Medical and procedural treatment of androgenetic alopecia – Where are we?

Novel medical and procedural options for androgenetic alopecia have arrived. Low-dose oral minoxidil has made its clinical debut, while data on spironolactone, finasteride, and nutritional supplements have advanced. Minimally invasive technological advancements include photobiomodulation and platelet-rich plasma. Within hair transplantation, follicular unit extraction and robotics are now at the clinicians’ fingertips. Novel medical and procedural options for androgenetic alopecia have arrived. Low-dose oral minoxidil has made its clinical debut, while data on spironolactone, finasteride, and nutritional supplements have advanced. Minimally invasive technological advancements include photobiomodulation and platelet-rich plasma. Within hair transplantation, follicular unit extraction and robotics are now at the clinicians’ fingertips. Capsule Summary•The evidence for novel medical and procedural treatment options for androgenetic alopecia is summarized.•Low-dose oral minoxidil along with technological advancements in photobiomodulation, platelet-rich plasma, and hair transplantation are highlighted. Clinicians now have an armamentarium of treatment options for androgenetic alopecia.CME Credit StatementThe American Academy of Dermatology is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The American Academy of Dermatology designates this Journal-based CME activity for a maximum of 8 AMA PRA Category 1 Credits™.To claim CME credit for this activity, the learner must read all eight supplement articles, complete post-test with a passing score of 70% or higher, and complete the post-activity evaluation survey. The post-test and evaluation are available here: https://learning.aad.org/URL/JAADSUP2023Commercial SupportAll content solely developed by the American Academy of Dermatology.Publication of this supplement was supported in part by educational grants from Pfizer Inc. and Lilly USA, LLC. •The evidence for novel medical and procedural treatment options for androgenetic alopecia is summarized.•Low-dose oral minoxidil along with technological advancements in photobiomodulation, platelet-rich plasma, and hair transplantation are highlighted. Clinicians now have an armamentarium of treatment options for androgenetic alopecia. CME Credit Statement The American Academy of Dermatology is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The American Academy of Dermatology designates this Journal-based CME activity for a maximum of 8 AMA PRA Category 1 Credits™. To claim CME credit for this activity, the learner must read all eight supplement articles, complete post-test with a passing score of 70% or higher, and complete the post-activity evaluation survey. The post-test and evaluation are available here: https://learning.aad.org/URL/JAADSUP2023 Commercial Support All content solely developed by the American Academy of Dermatology. Publication of this supplement was supported in part by educational grants from Pfizer Inc. and Lilly USA, LLC. Treatment options for androgenetic alopecia (AGA) have been stagnant, resulting in frustration for clinicians and patients. However, recent scientific advances have allowed for a period of rapid growth with different interventions. Low-dose oral minoxidil (LDOM) is the biggest medical game-changer for AGA, as highlighted by the New York Times in 2022. LDOM is not Food and Drug Administration (FDA) approved for AGA. LDOM dosing typically refers to 0.25 to 5 mg orally daily with higher doses often reserved for men (Fig 1) .1Vañó-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: 1644-1651https://doi.org/10.1016/j.jaad.2021.02.054Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar Early data suggest 0.25 mg may be suboptimal in women.2Silva M.N.E. Ramos P.M. Silva M.R. Silva R.N.E. Raposo N.R.B. Randomized clinical trial of low-dose oral minoxidil for the treatment of female pattern hair loss: 0.25 mg versus 1 mg.J Am Acad Dermatol. 