LWL | Effects of Parabens on the Female Endocrine System

Abstract 

Parabens are a popular group of synthetic preservatives. Their use in common consumer goods  has increased through the 20th and 21st centuries, causing concern over their impacts on the  female endocrine system. Research into the effects of parabens has shown that due to  ubiquitous exposure, their effects on females are more severe than initially estimated, leading  to their classification as endocrine disruptors (EDCs). Studies discovered correlations between  increased paraben exposure and increased likelihood of breast cancer development, decreased  median age of puberty, mother-child impacts, and increased preterm births. This article aims to  review the findings of studies that investigated these relationships. The included studies were  conducted in the last five years and selected due to their robust methodologies, quality of data  and contributing findings.  

Key words: parabens, female, endocrine system disruptions, menstruation, pregnancy.  Subject: Medicine; human physiology (endocrinology) 

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Introduction:  

Ways of preserving goods have been in development since the prehistoric ages. With  the first known preservative being salt, developments in both science and technology have  allowed for synthetic preservatives to be preferred in place of natural ones (The European Food  Information Council, 2022). Parabens, a type of synthetic preservatives, are known for their  multipurpose anti-microbial properties. This has made them staple ingredients in modern-day  personal care products, leading to an increase in the amount of parabens absorbed, ingested,  and/or inhaled. This increased exposure, in turn, has led to the discovery of the adverse effects  of parabens on the female endocrine system and their classification as endocrine disrupters  (EDCs). This literature review will focus on the adverse impacts of parabens on the female  endocrine system.  

Female Endocrine System: 

The endocrine system can be defined as: 

“[The system that] (…) regulates all biological processes in the body from conception  through adulthood and into old age, including the development of the brain and  nervous system, the growth and function of the reproductive system, as well as the  metabolism and blood sugar levels.” (“Overview of the Endocrine System”, 2023).  

This system is comprised of various key organs and glands, many of which overlap in males  and females (e.g., pineal, pituitary, parathyroid, thyroid, adrenal glands, and pancreas). The  presence of ovaries and the secretions of hormones from the pituitary gland are specific to those  assigned at females at birth (AFAB) and are responsible for the development of secondary  sexual characteristics (“Overview of the Endocrine System”, 2023). The pituitary gland  secretes follicle-stimulating hormone (FSH) and luteinizing hormone (LH), while the ovaries  secrete estrogen and progesterone. Estrogen and progesterone are the hormones that cause  secondary sexual characteristics such as breast development, the beginning of menstruation,  and hair growth on the underarms, legs, and pubic region (Eske, 2019). An increase in estrogen 

EFFECTS OF PARABENS ON THE FEMALE ENDOCRINE SYSTEM 4 

is also the cause of the thickening of the uterine lining before and after menstruation, with a  decrease in progesterone being the reason for menstruation occurring. FSH is the primary  hormone responsible for the development of follicles (potential eggs) in the ovaries. LH  stimulates ovulation, which is the release of an egg from the ovary into the oviducts. Estrogen,  progesterone, FSH, and LH all have set concentrations in the blood and work in accordance  with each other, utilizing a negative feedback loop. The menstrual cycle depends on these  hormones, and disruption to any of these hormones is responsible for delayed and/or absent  periods, heavy bleeding, and irregular cycle lengths (Eske, 2019).  

Parabens: 

Parabens are esters of para-hydroxybenzoic acid (see Figure 1,  

Source: Cashman & Warshaw, 2005). Almost all commercially used  parabens are synthetic, despite many being found in nature. They are  produced in an esterification reaction where para-hydroxybenzoic acid is  reacted with an appropriate acid, such as methanol, ethanol, n-propanol, etc.,  determining the ester's R(variable)-group (Cashman & Warshaw, 2005). In  

turn, para-hydroxybenzoic acid is industrially produced through a modified  Kolbe-Schmitt reaction, where the original reactant of sodium phenoxide is  

Figure 1 

General chemical  structure of a paraben

replaced with potassium phenoxide and heated with carbon dioxide (Valkova et al., 2001). Due  to their chemical structure, parabens possess a versatile set of antimicrobial properties that  allow for the extension of the shelf-life of many consumer goods such as hair care products  (e.g., shampoos, conditioners, hair creams, etc.), moisturizers, makeup, shaving creams, and  pharmaceutical (Stoiber, 2019). Their ability to dissolve in water makes them a common  preservative in foods and beverages, for example, frozen dairy products (e.g., ice cream), soft  drinks, processed vegetables, and flavoring syrups. More than one paraben can be used in a  single product at a time, with common combinations being methyl- and ethyl-paraben  

EFFECTS OF PARABENS ON THE FEMALE ENDOCRINE SYSTEM 5 

(Cashman & Warshaw, 2005). This causes parabens to have a wide medium of exposure,  including, but not limited to, inhalation, dermal absorption, and ingestion. Since parabens are  widely utilized in industrial production, exposure to these esters is ubiquitous, starting from  childhood to early teenage years (Kim & Chervier, 2020). 

