Environmental Endocrinology: Parabens Hazardous Effects on Hypothalamic-Pituitary-Thyroid Axis

Abstract

Parabens are classified as endocrine-disrupting chemicals (EDCs) capable of interfering with the normal functioning of the thyroid, affecting the proper regulation of the biosynthesis of thyroid hormones (THs), which is controlled by the hypothalamic-pituitary-thyroid axis (HPT). Given the crucial role of these hormones in health and the growing evidence of diseases related to thyroid dysfunction, this review looks at the effects of paraben exposure on the thyroid. In this study, we considered research carried out in vitro and in vivo and epidemiological studies published between 1951 and 2023, which demonstrated an association between exposure to parabens and dysfunctions of the HPT axis. In humans, exposure to parabens increases thyroid-stimulating hormone (TSH) levels, while exposure decreases TSH levels in rodents. The effects on THs levels are also poorly described, as well as peripheral metabolism. Regardless, recent studies have shown different actions between different subtypes of parabens on the HPT axis, which allows us to speculate that the mechanism of action of these parabens is different. Furthermore, studies of exposure to parabens are more evident in women than in men. Therefore, future studies are needed to clarify the effects of exposure to parabens and their mechanisms of action on this axis.

Keywords: endocrine disruptor; hypothalamus–pituitary–thyroid axis; parabens; thyroid; toxicity.

Figure 1

Main effects of exposure to parabens on human health [90,95,97,100]. (A) Effects of paraben exposureduring pregnancy on the HPT axis hormones and maternal and newborn health. (B) Effects of general human exposure to parabens on the HPT axis hormones. Legend: BuP—butylparaben; EP—ethylparaben; MP—methylparaben; PP—propylparaben; TSH—thyroid-stimulating hormone; THs—thyroid hormones; fT4—free thyroxine levels; fT3—free triiodothyronine levels; tT4—total thyroxine levels; tT3—total triiodothyronine levels. This figure was made using the Canva platform.

Figure 2

Main effects of exposure to parabens on rodents. Effects of parabens exposure in the HPT axis of female and male rodents. Legend: BuP—butylparaben; IBP—isobutylparaben; IPP—isopropylparaben; PP—propylparaben; TSH—thyroid-stimulating hormone; fT4—free thyroxine levels; fT3—free triiodothyronine levels; tT4—total thyroxine levels; tT3—total triiodothyronine levels. This figure was made using the Canva platform.

Figure 3

Main effects of exposure to parabens on vertebrates. (A) Consequences of paraben exposure in zebrafish larvae. The blue arrow indicates the effects of paraben exposure on the larvae’s thyroid gland, resulting in a decrease in thyroid hormones (THs). The studied parabens are listed below the larva in order of toxicity: BuP > PP > EP > MP. (B) Impacts of paraben exposure on tadpoles. On the left side of the image, we can see water with high levels of propylparaben (PP). Tadpoles exposed to parabens in the water experience a significant mortality rate, as shown on the right side of the image. The decrease in PP levels in the water indicates that tadpoles absorb PP from the water, accumulating the substance in their bodies. This figure was made using the Canva platform. Legend: THs—thyroid hormones; BuP—butylparaben; PP—propylparaben; EP—ethylparaben; MP—methylparaben.