Hair loss has been an issue for centuries, but scientific ways to treat hair loss began to take off in the past 60 or so years. Ointments, transplants, formulations, chemicals, snake oils, and many other products have emerged in the hair loss treatment markets, some of which work well, others which do not. When choosing a hair regrowth treatment, it is important to understand whether a product or method is approved by the U.S. Food and Drug Administration (FDA), whether it will treat your specific situation, and whether the treatment has any side effects that could be potentially hazardous to your overall physical or emotional health.
Hair follicles are self-regenerating; they produce strands of hair, shed it, and reproduce new hair constantly. However, at some point, the hair follicle stops producing new hair, or produces new hair at a slower rate than the hair is shed, causing hair loss and sometimes baldness. It is this concept that must be understood when creating new ways to treat hair loss. All hair loss treatments aim to assist (or in some cases, replace) hair follicles in producing new hair, whether naturally or synthetically.
As far as hair treatments from a lab go, two main drugs have emerged as the leaders in treating hair loss. Minoxidil slows hair loss and promotes hair growth when used correctly. It helps to maintain the hair you have, and is most effective when used in the earlier stages of hair loss, as opposed to when you are bald or close to it. The other drug commonly used is Propecia. Unlike Minoxidil, which has proven effective for both men and women, Propecia only works on men, because it works to stop male hormones (testosterone) from forming DHT, which shortens the hair growth phase. Several studies have revealed that Propecia produces more side effects than Minoxidil, including loss of sex drive, and several other side effects. (Avacor® hair loss treatment products use Minoxidil and are specifically formulated for men and women).
Men looking to treat hair loss can use one or both of these drugs. However, neither will be effective unless used correctly, as directed by the product.
Surgeries are another way people treat hair loss, and are an $800 Million industry in the U.S. alone, and a $2 Billion industry worldwide, according to the Wall Street Journal. Hair transplants have developed significantly over the last several decades. In the 1980s, large grafts of hair follicles were removed from one area of the head and inserted onto the area experiencing hair loss. The procedure was often painful and the results were mixed; in some cases, hair transplants were quite successful, but not for everyone. Results took a long time to look natural as well. Scalp reduction is another out of date procedure that involved several small incisions on the scalp, which left visible scars.
Nowadays, hair transplant surgery is less invasive than before, requiring much smaller grafts of just one to four hairs. These smaller grafts are less painful and invasive, and have a more natural look since the areas are smaller and more close together.
The Next Evolution: Hair Follicle Regeneration
The new wave of hair loss treatment is hair follicle regeneration. This is essentially a jump start for hair follicles that have stopped or slowed new hair production. Several labs and companies are working on this process, and have seen success manipulating hair follicle stem cells in a test tube. Some companies are experimenting with removing human hair follicles and growing them in a lab. The idea is that if the hair follicles can be re-stimulated using science, then reinserted onto a person’s head, the hair follicles will begin working properly again, growing hair naturally and combating hair loss. This takes hair transplant procedures to the next level by expanding the number of new hair follicles you receive from a hair transplant.
Some people have referred to this process as “hair cloning,” but this is not an entirely accurate description, since the process does not create a new organism. Rather, it is a duplication effort that puts follicles that have the potential to produce new hair into implants that stimulate new growth. M.D. George Cotsarelis predicts this new transplant process is between 5 and 10 years from becoming publicly available.
Another recent development in the hair loss treatment world is a new gene called “Sonic hedgehog.” This gene essentially is able to convert hair in the resting stage into new hair growth. Scientists are still in the early stages of experimenting with this gene (and others) to try to control hair follicle size and the growth rate for new hair. If successful, it could become a powerful and popular new way to treat hair loss. Similar experiments are occurring as you read this article in labs all over the world. Using genetics to treat hair loss is similar to how scientists are using genetics to treat disease and other human conditions. These processes and procedures are constantly being updated, and like many other areas of treatment, scientists are paving the way toward new and improved hair loss remedies.
