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Obstetrics & Gynecology:
doi: 10.1097/AOG.0b013e31824264c3
Original Research

Postoperative Levonorgestrel-Releasing Intrauterine System for Pelvic Endometriosis-Related Pain: A Randomized Controlled Trial

Tanmahasamut, Prasong MD; Rattanachaiyanont, Manee MD; Angsuwathana, Surasak MD; Techatraisak, Kitirat MD; Indhavivadhana, Suchada MD; Leerasiri, Pichai MD

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Author Information

From the Gynecologic Endocrinology Unit, Division of Reproductive Medicine, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Supported by the research fund of the Gynecologic Endocrinology Unit, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand. Bayer Schering Pharma Company provided the levonorgestrel-releasing intrauterine system but neither supported the funding for the study nor had influence on the study protocol, data analysis, and manuscript preparation.

The authors thank Chulaluk Komoltri, DrPH, a statistician of the clinical epidemiology unit, Faculty of Medicine Siriraj Hospital, Mahidol University, for statistical analysis and comment on methodology of the study.

Corresponding author: Prasong Tanmahasamut, MD, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, 2 Prannok Road, Bangkok 10700, Thailand; e-mail: sipta@mahidol.ac.th.

Financial Disclosure The authors did not report any potential conflicts of interest.

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Abstract

OBJECTIVES: To estimate the effectiveness of a postoperative levonorgestrel-releasing intrauterine system for relieving pelvic pain in patients with endometriosis.

METHODS: A double-blind randomized controlled trial was conducted in 55 patients with endometriosis and moderate-to-severe dysmenorrhea (visual analog scale, greater than 50 mm) undergoing laparoscopic conservative surgery. After surgery, patients were randomized to a levonorgestrel-releasing intrauterine system (n=28) or expectant management (n=27) group. Primary outcome was the change of dysmenorrhea visual analog scale. Secondary outcomes included changes of pelvic pain and dyspareunia visual analog scale, Short Form-36 score, and adverse effects.

RESULTS: The two groups were comparable in age, body mass index, parity, and baseline pain scores. At 12 months, the levonorgestrel-releasing intrauterine system group had a significantly lower median value of dysmenorrhea and noncyclic pelvic pain score. Compared with the control group, the levonorgestrel-releasing intrauterine system group had greater reduction in dysmenorrhea visual analog scale (−81.0 compared with −50.0 mm, P=.006) and pelvic pain visual analog scale (−48.5 compared with −22.0 mm, P=.038) but a comparable reduction in dyspareunia visual analog scale (−15.0 compared with −19.0 mm, P=.831). Two patients in levonorgestrel-releasing intrauterine system group (7.4%) and nine in the expectant management group (39.1%) had recurrent dysmenorrhea within 1 year postoperatively (P=.014). Number-needed-to-treat to prevent one case with recurrent dysmenorrhea within the first year was three cases. The Short Form-36 scores improved in the levonorgestrel-releasing intrauterine system group but did not change in the expectant management group. There was no serious adverse event during the study period.

CONCLUSION: The levonorgestrel-releasing intrauterine system is effective and well accepted for long-term therapy after conservative surgery for patients with moderate to severe pain related to endometriosis. It can improve the patient's quality of life, including physical and mental health.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00455845.

LEVEL OF EVIDENCE: I

Endometriosis is a common cause of chronic pelvic pain affecting 3–10% of women of reproductive age.1 The incidence of endometriosis is as high as 70–90% in women with cyclic and noncyclic chronic pelvic pain.2 Laparoscopic surgery, although it provides satisfactory outcomes for symptomatic disease,3 has recurrent symptoms of approximately 10–20% per year.4 Postoperative medical therapy for prevention of recurrence is still a controversial issue. Whereas some studies have observed a longer pain-free interval or higher pregnancy rate with postoperative medical treatment,5,6 others did not find such benefits.710

