{"paper_id":"ba692df8-f5a5-4b15-ae22-7c4909f5425d","body_text":"Citation: Swailum MB, Wahba KA, Labib KM and Islam BA. Oral Contraceptives for Endometriosis Associated \nPain: A Randomized Controlled Trial. Austin J Obstet Gynecol. 2017; 4(4): 1082.\nAustin J Obstet Gynecol - Volume 4 Issue 4 - 2017\nSubmit your Manuscript | www.austinpublishinggroup.com \nSwailum et al. © All rights are reserved\nAustin Journal of Obstetrics and Gynecology\nOpen Access\nAbstract\nObjective: To determine the efficacy and safety of oral contraceptive \npreparation in the treatment of painful symptoms associated with the diagnosis \nof endometriosis.\nDesign: Randomized controlled clinical trial- single blinded technique.\nSettings: Clinical trial sited in Egypt.\nPatient: Seventy patients with painful symptoms associated with \nendometriosis. \nIntervention: Patients were randomly assigned to receive OCPs + NSAID’s \nor Tri-B tablets + NSAID’s as a placebo. Participants allowed to use pain \nmedications as needed during the trial.\nMain Outcome Measure: After four cyclic treatments, Pain was assessed \nusing numbering rating scale (Wong-Baker FACES® Pain Rating Scale Figure \n1) from (0 to 10) for each of the three symptoms: dysmenorrhea, dyspareunia \nand non-menstrual pain, also recurrence and frequency of pain and use of pain \nkillers after treatment were measured.\nResult: Dysmenorrhea pain was significantly reduced after treatment for \npatient group (the pain score reduced to 2.69±1.95, while in the placebo group \ndysmenorrhea pain score was 4.66±2.17. As regard dyspareunia pain was \nreduced after treatment (the pain score reduced to 1.74±1.65, while for placebo \ngroup there are slight reduction 2.29±2.01), Non-menstrual pain was reduced \nafter treatment for patient group (1.89±2.05), while for placebo group pain score \nwas (2.14±2.25), the recurrence and frequency of pain and the use of pain killer \nwas lower in patient group than placebo group. \nConclusion: The present study demonstrated that continues use of low \ndose OCPs are an effective treatment for pain associated with endometriosis \nwith few adverse effects in women who did not wish to get pregnant in the near \nfuture.\nKeywords: Oral Contraceptive (OC); Endometriosis; Dysmenorrheal; \nDyspareunia; Non-menstrual pelvic pain\nResearch Article\nOral Contraceptives for Endometriosis Associated Pain: A \nRandomized Controlled Trial\nSwailum MB*, Wahba KA, Labib KM and Islam \nBA\nDepartment of Obstetrics and Gynecology, Faculty of \nMedicine-Ain-Shams University, Cairo, Egypt\n*Corresponding author:  Mohamed Abdelhafez \nSwailum, Department of Obstetrics and Gynecology, \nFaculty of Medicine - Ain-Shams University, Cairo, Egypt \nReceived: November 05, 2017; Accepted: November \n30, 2017; Published: December 07, 2017\nIntroduction\nEndometriosis, the presence of endometrial glands and stroma \noutside of the endometrial cavity, represents one of the most \nchallenging gynecologic conditions to manage given its insidious \nonset, surgical diagnosis, association with pelvic pain and infertility, \nand often progressive nature. Endometriosis is a chronic disease \naffecting at least 10% of reproductive-aged women, but is found in \napproximately40% of infertile women and up to 90% of women with \npelvic pain.\nThe classic triad of endometriosis symptoms, dysmenorrhea, \ndyspareunia, and dyschesia, raises clinical suspicion for this disorder \n[1].\nMedical and surgical treatments are mainstays in the management \nof endometriosis, and different approaches are dictated by the \npleiotropic manifestations of the disease as well as underlying patient \ncharacteristics. In general, medical treatment options are limited \nwhen fertility is desired because of the ovarian suppression inherent \nin their mechanisms of action. \nThe medical treatment options for endometriosis rely on the \nsuppression of endometriosis by manipulating the hormonal milieu \nbecause endometriosis growth and activation are stimulated by \nestrogen, and both estrogen and progesterone receptors are present \nin ectopic endometrial tissue. \nHormonal contraceptives containing both Ethinyl Estradiol (EE) \nand progestin can be used in a cyclic or continuous fashion for the \ntreatment of endometriosis. Continuous use appears to result in \nbetter pain control [2].