mesitylene oxide
Managing Androgenic Alopecia
In a previous post I described the basic anatomy of the hair follicle and provided an overview of the effects that hormones have on hair growth. In some regions (e.g. the scalp) androgens can cause hair to become thinner and less pigmented over time - this is the process of male-pattern baldness, aka androgenic alopecia (AGA). In this article I will discuss the causes of and strategies to reverse and prevent AGA.
There are a number of review articles in the literature on the subject which are also worth taking a look through1234.
There are also a number of forums and blogs on the topic567.
Causes
KRT37 is the only keratin that is regulated by androgens8. However, the gene is not expressed on the scalp, which may explain the different effects that androgens have on the body.
Testosterone upregulates prostaglandin D2 synthase and the action of prostaglandin D2 (PGD2) at DP2 is thought to contribute to AGA91011. On the other hand, PGE212 and PGF2α13 seem to induce hair growth. Women have elevated levels of PGES2 and PGFS, which may have implications for hair growth and for AGA being a condition primarily seen in men14. Some prostaglandins are known to be pro-inflammatory while others are anti-inflammatory15. Overall, prostaglandins are thought to be closely linked with hair growth and AGA16.
Another theory of AGA is DHT-induced progressive perifollicular fibrosis and calcification1718.
It is important to note that hair follicles are not gone in areas of complete hair loss but are dormant, as the scalp still contains the stem cell progenitor cells from which the follicles arose19. Wnt pathway activation induces endogenous dermal progenitor cells to differentiate into a hair bulge, leading to the formation of new hair follicles20. In addition, it has been demonstrated that androgens may inhibit Wnt/b-catenin signaling in AGA2122.
AGA has a complex dependence on genetics and is inheritable - twin studies identified heredity as accounting for around 80% of the predisposition to baldness23. Ellis et al. observed that the fathers of 81.5% of affected men have baldness that is higher than that that can be explained by autosomal dominant inheritance24.
Testosterone is converted to DHT by the action of 5α-reductase (5αR). There are three types of 5αR:
Type I expressed in the liver and sebaceous glands of the dermis. In the dermis, it is largely responsible for producing sebum, necessary for lubricating and protecting the skin from losing moisture.
Type II expressed in areas such as the prostate and dermal papilla cells of the skin. It contributes to the stimulation of the prostate and the hair follicles.
Type III is primarily expressed in peripheral tissue25.
Why is DHT so much more important than testosterone for AGA? Foremost, DHT binds to the androgen receptor with a 2-fold higher affinity and a decreased dissociation rate of 5-fold compared to testosterone26. Also, it is produced by 5αR in select tissues, and is the primary androgen in hair follicles27; Circulating levels of testosterone are 10 and 20 times that of DHT in terms of total and free concentrations, respectively,28 whereas local levels of testosterone in hair follicles are ~8 and ~4.6 times that of DHT for balding and non-balding men29.
Scalp tension has also been implicated in AGA3031 although this has not been a widely studied theory. Supposedly, the tension may induce a “pro-inflammatory cascade … which induces TGF-β1 alongside increased androgen activity (5-αR2, DHT, and AR), which furthers TGF-β1 expression in already-inflamed AGA-prone tissues.” Fibrosis from prolonged scalp tension could lead to poor blood flow to the hair follicles.
More generally, androgens have different effects on various inflammatory and growth factors: they stimulate IGF-1 at facial hair, leading to growth, but can also stimulate TGF β1, TGF β2, dickkopf1, and IL-6 at the scalp, leading to catagenic miniaturization32.
Hair loss is cumulative with age even though androgen levels fall, and finasteride does not reverse advanced stages of androgenetic alopecia; possible explanations are higher conversion of testosterone to DHT locally with age as higher levels of 5-αR are noted in balding scalp, and higher levels of DNA damage in the dermal papilla as well as senescence of the dermal papilla due to androgen receptor activation33, oxidative stress and the action of inflammatory cytokines such as those mentioned above.
Treatment - Pharmaceutical
A variety of nutrients are of course vital to hair growth and for reducing the risk of AGA34. One of these is vitamin D3536, of which a not insignificant proportion of the population is deficient. Ensuring a varied diet and appropriate micronutrient intake, while it probably won’t cure AGA, is still important for healthy hair.
