Introduction/History

Hair loss disorders are among the most common concerns encountered in dermatology, with profound psychosocial and quality-of-life impact. The understanding and treatment of alopecia areata have progressed significantly over the past several decades. In 1981, the National Alopecia Areata Foundation was formed to provide patient support and promote research. By 2000, the NIH established a patient registry to advance knowledge of disease pathophysiology and treatments. In 2008, the first Alopecia Areata Research Summit was held in Bethesda, Maryland, bringing together 44 hair health professionals and experts in genetics, immunology, patient registries, autoimmunity, and animal models.1 In 2010, inflammatory pathways were further characterized, including IFN-γ involvement in CD4+ Th1 responses, interleukins such as IL-1 with polymorphisms of the IL-1 receptor antagonist and IL-1a, TNF-α, Macrophage Migration Inhibitory Factor, and other mediators.2 A 2014 mouse model demonstrated successful hair regrowth, which was later corroborated in human cases. Clinical trials for alopecia were initiated in 2017, and between 2022 and 2024, several JAK inhibitors—baricitinib (2022), ritlecitinib (2023), and deuruxolitinib (2024)—received FDA approval, marking major therapeutic milestones in disease management.

Redefining Severity

FDA approvals for alopecia areata treatments are currently restricted to cases of severe scalp involvement as defined by the Severity of Alopecia Tool (SALT) criteria. However, in clinical practice, broader definitions are often necessary to identify patients in genuine need of systemic therapy. Collaborative efforts between dermatologists and industry partners have expanded the criteria for insurance qualification of “severe” disease to include patients with significant psychosocial functioning impact, eyelash or eyebrow loss, inadequate response to at least six months of treatment, or rapidly evolving and diffuse alopecia, such as cases with multifocal positive hair pull tests.3

Treatment Approach for Moderate to Severe Alopecia

Therapeutic strategies (Figure 1) for moderate to severe alopecia areata typically begin with foundational therapies such as systemic or topical corticosteroids, diphenylcyclopropenone (a topical immunotherapy aimed at shifting Th1 to Th2 responses under the principle of “antigenic competition”),4 contact sensitizers such as squaric acid or anthralin (which induce irritant dermatitis),5 topical or oral JAK inhibitors, and dupilumab.6 The latter is particularly relevant in patients with elevated total or specific IgE levels, recalcitrance to other therapies, contraindications to JAK inhibitors, pediatric disease, or even in those without a history of atopic dermatitis or asthma. Adjunctive options include intralesional corticosteroids and topical or oral minoxidil. Importantly, combination or “stacked” regimens are frequently required to achieve durable results.

Considerations in JAK Inhibitor Use

JAK inhibitors are generally considered second-line therapies. Breakthrough shedding is common and may be associated with non-adherence, intercurrent infection (such as COVID-19), or stress. To date, no comparative efficacy studies exist, and thus the JAK inhibitor of choice is often dictated by insurance coverage. Typically, agents are not switched unless a patient loses response despite adjunctive measures. These drugs should be avoided in patients with a history of smoking, thromboembolic disorders, cardiac disease, or malignancy, due to an increased risk of non-melanoma skin cancer.7 Treatment usually requires three to six months or longer before regrowth becomes evident, and results are not typically durable, making it critical to manage patient expectations for compliance.

Future Directions

Several emerging therapies hold promise for the future of alopecia areata treatment. Novel JAK inhibitors, including ivarmacitinib, are under investigation.8 Other approaches include OX40/OX40L inhibitors, which may provide durable remission by targeting memory T-cells, particularly across atopic backgrounds,9 as well as inhibition of the IL-7 pathway through agents such as bempikibart, currently being evaluated in an open-label phase 2a trial.10 Additionally, epidemiological research is exploring risk variations, with studies suggesting higher prevalence ratios among Black, Hispanic, and disaggregated U.S. Asian and Pacific Islander children, including subgroups such as South Asian, Filipino, Vietnamese, and Native Hawaiian/Pacific Islander populations.11

Menopause: A Vulnerable Window for Hair Follicles

Each year, approximately 1.3 million women in the United States enter menopause, a transitional period marked by profound hormonal changes that can precipitate or worsen hair loss. Despite the high prevalence of hair-related complaints during this time, research on estrogen receptor–mediated effects on the hair follicle remains limited. Preliminary evidence has demonstrated a measurable decline in hair density from pre- to post-menopause.12 Optimal follicular function is thought to rely on four key pillars: genetics, hormones, immune regulation, and environmental influences (Figure 2).

During menopause, multiple physiologic shifts contribute to follicular vulnerability.13 Hormonal imbalance occurs as estrogen and progesterone levels decline sharply, while circulating androgens such as testosterone and dihydrotestosterone rise due to reduced sex hormone–binding globulin. Alterations in the hair growth cycle are also observed, with fewer follicles in the growth (anagen) phase and more in the resting (telogen) phase, particularly in the frontal scalp. Follicle miniaturization ensues as terminal hairs are progressively replaced by vellus hairs, leading to decreased thickness and density. Additionally, loss of estrogen support for Wnt/β-catenin signaling disrupts follicle cycling, while unopposed androgens further impair regrowth. Reduced estrogen also weakens vascular and metabolic support to follicles, limiting energy delivery and growth potential. Immune regulation is altered, predisposing follicles to inflammation and scarring processes, as seen in conditions like frontal fibrosing alopecia (FFA). Finally, women often report changes in hair texture, including coarseness, dryness, or reduced manageability. Disruption in any of these processes may contribute to female pattern hair loss (FPHL) or, in severe cases, FFA.

Holistic Management Strategies

Management of FPHL and FFA requires a multifaceted approach targeting follicular health, stabilization of the hair cycle, and reduction of environmental and inflammatory triggers. For FPHL, strategies to reduce miniaturization include the use of minoxidil, 5-α reductase inhibitors such as finasteride (with consideration of teratogenic risks and ongoing evaluation of their association with estrogen-driven malignancies),14,15 spironolactone, platelet-rich plasma (PRP), and low-level laser therapy. Stabilization of the hair cycle may be achieved with minoxidil, melatonin supplementation, and attention to sleep hygiene. Inflammation can be mitigated with corticosteroids and anti-dandruff shampoos, while gentle hair care practices—avoiding heat, chemical treatments, and tight hairstyles—help preserve follicle integrity. Supportive lifestyle factors, including optimized nutrition, exercise, and stress management, play an important adjunctive role. Notably, there is no strong evidence supporting estrogen or hormone replacement therapy (HRT) for hair regrowth. This may relate to variability in hormone formulations, type, dose, and frequency. However, one small study of estradiol HRT in postmenopausal women demonstrated improvement in telogen hair rates at three months, as well as improved frontal hairline scores and plucking strength at six months.16

For patients with FFA, early intervention should focus on minimizing environmental triggers. This includes avoiding chemical or nanoparticle sunscreens, fragrances, and powders, while instead adopting fragrance-free, “free-and-clear” skincare regimens and zinc oxide–based non-nano particle sunscreens. Additional treatment strategies involve suppressing inflammation through corticosteroids, doxycycline, hydroxychloroquine, pioglitazone, JAK inhibitors, or systemic immunosuppressants such as cyclosporine or mycophenolate. To improve sebaceous function, dutasteride or pioglitazone may be used. Efforts to reverse miniaturization remain centered on minoxidil and 5-α reductase inhibitors. Collectively, these holistic strategies highlight the importance of addressing hormonal, environmental, and immunologic factors in order to protect follicular health during and after menopause.