Exposome in the News! Exposome Day: “Menopause and Environmental Exposures”

Exposome Day is celebrated on the second Wednesday of May.

It was established in 2022 at the Icahn School of Medicine at Mount Sinai, USA. Exposome Day aims to build awareness about how the environment shapes health from pregnancy through adulthood, as well as the health of future generations.

The 2023 Exposome Day webinar topic of discussion was “Women’s Health over 40: Menopause and Environmental Exposures.” The webinar was moderated by Dr. Sarah Evans, Assistant Professor of Environmental Medicine and Public Health for the Icahn School of Medicine at Mount Sinai.

Dr. Evans welcomed the speakers and audience attending Exposome Day 2023. She stated, “The webinar speakers are leading environmental health and exposomic scientists. They will discuss what is known and the research gaps regarding environmental exposures — from chemicals, nutrition, air pollution, and non-chemical exposures such as stress. They will also focus on the transition to menopause and what women can do to reduce harmful exposures.” 

Hormone Replacement Therapy and the Exposome 

The first speaker of the webinar was Dr. Rosalind Wright, Dean of Translational Biomedical Sciences and Co-Director of the Institute for Exposomic Research at the Icahn School of Medicine at Mount Sinai. Dr. Wright discussed the conflicting results from studies on hormones and women's health. She highlighted that there are a number of factors that should be considered before hormone replacement therapy (HRT).

She shared that pregnancy is a critical life course dimension, and there are windows of opportunity in studying the pregnancy exposome as pregnant women are exposed to external outdoor environments (ambient air pollution, allergens, green space, rural vs. urban environments, and climate), external indoor environments (smoking, diets, metals, indoor air pollution, molds, and family level stress), and internal environments (genomics, transcriptomics, metabolomics, epigenomics, and microbiome) that could lead to multiple physiological effects on them and their children.

Dr. Wright shed light on changing the perspective on the role of HRT in cancer by including exposome analysis for a better understanding. She also said that the future of medicine involves exposome analysis. In addition, she shared that she had started her career as a geneticist and has now moved to study the exposome as it provides a more holistic picture. Her concluding remarks were on the role of stress in maternal mortality, pregnancy, and overall women's health.

She also suggested some tips for keeping hormone levels in women's bodies balanced, which include:

1. Getting a good night's sleep
2. Regular exercise
3. Having an antioxidant-rich diet
4. Drinking adequate water
5. Living a stress-less life

#5 may be a stretch here but it's essential to find good ways to stress mitigate! Meditate, have sex, belly laugh, and/or use Tro Calm! 

PFAS and The Menopause Transition

The next speaker was Dr. Ronit Machtinger, Associate Professor at Sheba Medical Center in Tel-Aviv University. Her lecture was titled “Menopause Transition and Menopause.” In her lecture, she spoke about the vulnerable stages in women's health and how they get impacted by exposure to various chemicals like bisphenol A (BPA), heavy metals, phthalates, and per- and poly-fluoroalkyl substances (PFAS). She emphasized that PFAS is one of the most commonly available toxicants in our daily usage. It is present in non-stick cookware, fast food wrappers, cosmetics, cleaning supplies, and personal care products.

Exposure to PFAS is associated with an increased risk of gestational diabetes, placental dysfunction, adverse health outcomes, preeclampsia, and low birth weight [1]. She also discussed that most shampoos have phthalates as one of their ingredients. Exposure to phthalates is associated with a 15% increase in per-term childbirth [2], early menopausal symptoms [3], and fewer fertilized oocytes [4].

BPA can be ingested after it seeps into foods and beverages from plastic containers and can linings. BPA is a known endocrine disruptor chemical (EDCs) that impacts estrogen levels in women [5]; exposure to BPA is also associated with adverse birth outcomes and lower child weight at birth [6,7].

Dr. Machtinger also relayed that pesticide residue intake by consuming fruits and vegetables may have an adverse impact on women's health. Studies have found that dietary pesticide exposure within the range of typical human exposure may be associated with adverse reproductive consequences like decreased fecundability, decreased fertilization rate, decreased number of high-quality embryos, and increased risk of miscarriage [8]. 

She also highlighted that studies had shown that menopausal symptoms arrive almost five years earlier than the final menstrual period [9]. She then went on to discuss various factors affecting the menopausal transition, the most common of which are [10]:

1. Obesity: Related to the later onset of the menopausal transition
2. Race: African American women were shown to have a longer duration of the menopausal transition than White women
3. Smoking: Associated with earlier entry into the menopausal transition and a shorter duration of the transition

She also discussed the common symptoms of the menopausal transition, which include:

1. Vasomotor symptoms (VMS): VMS are episodes of profuse heat accompanied by sweating and flushing, experienced predominantly around the head, neck, chest, and upper back. These episodes lower quality of life. It starts five years before the FMP and can last for ten years [10,11]
2. Mood disorders [10]: Mood disorders are common during the menopause transition. The emotional disorders during menopause transitions are mood swings, anxiety, and depression. There is a 2-5-fold higher risk for major depressive episodes during perimenopause than late pre-menopause.
3. Temporary cognitive dysfunction [10]: : Some of the common cognitive dysfunctions during the menopause transition include cognitive decline, difficulty sleeping, and a decrease in libido.
4. Genitourinary symptoms: Including atrophy of the vulva and vagina, vaginal dryness, vaginal narrowing and shortening, uterine prolapse, and urinary incontinence [10].

