Androgenic alopecia: conventional treatment options and innovative approaches

Androgenetic alopecia is a progressive condition driven by the effects of dihydrotestosterone (DHT) on hair follicles in the scalp Current treatment strategies can be classified into pharmacological (hormonal and non-hormonal) treatments, physical interventions, and emerging therapeutic alternatives.

  Pharmacological treatments  

Hormonal Treatments

Hormonal treatments such us Finasteride and Dutasteride inhibit 5-alpha-reductase enzyme which converts testosterone to a more active androgen form, dihydrotestosterone, leading to a decrease of it and causing hair loss ultimately.  Unfortunately, this effect is usually reverted when treatment discontinues. 

Notably, Finasteride induces significant hair regrowth in patients following prolonged administration. Nevertheless, treatment has some downsides in terms of common side effects, such as sexual dysfunction and breast tissue enlargement. These side effects may persist even after drug discontinuation in some patients, which has led to concerns about a condition known as post-finasteride syndrome which can include sexual and neuropsychiatric symptoms^1,2.

Non-Hormonal Treatments

Minoxidil is one of the most widely used non-hormonal treatments for androgenetic alopecia. Originally developed as an antihypertensive vasodilator, minoxidil enhances blood flow in the scalp, improving oxygen supply and essential nutrients to hair follicles. This mechanism helps to prolong the anagen or hair growth phase, leading to increased hair density and thickness over time.

Clinical studies have reported that consistent use of topical Minoxidil can result in significant hair regrowth, with visible improvements typically showed within 4 to 8 months. Long-term adherence is essential, as discontinuation often leads to hair shedding and a return to pre-treatment conditions. 

Although Minoxidil is generally well tolerated, some users can experience dose-dependent side effects, which are usually reversible upon discontinuation. These may include: hypertrichosis (excess hair growth), dizziness and cardiovascular effects such as hypotension and tachycardia.^{1, 2}

Key considerations

While pharmacological treatments have showed efficacy against androgenetic alopecia, the observed positive effects are temporary and limited and its chronic use can be associated to potentially significant side effects.

  Physical Treatments  

In addition to pharmacological approaches, several physical treatments have been developed in order to address androgenetic alopecia. These interventions focus on either redistributing existing hair follicles and stimulating follicular activity to enhance hair growth.

• Low-level laser therapy uses red light to improve hair follicles function and improve blood circulation. It is effective in both men and women however regular sessions are required and results vary depending on individual response and hair loss severity.^{1, 3}

• Microneedling creates micro-injuries in the scalp, boosting topical treatment absorption (e.g., minoxidil) and stimulating hair follicle activity. Despite being minimally invasive, it may cause temporary redness, irritation or discomfort. In addition, multiple sessions are needed in order to achieve visible results.^{1, 2} 

• Hair Transplant is a surgical procedure that permanently relocates healthy hair follicles from donor areas (typically from the back or sides of the scalp) to bald regions. Although its proven efficacy; its cost, invasiveness and unsuitability for certain cases are its main disadvantages.

Key considerations

While physical treatments can improve hair density and delay hair loss, they can be not suitable for all patients or require ongoing maintenance through multiple sessions. They are costly, particularly hair transplants and they often need to be combined with pharmacological therapies for optimal results. 

The following table serves as an overview of the most important treatments used to date⁴

  Innovative approaches: Cellular Therapy  

Advanced therapies, also called as Advanced Therapy Medicinal Products (ATMP) includes innovative medicinal products related to gene therapy, somatic cell therapy, tissue-engineered therapies and combined ones^1-3. From a regulatory perspective, ATMP are classified as biological products.^{4, 5} 

Cellular therapy is now emerging as a promising alternative to revolutionize alopecia treatment by focusing on hair follicle niche restoration. This strategy ultimately aims to regenerate hair follicles offering a long-term solution for androgenetic alopecia.

