Changes in sex hormones and their interactions are related to pain perception between different menstrual subphases

Abstract

Whether sex hormones are related to pain perception across the menstrual cycle is unclear. We examined changes in experimental pain perception in healthy young females between the early to midfollicular subphase (emF) and the midluteal subphase (mL) and explored the role of sex hormones. Sixty-six participants were involved in the study. We tested pressure pain, cold pain, ischemic pain, and needle pain, while at the same time we measured sex hormones levels in two menstrual subphases. Only the right ulna pressure test showed a significant reduction in pain threshold (PPTh3) during the mL. The absolute change of PPTh3 (PPTh3_mL - PPTh3_emF) was related to the absolute change of prolactin. The relative change of the range of pain tolerance for pressure pain of the right ulna (RPT3_rc) was related to the relative change of progesterone (P_rc) and estradiol (E2_rc) levels, and the interaction effects showed that at P_rc ≤ 30, E2_rc was positively correlated with RPT3_rc. The same, the relative change of pressure pain tolerance of the pulp of the middle finger on the right hand (PPTo4_rc) was related to E2_rc and P_rc, and the results of the interaction between E2_rc and P_rc suggest that when E2_rc is ≤0.8, P_rc is positively correlated with PPTo4_rc. Two different formulas were applied in this study and showed inconsistent results. Most pain tests showed no difference between the two subphases of the menstrual cycle. Only the relative changes of the PPTo4 and RPT3 are related to the E2_rc and P_rc, respectively, between menstrual subphases in an interactive way in healthy young women.

Keywords: absolute change; menstrual cycle; pain perception; relative change; sex hormones.

Figure 1.

Study flow chart. emF, early to midfollicular phase; HADS, hospital anxiety and depression scale; mL, midluteal phase; PCS, pain catastrophizing scale; PSQI, Pittsburgh sleep quality index.

Figure 2.

Plasma levels of sex hormones in the early to midfollicular (emF) and midluteal (mL) phases. A: change of E2 between emF and mL analyzed by paired t test measures. t = −5.973, **P < 0.01 vs. the emF. B: change of P between emF and mL analyzed by paired t test measures. t = −9.169, **P < 0.01 vs. the emF. C: change of FSH between emF and mL analyzed by paired t test measures. t = 5.426, **P < 0.01 vs. the emF. D: change of LH between emF and mL analyzed by Wilcoxon test of paired samples. z = 2.46, *P < 0.05 vs. the emF. E: change of PRL between emF and mL analyzed by paired t test measures. t = −5.034, **P < 0.01 vs. the emF. F: change of T between emF and mL analyzed by paired t test measures. t = −0.315, P = 0.755. n = 66. E2, estradiol; F, early to midfollicular phase; FSH, follicle-stimulating hormone; L, midluteal phase; LH, luteinizing hormone; P, progesterone; PRL, prolactin; T, testosterone.

Figure 3.

Differences in pain perception between the early to midfollicular (emF) and midluteal (mL) phase, and the effect of sex hormones. A: change of pressure pain in the right ulna pain threshold (PPTh3) between emF and mL phase analyzed by paired t test measures. t =2.231, *P < 0.05 vs. the emF. B: forest plot of the relationship between sex hormones_ac and PPTh3_ac. Prolactin_ac between mL and emF phase related to the PPTh3_ac between two menstrual subphases analyzed by multivariate linear regression (β = −0.498, P = 0.039) (n = 66). E2_ac, absolute change of estradiol; F, early to midfollicular phase; FSH_ac, absolute change of follicle-stimulating hormone; L, midluteal phase; LH_ac, absolute change of luteinizing hormone; P_ac, absolute change of progesterone; PRL_ac, absolute change of prolactin; sex hormones_ac, absolute change of sex hormones; T_ac, absolute change of testosterone.

Figure 4.

Relationship between the RPT3_rc and sex hormones_rc levels. A: forest plot of the relationship between sex hormones_rc and RPT3_rc. The P_rc (β = 0.016, P = 0.008) and E2_rc (β = 0.232, P = 0.021) related to RPT3_rc, analyzed by multivariate linear regression. B: results of interaction between effect of P_rc and E2_rc on RPT3_rc. P_rc= 30 is the cutoff point selected in interaction analysis, the red line represents P_rc ≤ 30; E2_rc related to change in RPT3_rc (P < 0.05), the blue line represents P_rc > 30, the change of RPT3_rc is independent of E2_rc (P > 0.1) (n = 66). E2_rc, relative change of estradiol; FSH_rc, relative change of follicle-stimulating hormone; LH_rc, relative change of luteinizing hormone; P_rc, relative change of progesterone; PRL_rc, relative change of prolactin; RPT3, pain tolerance range for right ulna tenderness; RPT3_rc, relative change of RPT3; sex hormones_rc, relative change of sex hormones; T_rc, relative change of testosterone.

Figure 5.

Relationship between the PPTo4_rc and sex hormones_rc levels. A: forest plot of the relationship between sex hormone_rc and PPTo4_rc. E2_rc (β = 0.082, P = 0.016) and P_rc (β = 0.004, P = 0.027) related to PPTo4_rc, analyzed by multivariate linear regression. B: results of interaction between effect of E2_rc and P_rc on PPTo4_rc. E2_rc = 0.8 is the cutoff point selected in interaction analysis, the red line represents E2_rc ≤ 0.8; P_rc related to the change in PPTo4_rc (P < 0.05), the blue line represents E2_rc > 0.8, the change of PPTo4_rc is independent of P_rc (P > 0.1) (n = 66). E2_rc, relative change of estradiol; FSH_rc, relative change of follicle-stimulating hormone; LH_rc, relative change of luteinizing hormone; P_rc, relative change of progesterone; PPTo4, right middle finger pressure pain tolerance; PPTo4_rc, relative change of PPTo4; PRL_rc, relative change of prolactin; sex hormones_rc, relative change of sex hormones; T_rc, relative change of testosterone.