Androgenetic Alopecia Is not Associated With Major Vascular Comorbidities: A Retrospective Case-Control Study of 8230 Patients

Abstract

Androgenetic alopecia (AGA) affects approximately 80% of men and approximately 50% of women during their lifetimes [1]. There are reported associations between early-onset (≤ 35-years-old) AGA, and cardiovascular diseases, including hypertension and coronary artery disease (CAD) [2-4]. We examined for potential associations of vascular conditions with early onset AGA by sex to help stratify AGA patients who may benefit from early cardiovascular intervention.

AGA patients were identified from the All of Us database 5/6/2018–12/31/2023. Systematised Nomenclature of Medicine codes identified vascular diagnoses. Each AGA case was matched to nine controls based on age, sex, and race using nearest-neighbour propensity score matching. Unpaired t-tests and Fisher's exact tests compared continuous and discrete variables, respectively. Wald's test applied to multivariate logistic regression calculated odds ratios (ORs) and p-values. Age, sex, race, hyperlipidemia, obesity, and smoking were covariates in regression analyses. Benjamini–Hochberg adjusted for multiple hypothesis testing with false discovery rate ≤ 0.05.

We included 823 AGA patients and 7407 controls. AGA patients had mean age 60.30-years, with 68.65% female and 72.42% White (Table 1). Of AGA cases, 143 (17.4%) were early onset, with average age 33.43-years, 28.7% female, and 72.0% White. Baseline characteristics were similar between groups (p-values > 0.05). Hypertension, CAD, and varicose veins were the most common comorbidities for AGA and early onset AGA patients (Table 2). In multivariate models, overall and early onset AGA patients had increased risk of varicose veins (aOR = 1.51, p = 0.02; aOR = 7.91, p = 0.02, respectively), but no other vascular diseases (p-values > 0.05). With sex sub-analysis, increased varicose vein risk persisted for overall and early onset AGA men (aOR = 3.22, p = 0.02; aOR = 10.70, p = 0.02, respectively), but not women (aOR = 1.37, p = 0.19; aOR = 3.55, p = 0.99, respectively).

We found that male AGA, particularly early onset AGA, was associated with higher risk of varicose veins versus controls, but not other major vascular diseases. In contrast, in a retrospective case-control study of 85 males who underwent coronary revascularization, patients with early onset AGA (≤ 35-years-old) versus non-AGA patients or with later-onset AGA (> 35-years-old) had increased likelihood of coronary revascularization before 60-years-old (aOR = 3.18, 95%CI:1.01–10.03) [4]. Furthermore, a meta-analysis of nine studies including 44,806 patients (88.9% AGA) reported that men with AGA versus without hair loss had increased heart disease risk (RR = 1.32, 95%CI:1.08–1.63), especially younger men (< 55-years-old) (RR = 1.44, 95%CI:1.11–1.86) [5].

AGA was associated with increased varicose vein risk for only males, which to our knowledge, has not been previously characterised. In a prospective study of 40 men, average serum testosterone levels were higher in varicose versus healthy veins within the same patient (44.9-nmol/L vs. 15.5-nmol/L, respectively, p < 0.001) [6]. Therefore, the association between AGA and varicose veins might be mediated by androgenic activity rather than cardiovascular mechanisms. The androgen-mediated pathogenesis of male AGA versus less defined role in female AGA may explain these differences [7]. Systemic inflammation, connective tissue abnormalities, and/or vascular remodelling may also contribute to both AGA and varicose veins [8, 9]. Since varicose veins and AGA are both common, this finding may be coincidental.

Limitations include retrospective design, preventing establishment of causality, small number of early onset cases, which may limit power, inability to evaluate vascular risk by AGA severity, and inability to account for contributions of exercise and diet.

In conclusion, we found that male AGA was associated with varicose veins, but not with other major vascular diseases. Dermatologists treating male patients with early-onset AGA, particularly those with additional risk factors (e.g., family history and lifestyle factors), may consider discussing the potential association with vascular comorbidities and recommend routine cardiovascular health screenings. Dermatologists can encourage patients to monitor for symptoms, including leg swelling, and following with primary care/cardiology. Prospective studies are needed to explore vascular risk by AGA severity and sex and how lifestyle factors affect AGA and vascular outcomes.

Conceptualisation: Michael M. Ong and Shari R Lipner. Methodology: Michael M. Ong, Steven Zeldin, and Brendan Stone. Software: Steven Zeldin and Brendan Stone. Formal analysis: Steven Zeldin. Data curation: Michael M. Ong and Steven Zeldin. Writing–original draft: Michael M. Ong. Writing–review and editing: Steven Zeldin, Brendan Stone, and Shari R. Lipner. Supervision: Shari R. Lipner.

Dr. Lipner has has received research funding from Moberg Pharmaceuticals and BelleTorus Corporation.

This protocol (22-11026777-02) was reviewed and approved by the Weill Cornell Medicine IRB and determined to qualify for exemption per the Code of Federal Regulations on the Protection of Human Subjects.

The authors declare no conflicts of interest.