Postoperative medical therapy includes agents that induce either pseudomenopause or a pseudopregnancy state.2 Recently, an aromatase inhibitor has been shown to be effective in women with refractory endometriosis.11,12 Despite their effectiveness, systemic side effects of these agents commonly affect compliance, precluding their long-term use. Moreover, the need for regular administration further lessens the compliance, undermining the efficacy. These drawbacks are common in oral and injectable progestins, which are associated with poorly tolerated side effects of irregular vaginal bleeding, weight gain, fluid retention, seborrhea, and breast tenderness. In addition, there has been increasing concern regarding the possible adverse effects of long-term systemic progestins on bone metabolism.13 The use of progestin administered locally to the uterine cavity might be effective with less metabolic side effects.

A levonorgestrel-releasing intrauterine system provides an alternative mode of administering progestins. At the steady stage, it delivers levonorgestrel into the uterine cavity of 20 μg/day over its 5-year lifespan.14 The release rate and the systemic level are less than those provided by the progestin-only pill, depot progestin, and subcutaneous levonorgestrel implants1518; therefore, the side effects of a levonorgestrel-releasing intrauterine system are theoretically less severe. Previous pilot studies have shown that the levonorgestrel-releasing intrauterine system could relieve dysmenorrhea and reduce the recurrent rate of moderate to severe dysmenorrhea associated with endometriosis.19,20 There were a few randomized controlled trials on the use of the levonorgestrel-releasing intrauterine system in endometriosis.2,2022 Most of them had a small sample size.

The present study compared a postoperative levonorgestrel-releasing intrauterine system with expectant management of endometriosis, primarily in the reduction of dysmenorrhea and also their effects on noncyclic pelvic pain, dyspareunia, vaginal bleeding, treatment satisfaction, and quality of life.

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MATERIALS AND METHODS

The present double-blind randomized controlled trial was carried out in the Gynecologic Endocrinology Unit, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, a tertiary care hospital from February 2007 to December 2009. The study was conducted in accordance with the ethical principles of the Helsinki Declaration and the study protocol was approved by the Siriraj institutional review board.

The study population were women with moderate to severe dysmenorrhea, chronic pelvic pain, or both for more than 6 months and who were scheduled for laparoscopic surgery, excluding the patients who did not have endometriosis, had uterine or adnexal anomalies other than endometriosis, had previous or current treatments for endometriosis other than analgesic medications, were unable to perform conservative surgery, had contraindications to a levonorgestrel-releasing intrauterine system as defined by the World Health Organization (2004), were unwilling to tolerate menstrual changes, or planned for pregnancy within 1 year. Eligible patients were informed about the study protocol and invited to participate in the study without coercion. Signed informed consent was obtained before operation and before taking demographic data. Each patient was asked to complete a questionnaire on general data, quality of life, and various types of pelvic pain, including dysmenorrhea, noncyclic pelvic pain, and deep dyspareunia.

All patients underwent day-case laparoscopic surgery under general anesthesia. The operation was performed using only mechanical instruments and electrosurgery. Adhesions were dissected using microscissors. Ovaries were completely mobilized and endometriotic cysts were evacuated and excised by means of countertraction applied on its pseudocapsule and normal ovarian tissue using atraumatic forceps. Bleeding was stopped with limited application of bipolar current.

After completing the operation, before reversing anesthesia, the patients were allocated to either the experiment or control group. For those in the experiment group, a levonorgestrel-releasing intrauterine system was inserted into the uterine cavity by the surgeon while the patient was still unconscious under general anesthesia. For those in the control group, expectant management was planned. The follow-up management was the same in both groups. Therefore, the patient was blinded to the treatment group.

Treatment allocation was by simple randomization. Experiment codes were produced using a computer-generated list of random numbers. The codes were individually contained in a sealed opaque envelope, which was sequentially numbered and then chronologically opened in the operating room only after an eligible patient was identified.

