Rachel V. Reynolds, MD (Co-Chair),a Howa Yeung, MD, MSc,b Carol E. Cheng, MD,c
Fran Cook-Bolden, MD,d Seemal R. Desai, MD,e,f Kelly M. Druby, BSN,g Esther E. Freeman, MD, PhD,h Jonette E. Keri, MD, PhD,i,j Linda F. Stein Gold, MD,k Jerry K. L. Tan, MD,l,m Megha M. Tollefson, MD,n Jonathan S. Weiss, MD,b,o Peggy A. Wu, MD, MPH,p Andrea L. Zaenglein, MD,q
Jung Min Han, PharmD, MS,r and John S. Barbieri, MD, MBA (Co-Chair)s
Evidence-Based Guidelines for the Management of Acne Vulgaris (2024 – Journal of the American Academy of Dermatology)
Background:
Acne vulgaris is a common condition that affects adolescents, preadolescents (age 9 and above), and adults.
Objective:
To develop clear, evidence-based recommendations for the effective treatment of acne vulgaris.
Methods:
A multidisciplinary work group performed a systematic review of the literature and applied the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework to evaluate the quality of evidence and to develop and grade clinical recommendations.
Key Recommendations:
Strong Recommendations:
Topical therapies:
Benzoyl peroxide
Topical retinoids (e.g., adapalene, tretinoin, tazarotene, trifarotene)
Topical antibiotics (e.g., clindamycin)
Oral therapies:
Doxycycline
Isotretinoin – strongly recommended for severe acne, acne causing scarring or psychosocial distress, or acne unresponsive to standard therapies.
Conditional Recommendations:
Topical agents:
Clascoterone (androgen receptor inhibitor)
Salicylic acid
Azelaic acid
Oral agents:
Minocycline
Sarecycline
Combined oral contraceptives (COCPs)
Spironolactone (for hormonal acne)
Good Practice Statements:
Use combinations of topical therapies with complementary mechanisms of action.
Limit the use of systemic antibiotics and avoid monotherapy.
Combine systemic antibiotics with topical agents for enhanced efficacy.
Use intralesional corticosteroid injections for the management of large, inflamed lesions.
Scope and Objectives
Acne vulgaris is among the most common skin conditions diagnosed and treated by dermatologists in the United States and globally. These updated guidelines aim to provide evidence-based recommendations for the clinical management of acne vulgaris in adults, adolescents, and preadolescents aged 9 years or older, reflecting the perspectives of dermatologists in the US and Canada, other healthcare providers who treat acne, and patients.
This document updates the 2016 American Academy of Dermatology (AAD) guidelines and is based on a systematic review of the literature, covering:
Acne grading and classification
Laboratory testing
Treatment options including topical therapies, systemic antibiotics, hormonal agents, oral isotretinoin
Physical modalities
Complementary and alternative medicine
Dietary and environmental interventions
These guidelines focus on treatments that are FDA-approved and commonly used in the United States.
The following conditions are not included in the scope:
Acneiform eruptions (acne-like rashes)
Drug-induced acne
Infantile acne
Mid-childhood acne (under 9 years)
Post-acne hyperpigmentation and scarring
Methods
From May 2021 to November 2022, the American Academy of Dermatology (AAD), in collaboration with Evidinno, Inc., conducted a series of systematic and targeted literature reviews to assess the safety and effectiveness of currently approved acne treatments for individuals aged 9 years and older in the US.
The reviews were based on 9 pre-specified clinical questions with defined criteria for:
Patient population
Interventions
Comparators
Outcomes
Study eligibility
The guideline development panel included:
9 board-certified dermatologists (including one methodologist and one medical writer)
3 board-certified pediatric dermatologists
1 AAD staff liaison
1 patient representative
The panel used the GRADE approach (Grading of Recommendations, Assessment, Development, and Evaluation) to assess evidence and formulate recommendations. This method incorporates:
Benefits and harms of treatments
Patient values and preferences
Resource implications
Overall certainty of evidence
Recommendations were classified as:
Strong – when benefits clearly outweigh risks or vice versa.
Conditional – when benefits and risks are closely balanced, but most patients are still expected to prefer the recommended action.
Capsule Summary
The American Academy of Dermatology (AAD) has updated its 2016 acne management guidelines through a systematic review, resulting in 18 evidence-based recommendations and 5 good practice statements.