Various systemic antiandrogens (AAs) such as cyproterone, bicalutamide, topilutamide, flutamide and spironolactone will undoubtedly decrease androgens and prevent AGA, although this androgen decrease will also have many other effects on men, so it is not a viable option unless you want to undergo full hormone replacement therapy. These are still viable treatment options for women with female pattern hair loss; 88% of patients with female pattern hair loss taking AAs (cyproterone or spironolactone) showed improvement or no progression of the disease37.
Finasteride is a selective type II and III 5αR inhibitor and is a routine first-line treatment for AGA. Alfatradiol (17α-Estradiol) is also a 5αR inhibitor and has only limited action at the estrogen receptor. Dutasteride is both a more potent inhibitor of type II and III 5αR and also inhibits type I 5αR, and has been found to be more efficacious than finasteride38. Treatment with finasteride slows further hair loss and provides about 25% hair regrowth after six months of treatment, with effectiveness persisting as long as the drug is taken39. These can either be taken orally (1 mg finasteride or 0.5mg dutasteride once daily) or topically (1 % topical finasteride gel application once daily to scalp).
Nonsteroidal AAs such as cyanonilutamide (and its prodrugs such as RU-56187 and RU-58841) that were developed in France in the 1980s have the advantage of being powerful antiandrogens that are active topically but do not become systemic, i.e. they may be used by men with relatively few side effects. This seems to be supported by anecdotal evidence. However, research on these is limited to animal models and none of them were ever officially approved. Prostrakan conducted RU58841 (2.5% and 5% strength) human Phase I and II trials for which the results were never published, although “according to leaks, the results were comparable to finasteride, if not better” [citation needed]. Phase III trials were never conducted although the reason for this is unknown.
Clascoterone is a steroidal AA that acts topically. The FDA approved of its use for acne in August 202040. It is also under development for AGA, having passed a phase II dose ranging study and expecting to go to phase III in the near future41. Some of the results of the Phase II study were given in a press release42.
Setipiprant, a highly selective, orally bioavailable antagonist of DP2, has been tested in medical trials but did not differ from placebo by any measure of statistical significance43. Viprostol, a synthetic PGE2 analog, was not effective at treating AGA. Latanoprost, a PGF2α analogue that is used as to treat glaucoma, induces growth of lashes and ancillary hairs around the eyelids44, has been successfully used for the treatment of eyelash hypotrichosis (lack of hair), and has shown some mild success in treating AGA45. Another PGF2α analogue called bimatoprost has exhibited similar effects46 and is FDA approved for eyelash hypotrichosis. Many more DP2 antagonists have been developed474849 but none have yet seen promising results with regards to AGA. There are some anecdotal reports on these drugs and some people swear by them50.
The immunosuppressant drug cyclosporine A was known to induce hair growth (along with a myriad of other unpleasant side effects, so it would not be a viable AGA drug). Further investigation revealed that this was mediated by the inhibition of SFRP151, which itself inhibits the Wnt signaling pathway. Subsequently the researchers used WAY-316606, a selective SFRP1 antagonist, and indeed it promoted hair growth. However, few other research exists on this drug and the Wnt pathway is known to have implications for cancer52, so care must be exercised.
Minoxidil is a vasodilator and potassium channel opener. In theory this allows more oxygen, blood, and nutrients to the follicles. Minoxidil also stimulates PGE2 production by activating COX-1. Aside from this it has a range of other pharmacological activity that may or may not be relevant to its use in treating AGA, for which is it a routine first-line treatment. When compared to cyproterone it is more effective at treating AGA in some patients but less effective in other.53 Its efficacy has been compared to that of other drugs in treating AGA54:
Ketoconazole is an antifungal agent that also inhibits 17α-hydroxylase and 17,20-lyase (which are involved in the biosynthesis of testosterone), as well as being a weak androgen receptor antagonist. It has shown efficacy almost comparable to that of minoxidil (N.B. small sample size)55.
A number of plant-derived formulations are known such as Redensyl, Procapil, Baicapil and Capixyl. A comparative study between topical 5% minoxidil and a topical mixture of Redensyl, Capixyl, and Procapil (RCP) showed a significantly higher researcher score (minoxidil group 25.5% vs. RCP group 64.7%), higher global photographic evaluation score (minoxidil: 60% vs. RCP: 88.9%), and higher self-evaluation score for RCP56.