Parabens and the Female Endocrine System:  

Parabens have a chemical structure similar to estrogen, leading to them being  considered EDCs. due to their ability to rapidly metabolize, mimicking the estrogenic effect on  the female body. This, in turn, causes parabens to interfere with other estrogen-catabolic or  conjugating enzymes (Sandborgh-Englund et al., 2017). This results in elevated estrogen  levels, with symptoms such as heavy and/or irregular periods, weight gain, fibroids, breast  cysts, endometriosis, gallbladder disease,  

thyroid disorders, and sleep disturbances (see  

Figure 2 for further information; Source: Laws  

et al., 2021). Another result of high estrogen 

levels is an increased risk of breast cancer.  

Estrogen stimulates the development of breast  

tissue by increasing the rate of cell growth in  

Figure 2  

Diagram showing effects of parabens on the  female reproductive system

the breast. However, unlike normally  developed cells, parabens cause a decrease in  

the cell death rate, which is the body’s way of dealing with damaged and/or mutated cells. In a  study conducted by the Breast Cancer Prevention Partners (n.d.), it was observed that for in  vitro cells, after 20 weeks of exposure to different parabens, the persistence of these cells in  the body increases the risk of metastasized tumors. 

Estrogen is responsible for the development of secondary sexual characteristics. Studies  in this area reported that there has been a significant decrease in the median age of puberty in  

EFFECTS OF PARABENS ON THE FEMALE ENDOCRINE SYSTEM 6 

girls, a drastic fall from 16.5 in the 1840s to 11.9 in 2022 in the United States. This decrease in  the median age of puberty has been linked to the increased use of parabens throughout the 20th and 21st centuries. Dr Kim Harley, Associate Professor in Public Health at the University of  California, reported that their study “found evidence that some chemicals widely used in  personal care products are associated with earlier puberty in girls” (Independent, 2018). It was  also found that mothers who had exposure to high levels of parabens during their pregnancy  gave birth to daughters who went through puberty earlier, as seen by the decrease in the median  age of puberty over the years. 

Another group of studies showed that mothers’ (over)exposure to parabens during  pregnancy leads to a number of negative consequences (e.g., early puberty, childhood obesity,  preterm birth, etc.). Leppert et al. (2020) found that the children of mothers who were exposed  to parabens in high concentrations had a greater risk of developing childhood obesity. In their  in-vitro study on mouse models, they demonstrated that maternal exposure to parabens resulted  in increased food intake and weight gain in female offspring. This was supported by a closer  inspection of the hypothalamus, which plays a vital role in the satiation felt after eating. It was  found that a “gene by the name of proopiomelanocortin (POMC) that is decisive in controlling  the feeling of hunger was down-regulated in the brains of the young mice” (Berlin Institute of  Health, 2019). Besides an increased rate of childhood obesity, parabens also increase the  likelihood of preterm birth, with the conceived babies having a lower gestational age at birth,  lower birth weight, and decreased body length (Mustela, n.d.). Preterm is linked to immediate  complications such as underdeveloped organs (e.g., lungs, heart, brain, digestive system, etc.),  trouble regulating their core body temperature, a weakened immune system and later-occurring  complications such as learning complications, developmental issues (e.g., poor vision, auditory  processing, and dental health), and behavioral issues (Mayo Clinic, n.d.). 

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Conclusion:  

Parabens are a group of synthetic preservatives that have different industrial uses. From  shampoos to foods and beverages, parabens are a staple of 21st-century modern goods. Due to  their similarities in chemical structure to estrogen, parabens have been classified as EDCs,  resulting in their tight regulation in the United States and ban in Europe. Research about the  disruptive nature of parabens in relation to the female endocrine system is still ongoing, as  exposure to parabens is ubiquitous. Despite this, research done so far has shown three critical  consequences of paraben (over)use/(over)exposure. First, the presence of parabens in the body  increases the risk of breast cancer. Second, the median age of puberty has decreased due to the  rise in the use of parabens in the 20th and 21st centuries with girls who had mothers exposed  to high concentrations of parabens going through puberty at least a month earlier than their  mothers. Finally, pregnancies are negatively affected by parabens. Overexposure to parabens  may lead to premature birth and later-occurring developmental problems. The findings of  present-day research point in the direction that consumers should prefer paraben-free versions  of products to minimize or, if possible, avoid the aforementioned adverse effects of parabens. 

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