In both cases, decisions about TRT should be made with a specialist, and immune health should be monitored during treatment. Low testosterone can affect quality of life, energy, and sexual health. Importantly, these benefits have not been linked to any major harm to immune function. However, people who take very high doses of testosterone (such as bodybuilders using anabolic steroids) may face different risks. When taken in normal doses under medical supervision, TRT does not appear to raise infection risk in most healthy men. Their guidelines provide detailed advice on starting and adjusting therapy.Interaction terms (e.g. testosterone by BMI) were assessed, but did not achieve statistical significance and are thus omitted.Seven studies were eventually included in the systematic review (Table 1), and all of them showed beneficial impacts on a range of health outcomes, including depression, vascular endothelial function, muscle strength, bone health, and sexual function.Whether through lifestyle changes or testosterone therapy, maintaining healthy hormone levels can have a significant impact on your immune health.Doctors who treat HIV-positive patients must check hormone levels regularly and make sure TRT is used only when testosterone is clearly low.Although too much body fat isn’t good for your natural testosterone production, eating healthy fats have been proven to boost testosterone levels.As a primary hormone influencing bone metabolism, testosterone directly affects osteoclasts, osteoblasts, and osteocytes, promoting periosteal bone formation during puberty and decreasing bone resorption during adulthood; testosterone is also strongly correlated with bone density; lower testosterone levels result in decreased bone density .Autoimmune diseases happen when the immune system attacks the body’s own tissues.Immediately following the blood draw, leukocyte counts were measured with a QBC Autoread Plus (QBC Diagnostics). The authors suggest that this state may be representative of compensated hypogonadism, with elevated LH representing the bodies attempt to maintain testosterone levels. Specific to males, receptors have been identified in both the prostate and testis, as well as specifically Sertoli cells, Leydig cells and spermatogonia . While there’s no magic “healthy pill,” there are tried-and-true ways to take your immunity superpowers up a notch. You want — no, NEED — to stay healthy and functioning at a level 10 to keep up with the demands of day-to-day life. The data were arcsin h transformed with a cofactor of five using the flowCore package. This involved analyzing.fcs files from 60 samples from 20 series of participants receiving testosterone treatment. The antibodies used for this study are listed in Supplementary Tables 1–3. Purified antibodies were obtained in carrier/protein-free buffer and coupled to lanthanide metals using the MaxPar X8 or MCP9 antibody conjugation kits (Standard BioTools Inc.) as per the manufacturer’s recommendations. Hallmark IFNα responses decrease after 12 months of testosterone treatment, TNF signalling through NFκB and Hallmark inflammatory responses increased after 12 months of testosterone treatment as compared with baseline. We performed longitudinal blood sampling of 23 trans men, who were assigned female sex at birth and undergoing masculinizing treatment with testosterone undecaonate starting at the age of 18–37 years. It is important to understand how GAHT influences the immune response in these individuals, but this also provides a unique opportunity to investigate the immunomodulatory functions of gonadal steroids in vivo in humans of reproductive age. In individuals assigned female sex at birth and undergoing gender-affirming testosterone therapy (trans men), hormone concentrations change markedly but the immunological consequences are poorly understood. The decline in testosterone can impact the production and functionality of immune cells, potentially increasing the risk of infections and age-related diseases.There are no standard tests to measure how testosterone changes a patient’s immune system, and most of the research is still in early stages.This indicates that in well-nourished western populations the relationship between immune parameters and masculine traits is relatively low.Houman explained that following a Mediterranean diet has been linked to higher testosterone levels and better reproductive health in men.We found stronger IFNγ responses in NK cells following 3 months of testosterone treatment (Fig. 4c), whereas CD8+ (Fig. 4d) and CD4+ T cell responses were unchanged (Fig. 4e).For these reasons, experts say it’s best to get your vitamins and minerals through food rather than use supplements to improve your immune system.By reducing inflammation, testosterone may contribute to a healthier immune system and potentially lower the risk of chronic inflammatory conditions.A composition of lymphocytes allows them the development of almost all possible immune processes, including immune inflammation, and many forms of programmed cell death or tolerance. General health status, age, testosterone level, BMI, physical activity, and smoking were controlled. While some studies showed that sexually dimorphic traits are related to various aspects of biological condition such as general health, immunity or fertility, still little is known about the relationship between masculine traits and the effectiveness of innate and adaptive immunity in humans. Other contributing factors include a decline in Leydig cell number and function (Korenman et al. 1990), as well as LH levels (Veldhuis et al. 1999). The secretory capacity of Leydig cells has also been shown to decrease with age, specifically with the number of Leydig cells (Neaves et al. 1985). For these men, TRT brings testosterone back to a normal level. Testosterone may slow down the release of cytokines that cause swelling