Treatment of endometriosis with dienogest in combination with traditional Chinese medicine: A systematic review and meta-analysis

Abstract

Background: Endometriosis is now considered to be a systemic disease rather than a disease that primarily affects the pelvis. Dienogest (DNG) has unique advantages in the treatment of endometriosis, but it also has side effects. Alternatively, Traditional Chinese Medicine (TCM) has been used for over 2000 years in the treatment and prevention of disease and growing numbers of Chinese scholars are experimenting with the combined use of Dienogest and TCM for endometriosis treatment.

Objectives: This review evaluated the efficacy and safety of TCM in combination with Dienogest in the treatment of endometriosis through meta-analysis.

Methods: MEDLINE, Embase, the Cochrane Library, PubMed, Web of Science, China National Knowledge Infrastructure, Journal Integration Platform, and Wanfang were used in literature searches, with a deadline of May 31, 2022. Literature quality was assessed using the Cochrane Collaboration "risk of bias" (ROB2) tool, and the "meta" package of R software v.4.1 was used for meta-analysis. Dichotomous variables and continuous variables were assessed using the relative risk (RR) and 95% confidence intervals (95% CI); standard mean differences (MD) and 95% CI, respectively.

Results: Twelve human randomized controlled trials (RCTs) and one retrospective study, all 13 written in the Chinese language, were included in the meta-analysis (720 experiments and 719 controls). The result indicated that TCM plus Dienogest was superior to Dienogest/TCM alone in increasing the cure rates (RR = 1.3780; 95% CI, 1.1058, 1.7172; P = 0.0043), remarkable effect rate (RR = 1.3389; 95% CI, 1.1829, 1.5154; P < 0.0001), invalid rate (RR = 0.2299; 95% CI, 0.1591, 0.3322; P < 0.0001), and rate of adverse effects (RR = 0.6177; 95% CI, 0.4288, 0.8899; P = 0.0097). The same conclusion was drawn from the subgroup analysis.

Conclusion: Results suggest that TCM combined with Dienogest is superior to Dienogest or TCM alone and can be used as a complementary treatment for endometriosis. TCMs have potential to improve clinical efficacy and reduce the side effects of Dienogest. This study was financially supported by Annual Science and Technology Steering Plan Project of Zhuzhou. PROSPERO has registered our meta-analysis as CRD42022339518 (https://www.crd.york.ac.uk/prospero/record_email.php).

Keywords: dienogest; endometriosis; meta-analysis; review; traditional Chinese medicine.

Figure 1

The workflow of this study.

Figure 2

Quality assessment chart of all literature included in this study.

Figure 3

Overall meta-analysis forest plot of treatment effect rates. (A) cure rate, a fixed effects model was used as no significant heterogeneity (I² = 0.0%, P = 0.9611) was found. The result (RR = 1.3863; 95% CI, 1.1008; 1.7458, P = 0.0043) indicated that TCM plus DNG was superior to DNG/TCM alone in increasing the cure rate. (B) remarkable effect rates, a fixed effects model was used as no significant heterogeneity (I² = 0.0%, P = 0.9530) was found. The result (RR = 1.3389; 95% CI, 1.1829,1.5154; P < 0.0001) indicated that TCM plus DNG was superior to DNG/TCM alone in increasing remarkable effect rate. (C) effective rate, a fixed effects model was used as no significant heterogeneity (I² = 0.0%, P = 0.8638) was found. The result (RR = 0.9411; 95% CI, 0.7752, 1.1425; P = 0.5395) indicated that there was no significant difference between the two groups in terms of effective rate. (D) invalid rate, a fixed effects model was used as no significant heterogeneity (I² = 0.0%, P = 0.9629) was found. The result (RR = 0.2299; 95% CI, 0.1591, 0.3322; P < 0.0001) indicated that TCM plus DNG was superior to DNG/TCM alone in decreasing invalid rate.

Figure 4

Overall meta-analysis forest and sensitivity analysis plot of adverse effects rates. (A) Overall meta-analysis forest plot, there were no significant statistically significant differences (I² = 12.4%, P = 0.3316); thus, the fixed model was assumed. The combination of DNG with TCM for endometriosis can significantly reduce the rate of adverse reactions compared to DNG or TCM alone (RR = 0.6177; 95% CI, 0.4288, 0.8899; P = 0.0097). (B) sensitivity analysis plot of the adverse effects rates, according to the leave-one-out method sensitivity analysis, the individual study results had no impact on the meta-analysis results.

Figure 5

Subgroup analysis forest plot based on the treatment course, different TCM + DNG and different controls of treatment effect rates. (A–D) Subgroup analysis forest plot based on the treatment course of treatment effect rates. (E–H) Subgroup analysis forest plot based on different TCM + DNG of treatment effect rates. (I–K) Subgroup analysis forest plot based on different control of treatment effect rates. (A,E,I) cure rate; (B,F,J) remarkable effects rate; (C,G,K) effective rate; (D,H,L) invalid rates. Significant differences were not observed between the subgroups.

Figure 6

Sensitivity analysis plot of treatment effect rates. According to the leave-one-out method sensitivity analysis, the individual study results had no impact on the meta-analysis results in all four rates. (A) cure rate; (B) remarkable effect rate; (C) effective rate; (D) invalid rate.

Figure 7

Funnel plot of treatment effect rates and adverse effects rates. (A) cure rate; (B) remarkable effect rate; (C) effective rate; (D) invalid rate; and (E) adverse effects rate. According to the funnel plot, there is no evidence for publication bias.

Figure 8

Subgroup analysis forest plot based on post-treatment visual analogue scale/score. Study 1 and 5: Jingtong yushu granule and Bushen Huayu decoction. Study 2 and 3 Gui’e lengwu decoction; study 4 and 6: Gui Zhi Fu Ling capsules/wan.