Earth 2022 and Beyond: Strategic Avoidance of Female Health Risks
CHRIS D. MELETIS, ND
KIMBERLY WILKES, BSC
There is the tendency to implement identical protocols when treating women and men. However, it must be acknowledged that there are indeed gender differences. Women are more at risk of certain diseases, they can present with different symptoms and signs, they respond differently to therapy, and they tolerate and cope with certain health conditions differently than men.1 Consequently, in today’s world of cookbook medicine, it is important to realize that gender differences may require a conscious application of differentiated treatment algorithms. Ideally, however, whenever possible, we want to take a proactive stance in order to reduce the risks to female health before they can manifest. This is especially true in regards to exposure to toxins. In this article, we will focus on prevention and avoidance of common female risk factors for disease. The discussion will not be exhaustive, as it would take a tome to address such an expansive topic. However, we will pay close attention to 3 aspects of female health: 1) exposure to toxins; 2) other epigenetic factors; and 3) mitochondrial health.
Diseases That Affect Women Differently
Women are at greater risk for the development and progression of certain diseases. Autoimmune disorders, cardiovascular disease, chronic kidney disease, and dry eye syndrome all illustrate the effect that being female has on various disease states.
Women are disproportionately affected by autoimmune disease compared with men. It is estimated that approximately 80% of all patients diagnosed with autoimmune disease are women.2 In addition, women are twice as likely as men to develop autoimmune disease.2 Furthermore, compared with men, women are more likely to have more than 1 autoimmune disorder.3
A couple of different factors are implicated in the increased risk of autoimmune diseases among women. First, genetics play a role. The X chromosome has a larger number of genes. Because women have 2 X chromosomes, they’re more likely to experience a larger number of mutations that put them at risk of developing autoimmune disorders.2 Hormonal alterations are also involved. Autoimmune conditions often develop during major hormonal shifts, such as during puberty, pregnancy, and menopause.4 For example, in systemic lupus erythematosus (SLE), disease flare-ups often occur during pregnancy.4 Conversely, treating postmenopausal women with estrogen protects against active rheumatoid arthritis (RA) and osteoporosis.4 Finally, women are often exposed to more toxins that could predispose to autoimmune disorders and other diseases, a concept we’ll address in more detail later in this article.
In both females and males, cardiovascular disease (CVD) is the primary cause of death. However, annually, CVD kills more women than men.5 Sex hormones are involved in the development and progression of CVD.6 The decline in estrogen during menopause is thought to be related to increased CVD risk in aging women.5 Estrogen has been shown to modulate serotonin-induced vasoconstriction and to induce vasodilation,7 indicating it plays an important role in CVD health. Furthermore, hormonal alterations in women affect microvascular and endothelial function, vascular anatomy, systemic inflammation, and myocardial contractility.8
Women suffering from heart disease often present later than men do, they undergo care that is developed from data obtained mostly from male subjects, and they often have inferior access to diagnostic and therapeutic resources.8 Additionally, women are more susceptible to traditional cardiovascular risk factors such as type 2 diabetes, obesity, depression, and stress.8 For example, even moderate or borderline hypertension (<140/90 mm Hg) leads to more endothelial dysfunction and cardiovascular complications in females than in males.9
In my clinical experience, the novel key to addressing cardiovascular health in women is supporting the health of the mitochondria. One way this can be done is by modulating nicotinamide adenine dinucleotide (NAD+) pathways through supplementation with nicotinamide riboside, a compound that is highly effective at raising NAD+ levels.10 NAD+ is an essential resource for cellular energy production. The reduced form of NAD+ (NADH) is critical to the mitochondrial production of adenosine triphosphate (ATP).11 Conversely, low levels of NAD+ may be involved in mitochondrial dysfunction.12 Low NAD+ occurs in many diseases including cardiovascular.11
Chronic Kidney Disease
In patients with chronic kidney disease, there are sex/gender differences in kidney pathophysiology, kidney disease progression, outcomes, and management of hemodialysis treatment.1 Estrogen is thought to protect against chronic kidney disease.13 Therefore, the drop in estrogen levels that occur during menopause may leave women more vulnerable to renal problems.13 Estrogen triggers the release of nitric oxide (NO), which causes vasodilation in the renal vessels, lowers inflammation, and reduces ischemia mediators.13
Dry Eye Disease
Dry eye disease (DED) is a condition that can result in discomfort, pain, and disturbed vision. Compared to men, women are affected more often by DED, are diagnosed at an earlier age, and suffer from more intense symptoms.14 There is also a strong relationship between DED and autoimmune disorders, especially those that affect women more than men.14 The good news, however, is that women respond better to a wellness model of treatment compared with men.14
Factors Affecting Women’s Health
A number of risk factors can encourage the development and progression of disease in women. Many of these factors, such as environmental toxins, mental stress, obesity, and oral contraceptives, have epigenetic effects. Epigenetics are changes to gene expression (such as that which occurs during DNA methylation), rather than alterations to the genetic code itself. Epigenetic changes are caused by a person’s environment and behavior and can impact a woman’s genetic potential to tolerate a hostile ecology, whether it is exposure to environmental toxins or poor nutrition. That is why a women’s health journey really begins in utero. Epigenetic exposures can ripple through the generations. If a woman’s mother or grandmother experiences an epigenetic threat, its effects will be passed on to future generations. All of the risk factors mentioned below should be kept in mind when ensuring the optimal health of our female patients.
