A new trial comparing oral and topical minoxidil for male androgenetic alopecia found that 5 mg of the oral drug once daily did not demonstrate overall superiority to the topical drug, 5% twice daily after 24 weeks of treatment.

In the double-blind, placebo-controlled randomized clinical trial, published in JAMA Dermatology, researchers enrolled 90 men with androgenetic alopecia aged 18 to 55 years at a single specialized clinic in Brazil. The participants were randomized 1:1 to receive either 5 mg of oral minoxidil daily plus topical placebo or topical minoxidil, 5% twice daily plus oral placebo for 24 weeks. Eligibility criteria included androgenetic alopecia classified as 3V, 4V, or 5V on the Norwood-Hamilton scale. The researchers used standardized trichoscopic images for hair counting and automated detection with manual correction for hair density assessment.

The participants' baseline characteristics were:

• Mean age: 36.6 (standard deviation [SD] = 7.8) years
• Norwood-Hamilton scale distribution: 3V (53% to 60%), 4V (29% to 36%), 5V (11%)
• Mean BMI: 27.1 (SD = 3.9) in oral group, 28.1 (SD = 4.3) in topical group
• Baseline mean arterial pressure: 95.3 (SD = 8.0) mmHg in oral group, 95.0 (SD = 7.4) mmHg in topical group.

The primary outcomes were:

• Terminal hair density changes: frontal area = mean difference between groups was 3.1 hairs/cm² (95% confidence interval [CI] = –18.2 to 21.5, P = .27), vertex area = mean difference was 23.4 hairs/cm² (95% CI = –0.3 to 43.0, P = .09)
• Total hair density changes: frontal area = mean difference was 2.6 hairs/cm² (95% CI = –10.3 to 15.8, P = .32), vertex area = mean difference was 5.5 hairs/cm² (95% CI = –12.5 to 23.5, P = .32)
• Percentage increase in terminal hair density: vertex = 27.1% higher in oral minoxidil group (95% CI = 6.5 to 47.8, P = .005), frontal = 13.1% higher in oral minoxidil group (95% CI = –11.5 to 37.5, P = .15).

Detailed hair density measurements:

• Frontal baseline terminal hair density: 91.2 (SD = 47.6) hairs/cm² in oral group, 105.3 (SD = 42.2) hairs/cm² in topical group
• Vertex baseline terminal hair density: 96.8 (SD = 48.1) hairs/cm² in oral group, 134.3 (SD = 51.4) hairs/cm² in topical group
• Frontal baseline total hair density: 190.2 (SD = 61.2) hairs/cm² in oral group, 207.4 (SD = 63.7) hairs/cm² in topical group
• Vertex baseline total hair density: 190.3 (SD = 55.8) hairs/cm² in oral group, 211.6 (SD = 67.8) hairs/cm² in topical group.

Percentage changes in hair density:

• Frontal terminal hair density: 20.0% increase (95% CI = 4.8 to 39.9) in oral group vs 7.0% increase (95% CI = –4.7 to 20.4) in topical group
• Frontal total hair density: 7.0% increase (95% CI = 3.0 to 11.5) in oral group vs 6.4% increase (95% CI = 0.7 to 13.5) in topical group
• Vertex terminal hair density: 21.6% increase (95% CI = 8.6 to 34.0) in oral group vs 5.6% decrease (95% CI = –17.5 to 6.4) in topical group
• Vertex total hair density: 8.7% increase (95% CI = 1.5 to 16.2) in oral group vs 4.9% increase (95% CI = 0 to 10.8) in topical group.

The secondary outcomes were:

• Photographic evaluation: vertex = 70% of oral minoxidil group showed improvement vs 46% in topical group (difference = 24%, 95% CI = 0 to 48, P = .04), frontal = no significant difference between groups (60% vs 48%, P = .24)
• Global Aesthetic Improvement Scale (GAIS) for vertex: oral group = –1 (6%), 0 (24%), 1 (48%), 2 (21%); topical group = –1 (3%), 0 (51%), 1 (40%), 2 (6%)
• Adverse effects: hypertrichosis = more common in oral minoxidil group (49% vs 25%, P = .02), headache = more prevalent in oral minoxidil group (14% vs 2%, P = .046), scalp eczema = more common in topical minoxidil group (16% vs 2%, P = .02), itching on the scalp = 2% in oral group vs 11% in topical group (P = .09), nightmares = 2% in oral group vs 5% in topical group (P = .58), shedding: 9% in oral group vs 16% in topical group (P = .34), insomnia: 2% in oral group vs 5% in topical group (P = .58), lower limb edema = 2% in oral group vs 0% in topical group (P = .33)
• Cardiovascular parameters at 24 weeks: heart rate = 72.9 (SD = 7.6) beats/min in oral group, 72.2 (SD = 9.5) beats/min in topical group; systolic blood pressure = 123.0 (SD = 9.5) mmHg in oral group, 118.3 (SD = 9.9) mmHg in topical group; diastolic blood pressure = 80.9 (SD = 6.8) mmHg in oral group, 79.7 (SD = 8.6) mmHg in topical group; mean arterial pressure = 94.9 (SD = 7.1) mmHg in oral group, 92.6 (SD = 8.4) mmHg in topical group.

Dropout analysis:

• Oral minoxidil group: 12 dropouts (27%), 11 because of the COVID-19 pandemic, 1 because of headache
• Topical minoxidil group: 10 dropouts (22%), 7 because of the COVID-19 pandemic, 1 because of insomnia, 1 because of persistent scalp eczema, 1 because of intense hair shedding.

The trial limitations included its monocentric format, relatively small sample size, and substantial rates of follow-up loss. The sample size calculation was based on an expected increase of 35 terminal hairs/cm² in the oral group and 12 terminal hairs/cm² in the topical group, with a power of 80%, α of 5%, 0.7 correlation coefficient between measurements, and 30% expected dropout rate.

The researchers concluded that while oral minoxidil did not demonstrate overall superiority to topical minoxidil, it showed greater improvement in vertex hair density and photographic assessment. Low-dose oral minoxidil was well-tolerated and may be an option for patients who prefer oral therapy or are intolerant to topical treatment.

The lead author reported receiving grants from the Brazilian Dermatology Society Support Fund (FUNADERM) during the study; no other disclosures were reported.