DHT induces transforming growth factor-β1 (TGF-β1) in dermal papilla cells to suppress follicular epithelial cell growth. Botulinum toxin type A may inhibit TGF-β1 secretion. A number of studies have been conducted575859 (n=18, n=40, n=10), all of which saw significant improvements in hair growth (data comparable to values for finasteride) and no side effects. The advantage of Botox over other therapies such as finasteride or minoxidil is that it doesn’t need to be used every day, but rather perhaps two injections per year.
Melatonin has been known to modulate hair growth, pigmentation, and molting in many species including humans60. Topical application of melatonin 0.1 % solution was shown to significantly increase anagen hair in AGA in two controlled studies, with good tolerability6162.
A whole range of other vitamins, plant-derived formulations and all sorts of other waffle have been studied, most of which are not worth mentioning. Some of these are shown in the table below.
Treatment - adjuvant
Low-Level Light Therapy (LLLT) uses low-level lasers (694nm ruby) to stimulate the hair follicles. Possible mechanisms of action include stimulation of epidermal stem cells, increasing blood flow, and upregulate the production of growth factors and adenosine triphosphate that stimulate anagen hair63. It works better than placebo at treating AGA by a statistically significant margin6465. One study (n=44) saw a 35% increased hair count after 16 weeks of treatment once every other day66.
Microneedling is another treatment option, with a study showing significantly improved results in a microneedling+minoxidil vs minoxidil control group (see table below)67. Another study had four men already on finasteride+minoxidil who weren't experiencing any new hair growth treated with microneedling for six months - hair growth was significantly improved with lasting results on 18 months follow-up68. The same studies have proposed possible mechanisms of action that include: release of platelet-derived growth factor (PDGF) through platelet activation and skin wound regeneration mechanisms; activation of follicle stem cells under wound healing conditions; overexpression of hair growth-related genes including VEGF, b-catenin, Wnt3a, and Wnt10b.
Hair follicles localized in androgen-insensitive areas keep their properties even when transplanted into androgen-dependent scalp - thus, hair transplantation is possible. Follicular unit transplantation is considered the gold standard, using small follicular units, achieving a more natural result and better final outcomes. HT can lead to a long-lasting, natural result that becomes evident 6–8 months after the procedure. Topical minoxidil may speed the regrowth of transplanted follicles69.
A similar approach is hair cloning7071, wherein healthy hair follicle cells are extracted from a patient and cultivated in vitro before being implanted into areas of hair loss. Many companies are working on this approach right now (including Intecytex, Riken Centre for Developmental Biology, RepliCel Life Sciences) and, for example, Hairclone have created a "hair follicle bank" in hopes that cloning technology will allow you to implant your healthy young hair when you grow old. Hair cloning is still being heavily researched and is not yet commercially available.
Another surgical approach is scalp reduction (aka forehead reduction), although this is more invasive and requires a skilled surgeon. For some patients the results can be excellent. However, if the scalp tension theory is to be believed, you might want to avoid this procedure for treating AGA specifically.
Platelets contain growth factors and cytokines that stimulate stem cells. Platelet-rich plasma (PRP) is an autologous preparation (i.e. prepared from the patient) of plasma with a high concentration of platelets. The revitalization qualities of PRP are well-known and have been used for decades in various medical fields. Patients (n=11) with AGA who had not responded to minoxidil and finasteride treatment received four PRP injections at 2-week intervals and showed improvement on global photography and a 31% increase in hair count after 12 weeks72. Other studies have shown similarly effective treatment results from PRP on AGA73.
Stem cells can be isolated from a punch biopsy of the scalp of patients with AGA (n=11) and then injected back into the bald areas of the scalp - a 29% increase in hair density for the treated area was seen 23 weeks after treatment.74 Another company has conducted successful Phase III clinical trials on treating AGA using stem cells from adipose tissue7576. There are many varieties and techniques with regards to stem cell therapy, although most of them are still being researched.
“So what should I take?”, TL;DR
Of course the answer to this question will be highly subjective and will depend on the patient. If you want the tried-and-true, FDA approved method then a combination of minoxidil 5% topical, finasteride 1mg (oral or topical) and microneedling should be effective. Clascoterone or RU-58841 could additionally be used as topical AAs although these are more experimental.
The disadvantage of these is that they have to be used often (usually daily) and continuously. The Botox therapy seems extremely promising to me as it required an infrequent minimally invasive procedure with few side effects.
In specific cases where scalp reduction is appropriate it may be used although in serious cases of AGA the ideal procedure is a hair transplant (or, perhaps in the future, hair cloning). If you are willing to try something more experimental, stem cell therapy might be worth considering.
