Alopesia Androgenetik

01Pathophysiology

Androgenetic alopecia (AGA) is the most common cause of hair loss worldwide, affecting up to 50% of men by age 50 and a considerable proportion of women after menopause. Understanding the mechanism is essential because the pathophysiology directly explains both the clinical pattern and the rationale for every treatment option.

The central molecule is dihydrotestosterone (DHT). Circulating testosterone enters the dermal papilla cells of genetically susceptible hair follicles. There, the enzyme 5-alpha reductase type II converts testosterone into DHT, which has roughly five times greater binding affinity for the androgen receptor than testosterone itself. Once DHT binds the androgen receptor, it triggers a cascade that progressively shortens the anagen (growth) phase of the hair cycle while leaving the telogen (resting) phase unchanged. Over successive cycles, the follicle produces thinner, shorter, and less pigmented hairs. This process is called follicular miniaturization: terminal hairs gradually transform into vellus-like hairs until the follicle eventually produces no cosmetically visible hair at all.

The reason the pattern of loss differs between scalp regions is due to regional variation in androgen receptor density and 5-alpha reductase expression. The frontal, temporal, and vertex scalp regions have high concentrations of androgen receptors, making them susceptible to DHT-mediated miniaturization. The occipital and parietal regions are relatively androgen-insensitive, which is why these areas are spared and serve as the donor site for hair transplantation.

In women, the mechanism is identical but the clinical pattern differs because of the protective effect of aromatase, which converts testosterone to estradiol in the frontal scalp. This enzyme is expressed at higher levels in women, explaining why women typically preserve the frontal hairline and instead develop diffuse thinning over the crown.

The inheritance pattern is polygenic, involving the androgen receptor gene on the X chromosome (inherited from the mother) along with multiple autosomal loci. This is why a family history from either parental side is relevant.

02Classification and Clinical Manifestation

Male Pattern: Hamilton-Norwood Classification

Female Pattern: Ludwig Classification

A key clinical distinction for vignettes: men present with recession and vertex balding, while women present with diffuse thinning and a widened central part. Women almost never develop complete baldness, and frontal hairline recession in a woman should prompt evaluation for a hyperandrogenic state.

03Diagnostic Workup

Summary Table

AGA is overwhelmingly a clinical diagnosis. In men with a classic Hamilton-Norwood pattern and positive family history, no further workup is required. Trichoscopy has become the most useful bedside adjunct: the hallmark finding is hair diameter diversity, meaning a mix of thick terminal hairs and thin miniaturized hairs within the same field. This directly reflects the miniaturization process described in the pathophysiology.

The hair pull test is useful primarily for what it excludes. In AGA, the pull test is negative because the problem is not active shedding but rather gradual follicular shrinkage. A strongly positive pull test (more than 6 hairs per gentle traction) should redirect your thinking toward telogen effluvium or alopecia areata.

Scalp biopsy is reserved for diagnostically uncertain cases, particularly in women with diffuse thinning where the differential includes chronic telogen effluvium. If a biopsy is performed, horizontal sectioning (not vertical) is the technique of choice because it allows assessment of follicular density and the vellus-to-terminal ratio across an entire cross-section of scalp.

In women, the workup is broader. Any woman presenting with patterned hair loss, particularly if she also has acne, hirsutism, or menstrual irregularity, warrants a hormonal evaluation to exclude PCOS, congenital adrenal hyperplasia, or an androgen-secreting tumor. Ferritin below 40 ng/mL, even without frank anemia, has been associated with worsened hair shedding and should be corrected.

04Management and Treatment (Aligned with PERDOSKI 2024)

Non-Pharmacologic Measures

Education and expectation-setting are foundational. Patients must understand that AGA treatment is lifelong and that response assessment requires 6 to 12 months of consistent use before efficacy can be judged. Non-pharmacologic camouflage (hairstyling, wigs) is a valid and underappreciated intervention, especially for patients who decline or cannot tolerate medical therapy.

