Immune dynamics throughout life in relation to sex hormones and perspectives gained from gender-affirming hormone therapy.

Biological sex is associated with differences in immune response properties, with males and females showing different susceptibilities to diseases and variations in immunity.

• Males and females show different susceptibilities to infectious diseases and autoimmune conditions.
• These differences are influenced by hormonal, genetic, and environmental factors.
• Sex-based immune differences vary throughout different life stages.
• Sex hormones at least partially explain sex biases in different diseases, particularly autoimmune diseases in females.

Androgens, predominantly present in males, generally suppress immune responses.

• Testosterone is the predominant androgen and is more abundant in males.
• Androgenic effects on immunity include suppression of certain immune functions.
• Testosterone therapy in transgender men may suppress type I interferon responses.
• Testosterone therapy in transgender men increases inflammation markers like TNF-α.

Estrogens, more abundant in females, tend to enhance immune responses.

• Estrogens are associated with enhanced immunity compared to androgens.
• The immune-enhancing effects of estrogens are thought to contribute to the higher prevalence of autoimmune diseases in females.
• Estrogen therapy in transgender women leads to alterations in coagulation-related and inflammatory characteristics.
• Sex hormone-driven immune differences partially explain female sex bias in autoimmune diseases.

Testosterone therapy in transgender men suppresses certain immune functions, specifically type I interferon responses.

• Available research on gender-affirming hormone therapy revealed suppression of type I interferon responses with testosterone therapy.
• Studies on this topic are described as limited.
• Testosterone therapy simultaneously increases inflammation markers such as TNF-α.
• These findings are drawn from studies exploring gender-affirming hormone therapy in transgender men.

Transgender women receiving estrogen therapy experience alterations in coagulation-related and inflammatory characteristics.

• Estrogen therapy in transgender women leads to changes in coagulation-related markers.
• Inflammatory characteristics are also altered in transgender women on estrogen therapy.
• Additional possible alterations in immune regulation can be inferred from assessment of inflammatory and autoimmune markers in transgender individuals receiving hormone therapy.
• Studies on immunological effects of gender-affirming hormone therapy are described as limited.

Gender-affirming hormone therapy offers a novel opportunity to study the immunological effects of sex hormones.

• The advent of gender-affirming hormone therapy is described as providing 'a novel opportunity to study the immunological effects of sex hormones.'
• Studies in this area remain limited but have already revealed immune function changes.
• This approach allows examination of hormone effects on immune function independently of chromosomal sex.
• Findings from transgender individuals receiving hormone therapy can inform understanding of sex hormone-immune system interactions more broadly.

Understanding sex hormone and immune system interactions may facilitate development of targeted therapies for infections and autoimmune diseases.

• The complex interactions between sex hormones and the immune system may facilitate 'the development of targeted therapies for infections and autoimmune diseases.'
• Improved understanding may also improve healthcare outcomes for transgender individuals.
• The review covers immune dynamics throughout life in both sexes.
• Novel findings drawn from gender-affirming hormone therapy studies are summarized in the review.