By Miguel Aristizabal, MD; Alison Bruce, MB ChB; Thais Pincelli, MD; Jennifer Arthurs, ARNP; and Shane Shapiro, MD
Drs. Aristizabal, Bruce, and Pincelli are with Department of Dermatology, Mayo Clinic in Jacksonville, Florida. Ms. Arthurs is with Center for Regenerative Biotherapeutics, Mayo Clinic in Jacksonville, Florida. Dr. Shapiro is with Department of Orthopedic Surgery, Mayo Clinic in Jacksonville, Florida.
Funding: No funding was provided for this article.
Disclosures: The authors have no conflicts of interest relevant to the contents of this article.
J Clin Aesthet Dermatol. 2024;17(5–6 Suppl 1):S28–S30.
Abstract: Androgenetic alopecia (AGA) is a prevalent cause of hair loss with complex pathophysiologic mechanisms that pose challenges for effective treatment. Despite various therapeutic approaches yielding only partial results, regenerative treatments, such as platelet-rich plasma (PRP), have gained popularity. However, the lack of standardized PRP practices, encompassing product preparation and application, has been a significant concern. This article aims to contribute to fill this gap by presenting a comprehensive overview of PRP practices at a large academic center. Through detailing our protocols, this work not only contributes to the understanding of AGA treatment but also emphasizes the crucial aspect of treatment standardization in the context of PRP therapy. By providing a practical representation of our institutional PRP practices, we aim to contribute to the ongoing discourse on refining and implementing standardized protocols, fostering reproducibility, and improving clinical outcomes in the management of AGA.
Keywords: Platelet-rich plasma, androgenetic alopecia, trichology
Androgenetic alopecia (AGA) is a frequent cause of non-scarring hair loss. It is estimated to affect 80% of men and 50% of women over the age of 70 years, with White individuals being the most commonly affected group, followed by African American and Asian individuals.1 Evidence suggests that AGA can negatively impact quality of life, reduce self-esteem, and potentially contribute to the development of depression.2
Several factors have been associated with the development of AGA, including hormonal, genetic, and environmental influences. The conversion of testosterone to dihydrotestosterone (DHT) is considered pivotal to the miniaturization of affected hair follicles, resulting in a shorter anagen-growth phase and the progressive transformation of terminal hairs into fine vellus hairs.3 Genetically, while conventionally perceived as a condition transmitted through autosomal dominant inheritance with variable penetrance, the exact inheritance pattern of AGA remains elusive, hinting at a potential polygenic nature. The pathological landscape of AGA has broadened to incorporate inflammatory alterations within the hair follicle that may be associated with environmental factors.3 The diagnosis of AGA primarily relies on clinical assessment. In men, it commonly compromises the frontal and vertex scalp, while in women, a more diffuse pattern involving the frontoparietal area is prevalent. Anisotrichosis, defined as increased hair diameter diversity of up to 20%, is a classic sign of AGA.4
There are multiple treatment options available for AGA. Topical minoxidil is commonly considered a safe and well-established first-line choice for both men and women. Finasteride, an oral enzyme inhibitor of the testosterone-to-DHT conversion approved for male AGA since 1997, has shown efficacy with daily use; however, its use in female patients is still a matter of debate. In women, oral spironolactone is a valuable treatment option, demonstrating efficacy after 6 to 12 months of treatment. In addition, a plethora of alternative therapies with varying outcomes have emerged. These include novel topical, oral, and injectable antiandrogens, as well as vitamin and plant-based supplements, oral minoxidil, low-level light therapy, microneedling, intradermal botulinum toxin, and platelet-rich plasma (PRP).5
PRP is a popular treatment option among patients due to its autologous and minimally invasive nature. It involves the application of a fraction of plasma enriched with a high concentration of platelets, which harbor growth factors potentially capable of stimulating angiogenesis, matrix remodeling, cellular proliferation, and differentiation, thereby promoting anagen phase growth, within hair follicles. Key growth factors identified include transforming growth factor beta 1 (TGFβ1), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and fibroblast growth factor (FGF2), among others.6 Evidence has emphasized the potential benefits of PRP in treating AGA, either as a standalone therapy or in combination with other therapies, in early stages of the disease when the hair follicles are still viable.7
Recently, various systematic reviews have indicated that PRP may improve hair density in both men and women with AGA. However, persistent limitations observed across the included studies, such as small sample sizes, combined therapies, and a lack of standardization in the PRP preparation protocol, continue to be a cause for concern.8–10
Supported by multiple randomized controlled trials demonstrating its efficacy, PRP can be argued to have Level I evidence—sufficiently robust to be recommended as a procedure. However, the current issue, prompting our discussion, lies in the lack of standardized protocols and the variations in different PRP preparation procedures. While recommending PRP is reasonable, the precise methodology still requires further refinement.10
Addressing these concerns, evidence-based practices can be implemented to develop a standardized protocol that utilizes PRP in the treatment of AGA. Notably, our experience in the dynamic environment of an academic medical center has highlighted the value of interdepartmental interactions in optimizing clinical outcomes and fostering research alliances. These collaborations significantly contribute to advancing our understanding and application of regenerative therapies, enriching the professional knowledge base.