Topical Therapy

Topical minoxidil remains the cornerstone of first-line therapy for both men and women. It is a potassium channel opener and vasodilator that prolongs the anagen phase and stimulates follicular growth. Men may use 2% to 5% solutions or foam applied once to twice daily; women should use 2% solution applied once to twice daily. The 5% formulation in women carries a higher risk of facial hypertrichosis, which is why the lower concentration is preferred in guidelines, though some women tolerate 5% foam once daily.

A key counseling point: initial telogen shedding during the first 2 to 8 weeks of minoxidil therapy is a sign that the medication is working. The drug pushes telogen-phase hairs out to make way for new anagen-phase hairs. Patients who discontinue treatment during this phase lose the therapeutic benefit.

Topical finasteride (solution 0.25%, gel 1%) is a notable addition in the PERDOSKI 2024 guideline at evidence level 2B. The rationale is to deliver local DHT suppression at the follicular level while minimizing systemic absorption, partially addressing the sexual and psychiatric side-effect concerns that limit acceptance of oral finasteride in some patients.

Other topical agents such as caffeine, melatonin, retinoids, biochanin A, adenosine, prostaglandin analogs, and herbal preparations carry a 2C evidence level and serve as adjuncts rather than stand-alone therapies.

Systemic Therapy: Males

Oral finasteride is the highest-evidence systemic agent for men (1A). It is a selective type II 5-alpha reductase inhibitor that reduces scalp DHT by approximately 60-70%. PERDOSKI 2024 lists the dose range as 1 to 5 mg/day, which is broader than the traditional 1 mg/day used in many Western guidelines. This higher dose ceiling is relevant for vignettes that test dose adjustment in partial responders.

The contraindication profile per PERDOSKI 2024 is broader than pregnancy alone. 5-alpha reductase inhibitors (finasteride and dutasteride) are restricted to males aged 18 years and older and postmenopausal women only. They are contraindicated in patients with pre-existing sexual dysfunction, psychiatric disorders, women of reproductive age, and children. This is a testable distinction: a vignette describing a male patient with baseline depression or erectile dysfunction who presents with AGA would make finasteride the wrong answer choice.

Dutasteride inhibits both type I and type II 5-alpha reductase, reducing DHT by over 90%. It is listed at evidence level 2B with the explicit note that it is not yet available in Indonesia. Dutasteride is considered when finasteride alone produces an inadequate response.

Low-dose oral minoxidil at 2.5 mg/day (2C) is now part of the PERDOSKI armamentarium. This is clinically relevant for patients who develop contact dermatitis or scalp irritation from topical minoxidil, or who find topical application impractical. Monitor for fluid retention, pericardial effusion, and reflex tachycardia at higher doses.

Systemic Therapy: Females

A critical PERDOSKI 2024 principle for women: systemic anti-androgen therapy is indicated only when hyperandrogenism is present ("jika hiperandrogenisme"). This means the decision to add CPA, spironolactone, or flutamide is conditional on laboratory or clinical evidence of androgen excess, not simply the diagnosis of AGA. Women with AGA but no hyperandrogenism should be managed with topical minoxidil and procedural therapies.

Cyproterone acetate combined with ethinylestradiol (2B) is the highest-evidence systemic option for women with confirmed hyperandrogenism. It functions as both an anti-androgen and an oral contraceptive, which is advantageous given the mandatory contraception requirement for all anti-androgen agents.

Spironolactone at 25 to 200 mg/day (2C) is an androgen receptor antagonist that also reduces androgen synthesis. The PERDOSKI dose range starts at 25 mg, which is lower than the 100 mg floor commonly cited in other guidelines, allowing more gradual titration. Baseline and periodic monitoring of serum potassium is necessary, and caution is needed in patients taking ACE inhibitors, ARBs, or potassium-sparing diuretics.

Flutamide at 250 mg/day (2C) is a non-steroidal anti-androgen. Its use is limited by the risk of hepatotoxicity, and liver function tests must be monitored throughout treatment.

Low-dose oral minoxidil at 0.5 to 2 mg/day (2C) is available for women who cannot tolerate topical formulations. Note the lower dose range compared to men (0.5-2 mg versus 2.5 mg).

All anti-androgen agents in women of reproductive age must be co-administered with reliable contraception to prevent feminization of a male fetus.

