Hair loss evolving into a lifestyle and metabolic phenotype: A hypothesis exploring oxidative stress and acquired androgen sensitivity through reactive oxygen species

Objectives: Early hair loss is a biomarker for cardiovascular disease, dyslipidemias, insulin resistance, and metabolic syndrome, which are lifestyle disorders. Genomic analysis, metabolic studies, and cell cultures indicate the rising influence of oxidative stress, lifestyle factors like stress, diet, smoking, alcohol, sleep, and pollution, mediated through reactive oxygen species (ROS) and altered metabolism of lipids, glucose, and amino acids in hair loss. ROS lowers the sensitivity threshold of androgen receptors, triggering overexpression despite normal dihydrotestosterone (DHT) levels. ROS activate latent Transforming growth factor beta (TGFβ), leading to hair loss. Explore the role of lifestyle and metabolic factors in the etiology of androgenetic alopecia (AGA). Material and Methods: The study includes 198 male and 216 female patients with AGA aged 18 – 32 years, evaluated for family history, lifestyle, environmental factors, hormones, blood sugar, lipid profile, and nutritional deficiencies. Recent scientific data correlates with the role of lifestyle and metabolic factors in hair loss. Results: Males 68% and females 79% had no family history of hair loss. The average age of onset was 20 years. Three or more lifestyle factors were positive in all patients. Nearly 40% had low thyroid hormones T3 (Triiodothyronine), T4 (Tetraiodothyronine), and thyroid stimulating hormone (TSH). levels of DHT, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), and Free Testosterone were normal. Raised blood pressure appeared in 48%, raised fasting blood sugar 66%, high cholesterol 52%, raised very low-density lipoprotein (VLDL) 73%, low vitamin D3 70%, low B12 56%, and low Ferritin in 48% men and 63% women. Limitations: The hypothesis is concluded from a review of published data and requires specific clinical and experimental studies to confirm acquired androgen sensitivity and the role of reactive oxygen species in cellular metabolism of the hair follicles. Conclusion: Modern life has accelerated oxidative damage, metabolic imbalance, senile changes, and biological aging. Metabolomics, cell culture, biopsies, and genome-wide association studies (GWAS) data may suggest a new evolving hair loss phenotype influenced by ROS.