ONE-YEAR OBSERVATIONAL STUDY

Dermatologists conducted a one-year observational study in 984 men with male pattern hair loss. The study evaluated the effectiveness of a 4.5% minoxidil topical solution in halting hair loss and stimulating new hair growth, as well as the patients’ perceptions of efficacy and side effects. Over the one-year period of study, patients applied 1 ml of 4.5% minoxidil solution twice per day to hair-loss areas of the scalp. Every three months during the study, patients collected hair lost during washing and sent it to a laboratory for counting.

At the end of one year

	The dermatological investigators reported that hair-loss areas of the scalp had become smaller in 62 percent of the patients, unchanged in 35 percent, and larger in three percent.
	In evaluating minoxidil’s effectiveness for stimulating hair regrowth, the investigators found the 5% solution very effective in 16 percent of patients, effective in 48 percent, moderately effective in 21 percent, and ineffective in 16 percent.
	Hairs lost during washing numbered a mean 70 at the beginning of the study, and a mean 34 at the end of the study — a measure of the effectiveness of 4.5% minoxidil in halting hair loss in the patients studied.
	The mean score of patient satisfaction on a scale of 0 (extremely dissatisfied) to 10 (very satisfied) increased from 2.9 at the beginning of the study to 4.4 at the end. Patient satisfaction scores were lower than the estimates of the investigating physicians, who rated efficacy of treatment as good or very good 25 percent more often than did the patients.
	Side effects, mostly dermatological, were reported by 3.9 percent of patients in the study. None of the side effects was classified as serious.

FOUR-MONTH SURVEILLANCE STUDY

A four-month surveillance study involving 743 men with male pattern hair loss was designed to evaluate 1) how quickly men using 1 ml of 4.5% minoxidil solution twice a day began to notice reduced hair loss and/or new hair growth, 2) efficacy of the 4.5% minoxidil solution in improving hair density in areas affected by male pattern hair loss, and 3) side effects associated with use of 4.5% minoxidil solution.

All results were evaluated and reported by the men involved in the study, which included 150 physicians with male pattern hair loss.

At the end of four months

	The scalp area affected by male pattern hair loss was judged smaller by 67 percent of the men, unchanged by 32 percent, and larger by one percent.
	In stimulating new hair growth, the 4.5% minoxidil solution was judged very effective by seven percent of the men, effective by 55 percent, moderately effective by 31 percent, and ineffective by six percent.
	Hair density (fullness) was judged to be improved by 74 percent of the men, unchanged by 24 percent, and worsened by one percent.
	Of the 669 men who reported when the results of minoxidil treatment were first noticeable, 14 percent reported results in the first month, 52 percent during the second month, and 34 percent during the third month.
	Skin-related side effects were reported by 13 patients.

Results reported by the 150 physicians in the study did not differ substantially from those reported by other men in the study.

Results of these two post-marketing studies generally confirm results of previous studies of the efficacy and safety of minoxidil. While many persons benefit by 2% or 4.5% minoxidil in the treatment of male pattern hair loss, results vary from person to person for a variety of reasons including individual responses to the agent and relentlessness of hair-loss progression. Results that are satisfactory to some patients are unsatisfactory to others, perhaps because results do not meet pre-treatment expectations.

Best results are likely to be realized when the subject of hair loss consults a physician who specializes in hair restoration. Rational expectations for treatment outcomes are most reliably based on 1) diagnosis of the cause of hair loss, 2) assessment of the characteristics of hair loss in the individual patient, and 3) a treatment plan based on diagnosis and assessment and agreed upon by both the patient and physician.
A physician who specializes in hair restoration is able to monitor clinically the effectiveness of medical therapy, including through the use of comparison photos, and is able to provide additional medical and surgical options to augment the benefits of minoxidil, which is even more effective when combined with the oral medication finasteride (Propecia) and is compatible with hair-restoration surgery. For example, a patient may have follicular-unit transplantation to create a natural-looking hairline near the front of the scalp and use minoxidil and finasteride to preserve the hair on top of the scalp.

