Reducing endometriosis pain with LARC

Both the etonogestrel (ENG)-releasing subdermal implant and a levonorgestrel-releasing intrauterine system (LNG-IUS) significantly reduce pain in women with endometriosis, according to the results of a new randomized clinical trial (RCT). The findings, published in The European Journal of Contraception & Reproductive Health Care, showed that the two contraceptives decreased serum levels of soluble CD23 (P < 0.001).

Methods
The study was conducted at the University of Campinas Medical School in Brazil between June 2016 and January 2019. None of the 103 participants, aged 18 to 45, desired to conceive within the following 6 months. All had surgically or histologically confirmed endometriosis.

Blood sampling was scheduled prior to device placement and at 6-month intervals up to 24 months to measure ENG, LNG, CA-125 and soluble CD23 serum levels. The women were randomized to the ENG implant (n = 52; experimental treatment) or a 52-mg LNG intrauterine system (LNG-IUS) (n = 51; active comparator). The contraceptives were inserted within the first 5 days of a new menstrual cycle. 

All of the women had endometriosis-associated chronic pelvic pain and/or dysmenorrhea for more than 6 months. At 24 months, the rate of discontinuation and loss to follow-up was high in both study arms: 65% in the ENG implant group and 63% in the LNG-IUS group.

Pain scores were divided into no pain/mild pain (a score of 0-3) and moderate-to-severe pain (4-10), then correlated with ENG and LNG serum levels in each group.

Findings
The study found no statistical difference between pain scores and ENG or LNG serum levels over time. Mean ENG serum levels were 129.4 pg/mL at 6 months, 133.6 pg/mL at 12 months, 142.4 pg/mL at 18 months and 130.3 at 24 months, whereas mean LNG serum levels were 114.5 pg/mL at 6 months, 146.2 pg/mL at 12 months, 126.4 pg/mL at 18 months and 132.3 at 24 months. 

For either pain group, there were no significant differences in the two serum levels. However, the study found that serum levels of CA-125 decreased significantly only in the ENG implant group after using the device for 24 months (P < 0.001).

The study showed a significant reduction in VAS pain scores between the initial and final assessments in both treatment groups.

Conclusions
Besides a high discontinuation and loss-to-follow-up rate, the investigators were unable to conduct a double-blind RCT, due to the differences between the two contraceptives, thus representing potential bias. Nonetheless, the authors noted that the findings of their study could help healthcare professionals when counseling women with endometriosis-associated pain. “Progestins such as the ENG implant and the 52-mg LNG-IUS may inhibit oestrogen and progesterone receptor expression on the endometrial surface, reducing inflammatory acidity and pelvic pain,” they wrote.

However, information about using the two contraceptives to treat endometriosis is limited to roughly 300 women to date.