and tissue damage. In these men, TRT helped reduce inflammation markers and improved insulin sensitivity. Scientists are still studying how safe and effective TRT is for people with these diseases over the long term. Male investment into reproduction is much lower than that of females, and males allocate more resources into muscle growth and immune function and testosterone is a key regulator of such resource allocation in vertebrates53. Recent developments in immune-oncology have shown important roles for AR signalling in regulating T cell responses to tumours and limiting the efficacy of checkpoint blockade through T cell exhaustion28,29,30. Male patients are at increased risk of severe disease following SARS-CoV-2 infection due to less efficient IFN-I responses and excessive inflammation mediated by IL-6, IFNγ, TNF and IL-1/18 (ref. 1). Is it possible to intervene in this process and boost your immune system? On the whole, your immune system does a remarkable job of defending you against disease-causing microorganisms. Read our Editorial Process to know how we create content for health articles and queries. Seek advice from your physician or other qualified healthcare providers with questions you may have regarding your symptoms and medical condition for a complete medical diagnosis. However, these effects' exact mechanisms and consequences are still being studied. Immune system and age In a comparison study between hypogonadal men either treated with TRT or untreated, the TRT treatment group had a significantly decreased risk of death compared to the untreated group (Shores et al. 2012). Crohn’s disease has also been shown to improve following the normalization of androgen levels to physiological ranges (Bianchi 2019). The relationship between the microbiota, androgen production, and autoimmune conditions has also been studied. T has also been shown to have a more pronounced effect on visceral fat rather than subcutaneous fat, with the highest effects on intra-abdominal adipose stores (Mårin et al. 1996). DHEA has also been observed to increase resting metabolic rate (RMR) and increase the breakdown of lipids by oxidation (De Pergola 2000). Common Myths about the Male Hormone & How to Increase Testosterone Levels When used correctly, TRT may support better immune health—but only when part of a well-monitored medical plan. Large, high-quality clinical trials will help provide clearer answers about the safety and immune-related effects of TRT over time. More long-term research is needed to fully understand the immune effects of TRT. Based on current research, TRT appears to help improve immune balance in men with low testosterone. This is because the immune system naturally changes with age, a process known as immunosenescence. Conditions include medium only (RPMI) or stimulation with a B-cell and monocyte (LPS) or a T-cell mitogen (PHA). Interaction terms (e.g. testosterone by BMI) were assessed, but did not achieve statistical significance and are thus omitted. Cytokines were normalized across all stimulation conditions to place all cytokines on a similar scale, and allow for simultaneous testing of effects across multiple cytokines. Cytokines (baseline and ex vivo stimulated) and testosterone values were logged to normalize distributions unless otherwise noted, and converted to Z-scores. Research shows testosterone levels drop within five days of consuming alcohol. Foods rich in magnesium, such as spinach, almonds, cashews, and peanuts, can help elevate testosterone levels. Below are 12 natural foods that can help boost testosterone levels. The relationship between immunity and hormones was also tested with different multiple regression models, controlling for known immunomodulatory factors such as participants’ age and BMI. The hypothalamus releases several tropic hormones with Gonadotropin-Releasing Hormone (GnRH), a peptide hormone, controlling the HPG axis. This review explores current findings regarding androgens, aging, and inflammation. Testosterone levels have also been studied in relation to the impact of diseases, aging, nutrition and the environment on its circulating levels. Past, Present and Future of Testosterone Deficiency and Testosterone Replacement Therapy The participants were one hundred and thirty-four healthy men, aged 19–36. To evaluate immune system functioning we used a number of cell-mediated and humoral-mediated innate and adaptive immune parameters, constituting various immune mechanisms. Only a few correlational studies in humans have tried to verify these associations using selective masculine traits (mostly facial ones) and usually only indirectly measuring immunity (self-reported frequency of infections see 16, 62) or with a limited selection of immune parameters 15, 19, 63. The relationship between testosterone-dependent traits and immune system functioning has already been tested many times in non-human animals (mostly in birds) showing inconsistent results 58–61. Testosterone may have a calming effect on this kind of immune activity.There was a weak and positive relationship between year of publication and effect size for experimental studies of testosterone that became non-significant after we controlled for castration and immune measure, suggesting that the temporal trend was due to changes in these moderators over time.Specifically, 76% of ICU patients had testosterone levels below 300 ng/dL, and 90% of men who died had testosterone levels below this threshold.Currently, there are various approaches to treating patients with testosterone insufficiency, including the use of testosterone pellets and formulations combined with aromatase inhibitors, which need more studies for a better understanding of their effects .The immunomodulatory role of sex hormones was previously tested in many species, mostly birds, using both indirect measurement of immune system effectiveness, e.g. parasite