On discharge, a structured diary was provided to each patient for daily recording pelvic pain, vaginal bleeding, and type and number of analgesic medication. Follow-up visits were scheduled at 1, 3, 6, 9, and 12 months after surgery. At each visit, a research nurse, who was unaware of the patient treatment group, assessed the patient for subjective outcomes. The patient met a gynecologist who performed a clinical examination and transvaginal or transrectal ultrasonography and then provided treatment as indicated. The nurse and the gynecologist recorded the data independently. The former recorded data in a case record form, whereas the latter recorded it in an outpatient medical record; this step was taken to maintain the double-blind status, ie, the patients and the assessor nurse were blinded to the treatment groups. At the end of the study period, each patient was asked to guess the treatment group that she was in; this question was intended to assess the adequacy of our blinding technique.

The baseline characteristics being collected included age, parity, body mass index (calculated as weight (kg)/[height (m)]2), stage of endometriosis according to the revised American Society for Reproductive Medicine, and severity and types of pelvic pain including dysmenorrhea, chronic pelvic pain, and dyspareunia. The primary outcome was severity of dysmenorrhea. In the present study, dysmenorrhea was defined as pelvic pain associated with any vaginal bleeding episode, either cyclic or erratic bleeding. Secondary outcomes were severity of chronic pelvic pain and dyspareunia, changes in quality of life, overall satisfaction of the treatment, and side effects.

All types of pelvic pain were assessed using a visual analog scale, which is a 100-mm horizontal line with two descriptors, ie, “no pain” at the left end and “intolerable pain” at the right end. Pain score was measured using a ruler with a minimum measuring unit of 1 mm. The score was then transformed to severity of pain, ie, mild (score 1–50), moderate (score 51–80), and severe (score 81–100) pain. Recurrent pain was defined as a pain score of greater than 50 mm occurring after 3 months postoperative pain relief. The quality of life was assessed using a validated Thai version Short Form-36.23,24 The overall satisfaction was evaluated using a 5-point Likert scale, ie, very satisfied, satisfied, uncertain, dissatisfied, and very dissatisfied.

The pain scores were assessed at months 0, 1, 3, 6, 9, and 12. The maximum pain score within 30 days before the follow-up visit was used for analysis. For the intention-to-treat analysis, the worst-case scenario, ie, worst pain (visual analog scale=100 mm), was applied to the lost-to-follow-up cases. The quality of life was assessed at months 0, 6, and 12; the overall satisfaction at months 0 and 12; the side effects at months 1, 3, 6, 9, and 12.

The sample size was calculated using a formula to compare two proportions. When α=0.05, power=80%, and proportion of recurrent pain from a previous pilot study by Vercellini et al20 in the control group=.45 and in the treatment group=.1, sample size in each group plus 10% dropouts was 27.

Statistical analyses were performed with SPSS 14.0 for Windows. Data were presented in mean and standard deviation, median and range or interquartile range, number and percent, or relative risk (RR) and 95% confidence interval (CI), as appropriate.

Analyses of the efficacy outcomes were based on intent-to-treat population, whereas those of side effects were based on per-protocol population. All tests of hypotheses were conducted at the two-sided and .05 level of significance. Continuous data were tested for normality using histogram, Kolmogorov-Smirnov test, and normal Q-Q plot. The normal Q-Q plot is a graph comparing the distribution of a given variable with the normal distribution represented by a straight line. The closer the points are to the line, the more normally distributed the data looks.25 Because the pain scores were not normally distributed, the Mann-Whitney U test was used to examine the differences between the study groups in the maximum pain score, Wilcoxon's signed-rank test was used to compare between the pain score at month 12 and month 0 in the same group, and the Friedman nonparametric two-way analysis of variance was used to examine the pain profile. The Student's t test and the χ2 test (or Fisher's exact test) were used to analyze normally distributed continuous data and categorical data, respectively. The repeated-measures analysis of variance was used to analyze profiles of quality-of-life scores. The number-needed-to-treat and its 95% CI were calculated based on the absolute risk reduction: number-needed-to-treat=1/absolute risk reduction; whereas the absolute risk reduction was the reduction in the proportion of the patients who had a pain score greater than 50 in the levonorgestrel-releasing intrauterine system group compared with that in the control group.

