Skip to main content
SpringerLink
Log in

A randomized comparative trial of a combined oral contraceptive and azelaic acid to assess their effect on sleep quality in adult female acne patients

Archives of Dermatological Research volume 307, pages 905–915 (2015)Cite this article

Abstract

Several studies have reported an increase in the prevalence of adult female acne. This subtype of acne presents particular characteristics, and can be triggered by several factors such as smoking, stress, the use of oily cosmetics and even by poor sleep. Sleep quality is related to well-being and the maintenance of body homeostasis. In addition, several skin diseases present a bidirectional relationship with sleep, demonstrating an important connection between skin and the central nervous system. With this in mind, we aimed to compare the effect of two types of treatment for adult female acne (azelaic acid or a combined oral contraceptive) on sleep quality and on concentrations of stress hormones. Also, we proposed to assess the correlation of sleep and hormonal parameters with acne severity. In order to do this, 32 women underwent a clinical evaluation, completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire and had their blood collected for hormone assays. These procedures were performed at baseline and after 6 months of treatment. At baseline there were no differences between the groups in terms of body mass index, age, acne severity and hormone concentrations. Results showed that both treatments demonstrated effectiveness but that women treated with azelaic acid presented a better sleep quality after the treatment compared to baseline and to the group treated with the combined oral contraceptive. The combined oral contraceptive group presented an increase in cortisol and a decrease in free testosterone concentration in relation to baseline. These data suggest that both azelaic acid and combined oral contraceptive are effective in the treatment of adult female acne but, azelaic acid seems to be a more suitable option for those women who may benefit from a better subjective sleep quality.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. Adenekan B, Pandey A, McKenzie S, Zizi F, Casimir GJ, Jean-Louis G (2013) Sleep in America: role of racial/ethnic differences. Sleep Med Rev 17:255–262

    Article  PubMed Central  PubMed  Google Scholar 

  2. Ahmed AH, Gordon RD, Taylor PJ, Ward G, Pimenta E, Stowasser M (2011) Effect of contraceptives on aldosterone/renin ratio may vary according to the components of contraceptive, renin assay method, and possibly route of administration. J Clin Endocrinol Metab 96:1797–1804

    Article  CAS  PubMed  Google Scholar 

  3. Albuquerque RG, Rocha MA, Bagatin E, Tufik S, Andersen ML (2014) Could adult female acne be associated with modern life? Arch Dermatol Res 306:683–688

    Article  CAS  PubMed  Google Scholar 

  4. Andersen ML, Alvarenga TF, Mazaro-Costa R, Hachul HC, Tufik S (2011) The association of testosterone, sleep, and sexual function in men and women. Brain Res 1416:80–104

    Article  CAS  PubMed  Google Scholar 

  5. Andersen ML, Martins PJ, D’Almeida V, Bignotto M, Tufik S (2005) Endocrinological and catecholaminergic alterations during sleep deprivation and recovery in male rats. J Sleep Res 14:83–90

    Article  PubMed  Google Scholar 

  6. Bajuk Studen K, Jensterle Sever M, Pfeifer M (2013) Cardiovascular risk and subclinical cardiovascular disease in polycystic ovary syndrome. Front Horm Res 40:64–82

    Article  PubMed  Google Scholar 

  7. Baker FC, Mitchell D, Driver HS (2001) Oral contraceptives alter sleep and raise body temperature in young women. Pflugers Arch 442:729–737

    Article  CAS  PubMed  Google Scholar 

  8. Baker FC, Waner JI, Vieira EF, Taylor SR, Driver HS, Mitchell D (2001) Sleep and 24 hour body temperatures: a comparison in young men, naturally cycling women and women taking hormonal contraceptives. J Physiol 530:565–574

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Bataille V, Snieder H, MacGregor AJ, Sasieni P, Spector TD (2002) The influence of genetics and environmental factors in the pathogenesis of acne: a twin study of acne in women. J Invest Dermatol 119:1317–1322

    Article  CAS  PubMed  Google Scholar 

  10. Born J, Hansen K, Marshall L, Mölle M, Fehm HL (1999) Timing the end of nocturnal sleep. Nature 397:29–30

    Article  CAS  PubMed  Google Scholar 

  11. Buckley TM, Schatzberg AF (2005) On the interactions of the hypothalamic-pituitary-adrenal (HPA) axis and sleep: normal HPA axis activity and circadian rhythm, exemplary sleep disorders. J Clin Endocrinol Metab 90:3106–3114

    Article  CAS  PubMed  Google Scholar 

  12. Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ (1989) The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 28:193–213

