DHT Blockers for Androgenetic Alopecia
Primary Treatment Recommendation
Oral finasteride 1 mg daily is the gold standard DHT blocker for male androgenetic alopecia, with proven efficacy in reducing scalp DHT by approximately 64% and serum DHT by 71%, while topical finasteride 0.25% offers comparable DHT suppression with significantly lower systemic absorption for patients concerned about sexual side effects. 1, 2, 3
Mechanism and Efficacy
How DHT Blockers Work
- Finasteride competitively inhibits Type II 5α-reductase, forming a stable enzyme complex with extremely slow turnover (half-life ~30 days), preventing conversion of testosterone to DHT in the prostate, liver, and skin 1
- Scalp DHT reduction occurs rapidly, with maximum suppression at 8 hours after first dose and sustained throughout 24-hour dosing intervals 1
- Doses as low as 0.2 mg daily maximally decrease both scalp skin and serum DHT levels, though 1 mg is the FDA-approved dose 2
Expected Outcomes
- Meta-analysis confirms finasteride is superior to placebo (P < 0.00001) for promoting hair growth in men with androgenetic alopecia 4
- Dutasteride 0.5 mg demonstrates better responses than finasteride, especially in the frontal area, as it inhibits both Type I and Type II 5α-reductase isoforms 5, 6
- Treatment must continue indefinitely - discontinuation results in return of DHT levels to pretreatment values within approximately 2 weeks 1
Treatment Options by Route
Oral Finasteride (FDA-Approved)
- Standard dose: 1 mg daily for male pattern hair loss 1, 5
- Produces approximately 70% reduction in serum DHT with daily dosing for up to 4 years 1
- Testosterone levels increase by 10-20% but remain within physiologic range 1
- No effect on hypothalamic-pituitary-testicular axis, LH/FSH response to GnRH remains normal 1
Topical Finasteride (Emerging Option)
- Topical finasteride 0.25% applied twice daily reduces plasma DHT by 68-75% with significantly lower systemic exposure than oral formulation 3
- Plasma finasteride levels are 10-fold lower with topical versus oral administration (0.46 ng/mL vs 6.86 ng/mL), potentially reducing sexual side effects 3
- Efficacy demonstrated in clinical trials with less marked decrease in serum DHT than oral intake 5
Dutasteride
- Oral dutasteride 0.5 mg inhibits both Type I and Type II 5α-reductase, causing greater and more consistent DHT decrease than finasteride 6
- Superior efficacy compared to finasteride, particularly for frontal scalp 5
- Mesotherapy with dutasteride has become widespread, though evidence limited to retrospective studies 5
- Not FDA-approved for androgenetic alopecia but used off-label 5
Side Effect Profile and Management
Sexual Side Effects (Most Common Concern)
- Erectile dysfunction occurs in additional 2-4% of patients compared to placebo, with absolute rates of 4.2-15.8% depending on study duration 6, 7
- The magnitude is clinically modest: on 0-100 scale, finasteride causes mean difference of only 3.21 points compared to 1.26 points for each year of aging 6, 7
- Sexual side effects decrease over time and remain statistically significant but clinically small after first year 6, 7
- Decreased libido affects 2-4% more patients than placebo 7
- Reduced ejaculate volume reported in 1.5-7.2% of patients 7
Other Adverse Effects
- Gynecomastia occurs in 0.5-2.2% of patients versus 0.1-1.1% with placebo 6, 7
- Overall discontinuation rates approximately 15% for both finasteride and placebo groups 6, 7
- Discontinuation specifically due to adverse events is 6-7% in both treatment and placebo groups 6, 7
Critical Monitoring Requirement
- PSA levels must be doubled after 12 months of therapy to accurately interpret prostate cancer screening 6, 7
- Finasteride lowers PSA by 50% after 12 months, requiring multiplier of 2 as criterion for biopsy 6
- At 3 years, PSA decline exceeds 50%, requiring adjustment to multiplier of 2.3 6
- Delayed cancer diagnosis may occur if PSA adjustment not performed 7
Combination Therapy Strategies
DHT Blockers Plus Minoxidil
- Combination therapy is more effective than monotherapy for both male and female androgenetic alopecia 8, 9
- Protocol: Topical minoxidil 5% (1 mL) twice daily combined with oral finasteride 1 mg daily 8
- Continue indefinitely as discontinuation leads to reversal of benefits 8
DHT Blockers Plus PRP/PRF
- Complex therapy (PRP with minoxidil) significantly more effective than minoxidil monotherapy 6, 8
- Recommended protocol: 3-5 sessions at 1-month intervals using 5-7 mL PRP at 0.05-0.1 mL/cm², injections 1 cm apart, depth 2-4 mm 8
- Nonactivated PRP shows 31% greater improvement in hair density compared to activated PRP 8
- Maintenance phase: 1 session every 6 months after initial treatment 8
- 83% of patients achieve negative hair pull test with PRP combined with minoxidil 8
Treatment Algorithm
For Men with Androgenetic Alopecia
- First-line: Oral finasteride 1 mg daily for maximum efficacy with established safety profile 1, 4
- If concerned about sexual side effects: Topical finasteride 0.25% twice daily for comparable DHT suppression with lower systemic exposure 3
- For enhanced results: Add topical minoxidil 5% twice daily to finasteride regimen 8, 9
- For refractory cases: Consider dutasteride 0.5 mg daily for superior DHT suppression, especially frontal scalp 5
- For additional benefit: Add PRP therapy (3 sessions monthly, then maintenance every 6 months) 8
For Women with Androgenetic Alopecia
- DHT blockers (finasteride/dutasteride) are NOT recommended as first-line therapy in women 8
- Topical minoxidil is first-line treatment for female androgenetic alopecia 8
- PRP combined with minoxidil shows superior efficacy compared to either treatment alone 6, 8
Critical Caveats
Contraindications and Warnings
- Finasteride is contraindicated in women of childbearing potential due to teratogenic effects on male fetus 1
- Post-finasteride syndrome remains controversial, with FDA label amended to warn about persistent symptoms after discontinuation based on anecdotal reports rather than prospective trials 7
- No clinical data support triple androgen blockade (finasteride or dutasteride with combined androgen blockade) 6
Monitoring and Follow-Up
- Evaluate treatment response at 6 months using standardized photographs, trichoscopy for hair density/diameter, and patient self-assessment 8
- 25% improvement in hair density at 2 months predicts sustained response at 6 months 8
- Maximum response typically achieved by 6 months, though some patients require extended therapy 8
- PSA monitoring essential in men over 50 with appropriate doubling of values during interpretation 6, 7