Hair Loss Treatment: Minoxidil
brand name Rogaine or Regaine

Background: Topical minoxidil is the #1 selling hair loss treatment in the world. Minoxidil tablets was first used in patients as an antihypertensive drug. It was later discovered that minoxidil also has positive effects on hair growth when applied topically to the scalp. Minoxidil was first marketed as Rogaine or Regaine by Upjohn for the treatment of hair loss in the late 1980s. As of to date, Rogaine ® is still the only FDA approved topical medication for the treatment of hair loss in US.

Mechanism: Cutaneous blood flow is decreased in pattern baldness and minoxidil increases cutaneous blood flow to the scalp, possibly promoting hair growth by this mechanism. However, other vasodilators do not grow hair.

Side effects: Some of the possible side effects associated with topical minoxidil are rapid heart beat, dizziness, and shortness of breath. It has also been reported that topical minoxidil can cause facial hair growth in women. As of today, the most commonly reported side effects associated with topical minoxidil are scalp inflammatory conditions such as severe scalp itch, flakes, redness of the scalp and excessive dandruff. Topical minoxidil can also increase oiliness of the scalp.

Ingredients: Topical minoxidil in its most basic form contain the active ingredient minoxidil, water, alcohol and propylene glycol.

Treatment: In most instances, topical minoxidil is intended to be applied directly to the scalp twice daily. Some suggest that minoxidil is dose dependent, meaning that patients may have to increase the concentration of minoxidil over time in order to sustain the results. Consequently, it is recommended that people should start using a lower strength formula and gradually move up the scale to the super strength 12% version over time.

Minoxidil Alternatives:

Cromakalim / BRL 34915 - is a potassium (K+) channel opener used in the treatment of heart conditions. Research indicates that works similarly to minoxidil. Upjohn has patented it for potential treatment of hair loss. It stimulates potassium channel conductance and stimulates DNA synthesis in mouse epidermal keratinocyte and whole hair follicle cultures.

Diazoxide (Hyperstat IV, Proglycem) - an anti-hypertensive, potassium channel blocker, that has a positive effect on hair loss. It is reported to produces minimal to moderate hair growth and is FDA approved for lowering blood pressure. It is expensive and must be specially formulated for topical use.

Pinacidil - Pinacidil and a close analog PC-1075 are anti-hypertensive drugs and potassium channel blockers similar to minoxidil. They have been reported to stimulate hair growth when applied topically.


Minoxidil Products: Nowadays, there are over a dozen minoxidil based products on the market, from the most basic 2% topical minoxidil to super strength 12% formula. Also, the current trend is for doctors or pharmacists to include additives to the formula in an attempt to enhance the treatment's effectiveness and potency. Below are some of the more common ones people use for hair loss.

Minoxidil Products

Basic Minoxidil 2% - 6% - this is the most basic form with concentration ranging 2% - 6%.
Vendor: HairMedics.

Super Strength Minoxidil 12% - 15% - this is the highest concentration you can find on the market these days. Some suggest that minoxidil is dose dependent so it is recommended that people should start using the lower strength formula before they switch to 12% or 15%.
Vendor: Dr. Oscar Klein.

Propylene glycol free Minoxidil - this is appropriate for those who developed scalp inflammatory conditions such as scalp itch and flakes as a result of regular minoxidil. Perfect for those whose scalp is sensitive to propylene glycol.
Vendor: Dr. Oscar Klein.

Minoxidil with Corticosteroids - Corticosteroid is an anti-itch, anti-inflammatory agent that can alleviate scalp irritations such as scalp itch, flakes and redness commonly associated with topical minoxidil.
Vendor: Dr. Oscar Klein.

Minoxidil with Retin-A - Retin-A or Tretinoin are commonly used to exfoliate dead skin cells. Also, studies have shown that Retin-A or Tretinoin by itself may stimulate hair growth. When used in conjunction with topical minoxidil, the exfoliatory properties of Retin A or Tretionoin can also enhance penetration of minoxidil into the follicles.
Vendor: HairMedics & Dr. Oscar Klein.

