Androgenetic alopecia (AGA) is the most prevalent type of hair loss. Its morbility is mainly psychological although an increased incidence in melanoma has also been observed in affected subjects. Current drug based therapies and physical treatments are either unsuccessful in the long term or have relevant side effects that limit their application. Therefore, a new therapeutic approach is needed to promote regenerative enhancement alternatives. These treatment options, focused on the cellular niche restoration, could be the solution to the impact of dihydrotestosterone in the hair follicle microenvironment. In this context emerging regenerative therapies such as Platelet-rich plasma or Platelet-rich fibrine as well as hair follicle stem cells and mesenchymal stem cell based therapies and their derivatives (conditioned medium CM or exoxomes) are highlighting in the evolving landscape of hair restoration. Nanotechnology is also leading the way in AGA treatment through the design of bioinks and nanobiomaterials whose structures are being configuring in a huge range of cases by means of 3D bioprinting. Due to the increasing number and the rapid creation of new advanced therapies alternatives in the AGA field, an extended review of the current state of art is needed. In addition this review provides a general insight in current and emerging AGA therapies which is intented to be a guidance for researchers highlighting the cutting edge treatments which are recently gaining ground.

BACKGROUND: Despite numerous studies investigating the association between androgenetic alopecia (AGA) and serum uric acid (SUA), the causal relationship between AGA and SUA remains unknown.
METHODS: We utilized bidirectional Mendelian randomization (MR) to explore the causality between AGA and SUA. Our study chose single nucleotide polymorphisms associated with genome-wide significance (p < 5×10-8) for the exposure and showing low linkage disequilibrium (R2 < 0.001) as IVs. Various MR methods were employed to evaluate causality, including inverse-variance weighted (IVW), Weighted Median, MR-Egger, Weighted Mode and Simple Mode. Sensitivity analyses were performed to test the robustness of the results.
RESULTS: Using the IVW method, we did not find a significant causal relationship between AGA and SUA (OR = 1.00, 95% CI 0.99-1.01; p = 0.451). Similarly, the IVW method did not reveal evidence of causality between SUA and AGA (OR = 0.97, 95% CI = 0.91-1.03; p = 0.301). The results from other methods were consistent with those of the IVW approach.
CONCLUSIONS: The study did not identify a causal relationship between AGA and SUA. Future research should involve larger cohorts and advanced methods to validate the findings and explore the complex interactions between AGA and SUA levels in different populations.

Androgenetic alopecia, the most common cause of hair loss affecting both men and women, is typically treated using pharmaceutical options, such as minoxidil and finasteride. While these medications work for many individuals, they are not suitable options for all. To date, the only non-pharmaceutical option that the United States Food and Drug Administration has cleared as a treatment for androgenetic alopecia is low-level laser therapy (LLLT). Numerous clinical trials utilizing LLLT devices of various types are available. However, a myriad of other physical treatments for this form of hair loss have been reported in the literature. This review evaluated the effectiveness of microneedling, pulsed electromagnetic field (PEMF) therapy, low-level laser therapy (LLLT), fractional laser therapy, and nonablative laser therapy for the treatment of androgenetic alopecia (AGA). It also explores the potential of multimodal treatments combining these physical therapies. The majority of evidence in the literature supports LLLT as a physical therapy for androgenetic alopecia. However, other physical treatments, such as nonablative laser treatments, and multimodal approaches, such as PEMF-LLLT, seem to have the potential to be equally or more promising and merit further exploration.

Androgenetic alopecia (AGA) is defined as the alopecia induced by androgens in genetically predisposed individuals. AGA results in progressive miniaturization of the hair follicles leading to vellus transformation of terminal hair. The high prevalence and wide range of expressed phenotypes in AGA is a result of a polygenic inheritance mode. The androgen receptor (AR) gene located on the X chromosome at Xq11-12 is the first gene to show genetic association with AGA. Newer genetic associations with AGA are under study. In early-onset AGA, obesity, diabetes, hypertension, dyslipidaemia, insulin resistance, benign prostatic hyperplasia (BPH), prostate cancers and coronary artery disease (CAD) are associated with AGA. Screening of early-onset AGA patients and intervention for metabolic syndrome and insulin resistance can prevent the development of cardiovascular disease (CVD) at an early stage. As effective treatments continue to be topical minoxidil, systemic finasteride and hair transplantations, newer modalities are under investigation. Understanding the genetic factors involved in AGA and continued research into newer therapies, such as cell-based therapies, will lead to effective treatment and improve the quality of life in patients with AGA.

