85
Views
0
CrossRef citations to date
0
Altmetric
Review

An updated clinico-investigative approach to diagnosis of cutaneous hyperandrogenism in relation to adult female acne, female pattern alopecia & hirsutism a primer for dermatologists

ORCID Icon, ORCID Icon, , &
Pages 111-128 | Received 16 Jun 2023, Accepted 21 Dec 2023, Published online: 11 Jan 2024

References

  • Panidis D, Tziomalos K, Papadakis E, et al. The clinical significance and primary determinants of hirsutism in patients with polycystic ovary syndrome. Eur J Endocrinol. 2013;168(6):871–877. doi: 10.1530/EJE-13-0039
  • Taylor HS, Lubna P, Seli E. In:hirsustism. Speroff’s clinical gynecologic endocrinology and Infertility. 9th ed. Philadelphia: Lippincott Williams & Wilkins; 2020. p. 1050–1062.
  • Burger HG. Androgen production in women. Fertil Steril. 2002;77:S3–S5. doi: 10.1016/S0015-0282(02)02985-0
  • Thiboutot D, Jabara S, McAllister JM, et al. Human skin is a steroidogenic tissue: steroidogenic enzymes and cofactors are expressed in epidermis, normal sebocytes, and an immortalized sebocyte cell line (SEB-1). J Invest Dermatol. 2003;120:905–914. doi: 10.1046/j.1523-1747.2003.12244.x
  • Sardana K, Bansal P, Sharma LK, et al. A study comparing the clinical and hormonal profile of late onset and persistent acne in adult females. Int J Dermatol. 2020;59(4):428–433. doi: 10.1111/ijd.14748
  • Azzouni F, Godoy A, Li Y, et al. The 5 alpha-reductase isozyme family: a review of basic biology and their role in human diseases. Adv Urol. 2012;2012:530121. doi: 10.1155/2012/530121
  • Chen WC, Zouboulis CC. Hormones and the pilosebaceous unit. Dermatoendocrinol. 2009;1:81–86. doi: 10.4161/derm.1.2.8354
  • Carmina E, Stanczyk FZ, Matteri RK, et al. Serum androsterone conjugates differentiate between acne and hirsutism in hyperandrogenic women. Fertil Steril. 1991;55(5):872–876. doi: 10.1016/S0015-0282(16)54290-3
  • Cunha MG, Martins CP, Filho CD, et al. Acne in adult women and the markers of peripheral 3 alpha-diol G activity. J Cosmet Dermatol. 2016;15:330–334. doi: 10.1111/jocd.12232
  • Azziz R, Carmina E, Dewailly D, et al. The androgen excess and PCOS society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009;91(2):456–488. doi: 10.1016/j.fertnstert.2008.06.035
  • Rosenfield RL, Lucky AW. Acne, hirsutism, and alopecia in adolescent girls. Clinical expressions of androgen excess. Endocrinol Metab Clin North Am. 1993;22:507–532. doi: 10.1016/S0889-8529(18)30148-8
  • Lucky AW, McGuire J, Rosenfield RL, et al. Plasma androgens in women with acne vulgaris. J Invest Dermatol. 1983;81(1):70–74. doi: 10.1111/1523-1747.ep12539043
  • Deplewski D, Rosenfield RL. Role of hormones in pilosebaceous unit development. Endocr Rev. 2000;21(4):363–392. doi: 10.1210/edrv.21.4.0404
  • Makrantonaki E, Zouboulis CC. Testosterone metabolism to 5alpha-dihydrotestosterone and synthesis of sebaceous lipids is regulated by the peroxisome proliferator-activated receptor ligand linoleic acid in human sebocytes. Br J Dermatol. 2007;156:428–432. doi: 10.1111/j.1365-2133.2006.07671.x
  • Vexiau P, Husson C, Chivot M, et al. Androgen excess in women with acne alone compared with women with acne and/or hirsutism. J Invest Dermatol. 1990;94(3):279–283. doi: 10.1111/1523-1747.ep12874121
  • Chen W, Thiboutot D, Zouboulis CC. Cutaneous androgen metabolism: basic research and clinical perspectives. J Invest Dermatol. 2002;119(5):992–1007. doi: 10.1046/j.1523-1747.2002.00613.x
  • Rocha M, Cardozo KHM, Carvalho VM, et al. ADT-G as a promising biomarker for peripheral hyperandrogenism in adult female acne. Dermatoendocrinol. 2017;9:e1361571. doi: 10.1080/19381980.2017.1361571
  • Lookingbill DP, Demers LM, Tigelaar RE, et al. Effect of isotretinoin on serum levels of precursor and peripherally derived androgens in patients with acne. Arch Dermatol. 1988;124:540–543. doi: 10.1001/archderm.1988.01670040042019
  • Guzel AI, Kuyumcuoğlu U, Celik Y. Factors affecting the degree of hirsutism in patients with polycystic ovary syndrome. Arch Gynecol Obstet. 2012;285(3):767–770. doi: 10.1007/s00404-011-2077-5
  • Carmina E, Lobo RA. Evidence for increased androsterone metabolism in some normoandrogenic women with acne. J Clin Endocrinol Metab. 1993;76:1111–1114. doi: 10.1210/jc.76.5.1111
  • Teede HJ, Tay CT, Laven J, et al. International PCOS network. Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril. 2023;120(4):767–793. doi: 10.1016/j.fertnstert.2023.07.025.