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RESULTS

Flow of study participants is shown in Figure 1. Seventy patients satisfied the eligible criteria, but 15 refused the levonorgestrel-releasing intrauterine system and were not included in the study. The remaining 55 patients agreed for randomization; ie, treatment group (n=28) and expectant management group (n=27). In all cases, the diagnosis of endometriosis was made by direct visualization of typical endometriotic lesions. Histopathology of tissue samples confirming the diagnosis was available in 38 of 55 cases. One case in the expectant management group was excluded after randomization as a result of protocol violation. Therefore, 28 cases in the treatment group and 26 cases in the expectant management group were included in the intention-to-treat analysis. Four cases, one in the treatment group and three in the expectant management group, were lost to follow-up at 9 months; therefore, the worst-case scenario was applied in the analysis.

Fig. 1
Fig. 1
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Baseline characteristics of the intention-to-treat population are shown in Table 1. The two groups were comparable in age, weight, body mass index, obstetric history, and baseline pain scores. There was a significantly higher proportion of sexually active women in the treatment group than in the expectant management group (75% compared with 33.3%, P=.010).

Table 1
Table 1
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At 12 months, 92.6% (25 of 27 cases) of the treatment group had an alteration of menstruation, ie, amenorrhea (22.2%), spotting (59.3%), and light bleeding (11.1%). When the participants were asked to guess their allocated groups, 92.6% (25 of 27) of the treatment and 47.8% (11 of 23) of the expectant management groups gave the right guess. None of the cases had expulsion of the intrauterine device.

The efficacy outcomes at 12 months are shown in Table 2. At 12 months, both groups had significant improvement from baseline in dysmenorrhea score (P<.001 for both groups) and noncyclic pelvic pain score (P=.001 for the treatment group and P=.031 for the expectant management group). The visual analog scale of dysmenorrhea had reduced more in the treatment group than in the expectant management group (delta of median visual analog scale=−81 compared with −50, P=.006). The proportion of patients with moderate-to-severe dysmenorrhea (visual analog scale greater than 50 mm) was also significantly lower in the treatment group (RR 0.21, 95% CI 0.05–0.87; P=.031). Two patients in the treatment group (7.4%, 95% CI 2.3–23.5) and nine patients in the expectant management group (39.1%, 95% CI 19.4–54.0) had recurrent moderate to severe pain within 1 year after the operation (P=.014). The recurrent pain in the treatment group started at 9 and 10 months, whereas that in the expectant management group had median time-to-recurrence of 8 months. The number-needed-to-treat to prevent one case of recurrent moderate-to-severe dysmenorrhea was 3.7 (95% CI 2.1–15.6). The visual analog scale of noncyclic pelvic pain score was also significantly reduced from baseline scores in both groups but reduced more in the treatment group than in the expectant management group (delta of median visual analog scale=−48.5 compared with −22, P=.038). Dyspareunia score was also significantly reduced from baseline scores in the treatment groups (P=.023) but was not significantly reduced in the expectant management group (P=.345). The Short Form-36 score was significantly improved from the baseline in the treatment group but did not change in the expectant management group. The proportion of patients who rated the treatment as very satisfied were lower in the expectant management group than in the treatment group (RR 0.64, 95% CI 0.33–1.24; P=.184).

Table 2
Table 2
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Profiles of pain scores and Short Form-36 subscales are shown in Figures 2 and 3, respectively. Compared with the expectant management group, the treatment group had significantly less dysmenorrhea and noncyclic pain from the first month of treatment and the benefit persisted for at least 12 months. Similarly, the Short Form-36 score was also better in the treatment group, particularly in the physical health subscale. The Short Form-36 score in the treatment group significantly improved from baseline (for total score, P=.044; physical subscale, P=.015; mental subscale, P=.022) and significantly better than those in the expectant management group (for total score, P=.014; physical subscale, P=.036), but the mental subscale was not significantly different between groups (P=.229).