Normal results

Topical minoxidil is much more effective at treating baldness that occurs on the vertex (crown) of the head than it is on other parts of the head. Minoxidil does not work for everyone, and there is no predictor of whether it will be effective for any individual. Clinical tests on the effectiveness of topical minoxidil in men with baldness at the vertex showed that 48 percent who used minoxidil for one year reported moderate to dense regrowth. Thirty-six percent reported minimal regrowth, while 16 percent reported no regrowth. Similar percentages have been reported in women.

Hair regrowth generally does not begin until the medicine has been used for at least four months. The first signs that minoxidil may be effective for a particular person usually occur after approximately 90 days of treatment, when the patient notices that he or she is losing (shedding) much less hair.

When new growth begins, the first hairs may be soft and barely visible. For some patients, this is the extent to the effectiveness of this medication. For others, this downy hair develops into strands of the same color and thickness as the others.

Minoxidil is a treatment for hair loss; it is not a cure. Once a patient stops using minoxidil, he or she will most likely lose the regrown hair within 90 days, and no further hair growth will occur.



LONG-TERM EFFICACY OF TOPICAL MINOXIDIL
IN MALE PATTERN BALDNESS

Authors: Katz HI, Hien NT, Prawer SE, Goldman SJ
Source: J Am Acad Dermatol, 16: 3 Pt 2, 1987 Mar, 711-

Abstract

A 24-month clinical trial, begun on a double-blind basis, was conducted in 153 men with discernible male pattern baldness of the crown with the use of either topically applied placebo, 2% minoxidil, or 3% minoxidil solution. After four months, the patients using placebo were switched to 3% minoxidil solution.

At 12 months, there were statistically significant increases in terminal-hair growth within a one-inch target area in those treated with 2% or 3% minoxidil solution, in comparison with baseline counts. However, there were few patients who had appreciable cosmetic restoration. At 12- and 24-month intervals, progressive regression or stabilization of the size of the bald area was noted in the majority of patients. This therapeutic or preventive effect was statistically significant.

The data on actual target-area hair counts suggested that the 2% minoxidil solution was equal to or more efficacious than the 3% minoxidil solution. Baseline vital signs and laboratory parameters remained essentially unchanged. Topical minoxidil was well tolerated, with no serious drug-related adverse reactions noted during the study.



TOPICAL MINOXIDIL THERAPY
FOR ANDROGENIC ALOPECIA
IN THE MIDDLE EAST

Author: Karam P
Address: American University Hospital of Beirut, New York, NY 10022 USA
Source: Int J Dermatol, 32: 10, 1993 Oct, 763-6

Abstract

BACKGROUND. A 48-week open-label trial was conducted in five Middle Eastern countries (Lebanon, Egypt, Saudi Arabia, Jordan, and the United Arab Emirates) to determine the safety and efficacy of 2% minoxidil in the treatment of early androgenic alopecia and to compare the response with Western countries.

METHODS. One hundred ninety-five men aged between 19 and 47 years were enrolled. The duration of their baldness varied from six months to 10 years, and they all showed a type III vertex or type IV on the modified Hamilton scale. Baldness pattern, diameter of the balding area, hair count within a 2.5 cm bald patch, as well as investigators’ and patients’ evaluations were regularly noted.

RESULTS. No significant changes were observed in vital signs or laboratory parameters. Of the 161 patients considered evaluable at 48 weeks, 80 percent showed moderate to dense growth. The mean increase in non-vellus hair at 12 months was 234.

CONCLUSIONS. The age of the patient and the type of baldness, rather than its duration, affected the final outcome.



AUSTRALIAN TRIAL OF TOPICAL MINOXIDIL
AND PLACEBO IN EARLY MALE PATTERN BALDNESS

Authors: Connors TJ, Cooke DE, De Launey WE, Downie M, Knudsen RG, Shumack S, Eggleston AS
Address: Monash Medical Centre, Clayton, Victoria Australia
Source: Australas J Dermatol, 31: 1, 1990, 17-25

Abstract

One hundred sixty nine men with early male pattern baldness (androgenic alopecia) were treated in a random, double-blind fashion with either 2% minoxidil solution or placebo vehicle for 24 weeks, 1 ml applied twice daily. After 24 weeks, all patients received the active solution until week 48.