According to the Wall Street Journal, vitamin D is crucial to hair regrowth. Thus, many efforts to develop new hair loss treatments focus around adding more vitamin D into a person’s diet. In addition to stimulating hair growth, vitamin D also has other benefits for the body, such as improving bone growth. However, too much vitamin D can also cause kidney issues or general weakness, so take care not to overdo it. In many cases, simply changing your diet can actually help with hair loss. Adding the proper amount of vitamin D into your diet from fatty fish and sunlight can help you treat hair loss naturally.
We've all seen the term "FDA Approved." But, do you know what it means?
The United States Food and Drug Administration (FDA) is a federal government agency in charge of keeping the American public safe by regulating food, drugs, and medical devices. When a product or item is FDA-Approved, it has been rigorously tested and thoroughly inspected, and found to be both effective and completely safe for people to use or consume.
So, how does this relate to your hair?
Well, if you are experiencing hair loss, interested in hair restoration, or just curious about the process, you will undoubtedly encounter a wide variety of products to help stimulate hair growth. Many of these products are not FDA-Approved, which should be an automatic red flag. In other words, if a product is advertised to treat a medical condition, such as hair loss, but it does not indicate anywhere that it is FDA-Approved, then you should avoid using that product. You may be taking a major health risk using a product that is not FDA-Approved to treat any medical condition.
Avacor Physician's Formulation® is an FDA-Approved hair restoration product clinically proven to revitalize hair follicles and help you grow back your very own hair. The FDA has carefully tested and inspected how the product is manufactured, what ingredients are used, how much of each ingredient is used, how the product is stored and packaged, and how the product is administered. In other words, all aspects of Avacor Physician's Formulation production, including each ingredient, the bottling process, and the recommended dosage, have been deemed completely safe and effective for consumers to use for the treatment of hair loss, according to the FDA.
Unfortunately, some consumers continue to be tricked into buying "snake oil" products, or hair loss treatments not approved by the FDA. These products can cause unhealthy and unwanted side effects, such as acne, scalp hair loss, menstrual irregularities in women, irritability, and aggression, according to Dr. Ray Sahelian. The FDA also indicates other side effects of hair growth products that are not FDA-Approved include low blood pressure, heart palpitations and other cardiac symptoms, hair discoloration, sensitivity to sunburn, itching, rash, irritation, or stinging skin. "Snake oil" products are a waste of time and money. They also taint consumer's opinions of the entire industry, making consumers skeptical of all hair loss products, including the legitimate ones. Additionally, they can add more emotional stress in your life when you buy the product and it doesn’t work, and/or causes health problems.
The good news is that the FDA is starting to crack down more on snake oil salesmen and punishing people with fines and/or jail time for trying to sell hair regrowth products to consumers that are not FDA-Approved. However, consumers still need to be aware of the product they are buying.
The active ingredient found in Avacor Physician's Formulation is Minoxidil. Currently, the FDA has approved Minoxidil in two different strengths: 5% for men and 2% for women. The Avacor product has Minoxidil levels that adhere to these requirements. If the levels were anything different than the 2% and 5% required by the FDA, the product could not be advertised as FDA-Approved, and could be recalled by the FDA at anytime.
In January of 2012, the FDA issued a press release announcing the recall of some hair regrowth products because they were unapproved new drugs, and had high levels of Minoxidil that could cause health hazards to consumers. These products had Minoxidil levels between 10 and 15%. If you are currently using a hair regrowth product, be sure to check the Minoxidil level, and consider switching to Avacor's FDA-Approved Physician's Formulation, as well as other hair care products: the Avacor® All Natural Nutricap containing the active ingredient Saw Palmetto, which is widely thought to be a DHT inhibitor; Boost! by Avacor®, which is specially formulated to thicken hair from the very first application; and our Scalp Detoxifying Shampoo, which removes dirt and oil from the scalp, ensuring effective delivery of the Minoxidil to the scalp when applied after using the shampoo. Rest assured that all our products are manufactured in facilities that meet the highest safety and quality standards today. Furthermore, all our products are safe to use, and have been formulated to either help you grow a natural, full, healthy head of hair, or to maintain healthy, clean, and stylish hair.
When it comes to medications and your child, don't take any chances. It is very important to check with your doctor before using any medications while pregnant or breast-feeding.
