American Journal of Clinical Dermatology

, Volume 3, Issue 8, pp 571–578


Effect of Hormones on Pathogenesis and Management
Review Article


In the pathogenesis of acne, androgen hormones play a crucial role. In the treatment of acne, hormonal therapies provide valuable alternatives to standard modalities in selected women. Although numerous factors contribute to the development of acne, the requirement for androgens is absolute and is one that allows for effective treatments in women through inhibition of androgen expression. The two prerequisites for androgen expression at the level of the pilosebaceous unit are (i) the presence of androgen in the form of either testosterone or dihydrotestosterone; and (ii) functioning androgen receptors. A third component may be the metabolism of androgen precursors to active androgens within pilosebaceous units.

Hormonal treatment of hyperandrogenism (acne, hirsutism, androgenetic alopecia) such as that seen in polycystic ovary syndrome, centers on (i) reduction of circulating androgen levels and (ii) androgen receptor blockade. Combination oral contraceptives represent the primary treatment modality for reducing circulating androgens from ovarian and, to a lesser degree, adrenal sources. Newer formulations may also have clinically significant androgen receptor blocking and 5α-reductase inhibiting effects. Newer oral contraceptives have high safety profiles and are used widely internationally for this purpose. Androgen receptor blockers currently in use include spironolactone, cyproterone acetate, and flutamide. Androgen receptor blockers are frequently combined with oral contraceptives to achieve optimal results in selected women. In women with adrenal hyperplasia, low-dose corticosteroids may be added to reduce adrenal androgen precursors. Inhibition of enzymes of androgen metabolism in the pilosebaceous unit remain largely investigational in the treatment of acne, although the benefit of 5a-reductase (type 2) inhibition is established in androgenetic alopecia in men.

This article reviews the essentials of hormonal influence in acne pathogenesis, discusses the hormonal therapies most utilized in the treatment of acne, and the pre-treatment evaluation of women in whom hormonal therapies are being considered.