2022; 87: 396-399https://doi.org/10.1016/j.jaad.2022.01.017Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar In a key 2021 retrospective review of 1404 LDOM patients with a mean age of 43 years, the most experienced adverse effect was hypertrichosis (15.1%).1Vañó-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: 1644-1651https://doi.org/10.1016/j.jaad.2021.02.054Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar Other systemic effects reported include light-headedness (1.7%), fluid retention (1.3%), tachycardia (0.9%), headache (0.4%), periorbital edema (0.3%), or insomnia (0.2%).1Vañó-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: 1644-1651https://doi.org/10.1016/j.jaad.2021.02.054Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar Obtaining a blood pressure, complete metabolic panel, and primary care engagement should be considered along with the cardiac-focused black box warning.3Loniten, minoxidil tablets, USP, label.https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/018154s026lbl.pdfDate accessed: December 12, 2022Google Scholar Beyond LDOM, oral finasteride and dutasteride continue to be utilized with only finasteride being FDA-approved for AGA in men.4Ho R.S. Ongoing concerns regarding finasteride for the treatment of male-pattern androgenetic alopecia.JAMA Dermatol. 2021; 157: 25-26https://doi.org/10.1001/jamadermatol.2020.3384Crossref PubMed Scopus (7) Google Scholar,5Gupta A.K. Venkataraman M. Talukder M. Bamimore M.A. Relative efficacy of minoxidil and the 5-α reductase inhibitors in androgenetic alopecia treatment of male patients: a network meta-analysis.JAMA Dermatol. 2022; 158: 266-274https://doi.org/10.1001/jamadermatol.2021.5743Crossref PubMed Scopus (28) Google Scholar Finasteride can be combined with topical minoxidil to improve efficacy.6Hu R. Xu F. Sheng Y. et al.Combined treatment with oral finasteride and topical minoxidil in male androgenetic alopecia: a randomized and comparative study in Chinese patients.Dermatol Ther. 2015; 28: 303-308https://doi.org/10.1111/dth.12246Crossref PubMed Scopus (38) Google Scholar A finasteride pharmacovigilance study suggested screening needs for suicidality, depression, and anxiety, although causality remains unclear.7Nguyen D.D. Marchese M. Cone E.B. et al.Investigation of suicidality and psychological adverse events in patients treated with finasteride.JAMA Dermatol. 2021; 157: 35-42https://doi.org/10.1001/jamadermatol.2020.3385Crossref PubMed Scopus (44) Google Scholar Spironolactone remains a mainstay with a study demonstrating improvements in female AGA that can occur at one year or later.8Burns L.J. Souza B.D. Flynn E. Hagigeorges D. Senna M.M. Spironolactone for treatment of female pattern hair loss.J Am Acad Dermatol. 2020; 83: 276-278https://doi.org/10.1016/j.jaad.2020.03.087Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar One historical disadvantage of spironolactone has been laboratory monitoring. A recent publication focused on potassium monitoring in healthy women aged 18 to 45 years on spironolactone suggests this routine potassium monitoring is not necessary.9Barbieri J.S. Margolis D.J. Mostaghimi A. Temporal trends and clinician variability in potassium monitoring of healthy young women treated for acne with spironolactone.JAMA Dermatol. 2021; 157: 296-300https://doi.org/10.1001/jamadermatol.2020.5468Crossref PubMed Scopus (5) Google Scholar Spironolactone has also been proposed as the first line for AGA in transfeminine patients as gynecomastia may be preferred.8Burns L.J. Souza B.D. Flynn E. Hagigeorges D. Senna M.M. Spironolactone for treatment of female pattern hair loss.J Am Acad Dermatol. 2020; 83: 276-278https://doi.org/10.1016/j.jaad.2020.03.087Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar,10James J.F. Jamerson T.A. Aguh C. Efficacy and safety profile of oral spironolactone use for androgenic alopecia: a systematic review.J Am Acad Dermatol. 2022; 86: 425-429https://doi.org/10.1016/j.jaad.2021.07.048Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar,11Gao J.L. Streed C.G. Thompson J. Dommasch E.D. Peebles J.K. Androgenetic alopecia in transgender and gender diverse populations: a review of therapeutics.J Am Acad Dermatol. 2021; 0https://doi.org/10.1016/j.jaad.2021.08.067Abstract Full Text Full Text PDF Scopus (3) Google Scholar Transmasculine patients should avoid spironolactone because of testosterone reduction and/or gynecomastia.11Gao J.L. Streed C.G. Thompson J. Dommasch E.D. Peebles J.K. Androgenetic alopecia in transgender and gender diverse populations: a review of therapeutics.J Am Acad Dermatol. 2021; 0https://doi.org/10.1016/j.jaad.2021.08.067Abstract Full Text Full Text PDF Scopus (3) Google Scholar Although spironolactone does have indirect estrogenic activity, one study was unable to associate it with a substantial risk of cancer, including breast and ovarian.12Bommareddy K. Hamade H. Lopez-Olivo M.A. Wehner M. Tosh T. Barbieri J.S. Association of spironolactone use with risk of cancer: a systematic review and meta-analysis.JAMA Dermatol. 