What does Testosterone have to do with our Immunity and Autoimmunity?
Adult Autoimmune Diseases can often be prevented, delayed and/ or improved by testosterone replacement with bio-identical testosterone. This is a fact supported by hundreds of medical studies, but a treatment that has unfortunately been ignored by mainstream medicine.
Some of the most common autoimmune diseases include Rheumatoid Arthritis, SLE (Lupus), Multiple Sclerosis, ALS, and Scleroderma. These diseases have several risk factors in common, many of which cannot be changed.
- Sex: Women are affected more than men
- Age: Women over 35 and men over 50
- Genetic Risk: Positive family history
- Environmental toxin exposure
- Inflammation from obesity and diabetes
- Gut Microbiome that is unhealthy (poor diet and inadequate bacterial profile)
- Deficient Free Testosterone
- High estrone and estradiol environment
To understand the role of the sex hormones, estradiol and testosterone, it is important to understand how an adult autoimmune disease develops. I admit this is a simplistic explanation; however, it is how I explain these diseases to my patients.
Autoimmune disease is a disease of the Immune System. Your immune system is a complex system composed of white blood cells (T cells provide cellular immunity and B cells that provide antibodies that target foreign proteins (bacteria, viruses, cancer cells, parasites, and tissue proteins from other humans and animals), lymph nodes, bone marrow, your intestinal microbiome and your thymus gland. The purpose of the immune system is to protect you from harm or death from interaction with any of these foreign proteins that might cause our human body to be infected or die of cancer. Every day, 24 -7 your body is searching your system for foreign proteins to take down and dispose of. Your cells are always dividing and making new cells and mistakes occur that could become cancer if left without your white cells to kill and remove them.
When our immune system becomes ineffective or it becomes misdirected toward our healthy tissue there are one of three outcomes. If it is suppressed by cortisol (stress) or there are not enough white blood cells (AIDS or toxins) your immune system might let cancer cells slip through their protection and you might have one or more cancers. Other outcomes of an ineffective immune system might be chronic viruses, or chronic parasites, viral illnesses that don’t clear or leaky gut.
When the immune system becomes misdirected to attack our own cells because they “resemble” the target they are supposed to protect us from, it often results in an autoimmune disease. There are triggers that commonly misdirect our immune systems: viruses, bacterial infections, tick bites, some immunizations, exposure to other human’s tissue (human implants) and severe stress that cripples the protective immune system. Our immune system attacks our tissues as if they were a virus, bacteria or cancer cell, and our target tissues are slowly destroyed.
So what does Testosterone have to do with our Immunity and Autoimmunity?
In women Testosterone is secreted from the ovaries and in men it is made in the testes. Men make ten times the amount of testosterone as women when they are younger than 40, and their testes make Testosterone optimally for ten years longer than women. That physiologic fact leads to the greater incidence and earlier timing of the occurrence of autoimmune diseases in women.
Women get autoimmune diseases at a younger age than men, earlier than 40, if they have had their ovaries removed or have premature menopause. Men who have testosterone deficiency are more likely to get an autoimmune disease, and this usually occurs after age 50.
The role of Testosterone in the immune system is multi-faceted. Testosterone is anabolic which means it stimulates tissues to grow. The thymus gland is the center of cellular immunity and is also a source of immunoglobulins. In childhood the thymus gland is stimulated by growth hormone, and after puberty it is stimulated by testosterone. The thymus gland requires testosterone to remain healthy in adult hood, normal sized and active. As we age, the thymus shrinks and becomes inactive, due to decreasing testosterone. As the thymus gland shrinks it no longer protects a person from infection or autoimmunity. The shrinkage of the thymus gland is the basic anatomical and physiologic reason people who are over 60 get cancer, deadly viral illnesses and die of infections that would not kill someone younger. Men and women who replace testosterone in a non-oral bioidentical way maintain their healthy immune system as long as they take testosterone.
Testosterone is also an immune modulator. If a person has adequate testosterone and the immune system is over-reacting, testosterone decreases the reaction and therefore decreases the autoimmune response. This is protective for those people who genetically or environmentally are at risk for autoimmune diseases. SEE THE EXCERPTS FROM RESEARCH STUDIES BELOW.