Notes
Rathnayake, D.; Sinclair, R. Male Androgenetic Alopecia. Expert Opin. Pharmacother. 2010, 11 (8), 1295–1304. https://doi.org/10.1517/14656561003752730.
Varothai, S.; Bergfeld, W. F. Androgenetic Alopecia: An Evidence-Based Treatment Update. Am. J. Clin. Dermatol. 2014, 15 (3), 217–230. https://doi.org/10.1007/s40257-014-0077-5.
Kelly, Y.; Blanco, A.; Tosti, A. Androgenetic Alopecia: An Update of Treatment Options. Drugs 2016, 76 (14), 1349–1364. https://doi.org/10.1007/s40265-016-0629-5.
Fabbrocini, G.; Cantelli, M.; Masarà, A.; Annunziata, M. C.; Marasca, C.; Cacciapuoti, S. Female Pattern Hair Loss: A Clinical, Pathophysiologic, and Therapeutic Review. Int. J. Womens Dermatol. 2018, 4 (4), 203–211. https://doi.org/10.1016/j.ijwd.2018.05.001.
https://perfecthairhealth.com/articles/
https://www.hairlosstalk.com/interact/
https://www.hairguard.com/blogstream/
Jave-suarez, L. F.; Langbein, L.; Winter, H.; Praetzel, S.; Rogers, M. A.; Schweizer, J. Androgen Regulation of the Human Hair Follicle: The Type I Hair Keratin HHa7 Is a Direct Target Gene in Trichocytes. J. Invest. Dermatol. 2004, 122 (3), 555–564. https://doi.org/10.1111/j.0022-202X.2004.22336.x.
Garza, L. A.; Liu, Y.; Yang, Z.; Alagesan, B.; Lawson, J. A.; Norberg, S. M.; Loy, D. E.; Zhao, T.; Blatt, H. B.; Stanton, D. C.; Carrasco, L.; Ahluwalia, G.; Fischer, S. M.; FitzGerald, G. A.; Cotsarelis, G. Prostaglandin D2 Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia. Sci. Transl. Med. 2012, 4 (126), 126ra34-126ra34. https://doi.org/10.1126/scitranslmed.3003122.
Nelson, A. M.; Loy, D. E.; Lawson, J. A.; Katseff, A. S.; FitzGerald, G. A.; Garza, L. A. Prostaglandin D2 Inhibits Wound-Induced Hair Follicle Neogenesis through the Receptor, Gpr44. J. Invest. Dermatol. 2013, 133 (4), 881–889. https://doi.org/10.1038/jid.2012.398.
Nieves, A.; Garza, L. A. Does Prostaglandin D2 Hold the Cure to Male Pattern Baldness? Exp. Dermatol. 2014, 23 (4), 224–227. https://doi.org/10.1111/exd.12348.
Geng, L.; Hanson, W. R.; Malkinson, F. D. Topical or Systemic 16, 16 Dm Prostaglandin E2 or WR-2721 (WR-1065) Protects Mice from Alopecia after Fractionated Irradiation. Int. J. Radiat. Biol. 1992, 61 (4), 533–537. https://doi.org/10.1080/09553009214551291.
Sasaki, S.; Hozumi, Y.; Kondo, S. Influence of Prostaglandin F2alpha and Its Analogues on Hair Regrowth and Follicular Melanogenesis in a Murine Model. Exp. Dermatol. 2005, 14 (5), 323–328. https://doi.org/10.1111/j.0906-6705.2005.00270.x.
Colombe, L.; Vindrios, A.; Michelet, J.-F.; Bernard, B. A. Prostaglandin Metabolism in Human Hair Follicle. Exp. Dermatol. 2007, 16 (9), 762–769. https://doi.org/10.1111/j.1600-0625.2007.00586.x.
Mandal, A. K.; Zhang, Z.; Kim, S.-J.; Tsai, P.-C.; Mukherjee, A. B. Cutting Edge: Yin-Yang: Balancing Act of Prostaglandins with Opposing Functions to Regulate Inflammation. J. Immunol. 2005, 175 (10), 6271–6273. https://doi.org/10.4049/jimmunol.175.10.6271.