At the dedicated Hair Loss Clinic in Mayo Clinic Florida, we routinely assess and evaluate male and female patients affected by AGA and female pattern hair loss, respectively. Our approach is evidence-based, with a focus on personalized medicine, and we often incorporate combination treatments to provide comprehensive treatment options. Our initial assessment includes a detailed medical history, physical examination involving hair pull and tug tests, scrutiny of hair care practices, and subsequent diagnostic scalp biopsy and laboratory workup, if indicated. Following the diagnosis of AGA, professional clinical photographs are obtained along with TrichoScan® analysis. In cases where contraindications are not present, we advocate starting with topical treatments initially, and then, if necessary, contemplating the use of oral therapies. These first-line treatments have evidence supporting an increase in both hair diameter and count and are frequently employed for extended periods of time.11
As part of this integral and comprehensive approach, interventional regenerative treatment involving injectable PRP also is recommended, provided there are no contraindications, such as platelet disorders, immunosuppression, propensity for keloid formation, antiaggregating and anticoagulant therapy, bone marrow aplasia, neoplasias, or infection in the treatment area. Under this protocol, 3 to 4 injectable sessions on a monthly basis as an induction treatment have the potential to enhance long-term clinical outcomes and improve patient adherence to the treatment framework.11
PRP is prepared according to an internal standardized protocol involving the collection of 60mL of peripheral venous blood in vacuum-sealed tubes with citrate dextrose. The preparation utilizes a two-spin centrifugation method: an initial spin at 1,500rpm for 10 minutes to remove the red cell layer, followed by a second centrifugation at 3,500rpm for 10 minutes (with a G force of 684 and a radius of 50). The platelet-poor plasma fraction is then extracted using an 18-gauge blunt-tipped aspirating needle. The resulting viable product, amounting to up to 5mL, is subsequently distributed into five 1mL sterile syringes. This entire process is conducted in a sterile laminar flow hood to ensure maximum sterility throughout the procedure. Regularly, an additional 0.5mL of PRP is collected for quality control. Standardization has facilitated a consistent platelet concentration and stability, reaching up to one million platelets per microliter.7
To minimize discomfort, patients receive a local anesthetic in a “crown” pattern. Following preparation, PRP is then administered intradermally using a 30g needle. The entire affected area is treated with small aliquots of 0.1 to 0.3mL per injection point. In addition to the standard post-procedure recommendations for injectable therapies, patients are advised to avoid sun exposure, water sports, and hair styling interventions for a minimum of five days. The resumption of topical therapies is usually recommended after three days.