A risk factor unique to women is the use of hormonal birth control. Oral contraceptives (OCs) are associated with many adverse aspects of women’s health. For example, the use of OCs elevates cortisol.15 OCs are also associated with an increased risk of CVD.16 Use of oral contraceptives is linked to an increased risk of both venous and arterial thrombosis, especially in smokers and women with hypertension, diabetes, and high cholesterol.17 This risk increases with age.17 Use of hormonal contraceptives also correlates with subsequent use of antidepressants and first diagnosis of depression, especially among adolescents.18 Some or all of these adverse effects may be caused by epigenetic alterations, as OCs are known to modify DNA methylation.19 However, it should be noted that OCs may have a protective effect against endometrial and ovarian cancer.16
We have succeeded within the last 120 years or so to come up with new ways to sabotage our very existence. If just 1 woman was to be unduly exposed to a ubiquitous human-made chemical through no fault of her own actions, there rightfully should be a resounding outraged reaction. Yet, according to the latest global estimate, there are 3.905 billion females on planet earth.20 And all of these women are being exposed to countless chemicals on a daily basis.
In the workplace, women are exposed to toxins at a greater rate than men.21 This is because women worldwide are well represented in chemical-heavy industries (such as electronics and textiles) and experience worse working conditions compared with men.21
Biological factors also play a role. For instance, women have a higher prevalence of adipose tissue compared with men and are therefore more likely to store toxins in their bodies.21
In those females that choose to procreate and foster the creation of the next generation(s), there is an additional concern at a humanity level. Exposure to toxins is not just about the toxic milieu of a lifetime of burden that a woman and her children may experience from birth, but also about the passage of the very mitochondrial integrity that sustains all genders. When an egg is fertilized, it is the mother’s mitochondrial genes that are inherited.22 The father’s mitochondria, on the other hand, do not survive.22
Mitochondria are adversely impacted by exposure to toxins.23 Furthermore, mitochondrial damage plays an important role in much of the harm that occurs to a baby in a mother’s womb due to exposure to pesticides, herbicides, and other chemicals. Throughout a woman’s life, exposure to toxins is associated with the pathogenesis of a number of chronic diseases, such as different types of cancers, diabetes, Parkinson’s, Alzheimer’s, amyotrophic lateral sclerosis (ALS), and reproductive disorders.23 Some evidence also exists that pesticide and herbicide exposure may be linked to the development of asthma, chronic obstructive pulmonary disease, cardiovascular and kidney diseases, autoimmune disease such as SLE and RA, chronic fatigue syndrome, and aging.23 Some of the negative effect of exposure to toxins is mediated by their ability to induce mitochondrial dysfunction.23 Many agricultural chemicals are known to suppress mitochondrial transport chain activity.23 As noted under the cardiovascular health section of this article, nicotinamide riboside is an effective and useful tool for optimizing mitochondrial function and can be used to support mitochondrial health in women.
