Dienogest vs Levonorgestrel/Ethinyl Estradiol for Endometriosis

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Dienogest vs levonorgestrelethinyl estradiol for endometriosis

Dienogest versus continuous oral levonorgestrel/EE in patients with endometriosis: what’s the best choice?

A prospective cohort study was carried out to compare the effect of dienogest (2mg) vs a combined oral contraceptive (levonorgestrel 0.1mg/ethinyl estradiol 0.02mg) on ovarian endometriomas, deep infiltrating endometriosis (DIE), chronic pelvic pain (CPP), dyspareunia, pain relief, quality of life and the potential side effects.

Patients with pelvic endometriosis were recruited from the Policlinico Umberto I University Hospital in Rome between June 2017 and October 2019. Treatment with either oral dienogest or levonorgestrel/ethinyl estradiol was chosen independently before study recruitment according to patient preference. Patients with metabolic or chronic diseases, in pre-menarche or menopause, trying for pregnancy or contraindications to treatment were excluded from the study.

Overall a total of 100 women participated in the study, with 50 women in Group A (dienogest) and Group B (levonorgestrel/ethinyl estradiol) respectively. A complete medical history was taken of each patient, to identify any significant differences between the groups, which could cause bias in the results.

Follow up was then carried out at 3 and 6 months for assessment of dyspareunia and CPP (Visual analog score), use of non-steroidal pain relief, health status and quality of life (SF-12 validated questionnaire). The presence and size of endometriomas and deep infiltrating endometriosis lesions was recorded by transvaginal pelvic ultrasound scan (TVUS), with the same operator each time for consistency, while various symptoms and side effects was captured using a separate questionnaire.

At completion of the study period, 14 women had dropped out, leaving 43 patients per group for final analysis. Baseline characteristics of each group showed no difference in BMI, dysmenorrhea, dyspareunia, use of non-steroidal pain relief, parity, size of ovarian endometriomas and DIE lesions. Chronic pelvic pain was present in over 50% of women from each group (Group A = 53.5%, Group B = 51.2%) although group A did report a higher visual analog pain score (7.8 ±1.8 vs 6.4±2.5).

In group A (dienogest) at the end of 6 months, ultrasound results showed a significant decrease in the mean size of endometriomas (38.3mm to 25.9mm) and DIE lesions (16mm to 8.7mm). Similarly CPP also decreased (53.3% to 19.4%) along with dyspareunia (55.8% to 27.8%), resulting in a significant drop in the use of non-steroidal pain relief (88.4% to 22.2%) and increase in quality of life scores. Side effect analysis did show an increase in vaginal bleeding during the first 3 months (18.6% to 61.1%) which then decreased to only 30.6% of women at the end of 6 months.

In group B (levonorgestrel/ethinyl estradiol), no statistically significant improvements was seen in the size of endometriomas, volume of DIE lesions, dyspareunia and prevalence of CPP, although there was a mild downward trend in all 4 categories. Interestingly a significant decrease in the VAS of dyspareunia (6.7 to 4.7) was noted along with the use of non-steroidal pain relief (86% to 33.3%). Quality of life assessment showed a mild improvement in the physical component score (46.2 to 51.6) while vaginal bleeding was similarly higher, over the first 3 months (16.3% to 58.%), decreasing to 33.3% of women by the end of the 6th month.

When comparing the two groups, no significant differences was found at the end of treatment regarding outcomes or side effects, although group A patients did start treatment with a higher mean size of endometriomas (38.3 vs 30.1) and finished the treatment with smaller DIE lesions (8.7 vs 11.6).

Although the results are promising, the authors stated the need for a larger randomized control trial to confirm these findings.

SUMMARY: What is the best medication for endometriosis

In this study, comparing 2 types of medication for endometriosis (dienogest vs levonorgestrel/ethinyl estradiol), found that treatment with dienogest was better at reducing the size of endometriomas (-12.4 vs 5.7 mm) & deep infiltrating endometriosis lesions (-7.3 vs -4.2 mm) over a 6 month period.


  1. Small sample size
  2. Observational study design
  3. No histological confirmation of endometriosis

Similar studies

Angioni S, et al. (2019). Is dienogest the best medical treatment for ovarian endometriomas? Results of a multicentric case control study. https://doi.org/10.1080/09513590.2019.1640674

Lang J, et al. (2018). Dienogest for Treatment of Endometriosis in Chinese Women: A Placebo-Controlled, Randomized, Double-Blind Phase 3 Study. https://doi.org/10.1089/jwh.2017.6399

Vercellini P, et al. (2018). A stepped-care approach to symptomatic endometriosis management: a participatory research initiative. https://doi.org/10.1016/j.fertnstert.2018.01.037


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