  1. 1.
    Deplewski D., Rosenfield R.L. Role of hormones in pilosebaceous unit development. Endocr Rev 2000 Aug; 21: 363–392PubMedCrossRefGoogle Scholar
  2. 2.
    Webster G.F. Inflammation in acne vulgaris. J Am Acad Dermatol 1995 Aug; 33: 247–253PubMedCrossRefGoogle Scholar
  3. 3.
    Webster G.F. Inflammatory acne represents hypersensitivity to Propionibacterium acnes. Dermatology 1998; 196: 80–81PubMedCrossRefGoogle Scholar
  4. 4.
    Hamilton J.B. Male hormone substance: a prime factor in acne. J Clin Endocrinol Metab 1941; 1: 570–592CrossRefGoogle Scholar
  5. 5.
    Pochi P.E., Strauss J.S., Mescon H. Sebum secretion and urinary fractional 17-ketosteroid and total 17-hydoxycorticoid excretion in male castrates. J Invest Dermatol 1962; 39: 475–483PubMedCrossRefGoogle Scholar
  6. 6.
    Lookingbill D.P., Horton R., Demers L.M., et al. Tissue production of androgens in women with acne. J Am Acad Dermatol 1985; 12: 481–487PubMedCrossRefGoogle Scholar
  7. 7.
    Thiboutot D., Gilliland K., Light J., et al. Androgen metabolism in sebaceous glands from subjects with and without acne. Arch Dermatol 1999; 135: 1041–1045PubMedCrossRefGoogle Scholar
  8. 8.
    Lucky A.W., Biro F.M., Simbartl L.A., et al. Predictors of severity of acne vulgaris in young adolescent girls: results of a five-year longitudinal study. J Pediatr 1997; 130: 30–39PubMedCrossRefGoogle Scholar
  9. 9.
    Vexiau.P, Huson 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: 279–283PubMedCrossRefGoogle Scholar
  10. 10.
    Slayden S.M., Moran C., Sams Jr W.M., et al. Hyperandrogenemia in patients presenting with acne. Fertil Steril 2001 May; 75 (5): 889–892PubMedCrossRefGoogle Scholar
  11. 11.
    Cibula D., Hill M., Vohradnikova O., et al. The role of androgens in determining acne severity in adult women. Br J Dermatol 2000; 143: 399–404PubMedCrossRefGoogle Scholar
  12. 12.
    Merrill B.J., Gat U., SasGupta R., et al. Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin. Genes Dev 2001; 15: 1688–1705PubMedCrossRefGoogle Scholar
  13. 13.
    Deplewski D., Rosenfield R.L. Growth hormone and insulin-like growth factors have different effects on sebaceous cell growth and differentiation. Endocrinology 1999; 140: 4089–4094PubMedCrossRefGoogle Scholar
  14. 14.
    Rosenfield R.L., Deplewski D., Kentsis A., et al. Mechanisms of androgen induction of sebocyte differentiation. Dermatology 1998; 196: 43–46PubMedCrossRefGoogle Scholar
  15. 15.
    Choudhry R., Hodgins M.B., Vandr Kwast T.H., et al. Localization of androgen receptors in human skin by immunohistochemistry: implications for the hormonal regulation of hair growth, sebaceous glands and sweat glands. J Endocrinol 1992; 133: 467–475PubMedCrossRefGoogle Scholar
  16. 16.
    Liang T., Hoyer S., Yu R., et al. Immunocytochemical localization of androgen receptors in human skin using monoclonal antibodies against the androgen receptor. J Invest Dermatol 1993; 100: 663–666PubMedCrossRefGoogle Scholar
  17. 17.
    Imperato-McGinley J., Gautier T., Cai L., et al. The androgen control of sebum production: studies of subjects with dihydrotestosterone deficiency and complete androgen insensitivity. J Clin Endocrinol Metab 1993; 76: 524–528PubMedCrossRefGoogle Scholar
  18. 18.
    Zouboulis C.C., Xia L., Akamatsu H., et al. The human sebocyte culture model provides new insights into development and management of seborrhea and acne. Dermatology 1998; 196: 21–31PubMedCrossRefGoogle Scholar
  19. 19.
    Thiboutot D., Bayne E., Thorne J., et al. Immunolocalization of 5alpha-reductase isozymes in acne lesions and normal skin. Arch Dermatol 2000 Sep; 136: 1125–1129PubMedCrossRefGoogle Scholar
  20. 20.
    Thiboutot D., Harris G., Iles V., et al. Activity of the type 1 5 alpha-reductase exhibits regional differences in isolated sebaceous glands and whole skin. J Invest Dermatol 1995 Aug; 105: 209–214PubMedCrossRefGoogle Scholar
  21. 21.
    Goulden V., Clark S.M., Cunliffe W.J. Post-adolescent acne: a review of clinical features. Br J Dermatol 1997; 136 (1): 66–70PubMedCrossRefGoogle Scholar
  22. 22.