load3,4,5 or direct immune parameters6,7,8.This increase in neural connection can be stopped by administering finasteride, which inhibits 5α-reductase (Brandt et al. 2020).It is likely that the measurements of baseline immune functions in men who declared no health problems, had no chronic diseases or ongoing infections and had a normal level of inflammatory markers (both CRP and WBC) are still inadequate for measuring immune quality.Through the actions of 5α-reductase, testosterone is metabolized into DHT, which is neuroactive. But that doesn't mean the effects of lifestyle on the immune system aren't intriguing and shouldn't be studied. For now, there are no scientifically proven direct links between lifestyle and enhanced immune function. There is still much that researchers don't know about the intricacies and interconnectedness of the immune response. Make other lifestyle changes in the hope of producing a near-perfect immune response? Healthy immune system warriors need good, regular nourishment.Reducing oxidative stress benefits testosterone bioactivity because inflammation and oxidative stress can lower testosterone levels.However, recent studies and meta-analyses find mixed evidence that endogenous testosterone is an active immunosuppressant in free-living mammals (Foo et al. 2016; Nunn et al. 2009; Roberts et al. 2004).TRT's Influence on Reducing Autoimmune Symptoms Autoimmune diseases occur when the immune system mistakenly attacks healthy cells in the body.5 α-reductase catalyzes the conversion of testosterone into 5 α-dihydrotestosterone (DHT) (Randall 1994).Additionally, A study conducted by Zhang et al. investigated the association between the Dietary Inflammatory Index and male hormones, finding that men adhering to an inflammatory diet appeared to have a greater risk of TD24.Scientists have found that men and women have different rates of autoimmune diseases.The goal of this study is to learn more about the critical and varied roles that testosterone plays in healthy men's physiological functioning.LH acts on the interstitial Leydig cells to stimulate the production and release of testosterone (Choi and Smitz 2014). Some studies suggest that TRT may help improve certain parts of the aging immune system. The body becomes less able to fight infections, and there may be more inflammation in the body. However, how TRT affects the immune system may depend on both the age of the person and the dosage used. Extended Data Fig. 2 Immune cell changes during gender affirming testosterone therapy. Additionally, A study conducted by Zhang et al. investigated the association between the Dietary Inflammatory Index and male hormones, finding that men adhering to an inflammatory diet appeared to have a greater risk of TD24. Serum levels of TNF-α and MIP1α were significantly higher in men with below-normal testosterone levels23. In addition, anti-inflammatory activity may be a function of testosterone in the body22. The 95th percentile of men in the 80 to 99 years old age range has a total T level of 839 ng/dL (Travison et al. 2017). The 95th percentile of men in the 19–39 years old age range has a total T level of 850 ng/dL. Higher levels of cytokines have also been shown to downregulate the reproductive axis and decrease GnRH secretion (Igaz et al. 2006). Another study confirmed these findings by determining that GnRH secretion is lower in older men, but LH secretion is relatively stable (Veldhuis et al. 2012). In addition, serum LH levels are nearly doubled in older men, indicating testicular non-responsiveness and failure to secrete T (Neaves et al. 1984). Sex difference and COVID-19 SHR (shoulder width divided by hip width) is one of the most widely used body markers of androgen exposure during puberty, when skeletal development is strongly affected by sex hormones. It is also worth noting that intrasexual male-male competition is also usually based on such characters (e.g. body size and strength) that are costly to produce and therefore are supposed to signal biological quality. This would also mean that women’s preferences for highly masculine males may in consequence lead to selection for such male traits that signal viability benefits (e.g. immune quality) for offspring. Thus, if in accordance to the hypothesis that physically attractive (dimorphic) traits are the cues of biological condition, such traits (at least theoretically) should be linked with immune functioning. As a result, the decline in androgen levels in the aging male requires further examination and research due to its importance in a variety of diseases, as well as quality of life. However, it is essential to recognize that testosterone levels represent just one aspect of the complex immunological landscape, influenced by numerous factors. The interplay between testosterone and immunity affects various diseases, including autoimmune disorders, infections, and cancer. While testosterone has been found to exert suppressive and stimulatory effects on the immune system, the precise mechanisms and consequences still need to be understood. Androgen receptors are present on T-cells (Benten et al. 1999), but their numbers might be dynamically regulated in response to baseline androgen levels and other feedback mechanisms. Alternatively, long term differences in testosterone may have effects on leukocyte phenotypes that affect responsiveness to stimulation, irrespective of levels in the blood at the particular time of stimulation. First, those studies used exogenous testosterone administration, which while an excellent way to isolate the impact of testosterone on cytokines may not be ecologically valid, as many aspects of physiology other than just androgens are modified when androgens naturally increase. However, B-cells are much more abundant in Tsimane blood compared to industrialized populations, while monocytes are very rare (Blackwell