2022; 158: 275-282https://doi.org/10.1001/jamadermatol.2021.5866Crossref PubMed Scopus (13) Google Scholar Nutraceuticals for AGA have been popularized despite few investigator-initiated studies. In recent literature, a 2022 systematic review suggested a positive role for supplementation by ingredient and brand.13Ablon G. Nutraceuticals Dermatol Clin. 2021; 39: 417-427https://doi.org/10.1016/j.det.2021.03.006Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar However, Klein et al14Klein E.J. Karim M. Li X. Adhikari S. Shapiro J. Sicco K.L. Supplementation and hair growth: a retrospective chart review of patients with alopecia and laboratory abnormalities.JAAD Int. 2022; 9: 69-71https://doi.org/10.1016/j.jdin.2022.08.013Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar demonstrated a lack of statistically significant hair growth and an increase in hair fiber diameter with supplementation in those with primarily AGA or telogen effluvium. Data on biotin for AGA are lacking, and the FDA has warned against high doses due to laboratory interference (eg, troponin and thyroid-stimulating hormone).15Lipner S.R. Rethinking biotin therapy for hair, nail, and skin disorders.J Am Acad Dermatol. 2018; 78: 1236-1238https://doi.org/10.1016/j.jaad.2018.02.018Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar,16Walth C.B. Wessman L.L. Wipf A. Carina A. Hordinsky M.K. Farah R.S. Response to: “Rethinking biotin therapy for hair, nail, and skin disorders”.J Am Acad Dermatol. 2018; 79: e121-e124https://doi.org/10.1016/j.jaad.2018.07.055Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Lack of FDA oversight remains a continuing concern.17Pathoulas J.T. Bellefeuille G. Lofgreen S.J. et al.Unknown safety profile of ingredients in hair supplements: a call to action for improved patient safety.J Am Acad Dermatol. 2020; 83: e213-e214https://doi.org/10.1016/j.jaad.2020.05.033Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Platelet-rich plasma (PRP), although not FDA-approved for AGA, appears to be trending positively despite a litany of positive and negative studies and a lack of standardized product preparation. A single prospective blinded study of 40 AGA subjects demonstrated hair count increases with the regimen of monthly subdermal PRP administration for 3 months and booster 3 months later performing more optimally than 2 sessions every 3 months.18Hausauer A.K. Jones D.H. Evaluating the efficacy of different platelet-rich plasma regimens for management of androgenetic alopecia: a single-center, blinded, randomized clinical trial.Dermatol Surg. 2018; 44: 1191-1200https://doi.org/10.1097/DSS.0000000000001567Crossref PubMed Scopus (51) Google Scholar A recent meta-analysis found that decreased time between PRP treatments, chemically activated PRP, double centrifugation, younger age, female sex, and whole-head administration was most effective.19Gupta A.K. Bamimore M. Platelet-rich plasma monotherapies for androgenetic alopecia: a network meta-analysis and meta-regression study.J Drugs Dermatol. 2022; 21: 943-952https://doi.org/10.36849/JDD.6948Crossref PubMed Scopus (6) Google Scholar More research is needed to replicate these findings. Photobiomodulation (aka low-level light therapy) received FDA safety clearance for male AGA in 2007, and it remains a staple for AGA because of its low-risk profile.20Pathoulas J.T. Bellefeuille G. Raymond O. Khalid B. Farah R.S. Energy-based devices for hair loss.Dermatol Clin. 2021; 39: 447-461https://doi.org/10.1016/j.det.2021.04.002Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar,21Glass G.E. Photobiomodulation: the clinical applications of low-level light therapy.Aesthet Surg J. 2021; 41: 723-738https://doi.org/10.1093/asj/sjab025Crossref PubMed Scopus (34) Google Scholar These laser or light-emitting diode-based devices may be utilized in-office or at home.20Pathoulas J.T. Bellefeuille G. Raymond O. Khalid B. Farah R.S. Energy-based devices for hair loss.Dermatol Clin. 2021; 39: 447-461https://doi.org/10.1016/j.det.2021.04.002Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar,22Torres A.E. Lim H.W. Photobiomodulation for the management of hair loss.Photodermatol Photoimmunol Photomed. 2021; 37: 91-98https://doi.org/10.1111/phpp.12649Crossref PubMed Scopus (11) Google Scholar Wavelengths range from 620 to 678 nm and combination wavelength devices have emerged.20Pathoulas J.T. Bellefeuille G. Raymond O. Khalid B. Farah R.S. Energy-based devices for hair loss.Dermatol Clin. 2021; 39: 447-461https://doi.org/10.1016/j.det.2021.04.002Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar,22Torres A.E. Lim H.W. Photobiomodulation for the management of hair loss.Photodermatol Photoimmunol Photomed. 