Inflammatory Mechanisms of Dysmenorrhea: Novel Insights From Menstrual Effluent in an Adolescent Cohort

Objective

To examine how eicosanoid levels in menstrual effluent of adolescents within 3 years of menarche relate to the severity of menstrual pain.

Design

Prospective cohort study.

Setting

Community teaching hospital.

Population or Sample

Adolescents within 3 years after menarche.

Methods

Participants provided a menstrual effluent sample between 4 and 30 months after menarche. Eicosanoid and oxylipin concentrations were measured in the menstrual effluent. We compared effluent concentrations of participants with menstrual pain (n = 33) to age-matched pain-free controls (n = 18).

Main Outcome Measures

Eicosanoid and oxylipin concentrations in menstrual effluent.

Results

Participants with dysmenorrhea had higher PGF2α (4.5 [1.6, 8.9] ng/mL, p = 0.014) than controls (1.1 [0.07, 4.4] ng/mL). However, differences in PGE2 (7.1 [2.6, 10.1] vs. 3.5 [1.0, 5.1], p = 0.053) and 12-HETE (36.3 [23.7, 60.7] vs. 29.6 [13.4, 51.5], p = 0.305) were not significant. The correlations between PGF2α (r = 0.37, p = 0.004) or PGE2 concentration (r = 0.28, p = 0.046) and menstrual pain intensity were moderate to small. Overall, there were positive correlations between menstrual volume and eicosanoid concentrations (r's > 0.4, p's < 0.001). Participants with dysmenorrhea taking analgesics had more PGF2α (66.2 [43.0, 164.7]) than controls (19.1 [6.0, 47.5], p = 0.04). LC-MS/MS revealed higher concentrations of 12-HETE, 14,15-EET, 15-HETE, 18cdLTB4, LTB4 and PGF2α—and lower 6-kPGF1α—in the effluent of participants with dysmenorrhea compared to controls.

Conclusions

Elevated PGF2α in adolescents with dysmenorrhea, modest correlations between prostaglandin concentrations and menstrual pain, and the identification of additional oxylipins suggest that inflammatory processes beyond the prostaglandin pathway contribute to dysmenorrhea.