Fig. 2
Fig. 2
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Fig. 3
Fig. 3
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Side effects of the treatment are presented in Table 3. Twenty of 27 patients in the treatment and 18 of 23 in the expectant management groups reported one or more side effects, probably related to progestogen. Bloating was more common in the expectant management group than in the treatment group (P=.021). At the end of 12 months, four cases in the treatment group requested removing the intrauterine system as a result of the abnormal uterine bleeding problems. Two cases were further treated with combined oral contraceptive pills, one case with depomedroxyprogesterone acetate, and one case did not receive hormonal treatment. The substituted hormonal treatments were deemed acceptable by the patients for at least 24 months after the change.

Table 3
Table 3
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DISCUSSION

Endometriosis is a disease that is less likely to be cured by conservative surgery. Postoperative measures are needed to prevent the recurrence of disease. Although prevention of recurrent lesion is an ultimate goal of treatment, it is impossible to evaluate such therapeutic effect of any intervention because the evaluation method, ie, second-look operation, is invasive, and deemed unnecessary. Nowadays, the accepted outcome measurement for the treatment of endometriosis is evaluation of symptom recurrence and quality of life. The present study demonstrated that the levonorgestrel-releasing intrauterine system is beneficial for both outcomes. Moreover, it might be able to prevent recurrent endometriotic cyst as evaluated by ultrasonography.

The levonorgestrel-releasing intrauterine system can relieve dysmenorrhea, reduce the risk of recurrent dysmenorrhea, and suppress chronic pelvic pain associated with endometriosis.2,1922,26,27 The use of the levonorgestrel-releasing intrauterine system for postoperative treatment was first reported by Vercellini et al in 1999.19 In the present study, conservative laparoscopic surgery could significantly reduce dysmenorrhea, noncyclic pain, and dyspareunia. Moreover, the application of a postoperative levonorgestrel-releasing intrauterine system provided a greater magnitude of pain reduction and lower rate of recurrent pain, the results of which were comparable with those of a previous report.20 In the levonorgestrel-releasing intrauterine system group, time to recurrent pain was 9 and 10 months after surgery. Median time to recurrent pain was 8 months in the expectant management group.

The efficacy of the levonorgestrel-releasing intrauterine system has been studied in patients with peritoneal, superficial ovarian, and rectovaginal endometriotic lesions, but limited information is available on the risk of endometriotic cyst formation. In the present study, two patients in the expectant management group had recurrent endometriotic cysts at 6 and 9 months after surgery, whereas none in the levonorgestrel-releasing intrauterine system group had recurrent endometriotic cyst. Our finding suggested that the levonorgestrel-releasing intrauterine system may prevent the formation of endometriotic cysts. Because the development of endometriotic cysts is associated with ovulation,28 ovulation suppression might be an effective measure for prevention of endometriotic cysts. The levonorgestrel-releasing intrauterine system can suppress ovulation in 70–85% of users during the first few months after insertion of the device; however, ovulation rate increases to greater than 50% thereafter29 Another mechanism might be the reduction of menstrual blood and amount of reflux menses by means of pseudodecidualization of endometrium, decrease in endometrial proliferation, and increase in apoptosis in endometrial glands and stroma.29

Endometriosis impairs women's quality of life.30 The present study showed an increase in Short Form-36 scores in the levonorgestrel-releasing intrauterine system group. Whereas, Short Form-36 scores in the expectant management group did not change. The levonorgestrel-releasing intrauterine system can improve the physical health, mental health, and total Short Form-36 scores at 12 months.