et al. 2016), so much of the LPS response is likely a B-cell response. Understanding the interaction between testosterone and the immune system is crucial for maintaining overall health. Research suggests that testosterone may have an immunosuppressive effect, meaning it can help reduce the overactive immune response seen in autoimmune diseases. It is important to consult with a healthcare professional experienced in TRT to determine if it is the right option for you and to monitor your immune system’s response during treatment. Consequently, a higher level of any immune parameter might be misinterpreted as better immune quality rather than ongoing immune activation in response to an infection. During the process of participants’ selection for final analyses, it was necessary to exclude those with any health problems including elevated markers of inflammation that might signal asymptomatic infection or those who declared any infection symptoms. In the laboratory, fresh blood samples were immediately used for different tests (phagocytic uptake, ROS production, lymphocyte count and lymphocyte-proliferation response). The study group was also quite homogeneous with regard to socioeconomic status (SES), and the majority (99%) declared that their current financial status was at least average. When these men received TRT and their hormone levels reached normal, they had fewer infections. This means that TRT could help calm the body’s inflammation and lower the risk of chronic conditions such as heart disease or type 2 diabetes. However, it is important to look at both the risks and benefits of TRT on immune function, especially for men using it long term. Testosterone Replacement Therapy (TRT) affects many systems in the body, including the immune system. High doses can weaken immune defenses or create other health problems. In men, testosterone is primarily synthesized in the testes and the adrenal gland, with smaller amounts produced in the ovaries and adrenal glands in women . Dysregulation of this feedback mechanism can lead to a variety of pathophysiological conditions, particularly testosterone deficiency; such disruptions may occur due to aging, disease processes, or lifestyle factors, underscoring the importance of accurate diagnosis and appropriate therapeutic interventions . An outline of the major hormonal changes that take place in men throughout their lives is given in this introduction, with special attention to testosterone's crucial role in controlling a wide range of physiological processes. The data that support the findings of this study are available from the corresponding author, AM, upon reasonable request. The exceptions were β-hydroxy β-methylbutyrate and betaine, which can be considered effective for male athletes. Our results show that men with higher levels of fT produce more specific anti-influenza antibodies in response vaccination. Because of the small sample size (only 20 men) and no controlling for participant age, adiposity, or health status, the conclusions of Prall and Muehlenbien should be, however, treated with caution. These differences may suggest the influence of ecological factors on immune-testosterone interaction. Interestingly, the strength of the immune response to the influenza vaccine was positively predicted by the level of fT and marginally significantly by DHT. Another 2017 study examined the effects HIIT training had on male athletes and concluded it to increase free testosterone and muscle power (14). Getting into a healthy weight range is arguably the most important factor you have control over for naturally optimizing your testosterone levels. Another study from the University of Nebraska Medical Center researched the acute effects of weight lifting on serum testosterone levels. Inflammation is a natural immune response, but chronic or excessive inflammation can damage tissues and organs. Emerging research suggests that optimizing testosterone levels can enhance your body’s ability to fight off illnesses like the flu — and even COVID-19. Your doctor will likely measure your testosterone levels at least twice before recommending testosterone therapy. Testosterone and its derivatives have been shown to interact with the AR to activate genomic and non-genomic pathways that affect a wide variety of body tissues. Levels of SHBG have been observed to increase at a dramatic rate in older men (Feldman et al. 2002). Older men have been observed to have increased sensitivity to negative feedback from androgens (Deslypere et al. 1987; Winters et al. 1984; Mulligan et al. 1997; Winters and Atkinson 1997). The steroidogenic enzymes have been shown to decrease in number and activity with age. After administration of recombinant LH, older men had a 50% lower T secretion response (Veldhuis 2008). Right now, doctors must rely on general medical knowledge, existing TRT guidelines, and patient history when considering immune effects. Future updates may also help clarify which patients are most likely to benefit from TRT in terms of immune health—and which patients may need special care. Larger and longer trials are needed to fully understand the long-term impact of TRT on immune function. Because of this, professional societies may be waiting for more clear evidence before including immune system effects in their recommendations. Although many patients and doctors are interested in how TRT might affect immune function, current guidelines do not cover this topic clearly or fully. Low testosterone is detrimental for your health, correlated with anxiety, metabolic syndrome, depression, fatigue, and low sex drive. Today, low testosterone is on the rise, and it’s even more common to see it in young males. Research shows that it improves libido, muscle building, heart health, motivation, immunity, and brain health. This is especially true if you are beginning any new supplement for increased