Since its first identification in 1994, Frontal Fibrosing Alopecia (FFA)—a form of scarring hair loss that primarily affects women—has been diagnosed in an increasing number of patients. This trend has prompted researchers and clinicians to explore whether environmental factors might be contributing to its rise. On of these suspected environmental factors is the development of the oral contraceptive pill (OCP) and its widespread use over the past century. This study examines a possible link between a specific genetic variation in the CYP1B1 gene and the risk of developing FFA. The CYP1B1 gene produces a protein that helps break down hormones like estrogen and progesterone. Researchers found a specific change in the genetic code, known as a missense mutation, where one amino acid in the protein (serine, or Ser) is replaced by another (asparagine, or Asn) at a specific position (453). This genetic variation is associated with a 1.65-fold higher risk of developing FFA. The altered version of the enzyme is more stable and remains at higher levels in cells, which may affect hormone metabolism. The study hypothesized that this genetic risk might interact with environmental factors, such as the use of oral contraceptive pills (OCPs), which contain synthetic versions of estrogen and progesterone.
The researchers conducted a large study, analyzing data from 489 women with Frontal Fibrosing Alopecia (FFA) and 34,254 women without the condition, all of similar age and ancestry. They discovered that the increased risk of FFA linked to the altered CYP1B1 gene was primarily seen in women with a history of oral contraceptive pill (OCP) use. Women who carried the genetic variant and had used OCPs were found to have a 1.9-fold higher risk of developing FFA compared to those without the variant. In contrast, no significant association was observed in women who had never used OCPs. This suggests a gene-environment interaction where the presence of the genetic variant with the additional exposure to synthetic OCP hormones increases the risk of disease development. This study sheds light on the complex factors contributing to FFA, involving both genetic predisposition and environmental influences. However, the research also has important limitations. It relied on self-reported OCP use, which may be prone to inaccuracies, and the study population primarily consisted of white, postmenopausal women from the U.K., limiting its generalizability. Future studies are necessary to replicate these findings in more diverse populations, explore other hormonal exposures, and further clarify how genetic and environmental factors interact in FFA development. These additional steps are crucial to understanding the broader applicability of these findings and uncovering the full picture of FFA’s underlying causes.
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Article Summary By Andrea Quartey, MD Candidate at Lewis Katz School of Medicine at Temple University, 2025 | Reviewed by Melissa Piliang, MD