“Specifically Testosterone’s impact on the immune system is, on aggregate, anti-inflammatory. Specific mechanisms include: (1) lower secretion of IL-1β, IL-6, TNF, and other pro-inflammatory mediators by monocytes and macrophages; (2) increased production of anti-inflammatory IL-10 by T cells and (3) inhibition of the NFκB-mediated activation of the IL-6 gene promoter in human fibroblasts, and of T cell proliferation in animal models.”
Hundreds of studies have confirmed the importance of keeping the level of testosterone at a healthy youthful normal to avoid and treat autoimmune diseases, even though every study I read says, “there is insufficient research to confirm the replacement of inadequate testosterone to avoid and treat autoimmune disease.” I find that ludicrous! I did a Google Scholar search and found hundreds of recent (last 10-15 years) research that confirms the importance of testosterone replacement to the treatment of autoimmune diseases, and it only took me 15 minutes to find these articles! What are they researching to say there is not enough research?
I am attaching some of the excerpts from these research articles. In my next Blog and Health cast I will discuss my personal experience with treating autoimmune diseases with testosterone pellets in women and men with autoimmune diseases. The fact is that I have personally witnessed autoimmune disease regress under the influence of testosterone, so my patients can return to their productive lives.
It is a mystery to me that when there is one effective, affordable treatment for all autoimmune diseases, that the FDA prefers to advocate many very expensive immune suppressants that have severe risks, rather than approve one bio-identical hormone to treat them all. I look for other motivations. It’s usually “money honey” that is the cause of illogical actions by the powers that be. Would it be big profit of big pharma, or the fact the FDA hires folks who previously worked for big pharma and still hold their stock? Sadly, the FDA decisions affect more than just the US, their decisions ring throughout the whole world. Our FDA’s mistakes are multiplied worldwide and should be rectified! The simplest answer is usually the right one. Everyone over 40 with an autoimmune disease should be treated with non-oral, non-transdermal testosterone like pellets, or IM shots (men only). The answer is one natural hormone that can reverse autoimmune diseases and reverse aging! The answer maybe too simple and affordable for them!
This Health cast was written and presented by Dr. Kathy Maupin, M.D., Bio-identical Hormone Replacement Expert and Author. www.BioBalanceHealth.com • (314) 993-0963. Please subscribe to our YouTube channel and please check “ Like “. Follow us on Facebook and Instagram at BioBalanceHealth.
RESEARCH:
Autoimmune diseases and reproductive aging
https://doi.org/10.1016/j.clim.2013.02.010Get rights and content
Abstract
As the population ages, more individuals with autoimmune diseases are experiencing reproductive senescence. Understanding the impact of menopause and age-related androgen decline on disease onset and course, as well as the potential for hormonal interventions, is critically important. In men, lupus erythematosis (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS) are associated with lower androgen levels. However, the impact of age-related declines in testosterone, as well as of testosterone replacement, on disease course remains underexplored. In women, the course of all three diseases with onset after the age of menopause differs from that with onset before menopause. Early age at menopause is associated with increased disease risk, and after menopause, disease course changes in SLE and RA. Less is known about MS. This article summarizes what is known about the relationship between reproductive aging and autoimmune diseases in men and women, and highlights areas for further investigation.
Highlights
► Men with SLE, RA and MS may have lower testosterone levels than healthy controls. ► Early age at menopause increases risk for SLE and RA. ► After menopause, SLE and RA disease severity and progression changes; no investigations in MS. ► Onset of SLE, RA and MS after menopause confers a different course than onset before menopause. ► Hormone replacement therapies may not play a big role in altering disease course.
