From May 15, 2021 to January 31, 2022, 113 of 138 recruited women with PD met the screening criteria and were enrolled in the trial (75 participants in the LLLT group and 38 participants in the control group). Finally, 100 participants (68 in the LLLT group and 32 in the control group) finished the whole trial, and 13 women were excluded for inadequate treatment time or use of non-designated rescue drugs. The median number of treatments per menstrual cycle was 4 (Range from 3 to 6) for both groups. The workflow of the trial is illustrated in Fig. 3. No significant difference was found in the basic characteristics of participants in the two groups. (Table 1)
Table 1
Baseline characteristics of subjects in both groups
| LLLT group (n = 68) | Control group (n = 32) | P Value |
Age(year) | 25(22,26) | 24(21,26) | 0.44 |
Age of menarche(year) | 13(12,13) | 12(12,13) | 0.12 |
BMI(kg/m2) | 21.5(2.2) | 21.48(1.96) | 0.34 |
Medicine history for PD | | | 0.88 |
Yes | 50(74%) | 24(75%) | |
No | 18(26%) | 8(25%) | |
VAS | 6.59(1.26) | 6.72(1.05) | 0.61 |
CMSS | 37.49(10.04) | 40.28(5.94) | 0.09 |
Time of abdominal pain | 2.72(0.48) | 2.75(0.57) | 0.79 |
Degree of abdominal pain | 3.10(0.74) | 3.13(0.55) | 0.88 |
SAS | 44.29(3.48) | 44.94(3.23) | 0.38 |
SDS | 47.66(3.66) | 46.94(5.18) | 0.48 |
Number of treatments per menstrual cycle | 4(4,4) | 4(4,4) | 0.77 |
Abbreviations: BMI: Body Mass Index; PD, Primary Dysmenorrhea; VAS, Visual Analogue Scale; CMSS, COX Menstrual Symptom Scale; SAS, Self-Rating Anxiety Scale; SDS, Self-Rating Depression Scale. |
Therapeutic Effect On Somatic Symptoms Of Pd
The results of VAS, APT, APD and CMSS over time points are shown in Table 2 and Fig. 4 (A-D). As illustrated, all four indices gradually decreased during T0-3 and gradually increased during T4-6 in the LLLT group.
Table 2
Therapeutic effect of LLLT on pain and relevant symptoms of PD
| | VAS | APT | APD | CMSS |
T0 | LLLT(n = 68) | 6.59(1.26) | 2.72(0.48) | 3.10(0.74) | 37.49(10.04) |
| Control(n = 32) | 6.72(1.05) | 2.75(0.57) | 3.13(0.55) | 40.28(5.94) |
T1 | LLLT(n = 68) | 4.51(0.99) ab | 2.56(0.50) a | 2.01(0.61) ab | 29.04(8.04) ab |
| Control(n = 32) | 6.16(0.85) a | 2.59(0.50) | 2.72(0.52) a | 36.75(4.49) a |
T2 | LLLT(n = 68) | 3.96(1.04) ab | 2.32(0.47) ab | 1.74(0.59) ab | 26.94(8.34) ab |
| Control(n = 32) | 6.03(0.70) a | 2.66(0.48) | 2.81(0.40) a | 37.72(4.53) a |
T3 | LLLT(n = 68) | 3.68(0.92) ab | 2.19(0.40) ab | 1.60(0.55) ab | 22.16(8.86) ab |
| Control(n = 32) | 5.95(0.67) a | 2.63(0.49) | 2.72(0.46) a | 36.94(4.64) |
T4 | LLLT(n = 68) | 4.85(1.08) ab | 2.43(0.50) ab | 2.19(0.61) ab | 26.53(7.71) ab |
| Control(n = 32) | 6.50(0.67) | 2.66(0.55) | 3.03(0.31) | 38.38(4.78) |
T5 | LLLT(n = 68) | 5.53(1.06) ab | 2.60(0.49) | 2.50(0.59) ab | 29.69(8.06) ab |
| Control(n = 32) | 6.59(1.19) | 2.72(0.46) | 2.97(0.70) | 39.09(4.99) |
T6 | LLLT(n = 68) | 6.29(1.12) a | 2.68(0.50) | 2.85(0.63) ab | 33.04(8.72) ab |
| Control(n = 32) | 6.66(0.87) | 2.72(0.52) | 3.13(0.42) | 40.19(5.31) |
Abbreviations: LLLT, Low level laser therapy; PD, Primary Dysmenorrhea; VAS, Visual Analogue Scale; APT, Time of abdominal pain; APD, Degree of abdominal pain; CMSS, COX Menstrual Symptom Scale; a, compared with T0, p < 0.05; b, compared with control group, p < 0.05. The higher are the values of VAS, APT, APD, CMSS, the more severe the symptoms are. |
During the treatment period, significant decrease from baseline was found in the VAS, APT, APD and CMSS at all three menstrual cycles in the LLLT group, While only in VAS and APD at T1-3 and CMSS at T1-2 in the control group (P < 0.05). Compared with the control group, VAS, APD and CMSS at T1-3 and APT at T2-3 were significantly lower in the LLLT group (P < 0.05). During the follow-up period, VAS, APD and CMSS at T4-6 and APT at T4 were significantly lower than baseline in the LLLT group (P < 0.05). No significant reduction from baseline in any index was found in the control group at any time point. Compared with the control group, VAS at T4-5, APT at T4, APD and CMSS at T4-6 were significantly lower in the LLLT group (P < 0.05).
