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. 2022 Nov;39(11):4892-4909.
doi: 10.1007/s12325-022-02298-9. Epub 2022 Sep 1.

Efficacy of Low-Dose Estrogen-Progestins and Progestins in Japanese Women with Dysmenorrhea: A Systematic Review and Network Meta-analysis

Masaru Iwata  1 , Yoshihiro Oikawa  2 , Yutaka Shimizu  2 , Naotaka Sakashita  3 , Ayako Shoji  3   4 , Ataru Igarashi  4   5 , Yutaka Osuga  6
Affiliations

Efficacy of Low-Dose Estrogen-Progestins and Progestins in Japanese Women with Dysmenorrhea: A Systematic Review and Network Meta-analysis

Masaru Iwata et al. Adv Ther. 2022 Nov.

Abstract

Introduction: Although several studies suggest beneficial effects of low-dose estrogen-progestins (LEPs) and progestins on dysmenorrhea in Japanese women, the difference in efficacy between drugs remains unknown.

Methods: We identified studies by searching the MEDLINE, Cochrane Library, and ICHUSHI databases and included randomized controlled trials (RCTs) that used total dysmenorrhea score and visual analogue scale (VAS) as outcome measures to evaluate LEPs and progestins for primary and secondary dysmenorrhea. We analyzed results by meta-analysis and network meta-analysis (NMA).

Results: We identified 10 articles on eight RCTs and included seven drugs (six LEPs and one progestin, i.e., dienogest) and placebo in the analysis. Meta-analysis showed improvements in total dysmenorrhea score and VAS for almost all drugs compared with placebo. In NMA, VAS in secondary dysmenorrhea improved more with dienogest than with norethisterone/ethinylestradiol (mean difference - 25.84 [95% CrI - 44.46 to - 7.15]). In the comparison of administration regimens, VAS improved more with progestin-continuous than LEP-cyclic and the surface under the cumulative ranking (SUCRA) of LEP-extended and progestin-continuous appeared to be higher than that of LEP-cyclic.

Conclusions: We confirmed that LEPs and dienogest are effective for primary and secondary dysmenorrhea and suggest that continuous regimens may be more effective than cyclic regimens in improving outcomes.

Keywords: Dysmenorrhea; Low-dose estrogen–progestins; Meta-analysis; Progestins; Systematic review.

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Figures

Fig. 1
Fig. 1
Flow diagram of the literature selection process. RCT randomized controlled trial, SLR systematic literature review
Fig. 2
Fig. 2
Forest plot of direct meta-analysis of drug treatments for dysmenorrhea assessed by total dysmenorrhea score (a primary dysmenorrhea; c secondary dysmenorrhea) and visual analogue scale (b primary dysmenorrhea; d secondary dysmenorrhea). DNG dienogest with continuous regimen, DRSP/EE-cyclic drospirenone/ethinylestradiol betadex with cyclic regimen, DRSP/EE-extended drospirenone/ethinylestradiol betadex with extended regimen, LNG/EE-cyclic levonorgestrel/ethinylestradiol with cyclic regimen, LNG/EE-extended levonorgestrel/ethinylestradiol with extended regimen, NET/EE LD-cyclic norethisterone/ethinylestradiol with cyclic regimen, NET/EE ULD-cyclic ultra-low-dose norethisterone/ethinylestradiol with cyclic regimen, 95% CI 95% confidence interval, RE model random effects model
Fig. 3
Fig. 3
Network diagram of indirect comparisons. Each node represents intervention arm. The lines represent the direct comparison in the studies. a Total dysmenorrhea score in primary dysmenorrhea; b visual analogue scale in primary dysmenorrhea; c total dysmenorrhea score in secondary dysmenorrhea; d visual analogue scale in secondary dysmenorrhea. DNG dienogest with continuous regimen, DRSP/EE-cyclic drospirenone/ethinylestradiol betadex with cyclic regimen, DRSP/EE-extended drospirenone/ethinylestradiol betadex with extended regimen, LNG/EE-cyclic levonorgestrel/ethinylestradiol with cyclic regimen, LNG/EE-extended levonorgestrel/ethinylestradiol with extended regimen, NET/EE LD-cyclic norethisterone/ethinylestradiol with cyclic regimen, NET/EE ULD-cyclic ultra-low-dose norethisterone/ethinylestradiol with cyclic regimen
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References

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