  • Yildiz BO, Bolour S, Woods K, et al. Visually scoring hirsutism. Hum Reprod Update. 2010;16(1):51–64. doi: 10.1093/humupd/dmp024
  • Montalto J, Whorwood CB, Funder JW, et al. Plasma C19 steroid sulphate levels and indices of androgen bioavailability in female pattern androgenic alopecia. Clin Endocrinol (Oxf). 1990;32(1):1–12. doi: 10.1111/j.1365-2265.1990.tb03744.x
  • Sánchez P, Serrano-Falcón C, Torres JM, et al. 5α-reductase isozymes and aromatase mRNA levels in plucked hair from young women with female pattern hair loss. Arch Dermatol Res. 2018;310(1):77–83. doi: 10.1007/s00403-017-1798-0
  • Futterweit W, Dunaif A, Yeh HC, et al. The prevalence of hyperandrogenism in 109 consecutive female patients with diffuse alopecia. J Am Acad Dermatol. 1988;19(5):831–836. doi: 10.1016/S0190-9622(88)70241-8
  • Carmina E, Rosato F, Jannì A, et al. Extensive clinical experience: relative prevalence of different androgen excess disorders in 950 women referred because of clinical hyperandrogenism. J Clin Endocrinol Metab. 2006;91(1):2–6. doi: 10.1210/jc.2005-1457
  • Bermon S Manual of endocrinology and metabolism. 5th Edn. Norman Lavin: The Female Athelete; [cited 21 Jan 2023]. Available from: https://online.vitalsource.com
  • Tagatz GE, Kopher RA, Nagel TC, et al. The clitoral index: a bioassay of androgenic stimulation. Obstet Gynecol. 1979;54:562–564.
  • Afifi L, Saeed L, Pasch LA, et al. Association of ethnicity, Fitzpatrick skin type, and hirsutism: a retrospective cross-sectional study of women with polycystic ovarian syndrome. Int J Womens Dermatol. 2017;3:37–43. doi: 10.1016/j.ijwd.2017.01.006
  • Zawadski JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens J, Haseltine F Merriam G, editors. Polycystic ovary syndrome. Boston: Blackwell Scientific Publications; 1992. p. 377–384.
  • 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(1):19–25. doi: 10.1016/j.fertnstert.2003.10.004
  • Kumar A, Woods KS, Bartolucci AA, et al. Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (PCOS). Clin Endocrinol (Oxf). 2005;62(6):644–649. doi: 10.1111/j.1365-2265.2005.02256.x
  • Azziz R, Sanchez LA, Knochenhauer ES, et al. Androgen excess in women: experience with over 1000 consecutive patients. J Clin Endocrinol Metab. 2004;89(2):453–462. doi: 10.1210/jc.2003-031122.
