Is this the Golden Age of Hair Loss Treatment?

There are different ways substantial transformation can happen in medicine. Identifying mutations and understanding genotype-phenotype correlations changed the way we classify inherited skin conditions and approach their diagnosis and treatment. Biologics revolutionized how we manage certain skin diseases, and irrevocably altered our safety and efficacy expectations for new treatments. But not all transformations stem from a single discovery. A perfect storm of many new, unrelated scientific developments also has the potential to fundamentally reshape the way we think about a disease or disease group. I believe that many recent breakthroughs profoundly changed how general dermatologists can manage patients with hair loss.

Low-dose Oral Minoxidil

We have been using the topical formulation of the anti-hypertensive drug minoxidil for decades. Although it is one of the only two FDA approved treatments for androgenetic alopecia, the success rate is not stellar. For many years it looked like we had to accept the lower efficacy as a trade-off to avoid the very serious adverse effects associated with the use of oral minoxidil. Dermatological ingenuity created a solution: low dose oral minoxidil (LDOM). Turns out, sub-anti-hypertensive level oral dosing is actually very safe,1 not only in healthy individuals but also in patients with hypertension and arrythmias,2 with the most common side effect leading to treatment cessation being excessive hair growth in female patients. With a little help from the lay press, LDOM prescriptions for hair loss skyrocketed and thanks to the studies addressing safety concerns and offering dosing and monitoring guidance, any dermatologist can now confidently offer this treatment.3 It shows efficacy as a general promoter of hair growth not only in androgenetic alopecia, but also in other forms of hair loss.

Spironolactone

The potassium sparing diuretic has long been used (off-label) for androgenetic alopecia in women because it competitively blocks androgen receptors. Spironolactone is not without side effects, most of which are dose dependent, but occasionally lead to treatment discontinuation. On the other hand, it seems that laboratory monitoring of potassium levels (once considered a must, creating patient hesitancy) is not necessary when treating healthy women with no risk factors,4 especially if they are younger than 45 years of age.5 While it may be less effective as monotherapy, spironolactone is useful in combination with minoxidil for women.^6,7 In that setting we gain an extra benefit: The potential reduction of excessive hair growth induced by minoxidil, as spironolactone has been established as a safe and effective treatment for idiopathic hirsutism as well as hirsutism in the setting of polycystic ovary syndrome.8 It is therefore another medication that we can use with confidence.

Topical finasteride

Finasteride, the oral medication approved by the FDA to treat male androgenetic alopecia, showed favorable efficacy except there have always been concerns about rare, but possibly detrimental and even permanent side effects. Although it is still not settled if there is a casual link, the term Post-Finasteride Syndrome was created,9 and a patient advocacy group successfully petitioned the FDA to add suicidal ideation and behavior to the list of adverse effects on the label. Enthusiasm for the medication waned and many patients believed the potential risks outweighed the benefits. As the drug was too good to be discarded entirely, we did kind of the opposite of what was done with minoxidil: We started favoring topical application. A continuously growing number of studies now show that topical application is the way to go when it comes to finasteride.¹⁰ Topical use results in drastically lower systemic exposure and a side effect profile which is not meaningfully different from that of a placebo. Its efficacy is comparable to the oral version of the medication.¹¹ While it needs to be compounded, likely owing to its popularity, many pharmacies are now able to produce the topical foam or solution, not just the well-established compounding specialty pharmacies. The result is that we get to keep an effective treatment with almost no strings attached.

Janus Kinase Inhibitors

One of the most debilitating forms of hair loss is severe alopecia areata. Janus kinase inhibitors, members of a new and very important drug class for dermatology, seem to provide a solution.¹² Not only is it effective, but according to an increasing number of studies, but it is also safe when used in dermatology. Obtaining insurance coverage could be challenging, but the recent FDA approval is changing that. While patients have to be counselled on the potential risks and must be monitored closely, it is still a revolutionary treatment compared to anything we had to offer even just a few years ago and it truly changes lives.¹³ With more and more favorable safety data becoming available, now it is easy to consider using this treatment.

