Mediating effect of sex hormones and modification of lifestyle: Association between pyrethroid exposure and hypertension

This study aimed to investigate whether exposure to them increases the risk of hypertension (HTN) and evaluated the mediating role of sex hormones and the modifying effect of lifestyle. This study recruited 560 pairs of HTN cases and matched controls. After applying inclusion and exclusion criteria, 444 pairs were included. Plasma pyrethroid and serum sex hormone levels were measured. Cox regression models were used to assess the association between pyrethroid exposure and HTN risk. Quantile G-computation (QGC), Bayesian Kernel Machine Regression (BKMR),and adaptive elastic-net to (AENET) were employed to evaluate the effects of pyrethroid mixture exposure on HTN. Mediation analyses were performed to examine the role of sex hormones, and interaction analyses were conducted to assess the modifying effect of lifestyle. In model 3, six pyrethroids were positively associated with HTN in males and females (hazard ratio ( HR ): 1.216–1.930), and pyrethroid mixture exposure was positively associated with HTN in males( HR : 1.513, 95% confidence interval ( CI) : 1.299–1.762), with fenvalerate identified as the primary contributor. Meanwhile, the increased HTN risk associated with pyrethroid exposure was exacerbated by lower socioeconomic status, current or former smoking, current or former drinking, and a BMI ≥ 24 kg/m 2 . Progesterone exhibited a partial mediating effect on the association between pyrethroid exposure and HTN in males and females, with a mediation proportion of 2.9%-27.6% ( P < 0.05). Pyrethroid exposure was associated with an increased risk of HTN. This association was influenced by specific lifestyle and partially mediated by progesterone. • Pyrethroids exposure insecticides is associated with an increased risk of HTN. • HTN risk can be modified by socioeconomic and lifestyle factors. • Progesterone has been identified as significant mediators.