Minoxidil Mini-Series: Part 3 – Efficacy in Clinical Trials

In the last episode of the “Minoxidil Mini-Series,” we followed minoxidil from its inception in the laboratory through the world of cardiovascular medicine, ending with the exciting discovery that minoxidil was actually reversing male pattern baldness in some patients. This week on the Avacor® Hair Regrowth Blog the story continues with a summary of the clinical trials that proved minoxidil's effectiveness as a hair regrowth treatment.

Minoxidil’s success in clinical trials led to the first FDA approval for a hair loss drug, initially requiring a doctor’s prescription but available now as a popular over-the-counter product. This review is focused primarily on the findings of efficacy of minoxidil for hair regrowth; a summary of the side effects reported in the various trials will appear later in the Mini-Series.

After the initial reports of hair growth induced by minoxidil, several clinical groups began studying the safety and efficacy of minoxidil as a topical treatment for hair loss in both men and women.

Since there have been many studies on the efficacy of minoxidil for treating androgenetic alopecia, it would be impractical to go into great detail on each one here. If you would like to know more about the results of any of the studies listed in this post, please leave a comment about your particular area of interest and we will answer your question as quickly as possible.

Clinical Trials of Minoxidil for Male Pattern Hair Loss

A series of pivotal trials were conducted by Elise Olsen, M.D. and colleagues at the Duke University Medical Center, including one of the first major placebo-controlled, double-blind studies of minoxidil for male pattern baldness.

A dose escalation study by this group found that 1% was the minimum concentration of minoxidil that was effective at increasing total target area hair counts, but that 2% minoxidil produced superior results in the investigator’s assessment of cosmetic response.1

The same group conducted a double-blind, placebo-controlled crossover trial involving 126 men with early male pattern baldness (median age of ~36 years old) that compared topical minoxidil to a placebo control.2 After the first four months, patients receiving placebo were switched to a 3% minoxidil solution. The results showed that, during the first four months, patients using 3% minoxidil achieved significantly more hair growth than patients using placebo. When the placebo patients were switched over to 3% minoxidil, they experienced a “marked increase in terminal hair count,” achieving a greater than three-fold increase in average terminal hair count over the next eight months, from 59 (+/- 98) to 219 (+/- 168). The authors also note that none of the patients experienced a net hair loss in the target area during the study, suggesting that patients who do not achieve noticeable hair regrowth can at least maintain their baseline hair count with minoxidil treatment.

At the end of this trial, 41 of the patients enrolled in a long-term maintenance study in which they continued using minoxidil for another 90 weeks. At the end of the trial they were assessed for nonvellus hair counts (vellus hairs - fine, “peach fuzz” type hairs - were not evaluated).3 While some patients who continued applying 3% minoxidil solution twice a day lost a portion of the initial gains made during the first part of the trial, the average nonvellus hair count increased slightly from 323 (range of 15 to 589 hairs) to 335 (range of 13 to 808 hairs) during the maintenance study.

The Olsen group then extended this trial even further, following 31 patients who went on to complete 4.5 to 5 years of therapy.4 They ultimately concluded that “hair regrowth with topical minoxidil tends to plateau at about 12 months of treatment” and that “continued use of topical minoxidil is associated with a slow decline in the 12-month hair counts but continued maintenance of nonvellus hair regrowth well beyond that at baseline.”

Several other studies have been conducted, some of which are briefly summarized here:

Savin RC. J Am Acad Dermatol. 1987 Mar;16(3 Pt 2):696-704. PubMed
- Double-blind, randomized 12 month study
- 79 patients
Total hair counts showed significant increases at 12 months (p < 0.001) with a mean increase of 144.2 hairs in the 3% minoxidil group. The investigators' visual assessment showed moderate to dense regrowth in 64% of these patients. The author suggests that the increases in nonvellus hair count observed during the study support the conclusion that “minoxidil stops the progression of male pattern baldness.”

Civatte J, et al. Dermatologica. 1987;175 Suppl 2:42-9. PubMed
- Double-blind, randomized 48 week study
- 225 patients
Minoxidil (2%) showed superiority to placebo with respect to non-vellus hair counts (p = 0.0084), changes in non-vellus hair counts compared with baseline values (p = 0.0227), and investigators' evaluations of hair growth (p = 0.019). Moderate or dense hair growth was reported in 32.7% of the patients by investigator evaluation.

Rietschel RL, Duncan SH. J Am Acad Dermatol. 1987 Mar;16(3 Pt 2):677-85. PubMed
- Double-blind, randomized 12 month study
- 102 patients (up to 7 may have been female)
Hair counts at 12 months increased from 63.5 to 180.6 (2% minoxidil), 61.0 to 179.9 (3% minoxidil), and 65.0 to 191.1 (placebo crossover to 3%). Investigator evaluations showed visible hair growth in 89 patients (~87%) and dense hair growth (enough to cut or comb) in 33 patients (~32%), with patients reporting even more favorable results. The authors suggest that patients who considered themselves nonresponders in fact experienced prevention of hair loss, and suggest an “ultimate success rate for hair growth of about one third of the patients.”

Koperski JA, et al. Arch Dermatol. 1987 Nov;123(11):1483-7. PubMed
- Double-blind, randomized 30 month study
- 59 patients at 12 months, 33 patients at 30 months
Hair regrowth appeared to peak at 12 months. Of the patients who used minoxidil for the full 30 months, 70% finished the trial with “at least 50% more hairs than when they originally started the drug therapy” and a subset of patients “appeared to sustain a continued increase in hair counts.” The authors suggest that patients who are “excellent responders” in the first 12 months may be more likely to have a continued hair growth response.