Strong recommendations include the use of topical benzoyl peroxide, topical retinoids, topical antibiotics, their fixed-dose combinations, and oral doxycycline.
Oral isotretinoin is strongly recommended for:
Severe acne
Acne associated with psychosocial distress or scarring
Acne unresponsive to standard topical or oral therapies
Conditional recommendations are made for:
Topical clascoterone, salicylic acid, azelaic acid
Oral minocycline, sarecycline
Combined oral contraceptive pills
Spironolactone
Good clinical practices include:
Combining topical treatments with different mechanisms of action
Limiting the use of systemic antibiotics
Co-prescribing systemic antibiotics with benzoyl peroxide and other topicals
Considering intralesional corticosteroid injections for larger or inflamed lesions
Definition
Acne vulgaris is a chronic inflammatory skin condition that affects the pilosebaceous unit (hair follicle and associated sebaceous gland).
It typically presents with:
Open or closed comedones (blackheads and whiteheads)
Papules
Pustules
Nodules
These lesions commonly appear on the face and trunk and may lead to:
Pain
Redness (erythema)
Post-inflammatory hyperpigmentation
Scarring
Introduction / Background
Acne vulgaris is a highly prevalent skin condition, affecting 9.4% of the global population in 2010, making it the eighth most common disease worldwide.
It impacts approximately 85% of teenagers, though it can occur at any age and often persists into adulthood.
In terms of overall burden, acne ranked second among all skin diseases in 2013 when measured by disability-adjusted life years (DALYs). In the United States, over 50 million individuals are affected by acne. In 2013 alone, more than 5.1 million Americans sought medical care for acne, resulting in $846 million in direct medical costs and $398 million in productivity losses for patients and caregivers.
Beyond the physical symptoms, acne significantly affects:
Emotional and social functioning
Personal relationships
Leisure activities
Daily life, school performance, work productivity, and sleep
Its impact on health-related quality of life has been shown to be comparable to that of asthma, psoriasis, and arthritis.
Acne is associated with increased risks of:
Stigmatization and bullying
Depression and anxiety
Low self-esteem
Suicidal thoughts
The pathogenesis of acne is multifactorial, involving:
Follicular hyperkeratinization
Colonization by Cutibacterium acnes
Sebum overproduction
Complex inflammatory pathways involving innate and adaptive immunity
Neuroendocrine mechanisms
Genetic and environmental influences
Risk factors include:
Increasing age during adolescence
Positive family history of acne
Oily skin type
Acne Grading and Classification
Various grading and classification systems have been developed for acne to assess:
Overall severity of the condition
Number and type of lesions
Distribution across body regions
Secondary changes such as dyspigmentation and scarring
Standardized use of grading systems helps:
Guide treatment decisions
Evaluate therapeutic outcomes
Clinical Practice
Several acne grading systems are available and widely used in both research and clinical practice, including:
Investigator Global Assessment (IGA)
Leeds Revised Acne Grading System
Global Acne Grading System
Global Acne Severity Scale
Comprehensive Acne Severity Scale
Although no universally accepted grading system exists in clinical settings, the IGA is the most commonly used in the United States, demonstrating strong agreement between clinician and patient ratings. However, definitions within IGA scales have varied over time, highlighting the need for harmonization to enhance its usability and future meta-analyses.
The IGA has been used in numerous randomized controlled trials (RCTs) and is considered a potential foundation for developing a standardized acne grading tool. An ideal system should:
Evaluate types and number of primary lesions
Assess extent and anatomical distribution
Be psychometrically robust
Use clear text or photographic descriptors
Be simple to use
Gain broad stakeholder acceptance
A 5-point ordinal scale (0–4) — clear, almost clear, mild, moderate, severe — has been agreed upon by the International Dermatology Outcomes Measures and the American Academy of Dermatology to standardize assessment in clinical practice. Descriptors for this scale still require further validation, especially for facial and truncal acne.
Newer technologies for acne severity evaluation include:
Digital photography
Fluorescent and polarized light photography
Video microscopy
Multispectral imaging
In addition to clinical signs, core outcome measures for acne should consider:
Patient satisfaction with appearance and treatment
Extent of scarring or post-inflammatory hyperpigmentation
Long-term control of acne
Adverse events
Health-related quality of life (HRQoL)
Notably, HRQoL tools may not always correlate with clinical severity but are essential for capturing the patient experience. Shorter, validated tools are available for routine clinical use.
