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)
EFFECTS OF PARABENS ON THE FEMALE ENDOCRINE SYSTEM 3
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.).
EFFECTS OF PARABENS ON THE FEMALE ENDOCRINE SYSTEM 7
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.
EFFECTS OF PARABENS ON THE FEMALE ENDOCRINE SYSTEM 8
References:
- Berlin Institute of Health. (2019). Overweight from Cosmetics: If Pregnant Women Use Parabens, This May Have Consequences.
https://www.bihealth.org/en/notices/overweight-from-cosmetics-if-pregnant-women use-parabens-this-may-have-consequences
- Brausch, J. M., & Rand, G. M. (2012). A review of personal care products in the aquatic environment: Environmental concentrations and toxicity. Chemosphere, 87(8), 809-817. https://link.springer.com/article/10.1007/s11270-016-2785-3
- Breast Cancer Prevention Partners. (n.d.). Parabens.
https://www.bcpp.org/resource/parabens/
- Carmina, E., & Lobo, R. A. (2017). Polycystic ovary syndrome (PCOS): Arguably the most common endocrinopathy is associated with significant morbidity in women. https://pubmed.ncbi.nlm.nih.gov/28356401/
- Centers for Disease Control and Prevention. (n.d.). Parabens Fact Sheet. https://www.cdc.gov/biomonitoring/Parabens_FactSheet.html
- Darbre, P. D., Harvey, P. W., & Degen, G. H. (2013). Assessment of the toxicological properties of parabens and their chlorinated derivatives—A review.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855500/
- European Food Information Council. (2022, October 1). What are preservatives and what are common examples used in food? https://www.eufic.org/en/whats-in food/article/what-are-preservatives-and-what-are-common-examples-used-in-food
- Golden, R., Gandy, J., Vollmer, G., & Slone, T. H. (2005). A review of the endocrine activity of parabens and implications for potential risks to human health. Critical Reviews in Toxicology, 35(5), 435-458.
https://www.sciencedirect.com/science/article/abs/pii/S0048969719351083 9. Independent (2018, December 6). Makeup may cause girls to hit puberty early, chemicals found in cosmetics, lotion and shampoo could lead to early hormone disruption, study suggests. The Independent.
https://www.independent.co.uk/news/health/makeup-puberty-girls-chemicals-early cosmetics-lotion-hormone-disruption-study-california-a8665711.html
- Leonard, J. A. (2019). The Effects of Hormones on the Body.
https://www.medicalnewstoday.com/articles/324887#:~:text=Role%20in%20puberty &text=Increased%20levels%20of%20estrogen%20and,underarms%2C%20legs%2C %20and%20pubic%20region
EFFECTS OF PARABENS ON THE FEMALE ENDOCRINE SYSTEM 9
- Leppert, B., Strunz, S., Seiwert, B., Schlittenbauer, L., Schlichting, R., Pfeiffer, C., Röder, S., Bauer, M., Borte, M., Stangl, G. I., Schöneberg, T., Schulz, A., Karkossa, I., Rolle-Kampczyk, U., Thürmann, L., Von Bergen, M., Escher, B. I., Junge, K. M., Reemtsma, T., . . . Polte, T. (2020, February 11). Maternal paraben exposure triggers childhood overweight development. Nature Communications; Nature Portfolio. https://doi.org/10.1038/s41467-019-14202-1
- Mayo Clinic. (n.d.). Premature Birth. https://www.mayoclinic.org/diseases conditions/premature-birth/symptoms-causes/syc-20376730
- Medical News Today. (2019). The Effects of Hormones on the Body. https://www.medicalnewstoday.com/articles/324887
- Merck Manuals. (n.d.). Menstrual Cycle.
https://www.msdmanuals.com/home/women-s-health-issues/biology-of-the-female reproductive-system/menstrual
cycle#:~:text=Estrogen%20and%20progesterone%20stimulate%20the,to%20prepare %20for%20possible%20fertilization.&text=The%20menstrual%20cycle%20has%20t hree,Ovulatory%20(egg%20release)
- Mustela USA. (n.d.). Are Parabens Safe for You and Your Newborn? https://www.mustelausa.com/blogs/mustela-mag/are-parabens-safe-for-you-and-your newborn
- Natalist. (n.d.). Avoiding Parabens When TTC and Pregnant.
https://natalist.com/blogs/learn/avoiding-parabens-when-ttc-and-pregnant 17. National Institute of Environmental Health Sciences. (2019). Endocrine Disruption. https://www.ncbi.nlm.nih.gov/books/NBK538260/
- Philippat, C., Wolff, M. S., Calafat, A. M., Ye, X., Bausell, R., Meadows, M., ... & Engel, S. M. (2013). Prenatal exposure to environmental phenols: Concentrations in amniotic fluid and variability in urinary concentrations during pregnancy. https://ehjournal.biomedcentral.com/articles/10.1186/s12940-020-00580-3
- Qasim, S., & Niazi, S. (2021). Comprehensive Effects of Parabens in Human Physiology. https://www.researchgate.net/profile/Seeham
Qasim/publication/351293008_Comprehensive_Effects_of_Parabens_in_Human_Phy siology/links/609bf01b299bf10fbb119711/Comprehensive-Effects-of-Parabens-in Human-Physiology.pdf
- Sandborgh-Englund, G., Adolfsson-Erici, M., Odham, G., & Ekstrand, J. (2006). Pharmacokinetics of parabens in humans after single oral and topical doses.
EFFECTS OF PARABENS ON THE FEMALE ENDOCRINE SYSTEM 10
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618656/#:~:text=Since%20parabens %20are%20rapidly%20metabolized,and%20human%20skin%20%5B7%5D. 21. Strauch, R. C. (2001). Health implications of parabens. Environmental Health Perspectives, 109(4), 485-491.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC92888/
- Tasha Stoiber. (2019, April 9). What Are Parabens? https://www.ewg.org/what-are parabens
- U.S. Environmental Protection Agency. (n.d.). Overview of the Endocrine System. https://www.epa.gov/endocrine-disruption/overview-endocrine-system 24. U.S. Food and Drug Administration. (n.d.). Parabens in Cosmetics. https://www.fda.gov/cosmetics/cosmetic-ingredients/parabens-cosmetics 25. WebMD. (n.d.). What to Know About Parabens.
https://www.webmd.com/beauty/what-to-know-about-parabens
