Postoperative LNG-IUS for Chronic Pelvic Pain
Abstract & Commentary
By Jeffrey T. Jensen, MD, MPH , Leon Speroff, Professor and Vice Chair for Research, Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, is Editor for OB/GYN Clinical Alert.
Synopsis: Postoperative use of a levonorgestrel intrauterine system effectively manages pelvic pain and improves quality of life in women with moderate to severe chronic pelvic pain found to have endometriosis at laparoscopy.
Source: Tanmahasamut P, et al. Postoperative levonorgestrel-releasing intrauterine system for pelvic endometriosis-related pain: A randomized controlled trial. Obstet Gynecol 2012;119:519-526.
The authors conducted a double-blind, randomized, controlled trial to determine whether the postoperative use of a levonorgestrel intrauterine system (LNG-IUS) was an effective treatment for chronic pelvic pain in women with endometriosis. Subjects with moderate-to-severe dysmenorrhea (defined as a visual analog scale [VAS] score of > 50 mm) and/or chronic pelvic pain for ≥ 6 months who were scheduled to undergo conservative surgery were eligible if they had ASRM Stage 1-4 endometriosis and no other gynecologic abnormalities at the time of surgery. Women were excluded if they had had prior treatments (other than analgesics) for endometriosis, contraindications to the LNG-IUS, planned pregnancy within a year, or would be intolerant of menstrual changes. Women meeting eligibility criteria were randomized to receive the LNG-IUS while under anesthesia or no additional treatment (expectant management). Subjects were not informed as to their treatment group. The study protocol was written to maintain blinding by using a study nurse to collect all information about pain and quality of life (QOL). The primary outcome was the change in dysmenorrhea VAS score from baseline. Secondary outcomes included changes in pelvic pain and dyspareunia VAS scores, QOL (as measured using the Short Form [SF]-36 score), and adverse effects.
A total of 55 women were randomized (LNG-IUS: n = 28, expectant management: n = 27), and the two groups were comparable in age, body mass index, parity, and baseline pain scores. It is notable that most women in both groups were found to have Stage 3 (11% LNG-IUS, 19% expectant) or 4 (57% LNG-IUS, 50% expectant) endometriosis at the time of surgery. At 12 months, compared with the control group, the LNG-IUS group had greater VAS reductions in dysmenorrhea (-81.0 compared with -50.0 mm, P = 0.006) and pelvic pain (-48.5 compared with -22.0 mm, P = 0.038). There was a comparable reduction in dyspareunia (-15.0 compared with -19.0 mm, P = 0.831); however, a significantly higher proportion of the LNG-IUS-treated subjects reported being sexually active at baseline (21/28, 75% compared to 9/26, 33%). In the expectant management group, 39% had recurrent dysmenorrhea (defined as a pain score of > 50 mm occurring after 3 months of postoperative pain relief) within 1 year postoperatively, compared to only 7.4% of those managed with the LNG-IUS (P= 0.014). QOL improved in the LNG-IUS group, but did not change in the expectant management group. The vast majority (25/27, 93%) of LNG-IUS-treated women correctly guessed that they had received the device, and about half (52%) of the expectant group falsely believed that they had received the active treatment. No adverse effects of treatment were reported, but two women in the expectant group underwent repeat surgery for endometriotic cysts at 6 and 9 months after surgery, compared to none in the LNG-IUS group. Four subjects in the LNG-IUS group requested device removal after 1 year due to unacceptable bleeding.
The results of this study add to previous research that demonstrates the LNG-IUS is an effective and well-accepted long-term treatment option for women with moderate-to-severe pain related to endometriosis.
