What is the optimal first‑line treatment for a perimenopausal woman with endometriosis and acne?

Optimal Treatment for Endometriosis in a Perimenopausal Woman with Acne

For a perimenopausal woman with both endometriosis and acne, progestin-only therapy with dienogest is the optimal first-line treatment, as combined oral contraceptives containing estrogen are contraindicated in perimenopausal women due to age-related cardiovascular and thrombotic risks. 1, 2

Why Combined Oral Contraceptives Are Not Appropriate

• Age-related contraindications become critical in perimenopause. Women ≥35 years who smoke are absolutely contraindicated from receiving estrogen-containing contraceptives due to dramatically increased thrombotic risk 3
• Even non-smoking perimenopausal women face elevated cardiovascular risks with estrogen therapy, including increased myocardial infarction and stroke rates, particularly if hypertension, diabetes, or migraines are present 3
• The baseline VTE risk increases with age, and adding estrogen-containing COCs (which carry a VTE risk of 3-10 per 10,000 woman-years) compounds this danger 3

First-Line Treatment: Dienogest

Dienogest 1 mg twice daily is the preferred initial therapy for this patient population. 2, 4

Efficacy for Endometriosis

• Dienogest is considered first-line treatment for all endometriosis phenotypes (ovarian, deep, or superficial) and is highly effective for long-term management 2
• Progestins work by causing pseudodecidualization with consequent amenorrhea, impairing progression of endometriotic implants and blocking menstruation through hypothalamic-pituitary-ovarian axis suppression 4
• Clinical trials demonstrate dienogest effectively reduces dysmenorrhea and all endometriosis-related pain symptoms 2, 4

Impact on Acne

• Critical caveat: Progestin-only contraceptives may worsen acne in some patients 3
• However, dienogest has less androgenic activity compared to older progestins like norethindrone acetate or medroxyprogesterone acetate 2
• The acne-worsening effect is most pronounced with highly androgenic progestins; dienogest's profile is more favorable 3

Monitoring and Expectations

• Endometriosis pain improvement typically occurs within 3-4 months of initiating dienogest 4
• If acne worsens significantly after 2-3 months on dienogest, proceed to the algorithm below 3

Algorithm for Managing Acne While on Dienogest

Step 1: Add Topical Anti-Acne Therapy (Months 0-3)

• Initiate topical retinoid (adapalene 0.1-0.3%) plus benzoyl peroxide 2.5-5% immediately when starting dienogest 1, 5
• This combination addresses acne through non-hormonal mechanisms while dienogest treats endometriosis 1
• Apply daily with mandatory sunscreen use due to photosensitivity 5

Step 2: Add Topical Clascoterone if Needed (Month 3-6)

• If acne persists or worsens despite topical retinoid/benzoyl peroxide, add clascoterone cream 5
• Clascoterone is a topical anti-androgen specifically useful for androgen-driven acne, making it ideal for progestin-related acne flares 5
• Continue dienogest for endometriosis while clascoterone addresses the androgenic acne component 5

Step 3: Add Spironolactone if Acne Remains Uncontrolled (Month 6+)

• If topical therapy plus clascoterone fails, add oral spironolactone 50-100 mg daily 3
• Spironolactone has potent anti-androgen activity and is highly effective for hormonal acne, with 66% of women achieving clear or markedly improved skin 3
• Routine potassium monitoring is not required in young, healthy perimenopausal women without renal insufficiency, heart failure, or concurrent ACE inhibitors 3
• Baseline potassium and blood pressure should be checked before initiation, with follow-up at 3 months 3

Step 4: Consider Oral Doxycycline for Moderate-to-Severe Inflammatory Acne

• If acne is moderate-to-severe with significant inflammatory lesions, add doxycycline 100 mg daily 5
• Limit systemic antibiotics to 3-4 months maximum to minimize resistance 5
• Always continue benzoyl peroxide concurrently with oral antibiotics to prevent bacterial resistance 5
• Never use antibiotics as monotherapy—resistance develops rapidly without concurrent benzoyl peroxide 5

Alternative: GnRH Antagonist (Relugolix) Followed by Dienogest

If dienogest-induced abnormal uterine bleeding becomes problematic, consider starting with relugolix 40 mg daily for 16 weeks, then transitioning to dienogest. 6

• Relugolix is a non-peptide GnRH antagonist that does not induce flare-ups (unlike GnRH agonists) 6
• This approach may reduce dienogest-induced abnormal bleeding when dienogest is introduced after relugolix 6
• GnRH antagonists are highly effective for endometriosis pain relief and do not carry stroke risk 7
• Major limitation: GnRH antagonists cause hypoestrogenic side effects including hot flashes, vaginal dryness, and bone loss 8, 9
• Add-back therapy with low-dose progestin can reduce these side effects but adds complexity 9
• This approach is best reserved for severe endometriosis pain unresponsive to dienogest alone 2, 4

When to Consider Surgical Consultation

Refer for surgical evaluation if: 7

• Endometriosis pain remains severe despite 6 months of optimized medical therapy
• Large endometriomas (>4 cm) are present on imaging
• Significant scarring or anatomical distortion is documented
• Patient desires definitive treatment

Surgical excision by a specialist provides significant pain reduction, though 44% of women experience symptom recurrence within one year 7

Critical Pitfalls to Avoid

• Never prescribe estrogen-containing COCs to perimenopausal women with cardiovascular risk factors, smoking history, or age ≥35 with migraines 3, 7
• Never use topical or oral antibiotics as monotherapy for acne—resistance develops rapidly without concurrent benzoyl peroxide 5
• Never extend oral antibiotics beyond 3-4 months without re-evaluation 5
• Do not assume all progestins are equally androgenic—dienogest has a more favorable profile than older progestins 2

Pre-Treatment Evaluation Required

Before initiating dienogest: 3

• Comprehensive medical history focusing on cardiovascular disease, VTE risk factors, liver disease, and smoking status
• Blood pressure measurement
• Pregnancy test
• Baseline potassium if planning to add spironolactone later