Procedural Interventions

Procedural interventions are generally used as adjuncts to medical therapy, not as replacements. Medical therapy should continue post-transplant to prevent progressive loss of native, non-transplanted hairs. Microneedling has gained attention for its synergistic effect when combined with topical minoxidil, as the micro-channels improve drug penetration into the follicular unit.

Treatment Algorithm Summary

Men:

1. Start topical minoxidil 2-5% once to twice daily (1A).

2. Add oral finasteride 1-5 mg/day (1A) if not contraindicated by sexual dysfunction, psychiatric disorder, or age under 18.

3. Consider topical finasteride 0.25% solution or 1% gel (2B) as an alternative to oral if systemic side effects are a concern.

4. If topical minoxidil is poorly tolerated, switch to low-dose oral minoxidil 2.5 mg/day (2C).

5. If inadequate response to finasteride, consider dutasteride (2B, if available).

6. Adjunctive procedures (PRP, LLLT, microneedling) as needed.

7. Hair transplantation for stable, refractory cases with continued medical therapy.

Women:

1. Start topical minoxidil 2% once to twice daily (1A).

2. Evaluate for hyperandrogenism (labs, clinical signs).

3. If hyperandrogenism confirmed: add CPA + ethinylestradiol (2B) or spironolactone 25-200 mg/day (2C) or flutamide 250 mg/day (2C), all with mandatory contraception.

4. If topical minoxidil is poorly tolerated, switch to low-dose oral minoxidil 0.5-2 mg/day (2C).

5. Consider topical finasteride (2B) only in postmenopausal women; absolutely contraindicated in reproductive-age women.

6. Adjunctive procedures (PRP, LLLT, microneedling) as needed.

7. Refer to endocrinology if underlying hyperandrogenic disorder is suspected.

05Differential Diagnosis and Distractors

The highest-yield discriminator for exam purposes is the hair pull test and onset pattern. AGA is gradual with a negative pull test. Telogen effluvium is abrupt with a positive pull test. Alopecia areata shows smooth patches with exclamation point hairs. If the vignette includes scaling or broken hairs, think infectious (tinea) or mechanical (traction, trichotillomania).

06Traps and High-Yield Pearls

The most common way students get questions on androgenetic alopecia wrong is by confusing it with telogen effluvium in a female patient with diffuse hair thinning. The vignette will often describe a woman with gradual, progressive thinning over several months to years with a widened central part and no identifiable trigger. Students see "diffuse thinning" and jump to telogen effluvium, but the key distinguishing features are the chronicity (years, not weeks), the pattern (crown, not uniform), and the negative pull test. Telogen effluvium always has a temporal trigger 2 to 3 months prior.

The second major trap involves finasteride prescribing errors. Under PERDOSKI 2024, the contraindication list is broader than pregnancy alone: finasteride and dutasteride are restricted to males over 18 and postmenopausal women, and are contraindicated in patients with pre-existing sexual dysfunction or psychiatric disorders. A vignette describing a male patient with baseline depression or erectile dysfunction who presents with AGA would make oral finasteride the wrong next step. In that scenario, topical finasteride (2B) or topical minoxidil would be the appropriate choice.

The third trap is prescribing anti-androgens to women without confirmed hyperandrogenism. PERDOSKI 2024 is explicit: CPA, spironolactone, and flutamide are indicated in women "jika hiperandrogenisme" (only if hyperandrogenism is present). A woman with AGA but normal androgens should be managed with topical minoxidil and procedural adjuncts, not anti-androgen therapy.

The fourth commonly tested concept is the initial shedding phenomenon with minoxidil. The vignette may describe a patient who started treatment 4 weeks ago and is now experiencing increased hair loss, asking what to do next. The answer is reassurance and continuation of therapy, not discontinuation or switching. This shedding is paradoxically a sign of drug efficacy.

Finally, remember that AGA is non-scarring. If a vignette describes hair loss with visible scalp scarring, erythema, or follicular destruction, the diagnosis is not AGA. Scarring alopecias (such as discoid lupus, lichen planopilaris, or central centrifugal cicatricial alopecia) are a completely different category with different workup and management. The presence or absence of scarring is one of the first branch points in the diagnostic algorithm for any alopecia question.