**1. Introduction**

Alopecia is a common condition that affects a large part of the population, particularly Caucasian males, the most common type being androgenic alopecia (AGA), a progressive disorder with significant psychosocial effects that can lead to depression. There are several theories trying to explain the complex multifactorial pathogeny of this condition. One of them postulates that chronic perifollicular microinflammation amplifies the expression of pro-inflammatory cytokines, leading to oxidative stress. The oxidative profile acts in combination with high levels of androgens, genetic predisposition and environmental factors such as stress, affecting the corticotropin-releasing hormone pathway and cortisol levels, hence generating the condition [1]. Gene variants that lead to increased activity of 5 α-reductase or increased sensitivity of androgen receptors are deemed to play an important role [2]. There is no single key mechanism involved in the disease, but a plethora of interconnected mechanisms that need to be treated simultaneously for a successful result. The

**Citation:** Georgescu, S.R.; Amuzescu, A.; Mitran, C.I.; Mitran, M.I.; Matei, C.; Constantin, C.; Tampa, M.; Neagu, M. Effectiveness of Platelet-Rich Plasma Therapy in Androgenic Alopecia—A Meta-Analysis. *J. Pers. Med.* **2022**, *12*, 342. https://doi.org/ 10.3390/jpm12030342

Academic Editor: David S. Gibson

Received: 2 February 2022 Accepted: 22 February 2022 Published: 24 February 2022

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reestablishment of healthy hair cell follicles can be influenced by certain growth factors that can stimulate the anagen phase of hair cycle, favoring cell proliferation, improvement of extracellular matrix and neoangiogenesis [3,4]. Recent studies have evidenced inflammatory infiltrates located in perifollicular/perivascular areas with histiocytes and lymphocytes. These findings, together with the implication of certain inflammatory genes (e.g., CASP7, TNF), strongly suggest a relationship between AGA and inflammatory pathways [1].

The close relationship between chronic inflammation and oxidative stress is well known [5–8]. There are many studies that show the involvement of oxidative stress in alopecia areata [9–12]. Recent research indicates an imbalance between oxidants and antioxidants in AGA [13,14]. The skin appendages, especially the hair follicle, can be exposed to elevated levels of oxidative stress. Reactive oxygen species (ROS) accumulate in the hair follicle and the antioxidant defense capacity is exceeded, resulting in premature aging of dermal papilla cells and eventually to the loss of their function [13,15]. Furthermore, it has been hypothesized that ROS may mediate the response of cells to growth factors [13]. In the light of oxidative stress involvement in AGA, Kaya Erdogan et al. consider that antioxidant therapies may be useful in the treatment of these patients [14].

Beyond classical AGA therapies such as minoxidil or finasteride, several new strategies have been proposed in recent years, each of them claiming long-term beneficial effects on hair follicle homeostasis [1,16], and offering multiple choices for personalized treatments. Among these new therapies, platelet-rich plasma (PRP) has been tested in several randomized case-control clinical trials [17,18]. The procedure involves collecting autologous blood from the patient under sterile conditions, on anticoagulant, and separating a platelet-rich plasma fraction by centrifugation. After a first spin, the second intermediate layer of plasma can be collected with a sterile syringe, dropping out the first layer of PPP (Platelet-Poor Plasma or buffy coat) and the red blood cells at the bottom of the tube. Some practitioners use a second spin to concentrate the PRP, as well as an activator of platelet α-granules release such as calcium or thrombin before injection into the scalp. There is a wide variation of protocols for preparation of PRP [3].

PRP therapy is already extensively used in dermatology and plastic surgery [19], being successfully applied for facial rejuvenation, treatment of wrinkles, scars, striae distensae, atrophic acne, vitiligo, facelift surgery, periorbital rejuvenation, dermal augmentation, as well as in other medical specialties such as orthopedic and trauma surgery, ocular surgery, stomatology, wound healing, urology, etc. [20,21]. Due to the important effects of growth factors present in PRP on skin rejuvenation, fibroblast and macrophage chemotaxis, fibroblast proliferation and extracellular matrix synthesis [22], this treatment is expected to exert beneficial effects on hair follicle degeneration, particularly in AGA. Autologous platelet rich fibrin (PRF), another related therapy, has been successfully used in both solid and liquid form administered intralesionally to accelerate healing in a case of facial pyoderma gangrenosum, due to its capacity to promote the prolonged release of multiple growth factors including TGF, EGF, FGF, KGF, CTGF, TNF-α [23], as well as in oral and maxillofacial surgery to cure medication-related osteonecrosis [24,25].

Until now, the only two effective treatments of AGA approved by the FDA are minoxidil for both men and women and finasteride for men [26–28]. Other treatment options are low-level laser therapy or hair transplant surgery, both with limited effectiveness, as well as synthetic PRP analogues such as growth factors biomimetic cocktails [16] or hair follicle dermal papilla stem cell cloning [29]. Considering their potential adverse reactions and other limiting factors, published results of clinical trials have to be carefully assessed via meta-analyses like the present one, which can be expanded for finding new possible therapy targets.

#### **2. Materials and Methods**