  • Teede HJ, Misso ML, Costello MF, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod. 2018;33:1602–1618. doi: 10.1093/humrep/dey256
  • Azziz R, Carmina E, Sawaya ME. Idiopathic hirsutism. Endocr Rev. 2000;21(4):347–362. doi: 10.1210/edrv.21.4.0401
  • Paulson RJ, Serafini PC, Catalino JA, et al. Measurements of 3 alpha,17 beta-androstanediol glucuronide in serum and urine and the correlation with skin 5 alpha-reductase activity. Fertil Steril. 1986;46:222–226. doi: 10.1016/S0015-0282(16)49515-4
  • Barbieri RL, Ryan KJ. Hyperandrogenism, insulin resistance, and acanthosis nigricans syndrome: a common endocrinopathy with distinct pathophysiologic features. Am J Obstet Gynecol. 1983;147(1):90–101. doi: 10.1016/0002-9378(83)90091-1
  • Nagamani M, Van Dinh T, Kelver ME. Hyperinsulinemia in hyperthecosis of the ovaries. Am J Obstet Gynecol. 1986;154(2):384–389. doi: 10.1016/0002-9378(86)90676-9
  • Meczekalski B, Szeliga A, Maciejewska ‐Jeske M, et al. Hyperthecosis: an underestimated nontumorous cause of hyperandrogenism. Gynecol Endocrinol. 2021;37:677‐682. doi: 10.1080/09513590.2021.1903419
  • Rousset P, Gompel A, Christin-Maitre S, et al. Ovarian hyperthecosis on gray-scale and color doppler ultrasound. Ultrasound Obstet Gynecol. 2008;32:694–699. doi: 10.1002/uog.6131
  • Friedman CI, Schmidt GE, Kim MH, et al. Serum testosterone concentrations in the evaluation of androgen-producing tumors. Am J Obstet Gynecol. 1985;153(1):44–49. doi: 10.1016/0002-9378(85)90587-3
  • Yance VRV, Marcondes JAM, Rocha MP, et al. Discriminating between virilizing ovary tumors and ovary DHEAS in postmenopausal women: clinical data, hormonal profiles and image studies. Eur J Endocrinol. 2017;177:93–102. doi: 10.1530/EJE-17-0111
  • Derksen J, Nagesser SK, Meinders AE, et al. Identification of virilizing adrenal tumors in hirsute women. N Engl J Med. 1994;331(15):968–973. doi: 10.1056/NEJM199410133311502
  • Nanba AT, Rege J, Ren J, et al. 11-oxygenated C19 steroids do not decline with age in women. J Clin Endocrinol Metab. 2019;104(7):2615–2622. doi: 10.1210/jc.2018-02527
  • Moran C, Azziz R. 21-hydroxylase-deficient nonclassic adrenal hyperplasia: the great pretender. Semin Reprod Med. 2003;21:295–300.
  • White PC, Speiser PW. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev. 2000;21(3):245–291. doi: 10.1210/edrv.21.3.0398
  • Spritzer P, Billaud L, Thalabard JC, et al. Cyproterone acetate versus hydrocortisone treatment in late-onset adrenal hyperplasia. J Clin Endocrinol Metab. 1990;70(3):642–646. doi: 10.1210/jcem-70-3-642
  • Nieman LK, Biller BM, Findling JW, et al. The diagnosis of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2008;93:1526‐1540. doi: 10.1210/jc.2008-0125
  • O’Driscoll JB, Mamtora H, Higginson J, et al. 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 (Oxf). 1994;41(2):231–236. doi: 10.1111/j.1365-2265.1994.tb02535.x
  • Wu S, Divall S, Nwaopara A, et al. Obesity-induced infertility and hyperandrogenism are corrected by deletion of the insulin receptor in the ovarian theca cell. Diabetes. 2014;63(4):1270–1282. doi: 10.2337/db13-1514
  • Welt CK, Carmina E. Clinical review: lifecycle of polycystic ovary syndrome (PCOS): from in utero to menopause. J Clin Endocrinol Metab. 2013;98(12):4629–4638. doi: 10.1210/jc.2013-2375
  • Penttilä TL, Koskinen P, Penttilä TA, et al. Obesity regulates bioavailable testosterone levels in women with or without polycystic ovary syndrome. Fertil Steril. 1999;71(3):457–461. doi: 10.1016/S0015-0282(98)00473-7
  • Davis SR, Baber R, Panay N, et al. Global consensus position statement on the use of testosterone therapy for women. J Clin Endocrinol Metab. 2019;104:4660–4666. doi: 10.1210/jc.2019-01603
  • Markopoulos MC, Kassi E, Alexandraki KI, et al. Management of endocrine disease: Hyperandrogenism after menopause. Eur J Endocrinol. 2015;172(2):R79–R91. doi: 10.1530/EJE-14-0468
  • Löfgren E, Tapanainen JS, Koivunen R, et al. Effects of carbamazepine and oxcarbazepine on the reproductive endocrine function in women with epilepsy. Epilepsia. 2006;47:1441–1446. doi: 10.1111/j.1528-1167.2006.00506.x
