Therapy
Efficacy of a low-dose oral contraceptive containing 20 μg of ethinyl estradiol and 100 μg of levonorgestrel for the treatment of moderate acne: A randomized, placebo-controlled trial,☆☆,

https://doi.org/10.1067/mjd.2002.122192Get rights and content

Abstract

Background: Acne is a multifactorial disease in which androgens appear to play an important role. A low-dose oral contraceptive containing 20 μg of ethinyl estradiol and 100 μg of levonorgestrel (EE/LNG) has been shown to improve biochemical markers of androgenicity. Lowering bioavailable androgens may improve acne. Objective: The aim of this study was to evaluate the efficacy and safety of a low-dose oral contraceptive containing 20 μg of EE and 100 μg of LNG for the treatment of moderate acne. Methods: In a randomized, double-blind, placebo-controlled clinical trial, healthy female subjects (n = 371; ≥14 years old) with regular menstrual cycles and moderate facial acne were randomly assigned to receive EE/LNG or placebo for 6 cycles of 28 days. Acne lesion counts and clinician global assessment were performed at the end of each cycle. Patient self-assessments were collected and biochemical markers of androgenicity were also measured. Results: At the end of the study, the number of inflammatory and total lesions was significantly lower with EE/LNG compared with placebo (P < .05). Patients in the EE/LNG group also had significantly better scores for clinician global and patient self-assessments than those in the placebo group (P < .05). Biochemical markers of androgenicity improved during EE/LNG treatment compared with placebo and baseline values. Conclusion: A low-dose oral contraceptive containing EE/LNG is effective and safe for the treatment of moderate acne. (J Am Acad Dermatol 2002;47:399-409.)

Section snippets

Study population

Participants enrolled at 18 investigational sites were healthy women, at least 14 years of age, with regular menstrual cycles and moderate facial acne. Moderate facial acne was defined as a total facial count of 6 to 200 noninflammatory comedones, 10 to 75 inflammatory lesions (papules and pustules), and 5 or fewer nodules. Participants were required to have discontinued long-term retinoid therapy (oral or topical) for 6 weeks before enrollment, systemic antibiotics and other systemic acne

Patient disposition

A total of 371 patients were enrolled, with 185 randomly assigned to EE/LNG and 186 assigned to placebo. Two hundred forty-six patients completed the study and a similar number of patients discontinued treatment in both groups. The two most common reasons for discontinuation were “lost to follow-up” (EE/LNG, n = 11; placebo, n = 26) and “personal reason” (EE/LNG, n = 22; placebo, n = 13); significantly more patients in the placebo group than in the EE/LNG group were “lost to follow-up.”

Demographic and baseline characteristics

Discussion

This is one of two34 placebo-controlled trials demonstrating that a low-dose OC containing 20 μg of EE and 100 μg of LNG is efficacious and safe for the treatment of moderate acne vulgaris. Significantly greater reductions in total, inflammatory, and noninflammatory acne lesions were observed in patients treated with EE/LNG than in patients who received placebo, despite an impressive placebo response. For patients in the EE/LNG group, CGA scores were also significantly better compared with

Acknowledgements

We thank the additional investigators who participated in the study: PonJola Coney, MD, Douglass Forsha, MD, Michael Jarratt, MD, Steven Kempers, MD, Nellie Konnikov, MD, Richard G. B. Langley, MD, Anne Lucky, MD, Daniel Piacquadio, MD, Walter Powell, MD, David Rodriguez, MD, Hans Sander, MD, Daniel Stewart, DO, Edwardo Tschen, MD, and Guy Webster, MD, PhD. We also thank Robert Northington, PhD, and Dayong Li, PhD, for statistical analyses, and Kathleen Ohleth, PhD, for editorial assistance.

References (60)

  • AW Lucky et al.

    Effectiveness of norgestimate and ethinyl estradiol in treating moderate acne vulgaris

    J Am Acad Dermatol

    (1997)
  • GP Redmond et al.