UNASSIGNED: Oral finasteride and topical minoxidil are long-standing androgenetic alopecia (AGA) treatments; topical finasteride is a more recent medicine. Few studies have compared their therapeutic effects in postmenopausal women. We compared the therapeutic impact of topical finasteride (1-4 sprays of 0.25% topical finasteride solution daily for 12 months), oral finasteride (2.5 mg oral finasteride once daily for 12 months), and topical minoxidil (1 mL of topical minoxidil 5% twice daily for 12 months) in postmenopausal women with AGA.
UNASSIGNED: We conducted Bayesian network meta-analyses of individual patient-level data insofar as four clinically relevant endpoints, namely, 12-month change in (1) total hair density, (2) hair diameter, (3) clinical photographs, and (4) patients\' opinion of efficacy. Data were obtained through medical charts. Regimens\' surface under the cumulative ranking distribution (SUCRA) values and relative effects - as per odds ratios - were computed.
UNASSIGNED: As per SUCRA, the most and least effective regimens - across the four outcomes - were oral finasteride, and topical finasteride, respectively; however, no significant statistical differences were found (i.e., p > 0.05).
UNASSIGNED: Oral finasteride is ranked more effective than the topical forms of minoxidil and finasteride; however, more studies are needed to confirm this result.

UNASSIGNED: Environmental exposures profoundly impact cutaneous physiology, with hair follicles (HFs) being particularly vulnerable due to their high levels of proliferation and perfusion. HFs are exposed directly to contaminants that are absorbed transcutaneously and exposed indirectly to ingested and inhaled pollutants via the bloodstream.
UNASSIGNED: Some pollutants, such as particulate matter, trigger inflammatory responses and have been associated with alopecia areata. Others, like tobacco smoke and phthalates, exert endocrine effects with unclear ramifications for HF function. Pesticides and heavy metals have both been linked to alopecia areata and acute anagen effluvium, while polyaromatic hydrocarbons - ligands of aryl hydrocarbon receptors - are linked to androgenetic alopecia. Finally, UV exposure, which has increased due to anthropogenic ozone depletion, causes oxidative damage and perifollicular mast cell degranulation.
UNASSIGNED: Pollutants have far-reaching consequences for hair pathology, which remain incompletely characterized. The effects of environmental exposures on HFs are an active area of research that deserve further attention.

OBJECTIVE: This study aimed to assess differences in various scalp parameters between patients with androgenetic alopecia (AGA) and healthy volunteers using 22 MHz ultrasound.
METHODS: Thirty patients with AGA (AGA group) and 30 healthy volunteers (control group) who visited the Department of Dermatology at the Second Affiliated Hospital of Soochow University from September 2021 to June 2022 were randomly selected. The patients with AGA met the diagnostic criteria outlined in the Chinese Guidelines for the Diagnosis and Treatment of Androgenetic Alopecia. The severity of alopecia was assessed for males between grades 2 and 4 on the Norwood-Hamilton scale, and for females between stages 2 and 3 on the Ludwig scale. No artificial interventions were conducted at the vertex, and all examination conditions remained consistent. Ultrasound examinations at 22 MHz were performed on the scalp at the vertex in both the AGA and control groups. Seven parameters were measured, namely, epidermis + dermis thickness, entire scalp thickness, subcutaneous tissue thickness, average follicle width, average follicle length, follicle count, and the presence of color flow signals in the subcutaneous tissue. The differences in these parameters were then compared.
RESULTS: The AGA group showed reduced thickness of the entire scalp and subcutaneous tissue, narrower average follicle width, shorter average follicle length, lower hair follicle count, and fewer instances of color flow signals in the subcutaneous tissue at the vertex area (p < 0.05).
CONCLUSIONS: High-frequency (22 MHz) ultrasonography can be employed to visualize the entrance echo, dermis, subcutaneous tissue, and hair follicles of the scalp, thereby providing imaging for the clinical assessment of hair loss.