CLINICAL REUMATOLOGY: HYPOGONADISM AND THE RISK OF RHEUMATOID AUTOIMMUNE DISEASE. JUNE 2016
NOTE: TRANSMEN ARE GENETICALLY XX FEMALE
TRANS WOMEN ARE GENETICALLY XY MALE
Abstract
Testosterone deficiency has been linked with autoimmune disease and an increase in inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor, and interleukin-6 (IL-6). However, no large-scale longitudinal studies have examined this association. We examined whether untreated hypogonadism was associated with an increased risk of rheumatic autoimmune disease in a large nationally representative cohort. Using one of the nation’s largest commercial insurance databases, we conducted a retrospective cohort study in which we identified 123,460 men diagnosed with hypogonadism between January 1, 2002 and December 31, 2014 and with no prior history of rheumatic autoimmune disease. We matched this cohort to 370,380 men without hypogonadism, at a 1 to 3 ratio, on age and index/diagnosis date. All patients were followed until December 31, 2014 or until they lost insurance coverage or were diagnosed with a rheumatic autoimmune disease. Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHRs). Untreated hypogonadism was associated with an increased risk of developing any rheumatic autoimmune disease (HR = 1.33, 95 % CI = 1.28, 1.38), rheumatoid arthritis (HR = 1.31, 95 % CI = 1.22, 1.44), and lupus (HR = 1.58, 95 % CI = 1.28, 1.94). These findings persisted using latency periods of 1 and 2 years. Hypogonadism was not associated with the control outcome, epilepsy (HR = 1.04, 95 % CI = 0.96, 1.15). Patients diagnosed with hypogonadism who were not treated with testosterone had an increased risk of developing any rheumatic autoimmune disease, rheumatoid arthritis, and lupus. Future research should further examine this association, with particular attention to underlying mechanisms.
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JCI Insight
. 2025 Apr 22;10(8):e184544. doi: 10.1172/jci.insight.184544
Testosterone affects female CD4+ T cells in healthy individuals and autoimmune liver diseases
Lara Henze 1, Nico Will 1, Dakyung Lee 1, Victor Haas 1, Christian Casar 1,2, Jasper Meyer 1, Stephanie Stein 1, Franziska Mangler 1, Silja Steinmann 1, Tobias Poch 1, Jenny Krause 1, Johannes Fuss 3, Johanna Schröder 4, Alexandra E Kulle 5, Paul-Martin Holterhus 5, Stefan Bonn 6,7, Marcus Altfeld 8, Samuel Huber 1,9, Ansgar W Lohse 1,9, Dorothee Schwinge 1, Christoph Schramm 1,9,10,✉
PMCID: PMC12016935 PMID: 40260919
Abstract
Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) are autoimmune liver diseases with strong female predominance. They are caused by T cell–mediated injury of hepatic parenchymal cells, but the mechanisms underlying this sex bias are unknown. Here, we investigated whether testosterone contributes to T cell activation in women with PBC. Compared with sex- and age-matched healthy controls (n = 23), cisgender (cis) women with PBC (n = 24) demonstrated decreased testosterone serum levels and proinflammatory CD4+ T cell profile in peripheral blood. Testosterone suppressed the expression of TNF and IFN-γ by human CD4+ T cells in vitro. In trans men receiving gender-affirming hormone therapy (GAHT) (n = 25), testosterone affected CD4+ T cell function by inhibiting Th1 and Th17 differentiation and by supporting the differentiation into regulatory Treg. Mechanistically, we provide evidence for a direct effect of testosterone on T cells using mice with T cell–specific deletion of the cytosolic androgen receptor. Supporting a role for testosterone in autoimmune liver disease, we observed an improved disease course and profound changes in T cell states in a trans man with AIH/primary sclerosing cholangitis (PSC) variant syndrome receiving GAHT. We here report a direct effect of testosterone on CD4+ T cells that may contribute to future personalized treatment strategies.
Keywords: Autoimmunity, Hepatology, Immunology
Keywords: Autoimmune diseases, Sex hormones, T cells
We here report a direct effect of testosterone on CD4+ T cells that may contribute to future personalized treatment strategies.
