Which is better for endometriosis-related pain: oral contraceptives or long-acting progestogens?

Endometriosis is an estrogen-dependent condition that affects up to one in 10 women of reproductive age. It is characterized by the growth of endometrial-like tissue outside the uterus, which leads to severe pelvic pain and infertility that can seriously reduce quality of life. Laparoscopic excisional or ablative surgery for endometriosis improves pain symptoms, but postoperative recurrence of endometriosis is common. In a Scottish study, after initial surgery for endometriosis, 62% of treated women required at least one repeat operation, 45% had two or more, and nearly 25% needed surgical removal of their ovaries, often combined with a hysterectomy.Combined oral contraceptive pills and progestogens are widely used to treat endometriosis-related pain, but uncertainty exists regarding which of these two hormonal options is better for preventing recurrence of pain after endometriosis surgery.To examine this issue, UK researchers evaluated the clinical effectiveness of long-acting progestogens compared with the combined oral contraceptive pill in preventing the recurrence of endometriosis related pain. The PRE-EMPT (preventing recurrence of endometriosis) study, conducted in 34 UK hospital gynecology clinics, was a parallel group, open-label, randomized controlled trial. The study included 405 women of reproductive age undergoing conservative surgery for endometriosis. Participants were randomized in a 1:1 ratio to receive a long-acting reversible progestogen (depot medroxyprogesterone acetate or levonorgestrel-releasing intrauterine system) or the combined oral contraceptive pill (ethinyl estradiol 30 μg and levonorgestrel 150 μg).The primary outcome was pain measured three years after randomization using the pain domain of the Endometriosis Health Profile 30 (EHP-30) questionnaire. Secondary outcomes (evaluated at 6 months, and 1, 2 and 3 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 showed the following:405 women were randomized 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 two groups (adjusted mean difference −0.8, 95% confidence interval [CI] −5.7 to 4.2, p=0.76).Pain scores improved by about 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). On average, both groups maintained improved pain scores at all follow-up intervals compared with their preoperative scores.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 receiving a long-acting progestogen underwent fewer surgical procedures or second-line treatments compared with those receiving the combined oral contraceptive pill (73 v 97; hazard ratio 0.67, 95% CI 0.44–1.00).Choice of a particular long-acting progestogen (depot medroxyprogesterone acetate vs. levonorgestrel-releasing intrauterine system) before randomization did not alter the findings. The investigators concluded that postoperative use of a long-acting progestogen or the combined oral contraceptive pill resulted in similar levels of improvement in endometriosis-related pain at three years, with both groups showing around a 40% improvement compared with preoperative pain levels. Women can be reassured that both hormonal options are effective; however, some women may prefer the use of long-acting reversible progestogens, as this study showed that they reduce the risk of repeat surgery for endometriosis and hysterectomy, and the need for second-line treatments. Reference1. Cooper KG, Bhattacharya S, Daniels JP, et al; PRE-EMPT Collaborative Group. Long acting progestogens versus combined oral contraceptive pill for preventing recurrence of endometriosis related pain: the PRE-EMPT pragmatic, parallel group, open label, randomized controlled trial. BMJ 2024;385:e079006. (accessed May 21, 2024).

Which is better for endometriosis-related pain: oral contraceptives or long-acting progestogens?

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