It has been hypothesized that exposing PRP to dermal collagen and thrombin induces robust platelet activation in a gradual and controlled manner. The secretion of active growth factors initiates approximately 10 minutes after application and is believed to persist for up to seven days.12 In comparison to preactivated PRP (i.e., activation before injection), endogenous or autologous activation may offer additional benefits by preserving the integrity of platelets and facilitating tissue integration. This process induces growth factor modulation in favor of stimulatory factors versus inhibitory effects, a benefit that may not be achieved by growth factors alone when PRP is preactivated.13
Following this comprehensive approach and treatment framework, we anticipate an increase in hair count, terminal hair density, and thickness. As part of the follow-up process, measurement of hair count is also implemented, if feasible, at the six- and 12-month marks. Notably, we have not encountered complications, and we have observed an improvement in the quality of life among individuals treated with PRP. This finding is considered to strengthen the patient-physician relationship.7
Medical procedure standardization plays a crucial role in enhancing patient safety and may improve clinical outcomes.14 The implementation of protocols ensures uniform execution, with the ultimate goal of achieving reproducible results. This meticulous approach, when combined with a comprehensive assessment, not only promotes consistency but also contributes to an elevated standard of care and overall clinical excellence.
PRP and other regenerative therapies are consistently capturing attention within the medical community. At our institution, this heightened interest has facilitated the successful optimization of PRP therapy across various therapeutic areas. This achievement has fostered cross-departmental alliances, contributing significantly to treatment standardization.15 We firmly believe that this collaboration is of paramount importance for advancing patient care, medical education, and research.
Conclusion
AGA represents a prevalent condition affecting a significant proportion of the population, with potential implications for quality of life. The multifaceted nature of AGA, which involves hormonal, genetic, and environmental factors, underscores the challenges of treatment approaches and emphasizes the continued necessity of evidence-based management. While several treatments are available, PRP has gained popularity due to its autologous and minimally invasive nature. Despite promising results in stimulating hair follicle growth, the existing literature reveals persistent limitations, such as small sample sizes and a lack of standardization in PRP preparation protocols, necessitating further research and scrutiny. A precise and optimal formulation of PRP, along with its related biological properties, has not yet been defined. Additionally, a comprehensive list of potential clinical indications and effective application techniques remains undetermined. Thorough research is required to reveal potential clinical indications and treatment effects, or the absence thereof, as previously discussed in further evidence.16
A structured approach should be at the forefront of PRP-based therapies in the treatment of AGA. Treatment standardization allows for reproducible outcomes and homogeneous results, fostering cross-center collaboration as the uniform quality of PRP is assured. Research efforts should be dedicated to elucidating the intricate interactions between PRP and tissues, exploring treatment combinations, and refining application techniques. These endeavors will ultimately lead to treatment optimization, enhancing clinical outcomes.
References
- Devjani S, Ezemma O, Kelley KJ, et al. Androgenetic alopecia: therapy update. Drugs. 2023;83(8):701–715.
- Han S-H, Byun J-W, Lee W-S, et al. Quality of life assessment in male patients with androgenetic alopecia: result of a prospective, multicenter study. Ann Dermatol. 2012;24(3):311–318.
- Ntshingila S, Oputu O, Arowolo AT, Khumalo NP. Androgenetic alopecia: an update. JAAD Int. 2023;13:150–158.
- Workman K, Piliang M. Approach to the patient with hair loss. J Am Acad Dermatol. 2023;89(2S):S3–S8.
- Kaiser M, Abdin R, Gaumond SI, et al. Treatment of androgenetic alopecia: current guidance and unmet needs. Clin Cosmet Investig Dermatol. 2023;16:1387–1406.
- Paichitrojjana A, Paichitrojjana A. Platelet rich plasma and its use in hair regrowth: a review. Drug Des Devel Ther. 2022;16:635–645.
- Bruce AJ, Pincelli TP, Heckman MG, et al. A randomized, controlled pilot trial comparing platelet-rich plasma to topical minoxidil foam for treatment of androgenic alopecia in women. Dermatol Surg. 2020;46(6):826–832.
- Li C, Pan L, Yang L, et al. An umbrella review of the use of platelet-rich plasma in the treatment of androgenetic alopecia. J Cosmet Dermatol. 2023;22(5):1463–1476.
