By androgenetic alopecia, we refer to the common baldness we see in some women who are losing hair density in the most cranial part of the scalp, or in many men who experience a receding hairline, a bald spot on the crown of the head, or significant hair loss throughout their lives.
In this type of alopecia, hair miniaturization occurs, the proportion of hairs in the resting or telogen phase increases, and hairs become shorter due to the reduced follicle growth period. We know that a pathway called Wnt/ß catenin is altered, which increases a molecule called TGF-ß1 (transforming growth factor), which in turn triggers increased cell death in the dermal papilla (the root, a process known as apoptosis). As a result of this process, there are fewer cells contributing to hair growth and production, and hair growth time is reduced. To find an analogy, this process is similar to what plant roots experience in winter in cold countries.
In general, there is agreement that this process is induced by the hormone dihydrotestosterone (DHT), although researchers on this topic have been concerned about whether something else worsens baldness.
One of the most interesting findings in bald people is that the partial pressure of oxygen is significantly lower in the areas of the scalp where baldness develops. A study published in 1996 and conducted in Michigan by Goldman et al., comparing nine bald men with nine men with hair, found that the partial pressure of oxygen (PO2) was 32 mmHg in the bald areas and 51.8 mmHg in the hairy areas. In contrast, the hairy volunteers studied had much higher oxygen saturation in the skin of the scalp, and the PO2 was 53.9 mmHg and 61.4 mmHg, respectively [1]. It is as if blood circulation in the scalp of people with alopecia were defective or depleted in oxygen, or excessive contraction of the scalp muscles prevented proper blood flow to the hair.
So that you can read the exact results of this study by Goldman et al. I copy below the phrase that I understand is key.
“Transcutaneous PO2 was significantly lower in the bald frontal scalp (32.2 +/- 2.0 mmHg) than in the hair-bearing temporal scalp (51.8 +/- 4.4 mmHg) in men with male pattern baldness. In controls, there was no significant difference in transcutaneous PO2 of the frontal scalp (53.9 +/- 3.5 mmHg) and temporal scalp (61.4 +/- 2.7 mmHg).”
Below is the reference of the publication with the details of the study, its date and place of publication.
Comparative study > plast reconstr surg. 1996 May;97 (6): 1109 – 16; discussion 1117.
Doi: 10.1097/00006534-199605000-00003.
TRANSCUTANEOUS P02 OF THE SCALP IN MALE PATTERN BALDNESS: A NEW PIECE TO THE PUZZLE
B E Goldman 1, D M Fisher, S L Ringler
Affiliations – collapse
AFFILIATION
1- Department of plastic surgery , butterworth hospital, Grand rapids, Mich, USA.
PMID: 8628793 DOI: 10.1097/00006534-199605000-00003
Something strange happens with the oxygen supply to the bald areas of the scalp. It’s as if oxygen «isn’t getting there.» One of the most surprising things known today is that excessive muscle contraction increases the expression of a gene that probably doesn’t sound familiar to you, known as TGFß1-1 or ARA55 or HIC-5, whose product binds or sticks to the androgen receptor and multiplies its action by three or four. Since we know that androgen receptors are responsible for inhibiting hair growth, this would result in muscle contraction accentuating androgenetic alopecia through this androgen receptor activation mechanism that I just mentioned and which has been known for years.
In a study published in 1998 by Fujimoto et al. [2] one can clearly see how the activity of the androgen receptor (which is responsible for baldness) increases significantly when DHT is administered (see graph below) and even more so if ARA55 is added, this cofactor induced among other things by MUSCLE CONTRACTION.
Relative cat activity (graphic below)
In this graph from their study, the black bars represent androgen receptor activity. It can be seen that it increases in the presence of DHT and is much more pronounced when this cofactor, ARA55, is also added, which is produced to a greater extent by muscle contraction.
Below is the cover of the study demonstrating this link between baldness and muscle contraction in the scalp:
(BELOW JOURNAL OF BIOLOGICAL CHEMISTRY 1999 BY THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY PUBBLICATION)
A strong correlation has also been shown between muscle contraction and bald areas on the scalp [3]. All of these findings suggest that muscle relaxation, for example with onabotulinumtoxinA or botulinum toxin type A, could induce hair growth.
Many researchers have been active, and there are more than 70 studies and reviews published to date in the medical literature that record and describe this positive effect of botulinum toxin type A on alopecia, of which I will summarize five.
In 2010, a group led by Freund et al. published a study conducted on 50 individuals with androgenetic alopecia at a hospital in Ontario, Canada. These patients received two doses of 150 units of botulinum toxin type A or onabotulinum toxin separated by five months. Patients experienced an 18% increase in hair density according to their measurements [4]. The differences were statistically significant. You can see below in the table published in this study that the average number of hairs per cm2 increased from 235 to 276 in one year:
GRAPHIC
Below you can see the cover of the published article and photographs of some patients:
• PLASTIC AND RECONSTRUCTIVE SURGERY STUDY + PICTURES
Patient from Freund’s study.
Pretreatment and posttreatment photographs of subjects with androgenetic alopecia responsive to botulinum toxin therapy.
Reference: Treatment of Male Pattern Baldness with Botulinum Toxin: A Pilot Study
Plastic and Reconstructive Surgery 126(5):246e-248e, November 2010.
