Harnessing genetics in hair loss

Dr Gustavo Torres considers how genetics can help to navigate therapeutic challenges in androgenetic alopecia

DR GUSTAVO TORRES

Dr Gustavo Torres, the scientific director at Fagron Genomics, is an expert in applying genetics to personalise therapeutic interventions, particularly in hair loss treatment. He earned his PhD in Genetics and Biotechnology, specialising in genome editing, and continued his research postdoctorally in genetic marker identif ication, the production of genetically modif ied animals, and the development of innovative medical devices. His widely published work has significantly advanced personalised patient care in medicine.

Minoxidil was among the earliest pharmacological treatments demonstrated to promote hair regrowth in androgenetic alopecia (AGA). However, its use exemplifies a persistent challenge in managing this prevalent condition. Approximately 40 per cent of patients derive little or no benefit from the drug. A similar pattern is observed with other therapies, such as 5-alpha-reductase inhibitors (for example, finasteride and dutasteride), whereby outcomes vary considerably among individuals. This inconsistency extends beyond academic interest, reflecting the genuine frustration experienced by both patients and practitioners who pursue multiple regimens without achieving satisfactory results. In such cases, clinicians often suspect that intrinsic biological factors, particularly genetic variations, may be responsible.

Recent advancements in genetic research have begun to clarify why some individuals respond favourably to these medications while others do not. It appears that specific genes, most notably those regulating androgen sensitivity and drug metabolism, ultimately determine therapeutic success or failure. I would like to offer in this article an overview of how genetics may shape treatment outcomes in AGA and examine how emerging pharmacogenetic insights might pave the way for more targeted and effective interventions.

GENETIC UNDERPINNINGS OF TREATMENT RESISTANCE

Although AGA is a multifactorial condition, hormonal pathways involving dihydrotestosterone (DHT) remain central to its pathophysiology. The androgen receptor (AR) gene has long been recognised as a key contributor to this process; variants within this gene may increase local androgen sensitivity in hair follicles, heightening the risk of progressive miniaturisation. Furthermore, the SRD5A2 gene encodes the type 2 5-alpha-reductase enzyme responsible for converting testosterone into DHT. A widely studied variant in SRD5A2 (rs523349) has been linked to elevated enzyme activity, compounding risk and potentially influencing the efficacy of finasteride or dutasteride.

Beyond androgen metabolism, other genetic factors affect the processing or activation of medications within the scalp. For example, the SULT1A1 gene governs the conversion of minoxidil into its active sulphate form. Individuals harbouring variants that impair this sulphation reaction often exhibit a diminished benefit from minoxidil, which may explain why some patients do not experience noticeable hair regrowth. In addition, genes such as PTGES2, which is involved in prostaglandin synthesis, and ACE, which is linked to vascular tone, may modify scalp blood flow,influencing the efficacy of topical therapies.

APPLYING PHARMACOGENETICS IN CLINICAL PRACTICE

Both scientific evidence and accumulated clinical experience suggest that obtaining a comprehensive genetic profile before initiating treatment may substantially refine patient management in AGA.

Evidence indicates that genetic profiling may allow clinicians to anticipate treatment responses with greater precision and to tailor therapeutic regimens to the individual patient’s underlying biology. For example, certain genetic variants may indicate a reduced conversion of minoxidil to its active form or suggest a differential response to 5-alpha-reductase inhibitors. In this context, pre-treatment genetic evaluation has proved beneficial in guiding treatment choices and in mitigating the risk of ineffective interventions. While further research remains necessary, current observations support the integration of genetic profiling as a valuable element in the personalised management of AGA.

NEW HORIZONS: FUTURE THERAPIES AND PRECISION MEDICINE

Research into novel interventions promises to broaden the therapeutic options available for AGA. Scientists are investigating agents that target the prostaglandin pathway, a mechanism linked to both hair growth promotion and vasodilation. Preliminary data suggest that specific prostaglandin analogues might prove effective for certain patient subsets, particularly those whose genetic profile indicates alterations in these signalling pathways.

Looking further ahead, RNA interference (RNAi) technologies may enable clinicians to silence the expression of genes such as AR, reducing androgenic effects at the follicular level without necessarily inducing the systemic changes frequently associated with existing treatments. Although these approaches remain experimental, they exemplify a shift towards molecular precision, whereby interventions are designed to rectify specific dysregulated pathways in AGA.

An additional dimension is the use of predictive modelling through artificial intelligence. Large datasets incorporating patient genetics, hormone levels, and clinical responses might be employed to develop algorithms capable of forecasting individual outcomes. Although this field remains in its infancy, such efforts point to a future in which an individual’s genetic background, lifestyle factors, and scalp environment collectively inform a truly personalised care strategy.

IMPLICATIONS FOR AESTHETIC PRACTICE

For clinicians specialising in aesthetics, a deeper appreciation of the genetic basis of AGA may transform the consultation process. Rather than relying solely on trial-and-error methods, practitioners may discuss the potential influence of genetic factors and explain why one patient might respond rapidly to minoxidil while another experiences little improvement. Recognising these variations may help to mitigate patient disappointment, encouraging a more measured and informed approach to treatment planning.

Furthermore, this evolving knowledge enhances the overall reputation of aesthetic practice. When patients recognise that their clinician is incorporating the latest scientific insights – particularly in pharmacogenetics – they are more likely to trust the recommended course of action. Moreover, these genetic insights may prove invaluable in hair transplantation. Genetic profiling may assist in optimising the donor area prior to transplant by identifying zones with stable follicular health, facilitating improved graft survival. Preoperative genetic evaluation might also guide interventions designed to protect the patient from further hair loss, thus contributing to a comprehensive strategy for long-term hair preservation and enhancing overall surgical outcomes.

CONCLUSION

Although androgenetic alopecia remains a highly prevalent concern among both men and women, significant gaps persist between available therapies and actual patient responses. The burgeoning field of pharmacogenetics offers plausible explanations for these disparities, revealing how genetic variants may influence everything from local androgen sensitivity to the activation of topical agents. With ongoing research into targeted treatments and broader access to genetic profiling, it is foreseeable that truly individualised AGA management will become routine. In the interim, clinicians who remain abreast of these developments and incorporate genetic testing into their routine practice may be best placed to optimise patient satisfaction and long-term hair health.