Commentary
The levonorgestrel intrauterine system has moved beyond contraception to become a reliable and proven nonsurgical treatment for many gynecologic problems. Although the FDA-approved labeling for the LNG-IUS only lists intrauterine contraception and treatment of heavy menstrual bleeding (in women who choose to use intrauterine contraception) as approved indications, the literature is full of descriptive series and controlled studies demonstrating the utility of this local hormone delivery device for a variety of gynecologic complaints.1 The absence of a labeling indication is not a barrier to the prescription of most medications, as law does not bar the physician from using the state of the science rather than the label to guide practice. However, the laws and regulations promoted by some religious groups and members of congress that would allow employers to prohibit insurance coverage of contraception would compromise our ability to provide these important gynecologic therapies to many of our patients. The arguments raised against contraceptive coverage make no sense to me. It seems that opposition to any type of logical health care reform has become an orthodoxy that trumps any logic. The evidence clearly shows that universal contraceptive coverage makes sense from an economic standpoint2 and reduces unintended pregnancy and abortion. Furthermore, religious women are no less likely to use contraception than the general population.3 The important noncontraceptive and therapeutic benefits of hormonal contraception as treatments for serious gynecologic conditions, such as heavy menstrual bleeding and endometriosis, provide additional reasons to oppose any effort to restrict access to these important medicines.
The paper by Tanmahasamut provides further evidence documenting the benefit of the LNG-IUS in the treatment of pelvic pain and dysmenorrhea due to endometriosis. These results are not intuitive as endometriosis is a pelvic disease, and the action of the LNG-IUS is primarily local with the circulating level of LNG low in comparison to other delivery systems. Although the authors attempted to maintain blinding of the subjects, most correctly guessed whether they had received an IUS. While we cannot determine whether this influenced the perception of pain, the robust improvement seen in the LNG-IUS-treated women suggests a powerful treatment effect, particularly since more than half of the subjects presented with ASRM Stage 4 endometriosis. Other randomized studies of the LNG-IUS in women with moderate-to-severe endometriosis have shown a similar reduction with a GnRH analogue4 and with Depo-Provera5 as comparators. Biopsies obtained during second look laparoscopies have demonstrated that the ameliorative effect of the IUS on pain symptoms is associated with down regulation of estrogen and progesterone receptors in the ectopic endometrium, a "systemic effect."6
Clinicians should embrace these findings as further evidence that medical therapy effectively manages the symptoms of endometriosis. The LNG-IUS provides a great option to manage women with chronic pelvic pain and endometriosis. A surgical diagnosis of endometriosis is not needed prior to starting medical therapy, and laparoscopy should be avoided unless a pelvic mass is suspected. In my experience, women with high baseline levels of pelvic pain have more insertion-related discomfort, and often complain of post-insertion pain lasting more than 1 to 2 weeks. They should be followed closely to rule out the low likelihood of endometritis or expulsion, and encouraged to continue with the device. Strong analgesic medication may be needed to bridge this time. The prolonged bleeding and spotting common after insertion confuse the situation, but the vast majority of women will experience significant improvement of symptoms within several weeks.
References
- Bednarek PH, Jensen JT. Safety, efficacy and patient acceptability of the contraceptive and non-contraceptive uses of the LNG-IUS. Int J Women's Health 2010;1:45-58.
- Trussell J. The cost of unintended pregnancy in the United States. Contraception 2007;75:168-70.
- Jones R, Dreweke J. Countering Conventional Wisdom: New Evidence on Religion and Contraceptive Use. Guttmacher Institute, 2011 Available at: www.guttmacher.org/pubs/Religion-and-Contraceptive-Use.pdf. Accessed March 5, 2012.
- Bayoglu Tekin Y, et al. Postoperative medical treatment of chronic pelvic pain related to severe endometriosis: Levonorgestrel-releasing intrauterine system versus gonadotropin-releasing hormone analogue. Fertil Steril 2011;95:492-496.
- Wong AY, et al. Levonorgestrel-releasing intrauterine system (Mirena) and Depot medroxyprogesterone acetate (Depoprovera) as long-term maintenance therapy for patients with moderate and severe endometriosis: A randomised controlled trial. Aust N Z J Obstet Gynaecol 2010;50:273-279.
- Engemise SL, et al. Changes in glandular and stromal estrogen and progesterone receptor isoform expression in eutopic and ectopic endometrium following treatment with the levonorgestrel-releasing intrauterine system. Eur J Obstet Gynecol Reprod Biol 2011;157:101-106.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content