- Morkuzu S, McLennan AL, Kanapathy M, Mosahebi A. Use of activated platelet-rich plasma (A-PRP) on alopecia: a systematic review and meta-analysis. Aesthet Surg J. 2023;43(8):NP631–NP649.
- Zhang X, Ji Y, Zhou M, et al. Platelet-rich plasma for androgenetic alopecia: a systematic review and meta-analysis of randomized controlled trials. Cutan Med Surg. 2023;27(5):504–508.
- Sand J, Walen S. Noninvasive hair rejuvenation. Facial Plast Surg Clin North Am. 2022;30(3):419–431.
- Shimizu Y, Ntege EH, Sunami H, et al. Regenerative medicine strategies for hair growth and regeneration: a narrative review of literature. Regen Ther. 2022;21:527–539.
- Alexander S, Horo I, Johnson S, Daniel S. Platelet-rich plasma in hair loss-mechanism, preparation, and classification. J Cosmet Dermatol. 2022;21(3):970–978.
- Rozich JD, Howard RJ, Justeson JM, et al. Standardization as a mechanism to improve safety in health care. Jt Comm J Qual Saf. 2004;30(1):5–14.
- Shapiro SA, Master Z, Arthurs JR, Mautner K. Tiered approach to considering orthobiologics for patients with musculoskeletal conditions. Br J Sports Med. 2023;57(3):179–180.
- Pincelli T, Zawawi S, Shapiro S, et al. A pilot, randomized, single-blind, controlled study evaluating the use of platelet rich plasma (PRP) for hand skin rejuvenation. Plast Reconstr Surg. 2023. Epub ahead of print.
An Academic Dermatology Center’s Structured Platelet-rich Plasma Approach to Patients with Androgenetic Alopecia
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Drs. Aristizabal, Bruce, and Pincelli are with Department of Dermatology, Mayo Clinic in Jacksonville, Florida. Ms. Arthurs is with Center for Regenerative Biotherapeutics, Mayo Clinic in Jacksonville, Florida. Dr. Shapiro is with Department of Orthopedic Surgery, Mayo Clinic in Jacksonville, Florida.
Funding: No funding was provided for this article.
Disclosures: The authors have no conflicts of interest relevant to the contents of this article.
J Clin Aesthet Dermatol. 2024;17(5–6 Suppl 1):S28–S30.
Abstract: Androgenetic alopecia (AGA) is a prevalent cause of hair loss with complex pathophysiologic mechanisms that pose challenges for effective treatment. Despite various therapeutic approaches yielding only partial results, regenerative treatments, such as platelet-rich plasma (PRP), have gained popularity. However, the lack of standardized PRP practices, encompassing product preparation and application, has been a significant concern. This article aims to contribute to fill this gap by presenting a comprehensive overview of PRP practices at a large academic center. Through detailing our protocols, this work not only contributes to the understanding of AGA treatment but also emphasizes the crucial aspect of treatment standardization in the context of PRP therapy. By providing a practical representation of our institutional PRP practices, we aim to contribute to the ongoing discourse on refining and implementing standardized protocols, fostering reproducibility, and improving clinical outcomes in the management of AGA.
