Hormonal Acne Treatment in Females with Hyperandrogenism
Initial Assessment and Endocrine Evaluation
For female patients presenting with acne accompanied by signs of hyperandrogenism (hirsutism, male pattern baldness, irregular menses), endocrinologic testing is warranted before initiating treatment. 1
The American Academy of Dermatology recommends obtaining the following hormone panel for patients with clinical hyperandrogenism 1, 2:
- Free and total testosterone
- Dehydroepiandrosterone sulfate (DHEA-S)
- Luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
- Consider androstenedione 2
Polycystic ovary syndrome (PCOS) is the most common cause of hyperandrogenism in women, accounting for approximately 70% of cases 3, 4. PCOS diagnosis in adult females requires 2 of 3 criteria: androgen excess (clinical or biochemical), ovulatory dysfunction, or polycystic ovaries on ultrasonography 2.
First-Line Hormonal Treatment Options
Combined Oral Contraceptives (COCs)
Combined oral contraceptives are strongly recommended as first-line hormonal therapy for females with hormonal acne and hyperandrogenism. 1
The American Academy of Dermatology notes that COCs reduce inflammatory acne lesions by 62% at 6 months through multiple antiandrogenic mechanisms 1, 5:
- Decrease ovarian androgen production
- Increase sex hormone-binding globulin (SHBG), which binds free testosterone
- Reduce 5-alpha-reductase activity
- Block androgen receptors 1
Four COC formulations are FDA-approved specifically for acne treatment 1:
- Ethinyl estradiol/norgestimate
- Ethinyl estradiol/norethindrone acetate/ferrous fumarate
- Ethinyl estradiol/drospirenone
- Ethinyl estradiol/drospirenone/levomefolate
A 2012 Cochrane meta-analysis of 31 trials (12,579 women) demonstrated that all COC formulations effectively reduce acne, with no consistent superiority of one formulation over another 1. COCs can be used as monotherapy for mild-to-moderate acne or combined with topical agents for more severe disease 1, 5.
Critical contraindications to COC use include 1:
- Active smoking in women ≥35 years (absolute contraindication due to cardiovascular risk)
- History of venous thromboembolism or high thrombotic risk
- Uncontrolled hypertension or hypertension with vascular disease
- Migraine with focal neurologic symptoms
- Active liver disease or liver tumors
- Breast cancer
Spironolactone
Spironolactone 25-200 mg daily is the preferred antiandrogen for hormonal acne, particularly effective for premenstrual flares and in patients who cannot tolerate oral antibiotics. 1, 2, 5
The American Academy of Dermatology recommends spironolactone for 1, 2:
- Hormonal acne patterns (jawline/lower face distribution)
- Premenstrual acne flares
- Patients with documented hyperandrogenism
- Those who prefer to avoid or cannot tolerate oral antibiotics
Potassium monitoring is NOT required in healthy patients without risk factors for hyperkalemia (older age, renal disease, concurrent medications that increase potassium) 1, 2, 5. However, for patients on long-term medications that may increase potassium (NSAIDs, ACE inhibitors, potassium-sparing diuretics, heparin), check serum potassium during the first treatment cycle 1, 6.
Spironolactone is contraindicated in patients with 6:
- Renal impairment
- Adrenal insufficiency
- Pre-existing hyperkalemia
Combination Approach for Moderate-to-Severe Hormonal Acne
For moderate-to-severe inflammatory acne with hyperandrogenism, combine hormonal therapy with topical retinoid + benzoyl peroxide as foundation therapy. 1, 2, 5
Treatment Algorithm:
Mild hormonal acne:
Moderate hormonal acne:
- COC or spironolactone + fixed-dose combination topical retinoid/benzoyl peroxide + topical antibiotic (clindamycin 1% or erythromycin 3%) combined with benzoyl peroxide 1, 2, 5
Moderate-to-severe inflammatory hormonal acne:
- COC or spironolactone + oral doxycycline 100 mg daily + topical retinoid + benzoyl peroxide 1, 2, 5
- Limit oral antibiotics to 3-4 months maximum 1, 2, 5
- Always use benzoyl peroxide concurrently with oral antibiotics to prevent resistance 1, 2, 5
Severe, treatment-resistant, or scarring hormonal acne:
- Isotretinoin 0.5-1.0 mg/kg/day (cumulative dose 120-150 mg/kg) is the definitive treatment 1, 2
- Can be combined with spironolactone or COC as adjunctive therapy 2
- Mandatory pregnancy prevention through iPledge program 1, 2
- Monitor only liver function tests and lipids (CBC not needed in healthy patients) 1, 2
Special Considerations for Drospirenone-Containing COCs
Drospirenone is a fourth-generation progestin with antiandrogenic and antimineralocorticoid properties, making it theoretically advantageous for hormonal acne 1, 6. However, drospirenone-containing COCs carry specific warnings 6:
- Risk of hyperkalemia: Do not use in patients with renal, hepatic, or adrenal disease 6
- Patients on chronic medications that increase potassium (NSAIDs, ACE inhibitors, potassium-sparing diuretics, aldosterone antagonists) require potassium monitoring during the first treatment cycle 6
- Higher VTE risk: COCs containing drospirenone may have higher venous thromboembolism risk compared to levonorgestrel-containing COCs 1
Critical Pitfalls to Avoid
Never use oral or topical antibiotics as monotherapy—resistance develops rapidly without concurrent benzoyl peroxide. 1, 2, 5
Never extend oral antibiotics beyond 3-4 months without re-evaluation, as this dramatically increases antibiotic resistance risk. 1, 2, 5
Do not prescribe COCs to women with uncontrolled hypertension, history of thromboembolism, or who smoke and are ≥35 years old 1, 6.
For drospirenone-containing COCs specifically, avoid use in patients with renal impairment, adrenal insufficiency, or those on chronic medications that increase potassium without appropriate monitoring 6.
Maintenance Therapy
After achieving clearance, continue topical retinoid monotherapy indefinitely to prevent recurrence. 1, 2, 5
Hormonal therapy (COC or spironolactone) can be continued long-term for sustained control of hormonal acne 1, 5. Benzoyl peroxide may also be continued as maintenance 5.