First, we should mention that the FDA has not approved minoxidil for any indications other than pattern hair loss. According to a regulatory compliance guidance document from the FDA,1 minoxidil should not be used for hair loss associated with child birth. (“Do not use if… hair loss is associated with childbirth.”)
Information from both the FDA and the National Institutes of Health recommend speaking with a doctor or health professional before using minoxidil if you are pregnant or breast-feeding.
The FDA guidance document mentioned above states: “if pregnant or breast-feeding, ask a health professional before use.” The NIH's MedlinePlus website2 provides a similar recommendation: “Before using minoxidil… tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while using minoxidil, call your doctor.”
While we are not aware of any large, systematic studies of minoxidil use during pregnancy, a group of physicians from the Università di Firenze in Italy reported a case of a woman who used 2% topical minoxidil during her pregnancy and whose fetus developed abnormally.3 While no causal effect was established, the authors conclude: “Further knowledge on minoxidil-induced fetal toxicity would be beneficial before allowing its use in pregnant women.”
Remember - if you are pregnant or breast-feeding, talk to your doctor before using any products that contain minoxidil. And please keep the questions coming!
1. FDA Guidance: "Example Drug Facts Label for Minoxidil Topical Solution 2% for Men and Women". Link to FDA website
2. MedlinePlus drug information: Minoxidil Topical. http://www.nlm.nih.gov/medlineplus/druginfo/meds/a689003.html
3. Smorlesi C, Caldarella A, Caramelli L, Di Lollo S, Moroni F. Topically applied minoxidil may cause fetal malformation: a case report. Birth Defects Res A Clin Mol Teratol. 2003 Dec;67(12):997-1001. Link to PubMed
During the second half of the 20th century, advances in surgical techniques have led to significant improvements in the cosmetic appearance of hair transplants. Still, it often takes several months for grafted follicles to begin growing new hair and some patients require multiple surgeries to reach their desired cosmetic outcome.
Over the last 20 years a growing number of physicians have begun suggesting the use of minoxidil to improve the results of these procedures.
Minoxidil as an Adjunct to Hair Transplantation
A roundtable group of 11 international hair transplant physicians in 2002 reached a consensus that using hair regrowth medications like minoxidil after surgery "can increase hair density, speed regrowth in transplanted follicles, and complement the surgical result by slowing down or stopping further hair loss."1
They also suggested that using minoxidil prior to surgery could make transplanting easier by enlarging miniaturized suboptimal follicles, although most recommended suspending treatment for a few days before and one to three weeks after the procedure to reduce the risk of bleeding and allow graft sites to heal.
These observations were based on the physicians’ own experiences with patients, but are also supported by at least three published clinical studies.
A pilot study in 1987 suggested that some patients who used minoxidil (3% topical solution) after hair transplant surgery demonstrated hair growth within several weeks (rather than the usual time of several months), without experiencing the shedding that occurred in untreated patients in the weeks following transplantation.2
Another study, in which patients applied 2% topical minoxidil solution to the balding area of their scalp for four weeks before surgery, discontinued use for 3 weeks after surgery, then resumed treatment for an additional 3 months, concluded that “minoxidil seems to be an adjunct for a better evolution of grafts after hair transplantation surgery.”3
Finally, a double-blind trial involving 12 patients with male pattern baldness found that using 2% minoxidil for 6 weeks before and 17 weeks after surgery significantly decreased the shedding of grafted hair in the weeks after surgery.4
A review in 2008 concluded that minoxidil is “highly effective at helping to maintain existing hair, thereby creating more perceived density from the procedure” and that continuing treatment “will often help increase the density of transplanted hair, slow down the rate of loss of existing hair, and increase the caliber of existing and transplanted hair.” 5
Hair transplantation can be a very effective method for dealing with hair loss resulting from androgenetic alopecia, but it carries a hefty price tag. Using current hair transplantation methods, several thousand grafts can be required to cover the affected areas, with costs ranging from $3-12 per graft.
After investing so much time and money, it would make a lot of sense to spend a little bit of time each day using minoxidil to improve the results of your hair transplant and protect your investment for the future. At Avacor®, we provide hair loss treatments to help you regrow hair. Visit our product page to learn more.