Keywords: Platelet-rich plasma, androgenetic alopecia, trichology
Androgenetic alopecia (AGA) is a frequent cause of non-scarring hair loss. It is estimated to affect 80% of men and 50% of women over the age of 70 years, with White individuals being the most commonly affected group, followed by African American and Asian individuals.1 Evidence suggests that AGA can negatively impact quality of life, reduce self-esteem, and potentially contribute to the development of depression.2
Several factors have been associated with the development of AGA, including hormonal, genetic, and environmental influences. The conversion of testosterone to dihydrotestosterone (DHT) is considered pivotal to the miniaturization of affected hair follicles, resulting in a shorter anagen-growth phase and the progressive transformation of terminal hairs into fine vellus hairs.3 Genetically, while conventionally perceived as a condition transmitted through autosomal dominant inheritance with variable penetrance, the exact inheritance pattern of AGA remains elusive, hinting at a potential polygenic nature. The pathological landscape of AGA has broadened to incorporate inflammatory alterations within the hair follicle that may be associated with environmental factors.3 The diagnosis of AGA primarily relies on clinical assessment. In men, it commonly compromises the frontal and vertex scalp, while in women, a more diffuse pattern involving the frontoparietal area is prevalent. Anisotrichosis, defined as increased hair diameter diversity of up to 20%, is a classic sign of AGA.4
There are multiple treatment options available for AGA. Topical minoxidil is commonly considered a safe and well-established first-line choice for both men and women. Finasteride, an oral enzyme inhibitor of the testosterone-to-DHT conversion approved for male AGA since 1997, has shown efficacy with daily use; however, its use in female patients is still a matter of debate. In women, oral spironolactone is a valuable treatment option, demonstrating efficacy after 6 to 12 months of treatment. In addition, a plethora of alternative therapies with varying outcomes have emerged. These include novel topical, oral, and injectable antiandrogens, as well as vitamin and plant-based supplements, oral minoxidil, low-level light therapy, microneedling, intradermal botulinum toxin, and platelet-rich plasma (PRP).5
PRP is a popular treatment option among patients due to its autologous and minimally invasive nature. It involves the application of a fraction of plasma enriched with a high concentration of platelets, which harbor growth factors potentially capable of stimulating angiogenesis, matrix remodeling, cellular proliferation, and differentiation, thereby promoting anagen phase growth, within hair follicles. Key growth factors identified include transforming growth factor beta 1 (TGFβ1), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and fibroblast growth factor (FGF2), among others.6 Evidence has emphasized the potential benefits of PRP in treating AGA, either as a standalone therapy or in combination with other therapies, in early stages of the disease when the hair follicles are still viable.7
Recently, various systematic reviews have indicated that PRP may improve hair density in both men and women with AGA. However, persistent limitations observed across the included studies, such as small sample sizes, combined therapies, and a lack of standardization in the PRP preparation protocol, continue to be a cause for concern.8–10
Supported by multiple randomized controlled trials demonstrating its efficacy, PRP can be argued to have Level I evidence—sufficiently robust to be recommended as a procedure. However, the current issue, prompting our discussion, lies in the lack of standardized protocols and the variations in different PRP preparation procedures. While recommending PRP is reasonable, the precise methodology still requires further refinement.10
Addressing these concerns, evidence-based practices can be implemented to develop a standardized protocol that utilizes PRP in the treatment of AGA. Notably, our experience in the dynamic environment of an academic medical center has highlighted the value of interdepartmental interactions in optimizing clinical outcomes and fostering research alliances. These collaborations significantly contribute to advancing our understanding and application of regenerative therapies, enriching the professional knowledge base.
At the dedicated Hair Loss Clinic in Mayo Clinic Florida, we routinely assess and evaluate male and female patients affected by AGA and female pattern hair loss, respectively. Our approach is evidence-based, with a focus on personalized medicine, and we often incorporate combination treatments to provide comprehensive treatment options. Our initial assessment includes a detailed medical history, physical examination involving hair pull and tug tests, scrutiny of hair care practices, and subsequent diagnostic scalp biopsy and laboratory workup, if indicated. Following the diagnosis of AGA, professional clinical photographs are obtained along with TrichoScan® analysis. In cases where contraindications are not present, we advocate starting with topical treatments initially, and then, if necessary, contemplating the use of oral therapies. These first-line treatments have evidence supporting an increase in both hair diameter and count and are frequently employed for extended periods of time.11