  • Hu X, Wang J, Dong W, et al. A meta-analysis of polycystic ovary syndrome in women taking valproate for epilepsy. Epilepsy Res. 2011;97(1–2):73–82. doi: 10.1016/j.eplepsyres.2011.07.006
  • Redmond GP. Thyroid dysfunction and women’s reproductive health. Thyroid: Offic J Am Thyroid Association. 2004;14 Suppl 1:S5–S15. doi: 10.1089/105072504323024543
  • Krassas GE, Pontikides N, Kaltsas T, et al. Disturbances of menstruation in hypothyroidism. Clin Endocrinol (Oxf). 1999;50(5):655–659. doi: 10.1046/j.1365-2265.1999.00719.x
  • Schiebinger RJ, Chrousos GP, GB C Jr, et al. The effect of serum prolactin on plasma adrenal androgens and the production and metabolic clearance rate of dehydroepiandrosterone sulfate in normal and hyperprolactinemic subjects. J Clin Endocrinol Metab. 1986;62:202–209. doi: 10.1210/jcem-62-1-202
  • Kaltsas GA, Androulakis II, Tziveriotis K, et al. Polycystic ovaries and the polycystic ovary syndrome phenotype in women with active acromegaly. Clin Endocrinol (Oxf). 2007;67:917–922. doi: 10.1111/j.1365-2265.2007.02987.x
  • Abou Sherif S, Newman R, Haboosh S, et al. Investigating the potential of clinical and biochemical markers to differentiate between functional hypothalamic amenorrhoea and polycystic ovarian syndrome: a retrospective observational study. Clin Endocrinol (Oxf). 2021;95(4):618–627. doi: 10.1111/cen.14571
  • Carmina E, Stanczyk FZ, Lobo AR. Evaluation of hormonal status. In: Strauss F, Barbieri R, and Gargiulo A, editors. Yen & Jaffe’s reproductive endocrinology physiology, pathophysiology, and clinical. 8th ed. Vol. 34. Philadelphia: Elsevier; 2019, p. 887–915.e4.
  • Salameh WA, Redor-Goldman MM, Clarke NJ, et al. Specificity and predictive value of circulating testosterone assessed by tandem mass spectrometry for the diagnosis of polycystic ovary syndrome by the National Institutes of Health 1990 criteria. Fertil Steril. 2014;101(4):1135–1141.e2. doi: 10.1016/j.fertnstert.2013.12.056
  • Sharma A, Kapoor E, Singh RJ, et al. Diagnostic thresholds for androgen-producing tumors or pathologic hyperandrogenism in women by use of total testosterone concentrations measured by liquid chromatography-tandem mass spectrometry. Clin Chem. 2018;64(11):1636–1645. doi: 10.1373/clinchem.2018.290825
  • Redmond GP, Bergfeld WF. Diagnostic approach to androgen disorders in women: acne, hirsutism, and alopecia. Cleve Clin J Med. 1990;57(5):423–427. doi: 10.3949/ccjm.57.5.423
  • Elhassan YS, Idkowiak J, Smith K, et al. Causes, patterns, and severity of androgen excess in 1205 consecutively recruited women. J Clin Endocrinol Metab. 2018;103(3):1214–1223. doi: 10.1210/jc.2017-02426
  • Matteri RK, Stanczyk FZ, Gentzschein EE, et al. Androgen sulfate and glucuronide conjugates in nonhirsute and hirsute women with polycystic ovarian syndrome. Am J Obstet Gynecol. 1989;16:1704–1709. doi: 10.1016/0002-9378(89)90954-X
  • Vexiau P, Chaspoux C, Boudou P, et al. Role of androgens in female-pattern androgenetic alopecia, either alone or associated with other symptoms of hyperandrogenism. Arch Dermatol Res. 2000;292(12):598–604. doi: 10.1007/s004030000184
  • Azziz R, Hincapie LA, Knochenhauer ES, et al. Screening for 21-hydroxylase-deficient nonclassic adrenal hyperplasia among hyperandrogenic women: a prospective study. Fertil Steril. 1999;72:915–925. doi: 10.1016/S0015-0282(99)00383-0
  • Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(2):273–288. doi: 10.1210/jc.2010-1692
  • Dumont A, Robin G, Catteau-Jonard S, et al. Role of anti-müllerian hormone in pathophysiology, diagnosis and treatment of polycystic ovary syndrome: a review. Reprod Biol Endocrinol. 2015;13(1):137. doi: 10.1186/s12958-015-0134-9
  • Sahmay S, Aydin Y, Oncul M, et al. Diagnosis of polycystic ovary syndrome: AMH in combination with clinical symptoms. J Assist Reprod Genet. 2014;31(2):213–220. doi: 10.1007/s10815-013-0149-0
  • Anand S, Kumar A, Prasad A, et al. Updated meta-analysis on the diagnostic accuracy of serum anti-mullerian hormone in poly cystic ovary syndrome involving 13 509 subjects. J Obstet Gynaecol Res. 2022;48:2162–2174.