In regards to toxins, there are some generally agreed upon concepts:
- A human has a finite ability to handle and process toxins
- Detoxifying requires substantial biochemical effort
- Toxins can alter homeostasis
- Toxins add to the allostatic load, and without sufficient adaptive capacity, fuel disease risk
Prevention and avoidance of as many toxins as possible, rather than mechanisms to mitigate the effects of a given exposure, is always the best solution. There are already well-established testing and therapeutic approaches for removal of many known toxins. However, from my clinical experience, none of them are easy or provide results that equal not having been exposed in the first place. Even so, I do emphasize the importance of detoxification to women who are undergoing a weight loss program in order to mitigate the effect of toxins being released from adipose tissue.
Nevertheless, I focus on minimizing exposure by avoiding common chemicals such as phthalates, parabens, bisphenol-A (BPA), and other toxins such as pesticides and herbicides. Phthalates are used to make plastics flexible. They’re found in food packaging and materials used to process food, as well as in medical tubing and vinyl flooring. They’re also found in fragrances used in personal care and cleaning products. Parabens are artificial preservatives found in body care products such as shampoo, conditioner, and cosmetics. BPA is a chemical used to make plastics and epoxy resins. It can be found in baby bottles, food containers, and the inner lining of canned foods.
Many of these chemicals can mimic the actions of estrogen in the body and thus cause reproductive harm and other diseases in women.24 For example, studies have shown that women with polycystic ovarian syndrome (PCOS) had notably higher levels of BPA in the blood, serum, and follicular fluid compared with women without PCOS.24 Likewise, levels of BPA were higher in women with endometriosis compared with women without endometriosis, and women with fibroids had higher levels of BPA compared with women who did not have fibroids.24 Female patients should be urged to use products that do not contain these toxins and to eat organic food whenever possible to minimize exposure to pesticides and herbicides.
Toxins can be inhaled, ingested, and absorbed transdermally or intravenously including during medical procedures. Toxic exposure includes electromagnetic fields and radiation. One of the most widespread toxins is air pollution, which is known to affect fertility.25 Furthermore, women who live in urban areas, which have more air pollution than rural areas, may have significantly higher risks of breast, cervical, kidney, and brain cancer compared to women who live in rural areas.26 However, it should be kept in mind that due to the wildfires that have run rampant in many areas, air pollution knows no boundaries. Pregnant women are particularly susceptible to the effects of the PM 2.5 produced by wildfire smoke.27
Pregnant and lactating women should also be especially mindful of exposure to fluoride. Approximately 74% of Americans and 38% of Canadians are drinking municipal water containing added fluoride.28 Infants exposed to high levels of fluoride in tap water have reduced non-verbal intellectual abilities, indicating that fluoride may impair IQ.28 The effect has been more noticeable in formula-fed children, who are exposed to greater levels of fluoride than breastfed infants due to the reconstitution of formula with fluoridated water.28 Therefore, in pregnant and lactating patients, it is essential to emphasize the importance of breastfeeding.
One of the harmful effects caused by environmental toxins is their ability to fuel metabolic syndrome and weight gain,29 leading to an array of health concerns. For example, in animals, BPA can cause insulin resistance, potentially increasing the risk of type 2 diabetes, hypertension, and lipid imbalances.30 Metabolic syndrome is especially common in women with PCOS. In one study, 34.9% of women with PCOS had metabolic syndrome compared to only 6.8% of controls.31 When adjusted for age, 47.3% of women with PCOS had metabolic syndrome compared with 4.3% of women in the control group.31
Epigenetic alterations can contribute to obesity and type 2 diabetes. Lifestyle factors such as exercise and diet interact with the human epigenome and can counteract negative effects associated with adverse epigenetic changes.32 Women are busier than ever and often lead a sedentary lifestyle. Practitioners should emphasize the importance of exercising daily.
Women and men are known to have different responses to mental stress. When under mental stress, women have been shown to have more mental stress-induced myocardial ischemia, express more negative and less positive emotion, and have higher collagen-stimulated platelet aggregation responses compared with men.33 In addition, men are more likely than women to exhibit alterations in traditional physiological measures, such as blood pressure.33 It is extremely important that pregnant women tend to their mental health in order to prevent long-lasting effects in their child. Offspring of mothers who experience stress, depression, and anxiety during pregnancy undergo epigenetic modifications that serve as risk factors for developmental delay, as well as emotional and behavioral problems.34 We as providers can urge female patients to participate in relaxation techniques.
Special Testing in Women
There are specific tests I utilize in female patients to address their unique needs. One of these is the CA-125 blood test, which is a marker for ovarian cancer. A test I often order in women who have had breast cancer is CA-27.29, which serves as an early marker of recurrence among these women. These tests and others (such as CEA), though not recommended as screening tests, can serve as alters for closer diagnostics.