As part of this integral and comprehensive approach, interventional regenerative treatment involving injectable PRP also is recommended, provided there are no contraindications, such as platelet disorders, immunosuppression, propensity for keloid formation, antiaggregating and anticoagulant therapy, bone marrow aplasia, neoplasias, or infection in the treatment area. Under this protocol, 3 to 4 injectable sessions on a monthly basis as an induction treatment have the potential to enhance long-term clinical outcomes and improve patient adherence to the treatment framework.11
PRP is prepared according to an internal standardized protocol involving the collection of 60mL of peripheral venous blood in vacuum-sealed tubes with citrate dextrose. The preparation utilizes a two-spin centrifugation method: an initial spin at 1,500rpm for 10 minutes to remove the red cell layer, followed by a second centrifugation at 3,500rpm for 10 minutes (with a G force of 684 and a radius of 50). The platelet-poor plasma fraction is then extracted using an 18-gauge blunt-tipped aspirating needle. The resulting viable product, amounting to up to 5mL, is subsequently distributed into five 1mL sterile syringes. This entire process is conducted in a sterile laminar flow hood to ensure maximum sterility throughout the procedure. Regularly, an additional 0.5mL of PRP is collected for quality control. Standardization has facilitated a consistent platelet concentration and stability, reaching up to one million platelets per microliter.7
To minimize discomfort, patients receive a local anesthetic in a “crown” pattern. Following preparation, PRP is then administered intradermally using a 30g needle. The entire affected area is treated with small aliquots of 0.1 to 0.3mL per injection point. In addition to the standard post-procedure recommendations for injectable therapies, patients are advised to avoid sun exposure, water sports, and hair styling interventions for a minimum of five days. The resumption of topical therapies is usually recommended after three days.
It has been hypothesized that exposing PRP to dermal collagen and thrombin induces robust platelet activation in a gradual and controlled manner. The secretion of active growth factors initiates approximately 10 minutes after application and is believed to persist for up to seven days.12 In comparison to preactivated PRP (i.e., activation before injection), endogenous or autologous activation may offer additional benefits by preserving the integrity of platelets and facilitating tissue integration. This process induces growth factor modulation in favor of stimulatory factors versus inhibitory effects, a benefit that may not be achieved by growth factors alone when PRP is preactivated.13
Following this comprehensive approach and treatment framework, we anticipate an increase in hair count, terminal hair density, and thickness. As part of the follow-up process, measurement of hair count is also implemented, if feasible, at the six- and 12-month marks. Notably, we have not encountered complications, and we have observed an improvement in the quality of life among individuals treated with PRP. This finding is considered to strengthen the patient-physician relationship.7
Medical procedure standardization plays a crucial role in enhancing patient safety and may improve clinical outcomes.14 The implementation of protocols ensures uniform execution, with the ultimate goal of achieving reproducible results. This meticulous approach, when combined with a comprehensive assessment, not only promotes consistency but also contributes to an elevated standard of care and overall clinical excellence.
PRP and other regenerative therapies are consistently capturing attention within the medical community. At our institution, this heightened interest has facilitated the successful optimization of PRP therapy across various therapeutic areas. This achievement has fostered cross-departmental alliances, contributing significantly to treatment standardization.15 We firmly believe that this collaboration is of paramount importance for advancing patient care, medical education, and research.
Conclusion
AGA represents a prevalent condition affecting a significant proportion of the population, with potential implications for quality of life. The multifaceted nature of AGA, which involves hormonal, genetic, and environmental factors, underscores the challenges of treatment approaches and emphasizes the continued necessity of evidence-based management. While several treatments are available, PRP has gained popularity due to its autologous and minimally invasive nature. Despite promising results in stimulating hair follicle growth, the existing literature reveals persistent limitations, such as small sample sizes and a lack of standardization in PRP preparation protocols, necessitating further research and scrutiny. A precise and optimal formulation of PRP, along with its related biological properties, has not yet been defined. Additionally, a comprehensive list of potential clinical indications and effective application techniques remains undetermined. Thorough research is required to reveal potential clinical indications and treatment effects, or the absence thereof, as previously discussed in further evidence.16
A structured approach should be at the forefront of PRP-based therapies in the treatment of AGA. Treatment standardization allows for reproducible outcomes and homogeneous results, fostering cross-center collaboration as the uniform quality of PRP is assured. Research efforts should be dedicated to elucidating the intricate interactions between PRP and tissues, exploring treatment combinations, and refining application techniques. These endeavors will ultimately lead to treatment optimization, enhancing clinical outcomes.
References
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