Dienogest for endometriosis in short-term studies (3–6 months): a systematic review and meta-analysis

Summary

Over a 3–6 month horizon, dienogest 2 mg/day produces a clinically meaningful reduction in endometriosis-associated pain with favourable tolerability. The reduction is reproduced across all study types — from randomised trials to large real-world cohorts.

Introduction

Endometriosis is a chronic, oestrogen-dependent disease affecting about 10% of women of reproductive age. Its leading and most disabling manifestation is pelvic pain: secondary dysmenorrhoea, non-cyclic pelvic pain and dyspareunia. Because radical surgery does not eliminate the risk of recurrence, long-term hormonal therapy that suppresses disease activity remains the mainstay of management for most patients.

Dienogest is a fourth-generation oral progestin with selective progestogenic and antiproliferative effects on endometriotic tissue. At 2 mg/day it is approved for endometriosis and has become a first-line option for endometriosis-associated pain.

For both clinician and patient, the early response to therapy is decisive: pain dynamics over the first 3–6 months drive adherence and the decision to continue. We chose this short-term horizon as the focus of the review — unlike most studies, which report long-term (≥12-month) outcomes. From an evidence-based standpoint, the right answer about the magnitude of effect is not a narrative listing of individual studies but their quantitative synthesis.

Aim and review question

To quantitatively assess the efficacy of dienogest 2 mg/day for endometriosis-associated pain and to characterise its tolerability in short-term (3–6 month) studies.

Methods

Search

A systematic PubMed search combining intervention terms (dienogest and brand names) and disease terms (endometriosis). Primary reproducible query:

The query returned 411 records. Open the query in PubMed →

Inclusion criteria

RCT or prospective single-arm before–after study; women with established endometriosis; dienogest 2 mg/day monotherapy; assessment of pain (VAS/VRS) and/or lesions/quality of life; an assessment point within 3–6 months. Excluded: reviews and meta-analyses, retrospective studies and case series, combination products (dienogest within a COC), and studies without relevant outcomes or with long-term timepoints only.

Extraction and analysis

Data were extracted independently over several iterations with disagreement resolution; contested numeric values were checked against the source. Pain measures were harmonised to a single 0–10 scale. The primary synthesis pooled the within-arm pain change using a random-effects model (DerSimonian–Laird, Knapp–Hartung adjustment), with the I² heterogeneity statistic and a 95% prediction interval; when only baseline and end values were reported, the standard error of the change was derived assuming a paired-measurement correlation r = 0.5 (robustness checked for r = 0.3–0.7). Tolerability was pooled as proportions (proportion meta-analysis, logit transform). Physically impossible values or those incompatible with the denominator were automatically excluded and flagged for review.

Study selection flow (PRISMA 2020)

Characteristics of included studies

The included studies span the full range of short-term evidence — from placebo-controlled and active-comparator RCTs (vs GnRH agonists, COC, LNG-IUS, other progestins) to large prospective single-arm real-world cohorts (Cho 2020, n = 2777; Techatraisak 2022, n = 484).

Pain — before–after change meta-analysis

Each included study is shown as a point estimate of the mean pain change (a square whose area is proportional to the study weight in the analysis) and its 95% confidence interval (horizontal line); the diamond denotes the pooled random-effects estimate with its 95% confidence interval. Values are expressed in points on the 0–10 VAS scale; negative values indicate a reduction in pain. Clicking a row opens the publication in PubMed.

Sensitivity analysis

The pelvic-pain result is robust to the assumed correlation of paired measurements (MD estimates in points on the 0–10 VAS scale):

Tolerability

Dienogest tolerability over 3–6 months of treatment was favourable: about 89–94% of patients continued treatment. The most frequent adverse events were changes in the menstrual bleeding pattern, representing an expected progestin class effect; these generally warrant patient counselling rather than treatment discontinuation. Frequencies are reported as pooled proportions (% of patients) with 95% confidence intervals.

Discussion

The findings give an unambiguous answer: over 3–6 months, dienogest produces a clinically meaningful reduction in pain. The reduction in pelvic pain and dysmenorrhoea confidently exceeds the minimal clinically important difference and is consistent in direction across all study types. The effect on dyspareunia is weaker and less stable, which is explained by the more complex nature of this symptom.

A meaningful response is achieved within the first months of treatment — and it is this early dynamic that drives adherence and the decision to continue.

Comparison with prior reviews. Prior systematic reviews considered dienogest mainly in the post-surgical and long-term context; our work complements them by quantitatively characterising precisely the short-term window across several pain domains.

Limitations

• High statistical heterogeneity (I² ≈ 98–99%). Importantly, this does not mean the results are contradictory: every study shows a pain reduction in the same direction. The high I² here results from very large samples and correspondingly tiny standard errors, under which even small differences in baseline pain severity, scales used and population characteristics statistically inflate the heterogeneity statistic. Why this is acceptable: (1) we used a random-effects model from the outset, which explicitly incorporates between-study variability into the estimate and its confidence interval; (2) the 95% prediction intervals for pelvic pain and dysmenorrhoea do not cross the line of no effect and remain in the zone of clinical improvement — i.e. a pain reduction is expected even in a new, previously unobserved study.
• Single-arm design of most studies: the before–after change includes natural history, regression to the mean and placebo effect, and may somewhat overstate the net drug effect.
• Heterogeneity of pain scales, harmonised to a single 0–10 scale (approximate for some ordinal scales).
• Assumed correlation of paired measurements (the result is shown to be robust to it).
• Incomplete full-text retrieval (8 of 74 unavailable).
• A single search source (PubMed) in this iteration.
• Risk-of-bias assessment was not performed — the key direction for the full version.