Singh et al. [5] published another very interesting study in which they injected 150 units of botulinum toxin type A into the frontalis, temporalis, periauricularis, and occipital muscles in men with androgenetic alopecia. The study was conducted in India and recruited ten men between the ages of 22 and 42 who had received previous treatments for alopecia within the previous 6 months. After 6 months, the photographs obtained were evaluated and it was found that 8 (80%) patients showed an excellent response to treatment, 1 (10%) patient showed modest improvement, and one patient did not respond. No adverse effects were detected.
Another prospective study, conducted by Zhang et al. [6], evaluated the effects of a lower dose of botulinum toxin type A (50 units) in 25 men with alopecia, aged 30 to 45 years. At the 6-month evaluation, 11 (44%) subjects showed an increase in hair count of more than 10%, 8 (32%) showed a small improvement, and 5 (20%) showed no change, representing a response rate of 79.1%.
In another study conducted and published by Shon et al. [7], 18 men with a mean age of 49 years were recruited and received 30 units of botulinum toxin type A. Sessions were conducted every 4 weeks for 24 weeks. At 24 weeks, the number of hairs per square centimeter increased significantly, from 129.61 to 136.22, an increase of 5.1%. These authors also investigated the effects of botulinum toxin type A on TGF-β1 (transforming growth factor ß-1), which has such a negative effect on the dermal papilla cells of hair follicles in humans. They found that it was reduced, while DHT (dihydrotestosterone) increased it.
The most relevant study was conducted by Zhou et al. [8]. A total of 68 adult males between the ages of 18 and 60 were recruited for this study. They had not received any prior treatment with medications that could interfere with botulinum toxin in the previous 6 months.
Participants in this study were randomly assigned to one of two groups. The first group received ONLY botulinum toxin type A injections, and the second group received botulinum toxin type A injections along with 1 mg of finasteride orally daily. The injected dose was 100 IU of botulinum toxin type A in the frontalis, temporalis, and periauricularis muscles (i.e., the lateral area of the skull immediately above the ear) and the occipital muscles (corresponding to the back of the scalp). A total of 4 sessions were conducted, spaced every 3 months.
In the evaluation carried out at 12 months it was found that the number of hairs per cm2 in the group treated ONLY with botulinum toxin type A increased significantly (p < 0.001) from 180.57 to 218.26. In the second group where botulinum toxin type A was injected and oral finasteride was taken, it increased from 178.21 to 234.01, being equally statistically significant but very similar to the botulinum toxin group. These data are shown below in table number 2 of the study published by Zhou et al. which shows just below:
*GRAPHIC + PICTURES
The findings that can be seen in the images above, where in the top row we have a patient from the botulinum toxin type A group and in the bottom one from the finasteride group, show that botulinum toxin type A is virtually as effective as finasteride, which is the drug of choice approved for the treatment of Androgenetic Alopecia since 1997. Below you can see the cover of the publication, which is now having a great impact among Trichology specialists.
*ARTICLE + GRAPHIC
After the data we have presented and a detailed discussion of the research that has been conducted on botulinum toxin type A and androgenetic alopecia for almost 30 years, its efficacy and usefulness seem quite plausible. Considering the affordable cost of botulinum toxin and its large safety margin, its inclusion in alopecia treatments is highly recommended.
Literature
[1]. Goldman BE, Fisher DM, Ringler SL. Transcutaneous PO2 of the scalp in male pattern baldness: a new piece to the puzzle. Plast Reconstr Surg. 1996 May;97(6):1109-16; discussion 1117. doi: 10.1097/00006534-199605000-00003. PMID: 8628793.
[2]. Fujimoto N et al. Cloning an Characterization of Androgen receptor cofactor ARA55 in human prostate. J of Biol Chem. 1999; 274(12):8316-21
[3]. Tellez-Segura R. Involvement of Mechanical Stress in Androgenetic Alopecia. Int J Trichology. 2015 Jul-Sep;7(3):95-9. doi: 10.4103/0974-7753.167468. PMID: 26622151; PMCID: PMC4639964.
[4] Freund BJ, Schwartz M. Treatment of male pattern baldness with botulinum toxin: a pilot study. Plast Reconstr Surg. 2010 Nov;126(5):246e-248e. doi:10.1097/PRS.0b013e3181ef816d. PMID: 21042071.
[5]. Singh S, Neema S, Vasudevan B. A Pilot Study to Evaluate Effectiveness of Botulinum Toxin in Treatment of Androgenetic Alopecia in Males. J Cutan Aesthet Surg. 2017 Jul-Sep;10(3):163-167. doi: 10.4103/JCAS.JCAS_77_17. PMID: 29403190; PMCID: PMC5782443.
[6]. Zhang L, Yu Q, Wang Y, Ma Y, Shi Y, Li X. A small dose of botulinum toxin A is effective for treating androgenetic alopecia in Chinese patients. Dermatol Ther. 2019 Jul;32(4):e12785. doi:10.1111/dth.12785. Epub 2019 Jan 8. PMID: 30566260.
[7]. Shon U, Kim MH, Lee DY, Kim SH, Park BC. The effect of intradermal botulinum toxin on androgenetic alopecia and its possible mechanism. J Am Acad Dermatol. 2020 Dec;83(6):1838-1839. doi: 10.1016/j.jaad.2020.04.082. Epub 2020 Apr 25. PMID: 32339707.
[8]. Zhou Y, Yu S, Zhao J, Feng X, Zhang M, Zhao Z. Effectiveness and Safety of Botulinum Toxin Type A in the Treatment of Androgenetic Alopecia. Biomed Res Int. 2020 Aug 4;2020:1501893. doi: 10.1155/2020/1501893. PMID: 32802833; PMCID: PMC7424364.