  • Chang AY. Polycsytic ovarian syndrome. In: Lavin N, editor. Manual of endocrinology and metabolism. Norman Lavin. 5th edn ed. Wolter Kluwer; 2019. p. 301–304.
  • Cussen L, McDonnell T, Bennett G, et al. Approach to androgen excess in women: clinical and biochemical insights. Clin Endocrinol (Oxf). 2022;97(2):174–186. doi: 10.1111/cen.14710
  • Cibula D, Hill M, Starka L. The best correlation of the new index of hyperandrogenism with the grade of increased body hair. Eur J Endocrinol. 2000;143:405–408. doi: 10.1530/eje.0.1430405
  • Escobar-Morreale HF, Carmina E, Dewailly D, et al. Epidemiology, diagnosis and management of hirsutism: a consensus statement by the androgen excess and polycystic ovary syndrome society. Hum Reprod Update. 2012;18(2):146–170. doi: 10.1093/humupd/dmr042
  • Amiri M, Ramezani Tehrani F, Nahidi F, et al. Association between biochemical hyperandrogenism parameters and Ferriman-Gallwey score in patients with polycystic ovary syndrome: a systematic review and meta-regression analysis. Clin Endocrinol (Oxf). 2017;87(3):217–230. doi: 10.1111/cen.13389
  • Azziz R, Carmina E, Dewailly D, et al. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an androgen excess society guideline. J Clin Endocrinol Metab. 2006;91(11):4237–4245. doi: 10.1210/jc.2006-0178
  • Rosner W, Auchus RJ, Azziz R, et al. Position statement: utility, limitations, and pitfalls in measuring testosterone: an endocrine society position statement. J Clin Endocrinol Metab. 2007;92(2):405–413. doi: 10.1210/jc.2006-1864
  • Stanczyk FZ, Lee JS, Santen RJ. Standardization of steroid hormone assays: why, how, and when? Cancer Epidemiol Biomarkers Prev. 2007;16(9):1713–1719. doi: 10.1158/1055-9965.EPI-06-0765
  • Legro RS, Schlaff WD, Diamond MP, et al. Total testosterone assays in women with polycystic ovary syndrome: precision and correlation with hirsutism. J Clin Endocrinol Metab. 2010;95(12):5305–5313. doi: 10.1210/jc.2010-1123
  • Griffing GT, Melby JC. Hirsutism causes and treatments. Hosp Pract (Off Ed). 1991;26:43–58.
  • Wild RA, Umstot ES, Andersen RN, et al. Androgen parameters and their correlation with body weight in one hundred thirty-eight women thought to have hyperandrogenism. Am J Obstet Gynecol. 1983;146(6):602–606. doi: 10.1016/0002-9378(83)90998-5
  • Bailey-Pridham DD, Sanfilippo JS. Hirsutism in the adolescent female. Pediatr Clin North Am. 1989;36(3):581–599. doi: 10.1016/S0031-3955(16)36687-1
  • Lemay A, Dewailly SD, Grenier R, et al. Attenuation of mild hyperandrogenic activity in postpubertal acne by a triphasic oral contraceptive containing low doses of ethynyl estradiol and d,l-norgestrel. J Clin Endocrinol Metab. 1990;71(1):8–14. doi: 10.1210/jcem-71-1-8
  • Reingold SB, Rosenfield RL. The relationship of mild hirsutism or acne in women to androgens. Arch Dermatol. 1987;123:209–212. doi: 10.1001/archderm.1987.01660260079018
  • Levell MJ, Cawood ML, Burke B, et al. Acne is not associated with abnormal plasma androgens. Br J Dermatol. 1989;120(5):649–654. doi: 10.1111/j.1365-2133.1989.tb01351.x
  • Rittmaster RS, Loriaux DL. Hirsutism. Ann Intern Med. 1987;106:95–107. doi: 10.7326/0003-4819-106-1-95
  • Selby C. Sex hormone binding globulin: origin, function and clinical significance. Ann Clin Biochem. 1990;27(6):532–541. doi: 10.1177/000456329002700603
