What is the best approach to treat acne in a peri- or postmenopausal female patient caused by hormone replacement therapy (HRT)?

Treatment of HRT-Induced Acne

For acne caused by hormone replacement therapy in peri- or postmenopausal women, first-line treatment should be topical combination therapy with benzoyl peroxide plus a topical retinoid (adapalene or tretinoin), with the addition of topical dapsone 5% gel if inflammatory lesions predominate. 1

Initial Topical Therapy Approach

• Start with benzoyl peroxide combined with a topical retinoid as this addresses multiple pathogenic factors in acne development and is recommended for moderate acne regardless of hormonal etiology 1
• Add topical dapsone 5% gel for inflammatory acne, which is specifically recommended for adult females with acne 1
• Topical antibiotics (clindamycin or erythromycin) should only be used in combination with benzoyl peroxide, never as monotherapy, to prevent bacterial resistance 1
• Azelaic acid can be added as an adjunctive treatment, particularly if postinflammatory hyperpigmentation is present 1

Systemic Hormonal Modification Options

If topical therapy fails after 8-12 weeks, consider modifying the HRT regimen itself before adding systemic acne medications:

HRT Regimen Adjustment Strategy

• Switch from oral to transdermal estradiol if the patient is currently on oral conjugated equine estrogens, as transdermal delivery bypasses hepatic first-pass metabolism and may have different androgenic effects 2
• Change the progestin component to micronized progesterone if the patient is on synthetic progestins (particularly medroxyprogesterone acetate), as micronized progesterone has lower androgenic potential 2, 3
• Consider combined estradiol/progestin patches with levonorgestrel, which has established antiandrogenic properties when combined with ethinyl estradiol 1

Adding Antiandrogen Therapy

If HRT modification is not feasible or insufficient:

• Spironolactone 50-200 mg daily is the first-line systemic antiandrogen for adult women with acne, with clinical trial data supporting its use as first-line treatment 4, 3, 5
• Potassium monitoring is unnecessary unless the patient has renal impairment, takes ACE inhibitors/ARBs, or has other specific risk factors for hyperkalemia 3
• Combined oral contraceptives (COCs) containing drospirenone/ethinyl estradiol are FDA-approved for acne treatment in women who also desire contraception 1, 6
• However, COCs are generally not appropriate for postmenopausal women already on HRT, as they would provide redundant hormonal therapy 2

Topical Antiandrogen Option

• Clascoterone 1% cream is a topical antiandrogen FDA-approved for acne that can be used in conjunction with HRT without systemic hormonal effects 3
• This allows targeted antiandrogen activity at the skin level while maintaining the patient's systemic HRT regimen 3

Systemic Antibiotics (If Needed)

For moderate to severe inflammatory acne not responding to topical therapy:

• Oral antibiotics (doxycycline, minocycline) can be used in combination with topical retinoids and benzoyl peroxide 1
• Always combine with benzoyl peroxide to prevent bacterial resistance 1
• Limit duration to 3-4 months and transition to maintenance therapy with topical retinoids 1

Critical Pitfalls to Avoid

• Do not discontinue HRT solely due to acne in women who need it for vasomotor symptoms or premature menopause, as the benefits of HRT in appropriate candidates outweigh the inconvenience of treatable acne 2
• Do not use topical antibiotics as monotherapy due to bacterial resistance risk 1
• Do not assume all HRT formulations have equal androgenic effects—the specific estrogen and progestin components matter significantly 1, 2
• Do not add COCs to existing HRT—this creates excessive and inappropriate hormonal exposure 2

Treatment Algorithm

1. Assess acne severity: Comedonal vs. inflammatory, mild vs. moderate-severe 1
2. Start topical therapy: Benzoyl peroxide + retinoid ± topical dapsone 5% gel 1
3. Evaluate at 8-12 weeks: If inadequate response, proceed to step 4 1
4. Modify HRT regimen: Switch to transdermal estradiol and/or micronized progesterone 2, 3
5. If still inadequate at 8-12 weeks: Add spironolactone 50-100 mg daily (titrate to 200 mg if needed) OR topical clascoterone 4, 3
6. For severe inflammatory acne: Consider oral antibiotics (3-4 months maximum) with benzoyl peroxide 1
7. Maintenance: Continue topical retinoid long-term to prevent recurrence 1