testosterone. Adaptive immune parameters The AR is expressed throughout the body in many different tissues including muscle, bone, prostate, adipose, reproductive, cardiovascular, neural, immune, and hematopoietic systems (Davey and Grossmann 2016). The free hormone hypothesis postulates that only the unbound fraction of testosterone is active in the target tissues (Laurent et al. 2016a, b). Total testosterone represents both the bound and unbound concentrations of this hormone (Vankrieken 2000). Houman explained that following a Mediterranean diet has been linked to higher testosterone levels and better reproductive health in men. A healthy gut plays a role in inflammation and hormone metabolism, so eating gut-friendly foods is always good. A study of active young men found that drinking two cups of pure pomegranate juice each day for three weeks helped with muscle recovery, reduced inflammation and saw an increase in testosterone. One smaller study found that eating the whole egg will be better for testosterone levels than egg whites. This suggests that maintaining healthy testosterone levels may help mitigate severe outcomes from viral infections like COVID-19.Initially, it was hypothesized that the presence of receptors on male-specific tissue was contributory to some of the observed differences, including some clinical presentations such as orchitis.Smoking can damage your blood vessels and impede nitric oxide production, which is imperative for blood flow for a healthy erection.Fatty fish like salmon, tuna, and mackerel are rich in vitamin D, which is vital for natural testosterone production as it supports hormone synthesis.While the developmental costs of producing B-cells and immunoglobulins can be high, the maintenance and activation costs are relatively low, as are the collateral costs in terms of tissue damage when activated (McDade et al. 2016).Another study confirmed these findings by determining that GnRH secretion is lower in older men, but LH secretion is relatively stable (Veldhuis et al. 2012).Testosterone and its derivatives have been shown to interact with the AR to activate genomic and non-genomic pathways that affect a wide variety of body tissues.Conclusively, testosterone is an essential hormone that is involved in many physiological processes throughout men's lives; in addition to controlling libido, testosterone is closely linked to bone density, muscle growth, and repair; its influence on mental health, especially in reducing symptoms of depression, emphasizes its complex nature. When testosterone levels are too low, the immune system may not function properly. High levels of testosterone can suppress certain immune cells and raise the risk of infections. Some studies suggest that restoring testosterone to normal levels with TRT may help improve immune function. Research shows that men with lower testosterone levels often have a weaker immune response. Although some studies on humans supported immunomodulatory properties of sex hormones11,12,13,14,15 the findings of studies on testosterone influences on immune cells are inconclusive. This is the first study examining the relationship between multiple innate and adaptive immunity and serum levels of free testosterone, total testosterone, DHT and DHEA in ninety-seven healthy men. Regular monitoring can help ensure that your hormone levels remain within a healthy range, which can support your overall health and immune system function. While testosterone therapy can be beneficial for men with diagnosed testosterone deficiency, many men can maintain healthy testosterone levels through lifestyle changes. It is also important to note that most studies focus on men with low testosterone. Some researchers believe testosterone has a calming effect on the immune system. Since fat tissue can send out harmful signals that affect the immune system, lowering this fat through TRT may help control inflammation. Researchers are exploring the effects of diet, exercise, age, psychological stress, and other factors on the immune response, both in animals and in humans. Depending on the context and specific immune markers being studied, it can have both immunostimulatory (enhancing immune responses) and immunosuppressive (inhibiting immune responses) effects. In males, testosterone levels are typically much higher than in females. It contributes to the growth and maintenance of bones, stimulates the production of red blood cells, enhances libido and sexual function, and plays a role in mood regulation and cognitive function. In addition to its effects on sexual characteristics, testosterone has essential functions in other aspects of the body. Prepuce as the “Achilles’ heel” of the male immune system and whole male body It is tempting to speculate that the testosterone-driven induction of TNF described herein could be another driver of T cell exhaustion in cancer patients and a possible target for combination therapies in the future. However, analyses of chronic infection models (human immunodeficiency virus or lymphocytic choriomeningitis virus) have indicated TNF signalling in T cells as another important regulator of T cell exhaustion during chronic antigen stimulation50. Whether this reflects immune response differences and more symptomatic disease or differences in risks of contracting the virus through modulated ACE2 and or TMPRS2 expression remains to be determined. In support of this, Seillet et al previously showed that oestradiol supplementation potentiates IFNα responses in postmenopausal women44 and Griesbeck et al. reported that ESR signalling in mice potentiates IFNα responses in pDCs through IRF5 induction45. On the left side of the threshold, the rate of change in testosterone deficiency significantly alters as PIV values change, with statistical significance. We observed a non-linear relationship between PIV and testosterone deficiency. In