  • Gupta MK. Androgen assessment in hirsutism and alopecia. Cleve Clin J Med. 1990;57(3):292–297. doi: 10.3949/ccjm.57.3.292
  • Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84(10):3666–3672. doi: 10.1210/jcem.84.10.6079
  • Miller KK, Rosner W, Lee H, et al. Measurement of free testosterone in normal women and women with androgen deficiency: comparison of methods. J Clin Endocrinol Metab. 2004;89(2):525–533. doi: 10.1210/jc.2003-030680
  • Chang WY, Knochenhauer ES, Bartolucci AA, et al. Phenotypic spectrum of polycystic ovary syndrome: clinical and biochemical characterization of the three major clinical subgroups. Fertil Steril. 2005;83(6):1717–1723. doi: 10.1016/j.fertnstert.2005.01.096
  • Pasquali R, Zanotti L, Fanelli F, et al. Defining hyperandrogenism in women with polycystic ovary syndrome: a challenging perspective. J Clin Endocrinol Metab. 2016;101(5):2013–2022. doi: 10.1210/jc.2015-4009
  • Schwartz U, Moltz L, Brotherton J, et al. The diagnostic value of plasma free testosterone in non-tumorous and tumorous hyperandrogenism. Fertil Steril. 1983;40(1):66–72. doi: 10.1016/S0015-0282(16)47179-7
  • Keevil BG, Adaway J, Fiers T, et al. The free androgen index is inaccurate in women when the SHBG concentration is low. Clin Endocrinol (Oxf). 2018;88(5):706–710. doi: 10.1111/cen.13561
  • Fogh H, Worm AM, Forkert B, et al. Androgens in hirsute women referred for electroepilation. Acta Derm Venereol. 1989;69:179–182.
  • Blight LF, Judd SJ, White GH. Relative diagnostic value of serum non-SHBG-bound testosterone, free androgen index and free testosterone in the assessment of mild to moderate hirsutism. Ann Clin Biochem. 1989;26(Pt 4):311–316. doi: 10.1177/000456328902600402
  • Kirschner MA, Bardin CW. Androgen production and metabolism in normal and virilized women. Metabolism. 1972;21(7):667–688. doi: 10.1016/0026-0495(72)90090-X
  • Artar G, Tas B, Turan G, et al. Evaluation of androgen-dependent skin findings of polycystic ovary syndrome (PCOS). Gynecol Endocrinol. 2022;29:1–5. doi: 10.1080/09513590.2022.2162496
  • Bansal P, Sardana K, Sharma L, et al. A prospective study examining isolated acne and acne with hyperandrogenic signs in adult females. J DermatolTreat. 2021;32(7):752–755. doi: 10.1080/09546634.2019.1708245
  • Santoro N, Banwell T, Tortoriello D, et al. Effects of aging and gonadal failure on the hypothalamic-pituitary axis in women. Am J Obstet Gynecol. 1998;178(4):732–741. doi: 10.1016/S0002-9378(98)70483-1
  • Marynick SP, Chakmakjian ZH, McCaffree DL, et al. Androgen excess in cystic acne. N Engl J Med. 1983;308:981–986. doi: 10.1056/NEJM198304283081701
  • Medda F, Nieddu R, Fiore R, et al. Hormonal profile and androgen status during the menstrual cycle in women with acne. Clin Exp Obstet Gynecol. 1988;15:137–142.
  • Laue L, Peck GL, Loriaux DL, et al. Adrenal androgen secretion in postadolescent acne: increased adrenocortical function without hypersensitivity to adrenocorticotropin. J Clin Endocrinol Metab. 1991;73(2):380–384. doi: 10.1210/jcem-73-2-380
  • Maroulis GB, Maroulis GB. Evaluation of hirsutism and hyperandrogenemia. FertilSteril. 1981;36:273–305. doi: 10.1016/S0015-0282(16)45728-6
  • Khandekar S, Lata V, Dash RJ. Circulating androgens in hirsutism. J Assoc Physicians India. 1989;37:632–635.