1. Avram MR, Cole JP, Gandelman M, Haber R, Knudsen R, Leavitt MT, Leonard RT Jr, Puig CJ, Rose PT, Vogel JE, Ziering CL; Roundtable Consensus Meeting of The 9th Annual Meeting of The International Society of Hair Restoration Surgery. The potential role of minoxidil in the hair transplantation setting. Dermatol Surg. 2002 Oct;28(10):894-900; discussion 900. Link to PubMed
2. Kassimir JJ. Use of topical minoxidil as a possible adjunct to hair transplant surgery. A pilot study. J Am Acad Dermatol. 1987 Mar;16(3 Pt 2):685-7. Link to PubMed
3. Bouhanna P. Topical minoxidil used before and after hair transplantation. J Dermatol Surg Oncol. 1989 Jan;15(1):50-3. Link to PubMed
4. Roenigk HH, Berman MD. Topical 2% minoxidil with hair transplantation. Face. 1993;4:213-6.
5. Avram MR, Rogers NE. Hair transplantation for men. J Cosmet Laser Ther. 2008 Sep;10(3):154-60. Link to PubMed
6. Sandoval A. Minoxidil 5% following hair transplantation for increased growth. Abstract of presentation at European Society of Hair Restoration Surgery, June 2002. London, England
Part 5 – Minoxidil Benefits, Limitations, and Side Effects
This post will conclude the Avacor® Hair Regrowth Blog's five part “mini-series” on minoxidil, the first FDA-approved treatment for hair loss. Earlier episodes of the mini-series covered the early history of minoxidil, clinical trials showing its efficacy in treating androgenetic alopecia, and its approval by the FDA as a hair regrowth treatment. In this final segment we will highlight the benefits, limitations, and side effects associated with minoxidil.
Benefits of Minoxidil Treatment
Several clinical trials have proven that minoxidil is able to prevent hair loss and regrow hair, with investigators observing hair growth in anywhere from 30-60% of patients (for details see our previous post on clinical trials). These studies also suggest that even if patients do not achieve noticeable hair regrowth with minoxidil treatment, they can at least stop losing hair and maintain their baseline hair count.
Minoxidil is the only hair regrowth medication that has been approved by the FDA for both men and women, unlike finasteride (Propecia®) which is only approved for use by men.
One of the other benefits of minoxidil is that it has not been associated with the sexual side effects experienced by some patients taking finasteride (Propecia®), such as decreased arousal and erectile dysfunction.1 For a description of the side effects that have been associated with minoxidil, keep reading for the section below on “Reported Side Effects of Minoxidil.”
There is no magic cure for hair loss, so it is important to begin any hair regrowth regimen with accurate information and reasonable expectations. Minoxidil will not work for everyone; its effectiveness is limited to certain types of hair loss and the degree of hair regrowth experienced by each person will differ. In addition, minoxidil requires a consistent, diligent program of use to achieve maximum results.
Only Works for Certain Types of Hair Loss
The only types of hair loss for which minoxidil has been approved by the FDA are male and female androgenetic alopecia. Some studies have reported positive results for a small number of patients with alopecia areata, but the benefits have not been consistent enough to recommend widespread use of minoxidil for this condition.
Men: Minoxidil 5% topical solution, (such as Avacor Physicians Formulation® for Men) is only recommended for men with male pattern hair loss, and is not intended for treating frontal baldness or a receding hairline. Despite a conference presentation by the lead investigator of several early minoxidil trials suggesting that it is also effective in the frontal hairline area,2 the supporting data do not appear to have been published in any peer-reviewed journals or evaluated by the FDA. Patients using minoxidil should not expect to regrow hair in any areas other than the top of the scalp.
Women: Minoxidil 2% topical solution, (such as Avacor Physicians Formulation® for Women) is only recommended for women with female pattern hair loss (general thinning of hair on the top of the scalp). Minoxidil products are not indicated for hair loss that is sudden, patchy, or associated with stress or childbirth.
Minoxidil may not work for patients whose hair loss is too advanced. A general visual guide that shows the degrees of thinning hair for which minoxidil is most effective can be found on Avacor's product packaging (pictured above).