the unadjusted model (OR 0.81, 95% CI 1.46, 2.26) and the partially adjusted model (OR 1.68, 95% CI 1.34, 2.11), there was a positive correlation between PIV and the risk of testosterone deficiency. Moderate intensity endurance training leads to increases in testosterone (48). According to studies, having sex is beneficial for boosting your testosterone. Cortisol has an inverse relationship with testosterone, so lowering your cortisol will increase your testosterone. Another study found similar results and reported a 60% serum testosterone drop for men who slept 4 hours compared to those who slept 8 hours (35). Taken together, this indicates that these two groups of individuals are inherently different and not comparable simply because of a similar testosterone level, and perhaps there is an underlying physiologic difference in these individuals that requires further investigation. Men with hypogonadism have also been shown to have worsened respiratory outcomes, such as in chronic obstructive pulmonary disorder, further potentiating the worse COVID-19 disease course in men with low testosterone . While a similar trend was also observed for aging women, this may be secondary to menopause and a loss of immune protection from progesterone and estrogen . An understanding of the role of testosterone in other disease processes may also be helpful to understand and support the relationship between hypogonadal states and poor COVID-19 outcomes. Understanding how TRT might change immune function can help doctors make better choices for their patients. Hormones like testosterone can affect how the immune system works. The immune system protects the body from germs like bacteria, viruses, and fungi. For these men, doctors may recommend testosterone replacement therapy, or TRT. Testosterone levels are highest during young adulthood and slowly drop with age. Zinc can also be sourced from beef and beans, aiding the immune system to combat external threats. Oysters are rich in zinc, which is crucial for testosterone production and fertility. Insufficient protein intake can lead to testosterone deficiency. Onions and garlic are allies not only for general health but also for improving sexual health. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. Which Diseases Are Linked to Testosterone and Immunity? On the other hand, there is our understanding linking male infertility to the microbiota and data obtained by microbiomics and mass-spectrometry in the male reproductive system 44, 45. Over 30 viruses are found in the male genital tract , and many of them persist in semen, fall into the urethra, and can be spread due to sexual activity. Can influence the incidence of bacterial vaginosis in female sex partners . From one point of view, since there are no own tolerogenic microbes in male microbiota, the required factors originate from the gut and, additionally, have to come from the female vagina rich in Döderlein’s flora like Lactobacilli . We found IRF7 mRNA downregulated in pDCs following testosterone therapy, and IRF7 expression correlated with Hallmark IFNα transcripts in individual pDCs stimulated with R848 (Fig. 2j). This corroborates a recent report of pDC responses in six trans men14. Counts in stimulated cells, subtracting median counts in unstimulated pDCs. A, Immune cell clusters (FlowSOM) of 12,377,068 cells by 50-marker mass cytometry. E, PCA on the basis of nine sex hormones, first two principal components (PC1 and PC2; percentage variance explained) and sample points coloured by sample timepoint. TRT can help support immune health in older adults by lowering inflammation and restoring hormone balance. Both age and dosage make a big difference in how testosterone therapy affects the immune system. Younger men, especially those under age 40, usually have higher natural testosterone levels. Researchers have found that low testosterone levels in older men can be linked to higher levels of chronic inflammation. The increase in sex steroid production during puberty speeds up bone mineral accumulation and causes sex-specific variations in bone growth; after mid-puberty, the male population experiences a greater increase in periosteal bone growth than the female population, who shows more pronounced endocortical bone formation . The production of testosterone in men is primarily controlled by negative feedback mechanisms, whereby high levels of testosterone prevent the release of GnRH from the hypothalamus and LH from the pituitary, thereby limiting further testosterone synthesis; testosterone is made from cholesterol by a variety of enzymatic pathways in the testes . Additionally, it aims to clarify the effects of testosterone dysregulation on men's mental and physical wellness while advancing clinical procedures and treatment approaches. In men, the endocrine system, which includes glands like the pituitary, thyroid, adrenal, and gonads, releases hormones that control important functions like growth, metabolism, reproduction, and mood . The objective of this systematic review is to critically analyze the various functions of testosterone, including its physiological importance, regulatory processes, and possible repercussions if it is dysregulated in men. Both the medical procedure (medical examination, vaccination and blood collection) and anthropometry were performed in a private medical clinic in Wroclaw, Poland. Investment in masculine traits is an important component of male reproductive effort including inter and intra-sexual selection. The connection between actual circulating testosterone concentration and HGS has been verified in various groups. The previous correlational studies have mostly focused on a single immune function and one or two androgen fractions. Due to the complexity of immune-hormones interactions and possible viability-fecundity trade off affecting an individual’s fitness benefits, the correlational