    Norgestimate and ethinyl estradiol in the treatment of acne vulgaris: a randomized, placebo-controlled trial

    Obstet Gynecol

    (1997)
  • DF Archer et al.

    A new low-dose monophasic combination oral contraceptive (Alesse®) with levonorgestrel 100 μg and ethinyl estradiol 20 μg

    Contraception

    (1997)
  • DF Archer et al.

    Efficacy and safety of a low-dose monophasic combination oral contraceptive containing 100 μg levonorgestrel and 20 μg ethinyl estradiol (Alesse®)

    Am J Obstet Gynecol

    (1999)
  • H Reisman et al.

    A multicenter randomized comparison of cycle control and laboratory findings with oral contraceptive agents containing 100 μg levonorgestrel with 20 μg ethinyl estradiol or triphasic norethindrone with ethinyl estradiol

    Am J Obstet Gynecol

    (1999)
  • PE Pochi et al.

    Report of the Consensus Conference on Acne Classification. Washington, D.C., March 24 and 25, 1990

    J Am Acad Dermatol

    (1991)
  • E Carmina et al.

    Serum androsterone conjugates differentiate between acne and hirsutism in hyperandrogenic women

    Fertil Steril

    (1991)
  • RK Matteri et al.

    Androgen sulfate and glucuronide conjugates in nonhirsute and hirsute women with polycystic ovarian syndrome

    Am J Obstet Gynecol

    (1989)
  • R Södergard et al.

    Calculation of free and bound fractions of testosterone and estradiol-17β to human plasma proteins at body temperature

    J Steroid Biochem

    (1982)
  • D Thiboutot et al.

    A randomized, controlled trial of 20 μg ethinyl estradiol/100 μg levonorgestrel for acne treatment

    Fertil Steril

    (2001)
  • AA Murphy et al.

    The effect of tetracycline on levels of oral contraceptives

    Am J Obstet Gynecol

    (1991)
  • JV Joshi et al.

    A study of interaction of low-dose combination oral contraceptive with ampicillin and metronidazole

    Contraception

    (1980)
  • DJ Back et al.

    The lack of interaction between temafloxacin and combined oral contraceptive steroids

    Contraception

    (1991)
  • SE Helms et al.

    Oral contraceptive failure rates and oral antibiotics

    J Am Acad Dermatol

    (1997)
  • JA Pasco et al.

    Oral contraceptives and bone mineral density: a population-based study

    Am J Obstet Gynecol

    (2000)
  • P Garnero et al.

    Decreased bone turnover in oral contraceptive users

    Bone

    (1995)
  • MA. Gold

    Prescribing and managing oral contraceptive pills and emergency contraception for adolescents

    Pediatr Clin North Am

    (1999)
  • AM. Kaunitz

    Oral contraceptive health benefits: perception versus reality

    Contraception

    (1999)
  • L Panser et al.

    Type of oral contraceptive in relation to acute, initial episodes of pelvic inflammatory disease

    Contraception

    (1991)
  • SF Lanes et al.

    Oral contraceptive type and functional ovarian cysts

    Am J Obstet Gynecol

    (1992)
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    Funding sources: Wyeth Pharmaceuticals.

    ☆☆

    Disclosure: Drs Leyden, Shalita, Hordinsky, Swinyer, and Stanczyk have received research grants from and/or have served as consultants for Wyeth Pharmaceuticals. Dr Margaret Weber is an employee of Wyeth Pharmaceuticals. Competing conflicts of interest are: Dr Leyden (Parke-Davis and Ortho-McNeil Pharmaceutical, Inc); Dr Shalita (Ortho-McNeil Pharmaceutical, Inc); Dr Hordinsky (Parke-Davis); Dr Swinyer (RW Johnson Pharmaceutical Research Institute and Parke-Davis); and Dr Stanczyk (none).

    Reprint requests: Margaret E. Weber, MD, Wyeth Pharmaceuticals, 150 Radnor-Chester Rd, St Davids, PA 19087.

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