Therapeutic Effect On Anxiety And Depression Symptoms Of Pd
The results of SAS and SDS over time points are shown in Table 3 and Fig. 4(E, F). As illustrated, the two indices gradually decreased during T0-3 and gradually increased during T4-6 in the LLLT group.
Table 3
Therapeutic effect of LLLT on anxiety and depression symptoms of PD
| | SAS | SDS |
T0 | LLLT(n = 68) | 44.29(3.48) | 47.66(3.66) |
| Control(n = 32) | 44.94(3.23) | 46.94(5.18) |
T1 | LLLT(n = 68) | 41.47(3.16) ab | 44.74(3.40) a |
| Control(n = 32) | 44.19(2.88) | 45.63(4.56) a |
T2 | LLLT(n = 68) | 40.68(3.39) ab | 42.31(3.44) ab |
| Control(n = 32) | 43.78(2.72) a | 45.41(4.51) a |
T3 | LLLT(n = 68) | 40.40(3.26) ab | 41.59(3.67) ab |
| Control(n = 32) | 43.97(2.73) | 45.72(3.90) |
T4 | LLLT(n = 68) | 41.71(3.69) ab | 43.74(3.44) ab |
| Control(n = 32) | 44.50(2.84) | 46.25(4.19) |
T5 | LLLT(n = 68) | 43.57 (3.40) | 45.49(3.34) a |
| Control(n = 32) | 44.97(2.83) | 46.41(5.04) |
T6 | LLLT(n = 68) | 44.35(3.42) | 46.65(3.77) a |
| Control(n = 32) | 44.94(3.23) | 46.94(4.08) |
Abbreviations: LLLT, Low level laser therapy; PD, Primary Dysmenorrhea; SAS, Self-rating anxiety score; SDS, Self-rating depression score. a, compared with T0, p < 0.05; b, compared with control group, p < 0.05. |
During the treatment period, significant decrease from baseline was found in SAS and SDS of the LLLT groups at all three menstrual cycles (P < 0.05), while only in SAS at T2 and SDS at T1-2 in the control group (P < 0.05). Compared with the control group, SAS at T1-3 and SDS at T2-3 were significantly lower in the LLLT group (P < 0.05). During the follow-up period, SAS at T4 and SDS at T4-6 were significantly lower than baseline in the LLLT group (P < 0.05). No significant improvement in SAS or SDS from baseline was found in the control group during follow-up period. Compared with the control group, SAS and SDS at only T4 were significantly lower in the LLLT group (P < 0.05).
Cumulative Effect Of Lllt For Pd
The reduction in each index from baseline was calculated to assess the cumulative effect at different time points (Table 4). After three treatments in the LLLT group, all indexes at T3 showed greater improvement when compared with those at T1 (P < 0.05), and ΔVAS, ΔAPT, ΔCMSS, and ΔSDS at T3 were still greater when compared with T2 (P < 0.05). In contrast, no significant differences were found in any of the indicators between T1 and T3 or T2 and T3 in the control group.
Table 4
Accumulative effect of LLLT for PD
| Control group(n = 32) | LLLT group(n = 68) |
| T1 | T2 | T3 | T1 | T2 | T3 |
ΔVAS | -0.56(0.84) | -0.69(0.78) | -0.78(0.71) | -2.07(0.72) | -2.63(0.88) | -2.91(0.82) ab |
ΔAPT | -0.16(0.45) | -0.03(0.31) | -0.12(0.42) | -0.31(0.50) | -0.56(0.58) | -0.76(0.58) ab |
ΔAPD | -0.41(0.56) | -0.31(0.54) | -0.41(0.50) | -1.09(0.57) | -1.37(0.52) | -1.50(0.53) a |
ΔCMSS | -3.53(3.65) | -2.56(3.92) | -3.34(4.44) | -8.44(4.81) | -10.54(4.89) | -15.32(7.68) ab |
ΔSAS | -0.66(1.00) | -1.25(1.41) | -1.00(1.80) | -2.91(1.80) | -3.72(2.13) | -4.03(1.94) a |
ΔSDS | -1.41(1.64) | -1.62(1.70) | -1.31(2.12) | -2.94(2.07) | -5.40(2.72) | -6.15(2.99) ab |
Abbreviations: LLLT, Low level laser therapy; PD, Primary Dysmenorrhea; Δ, change from T0; VAS, Visual Analogue Scale; APT, Time of abdominal pain; APD, Degree of abdominal pain; CMSS, COX Menstrual Symptom Scale; SAS, Self-rating anxiety score; SDS, Self-rating depression score. a, T3 compared with of T1, p < 0.05; b, T3 compared with T2, p < 0.05. |
Utilization Of Rescue Medication And Safety Assessment Of Lllt
The rate of rescue medication use in the LLLT group was significantly lower than that in the control group at T3 (8 cases, 11.75% vs 13 cases, 40.63%, P < 0.05) and T6 (39 cases, 57.35% vs 23 cases, 71.88%, P < 0.05). During the study, there were no reports of adverse events.