Chronic stress and its endocrine effect, namely the release of persistent stress hormones at subclinical thresholds, is thought to be causative or add to the risk of developing a panoply of illnesses/conditions, including cardiovascular disease, neurological disorders (including dementia), diabetes, obesity, depression, and cancer. Women, particularly those suffering from gynecologic issues (such as menopause, excessive menstrual bleeding, or pelvic pain), are especially susceptible to ME/CFS while a study by Song and colleagues in 2017 examined 101,708 male and female Japanese participants (gender ratio 1:1.05) and found a 4–6% increased overall risk of cancer based on perceived stress levels
[59,60][58][59]. Chronic diseases in women, especially immune-driven conditions such as fibromyalgia or lupus, may also be exacerbated by chronic stress or perceptions of it as a 2004 study of 56 Spanish women with SLE found that, while high-stress life events did not clinically worsen disease symptoms, women reported that their perceptions of exacerbations seemed to coincide with such events and, after 2 days of such stress, clinical biomarkers of SLE did increase
[61][60]. In a study of 100 polycystic ovarian syndrome sufferers, aged 13 to 30 years of age, an Indian study found strong correlation between stress levels (reflected in a 6.64% increase in salivary cortisol in PCOS patients) and overweight status, increasing future risk of insulin resistance and PCOS-related metabolic disruptions
[62][61]. Another Spanish study in 45 SLE patients (all female) found that cognitive behavioral therapy did alleviate somatic symptoms in sufferers compared to controls, highlighting the effect of stress on chronic disease exacerbation
[63][62]. Additionally, immune competence and resistance to disease depends on low levels of stress hormones and sufferers of ME/CFS were found to have higher levels of inflammatory biomarkers while activity of NK cells and CD16+CD56+ lymphocytes were found to be compromised in 57 Japanese shift work nurses suffering from fatigue
[20,64][19][63]. A similar effect was found in a controlled study of 58 first-year graduate students (47 female) in which CD19+ B lymphocytes decreased in response to perceived stress, along with a blunted cortisol awakening response from an increase in stress-induced glucocorticoids
[65][64]. In women of childbearing age, this phenomenon of prenatal maternal stress is heightened, as a study in 89 women who experienced the Quebec ice storm of 1998 had children (37 participating) with up to a 10% decrease in CD4+ T cells and 0.5-log increase in pro-inflammatory TNF-a levels
[66][65]. This drives home the idea that stress and strain can create a stress-mediated immunodeficient condition, a relevant concern in the age of COVID-19 and especially a concern in frontline nurses caring for infected patients. As fatigue and strain also affects pregnant mothers and those caring for infants and young children, reductions in immune competence from fatigue, coupled with the complex regulation of immunity during and immediately after pregnancy, could have serious healthcare implications
[67,68][66][67].