Conclusions

References

Studies included in the quantitative pain synthesis (n = 27):

1. Abdou (2018). Dienogest Versus Leuprolide Acetate for Recurrent Pelvic Pain Following Laparoscopic Treatment of Endometriosis. Journal of obstetrics and gynaecology of India. PubMed
2. Bhoir (2026). Efficacy and Safety of Elagolix Versus Dienogest for Treatment of Moderate-to-Severe Endometriosis Pain: A Phase III, Multicentric, Double-Blind, Active-Controlled, Non-Inferiority Study. BJOG : an international journal of obstetrics and gynaecology. PubMed
3. Chaichian (2024). CGRP neuropeptide levels in patients with endometriosis-related pain treated with dienogest: a comparative study. BMC women's health. PubMed
4. Cho (2020). Safety and Effectiveness of Dienogest (Visanne®) for Treatment of Endometriosis: A Large Prospective Cohort Study. Reproductive sciences (Thousand Oaks, Calif.). PubMed
5. Kikuno (2025). Efficacy and Safety of 48-Week Low-Dose Dienogest Treatment in Patients with Endometriosis-Associated Dysmenorrhea: A Randomized, Open-Label, Parallel-Group Trial. Advances in therapy. PubMed
6. Lang (2018). Dienogest for Treatment of Endometriosis in Chinese Women: A Placebo-Controlled, Randomized, Double-Blind Phase 3 Study. Journal of women's health (2002). PubMed
7. Lee (2018). Comparison of the efficacy of diegnogest and levonorgestrel-releasing intrauterine system after laparoscopic surgery for endometriosis. The journal of obstetrics and gynaecology research. PubMed
8. Lee (2018). Effectiveness of Dienogest for Treatment of Recurrent Endometriosis: Multicenter Data. Reproductive sciences (Thousand Oaks, Calif.). PubMed
9. Long (2024). The clinical effect of dienogest on urinary and sexual symptoms in endometriosis patients. Journal of the Chinese Medical Association : JCMA. PubMed
10. Maiorana (2017). Efficacy of dienogest in improving pain in women with endometriosis: a 12-month single-center experience. Archives of gynecology and obstetrics. PubMed
11. Malik (2021). Role of Dienogest in Endometriosis in Young Women. Journal of obstetrics and gynaecology of India. PubMed
12. Mehdizadeh Kashi (2022). A randomized, double-blind, placebo-controlled pilot study of the comparative effects of dienogest and the combined oral contraceptive pill in women with endometriosis. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. PubMed
13. Momoeda (2009). Long-term use of dienogest for the treatment of endometriosis. The journal of obstetrics and gynaecology research. PubMed
14. Niakan (2021). Comparing the Effect of Dienogest and OCPS on Pain and Quality of Life in Women with Endometriosis: A Randomized, Double-Blind, Placebo-Controlled Trial. Archives of Iranian medicine. PubMed
15. Osuga (2020). Long-term use of dienogest for the treatment of primary and secondary dysmenorrhea. The journal of obstetrics and gynaecology research. PubMed
16. Park (2025). Association between depressive symptoms and dienogest in patients treated for endometriosis: Using the Center for Epidemiological Studies Depression (CES-D) and the State-Trait Anxiety Inventory (STAI). European journal of obstetrics, gynecology, and reproductive biology. PubMed
17. Piacenti (2021). Dienogest versus continuous oral levonorgestrel/EE in patients with endometriosis: what's the best choice?. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. PubMed
18. Rezaeinejad (2026). Synergistic effects of melatonin and dienogest on pain relief in endometriosis: a randomized controlled trial. Obstetrics & gynecology science. PubMed
19. Saglik Gokmen (2023). Effects of Dienogest Therapy on Endometriosis-Related Dysmenorrhea, Dyspareunia, and Endometrioma Size. Cureus. PubMed
20. Strowitzki (2010). Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial. Human reproduction (Oxford, England). PubMed
21. Strowitzki (2012). Detailed analysis of a randomized, multicenter, comparative trial of dienogest versus leuprolide acetate in endometriosis. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. PubMed
22. Suwan (2026). Efficacy and acceptability of dienogest among patients with endometriosis in Thailand. BMC women's health. PubMed
23. Techatraisak (2019). Effectiveness of dienogest in improving quality of life in Asian women with endometriosis (ENVISIOeN): interim results from a prospective cohort study under real-life clinical practice. BMC women's health. PubMed
24. Techatraisak (2022). Impact of Long-Term Dienogest Therapy on Quality of Life in Asian Women with Endometriosis: the Prospective Non-Interventional Study ENVISIOeN. Reproductive sciences (Thousand Oaks, Calif.). PubMed
25. Vahid-Dastjerdi (2023). Comparison of the effectiveness of Dienogest with medroxyprogesterone acetate in the treatment of pelvic pain and recurrence of endometriosis after laparoscopic surgery. Archives of gynecology and obstetrics. PubMed
26. Yanase (2014). Relief of uterine bleeding by cyclic administration of dienogest for endometriosis. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. PubMed
27. Yurtkal (2024). Comparison of dienogest or combinations with ethinylestradiol/estradiol valerate on the pain score of women with endometriosis: A prospective cohort study. Medicine. PubMed