In recent years, there has been significant progress in the development of stem cell-based therapies for androgenetic alopecia, some of which are based on different cell types administration. Stromal vascular fraction extracted from adipose tissue and micrograft solutions derived from the patient scalp are the most common examples. Furthermore, application of isolated and expanded cellular types has also been assessed in several clinical trials including bone marrow mononuclear cells, dermal papilla cells and bulge stem cells, last both the two main populations of hair follicle resident stem cells and responsible of hair growth. Lately, tissue engineering combining principles from biology and biomaterials has also been developed aiming to restore, maintain and improve tissue function^5, 6. In this regard, induced pluripotent stem cells (iPSCs) integrated with biomaterials have been greatly developed  in order to generate a functional follicular unit intended for transplantation.

  Allogenic therapies: a pioneering solution for androgenic alopecia  

Cells or tissues to be transferred may either be isolated from a tissue sample of the patient (autologous therapies) or isolated from another healthy donor (allogeneic therapies). 

Concerns with autologous therapies include the burden on patient associated with tissue collection, the potentially lower quality of the extracted cells due to the patient’s condition and the cost and time involved in extracting and tailoring cells individually to each patient. In contrast, allogeneic therapies solve these concerns by using high quality cells from a healthy donor, and offering the scalability and the possibility to treat multiple patients from the same cell extraction. It ensures a faster access for patients in terms of a “ready-to-use”-therapy.

  About Agacell®  

Agacell® is a pioneering allogeneic cell therapy for androgenic alopecia that restores the hair follicle cellular niche, thus promoting hair growth in the long-term. It is based on mesenchymal stem cells administration which are isolated from the adipose tissue of a healthy donor, expanded and cryopreserved in a stem cell bank. Adipose-derived stem cells  may interact with  resident hair follicle cells and promote hair formation by means of the release of growth and immunomodulating factors.  In addition the composition includes a molecule that serves as an energy booster. Finally it is administered to the patient by intradermal injections in the affected area. By combining stem cell technology and this molecule, the synergistic interaction halts the progression of hair loss and could also reverses existing damage.

Key considerations

Cellular therapy could promote hair follicle regeneration and cause hair density improvement. In addition of adipose derived stem cells based clinical trials have shown a well-tolerated profile which do not usually require chronic administration.

References

1. Devjani S, Ezemma O, Kelley KJ, Stratton E, Senna M. Androgenetic Alopecia: Therapy Update. Drugs. Jun 2023;83(8):701-715. doi:10.1007/s40265-023-01880-x

2. Nestor MS, Ablon G, Gade A, Han H, Fischer DL. Treatment options for androgenetic alopecia: Efficacy, side effects, compliance, financial considerations, and ethics. J Cosmet Dermatol. Dec 2021;20(12):3759-3781. doi:10.1111/jocd.14537

3. Dominguez-Santas M, Diaz-Guimaraens B, Saceda-Corralo D, Hermosa-Gelbard A, Muñoz-Moreno Arrones O, Pindado-Ortega C, Fernandez-Nieto D, Jimenez-Cauhe J, Ortega-Quijano D, Suarez-Valle A, Jaen-Olasolo P, Vaño-Galvan S. The state-of-the-art in the management of androgenetic alopecia: A review of new therapies and treatment algorithms. JEADV Clinical Practice. 2022;1(3):176-185. doi:https://doi.org/10.1002/jvc2.53

4. Gasteratos K, Kouzounis K, Goverman J. Autologous Stem Cell-derived Therapies for Androgenetic Alopecia: A Systematic Review of Randomized Control Trials on Efficacy, Safety, and Outcomes. Plast Reconstr Surg Glob Open. Feb 2024;12(2):e5606. doi:10.1097/gox.0000000000005606

5. Pizevska M, Kaeda J, Fritsche E, Elazaly H, Reinke P, Amini L. Advanced Therapy Medicinal Products' Translation in Europe: A Developers' Perspective. Perspective. Frontiers in Medicine. 2022-February-03 2022;9doi:10.3389/fmed.2022.757647

6. Iglesias-Lopez C, Agustí A, Vallano A, Obach M. Current landscape of clinical development and approval of advanced therapies. Mol Ther Methods Clin Dev. Dec 10 2021;23:606-618. doi:10.1016/j.omtm.2021.11.003