    Article  CAS  PubMed  Google Scholar 

  13. Capitanio B, Sinagra JL, Bordignon V, Cordiali Fei P, Picardo M, Zouboulis CC (2010) Underestimated clinical features of postadolescent acne. J Am Acad Dermatol 63:782–788

    Article  PubMed  Google Scholar 

  14. Carr BR, Parker CR Jr, Madden JD, MacDonald PC, Porter JC (1979) Plasma levels of adrenocorticotropin and cortisol in women receiving oral contraceptive steroid treatment. J Clin Endocrinol Metab 49:346–349

    Article  CAS  PubMed  Google Scholar 

  15. Chatterjee B, Suri J, Suri JC, Mittal P, Adhikari T (2014) Impact of sleep-disordered breathing on metabolic dysfunctions in patients with polycystic ovary syndrome. Sleep Med 15:1547–1553

    Article  PubMed  Google Scholar 

  16. Collier CN, Harper JC, Cafardi JA, Cantrell WC, Wang W, Foster KW, Elewski BE (2008) The prevalence of acne in adults 20 years and older. J Am Acad Dermatol 58:56–59 (Erratum in:58:874)

    Article  PubMed  Google Scholar 

  17. Conway G, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Franks S, Gambineri A, Kelestimur F et al (2014) The polycystic ovary syndrome: a position statement from the European Society of Endocrinology. Eur J Endocrinol 171:P1–P29

    Article  CAS  PubMed  Google Scholar 

  18. De Leo V, Morgante G, Piomboni P, Musacchio MC, Petraglia F, Cianci A (2007) Evaluation of effects of an oral contraceptive containing ethinylestradiol combined with drospirenone on adrenal steroidogenesis in hyperandrogenic women with polycystic ovary syndrome. Fertil Steril 88:113–117

    Article  PubMed  Google Scholar 

  19. Dréno B, Layton A, Zouboulis CC, López-Estebaranz JL, Zalewska-Janowska A, Bagatin E, Zampeli VA et al (2013) Adult female acne: a new paradigm. J Eur Acad Dermatol Venereol 27:1063–1070

    Article  PubMed  Google Scholar 

  20. Dréno B, Thiboutot D, Layton AM, Berson D, Perez M, Kang S, The Global Alliance to Improve Outcomes in Acne (2014) Large-scale international study enhances understanding of an emerging acne population: adult females. J Eur Acad Dermatol Venereol. doi:10.1111/jdv.12757

    PubMed Central  Google Scholar 

  21. Ebede TL, Arch EL, Berson D (2009) Hormonal treatment of acne in women. J Clin Aesthet Dermatol 2:16–22

    PubMed Central  PubMed  Google Scholar 

  22. Ekstedt M, Akerstedt T, Söderström M (2004) Microarousals during sleep are associated with increased levels of lipids, cortisol, and blood pressure. Psychosom Med 66:925–931

    Article  CAS  PubMed  Google Scholar 

  23. Fitzpatrick TB (1988) The validity and practicality of sun-reactive skin types I through VI. Arch Dermatol 124:869–871

    Article  CAS  PubMed  Google Scholar 

  24. Gambacciani M, Rosano G, Cappagli B, Pepe A, Vitale C, Genazzani AR (2011) Clinical and metabolic effects of drospirenone-estradiol in menopausal women: a prospective study. Climacteric 14:18–24

    Article  CAS  PubMed  Google Scholar 

  25. Ganceviciene R, Graziene V, Fimmel S, Zouboulis CC (2009) Involvement of the corticotropin-releasing hormone system in the pathogenesis of acne vulgaris. Br J Dermatol 160:345–352

    Article  CAS  PubMed  Google Scholar 

  26. Goulden V, Clark SM, Cunliffe WJ (1997) Post-adolescent acne: a review of clinical features. Br J Dermatol 136:66–70

    Article  CAS  PubMed  Google Scholar 

  27. Hachul H, Andersen ML, Bittencourt LR, Santos-Silva R, Conway SG, Tufik S (2010) Does the reproductive cycle influence sleep patterns in women with sleep complaints? Climacteric 13:594–603

    Article  CAS  PubMed  Google Scholar 

  28. Hirotsu C, Rydlewski M, Araújo MS, Tufik S, Andersen ML (2012) Sleep loss and cytokines levels in an experimental model of psoriasis. PLoS One 7:e51183

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Huang A, Brennan K, Azziz R (2010) Prevalence of hyperandrogenemia in the polycystic ovary syndrome diagnosed by the National Institutes of Health 1990 criteria. Fertil Steril 93:1938–1941

    Article  PubMed Central  PubMed  Google Scholar 

  30. Joish VN, Boklage S, Lynen R, Schmidt A, Lin J (2011) Use of drospirenone/ethinyl estradiol (DRSP/EE) among women with acne reduces acne treatment-related resources. J Med Econ 14:681–689