Shin, D. W. The Physiological and Pharmacological Roles of Prostaglandins in Hair Growth. Korean J. Physiol. Pharmacol. Off. J. Korean Physiol. Soc. Korean Soc. Pharmacol. 2022, 26 (6), 405–413. https://doi.org/10.4196/kjpp.2022.26.6.405.
English, R. S. A Hypothetical Pathogenesis Model for Androgenic Alopecia: Clarifying the Dihydrotestosterone Paradox and Rate-Limiting Recovery Factors. Med. Hypotheses 2018, 111, 73–81. https://doi.org/10.1016/j.mehy.2017.12.027.
McRobb, L.; Handelsman, D. J.; Heather, A. K. Androgen-Induced Progression of Arterial Calcification in Apolipoprotein E-Null Mice Is Uncoupled from Plaque Growth and Lipid Levels. Endocrinology 2009, 150 (2), 841–848. https://doi.org/10.1210/en.2008-0760.
Garza, L. A.; Yang, C.-C.; Zhao, T.; Blatt, H. B.; Lee, M.; He, H.; Stanton, D. C.; Carrasco, L.; Spiegel, J. H.; Tobias, J. W.; Cotsarelis, G. Bald Scalp in Men with Androgenetic Alopecia Retains Hair Follicle Stem Cells but Lacks CD200-Rich and CD34-Positive Hair Follicle Progenitor Cells. J. Clin. Invest. 2011, 121 (2), 613–622. https://doi.org/10.1172/JCI44478.
Kishimoto, J.; Burgeson, R. E.; Morgan, B. A. Wnt Signaling Maintains the Hair-Inducing Activity of the Dermal Papilla. Genes Dev. 2000, 14 (10), 1181–1185.
Leirós, G. J.; Attorresi, A. I.; Balañá, M. E. Hair Follicle Stem Cell Differentiation Is Inhibited through Cross-Talk between Wnt/β-Catenin and Androgen Signalling in Dermal Papilla Cells from Patients with Androgenetic Alopecia. Br. J. Dermatol. 2012, 166 (5), 1035–1042. https://doi.org/10.1111/j.1365-2133.2012.10856.x.
Chen, X.; Liu, B.; Li, Y.; Han, L.; Tang, X.; Deng, W.; Lai, W.; Wan, M. Dihydrotestosterone Regulates Hair Growth Through the Wnt/β-Catenin Pathway in C57BL/6 Mice and In Vitro Organ Culture. Front. Pharmacol. 2020, 10.
Hagenaars, S. P.; Hill, W. D.; Harris, S. E.; Ritchie, S. J.; Davies, G.; Liewald, D. C.; Gale, C. R.; Porteous, D. J.; Deary, I. J.; Marioni, R. E. Genetic Prediction of Male Pattern Baldness. PLOS Genet. 2017, 13 (2), e1006594. https://doi.org/10.1371/journal.pgen.1006594.
Ellis, J. A.; Stebbing, M.; Harrap, S. B. Genetic Analysis of Male Pattern Baldness and the 5α-Reductase Genes. J. Invest. Dermatol. 1998, 110 (6), 849–853. https://doi.org/10.1046/j.1523-1747.1998.00224.x.
Yamana, K.; Labrie, F.; Luu-The, V. Human Type 3 5α-Reductase Is Expressed in Peripheral Tissues at Higher Levels than Types 1 and 2 and Its Activity Is Potently Inhibited by Finasteride and Dutasteride. Horm. Mol. Biol. Clin. Investig. 2010, 2 (3), 293–299. https://doi.org/10.1515/HMBCI.2010.035.
Davey, R. A.; Grossmann, M. Androgen Receptor Structure, Function and Biology: From Bench to Bedside. Clin. Biochem. Rev. 2016, 37 (1), 3–15.
Marks, L. S. 5α-Reductase: History and Clinical Importance. Rev. Urol. 2004, 6 (Suppl 9), S11–S21.
Kelly, C. Pharmacology, Biology, and Clinical Applications of Androgens: Current Status and Future Prospects; John Wiley & Sons, 1996.
Choi, M. H.; Yoo, Y. S.; Chung, B. C. Biochemical Roles of Testosterone and Epitestosterone to 5α-Reductase as Indicators of Male-Pattern Baldness. J. Invest. Dermatol. 2001, 116 (1), 57–61. https://doi.org/10.1046/j.1523-1747.2001.00188.x.
Tellez-Segura, R. Involvement of Mechanical Stress in Androgenetic Alopecia. Int. J. Trichology 2015, 7 (3), 95–99. https://doi.org/10.4103/0974-7753.167468.