    Shaw J.C. Low-dose adjunctive spironolactone in the treatment of acne in women: a retrospective analysis of 85 consecutively treated patients. J Am Acad Dermatol 2000; 43 (3): 498–502PubMedCrossRefGoogle Scholar
  23. 23.
    Shaw J.C. Persistent acne in adult women. Arch Dermatol 2001; 137: 1252–1253PubMedGoogle Scholar
  24. 24.
    Petitti D.B., Sidney S., Bernstein A., et al. Stroke in users of low-dose oral contraceptives. N Engl J Med 1996; 335: 8–15PubMedCrossRefGoogle Scholar
  25. 25.
    Lemay A., Dewailly S.D., 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: 8–14PubMedCrossRefGoogle Scholar
  26. 26.
    Charoenvisal C., Thaipisuttikul Y., Pinjaroen S., et al. Effects on acne of two oral contraceptives containing desogestrel and cyproterone acetate. Int J Fertil 1996; 41: 423–429Google Scholar
  27. 27.
    Dieben T.O., Vromans L., Theeuwes A., et al. The effects of CTR-24, a biphasic oral contraceptive combination, compared to Diane-35 in women with acne. Contraception 1994; 50: 373–382PubMedCrossRefGoogle Scholar
  28. 28.
    Janaud A., Rouffy J., Upmalis D., et al. A comparison study of lipid and androgen metabolism with triphasic oral contraceptive formulations containing norgestimate or levonorgestrel. Acta Obstet Gynecol Scand 1992; 71: 33–38CrossRefGoogle Scholar
  29. 29.
    Lucky A.W., Henderson T.A., Olson W.H., et al. Effectiveness of norgestimate and ethinyl estradiol in treating moderate acne vulgaris. J Am Acad Dermatol 1997; 37: 746–754PubMedCrossRefGoogle Scholar
  30. 30.
    Redmond G.P., Olson W.H., Lippman J.S., et al. Norgestimate and ethinyl estradiol in the treatment of acne vulgaris: a randomized, placebo-controlled trial. Obstet Gynecol 1997; 89: 615–622PubMedCrossRefGoogle Scholar
  31. 31.
    Foidart J.M. The contraceptive profile of a new oral contraceptive with antimineralocorticoid and antiandrogenic effects. Eur J Contracept Reprod Health Care 2000; 5 Suppl. 3: 25–33Google Scholar
  32. 32.
    Fuhrmann U., Krattenmacher R., Slater E.P., et al. The novel progestin drospirenone and its natural counterpart progesterone: biochemical profile and antiandrogenic potential. Contraception 1996; 54: 243–251PubMedCrossRefGoogle Scholar
  33. 33.
    Shaw J.C. Hormonal therapy in dermatology. Dermatol Clin 2001; 19: 169–178PubMedCrossRefGoogle Scholar
  34. 34.
    Mant J., Painter R., Vessey M. Risk of myocardial infarction, angina and stroke in users of oral contraceptives: an updated analysis of a cohort study. Br J Obstet Gynaecol 1998; 105: 890–896PubMedCrossRefGoogle Scholar
  35. 35.
    Ober K.P., Hennessy J.F. Spironolactone therapy for hirsutism in a hyperandrogenic woman. Ann Intern Med 1978; 89: 643–644PubMedGoogle Scholar
  36. 36.
    Goodfellow A., Alaghband-Zadeh J., Carter G., et al. Oral spironolactone improves acne vulgaris and reduces sebum excretion. Br J Dermatol 1984; 111: 124–125CrossRefGoogle Scholar
  37. 37.
    Burke B.M., Cunliffe W.J. Oral spironolactone therapy for female patients with acne, hirsutism or androgenic alopecia [letter]. Br J Dermatol 1985; 112: 124–125PubMedCrossRefGoogle Scholar
  38. 38.
    Hatwal A., Bhatt R.P., Agrawal J.K., et al. Spironolactone and cimetidine in treatment of acne. Acta Derm Venereol Suppl (Stockh) 1988; 68: 84–87Google Scholar
  39. 39.
    Muhlemann M.F., Carter G.D., Cream J.J., et al. Oral spironolactone: an effective treatment for acne vulgaris in women. Br J Dermatol 1986; 115: 227–232PubMedCrossRefGoogle Scholar
  40. 40.
    Shaw J.C. Spironolactone in dermatologic therapy. J Am Acad Dermatol 1991; 24: 236–243PubMedCrossRefGoogle Scholar
  41. 41.
    Hughes B.R., Cunliffe W.J. Tolerance of spironolactone. Br J Dermatol 1988; 118: 687–691PubMedCrossRefGoogle Scholar
  42. 42.
    Cusan L., Dupont A., Belanger A., et al. Treatment of hirsutism with the pure antiandrogen flutamide. J Am Acad Dermatol 1990; 23: 462–469PubMedCrossRefGoogle Scholar
  43. 43.
    Wang H.S., Wang T.H., Soong Y.K. Low dose flutamide in the treatment of acne vulgaris in women with or without oligomenorrhea or amenorrhea. Changgeng Yi Xue Za Zhi 1999; 22: 423–432PubMedGoogle Scholar