2021; 37: 91-98https://doi.org/10.1111/phpp.12649Crossref PubMed Scopus (11) Google Scholar,23Lueangarun S. Visutjindaporn P. Parcharoen Y. Jamparuang P. Tempark T. A systematic review and meta-analysis of randomized controlled trials of United States Food and Drug Administration-approved, home-use, low-level light/laser therapy devices for pattern hair loss: device design and technology.J Clin Aesthet Dermatol. 2021; 14: E64-E75PubMed Google Scholar Combs or bands may cost less than caps and helmets.20Pathoulas J.T. Bellefeuille G. Raymond O. Khalid B. Farah R.S. Energy-based devices for hair loss.Dermatol Clin. 2021; 39: 447-461https://doi.org/10.1016/j.det.2021.04.002Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar,22Torres A.E. Lim H.W. Photobiomodulation for the management of hair loss.Photodermatol Photoimmunol Photomed. 2021; 37: 91-98https://doi.org/10.1111/phpp.12649Crossref PubMed Scopus (11) Google Scholar These devices are typically used 3 to 4 times/wk for up to 30 minutes/session.20Pathoulas J.T. Bellefeuille G. Raymond O. Khalid B. Farah R.S. Energy-based devices for hair loss.Dermatol Clin. 2021; 39: 447-461https://doi.org/10.1016/j.det.2021.04.002Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar,22Torres A.E. Lim H.W. Photobiomodulation for the management of hair loss.Photodermatol Photoimmunol Photomed. 2021; 37: 91-98https://doi.org/10.1111/phpp.12649Crossref PubMed Scopus (11) Google Scholar Hair transplantation has experienced advancement in harvesting and implantation techniques. Follicular unit extraction (FUE) now dominates procedures as it avoids the resulting linear scar seen in the traditional strip method.24International Society of Hair Restoration SurgeryPractice Census Results.https://ishrs.org/wp-content/uploads/2020/05/Report-2020-ISHRS-Practice-Census-05-22-20.pdfDate: 2020Date accessed: December 12, 2022Google Scholar,25Jimenez F. Alam M. Vogel J.E. Avram M. Hair transplantation: basic overview.J Am Acad Dermatol. 2021; 85: 803-814https://doi.org/10.1016/j.jaad.2021.03.124Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar FUE may be manual, motorized, or robotic, harvesting hundreds of units/h.26Avram M.R. Watkins S. Robotic hair transplantation.Facial Plast Surg Clin North Am. 2020; 28: 189-196https://doi.org/10.1016/j.fsc.2020.01.011Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar FUE limitations include a wider donor area, longer procedure, and higher transaction rate.27Collins K. Avram M.R. Hair transplantation and follicular unit extraction.Dermatol Clin. 2021; 39: 463-478https://doi.org/10.1016/j.det.2021.04.003Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar Robotic FUE has significant cost and space needs. Finally, interest continues in optimal holding media for follicular units along with operative applications of PRP. As regenerative therapies attempt to infiltrate medicine, patients may inquire about exosomes and AGA. Animal-based data are emerging.28Yuan A.R. Bian Q. Gao J.Q. Current advances in stem cell-based therapies for hair regeneration.Eur J Pharmacol. 2020; 881173197https://doi.org/10.1016/j.ejphar.2020.173197Crossref Scopus (26) Google Scholar However, data for human AGA are lacking. Just one human study involving exosomes for hair growth exists and is muddied by the concurrent use of microneedling.29Park B.S. Choi H.I. Huh G. Kim W.S. Effects of exosome from adipose-derived stem cell on hair loss: a retrospective analysis of 39 patients.J Cosmet Dermatol. 2022; 21: 2282-2284https://doi.org/10.1111/jocd.14846Crossref PubMed Scopus (6) Google Scholar,30Wipf A. Boysen N. Hordinsky M.K. Dando E.E. Sadick N. Farah R.S. The rise of transcutaneous drug delivery for the management of alopecia: a review of existing literature and an eye towards the future.J Cosmet Laser Ther. 2019; 21: 247-254https://doi.org/10.1080/14764172.2018.1525743Crossref PubMed Scopus (6) Google Scholar The use of exosomes for AGA is not FDA-approved, and the FDA has issued a “Consumer Alert on Regenerative Medicine Products Including Stem Cells and Exosomes.”31Center for Biologics Evaluation and ResearchConsumer Alert on Regenerative Medicine Products Including Stem Cells and Exosomes. FDA, 2020https://www.fda.gov/vaccines-blood-biologics/consumers-biologics/consumer-alert-regenerative-medicine-products-including-stem-cells-and-exosomesDate accessed: December 12, 2022Google Scholar Overall, oral therapeutic options along with minimally invasive procedures and hair transplantation have advanced significantly. Nutritional supplementation and exosomes may play a role in AGA, but strong evidence-based medicine is needed to stand the test of time.