studies might be not a conclusive test of ICHH assumptions. In contrast, correlational studies, which can reflect the immune-hormone interactions in natural/physiological conditions are still incomplete. In accordance with ICHH, the level of body masculinization (morphological traits that are under the influence of testosterone) reflects an individual’s biological quality, especially immune system effectiveness2. In consequence, only individuals with high biological quality, including immunity, can produce and maintain a high level of testosterone and can afford the physiological costs of this hormone-derived systemic immunosuppression. Testosterone is a hormone produced primarily in the testicles.Therefore we suggest treating androgens as immunomodulators rather than immunosuppressants, as supported by the important role of ecological factors in moderating the relationship between immunity and androgens.As more research is done on testosterone and immunity, future guidelines may include specific recommendations on how to monitor immune health during TRT.Testosterone deficiency seriously affects male reproductive function, growth and development, and quality of life.However, when it comes to the immune system, these guidelines often say very little.In mouse studies, giving testosterone to male mice reduced the severity of autoimmune diseases. Reeder pointed to zinc, vitamin D, magnesium, omega-3 fatty acids and high-quality protein as pivotal nutrients for healthy testosterone production. Your diet is equally important, so make sure to include these top foods (as picked out by our CNET experts) to boost your testosterone levels effectively. Frequent BPA exposure over six months is linked to a significant drop in testosterone levels. Chronic heavy drinking can lead to testicular shrinkage, hair loss, and increased estrogen levels, causing breast tissue enlargement. These results offer further insights to testosterone-mediated attenuation of IFN-I responses in pDCs. IRF7 is a master regulator of IFN-I responses in pDCs15 and individuals with loss of function mutations in IRF7 fail to control respiratory viruses such as influenza16 and SARS-CoV-2 (ref. 17). When investigating blood transcriptional modules (BTM) and hallmark gene pathways in these R848-stimulated pDC before and during testosterone, BTM S5 (DC surface signature) was induced, while the Hallmark IFNα gene set and the related M127 IFN-I response, were attenuated significantly (Fig. 2h). To study pre-DCs during GAHT, we gated these manually (Extended Data Fig. 2b)12 and found no change in abundance during testosterone therapy in vivo (Fig. 2f). CD5+CD81+ pDCs were reported previously to differ from CD5−CD81− pDCs with attenuated type-I IFN responses and more potent regulatory T (Treg) cell induction9. Before starting TRT, individuals should consult with a qualified healthcare professional who specializes in men’s health. While TRT can be beneficial for some men, it is essential to consider the potential risks and side effects. Testosterone may play a role in the development and progression of autoimmune diseases, which primarily affect women, but also affect men. It is also worth noting that although our study is mainly correlational, it is the first study testing the relationship between different androgens concentration and many other immune functions simultaneously.Onions and garlic are allies not only for general health but also for improving sexual health.The resulting matrix was used for immune composition analysis with the FlowSOM package74.This membrane-bound protein has also been shown to be constitutively expressed in adult Leydig cells (Douglas et al. 2004).In the light of previous results, the main question is why androgens exert different effects on immune cells in vitro and in vivo.IL12RB1 and IL12RB2 mRNA in individual NK cells were induced during GAHT.Four weeks later, during the second visit, participants submitted to blood sample collection to evaluate the strength of the immune response to vaccination and filled in questionnaires on illnesses after the first visit.GAHT enables the acquisition of secondary sex characteristics aligned with gender identity in transgender individuals but the immunological impacts and risks of immune-mediated and infectious diseases upon sex hormone therapy is unknown. 5 α-reductase catalyzes the conversion of testosterone into 5 α-dihydrotestosterone (DHT) (Randall 1994). Aromatase catalyzes the conversion of testosterone into estradiol, which binds to estrogen receptors (Stocco 2012). Aromatase is located in the male gonads, as well as bone, breast, brain, and adipose tissues (Durdiakova et al. 2011). Testosterone exerts its effects by binding to the androgen receptor (AR), a ligand-dependent nuclear transcription factor. These proteins include sex hormone binding globulin (SHBG), human serum albumin (HSA), and to a lesser extent corticosteroid-binding globulin (CBG). Although animal studies that observed immunosuppressive role of testosterone, suggests AR-independent pathway of this suppression33, the role of the AR-mediated pathway in immune modulation was confirmed in studies on androgen receptors knockout mice (ARKO mice)15. Another problem is that male traits that are under sexual selection and may signal immune quality are not only testosterone-dependent. Thus, to define the role of testosterone in immunocompetence, it would be necessary to investigate various immune functions, both innate and adaptive. It is worth noting that the immune system is a complex network consisting of many mechanisms, organs, cells, receptors, and mediators which cooperate with each other at the molecular level23. Age, overall health, medical history, and genetic factors can all affect how the immune system reacts to hormone therapy. TRT should always aim to restore testosterone to normal, healthy levels—not to go above