  44. 44.
    Cusan L., Dupont A., Gomez J.L., et al. Comparison of flutamide and spironolactone in the treatment of hirsutism: a randomized controlled trial. Fertil Steril 1994; 61: 281–287PubMedGoogle Scholar
  45. 45.
    Giordano N., Nardi P., Santacroce C. Acute hepatitis induced by cyproterone acetate. Ann Pharmcother 2001; 35: 1053–1055CrossRefGoogle Scholar
  46. 46.
    Rabe T., Kowald A., Ortmann J., et al. Inhibition of skin 5 alpha-reductase by oral contraceptive progestins in vitro. Gynecol Endocrinol 2000; 14: 223–230PubMedCrossRefGoogle Scholar
  47. 47.
    Roberts J.L., Fiedler V., Imperato-McGinley J., et al. Clinical dose ranging studies with finasteride, a type 2 5alpha-reductase inhibitor, in men with male pattern hair loss. J Am Acad Dermatol 1999; 41: 555–563PubMedGoogle Scholar
  48. 48.
    Kaufman K.D., Olsen E.A., Whiting D., et al. Finasteride in the treatment of men with androgenetic alopecia: Finasteride Male Pattern Hair Loss Study Group. J Am Acad Dermatol 1998; 39: 578–589PubMedCrossRefGoogle Scholar
  49. 49.
    Erenus M., Yucelten D., Durmusoglu F., et al. Comparison of finasteride versus spironolactone in the treatment of idiopathic hirsutism. Fertil Steril 1997; 68: 1000–1003PubMedCrossRefGoogle Scholar
  50. 50.
    Wong I.L., Morris R.S., Chang L., et al. A prospective randomized trial comparing finasteride to spironolactone in the treatment of hirsute women. J Clin Endocrinol Metab 1995; 80: 233–238PubMedCrossRefGoogle Scholar
  51. 51.
    Moghetti P., Tosi F., Tosti A., et al. Comparison of spironolactone, flutamide, and finasteride efficacy in the treatment of hirsutism: a randomized, double blind, placebo-controlled trial. J Clin Endocrinol Metab 2000; 85: 89–94PubMedCrossRefGoogle Scholar
  52. 52.
    Castello R., Tosi F., Perrone F., et al. Outcome of long-term treatment with the 5 alpha-reductase inhibitor finasteride in idiopathic hirsutism: clinical and hormonal effects during a 1-year course of therapy and 1-year follow-up. Fertil Steril 1996; 66: 734–740PubMedGoogle Scholar
  53. 53.
    Erel C.T., Senturk L.M., Oral I., et al. Results of the ACTH stimulation test in hirsute women. J Reprod Med 1999; 44: 247–252PubMedGoogle Scholar
  54. 54.
    Ostlere L.S., Rumsby G., Holownia P., et al. Carrier status for steroid 21-hydroxylase deficiency is only one factor in the variable phenotype of acne. Clin Endocrinol 1998; 48: 209–215CrossRefGoogle Scholar
  55. 55.
    Moran C., Azziz R., Carmina E., et al. 21-hydrozylase-deficient nonclassic adrenal hyperplasia is a progressive disorder: a multicenter study. Am J Obstet Gynecol 2000; 183: 1468–1474PubMedCrossRefGoogle Scholar
  56. 56.
    Ibanez L., Bonnin M.R., Zampolli M., et al. Usefulness of an ACTH test in the diagnosis of nonclassical 21-hydroxylase deficiency among children presenting with premature pubarche. Horm Res 1995; 44: 51–56PubMedCrossRefGoogle Scholar
  57. 57.
    Placzek M., Degitz K., Schmidt H., et al. Acne fulminans in late-onset congenital adrenal hyperplasia. Lancet 1999; 354: 739–740PubMedCrossRefGoogle Scholar
  58. 58.
    Rittmaster R.S., Givner M.L. Effect of daily and alternate day low dose prednisone on serum cortisol and adrenal androgens in hirsute women. J Clin Endocrinol Metab 1988; 67: 400PubMedCrossRefGoogle Scholar
  59. 59.
    Waggoner W., Boots L.R., Azziz R. Total testosterone and DHEAS levels as predictors of androgen-secreting neoplasms: a populational study. Gynecol Endocrinol 1999; 13: 394–400PubMedCrossRefGoogle Scholar
  60. 60.
    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: 2108–2116PubMedCrossRefGoogle Scholar
  61. 61.
    Ibanez L., Valls C., Potau N., et al. Sensitization to insulin in adolescent girls to normalize hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism after precocious pubarche. J Clin Endocrinol Metab 2000; 85 (10): 3526–3530PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  1. 1.Division of DermatologyUniversity of Toronto, Toronto Western HospitalTorontoCanada

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