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Randomized Controlled Trial
. 2024 May 15:385:e079006.
doi: 10.1136/bmj-2023-079006.

Long acting progestogens versus combined oral contraceptive pill for preventing recurrence of endometriosis related pain: the PRE-EMPT pragmatic, parallel group, open label, randomised controlled trial

Kevin G Cooper  1 , Siladitya Bhattacharya  2 , Jane P Daniels  3 , Andrew W Horne  4 , T Justin Clark  5 , Ertan Saridogan  6 , Versha Cheed  7 , Danielle Pirie  1 , Melyda Melyda  8 , Mark Monahan  8 , Tracy E Roberts  8 , Emma Cox  9 , Clive Stubbs  7 , Lee J Middleton  7 ; PRE-EMPT Collaborative Group
Collaborators, Affiliations
Randomized Controlled Trial

Long acting progestogens versus combined oral contraceptive pill for preventing recurrence of endometriosis related pain: the PRE-EMPT pragmatic, parallel group, open label, randomised controlled trial

Kevin G Cooper et al. BMJ. .

Abstract

Objectives: To evaluate the clinical effectiveness of long acting progestogens compared with the combined oral contraceptive pill in preventing recurrence of endometriosis related pain.

Design: The PRE-EMPT (preventing recurrence of endometriosis) pragmatic, parallel group, open label, randomised controlled trial.

Setting: 34 UK hospitals.

Participants: 405 women of reproductive age undergoing conservative surgery for endometriosis.

Interventions: Participants were randomised in a 1:1 ratio using a secure internet facility to a long acting progestogen (depot medroxyprogesterone acetate or levonorgestrel releasing intrauterine system) or the combined oral contraceptive pill.

Main outcome measures: The primary outcome was pain measured three years after randomisation using the pain domain of the Endometriosis Health Profile 30 (EHP-30) questionnaire. Secondary outcomes (evaluated at six months, one, two, and three years) included the four core and six modular domains of the EHP-30, and treatment failure (further therapeutic surgery or second line medical treatment).

Results: 405 women were randomised to receive a long acting progestogen (n=205) or combined oral contraceptive pill (n=200). At three years, there was no difference in pain scores between the groups (adjusted mean difference -0.8, 95% confidence interval -5.7 to 4.2, P=0.76), which had improved by around 40% in both groups compared with preoperative values (an average of 24 and 23 points for long acting progestogen and combined oral contraceptive pill groups, respectively). Most of the other domains of the EHP-30 also showed improvement at all time points compared with preoperative scores, without evidence of any differences between groups. Women randomised to a long acting progestogen underwent fewer surgical procedures or second line treatments compared with those randomised to the combined oral contraceptive pill group (73 v 97; hazard ratio 0.67, 95% confidence interval 0.44 to 1.00).

Conclusions: Postoperative prescription of a long acting progestogen or the combined oral contraceptive pill results in similar levels of improvement in endometriosis related pain at three years, with both groups showing around a 40% improvement compared with preoperative levels. While women can be reassured that both options are effective, the reduced risk of repeat surgery for endometriosis and hysterectomy might make long acting reversible progestogens preferable for some.

Trial registration: ISRCTN registry ISRCTN97865475.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Institute for Health and Care Research for the submitted work. SB declares receiving fees from Merck and Ferring. AWH declares receiving fees from Theramex. TJC declares receiving fees from Bayer and was president of the British Society of Gynaecological Endoscopy during the study. ES declares receiving fees from Hologic, Medtronic, Karl Storz, Intuitive, and Artrex. All other authors declare no financial relationships with any organisations that might have an interest in the submitted work in the previous three years and no other relationships or activities that could appear to have influenced the submitted work.

Figures

Fig 1
Fig 1
CONSORT (Consolidated Standards of Reporting Trials) trial profile. Completed EHP-30 pain score at any assessment time: LAP, n=195; COCP, n=186. COCP=combined oral contraceptive pill; EHP-30=Endometriosis Health Profile 30; LAP=long acting progestogen
Fig 2
Fig 2
EHP-30 pain scores over all time points. COCP=combined oral contraceptive pill; EHP-30=Endometriosis Health Profile 30; LAP=long acting progestogen
Fig 3
Fig 3
Kaplan-Meier plot of time without further therapeutic surgery or second line treatment. CI=confidence interval; COCP=combined oral contraceptive pill; LAP=long acting progestogen
See this image and copyright information in PMC

References

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