Needs to be Used Consistently
In order to achieve the best possible results with minoxidil, it is essential to apply the topical solution regularly and consistently. The best way to do this is to commit to making it part of your daily routine, even if it's not your favorite part of the day. An analogy for this would be brushing your teeth: while no one particularly enjoys the act of brushing their teeth (at least that we are aware of), most people find the benefits are worth the little bit of time each day.
Like all good things, regrowing hair takes time. You may need to use minoxidil for at least 4 months before you see results, although you may begin to notice the effects as early as 2 months.
Continued use is necessary to prevent hair loss from progressing. One of the longest studies of minoxidil for male pattern hair loss (5 years) found that patients who continued to apply minoxidil twice per day were able to maintain nonvellus hair regrowth well beyond their baseline hair counts.3 Patients who stop using minoxidil will likely not maintain hair that has regrown during the course of treatment and will begin losing hair again.
Reported Side Effects of Minoxidil
More than 20 years after minoxidil was first approved for treating hair loss, the list of commonly reported side effects remains fairly limited. However, there are some rare side effects that should be watched for and taken very seriously.
Some of the most common side effects are:
• Localized scalp reactions or skin irritation (i.e., dryness, itching, redness and mild burning)
• GI discomforts (e.g., mild heartburn, nausea, constipation and diarrhea)
• Hair growth in other body areas (i.e., face, arms, back)
If you experience any of the following rare side effects, you should discontinue use immediately and consult your physician:
• Dizziness, light headedness, faintness, headaches
• Sudden unexplained weight gain, water retention
• Rapid heart beat or chest tightness/discomfort
• Swelling of the mouth, face, lips, or tongue
In addition to these side effects, some people have experienced changes in hair color and/or texture.
If you have heart disease you should talk to your doctor before using minoxidil. Minoxidil may be harmful if used when pregnant or breast-feeding, should not be used by children under the age of 18, and should be kept out of reach of children at all times.
Thanks again for checking out the “Minoxidil Mini-Series” here on the Avacor Hair Regrowth Blog. We hope the information we have collected here has given you a better understanding of the history, benefits, and limitations of minoxidil and that it will help you choose the best course of action for regrowing your hair.
If you have any questions or would like to see more information on a particular topic, please leave a comment below. We'd love to hear from you!
1. Irwig MS, Kolukula S. Persistent sexual side effects of finasteride for male pattern hair loss. J Sex Med. 2011 Jun;8(6):1747-53. Link to Pubmed
2. Olsen EA, Whiting DA, Miller JJ. Increased Frontal Scalp Coverage and Frontal Hair Regrowth with 5% and 2% Minoxidil Solution. Presented at the American Academy of Dermatology 61st Annual Meeting, March 2003.
3. 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
Part 4 – FDA Approval and Transition to OTC
So far in the Avacor® Hair Regrowth Blog’s “Minoxidil Mini-Series,” we have documented the initial use of minoxidil as a blood pressure medication, the surprising discovery that it regrew hair in patients with androgenetic alopecia, and the clinical trials that eventually proved minoxidil’s effectiveness for treating hair loss.
Today the story continues with the Food and Drug Administration’s initial approval of 2% minoxidil for male pattern baldness in 1988, supplemental approvals allowing use by women and availability over-the-counter, and finally the approval of 5% minoxidil (extra-strength) for men in 1997.
FDA Approves Minoxidil for Male and Female Pattern Hair Loss
After the efficacy of minoxidil for treating hair loss was demonstrated in clinical trials (see our last post for a summary), Pharmacia & Upjohn submitted a New Drug Application (NDA) to the FDA seeking approval to market a 2% topical minoxidil solution for male pattern hair loss.
NDA 19-501 for “Rogaine® Topical Solution” presented data on the safety and efficacy of the formulation, pharmacokinetic studies of drug absorption, a statistical review of the clinical results, and proposed package labeling for the product. With its approval on August 17, 1988, minoxidil became the first-ever FDA-approved treatment for hair regrowth.
