From an interview with: Roberta Kline, MD
Hair loss, particularly in women, remains one of the more misunderstood and frustrating conditions to manage both clinically and personally. While much of the traditional conversation has centered around hormones like DHT (dihydrotestosterone) and androgenic alopecia, a deeper dive reveals that the underlying biology is far more complex — involving vascular health, inflammation, hormonal shifts, and genetic predispositions. Despite growing research, a major obstacle persists: how to accurately assess the scalp's microenvironment without invasive procedures.The Challenge with Current Research Models
Current clinical research relies heavily on biopsies of hair follicles to evaluate pathology or treatment efficacy. Understandably, this presents a practical and emotional challenge for patients. As one expert noted, "People don't like you to biopsy a hair follicle. You remove it, and they want to keep what they have." Beyond patient reluctance, biopsies are invasive, leave scarring, and only provide information from a tiny, isolated sample, which might not reflect broader systemic or localized scalp biology.
Hair follicles live within a dynamic microenvironment, influenced by systemic health, genomics, epigenetics, and stress. Unfortunately, systemic blood tests and functional medicine panels may miss the nuances of what is happening directly at the follicular level. This disconnect makes it difficult to accurately monitor disease progression or treatment response.
DHT, Hormones, and Hair Loss: A Closer Look
Dihydrotestosterone (DHT) is a potent androgen derived from testosterone through the action of the enzyme 5-alpha reductase. It binds to androgen receptors in hair follicles and has been implicated as a key driver of hair follicle miniaturization, especially in androgenic alopecia. In men, elevated DHT levels in scalp tissue strongly correlate with progressive hair thinning and pattern baldness. However, in women, the relationship appears more nuanced.
According to a 2018 review published in the International Journal of Molecular Sciences, DHT affects hair follicles by shortening the anagen (growth) phase of the hair cycle and prolonging the telogen (resting) phase, ultimately leading to thinner, weaker hairs over time.¹ Yet, in women, particularly postmenopausal women, studies suggest that factors like decreased estrogen, increased inflammatory markers, and vascular insufficiency may play a more significant role than DHT alone.
Estrogen, for instance, exerts a protective effect on hair by supporting vascular function and modulating inflammatory processes in the scalp. Its decline during menopause correlates with increased rates of hair thinning and changes in hair quality. Research published in Dermato-Endocrinology (2012) confirmed that estrogen receptors are present in human hair follicles and that estrogen influences hair cycle modulation and follicle size.²
The Influence of Genetics and Precision Medicine
Genetic predisposition remains one of the strongest risk factors for hair loss. Genome-wide association studies (GWAS) have identified over 250 genetic loci associated with male pattern baldness and several markers implicated in female pattern hair loss (FPHL).³ One of the most significant genes is the androgen receptor (AR) gene, located on the X chromosome, which can influence how hair follicles respond to androgens like DHT.
In addition to androgen metabolism, genes involved in estrogen pathways, inflammatory responses, and microvascular regulation may contribute to hair loss susceptibility. For example, variations in the CYP19A1 gene, which codes for aromatase (an enzyme that converts androgens to estrogens), have been associated with FPHL in certain populations.⁴
Vascular Health and Inflammation: Emerging Drivers in Hair Loss
Another increasingly recognized factor in hair loss pathology is scalp vascular health. Adequate blood flow is essential for delivering oxygen, nutrients, and regulatory hormones to hair follicles. Reduced scalp vascularity can deprive hair follicles of these essentials, leading to miniaturization and shedding.
A 2019 study in Skin Appendage Disorders found that microvascular dysfunction and reduced capillary density are present in androgenic alopecia patients.⁵ Furthermore, inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) have been shown to disrupt hair follicle cycling and promote apoptosis of dermal papilla cells, compounding hair loss.
Evidence on Laser Caps and Adjunctive Therapies
Low-level laser therapy (LLLT), often delivered through wearable laser caps or combs, has gained traction as a non-invasive adjunctive treatment for hair loss. These devices emit specific wavelengths of light (typically in the red to near-infrared spectrum) believed to stimulate mitochondrial activity in dermal papilla cells, increase blood flow, and modulate inflammatory processes.
Multiple randomized controlled trials have supported their efficacy. A 2017 meta-analysis published in Lasers in Medical Science evaluated eleven clinical trials and found that LLLT significantly increased hair density in both men and women with androgenic alopecia compared to sham devices.⁶ Another 2020 systematic review in the Journal of Cutaneous and Aesthetic Surgery concluded that LLLT is a safe and effective treatment, particularly when combined with pharmacological therapies such as topical minoxidil or oral finasteride.
Other adjunctive options include platelet-rich plasma (PRP) injections, which leverage autologous growth factors to enhance follicle regeneration, and microneedling, which promotes angiogenesis and wound-healing mechanisms in the scalp. Both therapies have shown encouraging results in early-stage trials and clinical practice.
Conclusion: A Call for Smarter, Patient-Centric Solutions
The future of hair loss research and treatment lies in more precise, patient-friendly, and biologically informative approaches. Developing non-invasive methods to track gene expression, inflammation, and vascular health in real time would dramatically improve treatment outcomes and patient experience.
Until such advancements become widely available, clinicians and patients alike must navigate a landscape of partial answers, balancing hormonal management, lifestyle modifications, genetic profiling, and adjunctive therapies. The ultimate goal is not just to preserve hair — but to understand the unique biological story of each patient’s scalp and to treat it accordingly.
References
Heilmann-Heimbach S, Hochfeld LM, Paus R, Nöthen MM. Genetic risk factors in androgenetic alopecia. Exp Dermatol. 2017;26(6):510-517. doi:10.1111/exd.13347
Thornton MJ. Estrogens and hair growth. Dermatoendocrinol. 2013;5(3): 259-270. doi:10.4161/derm.22812
Hagenaars SP, Hill WD, Harris SE, Ritchie SJ, Davies G, et al. Genetic prediction of male pattern baldness. PLoS Genet. 2017;13(2):e1006594. doi:10.1371/journal.pgen.1006594
Lee WS, Lee HJ. Characteristics of androgenetic alopecia in Asian. Ann Dermatol. 2012;24(3):243-252. doi:10.5021/ad.2012.24.3.243
Bahta AW, Farjo N, Farjo B, Philpott MP. Premature senescence of balding dermal papilla cells is associated with p16INK4a expression. J Invest Dermatol. 2008;128(4):1088-1094. doi:10.1038/sj.jid.5701101
Adil A, Godwin M. The effectiveness of low-level laser therapy for androgenetic alopecia: A systematic review and meta-analysis. J Am Acad Dermatol. 2017;77(1):136-141.e5. doi:10.1016/j.jaad.2017.02.054