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IL-6 is a cytokine, or immune signaling molecule, that is commonly used by immune actors such as macrophages and T cells to stimulate or target inflammation processes. There are clearly critical factors missing from the research on the effect of T on women’s immune function. Exogenous T added to blood cells taken from women at several cycle phases (e.g., follicular and luteal phases) yielded similar effects on B-cell suppression (Sthoeger et al., 1988) and T-cell differentiation (Giron-Gonzalez et al., 2000). In one study, exogenous T was added to blood cells taken from women several times across the menstrual cycle. It has been argued that inconsistent findings in studies of immune markers in premenopausal women may be due to natural variation in sex steroid hormones – that is, due to the menstrual cycle (Schisterman et al., 2014).
T does appear to be involved in tradeoffs between immunity and reproduction (broadly construed, potentially including fertility/fecundity, reproductive development, frequency of sexual behavior, and other variables pertaining to investing in the creation of offspring). Very little is known about the immune effects of T in healthy females, and even less about how reproductive effort modulates the immune effects of T in humans. Although testosterone (T) has been characterized as universally immunosuppressive across species and sexes, recent ecoimmunology research suggests that T’s immunomodulatory effects (enhancing/suppressing) depend on the organism’s reproductive context.
Interestingly, sex-specific immune response by MHCII molecules in humanized mice showed that males generated higher response to antigens presented by HLA-DQ alleles while females showed higher immune response to HLA-DR-presented antigens (32, 30). Thus, even in the presence of similar MHC II, women pay the price of higher incidence of sex-biased diseases but generate a superior response to infections. The X-linked miRNAs have also been shown to contribute to sex differences in immune responses, leading to much higher responses in females. The lower abundance of Prevotella and Bacteroides in females compared to males further supports sex-dependent differences in microbial composition (41), which impact intestinal and systemic immune responses. Although consideration of patient's sex for treatment is not a practice, sex differences in immune response suggest that sex-based treatments would be optimal.
While ex vivo whole blood antigen stimulation only provides a small window into the role of testosterone in modulating immune function, it is also a powerful tool that allows us to examine immune responses that would otherwise be unethical or impossible to study in non-laboratory settings. To the best of our knowledge, apart from the study on body height , there are no studies on the direct relationship between body masculinity and various immune functions whilst controlling for testosterone concentration, age or BMI in men. While much work has documented how condom use reduces the risk of sexually-transmitted infections, is unknown what effect condoms (or IUDs) may have on mucosal immunity in healthy (pre-infection) women.
Certain dietary supplements, such as vitamin D, zinc, and vitamin C, are known to support immune function. Chronic stress can suppress the immune system and potentially exacerbate any negative effects of testosterone. Yes, age can influence the effect of testosterone on the immune system. This may contribute to the observed differences in immune function between males and females. While high levels of testosterone may potentially modulate certain aspects of the immune system, the overall impact is not necessarily one of generalized weakening. Testosterone exerts its effects by binding to androgen receptors, which are found in various tissues throughout the body, including immune cells. Nonetheless this demonstrates the importance of field-friendly experimental manipulations; had this been a purely observational study of baseline cytokines and testosterone we would have observed no relationship between testosterone and circulating cytokines (see results above).
The association between inflammation and testosterone has been widely investigated since chronic inflammation is one of the pathogeneses of numerous diseases (8, 22). TD, also known as hypogonadism, due to testicular dysfunction or hypothalamic-pituitary dysfunction and it can either develop congenitally or acquired (5). DAdjust II model adjusts for age, race, BMI, coronary artery disease, heart failure, stroke, smoking status, alcohol consumption, education level, hypertension, diabetes, triglycerides, urine creatinine, and serum total cholesterol. Logistic regression analysis was used to assess the correlation between the prevalence of testosterone deficiency and SII. BMI, body mass index; SII, systemic immune-inflammation index. Sociodemographic and clinical characteristics of the 7389 subjects related to the NHANES 2011–2016 cycle according to normal vs. low total testosterone level (ng/dl). " Defined diabetes as being "told by a doctor you have diabetes." Urinary creatinine, triglycerides, and serum total cholesterol levels were derived from the standard biochemistry profiles.
Given that we do not yet know the mechanisms by which sexuality, T and immune function interact in healthy women, it is reasonable to examine if these effects replicate across a broad range of sexual activities. Both aspects of immune response are relevant to women’s health, but vaginal responses are likely more directly critical for fertility and sexually transmitted disease risk. We examined changes in T as a predictor of immune response across the menstrual cycle in healthy women who were or were not sexually active. Based on the role of androgens in the immune response and on the variation in androgen levels throughout life, we may speculate that testosterone could play a double-edged role in the natural history of COVID-19 infection.44 In the early phase, the immunosuppressive action of testosterone could explain males’ greater susceptibility to infection when compared with women in all age groups. PC is an age-related disease and ADT is the first-line treatment for locally advanced and metastatic disease.25 If testosterone impairs the immune response, we may predict that ADT can restore immune function and protect against infections.