She concluded her lecture by stressing that menopausal transition is affected by genetics, environment, and lifestyle of the individuals.

Quick side note: We've have many perimenopausal women swear by Blue Cannatine to help with the brain fog that can happen during this time. 

Menopause and Environmental Exposure

The last lecture of the webinar was by Dr. Lauren Petrick, Associate Professor of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai and Sheba Medical Center.

Her topic was “Menopause and Environmental Exposure.” She stated menopausal symptoms occur up to a decade before the last menstrual period. She also informed the audience that an earlier age at menopause is associated with an increased cancer risk.

In contrast, later age at menopause is associated with longer life expectancy, less bone density loss, and reduced risk of cardiovascular disease. She highlighted how exposure to EDCs is associated with earlier menopause. She also discussed the role of PFAS, BPA, and other toxicants on women's health and menopause. 

Dr. Petrick also discussed the role of air pollution in women's reproductive health. She advocated for an exposomic approach to understanding women's reproductive health as women throughout their life undergo exposure to EDCs, pollution, metals, pesticides, nutrition, medication, and changes in lifestyle which impact their microbiome, genome, proteome, and metabolome, thus impacting their overall health. 

She described her recent research which has found an association between exposure to air pollution during pregnancy and postpartum depression [12]. Her research group is using an untargeted metabolomics exposomic approach to find molecular mechanisms. She shared that they have discovered that exposure to PM2.5 during pregnancy is positively associated with an increased risk of postpartum depression [12]. Their exposomic approach linked inflammation, PM2.5, and postpartum depression. They also found that itaconate, a biomarker for postpartum depression, was found to be increased with PM2.5 exposure in their untargeted metabolomics study [13].

Final Thoughts

At the end of the webinar, all speakers unequivocally advocated for more exposome-based research on reproductive health.

Dr. Petrick suggested that minimally invasive sampling techniques are needed for better sample collection for exposome analysis.

Dr. Machtinger concluded that over the past few decades, increased pollution and exposure to chemicals have significantly impacted our overall reproductive health. She said that their group had observed a decrease in sperm value, quality, and quantity due to said exposure [14].

Dr. Wright emphasized how leading a healthy lifestyle with reduced stress could elevate women's reproductive health quality. She also advocated regular exercise and meditation for a healthy lifestyle. 

Troscriptions note: This is why it is so important to be aware as much as possible of potential exposures and, at the same time, detect and correct for them. If you are a clinician, check out homehope.org and the exposomics module for more information.

References

1. Szilagyi, J. T., Avula, V. & Fry, R. C. Perfluoroalkyl substances (PFAS) and their effects on the placenta, pregnancy, and child development: a potential mechanistic role for placental peroxisome proliferator–activated receptors (PPARs). Curr Environ Health Rep 7, 222–230 (2020).
2. Welch, B. M. et al. Associations between prenatal urinary biomarkers of phthalate exposure and preterm birth: a pooled study of 16 US cohorts. JAMA Pediatr 176, 895–905 (2022).
3. Ziv-Gal, A. et al. Phthalate metabolite levels and menopausal hot flashes in midlife women. Reproductive toxicology 60, 76–81 (2016).
4. Machtinger, R. et al. Urinary concentrations of biomarkers of phthalates and phthalate alternatives and IVF outcomes. Environ Int 111, 23–31 (2018).
5. Hafezi, S. A. & Abdel-Rahman, W. M. The endocrine disruptor bisphenol A (BPA) exerts a wide range of effects in carcinogenesis and response to therapy. Curr Mol Pharmacol 12, 230 (2019).
6. Chang, C.-H. et al. Associations between prenatal exposure to bisphenol a and neonatal outcomes in a Taiwanese cohort study: Mediated through oxidative stress? Chemosphere 226, 290–297 (2019).
7. Zhou, Z. et al. Association between prenatal exposure to bisphenol a and birth outcomes: A systematic review with meta-analysis. Medicine 98, (2019).
8. Chiu, Y.-H. et al. Association between pesticide residue intake from consumption of fruits and vegetables and pregnancy outcomes among women undergoing infertility treatment with assisted reproductive technology. JAMA Intern Med 178, 17–26 (2018).
9. Santoro, N. et al. Menstrual cycle hormone changes in women traversing menopause: study of women’s health across the nation. J Clin Endocrinol Metab 102, 2218–2229 (2017).
10. Santoro, N., Roeca, C., Peters, B. A. & Neal-Perry, G. The menopause transition: signs, symptoms, and management options. J Clin Endocrinol Metab 106, 1–15 (2021).
11. Thurston, R. C. & Joffe, H. Vasomotor symptoms and menopause: findings from the Study of Women’s Health across the Nation. Obstetrics and Gynecology Clinics 38, 489–501 (2011).
12. Sheffield, P. E. et al. Association between particulate air pollution exposure during pregnancy and postpartum maternal psychological functioning. PLoS One 13, e0195267 (2018).
13. Niedzwiecki, M. M. et al. Untargeted metabolomic profiles of air pollution exposure during pregnancy and postpartum depression risk: a pilot study. in ISEE Conference Abstracts vol. 2020 (2020).
14. Wu, H. et al. Exposomic Analysis of Organic Pollutants in Seminal Plasma and Male Reproductive Parameters. in ISEE Conference Abstracts vol. 2022 (2022).