English, R. S. A Hypothetical Pathogenesis Model for Androgenic Alopecia: Clarifying the Dihydrotestosterone Paradox and Rate-Limiting Recovery Factors. Med. Hypotheses 2018, 111, 73–81. https://doi.org/10.1016/j.mehy.2017.12.027.
Inui, S.; Itami, S. Androgen Actions on the Human Hair Follicle: Perspectives. Exp. Dermatol. 2013, 22 (3), 168–171. https://doi.org/10.1111/exd.12024.
Yang, Y.-C.; Fu, H.-C.; Wu, C.-Y.; Wei, K.-T.; Huang, K.-E.; Kang, H.-Y. Androgen Receptor Accelerates Premature Senescence of Human Dermal Papilla Cells in Association with DNA Damage. PLOS ONE 2013, 8 (11), e79434. https://doi.org/10.1371/journal.pone.0079434.
Ashique, S.; Sandhu, N. K.; Haque, Sk. N.; Koley, K. A Systemic Review on Topical Marketed Formulations, Natural Products, and Oral Supplements to Prevent Androgenic Alopecia: A Review. Nat. Prod. Bioprospecting 2020, 10 (6), 345–365. https://doi.org/10.1007/s13659-020-00267-9.
Bikle, D. D.; Elalieh, H.; Chang, S.; Xie, Z.; Sundberg, J. P. Development and Progression of Alopecia in the Vitamin D Receptor Null Mouse. J. Cell. Physiol. 2006, 207 (2), 340–353. https://doi.org/10.1002/jcp.20578.
Amor, K. T.; Rashid, R. M.; Mirmirani, P. Does D Matter? The Role of Vitamin D in Hair Disorders and Hair Follicle Cycling. Dermatol. Online J. 2010, 16 (2), 3.
Sinclair, R.; Wewerinke, M.; Jolley, D. Treatment of Female Pattern Hair Loss with Oral Antiandrogens. Br. J. Dermatol. 2005, 152 (3), 466–473. https://doi.org/10.1111/j.1365-2133.2005.06218.x.
Zhou, Z.; Song, S.; Gao, Z.; Wu, J.; Ma, J.; Cui, Y. The Efficacy and Safety of Dutasteride Compared with Finasteride in Treating Men with Androgenetic Alopecia: A Systematic Review and Meta-Analysis. Clin. Interv. Aging 2019, 14, 399–406. https://doi.org/10.2147/CIA.S192435.
Mella, J. M.; Perret, M. C.; Manzotti, M.; Catalano, H. N.; Guyatt, G. Efficacy and Safety of Finasteride Therapy for Androgenetic Alopecia: A Systematic Review. Arch. Dermatol. 2010, 146 (10), 1141–1150. https://doi.org/10.1001/archdermatol.2010.256.
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=213433
https://www.cosmopharma.com/pipeline/breezula
https://web.archive.org/web/20210116203142/https://www.cassiopea.com/2019/04/16/cassiopea-announces-very-positive-phase-ii-twelve-months-results-for-breezula-clascoterone-in-treating-androgenetic-alopecia-3/
DuBois, J.; Bruce, S.; Stewart, D.; Kempers, S.; Harutunian, C.; Boodhoo, T.; Weitzenfeld, A.; Chang-Lin, J.-E. Setipiprant for Androgenetic Alopecia in Males: Results from a Randomized, Double-Blind, Placebo-Controlled Phase 2a Trial. Clin. Cosmet. Investig. Dermatol. 2021, 14, 1507–1517. https://doi.org/10.2147/CCID.S319676.
Johnstone, M. A.; Albert, D. M. Prostaglandin-Induced Hair Growth. Surv. Ophthalmol. 2002, 47 Suppl 1, S185-202. https://doi.org/10.1016/s0039-6257(02)00307-7.
Blume-Peytavi, U.; Lönnfors, S.; Hillmann, K.; Garcia Bartels, N. A Randomized Double-Blind Placebo-Controlled Pilot Study to Assess the Efficacy of a 24-Week Topical Treatment by Latanoprost 0.1% on Hair Growth and Pigmentation in Healthy Volunteers with Androgenetic Alopecia. J. Am. Acad. Dermatol. 2012, 66 (5), 794–800. https://doi.org/10.1016/j.jaad.2011.05.026.
