New Treatment Options for AGA and AA: What’s Changing in Hair Loss Management

Pathophysiology of Androgenic Alopecia (AGA) vs. Alopecia Areata (AA)

Androgenic Alopecia (AGA): The Role of Genetics and Hormones

• AGA, commonly known as male-pattern baldness or female-pattern hair loss, is a genetically predetermined condition influenced by androgens, especially dihydrotestosterone (DHT).
• DHT binds to androgen receptors in susceptible hair follicles, leading to progressive miniaturization of hair follicles, shortened anagen (growth) phase, and prolonged telogen (resting) phase.
• The process starts typically in the frontotemporal regions and vertex in men, while women experience diffuse thinning over the crown.
• Genes involved: AR gene polymorphism (Androgen Receptor), 5-alpha reductase enzyme variations.

Alopecia Areata (AA): Autoimmunity at the Core

• AA is an autoimmune disorder where the body’s immune system mistakenly attacks the hair follicles, specifically targeting the anagen hair bulb.
• Cytotoxic T lymphocytes infiltrate the peribulbar region, producing an inflammatory response known as the “swarm of bees” pattern on histology.
• AA is associated with other autoimmune conditions like vitiligo, thyroid disease, and Type 1 diabetes.
• Environmental triggers, psychological stress, and infections are implicated as initiating factors.

Epidemiology and Demographics

Androgenic Alopecia (AGA): A Common Adult Issue

• Affects approximately 50% of men by age 50 and up to 80% by age 70.
• Female AGA affects 40% of women by age 50, especially post-menopause.
• Prevalence increases with age but can start as early as puberty.

Alopecia Areata (AA): Can Strike Any Age

• Lifetime risk is about 2%, affecting males and females equally.
• Peak onset: childhood and young adulthood, but can occur at any age.
• Often associated with a family history of autoimmune diseases.

Clinical Presentation and Patterns

Androgenic Alopecia (AGA): Predictable Hair Loss Patterns

• Hamilton-Norwood Scale in men: stages from bitemporal recession to complete baldness.
• Ludwig Scale in women: diffused thinning over the crown, often preserving the frontal hairline.
• Hair shafts miniaturize progressively; vellus-like hairs replace terminal hairs.

Alopecia Areata (AA): Sudden and Patchy

• Well-circumscribed round or oval patches of hair loss, commonly on the scalp, beard, eyebrows, and eyelashes.
• Subtypes:
  • Alopecia Totalis: entire scalp hair loss.
  • Alopecia Universalis: loss of all body hair.
  • Ophiasis: band-like hair loss at the temporal and occipital scalp.
• “Exclamation mark hairs” are diagnostic – narrow at the scalp and wider distally.

Diagnosis and Differentiation Methods

Androgenic Alopecia (AGA): Diagnosed Primarily Clinically

• History and examination sufficient in most cases.
• Trichoscopy findings: hair shaft miniaturization, increased vellus hair, peripilar signs (brown peripilar halos).
• Hormonal evaluations are rare unless signs of hyperandrogenism in women (hirsutism, acne).

Alopecia Areata (AA): Requires Dermatological Assessment

• Trichoscopy: yellow dots, black dots, broken hairs, exclamation mark hairs.
• Scalp biopsy: peribulbar lymphocytic infiltration (“swarm of bees”).
• Autoimmune panel may be indicated if other autoimmune diseases are suspected.

Histopathology: A Microscopic Insight

Androgenic Alopecia (AGA)

• Increased telogen to anagen ratio.
• Follicular miniaturization, replacing terminal hairs with vellus hairs.
• No significant inflammation.

Alopecia Areata (AA)

• Lymphocytic infiltration around anagen hair bulbs.
• “Swarm of bees” pattern.
• Hair follicles in different phases, often sudden shift into telogen.