After 24 weeks, the minoxidil-treated patients had increased their non-vellus hair counts significantly more than the placebo-treated group; means were 37.6 and 8.8 hairs per reference area, 95 percent CI for difference = 10.85 to 60.75. The rate of non-vellus hair regrowth was also greater among minoxidil-treated patients than placebo-treated patients. Nine (12.5 percent) evaluable minoxidil-treated patients compared with two (2.7 percent) evaluable placebo-treated patients reported moderate or dense hair regrowth at week 24. Minimal regrowth was reported by 18 (25 percent) active group and 15 (20 percent) placebo-group patients. The investigators considered that three (2 percent) of the minoxidil group and none of the placebo group had moderate hair regrowth and that none had dense regrowth.

After 48 weeks of treatment, 28 (23 percent) patients considered that they had moderate hair regrowth and the investigators considered that 14 (12 percent) patients had moderate regrowth. None had dense growth.

No serious adverse reactions or deaths were reported. Minoxidil solution appeared to be an efficacious and safe treatment for early androgenic alopecia.



TREATMENT OF ANDROGENIC ALOPECIA
WITH TOPICAL MINOXIDIL

Authors: Brenner S, Tamir A
Address: Dermatology Department, Sourasky Medical Center, Tel Aviv, Israel.
Source: Harefuah, 121: 9, 1991 Nov 1, 297-302

Abstract

Minoxidil, a vasodilator, was first marketed in 1979 as an oral antihypertensive. Since hypertrichosis occurred as an adverse effect in most patients treated, a 2% topical solution was developed for use in men with androgenic alopecia. It was approved by the American Food and Drug Administration and by the Israel Ministry of Health. A follow-up of 30 cases treated with the preparation is presented.

Efficacy of treatment was assessed by hair counts in a marked area on the balding scalp, as well as by subjective evaluations of patients and physicians. The treatment was beneficial in 63 percent: balding was slowed in most, while in a minority hair density actually increased. However, in only 6.6 percent was dramatic cosmetic improvement achieved.



A CRITICAL REVIEW OF THE RESULTS
OF CLINICAL EXPERIMENTATION
WITH TOPICAL MINOXIDIL 2%

Italian title: “Revisione critica di alcuni risultati della sperimentazione clinica con minoxidil topico al 2%”

Authors: D’Ovidio R, Di Prima T, De Pasquale R, D’Ovidio F
Address: Istituto Semeiotica Chirurgica, Università di Bari, Bari, Italia
Source: G Ital Dermatol Venereol, 125: 4, 1990 Apr, V-IX

Abstract

The results of clinical double-blind trials using minoxidil 2% demonstrate the real efficacy of the drug in producing satisfactory esthetic results in some 30 percent of treated patients. One aspect of the results of this research that is not yet clear is the significant increase in the number of hairs also found in voluntary subjects treated with a placebo. In the present study, it is hypothesized that this increase may be partially explained by the failure to take into account physiological seasonal variations in hair density and by confusion caused by the use of the non-vellus category, which is used to describe terminal (thick) and indeterminate (thin) hairs.

In our study, the placebo failed to produce a significant increase in the number of terminal hairs, thus explaining why, even in the presence of an increased number of non-vellus hairs, on average there was no real cosmetic benefit in these subjects.



ENHANCED IN-VITRO HAIR GROWTH
AT THE AIR-LIQUID INTERFACE:
MINOXIDIL PRESERVES THE ROOT SHEATH
IN CULTURED WHISKER FOLLICLES.

Authors: Waldon DJ, Kawabe TT, Baker CA, Johnson GA, Buhl AE
Address: Upjohn Laboratories, Department of Dermatology Research, Kalamazoo, Michigan 49001 USA

Source: In Vitro Cell Dev Biol Anim, 29A: 7, 1993 Jul, 555-61

Abstract

Inasmuch as hair follicles are difficult to maintain in culture, the study of hair biology using cultured hair follicles has met with only limited success. In our attempts to solve the problem of follicle degeneration, we cultured follicles at the air-surface interface on a modified collagen matrix (Gelfoam). In follicles cultured at the air surface or submerged, we examined follicular morphology, hair shaft growth, sulfotransferase levels, cysteine incorporation, an expression of a tissue inhibitor of metalloproteinase (TIMP), and ultra-high-sulfur keratin (UHSK).