Androgenetic alopecia (AGA) is a highly prevalent condition in contemporary society. The conventional treatment of minoxidil tincture is hindered by issues such as skin irritation caused by ethanol, non-specific accumulation in hair follicles, and short retention due to its liquid form. Herein, we have developed a novel minoxidil-incorporated engineered exosomes biopotentiated hydrogel (Gel@MNs) that has the capability to modulate the perifollicular microenvironment for the treatment of AGA. Leveraging the exceptional skin penetration abilities of flexible liposomes and the targeting properties of exosomes, the encapsulated minoxidil can be effectively delivered to the hair follicles. In comparison to free minoxidil, Gel@MNs demonstrated accelerated hair regeneration in an AGA mouse model without causing significant skin irritation. This was evidenced by an increase in both the number and size of hair follicles within the dermal layer, enhanced capillary formation surrounding the follicles, and the regulation of the transition of hair follicle cells from the telogen phase to the anagen growth phase. Therefore, this safe and microenvironment-modifying hybrid exosome-embedded hydrogel shows promising potential for clinical treatment of AGA.

Androgenetic alopecia (AGA) is the most prevalent hair loss disorder worldwide, driven by excessive sensitivity or response to androgen. Herbal extracts, such as Curcuma aeruginosa Roxb., have shown promise in AGA treatment due to their anti-androgenic activities and hair growth effects. However, the precise mechanism of action remains unclear. Hence, this study aims to elucidate the active compounds, putative targets, and underlying mechanisms of C. aeruginosa for the therapy of AGA using network pharmacology and molecular docking. This study identified 66 bioactive compounds from C. aeruginosa, targeting 59 proteins associated with AGA. Eight hub genes were identified from the protein-protein interaction network, namely, CASP3, AKT1, AR, IL6, PPARG, STAT3, HIF1A, and MAPK3. Topological analysis of components-targets network revealed trans-verbenol, myrtenal, carvone, alpha-atlantone, and isoaromandendrene epoxide as the core components with potential significance in AGA treatment. The molecular docking verified the binding affinity between the hub genes and core compounds. Moreover, the enrichment analyses showed that C. aeruginosa is involved in hormone response and participates in HIF-1 and MAPK pathways to treat AGA. Overall, this study contributes to understanding the potential anti-AGA mechanism of C. aeruginosa by highlighting its multi-component interactions with several targets involved in AGA pathogenesis.

Background: Angrogenetic alopecia (AGA) is one of the most prevalent hair loss disorders worldwide. The hair follicle stem cell (HFSC) is closely related to the formation of hair follicle (HF) structure and HF self-renewal. The activation of HFSC in AGA is critical for hair growth. Pilose antler has been reported to have hair growth-promoting activity, but the mechanism of action on AGA and HFSC has not been reported. Methods: We previously extracted an active component from the pilose antler known as PAEs. In this study, we conducted experiments using AGA mice and HFSC. The effects of PAEs on hair growth in AGA mice were firstly detected, and then the mechanisms of PAEs for AGA were predicted by integrating network pharmacology and de novo transcriptomics data of pilose antler. Finally, biological experiments were used to validate the molecular mechanism of PAEs in treating AGA both in vivo and in vitro. Results: It was found that PAEs promoted hair regrowth by accelerating the activation of anagen, delaying the anagen-catagen transition. It also alleviated the morphological changes, such as hair shortening, thinning, miniaturization, and HF number reduction, and regulated the hair regeneration process of four subtypes of hair. We further found that PAEs could promote the proliferation of HFSC, outer root sheath (ORS) cells, and hair bulb cells in AGA mice. We then integrated network pharmacology and pilose antler transcriptomics data to predict that the mechanism of PAEs treatment in AGA mice is closely related to the PI3K-AKT/Wnt-β-Catenin pathways. Subsequently, it was also verified that PAEs could activate both pathways in the skin of AGA mice. In addition, we found that PAEs perhaps increased the number of blood vessels around dermal papilla (DP) in experiments in vivo. Meanwhile, the PAEs stimulated the HFSC proliferation in vitro and activated the AKT and Wnt pathways. However, the proliferative activity of HFSC was inhibited after blocking the Wnt pathway and AKT activity. Conclusion: This study suggests that the hair growth-promoting effect of PAEs in AGA mice may be closely related to the stimulation of the AKT and Wnt pathways, which in turn activates the proliferation of HFSC.