Wester, S. T.; Lee, W. W.; Shi, W. Eyelash Growth from Application of Bimatoprost in Gel Suspension to the Base of the Eyelashes. Ophthalmology 2010, 117 (5), 1024–1031. https://doi.org/10.1016/j.ophtha.2009.10.017.
Ulven, T.; Kostenis, E. Novel CRTH2 Antagonists: A Review of Patents from 2006 to 2009. Expert Opin. Ther. Pat. 2010, 20 (11), 1505–1530. https://doi.org/10.1517/13543776.2010.525506.
Norman, P. Update on the Status of DP2 Receptor Antagonists; from Proof of Concept through Clinical Failures to Promising New Drugs. Expert Opin. Investig. Drugs 2014, 23 (1), 55–66. https://doi.org/10.1517/13543784.2013.839658.
Cotsarelis, G.; Fitzgerald, G.; Garza, L. Compositions and Methods for Regulating Hair Growth. US20150072963A1, March 12, 2015. https://patents.google.com/patent/US20150072963/en (accessed 2023-01-14).
https://web.archive.org/web/20180830144343/http://swisstemples.com/the-prostaglandin-protocol/
Hawkshaw, N. J.; Hardman, J. A.; Haslam, I. S.; Shahmalak, A.; Gilhar, A.; Lim, X.; Paus, R. Identifying Novel Strategies for Treating Human Hair Loss Disorders: Cyclosporine A Suppresses the Wnt Inhibitor, SFRP1, in the Dermal Papilla of Human Scalp Hair Follicles. PLOS Biol. 2018, 16 (5), e2003705. https://doi.org/10.1371/journal.pbio.2003705.
Zhan, T.; Rindtorff, N.; Boutros, M. Wnt Signaling in Cancer. Oncogene 2017, 36 (11), 1461–1473. https://doi.org/10.1038/onc.2016.304.
Vexiau, P.; Chaspoux, C.; Boudou, P.; Fiet, J.; Jouanique, C.; Hardy, N.; Reygagne, P. Effects of Minoxidil 2% vs. Cyproterone Acetate Treatment on Female Androgenetic Alopecia: A Controlled, 12-Month Randomized Trial. Br. J. Dermatol. 2002, 146 (6), 992–999. https://doi.org/10.1046/j.1365-2133.2002.04798.x.
Khandpur, S.; Suman, M.; Reddy, B. S. Comparative Efficacy of Various Treatment Regimens for Androgenetic Alopecia in Men. J. Dermatol. 2002, 29 (8), 489–498. https://doi.org/10.1111/j.1346-8138.2002.tb00314.x.
Piérard-Franchimont, C.; Doncker, P. D.; Cauwenbergh, G.; Piérard, G. E. Ketoconazole Shampoo: Effect of Long-Term Use in Androgenic Alopecia. Dermatology 1998, 196 (4), 474–477. https://doi.org/10.1159/000017954.
Karaca, N.; Akpolat, N. D. A Comparative Study between Topical 5% Minoxidil and Topical. J. Cosmetol. Trichology 2019, 5 (1), 0–0.
Freund, B. J.; Schwartz, M. Treatment of Male Pattern Baldness with Botulinum Toxin: A Pilot Study. Plast. Reconstr. Surg. 2010, 126 (5), 246e–248e. https://doi.org/10.1097/PRS.0b013e3181ef816d.
Shon, U.; Kim, M. H.; Lee, D. Y.; Kim, S. H.; Park, B. C. The Effect of Intradermal Botulinum Toxin on Androgenetic Alopecia and Its Possible Mechanism. J. Am. Acad. Dermatol. 2020, 83 (6), 1838–1839. https://doi.org/10.1016/j.jaad.2020.04.082.
Singh, S.; Neema, S.; Vasudevan, B. A Pilot Study to Evaluate Effectiveness of Botulinum Toxin in Treatment of Androgenetic Alopecia in Males. J. Cutan. Aesthetic Surg. 2017, 10 (3), 163–167. https://doi.org/10.4103/JCAS.JCAS_77_17.
Fischer TW, Slominski A, Tobin DJ, Paus R. Melatonin and the hair follicle. J Pineal Res. 2008;44:1–15.
Fischer TW, Burmeister G, Schmidt HW, Elsner P. Melatonin increases anagen hair rate in women with androgenetic alopecia or diffuse alopecia: results of a pilot randomized controlled trial. Br J Dermatol. 2004;150:341–5.
