Have you ever noticed that you get sick more often than your best friend or close friend of the opposite sex? Or is it vice versa? You never get sick but your partner seems to catch every virus around the corner. Did you ever wonder if there is a difference between the immune system of females and males, and why that is? Certainly, we have observed this phenomenon during the COVID-19 pandemic. Men have more likely tested positive for COVID-19 with higher rates of severity and even deaths than women   . We also observed women reacting to the vaccine with stronger side effects than men  while young boys seem to more likely develop myocarditis as a vaccine side effect, than girls .
The connection between sex hormones and immunity
Most of the genes that regulate the immune system are encoded by the X chromosome, which supports the observation that premenopausal women (XX) have stronger immune systems than men (XY). Estrogen promotes immune cell production and infection response. Progesterone increases risk of sexually transmitted viruses, particularly during the luteal phase of menstruating women when progesterone peaks. Estrogen and progesterone both regulate the immune response to prevent over-reactions to infections that may result in hyper-inflammation, such as the cytokine storm experienced with severe COVID-19 .
As women age, declining estrogen and progesterone levels are a key characteristic of the menopause trajectory. Remarkably, researchers in Wuhan China found that women with low estrogen had more severe COVID-19 symptoms than women with higher estrogen levels . The COVID Symptom Study observed women between the ages of 55-60 had increased COVID-19 related symptoms , possibly reflecting a low level of immuno-protective estrogen found in this age group. Long COVID is characterized by hyper-inflammation , being more prominent in women with low estrogen. In the Long COVID study, in addition, more women reported long COVID syndrome than their male counterparts .
Testosterone plays a role, as well. While high testosterone enhances male reproductive potential and maintains muscle tissue, it also compromises longevity by suppressing immune function . Research has suggested testosterone also reduces vaccination response, suggesting that perhaps vaccination dosage should be tailored for males vs. females. The good news is that testosterone can suppress inflammation, potentially offering an explanation for less men suffering from long COVID-19 vs. women and older men with naturally lower testosterone being at greater risk of severe COVID-19 and death .
Elevated estrogen and activation of estrogen receptors have been associated with a decreased (improved) viral load . Both estrogen and progesterone have been shown to protect against COVID-19 infection severity. Testosterone down regulates pro-inflammatory proteins, thereby reducing inflammation in the body. A published report has suggested testosterone supplementation decreases the COVID-19 cytokine storm associated with severity and increased risk of death in males . This information suggests sex hormones augmentation could be used in patients at risk of or suffering from COVID-19 . The importance of sex hormones is so remarkable that researchers are now investigating the potential short-term use of estrogen and progesterone therapy to help treat COVID-19. Stay tuned for more on this topic .
The recent events highlighted during the COVID-19 pandemic, in particular its gender specific immune system response differences, emphasize now more than ever, the importance of including both genders in pre-clinical and clinical studies when developing therapies to strengthen immunity.
What about nutrition?
Targeted nutrition can be used to strengthen the immune system and control levels of inflammation, in order to protect against viral infections and reduce symptom severity. There is a great deal of literature now published on the immune strengthening effects of nutrition on COVID-19 prevention, acute and chronic infection. Nutrients, such as vitamin D, zinc, selenium, vitamin C, A, carotenoids, polyphenols, protein rich foods, omega 3 fatty acids and prebiotic fibers are highly regarded options for nutrition therapy; as well as diets that address cardiovascular disease, diabetes and obesity . Additionally, a Mediterranean diet has been suggested to have a protective effect against COVID-19 . Stay tuned for future posts on sex-specific connections with nutrition and immunity!
At PhenomX Health, we are passionate about the topic of sex and gender differences and immunity as the world’s immune capacity has been challenged over the last two years of the COVID-19 pandemic. We love using supplementation along with optimal nutrition to maximize the body’s natural capacity to protect itself. PhenomX Health has collaborated with the Caligenix team to develop the Immunotype supplement to strengthen immune system response. If you are interested in powering up your immune system, click here* to find out more about the Caligenix Immunotype and receive a 10% discount.
If you are interested in helping us understand further how to help women meet their hormonal health nutrition and aging needs, would you take a moment to fill in our questionnaire? If so , please click here to go to our survey!
Best in Health,
The PhenomX Health Team
*Please note Immunotype is currently only available to US residents.
Writers: Colleen Fogarty Draper PhD, RD; Ksenia Tugay PhD, MBA; Arianna Bianchi PhD
Graphics: Michel Combes PhD