Microbiological and Endocrine Testing
Microbiologic Considerations
Cutibacterium acnes (formerly Propionibacterium acnes) is a Gram-positive anaerobic rod central to acne pathogenesis.
Certain strains are pathogenic, while others are commensal.
Routine microbial or antibiotic susceptibility testing is not recommended, as it does not alter standard management.
Exceptions include:
Gram-negative folliculitis: suspected in patients with pustular eruptions in periorificial areas following prolonged tetracycline use. Culture is warranted.
Pityrosporum folliculitis: suspected in monomorphic papules or pustules on the trunk; fungal testing may be appropriate.
Endocrine Considerations
Androgens (e.g., testosterone, DHEAS) play a central role in acne development.
Evidence linking acne severity to androgen levels is mixed.
Routine endocrine testing is not recommended for most patients.
Testing is indicated in patients with clinical features of hyperandrogenism, such as:
Hirsutism
Oligomenorrhea or amenorrhea
Androgenic alopecia
Infertility
Truncal obesity
Clitoromegaly
Polycystic ovarian features
Possible tests include:
Total and free testosterone
DHEAS
Androstenedione
LH and FSH
17-hydroxyprogesterone (to evaluate for nonclassic congenital adrenal hyperplasia)
Insulin, prolactin, SHBG, free androgen index, lipid panel, estrogen, progesterone, IGF-1, and growth hormone, as needed
Patients with abnormal results or persistent clinical suspicion should be referred to an endocrinologist for further evaluation.
Acne treatment options include:
Topical therapies (OTC or prescription)
Complementary & alternative medicine
Dietary/environmental interventions
Shared decision-making is key to tailoring treatment based on:
Derived from vitamin A; comedolytic and anti-inflammatory.
Improve dark spots and maintain acne clearance.
FDA-approved options: Tretinoin, Adapalene (OTC), Tazarotene, Trifarotene.
No one product is superior—tolerability varies by concentration and formulation.
Side effects: dryness, burning, redness, peeling.
Use at night; avoid mixing tretinoin with BP due to oxidation.
Use sunscreen daily to prevent photosensitivity.
Discontinuation due to side effects is rare (1.4%).
OTC antibacterial and mildly comedolytic.
No resistance reported against C. acnes.
Available in various concentrations and forms.
Side effects: burning, dryness, irritation, bleaching of fabric.
Lower concentrations or wash-off types are better tolerated.
Highly effective in reducing both inflammatory and noninflammatory lesions.
Examples: Clindamycin, Erythromycin, Minocycline, Dapsone.
Work via antibacterial and anti-inflammatory action.
Not to be used alone due to resistance risk.
Combine with BP to increase efficacy and reduce resistance.
Side effects: mild irritation, very rarely digestive issues (e.g., diarrhea).
Dapsone + BP may cause temporary orange-brown discoloration (washable).
Combine: BP + Retinoid, BP + Antibiotic, Retinoid + Antibiotic.
Improve patient adherence and simplify treatment.
More effective than monotherapy.
BP component helps prevent antibiotic resistance.
Side effects are consistent with individual agents.
Can be more affordable than purchasing components separately.
Clascoterone
A topical antiandrogen that binds androgen receptors and inhibits oil (sebum) and inflammatory cytokine production from sebaceous glands.
Recommended conditionally based on high-certainty evidence (2 RCTs).
At 12 weeks: Significantly better IGA success vs placebo (RR: 2.08).
Limitation: High cost, which affects accessibility. Recommendation might change with improved affordability.
🔹 Salicylic Acid
OTC comedolytic agent (0.5%–2% concentration).
Conditionally recommended based on moderate certainty evidence from 1 RCT:
↓ Inflammatory lesions by 25%
↓ Open comedones by 11%
No effect on closed comedones
Higher concentrations (10–30%) used in chemical peels, discussed separately.
🔹 Azelaic Acid
Topical comedolytic, antibacterial, and anti-inflammatory agent.
Particularly useful for sensitive or darker skin types due to its skin-lightening effects.
Conditionally recommended based on moderate certainty evidence from 3 RCTs.
In 1 trial, 28% more patients using azelaic acid 20% cream achieved ≥50% reduction in lesions at 3 months.
