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

Abstract

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.

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

“…The higher the frequency of intercourse, the greater the mid-cycle decline in pro-inflammatory markers (and mid-cycle increase in anti-inflammatory markers). Prior research in healthy women has shown that sexual activity is associated with lower levels of IgA (16, 19), IgE-mediated allergic responses (57), and Th1-dominant cytokine profiles (20). One common theme throughout these seemingly diverse immune factors is their potential detrimental effect on reproduction, via disruption of conception (as IgA may disrupt sperm transport and viability (58)), interference with establishment of the placenta (as when IgE is diverted from supporting the placenta towards allergic reactions(59)), or through early termination of the pregnancy (as is the case for Th1 cells(60) particularly in the context of low Th2 cells(61)).…”

“…If so, it would follow that these effects would be most critical (and most subject to evolutionary selective pressure) in individuals who are reproductively active, i.e., regularly engaging in sexual activity. Indeed, several studies suggest that immune parameters, including inflammatory cytokines, differ in sexually active vs. abstinent women (16–18), with sexually active women showing more variation in immune markers across the menstrual cycle than abstinent women (13, 19, 20). Thus, we would expect that inflammation would differ significantly across the menstrual cycle in sexually active, but not abstinent, women.…”

Testosterone and immune-reproductive tradeoffs in healthy women

“…The present analysis was drawn from a larger study on the effects of sexual activity on women’s health; other papers from this study include (Lorenz et al, 2015a; Lorenz et al, 2015b). …”

“…One study of healthy participants found no association between endogenous T and SIgA in either men or women (van Anders, 2010); however, this study did not report the menstrual phase of the female participants. IgA has been found to be significantly different across cycle phases (Gomez et al, 1993; Lorenz et al, 2015a), although other studies have found no significant cycle-related variation (Brown et al, 2008; Garde et al, 2000; Gillum et al, 2014). …”

“…Menstrual cycle-related variations in immunity may support fertility by downregulating immune responses that may interfere with conception (e.g., inflammation, mucosal antibodies) near ovulation (Lorenz et al, 2015a; Lorenz et al, under review; Lorenz et al, 2015d), and upregulating immune responses that promote implantation (e.g., T-helper 2 cell activity) in the luteal phase (Lorenz et al, 2015c). As T appears to be relevant to tradeoffs between fertility and immunity, among premenopausal women the effect of T may vary across cycle phases (e.g., from the follicular to luteal phase).…”