\nMaterials and Methods\nThe study patients were recruited from women attending \noutpatient clinic at (Ain-Shams University Maternity Hospital). \nSeventy women of reproductive age who complained of symptoms \n\nAustin J Obstet Gynecol 4(4): id1082 (2017)  - Page - 02\nSwailum MB Austin Publishing Group\nSubmit your Manuscript | www.austinpublishinggroup.com\nreferred to the diagnosis of endometriosis were randomly assigned as \npatient and placebo group those will receive (OCPs + NSAID’s) and \n(Tri-B tablets +NSAID’s) as a placebo in continues pattern for four \nsuccessive cycles, respectively. \nThe study patients must have had moderate or severe \ndysmenorrhea, scoring higher than three points at the admission \non verbal rating scale. Each patient underwent a pre-recruitment \nevaluation, consisting of a general medical and gynecologic history, \nphysical and pelvic examination, clinical evaluation of signs and \nsymptoms, patient evaluation of pain, and review of the menstrual \nrecord, pain scoring dysmenorrhea, dyspareunia and non menstrual \npain and recording details about the use of analgesics.\nInclusion criteria: Age between 20-42 years old, Patient diagnosed \nas endometriosis based on laparoscopic or surgical diagnosis or \npresence of chocolate cysts and Patient must have one painful \nsymptom associated with endometriosis.\nExclusion criteria\nPatients who had received any hormonal therapy within the last \nthree months patients, Patients with contraindications to the OCP, \nPatients had surgery other than biopsy had been performed in the \nthree months prior to recruitment, Urinary tract infection causing \npelvic pain, local focal uterine lesion or ovarian cyst causing pain \nand GIT disease causing dyschazia or pelvic pain eg. GI ulcer, piles, \nulcerative colitis, etc.\nPrimary outcome measures were improvement of pain symptoms \nof endometriosis: dysmenorrhea, dyspareunia non-menstrual pain \nand improvement of any other pain symptom of endometriosis such \nas (Post-coital pain, dyschezia and/or cyclical pain not associated \nwith menstruation), also measurement of any side effects occurring \nduring therapy (including pregnancy).\nAfter four month of therapy, Pain was reassessed at the end of \ntreatment for each of the three symptoms. Also recurrence, frequency \nof pain and the use of pain killers were reassessed at end of treatment. \nThe numbers of women at trial entry and at the end of treatment \nwho had either no pain or any pain (mild, moderate or severe) were \ncalculated from the data presented. \nStatistical analysis\nData were analyzed using Statistical Program for Social \nScience (SPSS) version 20.0. Quantitative data were expressed as \nmean±Standard Deviation (SD). Qualitative data were expressed as \nfrequency and percentage.\n–P-value <0.05 was considered significant.\n–P-value <0.001 was considered as highly significant.\n–P-value >0.05 was considered insignificant.\nResults\nDemographic characteristics and disposition of patient group \nand placebo group are demonstrated in Table 1. This table shows \nthat the demographic characteristics of the two groups were similar. \nThe mean age of the patient and placebo groups was ~ 31years (range \n23–42), and ~ 30 years (range 22–42), respectively. The mean parity \nof both groups was ~ 1 (range 0–3), and BMI mean was 25.5 and \n25.6 for patient group and placebo group respectively . None of them \nhad hypertension or recently used any hormonal treatment. There \nis no statistically significant difference between groups according to \ndemographic characteristics and anthropometric measurements\nEndometriosis associated Pain was assessed at start of study in \nNumerical Rating Scale (NRS) for each type of pain pretreatment in \nboth groups, each pain scale had score from 0 to 10 resembling no \npain to worst possible pain. This date was shown in Table 2, 3.\nDysmenorrhea means score was 5.80±1.68 (range 4-10) for patient \ngroup and 5.60±1.52 (range 4-10) for control group. Dyspareunia \nmean score was 2.57 ±1.75 (range 1-8) and 2.37±1.99 (range 0-7) for \nFigure 1: Wong-Baker FACES® Pain Rating Scale.