Minoxidil Mini-Series: Part 5 – 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
Minoxidil products, such as Avacor Physicians Formulation® and Rogaine®, have helped thousands of men and women stop their hair loss and begin regrowing hair.
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.”
Minoxidil’s Limitations
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.
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.
Conclusion
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!
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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
Minoxidil Mini-Series: 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.
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1. Gellene, Denise. “TV Ads for Rogaine to Sprout.” Los Angeles Times. April 19, 1996. (Accessed July 22, 2011)
http://articles.latimes.com/1996-04-19/business/fi-60266_1_rogaine-sales
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
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
Minoxidil Mini-Series: Introduction
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 “New” Molecular Mechanism Proposed For Minoxidil
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.
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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
Mouse Pattern Baldness: A Step Forward in Androgenetic Alopecia Research
Animal models of human medical conditions are valuable tools for biomedical research and preclinical drug discovery. Last year a group of hair growth scientists at Wyeth Research (now part of Pfizer) unveiled a strain of genetically altered mice that were developed to mimic the biology of androgenetic alopecia (AGA).1
The mice were genetically engineered to express the human androgen receptor (AR) gene in their hair follicle cells. AR is the receptor for dihydrotestosterone (DHT), the hormone implicated in male pattern hair loss (see our previous post on anti-androgens for more information on AR and DHT).
As expected, DHT inhibited hair regeneration in these mice. When a patch of hair was removed from the backs of the mice, DHT treatment significantly reduced the rate of hair regrowth, simulating the action of androgens in AGA (see a picture of the results here on the Endocrinology website).
The effect of DHT on hair regrowth was completely reversed by treatment with an AR antagonist (hydroxyflutamide) and was not observed in genetically normal mice, proving that DHT's effects on hair were dependent on AR. One notable difference between these mice and human patients with AGA is that the inhibition of hair regrowth by DHT was only a temporary delay, rather than a persistent lack of growth.
The authors go on to suggest that AR influences hair growth by affecting a cell signaling pathway known as the Wnt/β-catenin pathway, which is essential for hair follicle development and hair growth.2
Based on the observation that AR inhibits β-catenin signaling in other cell types,3, 4 this study suggests that DHT may interfere with hair growth by blocking the actions of β-catenin in the hair follicle.
In the future the group plans to directly test the role of β-catenin by introducing another genetic modification that would allow them to easily turn the pathway on and off during the hair regeneration process. The authors conclude that this “mouse model will be a valuable tool for elucidating the mechanisms responsible for androgen-AR-dependent hair loss and the development of effective treatments for hair loss in humans.”
A companion article in the same issue of Endocrinology shares the same optimism and enthusiasm: "the potential for AR blocking β-catenin actions is interesting given the evidence that hair follicle development and cycling is dependent on Wnt-β-catenin signaling... The new mouse model will permit further characterization of the mechanism by which androgens alter β-catenin activity."
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1. Crabtree JS, Kilbourne EJ, Peano BJ, Chippari S, Kenney T, McNally C, Wang W, Harris HA, Winneker RC, Nagpal S, Thompson CC. A mouse model of androgenetic alopecia. Endocrinology. 2010 May;151(5):2373-80. Link to Pubmed
2. Kishimoto J, Burgeson RE, Morgan BA. Wnt signaling maintains the hair-inducing activity of the dermal papilla. Genes Dev. 2000 May 15;14(10):1181-5. Link to Pubmed
3. Chesire DR, Isaacs WB. Ligand-dependent inhibition of beta-catenin/TCF signaling by androgen receptor. Oncogene. 2002 Dec 5;21(55):8453-69. Link to Pubmed
4. Pawlowski JE, Ertel JR, Allen MP, Xu M, Butler C, Wilson EM, Wierman ME. Liganded androgen receptor interaction with beta-catenin: nuclear co-localization and modulation of transcriptional activity in neuronal cells. J Biol Chem. 2002 Jun 7;277(23):20702-10. Link to Pubmed
5. Walker WH. Is the "comb over" dying? A mouse model for male pattern baldness (androgenic alopecia). Endocrinology. 2010 May;151(5):1981-3. Link to Pubmed
FDA: “Label Change – Increased Risk of Prostate Cancer” for the hair loss drug Propecia®
On June 9, 2011, the FDA issued a Drug Safety Communication1 about a class of drugs called 5-alpha reductase inhibitors, which includes the hair loss drug Propecia® (finasteride).