🔸 Topical Therapy Considerations in Pregnancy
Safe during pregnancy (based on low systemic absorption):
Azelaic acid
BP
Erythromycin
Clindamycin
Use cautiously:
Salicylic acid (small areas, short-term use only)
Not recommended / Contraindicated:
Tazarotene (animal studies show teratogenicity)
Topical minocycline
No data: Dapsone, Clascoterone
Retinoids should generally be avoided in pregnancy, though no confirmed human teratogenicity.
🔸 Age Restrictions
FDA-approved from age 9 and up:
BP 2.5%/adapalene 1% gel
Tretinoin 0.1%/BP 3% cream
Trifarotene 0.005% cream
Dapsone 5% gel
Minocycline 4% foam
Most other topical therapies approved from age 12.
🔹 Systemic Antibiotics
Used for moderate-to-severe acne.
Common oral options:
Doxycycline
Minocycline
Sarecycline
Mechanism:
Block protein synthesis via 30S ribosomal subunit
Reduce inflammation by blocking neutrophils and inflammatory cytokines
Contraindicated in:
Pregnancy
Breastfeeding
Children <9 (risk of tooth discoloration and enamel damage)
✔️ Limiting use is strongly advised to reduce resistance and complications. 📊 Dermatologists prescribe more oral antibiotics than any other specialty (most often for acne).
Systemic Antibiotics in Acne Treatment – Full English Summary
General Considerations
In addition to concerns about antibiotic resistance, oral tetracycline-class antibiotics have been associated with inflammatory bowel disease (IBD), pharyngitis, Clostridium difficile infection, and Candida vulvovaginitis. Outpatient antibiotic stewardship promotes appropriate antibiotic use, ensuring the right dose of the right antibiotic is given at the right time and for the right duration.
The Centers for Disease Control and Prevention (CDC) recommend outpatient antibiotic stewardship programs that include:
Commitment to optimizing antibiotic prescribing and patient safety
Implementation of policies or practices to support stewardship
Tracking and feedback on prescribing practices
Access to educational resources and expert support
When treating acne with systemic antibiotics:
Concomitant use of benzoyl peroxide (BP) and other topical therapies is recommended to reduce resistance.
Oral antibiotics should not be used as monotherapy.
Systemic antibiotics should be used for the shortest possible duration, ideally no more than 3–4 months.
In patients who do not respond or cannot tolerate non-antibiotic therapies, longer courses of antibiotics may be needed — but regular follow-up and continued use of topical treatments are essential to limit antibiotic duration and sustain results.
Doxycycline
Doxycycline is recommended for acne treatment based on moderate certainty evidence from 5 studies.
In 2 RCTs, a greater proportion of patients receiving doxycycline achieved Investigator’s Global Assessment (IGA) success at 4 months (RR: 1.80 [1.17, 2.77]).
Adverse effects led to treatment withdrawal more often in doxycycline than placebo groups (1.3% vs 0.3%; RR: 2.25).
Gastrointestinal side effects (nausea, vomiting, diarrhea) occurred in 15.7% of patients on doxycycline vs 5.9% on placebo (RR: 2.56).
Rare risks include esophagitis, phototoxicity, and intracranial hypertension.
Recommendations to reduce GI side effects:
Take doxycycline with food and sufficient water
Stay upright for a while after ingestion
Low-dose doxycycline (20 mg twice daily or 40 mg extended-release daily) has shown effectiveness in moderate inflammatory acne, but evidence comparing dosages is insufficient.
We conditionally recommend doxycycline over azithromycin for acne based on low-certainty evidence from 4 studies. One study showed a greater reduction in total lesion counts with doxycycline vs azithromycin at 12 weeks (mean difference: –6.0 lesions).
Azithromycin is a broad-spectrum macrolide often used for respiratory infections. Increasing its use for acne may promote antibiotic resistance.
Minocycline
Minocycline is conditionally recommended for acne treatment based on moderate-certainty evidence from 5 studies, along with expert discussion of rare but serious side effects.
In 2 RCTs, more patients on minocycline achieved IGA success at 12 weeks (RR: 1.82 [1.28, 2.57]).
Adverse events requiring treatment discontinuation were more frequent with minocycline vs placebo (9.1% vs 1.0%; RR: 6.23).