    Article  PubMed  Google Scholar 

  31. Koltun W, Maloney JM, Marr J, Kunz M (2011) Treatment of moderate acne vulgaris using a combined oral contraceptive containing ethinylestradiol 20 μg plus drospirenone 3 mg administered in a 24/4 regimen: a pooled analysis. Eur J Obstet Gynecol Reprod Biol 155:171–175

    Article  CAS  PubMed  Google Scholar 

  32. Krattenmacher R (2000) Drospirenone: pharmacology and pharmacokinetics of a unique progestogen. Contraception 62:29–38

    Article  CAS  PubMed  Google Scholar 

  33. Lehmann HP, Robinson KA, Andrews JS, Holloway V, Goodman SN (2002) Acne therapy: a methodologic review. J Am Acad Dermatol 47:231–240

    Article  PubMed  Google Scholar 

  34. Lidegaard O, Nielsen LH, Skovlund CW, Løkkegaard E (2001) Venous thrombosis in users of non-oral hormonal contraception: follow-up study, Denmark 2001–10. BMJ 344:e2990

    Article  Google Scholar 

  35. Liu RH, Smith MK, Basta SA, Farmer ER (2006) Azelaic acid in the treatment of papulopustular rosacea: a systematic review of randomized controlled trials. Arch Dermatol 142:1047–1052

    CAS  PubMed  Google Scholar 

  36. Palli MB, Reyes-Habito CM, Lima XT, Kimball AB (2013) A single-center, randomized double-blind, parallel-group study to examine the safety and efficacy of 3 mg drospirenone/0.02 mg ethinyl estradiol compared with placebo in the treatment of moderate truncal acne vulgaris. J Drugs Dermatol 12:633–637

    CAS  PubMed  Google Scholar 

  37. Poli F, Dreno B, Verschoore M (2001) An epidemiological study of acne in female adults: results of a survey conducted in France. J Eur Acad Dermatol Venereol 15:541–545

    Article  CAS  PubMed  Google Scholar 

  38. Rodenbeck A, Huether G, Rüther E, Hajak G (2002) Interactions between evening and nocturnal cortisol secretion and sleep parameters in patients with severe chronic primary insomnia. Neurosci Lett 324:159–163

    Article  CAS  PubMed  Google Scholar 

  39. Rogers SM, Baker MA (1997) Thermoregulation during exercise in women who are taking hormonal contraceptives. Eur J Appl Physiol 75:34–38

    Article  CAS  Google Scholar 

  40. Schürmann R, Holler T, Benda N (2004) Estradiol and drospirenone for climacteric symptoms in postmenopausal women: a double-blind, randomized, placebo-controlled study of the safety and efficacy of three dose regimens. Climacteric 7:189–196

    Article  PubMed  Google Scholar 

  41. Sieber MA, Hegel JK (2014) Azelaic acid: properties and mode of action. Skin Pharmacol Physiol 27(Suppl 1):9–17

    Article  CAS  PubMed  Google Scholar 

  42. Silverberg JI, Garg NK, Paller AS, Fishbein AB, Zee PC (2015) Sleep disturbances in adults with eczema are associated with impaired overall health: a US population-based study. J Invest Dermatol 135:56–66

    Article  CAS  PubMed  Google Scholar 

  43. Simpson ER, Waterman MR (1988) Regulation of the synthesis of steroidogenic enzymes in adrenal cortical cells by ACTH. Annu Rev Physiol 50:427–440

    Article  CAS  PubMed  Google Scholar 

  44. Simůnková K, Stárka L, Hill M, Kríz L, Hampl R, Vondra K (2008) Comparison of total and salivary cortisol in a low-dose ACTH (Synacthen) test: influence of three-month oral contraceptives administration to healthy women. Physiol Res 57(Suppl 1):S193–S199

    PubMed  Google Scholar 

  45. Strauss JS, Krowchuk DP, Leyden JJ, Lucky AW, Shalita AR, Siegfried EC, Thiboutot DM et al (2007) Guidelines of care for acne vulgaris management. J Am Acad Dermatol 56:651–663

    Article  PubMed  Google Scholar 

  46. Tien KJ, Chou CW, Lee SY, Yeh NC, Yang CY, Yen FC, Wang JJ et al (2014) Obstructive sleep apnea and the risk of atopic dermatitis: a population-based case control study. PLoS One 9:e89656

    Article  PubMed Central  PubMed  Google Scholar 

  47. Tufik S, Andersen ML, Bittencourt LR, Mello MT (2009) Paradoxical sleep deprivation: neurochemical, hormonal and behavioral alterations. Evidence from 30 years of research. An Acad Bras Cienc 81:521–538

