Testosterone and immune-reproductive tradeoffs in healthy women

Abstract

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. 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. We investigated how the interaction between endogenous T and sexual activity predicted menstrual cycle-related changes in several measures of immunity: inflammation (indexed by interleukin-6, IL-6), adaptive immunity (indexed by immunoglobulin A, IgA), and functional immunity (indexed by bactericidal assay). Thirty-two healthy women (sexually abstinent, N=17; sexually active with one male partner, N= 15) provided saliva samples at four points in the menstrual cycle: menses, follicular, ovulation, and luteal phases. Among sexually abstinent women, T was positively associated with IL-6 across the cycle; for sexually active women, however, T was positively associated with IL-6 in the luteal phase only, and negatively associated with IL-6 at ovulation. High T predicted higher IgA among women who reported infrequent intercourse, but lower IgA among women who reported very frequent intercourse. Finally, across groups, T was positively associated with greater bacterial killing at menses, but negatively associated in the luteal phase. Overall, rather than being universally immunosuppressive, T appeared to signal immunomodulation relevant to reproduction (e.g., lowering inflammation at ovulation, potentially preventing immune interference with conception). Our findings support the hypothesis that the immunomodulatory effects of endogenous T in healthy females depend on sexual and reproductive context.

Circulating sex-steroids and Staphylococcus aureus nasal carriage in a general female population

“…Testosterone has been characterized as immunosuppressive, but recent research suggests that testosterones immunomodulatory effects depend on the reproductive context and menopausal status. There are also inconsistency of results for testosterone in both postmenopausal and premenopausal women where testosterone has been characterized as both pro-inflammatory and anti-inflammatory (36). Cutibacterium acnes that suppress the growth of other bacteria like S. aureus (42).…”

Higher testosterone is associated with increased inflammatory markers in women with SARS-CoV-2 pneumonia: preliminary results from an observational study

“…Although supported by a weaker evidence, an immunomodulatory effect of T is also documented in women [ 12 , 13 ]. To assess the role of this hormone in SARS-CoV-2 women and compare it to findings in the male counterpart, we collected data on T levels in female patients from the same clinical setting.…”

Molecular and Neuroendocrine Approaches to Understanding Trade-offs: Food, Sex, Aggression, Stress, and Longevity—An Introduction to the Symposium

“…In female rodents, however, testosterone lowers inflammation at ovulation, presumably preventing immune interference toward the sperm at conception. Thus, gonadal steroids can have positive influences on fertility while at the same time promoting an immune response ( Lorenz et al 2017 ).…”