A common side effect of a levonorgestrel-releasing intrauterine system is abnormal uterine bleeding, but it was deemed tolerable in most patients because only four requested levonorgestrel-releasing intrauterine system removal at the end of 12 months because of frequent vaginal spotting. Three of the patients received other hormonal treatments, ie, oral contraceptive pills or depomedroxyprogesterone acetate, which seemed to be effective for the prevention of recurrent pain. Therefore, the oral contraceptive pill or depomedroxyprogesterone acetate might be a reasonable option for patients who did not want the levonorgestrel-releasing intrauterine system, and the patient who had bleeding problems from the levonorgestrel-releasing intrauterine system might not have the problem with the depomedroxyprogesterone acetate. Interestingly, other side effects were similar in both groups, except for bloating that was more common in the expectant management group. Wong et al22 reported that levonorgestrel-releasing intrauterine system users showed a better compliance than depomedroxyprogesterone acetate users; moreover, bone gain was noted with the levonorgestrel-releasing intrauterine system, but bone loss with depomedroxyprogesterone acetate after 3 years.

There were some limitations in the present study. First, the duration of follow-up was only 1 year. At the end of the first year, the study code was opened; however, we plan to follow up these patients for 5 years. Second, although we tried to mask our patient from the study group, most of the patients in the treatment group (92.6%) made the right guess that they were in the treatment group. This was owing to the side effects of the levonorgestrel-releasing intrauterine system that caused various types of abnormal uterine bleeding. Therefore, the present study was not a real double-blind study; consequently, it might give a bias result in favor of the treatment group.

In conclusion, the levonorgestrel-releasing intrauterine system is an effective mode of long-term therapy after conservative surgery for patients with moderate to severe pain related to pelvic endometriosis. It can improve the patient's quality-of-life scores on both physical and mental health. It is well accepted with tolerable side effects.

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REFERENCES

1. Fritz MA, Speroff L. Endometriosis. In: Fritz MA, Speroff L, editors. Clinical gynecologic endocrinology and infertility. 8th ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2011. p. 1221–48.

2. Bayoglu Tekin Y, Dilbaz B, Altinbas SK, Dilbaz S. Postoperative medical treatment of chronic pelvic pain related to severe endometriosis: levonorgestrel-releasing intrauterine system versus gonadotropin-releasing hormone analogue. Fertil Steril 2011;95:492–6.

3. Vercellini P, De Giorgi O, Pisacreta A, Pesole AP, Vicentini S, Crosignani PG. Surgical management of endometriosis. Baillieres Best Pract Res Clin Obstet Gynaecol 2000;14:501–23.

4. Sutton CJ, Pooley AS, Ewen SP, Haines P. Follow-up report on a randomized controlled trial of laser laparoscopy in the treatment of pelvic pain associated with minimal to moderate endometriosis. Fertil Steril 1997;68:1070–4.

5. Hornstein MD, Hemmings R, Yuzpe AA, Heinrichs WL. Use of nafarelin versus placebo after reductive laparoscopic surgery for endometriosis. Fertil Steril 1997;68:860–4.

6. Wheeler JM, Malinak LR. Postoperative danazol therapy in infertility patients with severe endometriosis. Fertil Steril 1981;36:460–3.

7. Vercellini P, Frontino G, De Giorgi O, Pietropaolo G, Pasin R, Crosignani PG. Endometriosis: preoperative and postoperative medical treatment. Obstet Gynecol Clin North Am 2003;30:163–80.

8. Parazzini F, Fedele L, Busacca M, Falsetti L, Pellegrini S, Venturini PL, et al.. Postsurgical medical treatment of advanced endometriosis: results of a randomized clinical trial. Am J Obstet Gynecol 1994;171:1205–7.

9. Lin KC, Chen HF, Huang PT, Wu MY, Ho HN, Yang YS. Effectiveness of postoperative adjuvant therapy in improving reproductive outcome of endometriosis-associated infertility. J Formos Med Assoc 2001;100:466–70.

10. Busacca M, Somigliana E, Bianchi S, De Marinis S, Calia C, Candiani M, et al.. Post-operative GnRH analogue treatment after conservative surgery for symptomatic endometriosis stage III–IV: a randomized controlled trial. Hum Reprod 2001;16:2399–402.

11. Ailawadi RK, Jobanputra S, Kataria M, Gurates B, Bulun SE. Treatment of endometriosis and chronic pelvic pain with letrozole and norethindrone acetate: a pilot study. Fertil Steril 2004;81:290–6.