    Article  PubMed  Google Scholar 

  48. Van Cauter E, Leproult R, Plat L (2000) Age-related changes in slow wave sleep and REM sleep and relationship with growth hormone and cortisol levels in healthy men. JAMA 284:861–868

    Article  PubMed  Google Scholar 

  49. Vandenbroucke JP, Rosing J, Bloemenkamp KW, Middeldorp S, Helmerhorst FM, Bouma BN, Rosendaal FR (2001) Oral contraceptives and the risk of venous thrombosis. N Engl J Med 344:1527–1535

    Article  CAS  PubMed  Google Scholar 

  50. Vargas-Diez E, Hofmann MA, Bravo B, Malgazhdarova G, Katkhanova OA, Yutskovskaya Y (2014) Azelaic acid in the treatment of acne in adult females: case reports. Skin Pharmacol Physiol 27(Suppl 1):18–25

    Article  PubMed  Google Scholar 

  51. White WB, Hanes V, Mallareddy M, Chauhan V (2008) Effects of the hormone therapy, drospirenone and 17-beta estradiol, on early morning blood pressure in postmenopausal women with hypertension. J Am Soc Hypertens 2:20–27

    Article  PubMed  Google Scholar 

  52. Winkler UH, Sudik R (2009) The effects of two monophasic oral contraceptives containing 30 mcg of ethinyl estradiol and either 2 mg of chlormadinone acetate or 0.15 mg of desogestrel on lipid, hormone and metabolic parameters. Contraception 79:15–23

    Article  CAS  PubMed  Google Scholar 

  53. Yang YW, Kang JH, Lin HC (2012) Increased risk of psoriasis following obstructive sleep apnea: a longitudinal population-based study. Sleep Med 13:285–289

    Article  PubMed  Google Scholar 

  54. Zimmerman Y, Eijkemans MJ, Coelingh Bennink HJ, Blankenstein MA, Fauser BC (2014) The effect of combined oral contraception on testosterone levels in healthy women: a systematic review and meta-analysis. Hum Reprod Update 20:76–105

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Zouboulis CC (2000) Acne venenataund Acne cosmetica. In: Braun-Falco O, Gloor M, Korting HC (eds) Nutzen und Risiko von Kosmetika. Springer, Berlin, pp 116–123

    Chapter  Google Scholar 

  56. Zouboulis CC, Böhm M (2004) Neuroendocrine regulation of sebocytes—a pathogenetic link between stress and acne. Exp Dermatol 13(Suppl 4):31–35

    Article  CAS  PubMed  Google Scholar 

  57. Zouboulis CC, Rabe T (2010) Hormonal antiandrogens in acne treatment. J Dtsch Dermatol Ges 8(Suppl 1):S60–S74

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Our studies are supported by a fellowship from the Associação Fundo de Incentivo à Pesquisa (AFIP), São Paulo Research Foundation (FAPESP, grant #2014/00923-4 to RGA, grant #2014/15259-2 to CH, grant #2012/21794-2 to MLA). ST and MLA also received support from Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq).

Author information

Author notes

    Authors and Affiliations

    1. Departamento de Psicobiologia, Universidade Federal de São Paulo, Rua Napoleão de Barros, 925, 04024-002, São Paulo, SP, Brazil

      Rachel Gimenes Albuquerque, Camila Hirotsu, Helena Hachul, Sergio Tufik & Monica Levy Andersen

    2. Departamento de Dermatologia, Universidade Federal de São Paulo, Rua Borges Lagoa, 508, 04038-001, São Paulo, SP, Brazil

      Marco Alexandre Dias da Rocha & Edileia Bagatin

    Authors
    1. Rachel Gimenes Albuquerque
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Marco Alexandre Dias da Rocha
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Camila Hirotsu
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Helena Hachul
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Edileia Bagatin
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Sergio Tufik
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Monica Levy Andersen
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Monica Levy Andersen.

    Ethics declarations

    Conflict of interest

    Combined oral contraceptive (20 µg of EE and 3 mg of DRSP) and 15 % AA gel were provided by Bayer® (Germany).

    Additional information

    R. G. Albuquerque and M. A. D. da Rocha are equal contributors.

    Rights and permissions

    Reprints and Permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Albuquerque, R.G., da Rocha, M.A.D., Hirotsu, C. et al. A randomized comparative trial of a combined oral contraceptive and azelaic acid to assess their effect on sleep quality in adult female acne patients. Arch Dermatol Res 307, 905–915 (2015). https://doi.org/10.1007/s00403-015-1600-0

    Download citation

    • Received:

    • Revised:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00403-015-1600-0

    Keywords

    search

    Navigation