Additionally, running an organic acids profile along with an environmental pollutant panel can offer insights into mitochondrial function and xenoestrogen toxic burden. It is important to ensure that the gastrointestinal tract has a sufficiently balanced microbiome, leaky gut is not present, diverse eubiotic colonization is present, and beta-glucuronidase activity is not excessive. Testing nitric oxide (NO) levels with home or in-office salivary test strips can also help quantify NO insufficiency and allow for target thresholds to be optimized.
Research indicates that we as providers may need to adapt our medical interventions when treating female patients. Furthermore, women may be more vulnerable to certain risk factors such as environmental toxins and may have other gender-specific risk factors such as oral contraceptives. We are united as a human race regardless of gender. However, when it comes to treating individual patients, unique biochemical pathways and hormonal receptor activity, epigenetic and other functional medicine considerations are warranted. The peer-review literature supports individual care no matter the gender, socioeconomics, and ethnicity. When there is compelling or suggestive scientific literature, we as providers must use our clinically trained and scientific minds to look at the deeper life journey including epigenetic exposures experienced by parents and grandparents, not just the moment that a patient presents to our clinic.
- Cobo G, Hecking M, Port FK, et al. Sex and gender differences in chronic kidney disease: progression to end-stage renal disease and haemodialysis. Clin Sci (Lond). 2016;130(14):1147-1163.
- Angum F, Khan T, Kaler J, et al. The Prevalence of Autoimmune Disorders in Women: A Narrative Review. Cureus. 2020;12(5):e8094.
- Desai MK, Brinton RD. Autoimmune Disease in Women: Endocrine Transition and Risk Across the Lifespan. Front Endocrinol (Lausanne). 2019;10:265.
- Walker SE. Estrogen and autoimmune disease. Clin Rev Allergy Immunol. 2011;40(1):60-65.
- Giordano S, Hage FG, Xing D, et al. Estrogen and Cardiovascular Disease: Is Timing Everything? Am J Med Sci. 2015;350(1):27-35.
- Ahn SY, Choi YJ, Kim J, et al. The beneficial effects of menopausal hormone therapy on renal survival in postmenopausal Korean women from a nationwide health survey. Sci Rep. 2021;11(1):15418.
- Kim JG, Leem YE, Kwon I, et al. Estrogen modulates serotonin effects on vasoconstriction through Src inhibition. Exp Mol Med. 2018;50(12):1-9.
- Leonard EA, Marshall RJ. Cardiovascular Disease in Women. Prim Care. 2018;45(1):131-141.
- Collins P, Webb CM, de Villiers TJ, et al. Cardiovascular risk assessment in women – an update. Climacteric. 2016;19(4):329-336.
- Martens CR, Denman BA, Mazzo MR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD(+) in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286.
- Fang EF, Lautrup S, Hou Y, et al. NAD(+) in Aging: Molecular Mechanisms and Translational Implications. Trends Mol Med. 2017;23(10):899-916.
- Fang EF, Scheibye-Knudsen M, Brace LE, et al. Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)/SIRT1 reduction. Cell. 2014;157(4):882-896.
- Farahmand M, Ramezani Tehrani F, et al. Endogenous estrogen exposure and chronic kidney disease; a 15-year prospective cohort study. BMC Endocr Disord. 2021;21(1):155.
- Matossian C, McDonald M, Donaldson KE, et al. Dry Eye Disease: Consideration for Women’s Health. J Womens Health (Larchmt). 2019;28(4):502-514.
- Eick C, Klinger-König J, Zylla S, et al. Broad Metabolome Alterations Associated with the Intake of Oral Contraceptives Are Mediated by Cortisol in Premenopausal Women. Metabolites. 2021;11(4).
- Xu B, Xu Z. Oral contraceptive and risk of disease. Zhonghua Fu Chan Ke Za Zhi. 1996;31(12):724-727. [Article in Chinese]
- Tanis BC, Rosendaal FR. Venous and arterial thrombosis during oral contraceptive use: risks and risk factors. Semin Vasc Med. 2003;3(1):69-84.
- Skovlund CW, Mørch LS, Kessing LV, Lidegaard Ø. Association of Hormonal Contraception With Depression. JAMA Psychiatry. 2016;73(11):1154-1162.