12. Takayama K, Zeitoun K, Gunby RT, Sasano H, Carr BR, Bulun SE. Treatment of severe postmenopausal endometriosis with an aromatase inhibitor. Fertil Steril 1998;69:709–13.

13. Scholes D, LaCroix AZ, Ichikawa LE, Barlow WE, Ott SM. Injectable hormone contraception and bone density: results from a prospective study. Epidemiology 2002;13:581–7. Erratum in Epidemiology 2002;13:749.

14. Luukkainen T, Lahteenmaki P, Toivonen J. Levonorgestrel-releasing intrauterine device. Ann Med 1990;22:85–90.

15. Du M, Shao Q, Zhou X. Serum levels of levonorgestrel during long-term use of Norplant [in Chinese]. Zhonghua Fu Chan Ke Za Zhi 1999;34:363–5.

16. Nilsson CG, Lahteenmaki P, Robertson DN, Luukkainen T. Plasma concentrations of levonorgestrel as a function of the release rate of levonorgestrel from medicated intra-uterine devices. Acta Endocrinol (Copenh) 1980;93:380–4.

17. Luciano AA, Turksoy RN, Carleo J. Evaluation of oral medroxyprogesterone acetate in the treatment of endometriosis. Obstet Gynecol 1988;72:323–7.

18. Odlind V. Long-term experience of a levonorgestrel-releasing intrauterine system. Eur J Contracept Reprod Health Care 1996;1:319–23.

19. Vercellini P, Aimi G, Panazza S, De Giorgi O, Pesole A, Crosignani PG. A levonorgestrel-releasing intrauterine system for the treatment of dysmenorrhea associated with endometriosis: a pilot study. Fertil Steril 1999;72:505–8.

20. Vercellini P, Frontino G, De Giorgi O, Aimi G, Zaina B, Crosignani PG. Comparison of a levonorgestrel-releasing intrauterine device versus expectant management after conservative surgery for symptomatic endometriosis: a pilot study. Fertil Steril 2003;80:305–9.

21. Petta CA, Ferriani RA, Abrao MS, Hassan D, Rosa ESJC, Podgaec S, et al.. Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis. Hum Reprod 2005;20:1993–8.

22. Wong AY, Tang LC, Chin RK. 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;50:273–9.

23. Leurmarnkul W, Meetam P. Properties testing of the retranslated SF-36 (Thai version). Thai J Pharm Sci 2005;29:69–88.

24. Leurmarnkul W, Meetam P. Development of a quality of life questionnaire: SF-36 (Thai version). Thai J Pharm Sci 2000;24:92–111.

25. Wilk MB, Gnanadesikan R. Probability plotting methods for the analysis of data. Biometrika 1968;55:1–17.

26. Lockhat FB, Emembolu JO, Konje JC. The evaluation of the effectiveness of an intrauterine-administered progestogen (levonorgestrel) in the symptomatic treatment of endometriosis and in the staging of the disease. Hum Reprod 2004;19:179–84.

27. Lockhat FB, Emembolu JO, Konje JC. The efficacy, side-effects and continuation rates in women with symptomatic endometriosis undergoing treatment with an intra-uterine administered progestogen (levonorgestrel): a 3 year follow-up. Hum Reprod 2005;20:789–93.

28. Jain S, Dalton ME. Chocolate cysts from ovarian follicles. Fertil Steril 1999;72:852–6.

29. Vercellini P, Vigan ò P, Somigliana E. The role of the levonorgestrel-releasing intrauterine device in the management of symptomatic endometriosis. Curr Opin Obstet Gynecol 2005;17:359–65.

30. Marques A, Bahamondes L, Aldrighi JM, Petta CA. Quality of life in Brazilian women with endometriosis assessed through a medical outcome questionnaire. J Reprod Med 2004;49:115–20.

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© 2012 The American College of Obstetricians and Gynecologists

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