Soon after, a supplemental application was made for the use of 2% minoxidil by women suffering from female androgenetic alopecia. Supported by several clinical trials that showed the effectiveness of minoxidil for treating hair loss in women (also summarized in our last post), the application was approved in 1991 and Rogaine® became available to women on a prescription basis.
The product was a huge success, reaching sales of $100 million per year by 1995.1 On February 9, 1996, just two days before Pharmacia & Upjohn's patent on minoxidil expired, the FDA approved a supplement to NDA 19-501 allowing over-the-counter distribution of 2% minoxidil for men (in a blue package) and women (pink package).
FDA Approval of “Extra-Strength” Minoxidil (5%) for Men
Since earlier studies had shown a dose-dependent increase in the effectiveness of minoxidil for hair regeneration in men,2 it was only a matter of time before studies began to test whether doses higher than 2% minoxidil could be more effective in regrowing hair.
The results of a 48-week, double-blind, placebo-controlled, randomized, multicenter trial in 393 balding men showed that “5% topical minoxidil was clearly superior to 2% topical minoxidil,” producing an earlier response to treatment and resulting in 45% more hair regrowth without evidence of systemic effects from the increased concentration.2 In light of the clear benefits of 5% minoxidil, NDA 20-834 for “Rogaine® Extra Strength For Men (5% Topical Minoxidil Solution),” was approved by the FDA on November 14, 1997.
While the benefits for men were clear, a subsequent trial comparing 5% minoxidil to 2% minoxidil or placebo in female patients did not support its use by women.3 Although the 5% minoxidil solution proved superior to placebo (and resulted in favorable impressions from patients), it did not provide a statistically significant benefit over 2% minoxidil for any of the objective measures of hair regrowth.
Avacor Products’ ANDA for Minoxidil
When Pharmacia & Upjohn’s patents covering topical minoxidil for hair regrowth expired, other companies received FDA approval through the Abbreviated New Drug Application (ANDA) process to manufacture and sell minoxidil for hair regrowth. Avacor Products LLC currently holds such approval in the form of ANDA #075619 and provides topical minoxidil solutions (Avacor Physicians Formulation®) for both men and women.
Make sure to tune in next week when we wrap up the story with the final episode of the Avacor Hair Regrowth Blog’s “Minoxidil Mini-Series.” Our goal with this blog is to provide you with the information you need so that you can make an informed decision about your approach to hair regrowth; part of this process is making sure you have a clear understanding of what you can and cannot expect from using minoxidil.
In the last installment we will give a summary of the benefits that minoxidil can provide, but also explain the limitations and potential side effects you might experience. In the end we hope that having all this information in one place will make it easier for you to navigate the world of hair regrowth treatments and find the right solution for you.
1. Gellene, Denise. “TV Ads for Rogaine to Sprout.” Los Angeles Times. April 19, 1996. (Accessed July 22, 2011)
2. Shupack JL, Kassimir JJ, Thirumoorthy T, Reed ML, Jondreau L. Dose-response study of topical minoxidil in male pattern alopecia. J Am Acad Dermatol. 1987 Mar;16(3 Pt 2):673-6. Link to PubMed
3. Olsen EA, Dunlap FE, Funicella T, Koperski JA, Swinehart JM, Tschen EH, Trancik RJ. A randomized clinical trial of 5% topical minoxidil versus 2% topical minoxidil and placebo in the treatment of androgenetic alopecia in men. J Am Acad Dermatol. 2002 Sep;47(3):377-85. Link to PubMed
4. Lucky AW, Piacquadio DJ, Ditre CM, Dunlap F, Kantor I, Pandya AG, Savin RC, Tharp MD. A randomized, placebo-controlled trial of 5% and 2% topical minoxidil solutions in the treatment of female pattern hair loss. J Am Acad Dermatol. 2004 Apr;50(4):541-53. Link to PubMed
Part 3 – Minoxidil 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® 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.
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.
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
Part 2 – From Blood Pressure to Baldness
In Part 2 of the Avacor® Hair Regrowth Blog “Minoxidil Mini-Series” we will trace the path of minoxidil through the 1970s and 1980s as reports of hair growth led a potent blood pressure (BP) medication to be proposed as a treatment for male pattern baldness (MPB).