Platelet Rich Plasma (PRP)

Another treatment important to dermatology is PRP, which comes to us from orthopedics, where it is used to treat musculoskeletal injuries and conditions.¹⁴ The premise is simple: Platelets are mechanically separated from blood drawn from the patient and injected into the scalp where they release biologically active molecules to induce hair growth. The procedure itself is very straightforward and ready-to-use systems that include everything necessary to perform the treatment are available from multiple sources.¹⁵ Any dermatologist who performs even the simplest procedures will be able to start doing PRP with minimal training and practice. PRP treatments show benefit in inflammatory and non-inflammatory forms of hair loss alike, either as monotherapy or as part of a complex approach. No insurance coverage is available, and it is important to manage patients’ expectations as the treatments are costly. However, the procedure is very safe and if the right candidates are selected, it can be a very rewarding option.^16,17

Digital trichoscopy

Even when using the best treatments, monitoring improvement in hair loss is challenging. Clinical photos are great for alopecia areata, but they are much less useful to evaluate regrowth in androgenetic alopecia, for example. Patients often ask: Do you think I am improving? Not surprisingly, it is an artificial intelligence-powered system that helps to answer that question. HairMetrix by Canfield uses digital trichoscopy imaging of non-clipped hair to collect hair density and thickness data, which can be compared between office visits to offer an objective assessment of hair treatment success. The data collection is not covered by insurance companies, and it is a business decision whether to bill the patient or to consider the cost as part of the overhead. Having such objective data can be invaluable when making treatment decisions or just reassuring patients uncertain about their progress.

Diversity in hair Loss

Dermatologists can only deliver care to their entire patient population successfully if they understand how to approach every patient according to their specific needs. Thankfully, there is a lot of ongoing work that guides us every step of the way, including addressing potential bias in hair loss diagnosis,¹⁸ understanding the demographics of hair loss,^19,20 improving cultural competency,^21,22 and even variability of counseling styles of medical professionals treating hair loss patients.²³

And so much more

All the above is still just a part of the hair loss revolution. Now we have cold-therapy to prevent chemotherapy related hair loss.²⁴ We have mesotherapy,²⁵ stem-cell based therapies,²⁶ photo-biomodulation,²⁷ and also exosome treatment,²⁸ topical tretinoin,²⁹ nutraceuticals.^30,31 With multiple available treatment modalities it is much easier to tailor treatment plans to the unique circumstances of every patient. Hair transplantation techniques also underwent substantial improvement and the procedure is now widely available for patients.³² Those of us who don’t perform hair transplants can find excellent centers to refer our patients more easily than in the past.

We also have a growing consensus that there is no single silver bullet to fight hair loss: Most treatments work for a broad spectrum of hair loss types. Thoughtfully adjusted combinations of modalities that are right for the specific type of hair loss and the individual patient, and combine benefits from different approaches seem to be the way to go.³³

Golden Age

The 2024 Annual Meeting of the American Academy of Dermatology in March of this year will have as many sessions related to alopecia as to psoriasis. The yearly number of published papers addressing hair loss doubled over the course of the last 10 years. There is easy access to information and educational resources that can help every dermatologist to offer state-of-the-art treatment to patients with hair loss. But there is more to come, as there is a cascade effect: The current progress creates enthusiasm among dermatologists and patients alike, which powers more research and more innovation. There are nearly 500 alopecia related clinical trials currently registered on clinicaltrials.gov. Every day there are new publications with new ideas for hair loss management. We continue to refine how to use what we already have, and we continue to learn about new treatment options.

As a general dermatologist, I have treated many hair loss patients, but I used to often feel frustrated because I had little to offer to them compared to the large number of therapeutic tools for other skin conditions. Today I look forward to hair loss appointments. I love seeing these patients, because now I have many meaningful solutions that will bring positive change to their lives.

