Hormonal agents: Recommendations

What is the effectiveness and what are the potential side effects of hormonal agents in the treatment of adult acne and acne vulgaris in adolescents to adults including:

  • Contraceptive agents
  • Spironolactone
  • Antiandrogens
  • Oral corticosteroids

  • Estrogen-containing combined oral contraceptives are effective and recommended in the treatment of inflammatory acne in females.
  • Spironolactone is useful in the treatment of acne in select females. 
  • Oral corticosteroid therapy can be of temporary benefit in patients who have severe inflammatory acne while starting standard acne treatment.
  • In patients who have well-documented adrenal hyperandrogenism, low-dose oral corticosteroids are recommended in treatment of acne.
  Strength of Recommendation  Level of Evidence 
Combined oral contraceptives 
Spironolactone  II,III 
Flutamide  III 
Oral corticosteroids  II 

Review prescribing information for recommended acne treatments.

Combination oral contraceptive pills (COC’s) contain both an estrogen and a progestin component. COC’s were first FDA-approved for contraception in the United States in 1960. They prevent ovulation and pregnancy by inhibiting gonadotropin-releasing hormone and, subsequently, follicle stimulating hormone and luteinizing hormone. These hormones are needed to begin follicular maturation and for ovulation; in their absence ovulation does not occur. World Health Organization (WHO) recommendations for COC usage eligibility are listed in the table below.

World Health Organization Recommendations for COC Usage Eligibility 
COC Use Not Recommended  Caution or Special Monitoring 
Pregnancy  Breastfeeding (6 wk-6 mo postpartum) 
Current breast cancer  Postpartum (<21 d) 
Breastfeeding <6 wk postpartum  Age ≥35 y and light smoker (<15 cigarettes per day) 
Age ≥35 y and heavy smoker (≥15 cigarettes per day)  History of hypertension (including pregnancy) or if monitoring is not feasible 
Hypertension: systolic, ≥160mm Hg; diastolic, ≥100mm Hg  Hypertension: systolic, 14-159 mm Hg; diastolic, 90-99 mm Hg; or controlled and monitored 
Diabetes with end-organ damage  Headaches: migraine without focal neurologic symptoms <35 y 
Diabetes >20 y duration  Known hyperlipidemia should be assessed (e.g., type, severity) 
History of or current DVT or PE  History of breast cancer with ≥5 y of no disease 
Major surgery with prolonged immobilization  Biliary tract disease 
Ischemic heart disease (history or current); valvular heart disease with complications  Mild compensated cirrhosis 
History of CVA  History of cholestasis related to COC use 
Headaches (e.g., migraine with focal neurologic symptoms at any age, or without aura if ≥35 y)  Concurrent use of drugs that affect liver enzymes 
Active viral hepatitis   
Severe decompensated cirrhosis   
Liver tumor (benign or malignant)   

COCs have evolved since 1960. Ethinyl estradiol levels have gradually decreased from around 50 to 150
μg per pill to as low as 10 μg. A variety of different progestational moieties have been used, beginning with the first-generation progestins, the estranes (ie, norethindrone and ethynodiol diacetate). Second-generation progestins include levonorgestrel and norgestimate; these progestins are referred to as the gonanes. Third-generation progestins include less androgenic gonane progestins, such as desogestrel and gestodene. First-, second-, and third-generation progestins are derived from testosterone and alone have androgenic potential. Fourth-generation progestins are not derived from testosterone and include the antiandrogenic progestin drospirenone. While progestins vary in their androgenic potential, evidence suggests that when combined with ethinyl estradiol, the net effect of all COCs is antiandrogenic.219,220

There are currently 4 COCs approved by the FDA for the treatment of acne. They are ethinyl estradiol/norgestimate, ethinyl estradiol/norethindrone acetate/ferrous fumarate, ethinyl estradiol/drospirenone, and ethinyl estradiol/drospirenone/levomefolate. The mechanism of action of COCs in the treatment of acne is based on their antiandrogenic properties. These pills decrease androgen production at the level of the ovary and also increase sex hormone–binding globulin, binding free circulating testosterone and rendering it unavailable to bind and activate the androgen receptor. In addition, COCs reduce 5-alfa-reductase activity and block the androgen receptor.219,221-223

Numerous randomized controlled clinical trials have assessed the efficacy of COCs in the management of acne.98-101,221,224-226 It is evident from these trials that COCs reduce acne—both inflammatory and comedonal lesion counts. It is more difficult to determine which, if any, COC is consistently superior in the treatment of acne. A 2012 Cochrane metaanalysis assessed the effect of birth control pills on acne in women and included 31 trials with a total of 12,579 women. Nine trials compared a COC to placebo, and all of these COCs worked well to reduce acne. The progestins included in these 9 trials were levonorgestrel, norethindrone acetate, norgestimate, drospirenone, dienogest, and chlormadinone acetate. Seventeen trials compared 2 COCs, but no consistent differences in acne reduction were appreciated based on formulation or dosage of the COC. Only 1 small study compared a COC to an oral antibiotic; no significant difference in self-assessed acne improvement was identified.221

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