Minoxidil was first synthesized in the 1960s by William Anthony and Joseph Ursprung of The Upjohn Company (US Patent No. 3,461,461) and was initially prescribed as a vasodilator for lowering blood pressure in patients with hypertension.1
A few years later, some doctors began to note an unintended effect in patients taking the drug: hair growth.
Early Reports of Hair Growth
Compared to other antihypertensive treatments available at the time, such as propranolol and hydralazine, a 1972 study found that oral minoxidil therapy (later known as Loniten®) provided a significant improvement in blood pressure reduction.2 However, the authors also observed hypertrichosis (excessive hair growth) in five of the eight patients who were treated with the drug for more than two months.
Many subsequent publications during the 1970s confirmed these initial reports of increased hair growth with minoxidil, with observations such as: “side effects included increased hair growth.” 3
This effect may not have been particularly surprising since another vasodilator, diazoxide, had been associated with hypertrichosis in the early 1960s.4 Although chemically unrelated to minoxidil, diazoxide relaxes blood vessels by a similar mechanism (activation of ATP-sensitive potassium channels).
“Reversal of male pattern baldness by minoxidil…”
In the early 1980s, isolated case reports began to emerge that described the “reversal of baldness” by minoxidil.5,6 One patient’s experience was particularly compelling:6
“Within four weeks dark-brown hair (the normal color for this patient) grew over the area of the scalp that had previously been devoid of hair visible to the naked eye and had made up the major portion of his scalp except for the sides and back of his head. By eight weeks these new hairs were approximately 1.3 cm (0.5 in) long. The density of hair and the hair-shaft thickness were equal to those of the areas of this patient's scalp that were normally not subject to balding.”
One prescient report of minoxidil causing “excessive hair growth” on the “temples and forehead,” which was published before the other two reports on baldness, even proposed its use as a topical treatment for androgenetic alopecia:7
“The high incidence of hypertrichosis produced by both diazoxide and minoxidil suggests the possibility that an effective topical formulation might stimulate local hair growth in early male-pattern alopecia…”
The drug’s maker, Upjohn, was already well-prepared to capitalize on the new indication that was being proposed for its drug. By February, 1979, the company had already received a patent covering the use of topical minoxidil compositions for growing hair.
The Upjohn Company Patents Minoxidil for Alopecia
“The invention claimed is: 1. A method of treating humans for alopecia…”
Upjohn was granted two critical U.S. patents covering the use of minoxidil for treating male pattern baldness:
US Patent No. 4,139,619 claimed a “topical composition” that could be used for “increasing the rate of terminal hair growth in mammalian species” and “conversion of vellus hair to growth as terminal hair.”
US Patent No. 4,596,812 claimed a “method of treating humans for alopecia which comprises topically applying to the human scalp an effective amount of a solution containing 6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine and a solvent.”
These patents laid the foundation for the successful commercialization of minoxidil as a treatment for male pattern baldness, under the trade name Rogaine®.
In the next installment of the Avacor Hair Regrowth Blog “Minoxidil Mini-Series,” we will describe the clinical trials that proved minoxidil’s effectiveness against alopecia in men and women, as well as the approval by the FDA of minoxidil as the first treatment for male pattern hair loss. Check back here soon for Part 3 – Efficacy in Clinical Trials.
1. Gilmore E, Weil J, Chidsey C. Treatment of essential hypertension with a new vasodilator in combination with beta-adrenergic blockade. N Engl J Med. 1970 Mar 5;282(10):521-7. Link to Pubmed
2. Gottlieb TB, Katz FH, Chidsey CA 3rd. Combined therapy with vasodilator drugs and beta-adrenergic blockade in hypertension. A comparative study of minoxidil and hydralazine. Circulation. 1972 Mar;45(3):571-82. Link to Pubmed
3. Jacomb RG, Brunnberg FJ. The use of minoxidil in the treatment of severe essential hypertension: a report on 100 patients. Clin Sci Mol Med Suppl. 1976 Dec;3:579s-581s. Link to Pubmed
4. Okun R, Russell RP, Wilson WR. Use of diazoxide with trichlormethiazide for hypertension. Arch Intern Med. 1963 Dec;112:882-8. Link to Pubmed
5. Seidman M, Westfried M, Maxey R, Rao TK, Friedman EA. Reversal of male pattern baldness by minoxidil. A case report. Cutis. 1981 Nov;28(5):551-3. Link to Pubmed
6. Zappacosta AR. Reversal of baldness in patient receiving minoxidil for hypertension. N Engl J Med. 1980 Dec 18;303(25):1480-1. Link to Pubmed
7. Burton JL, Marshall A. Hypertrichosis due to minoxidil. Br J Dermatol. 1979 Nov;101(5):593-5. Link to Pubmed
Of all the products sold to combat hair loss and regrow hair, only two have ever been approved by the U.S. Food and Drug Administration (FDA) for regrowing hair: minoxidil and finasteride.