Minoxidil with Finasteride - Probably the most synergistically ideal solution for hairloss. Minoxidil works as a hair regrowth stimulant while 5-alpha reductase inhibitor finasteride is known to halt further hairloss. Targeting hairloss at both angles.
Vendor: HairMedics

Minoxidil with Azelaic Acid - DHT is commonly suggested to be the main cause for hairloss. Studies have shown that azelaic acid may function as an DHT inhibitor and may work synergistically together with minoxidil to stimulate hair regrowth while halting further hairloss.
Vendor: HairMedics & Dr. Oscar Klein

Minoxidil with Azelaic Acid, Zinc, B6 and Grape Seed Extract - DHT is commonly suggested to be the main cause for hairloss. Studies by Stamatiadis et al have shown that azelaic acid when used in conjunction with topical zinc and B6 can inhibit up to 90% of DHT in human skin.
Vendor: HairMedics & Dr. Oscar Klein

Minoxidil with Nicotinate - Nicotinate is a blood vessels dilator. This additive when used in conjunction with minoxidil may enhance the penetration and potency of minoxidil.
Vendor: HairMedics

Minoxidil with Progesterone - Progesterone is a female hormone added in very small quantities to neutralize the local action of DHT. Not a lot of studies on the effect of topical progesterone on hairloss but some people think this may be beneficial for women pattern baldness.
Vendor: HairMedics  & Dr. Oscar Klein
 

Minoxidil Studies

One-Year Study

Dermatologists conducted a 1-year observational study in 984 men with male-pattern hair loss. The study evaluated the effectiveness of a 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 1-year period of the study, patients applied 1 milliliter (ml) of 5% minoxidil solution twice day to hair-loss areas of the scalp. Every 3 months during the study, patients collected hair lost in a hair washing and sent the collected hair to a laboratory for counting.

At the end of 1 year:

The dermatologist investigators reported that hair loss areas of the scalp had become smaller in 62% of the patients, unchanged in 35.1% and larger in 2.9%.

In evaluating minoxidil effectiveness in stimulating hair regrowth, the investigators found the 5% solution very effective in 15.9% of patients, effective in 47.8%, moderately effective in 20.6% and ineffective in 15.7%.

Hairs lost during washing numbered a mean 69.7 at the beginning of the study, and a mean 33.8 at the end of the study-a measure of the effectiveness of 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 study beginning to 4.4 at study end. Patient satisfaction scores were lower than the estimates of the physician investigators: the investigators rated efficacy of treatment as good or very good 25% more often than did the patients.

Side effects, mostly dermatologic, were reported by 3.9% of patients in the study. None of the side effects was classified as serious.

Four-Month Study

A 4-month surveillance study involving 743 men with male-pattern hair loss was designed to evaluate (1) how quickly men using 1 ml of 5% minoxidil solution twice a day began to notice reduced hair loss and/or new hair growth, (2) efficacy of 5% minoxidil solution in improving hair density in areas affected by male-pattern hair loss, and (3) side effects associated with use of 5% minoxidil solution.

All results were evaluated and reported by the men involved in the study; 150 physicians with male-pattern hair loss were among the 743 patients studied.

At the end of 4 months:

The scalp area affected by male-pattern hair loss (the "balding" area) was judged smaller by 67.3% of the men, unchanged by 31.9% and larger by 0.8%.

The 5% minoxidil solution was judged very effective in stimulating new hair growth by 7.5% of the men, effective by 55%, moderately effective by 31.3% and ineffective by 6.2%.

Hair density (the "fullness" of scalp hair) was judged improved by 74.2% of the men, unchanged by 24.3% and worsened by 1.5%.
Of the 669 men who reported when results of minoxidil treatment were first noticeable, 13.9% reported results in the first month, 52.3% during the second month, and 33.8% 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 results reported by the 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 are benefited by 2% or 5% minoxidil in treatment of 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 treatment results are likely to be realized when the person with hair loss consults a physician hair restoration specialist. Rational expectations for treatment outcome 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 upon diagnosis and assessment, and agreed upon by the patient and physician hair restoration specialist. A physician hair restoration specialist is able to monitor the effectiveness of medical therapy clinically and through use of comparison photos, as well as provide other medical and surgical options to augment the benefits of minoxidil. Minoxidil solution is even more effective when combined with the oral medication finasteride (Propecia®), and is also 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.

Pharmacia & Upjohn 1998 Minoxidil Study - Hair Growth Results - results reported on crown area. Ronald Trancik, Ph.D, from Pharmacia & Upjohn presented data on 5% Minoxidil at the American Association of Dermatology in March, 1998. In a 120 week study of 5% Minoxidil, hair growth continued until the end of the study. In two other studies using hair count and photographic assessment, the following results were shown:

Minoxidil helps inhibit apoptosis (programmed cell death) in hair follicles:

"Minoxidil helps inhibit apoptosis (programmed cell death) in hair follicles, according to this new study below. Hair follicles undergo massive apoptosis when switching from anagen to catagen.

One of the hallmarks of MPB is a decrease in the length of anagen. So, it would seem that minoxidil is capable of countering this specific aspect of pattern baldness (i.e., short anagen phases). The study below also notes that minoxidil increases the proliferation rate of dermal papilla cells (this also likely contributes to lengthening of anagen)." from Almight in HairSite's Men's Forum.