FDA Drug Safety Communication: 5-alpha reductase inhibitors (5-ARIs) may increase the risk of a more serious form of prostate cancer
[6-9-2011] The U.S. Food and Drug Administration (FDA) is informing healthcare professionals that the Warnings and Precautions section of the labels for the 5-alpha reductase inhibitor (5-ARI) class of drugs has been revised to include new safety information about the increased risk of being diagnosed with a more serious form of prostate cancer (high-grade prostate cancer). This risk appears to be low, but healthcare professionals should be aware of this safety information, and weigh the known benefits against the potential risks when deciding to start or continue treatment with 5-ARIs in men.
Two large clinical trials, known as PCPT and REDUCE, were conducted to assess the use of 5-ARIs for preventing prostate cancer. The PCPT trial raised concern at the FDA because patients being treated with finasteride had a slightly higher risk of developing high-grade prostate cancer than patients receiving placebo (1.8% versus 1.1%, respectively). It should be noted that although the title of the FDA's Safety Alert2 reads "Increased Risk of Prostate Cancer," the data on increased risk appear to relate only to the incidence of high-grade prostate cancer (Gleason Score 8-10).
While the “risk appears to be low,” the labels for drugs including Propecia®, Proscar® (finasteride) and Avodart® (dutasteride) are all being modified to warn patients of this potential risk. Propecia® is also associated with sexual side effects3 in some men, including less desire for sex and difficulty in achieving an erection.
The FDA has provided a page of Questions and Answers on the change in label information for 5-ARIs. Below are a few Q/A’s pertaining to the use of Propecia® for male pattern hair loss.
Q6. Does FDA believe the benefits of 5-alpha reductase inhibitors (5-ARIs) still outweigh their risks for the approved indications?
A. Yes. FDA believes that 5-ARIs remain safe and effective for their approved indications. Proscar and Avodart have been effective in controlling symptoms of benign prostatic hyperplasia (BPH), as well as in reducing the risks of acute urinary retention and the need for surgical intervention related to BPH. Healthcare professionals and patients are still encouraged to discuss the risks and benefits of 5-ARIs when deciding the best treatment for their disease.
FDA will continue its risk/benefit assessment of using 5-ARIs for the treatment for male pattern hair loss and will update the public when additional information is available.
Q9. Are there other medications to treat benign prostatic hyperplasia (BPH) or male pattern baldness?
A. Yes. Another class of medications called alpha-blockers is approved to treat the symptoms of BPH. Medications in the alpha-blocker class include tamsulosin (Flomax), doxazosin (Cardura), terazosin (Hytrin), alfuzosin (Uroxatral), and silodosin (Rapaflo). However, 5-ARIs are the only medications that have been shown to reduce the risk of urinary retention or surgery related to an enlarged prostate.
Minoxidil is a topical product that is available over the counter in various formulations to treat male pattern hair loss.
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1. FDA Drug Safety Communication: 5-alpha reductase inhibitors (5-ARIs) may increase the risk of a more serious form of prostate cancer. June 9, 2011.
http://www.fda.gov/Drugs/DrugSafety/ucm258314.htm
2. 5-alpha reductase inhibitors (5-ARIs): Label Change - Increased Risk of Prostate Cancer. June 9, 2011.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm258529.htm
3. PROPECIA® labeling information, FDA website.
http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020788s018lbl.pdf
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