1. Vañó-Galván S, Pirmez R, Hermosa-Gelbard A, et al. Safety of low-dose oral minoxidil for hair loss: A multicenter study of 1404 patients. J Am Acad Dermatol. 2021;84(6):1644-1651. doi:10.1016/j.jaad.2021.02.054

2. Cauhe JJ, Pirmez R, Ramos PM, et al. Safety of Low-Dose Oral Minoxidil in Patients With Hypertension and Arrhythmia: A Multicenter Study of 264 Patients. Actas Dermosifiliogr. 2023;(xxxx):1-8. doi:10.1016/j.ad.2023.10.033

3. Goodwin Cartwright BM, Wang M, Rodriguez P, et al. Changes in Minoxidil Prescribing After Media Attention About Oral Use for Hair Loss. JAMA Netw Open. 2023;6(5):e2312477. doi:10.1001/jamanetworkopen.2023.12477

4. Plante J, Robinson I, Elston D. The need for potassium monitoring in women on spironolactone for dermatologic conditions. J Am Acad Dermatol. 2022;87(5):1097-1099. doi:10.1016/j.jaad.2022.01.010

5. Wang Y, Lipner SR. Retrospective analysis of adverse events with spironolactone in females reported to the United States Food and Drug Administration. Int J Women’s Dermatology. 2020;6(4):272-276. doi:10.1016/j.ijwd.2020.05.002

6. James JBF, Jamerson TA, Aguh C. Efficacy and safety profile of oral spironolactone use for androgenic alopecia: A systematic review. J Am Acad Dermatol. 2022;86(2):425-429. doi:10.1016/j.jaad.2021.07.048

7. Wang C, Du Y, Bi L, Lin X, Zhao M, Fan W. The Efficacy and Safety of Oral and Topical Spironolactone in Androgenetic Alopecia Treatment: A Systematic Review. Clin Cosmet Investig Dermatol. 2023;16(February):603-612. doi:10.2147/CCID.S398950

8. Spritzer PM, Lisboa KO, Mattiello S, Lhullier F. Spironolactone as a single agent for long-term therapy of hirsute patients. Clin Endocrinol (Oxf). 2000;52(5):587-594. doi:10.1046/j.1365-2265.2000.00982.x

9. Leliefeld HHJ, Debruyne FMJ, Reisman Y. The post-finasteride syndrome: possible etiological mechanisms and symptoms. IntJ Impot Res. September 2023. doi:10.1038/s41443-023-00759-5

10. Gupta AK, Talukder M. Topical finasteride for male and female pattern hair loss: Is it a safe and effective alternative? J Cosmet Dermatol. 2022;21(5):1841-1848. doi:10.1111/jocd.14895

11. Piraccini BM, Blume-Peytavi U, Scarci F, et al. Efficacy and safety of topical finasteride spray solution for male androgenetic alopecia: a phase III, randomized, controlled clinical trial. J Eur Acad Dermatology Venereol. 2022;36(2):286-294. doi:10.1111/jdv.17738

12. Liu M, Gao Y, Yuan Y, et al. Janus Kinase Inhibitors for Alopecia Areata: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2023;6(6):e2320351. doi:10.1001/jamanetworkopen.2023.20351

13. Mateos-Haro M, Novoa-Candia M, Sánchez Vanegas G, et al. Treatments for alopecia areata: a network meta-analysis. Cochrane Database Syst Rev. 2023;2023(10). doi:10.1002/14651858.CD013719.pub2

14. Pretorius J, Habash M, Ghobrial B, Alnajjar R, Ellanti P. Current Status and Advancements in Platelet-Rich Plasma Therapy. Cureus. October 2023. doi:10.7759/cureus.47176

15. Dubin DP, Lin MJ, Leight HM, et al. The effect of platelet-rich plasma on female androgenetic alopecia: A randomized controlled trial. J Am Acad Dermatol. 2020;83(5):1294-1297. doi:10.1016/j.jaad.2020.06.1021

16. Badran KW, Sand JP. Platelet-Rich Plasma for Hair Loss. Facial Plast Surg Clin North Am. 2018;26(4):469-485. doi:10.1016/j.fsc.2018.06.008

17. Gupta A, Bamimore M. Platelet-Rich Plasma Monotherapies for Androgenetic Alopecia: A Network Meta-Analysis and Meta-Regression Study. J Drugs Dermatol. 2022;21(9):943-952. doi:10.36849/JDD.6948