  • O’Reilly MW, Taylor AE, Crabtree NJ, et al. Hyperandrogenemia predicts metabolic phenotype in polycystic ovary syndrome: the utility of serum androstenedione. J Clin Endocrinol Metab. 2014;99(3):1027–1036. doi: 10.1210/jc.2013-3399
  • Joura EA, Geusau A, Schneider B, et al. Serum 3 alpha-androstanediol-glucuronide is decreased in nonhirsute women with acne vulgaris. Fertil Steril. 1996;66:1033-1035–6. doi: 10.1016/S0015-0282(16)58705-6
  • Maffazioli GDN, Bachega T, Hayashida SAY, et al. Steroid screening tools differentiating nonclassical congenital adrenal hyperplasia and polycystic ovary syndrome. J Clin Endocrinol Metab. 2020;105:dgaa369. doi: 10.1210/clinem/dgaa369
  • Carmina E, Dewailly D, Escobar-Morreale HF, et al. Non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency revisited: an update with a special focus on adolescent and adult women. Hum Reprod Update. 2017;23(5):580–599. doi: 10.1093/humupd/dmx014
  • Chen K, Chen S, Lu L, et al. An optimized pathway for the differential diagnosis of ACTH-dependent cushing’s syndrome based on low-dose dexamethasone suppression test. Front Endocrinol. 2021;12:720823. doi: 10.3389/fendo.2021.720823
  • Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and treatment of primary adrenal insufficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(2):364–389. doi: 10.1210/jc.2015-1710
  • Polan ML, Behrman HR. Prolactin-stimulated ovarian androgen metabolism. Am J Obstet Gynecol. 1981;139(4):487–491. doi: 10.1016/0002-9378(81)90330-6
  • Gruijters MJ, Visser JA, Durlinger AL, et al. Anti-Müllerian hormone and its role in ovarian function. Mol Cell Endocrinol. 2003;211:85–90. doi: 10.1016/j.mce.2003.09.024
  • Pigny P, Merlen E, Robert Y, et al. Elevated serum level of anti-mullerian hormone in patients with polycystic ovary syndrome: relationship to the ovarian follicle excess and to the follicular arrest. J Clin Endocrinol Metab. 2003;88(12):5957–5962. doi: 10.1210/jc.2003-030727
  • Bansal P, Sardana K, Arora P, et al. A prospective study of anti-mullerian hormone and other ovarian and adrenal hormones in adult female acne. Dermatol Ther. 2020;33(6):e13974. doi: 10.1111/dth.13974
  • Zhang M, Liu X, Xu X, et al. The reference value of anti-Müllerian hormone to diagnose polycystic ovary syndrome is inversely associated with BMI: a retrospective study. Reprod Biol Endocrinol. 2023;21(1):15. doi: 10.1186/s12958-023-01064-y
  • Ramezani Tehrani F, Rahmati M, Mahboobifard F, et al. Age-specific cut-off levels of anti-Müllerian hormone can be used as diagnostic markers for polycystic ovary syndrome. Reprod Biol Endocrinol. 2021;19(1):76. doi: 10.1186/s12958-021-00755-8
  • Jacob SL, Field HP, Calder N, et al. Anti-Müllerian hormone reflects the severity of polycystic ovary syndrome. Clin Endocrinol (Oxf). 2017;86(3):395–400. doi: 10.1111/cen.13269
  • Yue CY, Lu LK, Li M, et al. Threshold value of anti-Mullerian hormone for the diagnosis of polycystic ovary syndrome in Chinese women. PLoS One. 2018;13:e0203129. doi: 10.1371/journal.pone.0203129
  • van den Berg MH, van Dulmen-den Broeder E, Overbeek A, et al. Comparison of ovarian function markers in users of hormonal contraceptives during the hormone-free interval and subsequent natural early follicular phases. Hum Reprod. 2010;25:1520–1527. doi: 10.1093/humrep/deq071
  • Visser JA, Schipper I, Laven JS, et al. Anti-Müllerian hormone: an ovarian reserve marker in primary ovarian insufficiency. Nat Rev Endocrinol. 2012;8:331–341. doi: 10.1038/nrendo.2011.224
  • Tsukui Y, Kitahara Y, Hasegawa Y, et al. Anti-Müllerian hormone levels in the diagnosis of adolescent polycystic ovarian syndrome: a systematic review and meta-analysis. Endocr J. 2022;69(8):897–906. doi: 10.1507/endocrj.EJ22-0081
