Androgenetic alopecia (AGA), also known as male or female pattern baldness, is a common type of hair loss that affects 80% of men and 50% of women by age 70, with the incidence increasing with age [16]. AGA is a condition related to androgens that manifests in individuals with a genetic predisposition. AGA is marked by the gradual miniaturization of hair follicles, brought about by changes in the dynamics of the hair cycle. This leads to a continuous reduction in the density of visible scalp hair over time [17]. AGA can be a challenging condition to address as treatment selection often involves a complex consideration of multiple factors and ethical decision-making. Effectiveness, side effect profiles, practicality leading to compliance, and cost of treatment are among the factors that need to be considered especially given the chronic nature of AGA [18]. Currently, the management of AGA primarily involves systemic medications (finasteride and spironolactone), topical medications (minoxidil), and various alternative approaches (hair transplantation, platelet-rich plasma, and low-energy laser) [19]. However, oral medications require long-term usage and come with specific associated side effects. Topical medications, on the other hand, exhibit limited and imprecise efficacy, while invasive treatments entail surgical risks [20].
Botulinum Toxin has found widespread application in dermatology clinics for purposes such as reducing wrinkles, adjusting facial muscles, addressing hyperhidrosis, correcting masseter hypertrophy, and managing gastrocnemius hypertrophy [21, 22]. Additionally, Botulinum toxin intramuscular injections are associated with increased hair counts, and proposed theories suggest mechanisms are the indirect support of artery branches in balding areas and the reduction of tension across the galea aponeurotic, a fibrous membrane spanning the scalp. Frontal balding scalps exhibit lower transcutaneous oxygen levels, potentially caused by constriction of circulatory networks by facial muscles. This hypoxic environment may favor DHT conversion over estradiol, contributing to AGA [23]. Additionally, intramuscular injections may alleviate stress on the galea aponeurotic, impacting AGA progression. Increased DHT and TGF-ß1 activity, as well as intracellular oxidation, result from tissues under pressure. Hic-5/ARA55, an androgen receptor co-activator, may play a role in activating TGF-ß1 and sensitizing dermal papilla cells to androgens. Subsequently, tension-induced stretching across the galea aponeurotica may induce inflammation, transactivating to upper scalp layers and accelerating AGA progression [24].
Hence, the present randomized controlled clinical trial aimed to assess the efficacy of Botulinum Toxin Type A in combination with 5% Minoxidil in the treatment of male patients with AGA. Our study observed improvement in hair growth, as evidenced by the Global Head Photos Scores on a seven-point scale, which is noteworthy. The BTA combined with the topical 5% Minoxidil group consistently outperformed the topical 5% Minoxidil-only group at the 4-month and 6-month assessments, indicating sustained efficacy in promoting hair growth. Similar to our results, Tian K et al study showed Finasteride and minoxidil combined with botulinum toxin A subcutaneous injection has a significant effect on androgenic alopecia [25]. This outcome aligns with the proposed mechanism of action of BTA, which, through neuromuscular modulation, may contribute to enhanced blood flow and reduced oxidative stress in the scalp, fostering a conducive environment for hair follicle rejuvenation [26].
Our analysis of the Investigator's Global Assessment (scaling, erythema, seborrhea, pruritus) provides valuable insights into the impact of the treatment on a patient's scalp with androgenetic alopecia. Initially, both treatment and control groups demonstrated comparable scores, indicating a balanced baseline with no significant differences (p > 0.05). As the study progressed, particularly at the 2-month mark, minimal changes were observed, and non-significant differences persisted between the groups (p > 0.05).
However, a notable shift occurred by the 4-month evaluation, highlighting substantial improvements in the treatment group. This was evidenced by marked reductions in scaling, erythema, seborrhea, and pruritus, as reflected in the t-values ranging from − 2.7108 to -5.6472 (all p < 0.01). The sustained positive impact of the intervention was evident at the 6-month follow-up (seborrhea, pruritus), reinforcing the efficacy of the treatment. This may be due to Botox being known for its muscle-paralyzing effect and its anti-inflammatory properties. This indicates that Botulinum Toxin A may influence the muscles and skin structures, potentially reducing tension and enhancing blood flow [26]. This could positively impact scalp health and alleviate symptoms like scaling and pruritus.
Our study showed a slightly increased score in the Investigator's Global Assessment score in 6 months compared to 4 months in the treatment group. This may be attributed to factors such as the transient nature of Botox effects, variations in individual responses, treatment frequency, and the natural progression of androgenetic alopecia.
Furthermore, Evaluating QoL before and after treatment is of paramount importance in assessing the overall effectiveness and impact of interventions. It provides valuable insights into the holistic well-being of patients beyond just physical symptom relief. Our study explored the impact on patients' quality of life using the Dermatology Life Quality Index (DLQI). The treatment group demonstrated a more substantial improvement in quality of life compared to the control group, particularly at the 4-month and 6-month time points. This suggests that the positive aesthetic outcomes achieved with combination therapy may extend beyond the physical realm, influencing psychological well-being and overall satisfaction with one's appearance. In terms of adverse effects, the patients in neither group experienced any serious adverse effects, However, BTA caused mild discomfort and pain on site of injection which got better after applying the ice pack after the section.
It is crucial to acknowledge the limitations of this study, including the relatively small sample size and the focus on male patients. Future research with larger and more diverse cohorts, including female participants, will contribute to a more comprehensive understanding of the generalizability and effectiveness of BTA combined with Minoxidil therapy.
In conclusion, our results provide compelling evidence for the potential of combining Botulinum Toxin Type A with 5% Minoxidil as an effective and well-tolerated treatment strategy for male patients with Androgenetic Alopecia. The observed improvements in hair growth and quality of life underscore the promising prospects of this therapeutic approach, opening avenues for further exploration and refinement in the management of AGA.