Minoxidil is available for both men and women as a topical treatment, while finasteride (Propecia®) comes in pill form and is not currently indicated for use by women. Minoxidil was first approved by the FDA for hair regrowth in 1988 and continues to be one of the most effective known treatments for androgenetic alopecia (AGA) to date.
In the next few Avacor® Hair Regrowth Blog posts we will recount the history of minoxidil, from its origins as a prescription blood pressure medication to its current use as an over-the-counter hair growth treatment.
We will highlight some of the clinical trials that have shown minoxidil’s effectiveness in stopping hair loss and regrowing hair (for both men and women), explain some of the benefits and limitations of using minoxidil, and describe some potential side effects you might experience.
Stay tuned to the Avacor Hair Regrowth Blog in the next few days for Part 2 of the “Minoxidil Mini-Series”: From Blood Pressure to Baldness.
A study1 published in the June 2011 issue of the Journal of Dermatological Science may shed some light on the mechanisms by which minoxidil promotes hair regrowth.
Minoxidil, the FDA-approved active ingredient in Avacor Physicians Formulation®, has been clinically proven to regrow hair in patients with androgenetic alopecia (AGA). Although minoxidil is a vasodilator and is known to increase circulation and blood flow to the scalp, it is not completely clear how it achieves hair regrowth in AGA patients at the molecular level.
This exciting research shows that minoxidil activates the β-catenin pathway in vitro in cultured human dermal papilla cells, a population of cells in the hair follicle involved in the induction and maintenance of hair growth.
Previous research on β-catenin from Harvard Medical School has shown that β-catenin activity in the dermal papilla regulates the regeneration of hair2 and scientists at the University of Michigan found that simply activating β-catenin in skin cells is sufficient to trigger the active growth phase of the hair cycle in mice.3
While this finding still needs to be confirmed by other research groups, the authors’ suggestion that “minoxidil extends the anagen phase by activating β-catenin activity” offers an exciting hypothesis on the mechanism of action of minoxidil.
This hypothesis is especially interesting in light of other research showing that dihydrotestosterone (DHT), the hormone that causes AGA, inhibits β-catenin activity in hair follicle cells (see our previous post on "Mouse-Pattern Baldness").
Taken together, these two conclusions raise the possibility that 5-alpha reductase inhibitors (which block DHT production) could work in concert with minoxidil to further increase β-catenin activity and hair regeneration. Future research into any such potential additive or synergistic effects would be of great interest to the hair regrowth community.
1. Kwack MH, Kang BM, Kim MK, Kim JC, Sung YK. Minoxidil activates beta-catenin pathway in human dermal papilla cells: A possible explanation for its anagen prolongation effect. J Dermatol Sci. 2011 Jun;62(3):154-9. Link to Pubmed
2. Enshell-Seijffers D, Lindon C, Kashiwagi M, Morgan BA. Beta-catenin activity in the dermal papilla regulates morphogenesis and regeneration of hair. Dev Cell. 2010 Apr 20;18(4):633-42. Link to Pubmed
3. Van Mater D, Kolligs FT, Dlugosz AA, Fearon ER. Transient activation of beta-catenin signaling in cutaneous keratinocytes is sufficient to trigger the active growth phase of the hair cycle in mice. Genes Dev. 2003 May 15;17(10):1219-24. Link to Pubmed