Introduction
There is increasing interest in sex- and gender-related differences in immune responses. Whereas females show better control of viral infections, they are generally more prone to develop autoimmune diseases (1–4). This partly relates to sex, as determined by the sex chromosomes, for example via selective X-chromosomal inactivation (5, 6). However, sex hormones also directly or indirectly contribute to the regulation of the immune system (7). A substantial role in modulating the immune system has been described for 17-β estradiol (E2). The effects of E2 on immune cells varies depending on factors such as the concentration, the specific immune cell type, and the context of the immune response. Low concentrations of E2 have been associated with proinflammatory immune responses, whereas high concentrations of estrogens have been reported to be antiinflammatory and to augment Th2 responses and humoral immunity (8). Immunomodulatory effects have also been demonstrated for androgens, and testosterone has been shown to suppress the activity of immune cells, leading to immunosuppression. Thus, testosterone has been demonstrated to reduce proinflammatory responses of macrophages and to suppress extracellular signal–regulated kinases and leukotriene formation in neutrophils (9, 10). It has also been shown that healthy female mice have higher numbers of ILC2 cells in multiple tissues and that they can be modulated by testosterone (11). In murine-derived splenocytes, testosterone reduced the production of proinflammatory cytokines such as IL-1, IL-6, and TNF, while potentially increasing the production of antiinflammatory cytokines such as IL-10 in antigen-specific stimulated CD4+ T cells (12). Little is known about the effects of androgens on T cells in humans, but lower CD8+ T cell and higher CD4+ T cell frequencies, and specifically a higher frequency of circulating Treg, have been described in cisgender (cis) women compared with cis men (13, 14). Moreover, in serum from men with androgen deficiency, higher concentrations of proinflammatory cytokines and higher CD4+/CD8+ T cell ratios were reported (15–17). Notably, lower serum levels of testosterone were reported for autoimmune diseases, including systemic lupus erythematosus (SLE), multiple sclerosis (MS), and rheumatoid arthritis (RA) (18, 19). So far, it is unclear whether those effects might contribute to T cell regulation in autoimmune diseases.
___________________-
Clinical Immunology (2013) 149, 251–264
a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m
C l i n i c a l I m m u n o l o g y
w w w . e l s e v i e r . c o m / l o c a t e / y c l i m
REVIEW
Autoimmune diseases and reproductive aging
Partners Multiple Sclerosis Center, Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School,
Boston, MA, USA
Received 8 January 2013; accepted with revision 11 February 2013
Available online 28 February 2013
KEYWORDS
Multiple sclerosis;
Systemic lupus
erythematosus;
Rheumatoid arthritis;
Menopause;
Andropause;
Hormone replacement
therapy
Abstract
As the population ages, more individuals with autoimmune diseases are experiencing reproductive senescence. Understanding the impact of menopause and age-related androgen
decline on disease onset and course, as well as the potential for hormonal interventions, is critically important. In men, lupus erythematosis (SLE), rheumatoid arthritis (RA), and multiple
sclerosis (MS) are associated with lower androgen levels. However, the impact of age-related declines in testosterone, as well as of testosterone replacement, on disease course remains
underexplored. In women, the course of all three diseases with onset after the age of menopause differs from that with onset before menopause. Early age at menopause is associated with
increased disease risk, and after menopause, disease course changes in SLE and RA. Less is known about MS. This article summarizes what is known about the relationship between reproductive aging and autoimmune diseases in men and women, and highlights areas for further investigation.
© 2013 Elsevier Inc. All rights reserved._______
1/26, 7:12 AM Sex hormones and autoimmunity – ScienceDirect
Immunology Letters
Date: 6 September 2010
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Review article Full text access Get rights and content
Review
Sex hormones and autoimmunity
Delia Almeida González a b a a
, Buenaventura Brito Díaz , María del Cristo Rodríguez Pérez ,
Ana González Hernández a c c d a c e
, B. Nicolás Díaz Chico , Antonio Cabrera de León
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Abstract
Autoimmune diseases occur more in women than in men, and this may be attriutable to the role of estrogens. Androgens promote autoimmune diseases with a profile of type 1 cytokines, h as rheumatoid arthritis, whereas estrogens promote autoimmune diseases with a type 2 cytokine profile, like systemic lupus erythematosus. Both androgens and estrogens regulate the Th1/Th2 balance. Type 1 autoimmune diseases are improved when decrease type 1 cytokines (i.e. during fasting), or when there is a rise in type 2 cytokines (increased estrogens, as in pregnancy). Type 2 autoimmune diseases improve when type 2 cytokines are diminished (decreased estrogen, as in post-partum period) or when type 1 response is stimulated.
Keywords
Autoimmune diseases; Sex hormones; Th1/Th2 balance; Cytokines; Systemic lupus
Erythematosus