Side effects are generally similar to doxycycline but may also include:
Vertigo
Autoimmune hepatitis
Skin hyperpigmentation
Drug-induced lupus
Hypersensitivity syndrome
There is insufficient direct evidence comparing minocycline and doxycycline, so the choice should be based on patient-specific risks and benefits.
Monotherapy with oral minocycline is not superior to topical benzoyl peroxide (BP 5%) or erythromycin 2%/BP 5% combination in mild to moderate acne.
There is also insufficient evidence to recommend long-term use of minocycline or its use as maintenance therapy with tazarotene beyond 3–4 months.
Sarecycline
Sarecycline is a narrow-spectrum tetracycline-class antibiotic recommended for moderate to severe acne treatment. Clinical trials have shown that sarecycline significantly reduces inflammatory lesions compared to placebo, with 52.7% reduction at 1.5 mg/kg dosage. It is generally well tolerated, with low rates of gastrointestinal side effects and no serious adverse events reported. However, due to its high cost, its use is conditionally recommended, pending changes in treatment cost and access.
PubMed
Systemic Antibiotics Considerations
Oral tetracycline-class antibiotics, including doxycycline, minocycline, and sarecycline, are FDA-approved for acne management. They should be avoided during pregnancy and lactation due to potential risks to the fetus or nursing infant. The use of systemic antibiotics should be limited to the shortest duration necessary, typically no more than 3-4 months, to minimize the risk of antibiotic resistance.
Combined Oral Contraceptives (COCs)
COCs containing estrogen and progestin can effectively treat acne by reducing androgenic activity. Studies have shown that COCs lead to significant reductions in both inflammatory and non-inflammatory acne lesions. Commonly used COCs for acne treatment include those containing drospirenone, norgestimate, and norethindrone acetate. While COCs are effective, they are associated with potential risks such as venous thromboembolism, myocardial infarction, and stroke, particularly in women over 35 who smoke or have certain health conditions. Therefore, their use should be carefully considered based on individual health profiles and preferences.
Combined Oral Contraceptives (COCs)
COCs can be used alongside other acne medications, including tetracycline antibiotics and spironolactone.
Tetracycline antibiotics do not reduce the effectiveness of COCs.
Rifampin and griseofulvin are two anti-infectives known to reduce COC effectiveness.
Using spironolactone and drospirenone together doesn’t significantly increase potassium levels or adverse effects.
FDA approval for acne-related COC use:
Drospirenone/EE or Drospirenone/EE/Levomefolate: age 14+
Norgestimate/EE or Norethindrone/EE/Ferrous fumarate: age 15+
A newer COC (drospirenone/estetrol) was FDA-approved in 2021 for contraception, but its role in acne treatment is unclear.
Spironolactone
Mechanism: Blocks androgen receptors, reduces testosterone, and may inhibit 5α-reductase.
Not FDA-approved for acne, but conditionally recommended based on moderate certainty evidence.
Shown to be effective at 50–200 mg/day, with or without benzoyl peroxide.
Similar effectiveness to oral tetracyclines, according to cohort studies.
Side effects:
Most common: menstrual irregularities (especially without COC use)
Others: breast tenderness/enlargement, dizziness, headache, fatigue, diuresis
Potassium monitoring:
Not usually necessary in healthy young women
Advised in older adults or those with health issues or on medications affecting kidney function
Rare cases of hyperkalemia have been documented, mostly mild and asymptomatic.
Not safe during pregnancy: Animal studies show possible feminization of male fetus; limited human data also suggest caution.
Tumor warning exists based on long-term animal studies with high doses (not directly confirmed in humans).
Intralesional Corticosteroids
Used as adjunctive therapy for inflammatory acne (especially large papules or nodules).
In a small study (9 patients), triamcinolone injections resolved cysts within 3–7 days, faster than saline.
Also effective for other skin conditions: granuloma annulare, hidradenitis suppurativa, keloids, inflamed cysts.
Best for quick relief of inflammation, pain, or scarring risk.
Risks include skin atrophy, adrenal suppression, or systemic absorption.
Safer when used in low doses (e.g., 2.5–5 mg/ml of triamcinolone).
Hormonal Agents – Oral Corticosteroids, Flutamide, Metformin
Not enough evidence to recommend these for routine acne treatment.
