Quality of Life in Women with Endometriosis Pelvic Pain Treated with the Levonorgestrel-Releasing Intrauterine System

Objective: To evaluate the quality of life in patients with endometriosis pelvic pain before and after the application of the levonorgestrel-releasing intrauterine system (LNG-IUS). Design: Open non-comparative study. Setting: Obstetrics and Gynecology Hospital at Monterrey, Mexico. Sample: 29 women aged 18 to 40 years with pelvic pain associated with endometriosis confirmed by laparoscopy. Methods: After laparoscopy but before LNG-IUS insertion (basal visit) and 6 months afterwards, modified Endometriosis Health Profile (EHP-30) was applied. Main outcomes measures: Size of change of questionnaire scores, need of additional analgesic therapy and adverse effects. Statistical Analysis: Differences in the questionnaire scores before and after intervention were analyzed by Student t-test. Results: Final analysis set included 29 women aged 31.7 ± 4.7 years years. The ASRM surgical staging of endometriosis was mild in 19.3 moderate in 13.7 and severe in 76% of the patients. The general perception of quality of life improved from 52 at baseline to 98% at six months (p < 0.001). Adverse events were mild in nature, 19 patients reported no adverse events during the study (65.5%). Two patients (6.9%) required the use of concomitant therapy with non-steroidal analgesics for relief of pain. Conclusion: The application of LNG-IUS in patients with pelvic pain associated with endometriosis improved significatively all aspects related with quality of life as measured with Endometriosis Health Profile (EHP-30). We concluded that LNGIUS may be an effective and convenient therapeutic alternative for the management of pain associated with endometriosis.


Introduction
Endometriosis is a relatively common disorder clinically manifested as chronic pelvic pain and/or infertility.It is characterized by the presence of functional endometrial glands and stroma outside the uterus [1].Presumably 80 million women are affected by the disease worldwide.It is assumed that the prevalence of endometriosis is up to 15 percent of all women of reproductive age [2].Endometriosis affects 21 to 47 percent of women with infertility, 71 to 87 percent of those with chronic pelvic pain, and 69 percent of adolescents with pelvic pain refractory to treatment [3] [4].In Mexico, there is scant epidemiological data on endometriosis; the incidence is reported only in groups of patients with specific ailments as infertility in whom incidence is around 34.5% [5].
Traditionally, the therapeutic goal in the hormonal treatment of endometriosis has been the suppression of ovarian activity.Accordingly, approved treatments in the management of endometriosis include aGnRH analogues, progestins and danazol.Although oral combined contraceptives have not approved indication, they have been investigated and are widely prescribed for the treatment of endometriosis pelvic pain [6].
The levonorgestrel-releasing intrauterine system (LNG-IUS), besides its contraceptive effect, has a strong effect on the endometrium causing its inactivation and atrophy without suppressing ovulation; this is due to the high hormonal dose locally released that stops endometrial proliferation increasing apoptosis of endometrial glands and stroma.LNG-IUS is a T-shaped flexible structure, which includes a hormonal reservoir in its vertical arm containing 52 mg of levonorgestrel.Hormonal initial release is 20 mcg/day, decreasing progressively to a release of 12 mcg at the end of the 5th year of use [7].Considering the strong local action on endometrium, some studies have shown the plausibility to use the LNG-IUS as an effective option in the treatment of chronic pelvic pain associated with endometriosis, with few systemic adverse events.
The quality of life related to health is a multidimensional and dynamic concept that encompasses the physical, psychological and social aspects associated with a disease or its treatment [8].One method to assess the outcome of different treatments for endometriosis is based on the concept of quality of life as the patient's perception of the impact in different areas of her life, especially physical, emotional and social well-being comprised by her disease [9].The Endometriosis Health Profile (EHP-30) is a Health Related Quality of Life (HRQoL) patient self-report of outcomes (PRO); used to measure the wide range of effects that endometriosis can have on women's lives.The EHP-30 is the only condition-specific PRO designed from the patient's perspective to assess health related quality of life in endometriosis.Published evidence concludes that the EHP-30 is a reliable and valid instrument for assessing areas of concern to women with endometriosis that are not addressed by other condition-specific and generic questionnaires [10] [11].The core instruments have five scale scores covering: Pain, control and powerlessness, social support, emotional well-being and self-image.
With the aim to evaluate the quality of life in patients with endometriosis pelvic pain before and after the application of the levonorgestrel-releasing intrauterine system (LNG-IUS), we designed this quasi-experimental pre-post test study using The Endometriosis Health Profile (EHP-30) questionnaire.consultation at Obstetrics and Gynecology Hospital, who signed informed consent for participation in the study, were included.The mean age was 31.7 ± 4.7 years.Only two patients were referred with suspected diagnosis of endometriosis.Laparoscopy procedures were done in all patients to diagnose, and treat endometriosis.The severity of the disease by ASRM Staging System were mild (Stage II) in three patients (10.3%); moderate (Stage III) in four patients (13.7%); and severe (Stage IV) in 22 patients (76%).Surgical treatment consisting in resection of endometriotic foci and adhesiolysis was performed in 17 patients, Laparoscopic Uterine Nerve Ablation (LUNA) in 7 patients, resection of endometriomas in 2, and no surgical treatment in 3 patients.Main exclusion criteria were: patients on hormone therapy in the 3 months prior to inclusion; patients with contraindications for the use of LNG-IUS or patients whom desire to become pregnant.
The LNG-IUS was applied during the first menstruation after laparoscopy.