  • Dumesic DA, Oberfield SE, Stener-Victorin E, et al. Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndrome. Endocr Rev. 2015;36(5):487–525. doi: 10.1210/er.2015-1018
  • Taylor AE, McCourt B, Martin KA, et al. Determinants of abnormal gonadotropin secretion in clinically defined women with polycystic ovary syndrome. J Clin Endocrinol Metab. 1997;82:2248–2256. doi: 10.1210/jc.82.7.2248
  • Outwater EK, Wagner BJ, Mannion C, et al. Sex cord-stromal and steroid cell tumors of the ovary. Radiographics. 1998;18(6):1523–1546. doi: 10.1148/radiographics.18.6.9821198
  • Prassopoulos V, Laspas F, Vlachou F, et al. Leydig cell tumour of the ovary localised with positron emission tomography/computed tomography. Gynecol Endocrinol. 2011;27(10):837–839. doi: 10.3109/09513590.2010.521263
  • Bancos I, Taylor AE, Chortis V, et al. Urine steroid metabolomics for the differential diagnosis of adrenal incidentalomas in the EURINE-ACT study: a prospective test validation study. Lancet Diabetes Endocrinol. 2020;8(9):773–781. doi: 10.1016/S2213-8587(20)30218-7
  • Rennert J, Doerfler A. Imaging of sellar and parasellar lesions. Clin Neurol Neurosur. 2007;109(2):111–124. doi: 10.1016/j.clineuro.2006.11.001
  • Bricaire C, Raynaud A, Benotmane A, et al. Selective venous catheterization in the evaluation of hyperandrogenism. J Endocrinol Invest. 1991;14(11):949–956. doi: 10.1007/BF03347121
  • Taylor L, Ayers JW, Gross MD, et al. Diagnostic considerations in virilization: iodomethyl-norcholesterol scanning in the localization of androgen secreting tumors. Fertil Steril. 1986;46:1005–1010. doi: 10.1016/S0015-0282(16)49871-7
  • Merhi ZO, Santoro N. Postmenopausal virilization after spousal use of topical androgens. Fertil Steril. 2007;87:976.e13–5. doi: 10.1016/j.fertnstert.2006.07.1547
  • Karrer-Voegeli S, Rey F, Reymond MJ, et al. Androgen dependence of hirsutism, acne, and alopecia in women: retrospective analysis of 228 patients investigated for hyperandrogenism. Medicine (Baltimore). 2009;88(1):32–45. doi: 10.1097/md.0b013e3181946a2c
  • Stuenkel CA, Manson JE. Compounded bioidentical hormone therapy: does the regulatory double standard harm women? JAMA Intern Med. 2017;177(12):1719–1720. doi: 10.1001/jamainternmed.2017.5141
  • Smit DL, Buijs MM, de Hon O, et al. Positive and negative side effects of androgen abuse. The HAARLEM study: a one-year prospective cohort study in 100 men. Scand J Med Sci Sports. 2021;31(2):427–438. doi: 10.1111/sms.13843
  • Carmina E, Gonzalez F, Chang L, et al. Reassessment of adrenal androgen secretion in women with polycystic ovary syndrome. Obstet Gynecol. 1995;85(6):971–976. doi: 10.1016/0029-7844(95)00065-Y
  • Carmina E. Ovarian and adrenal hyperandrogenism. Ann N Y Acad Sci. 2006;1092(1):130–137. doi: 10.1196/annals.1365.011
  • Rosner W. Letter to the editor: an extraordinarily inaccurate assay for free testosterone is still with us. J Clin Endocrinol Metab. 2001;86(6):2903. doi: 10.1210/jcem.86.6.7643
  • Morley JE, Patrick P, Perry HM. Evaluation of assays available to measure free testosterone. Metabolism. 2002;51:554–559. doi: 10.1053/meta.2002.31975
  • Horton R, Hawks D, Lobo R. 3 alpha, 17 beta-androstanediol glucuronide in plasma. A marker of androgen action in idiopathic hirsutism. J Clin Invest. 1982;69(5):1203–1206. doi: 10.1172/JCI110558
  • Kamilaris TC, DeBold CR, Manolas KJ, et al. Testosterone-secreting adrenal adenoma in a peripubertal girl. JAMA. 1987;258:2558–2561. doi: 10.1001/jama.1987.03400180092034
  • Kaltsas GA, Mukherjee JJ, Kola B, et al. Is ovarian and adrenal venous catheterization and sampling helpful in the investigation of hyperandrogenic women? Clin Endocrinol (Oxf). 2003;59(1):34–43. doi: 10.1046/j.1365-2265.2003.01792.x

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.