sexual intercourse; immunity

Vaginal Immune Mediators Rise Dramatically After First Intercourse Interview with:
Sean HughesSean M Hughes MA

Department of Obstetrics and Gynecology
University of Washington
Seattle, WA What is the background for this study?

Response: Young women are at elevated risk of getting sexually transmitted infections at the age when they typically start to have sexual intercourse. It’s not known whether this elevated risk is a consequence of behavioral factors (such as choices around use of barrier protection), physiological factors (such as a difference in the immune system) or a combination of both. In this study, we investigated a physiological factor: the immune system in the vagina. What are the main findings?

Response:  This work shows that cytokine/immune mediator concentrations rise dramatically in the vagina after young women start to have sexual intercourse. Further, it shows that the increase is not a stepwise change; instead, the concentrations increase continuously over time for at least a year, doubling after about 5 months.

A second significant contribution is the meta-analysis (Figure 6). There, we combine the results of our study with the results of two other similar studies, one from Belgium and one from the US. The similarity of the results of all three studies increases our confidence in our findings. It’s especially nice for something like CCL4, which had non-significant (p > 0.05) results in both of the two studies where it was measured, but because those two studies had very similar results, it comes out as significant in the meta-analysis. What should readers take away from your report?

Response: The main takeaway from this report is that starting to have sexual intercourse initiates a large amount of immune activity in the vagina. The consequences of that immune activity for risk of sexually transmitted infections remains unknown. What recommendations do you have for future research as a results of this study?

1.  The first and most important follow-up question is the role of the increased cytokine levels: do they help prevent sexually transmitted infections? Are they a sign of the immune system maturing at a site that is now being exposed to more foreign antigens? Do they increase HIV risk by recruiting CD4s to the site?

  1. Additionally, a wide range of cytokines increased in concentration: pro-inflammatory, anti-inflammatory, chemokines, etc. A second important follow-up question for future research is: Why are they all moving in tandem despite their differing functions?
  2. A third important direction for future research is to determine how long after first sexual intercourse the cytokines continue to increase in concentration. We only looked at about a year afterwards (and most samples were even earlier than that). Presumably vaginal cytokine concentrations eventually plateau, rather than increasing for the rest of the woman’s life, but we don’t know if that’s the case. This is a question that we hope to address in the future. We have samples collected later after first sex, so we can follow the same women up to several years after they have sexual intercourse for the first time.


Hughes SM, Levy CN, Calienes FL, Martinez KA, Selke S, Tapia K, Chohan BH, Oluoch L, Kiptinness C, Wald A, Ghosh M, Hardy L, Ngure K, Mugo NR, Hladik F, Roxby AC. Starting to have sexual intercourse is associated with increases in cervicovaginal immune mediators in young women: a prospective study and meta-analysis. Elife. 2022 Oct 25;11:e78565. doi: 10.7554/eLife.78565. PMID: 36281966; PMCID: PMC9596159.

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Last Updated on November 4, 2022 by Marie Benz MD FAAD