Oral corticosteroids may be temporarily useful in:
Severe inflammatory acne
Acne fulminans
Isotretinoin-induced flares
Prednisone (0.5–1 mg/kg/day) has been used in these cases.
Long-term steroid use is discouraged due to adverse effects.
Isotretinoin
FDA-approved since 1982 for severe nodular acne.
Works by reducing:
Sebaceous gland size
Sebum production
C. acnes population
Inflammation and comedone formation
Despite limited high-quality RCTs, real-world effectiveness is well-documented.
Studies show:
Up to 89% success rate after 20 weeks (standard dosing).
Even low doses (5 mg/day) showed benefit in moderate acne.
Best for:
Severe, scarring, or persistent acne
Psychosocial burden related to acne
Relapses after oral antibiotics
Considered the gold standard in severe acne by many experts.
Good practice recommendation issued for patients unresponsive to other treatments.
Lab Monitoring During Isotretinoin Treatment
Required tests:
Liver function tests (LFTs)
Fasting lipid panel (triglycerides, cholesterol)
Pregnancy test (for people who can become pregnant)
Not recommended:
Routine complete blood count (CBC)
Key stats from studies:
Abnormal liver tests: 0.8%–10.4%
Abnormal triglycerides: 7.1%–39.0%
Abnormal cholesterol: 6.8%–27.2%
CBC abnormalities:
Mild anemia: 0.4%
Platelet issues: 1.2%–2.9%
White blood cell issues: 7%–10.8%
No serious (grade 3+) CBC issues observed
Consensus suggests monitoring ALT and triglycerides only, not LDL/HDL or CBC.
Pregnancy Risk & iPLEDGE Program
Isotretinoin is highly teratogenic → strict pregnancy prevention is mandatory.
iPLEDGE is the U.S. FDA-mandated program to prevent pregnancy exposure.
As of 2021, patients are grouped in gender-neutral categories:
Cannot become pregnant
Can become pregnant
Requirements for patients who can become pregnant:
Must use 2 forms of contraception or abstain:
At least 1 month before, during, and 1 month after treatment
Despite this, ~150 pregnancies/year still occur (mostly due to non-compliance).
Long-acting contraceptives (IUDs, implants) are recommended as they are more effective than pills or condoms.
Safety & Risk of Other Conditions
No proven link to:
Inflammatory bowel disease (IBD): RR = 1.13 (not statistically significant)
Neuropsychiatric effects (e.g., depression, suicidal thoughts): RR = 0.88
Some reports suggest mood changes during treatment, but current data does not support a causal relationship.
Mental Health Monitoring
Important context: Depression, anxiety, and suicidal ideation are already common—especially in teens (primary candidates for isotretinoin).
Clinician recommendation: Monitor for neuropsychiatric symptoms during treatment.
Screening tools:
PHQ-2 and PHQ-9 are recommended tools for depression screening.
National guidelines:
USPSTF recommends depression screening in adults and adolescents (12–18 yrs).
Anxiety screening in ages 8–18.
💊 Dosing Regimens
Daily dosing (0.5–0.7 mg/kg) is conditionally recommended over intermittent dosing.
Daily dosing led to:
Greater reduction in acne severity
Slightly more withdrawals due to side effects (6.7% vs 0%)
🧪 Formulation: Standard vs Lidose-Isotretinoin
Lidose-isotretinoin: More stable absorption regardless of food.
Standard isotretinoin: Needs high-fat meals for optimal absorption.
Both are equally effective and safe per 782-patient RCT.
⚠️ Procedures & Devices
Safe during or post isotretinoin:
Superficial peels
Nonablative lasers (e.g., hair removal)
Avoid within 6 months:
Full-face ablative lasers
Mechanical dermabrasion
Not recommended:
Pneumatic broadband light + adapalene → no added benefit, risk of hyperpigmentation/purpura.
🌿 Complementary Therapies
No recommendations due to insufficient evidence for:
Tea tree oil, green tea, witch hazel, zinc, niacinamide, pantothenic acid
🥦 Diet
Evidence is conflicting for:
Low-glycemic diets: Some RCTs show benefit, others not.
Dairy, whey, omega-3, chocolate: No conclusive data.
📉 Research Gaps
Lack of RCTs on:
Diverse populations (e.g. skin of color, LGBTQ+)
Hormonal therapies
Dietary interventions
Microbiological/endocrine testing
Cost-effectiveness
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