Fischer TW, Trueb RM, Hanggi G, Innocenti M, Elsner P. Topical melatonin for treatment of androgenetic alopecia. Int J Trichol. 2012;4:236–45.
Oron, U.; Ilic, S.; De Taboada, L.; Streeter, J. Ga-As (808 Nm) Laser Irradiation Enhances ATP Production in Human Neuronal Cells in Culture. Photomed. Laser Surg. 2007, 25 (3), 180–182. https://doi.org/10.1089/pho.2007.2064.
Suchonwanit, P.; Chalermroj, N.; Khunkhet, S. Low-Level Laser Therapy for the Treatment of Androgenetic Alopecia in Thai Men and Women: A 24-Week, Randomized, Double-Blind, Sham Device-Controlled Trial. Lasers Med. Sci. 2019, 34 (6), 1107–1114. https://doi.org/10.1007/s10103-018-02699-9.
Zarei, M.; Wikramanayake, T. C.; Falto-Aizpurua, L.; Schachner, L. A.; Jimenez, J. J. Low Level Laser Therapy and Hair Regrowth: An Evidence-Based Review. Lasers Med. Sci. 2016, 31 (2), 363–371. https://doi.org/10.1007/s10103-015-1818-2.
Lanzafame, R. J.; Blanche, R. R.; Bodian, A. B.; Chiacchierini, R. P.; Fernandez-Obregon, A.; Kazmirek, E. R. The Growth of Human Scalp Hair Mediated by Visible Red Light Laser and LED Sources in Males. Lasers Surg. Med. 2013, 45 (8), 487–495. https://doi.org/10.1002/lsm.22173.
Dhurat, R.; Sukesh, M.; Avhad, G.; Dandale, A.; Pal, A.; Pund, P. A Randomized Evaluator Blinded Study of Effect of Microneedling in Androgenetic Alopecia: A Pilot Study. Int. J. Trichology 2013, 5 (1), 6–11. https://doi.org/10.4103/0974-7753.114700.
Dhurat, R.; Mathapati, S. Response to Microneedling Treatment in Men with Androgenetic Alopecia Who Failed to Respond to Conventional Therapy. Indian J. Dermatol. 2015, 60 (3), 260–263. https://doi.org/10.4103/0019-5154.156361.
Avram, M. R.; Cole, J. P.; Gandelman, M.; Haber, R.; Knudsen, R.; Leavitt, M. T.; Leonard, R. T.; Puig, C. J.; Rose, P. T.; Vogel, J. E.; Ziering, C. L.; 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. Off. Publ. Am. Soc. Dermatol. Surg. Al 2002, 28 (10), 894–900; discussion 900. https://doi.org/10.1046/j.1524-4725.2002.02068.x.
https://en.wikipedia.org/wiki/Hair_cloning
Kim, J.-C. Hair Cloning and Follicular Cell Implantation. In Hair Restoration Surgery in Asians; Pathomvanich, D., Imagawa, K., Eds.; Springer Japan: Tokyo, 2010; pp 273–275. https://doi.org/10.1007/978-4-431-99659-0_55.
Khatu, S. S.; More, Y. E.; Gokhale, N. R.; Chavhan, D. C.; Bendsure, N. Platelet-Rich Plasma in Androgenic Alopecia: Myth or an Effective Tool. J. Cutan. Aesthetic Surg. 2014, 7 (2), 107–110. https://doi.org/10.4103/0974-2077.138352.
Gkini, M.-A.; Kouskoukis, A.-E.; Tripsianis, G.; Rigopoulos, D.; Kouskoukis, K. Study of Platelet-Rich Plasma Injections in the Treatment of Androgenetic Alopecia through an One-Year Period. J. Cutan. Aesthetic Surg. 2014, 7 (4), 213–219. https://doi.org/10.4103/0974-2077.150743.
Gentile, P.; Scioli, M. G.; Bielli, A.; Orlandi, A.; Cervelli, V. Stem Cells from Human Hair Follicles: First Mechanical Isolation for Immediate Autologous Clinical Use in Androgenetic Alopecia and Hair Loss. Stem Cell Investig. 2017, 4, 58. https://doi.org/10.21037/sci.2017.06.04.
https://kerastem.com/product-pipeline/
https://clinicaltrials.gov/ct2/show/NCT02503852?term=Kerastem&rank=1