Sexual activity, endogenous reproductive hormones and ovulation in premenopausal women

2017

Hormones and Behavior

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.

Section: Discussionmentioning

confidence: 73%

Section: Methodsmentioning

confidence: 99%

Testosterone and immune-reproductive tradeoffs in healthy women

2017

Hormones and Behavior

“…Most notably, several studies have suggested that sexually active women have significantly higher estrogen and luteal-phase progesterone than do abstinent women [46–49]; given the powerful immune effects of ovarian hormones, it is reasonable to suspect the effects reported here are at least partially mediated by endocrine mechanisms. However, given the complex patterns of immune effects (e.g., different patterns in condom users vs. non-users), the effects of sexual activity are likely not driven solely by hormonal differences.…”

Section: Discussionmentioning

confidence: 93%

Interaction of menstrual cycle phase and sexual activity predicts mucosal and systemic humoral immunity in healthy women

2015

Physiology & Behavior

Several studies have documented shifts in humoral immune parameters (e.g., immunoglobulins) across the menstrual cycle in healthy women. It is thought that these shifts may reflect dynamic balancing between reproduction and pathogen defense, as certain aspects of humoral immunity may disrupt conception and may be temporarily downregulated at ovulation. If so, one could expect maximal cycle-related shifts of humoral immunity in individuals invested in reproduction – that is, women who are currently sexually active – and less pronounced shifts in women who are not reproductively active (i.e., abstinent). We investigated the interaction of sexual activity, menstrual cycle phase, and humoral immunity in a sample of 32 healthy premenopausal women (15 sexually active, 17 abstinent). Participants provided saliva samples during their menses, follicular phase, ovulation (as indicated by urine test for LH surge), and luteal phase, from which IgA was assayed. Participants also provided blood samples at menses and ovulation, from which IgG was assayed. Sexually active participants provided records of their frequency of sexual activity as well as condom use. At ovulation, sexually active women had higher IgG than abstinent women (d = 0.77), with women reporting regular condom use showing larger effects (d = 0.63) than women reporting no condom use (d = 0.11). Frequency of sexual activity predicted changes in IgA (Cohen’s f2 = 0.25), with women reporting high frequency of sexual activity showing a decrease in IgA at ovulation, while women reporting low frequency or no sexual activity showing an increase in IgA at ovulation. Taken together, these findings support the hypothesis that shifts in humoral immunity across the menstrual cycle are associated with reproductive effort, and could contribute to the mechanisms by which women’s physiology navigates tradeoffs between reproduction and immunity.

“…Given significant differences between sexually active and inactive women in estradiol (E2) and P4 across the cycle (82), it is possible that endocrine factors play a role. Both E2 and P4 have immune effects, with the former thought to be generally anti-inflammatory (with notable exceptions (83)) and the latter thought to be generally pro-inflammatory, particularly within the female reproductive tract (84).…”

Section: Discussionmentioning

confidence: 99%

Partnered sexual activity moderates menstrual cycle–related changes in inflammation markers in healthy women: an exploratory observational study

Fertility and Sterility

2017

Objective To examine differences in inflammation markers in sexually active vs. abstinent women, and observe changes in inflammation markers across the menstrual cycle. Cycle-related immune fluctuations may have evolved to reduce interference with conception. If so, reproductively active (i.e., sexually active) women should show the most variability in cytokine expression. Design Participants provided serum samples at menses and ovulation (from which cytokines were assayed) and saliva samples at menses, follicular, ovulation, and luteal phases (from which C-reactive protein was assayed). Participants self-reported intercourse frequency during the study. Setting Academic research laboratory. Participants 32 healthy, naturally cycling premenopausal women (sexually active, N = 15, abstinent, N = 17). Interventions Observational study. Main outcome measures Pro-inflammatory cytokines (Interleukin-6, IL-6; Interferon γ, IFN-γ; Tumor Necrosis Factor α, TNF-α), an anti-inflammatory cytokine (Interleukin-4, IL-4), and a marker of total inflammation (C-reactive protein, CRP). Results Sexually active women had higher levels of all of the immune markers measured, including both pro- and anti-inflammatory cytokines, than abstinent women. Relative to sexually active women, abstinent women had less change across the menstrual cycle in levels of CRP. Among sexually active women, higher intercourse frequency predicted greater mid-cycle decreases in CRP, IL-6, and IFN-γ and mid-cycle increases in IL-4. Conclusions Sexual activity may stimulate a complex interaction between pro- and anti-inflammatory cytokines that subsequently drive mid-cycle declines in inflammation.