them. While more studies are needed, these early results suggest that restoring testosterone levels may help some people fight off infections better. Some research shows that men with low testosterone have fewer or less active immune cells. Don't cut out all fats from your diet or you may see a hormone level drop. "Very low-fat diets can be problematic. Fats, especially those from whole food sources, provide cholesterol, a crucial building block for hormone production," Reeder said. You'll always want to stay away from trans fats and packaged snacks. Houman explained that ultra-processed foods and high-sugar diets can suppress testosterone by promoting insulin resistance. When testosterone levels return to normal, some studies have shown that markers of inflammation also go down. That is why doctors often monitor blood tests, including hormone levels and immune markers, during therapy. High levels of testosterone have been shown to reduce the activity of some types of white blood cells, like T-cells and natural killer (NK) cells. The first visit included medical qualification to vaccination, blood sample collection for biochemical, immunological, and hormonal analyses, influenza or both influenza and tetanus vaccine injection, and height, weight, and body fat percentage measurements. Thirty-five of these men were also tetanus-vaccinated (aged 20.7–36.7; mean age 28.7) and evaluated for immune response to tetanus toxoid. One hundred and thirty-four men (aged 18.9–36.7 years) who were volunteers and declared no health problems were recruited for the study. These two reactive forms of androgens positively influence adaptive immunity, i.e. the strength of the response to the influenza vaccine, and appear to have no effect on humoral or cell-mediated innate immunity. In summary, we found that fT and DHT are probably the hormones most relevant for studying immune parameters potentially affected by androgens. While it is clear that any energetic stress, whether due to immune activation from infection (Muehlenbein et al. 2010) or caloric restriction (Trumble et al. 2010), results in decreased testosterone production, it is less clear that endogenous testosterone actively down-regulates human immune function. Studying the role of testosterone in modulating immune function under naturalistic conditions is notoriously difficult in humans, where ethical concerns limit the use of various experimental protocols commonly used in nonhuman animal models. Thus, while there may be trade-offs between testosterone and some more energetically costly aspects of immune function (Best and Hoyle 2013), one would not expect that testosterone would down-regulate all aspects of immune function equally. Innate immune responses, which include pro- and anti-inflammatory cytokines, not only are crucial rapid responses to injury, but also play a role in subsequent wound healing (Werner and Grose 2003). Testosterone influences several components of the immune system, including white blood cells, which are critical for fighting infections. This research, published in Aging Male, found that as serum testosterone levels decreased, the likelihood of ICU admission and mortality significantly increased. For instance, a 2020 study found that men with lower baseline testosterone levels were more likely to be admitted to intensive care units (ICUs) and had higher mortality rates compared to men with normal testosterone levels. She is passionate about incorporating lifestyle medicine and plant-based nutrition into endocrinology, particularly for diabetes and obesity management. But overall, the science is still mixed, and their effects are likely mild at best.” She also suggests pairing these types of moves with progressive overload, a type of training where you gradually increase intensity from one workout to the next by adding more weight, reps, or sets. “Fat tissue converts testosterone into estrogen, so losing weight, especially trimming your waistline, can help reverse this process.” This membrane-bound protein has also been shown to be constitutively expressed in adult Leydig cells (Douglas et al. 2004). Feline studies have demonstrated that DHEA administration decreased inflammatory gene transcripts while promoting CD4 + T cell production and neuronal preservation (Maingat et al. 2013). Testosterone administration has been shown to increase lean body mass (LBM) and one repetition strength. Testosterone treatment increases the quality of life and mental health in HIV + patients (Knapp et al. 2008). In addition, these patients were noted to have increased levels of muscle wasting and loss of bone density (Reid et al. 1985). This suggests that hormonal correction of men into a eugonadal state may be removing the harmful effects that have been observed from hypogonadism. So, if there is an androgen-dependent effect on COVID-19, it seems plausible that hormone manipulation, in the form of TRT, could provide a possible solution to mitigate disease severity. Furthermore, even amongst those who are hypogonadal without the use of ADT, is it that the lower testosterone is responsible for worse outcomes or does severe disease result in a more prominent decline in testosterone? Immune function involves multiple coordinated responses, each with their own costs, benefits and interactions with other immune and endocrine responses. Another major issue is that most studies assessing trade-offs between immune function and testosterone rely on only a single biomarker of immune function, precluding the ability to examine a potential immuno-modulatory role of testosterone. Potentially costlier forms of immune activation like those induced by PHA (largely T-cell biased immune activation) are down-regulated in men with higher testosterone, but testosterone has less impact on potentially less costly immune activation following LPS stimulation (largely B-cell mediated immunity).