Sowers M, Derby C, Jannausch ML, Torrens JI, Pasternak R. Insulin Resistance, Hemostatic Factors, and Hormone Interactions in Pre- and Perimenopausal Women: SWAN. J Clin Endocrinol Metab 2003; 88: 4904-10. 43 Escobar-Morreale HF, Asuncion M, Calvo RM, Sancho J, San Millan JL. Receiver operating characteristic analysis of the performance of basal serum hormone profiles for the diagnosis of polycystic ovary syndrome in epidemiological studies. Eur J Endocrinol 2001; 145: 619-24. 44 Azziz R, Sanchez LA, Knochenhauer ES, et al. Androgen excess in women: experience with over 1000 consecutive patients. J Clin Endocrinol Metab 2004; 89: 453-62. 45 Wild RA, Umstot ES, Andersen RN, Ranney GB, Givens JR. Androgen parameters and their correlation with body weight in one hundred thirty-eight women thought to have hyperandrogenism. Am J Obstet Gynecol 1983; 146: 602-6. 46 Rittmaster RS. Hirsutism. Lancet 1997; 349: 191-5. 47 Sathyapalan T, Atkin SL. Rational testing: Investigating hirsutism. Br Med J 2009; in press. 48 Wajchenberg BL, Albergaria Pereira MA, Medonca BB, et al. Adrenocortical carcinoma: clinical and laboratory observations. Cancer 2000; 88: 711-36. 49 Azziz R. Diagnostic criteria for polycystic ovary syndrome: a reappraisal. Fertil Steril 2005; 83: 1343-6. |
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