Sexual activity modulates shifts in TH1/TH2 cytokine profile across the menstrual cycle: an observational study

Fertil Steril. 2015 Dec;104(6):1513-21.e1-4. doi: 10.1016/j.fertnstert.2015.09.001. Epub 2015 Sep 16.


Objective: To investigate if sexual activity moderated menstrual cycle-related shifts in cytokines associated with T-helper type 1 (TH1) cells (e.g., interferon [IFN] γ) and T-helper type 2 (TH2) cells (e.g., interleukin [IL] 4). Immune activity shifts across the menstrual cycle, with higher follicular-phase TH1-cell activity but higher luteal-phase TH2-cell activity. Little is known about how social behaviors alter TH1-TH2 ratios, despite evidence that psychosocial factors can influence immunity. Of particular interest is how sexual activity influences immune responses that may support conception, such as the TH1-TH2 balance.

Design: Participants provided saliva samples at four time points (menstrual, follicular, ovulatory, and luteal phases), which were assayed by means of ELISA.

Setting: Academic laboratory.

Participant(s): Thirty healthy premenopausal women (16 sexually abstinent, 14 sexually active) not taking hormonal or immunoactive medications.

Intervention(s): None.

Main outcome measure(s): Salivary E2, P, IFN-γ, and IL-4.

Result(s): Sexually active, but not abstinent, women were significantly more likely to express TH2-like cytokine ratios (IFN-γ < IL-4) in the luteal phase than in other phases. Similarly, sexually active women had significantly higher P, and higher P-E2 ratios, in the luteal phase than did abstinent women. The P-E2 ratio mediated menstrual variations in cytokine ratios in sexually active women.

Conclusion(s): These results support the hypothesis that shifts in immune response across the menstrual cycle may reflect tradeoffs between reproduction and immunity. These findings point to the need for further research on the interaction between sexual behavior, the menstrual cycle, and immune response.

Keywords: Immunity; T(H)1-T(H)2; cytokine; menstrual cycle; sex differences.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Estradiol / metabolism
  • Female
  • Humans
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism
  • Menstrual Cycle / immunology*
  • Menstrual Cycle / metabolism
  • Progesterone / metabolism
  • Saliva / immunology
  • Saliva / metabolism
  • Sexual Abstinence*
  • Sexual Behavior*
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th1-Th2 Balance*
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Time Factors
  • Young Adult


  • Cytokines
  • IFNG protein, human
  • IL4 protein, human
  • Interleukin-4
  • Progesterone
  • Estradiol
  • Interferon-gamma