Shupack JL, et al. J Am Acad Dermatol. 1987 Mar;16(3 Pt 2):673-6. PubMed
- Double-blind, randomized 6 month study
- 58 patients
The investigators identified a “clear dose-response correlation for the increase of nonvellus hairs” with escalating doses of minoxidil. Mean nonvellus hair counts increased by 25.9 with 0.1% minoxidil, 36.8 with 1% minoxidil, and 54.1 with 2% minoxidil, however “clinically perceptible hair growth” occurred only in patients treated with 1% or 2% minoxidil solution.

Clinical Trials of Minoxidil for Female Pattern Hair Loss

One of the first studies published on the effectiveness of minoxidil for female androgenetic alopecia was conducted at the University of Minnesota School of Medicine. In this trial, 25 patients were treated for 48 weeks with a 3% topical minoxidil solution.5 Each patient's degree of hair loss was assessed at study entry and classified as either 25-50% hair loss (13/25), 50-75% hair loss (10/25), or 75-99% hair loss (2/25). The study reported significant improvement (P = 0.0083) at 48 weeks, with five of the 25 patients moving to a lower category, and patient self-assessments were positive with 17 patients reporting hair regrowth. While these results were promising, the lack of a placebo control group necessitated further trials with a placebo control group.

Two multicenter, double-blind, placebo-controlled 32 week trials were then conducted in Europe (10 sites, 294 patients)6 and the U.S. (11 sites, 256 patients)7 to compare 2% topical minoxidil solution with placebo.

The trial in Europe revealed that women using 2% minoxidil achieved a significantly greater increase in nonvellus hair count than women in the placebo group (P = 0.0001), with an increase of 33 hairs compared to 19 hairs, respectively. The U.S. study found that average nonvellus hair counts in a 1 cm2 target area increased by approximately twice as much in the 2% minoxidil group (23 hairs) as the placebo group (11 hairs).

These trials were notable for the relatively high percentage of patients in the placebo group who were reported to experience hair growth, both by investigator assessment (~30-40%) and patient self-reporting (~40%).

The results of two smaller studies are summarized here:

Olsen EA. Cutis. 1991 Sep;48(3):243-8. Pubmed
- Randomized, placebo-controlled 32 week study
- 28 patients
The study reported statistically significant increases in both nonvellus target area hair counts (p = 0.006) and investigator's assessment of hair regrowth (p = 0.007), although the study participants were unable to discern a difference between treatment groups.

Whiting DA, Jacobson C. Int J Dermatol. 1992 Nov;31(11):800-4. Pubmed
- Double-blind, randomized 32 week study
- 28 patients
Nonvellus hair counts for patients in the minoxidil group increased from a baseline mean of 169 hairs to a final count of 195 hairs (~15.4% increase) at study completion, compared to an increase from 161 hairs to 177 (~9.9%) in the placebo group. Assessment of hair growth showed 60% of women using minoxidil experienced minimal to moderate hair growth compared to 46% of placebo patients.

Conclusions

Together these trials provided significant evidence of the effectiveness of minoxidil for stopping hair loss and regrowing hair in both male and female patients suffering from androgenetic alopecia. While not all study participants experienced significant hair regrowth, many male patients grew hair that in some cases persisted for up to 4-5 years of minoxidil use. The results of the women's trials were not as simple to interpret as those for men. Many women in the placebo groups appeared to regrow hair during the course of the trials, but in most cases the increased hair growth achieved with minoxidil was statistically significant compared to the placebo group.

Next time on the Avacor Hair Regrowth Blog's “Minoxidil Mini-Series,” we will document minoxidil's approval by the FDA for treating hair loss and its eventual approval as an over-the-counter medication.

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1. Olsen EA, DeLong ER, Weiner MS. Dose-response study of topical minoxidil in male pattern baldness. J Am Acad Dermatol. 1986 Jul;15(1):30-7. Link to Pubmed

2. Olsen EA, Weiner MS, Delong ER, Pinnell SR. Topical minoxidil in early male pattern baldness. J Am Acad Dermatol. 1985 Aug;13(2 Pt 1):185-92. Link to Pubmed

3. Olsen EA, DeLong ER, Weiner MS. Long-term follow-up of men with male pattern baldness treated with topical minoxidil. J Am Acad Dermatol. 1987 Mar;16(3 Pt 2):688-95. Link to Pubmed

4. Olsen EA, Weiner MS, Amara IA, DeLong ER. Five-year follow-up of men with androgenetic alopecia treated with topical minoxidil. J Am Acad Dermatol. 1990 Apr;22(4):643-6. Link to Pubmed

5. Hordinsky MK, Shank J. Three percent topical minoxidil therapy for female androgenetic alopecia. Clin Dermatol. 1988 Oct-Dec;6(4):213-7. Link to Pubmed

6. Jacobs JP, Szpunar CA, Warner ML. Use of topical minoxidil therapy for androgenetic alopecia in women. Int J Dermatol. 1993 Oct;32(10):758-62. Link to Pubmed

7. DeVillez RL, Jacobs JP, Szpunar CA, Warner ML. Androgenetic alopecia in the female. Treatment with 2% topical minoxidil solution. Arch Dermatol. 1994 Mar;130(3):303-7. Link to Pubmed