J Dermatol Sci. 2004 Apr;34(2) 1-8.

Effect of minoxidil on proliferation and apoptosis in dermal papilla cells of human hair follicle.

Han JH, Kwon OS, Chung JH, Cho KH, Eun HC, Kim KH.

Department of Dermatology, Clinical Research Institute, Seoul National University College of Medicine, Seoul National University Hospital, 28 Yongon-Dong, Chongno-Gu, Seoul 110-744, South Korea.

Background: Minoxidil has been widely used to treat androgenetic alopecia, but little is known about its pharmacological activity or about the identity of its target cells in hair follicles. We hypothesized that minoxidil has direct effects on the proliferation and apoptosis of dermal papilla cells (DPCs) of human hair follicle.

Objective: To elucidate the mechanism of topical minoxidil action in terms of stimulating hair growth.

Methods: We evaluated cell proliferations in cultured DPCs by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and measured the expressions of extracellular signal-regulated kinase (ERK), Akt, Bcl-2, and Bax by Western blot. We also measured elongation of hair follicles in organ culture.

Results: Minoxidil significantly increased the proliferation of DPCs. The levels of ERK phosphorylation and of phosphorylated Akt increased significantly 1 h post-treatment; percentage increase of ERK phosphorylation was 287% at 0.1microM and 351% at 1.0microM of minoxidil, and that of Akt phosphorylation was 168% at 0.1microM and 257% at 1.0microM of minoxidil. 1.0microM of minoxidil increased Bcl-2 expression over 150%, while 1.0microM of minoxidil decreased Bax expression by more than 50%. Moreover, a significant elongation of individual hair follicles in organ culture was observed after adding minoxidil.

Conclusion: Minoxidil promotes the survival of human DPCs by activating both ERK and Akt and by preventing cell death by increasing the ratio of Bcl-2/Bax. We suggest that minoxidil stimulates the growth of human hairs by prolonging anagen through these proliferative and anti-apoptotic effects on DPCs.
 

Minoxidil Effectiveness Study on Women: A total of 381 women were entered into the 48-week study, 260 women completed the study.

A randomized, double-blind, placebo-controlled trial of 5% and 2% topical minoxidil solutions in the treatment of female pattern hair loss was conducted at nine research sites for a 48-month period in 1992-93.

Women in the Study

A total of 381 women were entered into the 48-week study, 260 women completed the study.

Women accepted into the study were 18 to 49 years old with naturally dark hair. Average age was 37 years; 74% of the women were of Caucasian ancestry. All had female pattern hair loss characterized as gradual and conspicuous, with diffuse (patchy) thinning from front to back over the mid-scalp area. Some patients also had thinning of the frontal hairline.

The degree of hair loss was rated according to the widely accepted Savin Female Density Scale; a density rating of 4 to 7 was required for acceptance into the study. On the basis of the Savin Density Score, the mean density score was 4.8, 4.7 and 4.7 in the 5%, 2% and placebo groups respectively.

Patients were not accepted if other reasons for hair loss were present, such as systemic disease, scalp disease, current or recent pregnancy, and use of certain drugs.

Results of the Study

At the end of the 48-week study, 260 patients were available for evaluation. Of the 381 patients who entered the study, 121 withdrew:

40 for non-serious drug-related adverse events such as itching and scaling

25 at the request of the patients (moved away, could not make appointments, etc.)

26 lost to follow-up for unknown reasons.

Hair Count

At 48 weeks, the mean change from baseline hair counts showed that 5% and 2% minoxidil solution had results significantly superior to placebo. The superior results began at Week 8 and continued to the end of the study. Results were slightly better for 5% minoxidil solution, but the superiority of 5% over 2% solution was less than the superiority of both over placebo.

Mean change from baseline at Week 48 in 1-square-centimeter hair counts were 24.5 in the 5% minoxidil group, 20.7 in the 2% minoxidil group, and 9.4 in the placebo group.

Investigator Evaluation

Investigators rated scalp coverage in the 2% and 5% minoxidil group significantly superior to scalp coverage in the placebo group at 48 weeks.

No statistically significant difference was found between the 5% and 2% minoxidil groups in evaluation of scalp coverage.

Safety Evaluation

Drug-related adverse events were more common in the 5% minoxidil group (14%) than in the 2% minoxidil group (6%) and the placebo group (4%).

The most common drug-related adverse events were pruritis (itching), scalp dermatitis, scalp skin scaling, and hypertrichosis (excessive facial hair growth).

Four patients had excessive facial hair growth and three of those dropped out of the study. One unexplained adverse event was excessive hair shedding at Week 48 in two patients in the 5% minoxidil group at the same research site.