18. Balazic E, Axler E, Nwankwo C, et al. Minimizing Bias in Alopecia Diagnosis in Skin of Color Patients. J Drugs Dermatol. 2023;22(7):703-705. doi:10.36849/JDD.7117

19. Sy N, Mastacouris N, Strunk A, Garg A. Overall and Racial and Ethnic Subgroup Prevalences of Alopecia Areata, Alopecia Totalis, and Alopecia Universalis. JAMA Dermatol. 2023;159(4):419-423. doi:10.1001/jamadermatol.2023.0016

20. Lee H, Jung SJ, Patel AB, Thompson JM, Qureshi A, Cho E. Racial characteristics of alopecia areata in the United States. J Am Acad Dermatol. 2020;83(4):1064-1070. doi:10.1016/j.jaad.2019.06.1300

21. Gathers RC, Mahan MG. African American women, hair care, and health barriers. J Clin Aesthet Dermatol. 2014;7(9):26-29.

22. Haskin A, Aguh C. All hairstyles are not created equal: What the dermatologist needs to know about black hairstyling practices and the risk of traction alopecia (TA). J Am Acad Dermatol. 2016;75(3):606-611. doi:10.1016/j.jaad.2016.02.1162

23. Gregoire S, Mostaghimi A. Effective counseling of patients with hair loss. J Am Acad Dermatol. 2023;89(2):S40-S42. doi:10.1016/j.jaad.2023.03.059

24. Contreras Molina M, Álvarez Bueno C, Cavero Redondo I, Lucerón Lucas-Torres MI, Jiménez López E, García Maestro A. Effectiveness of Scalp Cooling to Prevent Chemotherapy-Induced Alopecia in Patients Undergoing Breast Cancer Treatment. Cancer Nurs. 2023;Publish Ah. doi:10.1097/NCC.0000000000001234

25. Rodríguez-Cuadrado FJ, Pinto-Pulido EL, Fernández-Parrado M. Mesotherapy with dutasteride for androgenetic alopecia: a concise review of the literature. Eur J Dermatology. 2023;33(1):72-72. doi:10.1684/ejd.2023.4443

26. Gentile P, Garcovich S. Systematic review: Impact of stem cells-based therapy, and platelet-rich plasma in hair loss and telogen effluvium related to COVID-19. Regen Ther. 2023;24:267-273. doi:10.1016/j.reth.2023.07.001

27. Torres AE, Lim HW. Photobiomodulation for the management of hair loss. Photodermatol Photoimmunol Photomed. 2021;37(2):91-98. doi:10.1111/phpp.12649

28. Park B, Choi H, Huh G, Kim W. Effects of exosome from adipose‐derived stem cell on hair loss: A retrospective analysis of 39 patients. J Cosmet Dermatol. 2022;21(5):2282-2284. doi:10.1111/jocd.14846

29. Sharma A, Goren A, Dhurat R, et al. Tretinoin enhances minoxidil response in androgenetic alopecia patients by upregulating follicular sulfotransferase enzymes. Dermatol Ther. 2019;32(3). doi:10.1111/dth.12915

30. Sadgrove N, Batra S, Barreto D, Rapaport J. An Updated Etiology of Hair Loss and the New Cosmeceutical Paradigm in Therapy: Clearing ‘the Big Eight Strikes.’ Cosmetics. 2023;10(4). doi:10.3390/cosmetics10040106

31. Drake L, Reyes-Hadsall S, Martinez J, Heinrich C, Huang K, Mostaghimi A. Evaluation of the Safety and Effectiveness of Nutritional Supplements for Treating Hair Loss. JAMA Dermatology. 2023;159(1):79. doi:10.1001/jamadermatol.2022.4867

32. Jimenez F, Alam M, Vogel JE, Avram M. Hair transplantation: Basic overview. J Am Acad Dermatol. 2021;85(4):803-814. doi:10.1016/j.jaad.2021.03.124

33. Deoghare S, Sadick NS. Combination therapy in female pattern hair loss. J Cosmet Laser Ther. 2023;25(1-4):1-6. doi:10.1080/14764172.2023.2222942