## 4 Discussion  
Clinical presentation of AGA in MPHL and FPHL consists of progressive hair miniaturization developing due to the influence of DHT, on a background of genetic susceptibility of the hair follicles, in specific areas of the scalps such as the temporal, frontal, and vertex regions. AGA outcome is a slow progression that, if not cured, causes diffuse hair thinning in the androgen-sensitive regions of the scalp. According to the latest European Guidelines, effective medical therapies, such as Minoxidil(r) and Finasteride(r), are classified as evidence-based medicine (EBM) of level one. To maintain clinical efficacy, these therapies should be continued for life, but it is well known that they can lose their effectiveness over time. In the other way, the encouraging results obtained with LLLT in HL, as also confirmed by a recent systematic review [21], pushed several authors and companies to develop new treatments and/or devices, combining two or more procedures. In this way, the combined use of MND with LLLT and GFs in patients suffering from AGA has been recently described as aiming to improve HRG [8; 9]. In detail, two studies have been conducted by the author [PERSON] et al. [8; 9]. The first study, published in 2020 [8], aimed to report the combined effects of autologous PRP with MND and LLLT in 23 patients affected by AGA (13 males were classified in stage I-V by the Norwood-Hamilton scale, and 10 females were classified in stage I-III by the Ludwig scale) with a follow-up of 12 wks (T1), 23 wks (T2), 44 wks (T3), and 58 wks (T4). In the first work of [PERSON] et al. [8], interesting results were shown, represented by an HD increase of 81 \(\pm\) 5 hairs/cm\({}^{2}\) and 57 \(\pm\) 7 hairs/cm\({}^{2}\) respectively at T1 and T2 compared with baseline (173 \(\pm\) 5 hairs/cm\({}^{2}\) at T1 and 149 \(\pm\) 9 hairs/cm\({}^{2}\) at T2 versus 92 \(\pm\) 2 hairs/cm\({}^{2}\) at baseline) using trichograms. The extreme variability of the PRP products used, and contextually, the absence of standardized protocols of PRP preparation widely shared, and the necessity to perform the procedures in an operatory room of an authorized clinic (the PRP was subjected to the approval of transfusion service in Italy) were the limitations of the study. In the second study published in the current year 2022, [PERSON] et al. [9] reported the effects of the combining use of MND, LLLT, and synthetic GFs (without autologous PRP use) in a single hand-homemade application device in 26 patients suffering from several degrees of AGA (I-III vertex according to Norwood Hamilton and I-II by the Ludwig scale) on HRG showing an HD increase of 12 \(\pm\) 2 hairs/cm\({}^{2}\) at T1 after 16 wks (16 wks vs. 0 wks) in the TA compared with baseline using computerized trichograms, with a statistically significant difference in HRG (\(p\) = 0.0238), In this case, the absence of PRP use seems to be incisive in the results obtained (57 \(\pm\) 7 hairs/cm\({}^{2}\) at 23 wks versus 12 \(\pm\) 2 hairs/cm\({}^{2}\) at 16 wks) but on the other hand, the introduction of the hand-home-made device-based MND-LLLT-GFs at the same time made the patient free to perform the treatment at home with great comfort and with promising results. LLLT, through the red light, stimulates the CCO in the membrane of mitochondria positioned in hair bulge stem cells, acting on ROS and ATP that stimulate cellular proliferation, migration, and oxygenation, leading to HRG improvement [10]. The first LLLT device for MPHL approved by US FDA was introduced in 2007 [22]. LLLT comprises both Light Emitting Diodes (LED) and Laser Diodes (LD), which showed effectiveness for HL treatment through the red lights and lasers emission at 660 nm. For these reasons, the LLLT use, such as phototherapy with LED [23], has been intensified into the market of devices aiming to stimulate HG in AGA [24; 25]. Precedently, LED phototherapy was described as a good and safe procedure for the treatment of acne [26], vaginal atrophy [27], facial aging [28; 29], and in HL disorders [30].