Follicles cultured at the air-liquid interface produced a 2.7-fold increase in hair growth and maintained an anagen-like morphology. Substrates such as nylon mesh seeded with fibroblasts, Full Thickness Skin, or 5 ?m polycarbonate filter also supported hair growth, whereas Gelfilm, GF-A glass filter, filter paper, or 1 ?m polycarbonate filter did not. The UHSK expression was significantly higher in the air-liquid interface cultures compared to the submerged culture.

Several potassium channel openers, including minoxidil, a minoxidil analog, and the pinacidil analog (P-1075) all stimulated significant cysteine incorporation in follicles. Minoxidil and its analog specifically preserved the follicular root sheath, in contrast to P-1075 which did not, indicating a difference in the two drug types. The preservation of the root sheath was measured by increased TIMP expression and sulfotransferase activity and indicates that the root sheath is a target tissue for minoxidil.

Our results show that follicles cultured at the air-liquid interface maintain a better morphology and produce greater hair growth than follicles cultured on tissue-culture plastic.

GENERAL INFORMATION ABOUT MINOXIDIL

Purpose

Minoxidil was the first drug approved by the FDA for the treatment of androgenetic alopecia (male pattern baldness). Before that, minoxidil had been an oral tablet used as a vasodilator prescribed to treat high blood pressure, with side effects that included hair growth and reversal of male pattern baldness.

In the 1980s, the Upjohn Company came out with a topical solution of 2% minoxidil called Rogaine for the specific treatment of androgenetic alopecia. Since the 1990s, numerous generic forms of minoxidil have become available to treat hair loss while the oral form is still used to treat high blood pressure.

The popularity of hair-loss treatments is due to the cosmetic preference in the population for the appearance of a full head of hair. Minoxidil is used to stimulate hair growth in areas of the vertex that have stopped growing hair. Despite much research and hypothesizing, the exact mechanism of action is still not known.

Precautions

People who have experienced an unusual allergic reaction either to minoxidil or to propylene glycol, a non-active chemical in many solutions, should not use topical minoxidil. People who have had a previous allergic reaction to preservatives or dyes may also be at risk of an allergic reaction to minoxidil.

People who are using cortisone or cortisone-like drugs (corticosteroids), petroleum jelly (Vaseline), or tretinoin (Retin-A) on their scalps should consult their doctors prior to using minoxidil. The use of any of these products in conjunction with minoxidil may cause excessive minoxidil absorption into the body and increase the risk of side effects.

People who have skin problems or irritations of the scalp, including sunburn, may absorb too much minoxidil and increase their risk of side effects. If using oral minoxidil, the form prescribed for high blood pressure, patients should use topical minoxidil only under medical supervision to ensure that excessive amounts of the drug are not absorbed. Large amounts of minoxidil may increase the severity of symptoms and side effects.

Minoxidil may pass from mother to child through breast milk. Therefore, women who are breastfeeding should not use minoxidil.

Description

For the treatment of hair loss, minoxidil is available as a topical solution that is generally either 2% or 4.5% minoxidil in propylene glycol. The propylene glycol ensures that the applied minoxidil is evenly spread across the affected area and easily absorbed through the skin. Approximately 1 ml of minoxidil solution is applied to the scalp once a day using the fingertips or a pump spray. It should be applied from the center of the area being treated outward.

In the treatment of high blood pressure, oral minoxidil is usually prescribed when other medications have failed to treat the condition. Dosage is usually 2.5–100 mg per day as a single dose for adults and 200 µg to 1 mg per kilogram of body weight for children.

Risks

The most common side effects of topical minoxidil use are itching and skin irritation of the treated area. Unwanted hair growth may also occur adjacent to treated areas or in areas where the medicine has been inadvertently transferred several times, which may be particularly distressing to women when the face is involved. The itching and irritation usually subside after the drug has been used for approximately two weeks. If symptoms persist after this time, minoxidil use should be halted until a physician has been consulted.

Extremely rare side effects that may occur if too much topically or orally administered minoxidil is being absorbed in the body include:

Changes in vision, most commonly blurred vision,
Chest pain,
Very low blood pressure,
Decreased sexual desire,
Fast or irregular heartbeat,
Flushing of the skin,
Headache,
Lightheadedness,
Numbness or tingling in the hands, feet, or face,
Partial or complete impotence,
Rapid weight gain, or Swelling of the hands, feet, lower legs, or face.