Risk Factors and Associated Conditions

Androgenic Alopecia (AGA)

• Genetics: Strong family history link.
• Androgen excess.
• Associated with metabolic syndrome, coronary artery disease, and benign prostatic hyperplasia.

Alopecia Areata (AA)

• Genetic predisposition (HLA associations).
• Autoimmune conditions: Hashimoto’s thyroiditis, Type 1 Diabetes, Vitiligo.
• Psychological stress can precipitate or exacerbate attacks.

Treatment Approaches and Efficacy

Androgenic Alopecia (AGA): Targeting Hormonal Pathways

• FDA-Approved Treatments:
  • Minoxidil (topical): Vasodilator, prolongs anagen phase.
  • Finasteride (oral): 5-alpha reductase inhibitor, reduces DHT.
• Off-Label Options:
  • Dutasteride (stronger 5-alpha reductase inhibitor).
  • Low-level laser therapy (LLLT).
  • Platelet-rich plasma (PRP).
  • Hair transplant surgery for advanced cases.

Alopecia Areata (AA): Immunomodulatory Treatments

• Topical/Intralesional Steroids: First-line for limited patches.
• Topical Immunotherapy: Diphenylcyclopropenone (DPCP), squaric acid dibutylester (SADBE).
• Systemic Immunosuppressants: Methotrexate, cyclosporine for severe cases.
• JAK Inhibitors (Emerging Therapy): Baricitinib, Tofacitinib, showing promise in recent trials.
• Psychological support due to psychosocial impact.

Prognosis and Disease Course

Androgenic Alopecia (AGA): Chronic and Progressive

• Untreated AGA leads to permanent hair loss.
• Early intervention halts progression but does not reverse miniaturization significantly.
• Hair transplantation offers cosmetic recovery.

Alopecia Areata (AA): Unpredictable, Relapsing-Remitting

• 50% of patients experience spontaneous regrowth within a year.
• Recurrences are common; some develop chronic or severe variants like totalis or universalis.
• Nail changes like pitting may indicate severe disease.

Psychosocial Impact

Androgenic Alopecia (AGA): Affects Self-Esteem

• Men often seek treatment due to societal pressure about hair as a sign of masculinity.
• Women face distress due to noticeable scalp visibility, especially post-menopause.

Alopecia Areata (AA): Profound Psychological Toll

• Sudden hair loss can cause severe anxiety, depression, and social withdrawal.
• Children and adolescents are particularly vulnerable.
• Support groups and psychological counseling recommended.

Differentiating Factors at a Glance

Feature

Androgenic Alopecia (AGA)

Alopecia Areata (AA)

Etiology

Genetic + hormonal (DHT)

Autoimmune-mediated follicle attack

Onset

Gradual, puberty onwards

Sudden, any age, peaks in youth

Pattern

Predictable recession, crown thinning

Patchy, circular hair loss, random areas

Histopathology

Miniaturized follicles, no inflammation

Peribulbar lymphocytic infiltrates

Associated Conditions

CAD, prostate enlargement

Autoimmune diseases (thyroiditis, vitiligo)

Treatment

DHT blockers, minoxidil, transplant

Steroids, immunotherapy, JAK inhibitors

Prognosis

Progressive without treatment

Variable, unpredictable

Psychosocial Impact

High, but gradual adaptation

Severe, sudden changes, psychological impact

Why Differentiation is Critical in Clinical Practice

• AGA misdiagnosed as AA or vice versa leads to improper treatment plans.
• Steroids used for AA may not help AGA and can cause adverse effects.
• Recognizing AA early allows intervention before progression to universalis.
• For women, distinguishing AGA from diffuse AA or telogen effluvium is crucial, requiring careful history and investigation.

Future Directions in Research and Therapy

• Genetic testing for personalized AGA therapy.
• Advances in stem cell therapy and hair cloning for AGA.
• Targeted immunotherapy and biologics for AA.
• Further studies on the psychological impact and holistic management of hair loss disorders.