Methods
The EHP-30 consists of a Likert scale with five possible responses (never, rarely, sometimes, often, and always).
The questionnaire assesses core aspects of pain (9 items), emotional well-being and self-image (11 items), alongside we selected supplementary modules including work (5 items), sexual intercourse (5 items) and perceptions about treatment (5 items).Section of questions in the original questionnaire about fertility was removed because of the nature of the proposed contraceptive treatment.All patients answered the questionnaire before the application of LNG-IUS and six months after.
The purpose of the EHP-30 is to indicate the extent of self-reported ill health on each domain measured.Therefore, each scale is standardized on a scale of 0 -100, where 0 indicates the best health status through to 100 worst health status.Scale scores for each scale are calculated from the total of the raw scores of each item in the scale divided by the maximum possible raw score of all the items in the scale, multiplied by 100.To measure the reliability of the instrument, the Cronbach's alpha (a coefficient of internal consistency) was used.Measures with reliability greater than 0.7 have been recommended as most useful in group-level hypothesis testing.To measure the temporal stability of the sample, the Intraclass Correlation Coefficient (ICC) was used.To estimate the magnitude of the sensitivity of the instrument to detect the change in quality of life among the two different times, the effect size was calculated by the difference between pre-treatment and post-treatment averages divided by the pre-treatment standard deviation, as recommended by Kazis et al. [12] A size of the effect equal to 0.20 indicates a small change, while measures of 0.50 and 0.80 indicate moderate and large changes respectively.A small effect size implies that treatment had little influence on the quality of life.To measure the difference between the means of each category Student t-test was used.

Results
The reliability of the EHP-30 was 0.99, the ICC for single measures was 0.73 (95% CI 0.66 to 0.84, p = 0.000) (Table 1).It proved to be sensitive to detect the effect size in the change of the responses.The comparative analysis of mean scores pre-post LNG-IUS application showed that the perception of quality of life improved significantly in all areas size effect of pain was 2.0 (p < 0.0001); well-being and self-image 2.1 (p < 0.0001); labor performance 0.6 (p < 0.01); sexual intercourse 1.5 (p < 0.0001) and overall treatment satisfaction 2.6 (p < 0.0001), respectively (Table 2).
Endometriosis is primarily associated with pain and infertility and has been postulated that the pain is responsible for causing the most negative effect on quality of life.LNG-IUS showed considerable improvement in the perception of pain with effect size of 2 (p < 0.001) at the end of observation period.
Two patients (6.9%) required the use of concomitant therapy with non-steroidal analgesics for relief of pain.Only one patient prematurely discontinued the treatment because bias of selection (she wanted to seek pregnancy).

Discussion
The present study showed short term significant improvement of QoL in patients with pain associated with endometriosis, treated with LNG-IUS using Endometriosis Health Profile (EHP-30-30) questionnaire.The effect  size magnitude in this study was higher with LNG-IUS treatment compared with the results obtained by Jones G. et al. [11], in women with only conservative surgery for the treatment of endometriosis-associated pain, precluding the necessity to develop further comparative studies.In this study, the EPH-30 questionnaire showed high reliability in our population and a high sensitivity to detect the magnitude of change, demonstrating that treatment had clinically significant positive influence on our patients' health.The diagnosis of clinical suspicion by primary care physicians was low in this study (6.9%), suggesting that provision of Continuing Medical Education should be done in order to improve the knowledge and awareness of this entity.
The limitations of this study are: a small number of subjects, the lack of a comparator (only 3 of 29 patients were not surgical treated) which is a strong bias to conclude any pure effect of LNG-IUS treatment of pain associated with endometriosis at least in the short term.Thus, it is recommend to perform comparative studies (LNG-IUS vs. surgical treatment alone) with longer follow up to further determine the long lasting effect of LNG-IUS treatment in the control of endometriosis pelvic pain.

Conclusion
In this study, the LNG-IUS improved the quality of life of patients with endometriosis in all areas evaluated by EHP-30 including self-esteem, sexual intercourse, work and overall treatment satisfaction.We believe that LNG-IUS may represent an effective and convenient alternative in the long-term management of pelvic pain associated with endometriosis.

Table 1 .
Corrected item to total correlation and scale internal reliability consistency on the EHP-30.

Table 2 .
Effect size of change on EHP-30 parameters.