- Campesi I, Sanna M, Zinellu A, et al. Oral contraceptives modify DNA methylation and monocyte-derived macrophage function. Biol Sex Differ. 2012;3:4.
- Statistics Times. Gender Ratio in the World. Available at: https://statisticstimes.com/demographics/world-sex-ratio.php. August 26, 2021. Accessed October 19, 2021.
- Brosché S. Women, Chemicals and the SDGs. IPEN for a Toxics-Free Future. 2021. Available at: https://ipen.org/sites/default/files/documents/ipen-gender-chemicals-report-v1_6dw-en.pdf. Accessed October 19, 2021.
- Kramer P, Bressan P. Our (Mother’s) Mitochondria and Our Mind. Perspect Psychol Sci. 2018;13(1):88-100.
- Mostafalou S, Abdollahi M. Pesticides and human chronic diseases: evidences, mechanisms, and perspectives. Toxicol Appl Pharmacol. 2013;268(2):157-177.
- Chiang C, Mahalingam S, Flaws JA. Environmental Contaminants Affecting Fertility and Somatic Health. Semin Reprod Med. 2017;35(3):241-249.
- Canipari R, De Santis L, Cecconi S. Female Fertility and Environmental Pollution. Int J Environ Res Public Health. 2020;17(23):8802.
- Sharp L, Donnelly D, Hegarty A, et al. Risk of several cancers is higher in urban areas after adjusting for socioeconomic status. Results from a two-country population-based study of 18 common cancers. J Urban Health. 2014;91(3):510-525.
- Cascio WE. Wildland fire smoke and human health. Sci Total Environ. 2018;624:586-595.
- Till C, Green R, Flora D, et al. Fluoride exposure from infant formula and child IQ in a Canadian birth cohort. Environ Int. 2020;134:105315.
- Ropero AB, Alonso-Magdalena P, Quesada I, Nadal A. The role of estrogen receptors in the control of energy and glucose homeostasis. Steroids. 2008;73(9-10):874-879.
- Alonso-Magdalena P, Morimoto S, Ripoll C, et al. The estrogenic effect of bisphenol A disrupts pancreatic beta-cell function in vivo and induces insulin resistance. Environ Health Perspect. 2006;114(1):106-112.
- Azziz R. How prevalent is metabolic syndrome in women with polycystic ovary syndrome? Nat Clin Pract Endocrinol Metab. 2006;2(3):132-133.
- Ling C, Rönn T. Epigenetics in Human Obesity and Type 2 Diabetes. Cell Metab. 2019;29(5):1028-1044.
- Samad Z, Boyle S, Ersboll M, et al. Sex differences in platelet reactivity and cardiovascular and psychological response to mental stress in patients with stable ischemic heart disease: insights from the REMIT study. J Am Coll Cardiol. 2014;64(16):1669-1678.
- Stonawski V, Frey S, Golub Y, et al. Epigenetic modifications in children associated with maternal emotional stress during pregnancy. Z Kinder Jugendpsychiatr Psychother. 2018;46(2):155-167. [Article in German]
Chris D. Meletis, ND is an educator, international author, and lecturer. He has authored 18 books and more than 200 scientific articles in prominent journals and magazines. Dr Meletis served as Dean of Naturopathic Medicine and CMO for 7 years at NUNM. He was recently awarded the NUNM Hall of Fame award by OANP, as well as the 2003 Physician of the Year by the AANP. Dr Meletis spearheaded the creation of 16 free natural medicine healthcare clinics in Portland, OR. Dr Meletis serves as an educational consultant for Fairhaven Health, Berkeley Life, TruGen3, US BioTek, and TruNiagen. He has practiced in Beaverton, OR, since 1992.
Kimberly Wilkes, BSc, has more than 2 decades of experience as a health and medical writer. She has authored or co-written articles that have appeared in publications such as Alternative Therapies in Health and Medicine, Integrative Medicine Journal, Townsend Letter, and Whole Health Insider. She frequently coauthors and edits books for doctors, including The Disciples’ Diet with Chris D. Meletis, ND. Her writing covers a vast array of health-related topics, including fertility in women and men, the endocannabinoid system, and the potential benefits of low-intensity extracorporeal shock wave therapy (Li-ESWT) in erectile dysfunction.