\nDemographic measurements Patients Control t-test/z* p-value\nAge (years)\nMean±SD 31.11±5.47 30.49± 6.17 0.204 0.653\nRange 23-42 22-42\nParity\nMedian(IQR) 1 (2) 1 (2) 0.168 0.684\nRange 0-3 0-3\nBMI\nMean±SD 25.49±3.18 25.62±3.21 0.029 0.865\nRange 19.38-32.03 19.38-32.03\nTable 1: Comparison between groups according anthropometric measurements.\nAs regard table one, this table shows no statistically significant difference \nbetween groups according anthropometric measurements.\nDysmenorrhea Patients Control t-test p-value\nMean±SD 2.69±1.95 4.66±2.17\n15.98 <0.001\nRange 0-7 9-Feb\nRecurrence\nNo 29(82.9%) 14(40.0%)\n13.57 <0.001\nYes 6(17.1%) 21(60.0%)\nFrequency\nMild 3(50%) 8(38.1%)\n13 0.005Moderate 3(50%) 8(38.1%)\nSevere 0(0.0%) 5(23.8%)\nUse of pain killers\nNo pain 1(25%) 6(28.6%)\n9.611 0.022\nMild 4(50%) 5(23.8%)\nModerate 1(25%) 7(33.3%)\nSevere 0(0%) 3(14.3%)\nTable 2: Comparison between groups according to dysmenorrhea post treatment.\nAs regard table two, this table shows highly statistically significant difference \nbetween groups according to dysmenorrhea.\n\nAustin J Obstet Gynecol 4(4): id1082 (2017)  - Page - 03\nSwailum MB Austin Publishing Group\nSubmit your Manuscript | www.austinpublishinggroup.com\npatient and control group respectively and non-menstrual pain mean \nscore was 2.71±2.36 (range 0-9) for patient group and 2.29±2.36 \n(range 0-9) for control group.\nThere is no statistically significant difference between groups \naccording to (NRS).\nAt the end of treatment, pain was reassessed for each of the \nthree symptoms. Dysmenorrhea pain was significantly reduced after \ntreatment for patient group (the pain score reduced to 2.69±1.95 \n(range 0-7), while in the placebo group dysmenorrhea pain score was \n4.66±2.17 (range 2-9).\nThe recurrence of pain was higher in placebo group than in \npatient group (21 vs. 6 patients) with higher frequency of pain in \nplacebo group (3 patients had mild pain and 3 patients had moderate \npain in patient group while 8 patients had mild pain, 8 patients had \nmoderate pain and 5patients had severe pain in control group). \nAlso the use of pain killer was much higher in placebo group \n(15 vs. 10 in placebo group and patient group respectively). There \nis highly statistically significant difference between groups (P. value \n<0.001).\nAs regard dyspareunia pain was reduced after treatment (the pain \nscore reduced to 1.74 ± 1.65 (range 0-7)), while for placebo group \nthere are slight reduction (2.29±2.01) (range 0-7). \nThe recurrence of pain was low in both groups but higher in \nplacebo group than in patient group (3 & 6 patients in OCP and \nplacebo group respectively). Also the use of pain killer was low in \nboth groups. The frequency of pain in placebo group was also higher \n(1 patient had mild pain and 2 patients had moderate pain in patient \ngroup while 1 patient had mild pain, 5 patients had moderate pain in \ncontrol group). \nAlso the use of pain killer was higher in placebo group (3 vs. 5 \nin patient group and placebo group respectively). The data shows \nno statistically significant difference between groups according to \ndyspareunia post-treatment (P. value=0.221).\nNon-menstrual pain was reduced after treatment for patient \ngroup (1.89±2.05) (range 0-8), while for placebo group pain score \nwas (2.14±2.25) (range 0-8). The recurrence of pain was low in both \ngroups (5 and 7 patients in OCP and placebo group respectively). \nAs regard frequency of pain;4 patients had mild pain and 1 patient \nhad moderate pain in patient group while 4 patients had mild pain, 1 \npatient had moderate pain and 2 patients had severe pain in control \ngroup). The use of pain killer was higher in placebo group (1 vs. 5 in \npatient group and placebo group respectively) (Table 4, 5). \nThe data shows no statistically significant difference between \ngroups according to non-menstrual pain post treatment.\nDiscussion\nEndometriosis is a common gynecological condition which \naffects many women of reproductive age worldwide and is a major \ncause of pain and infertility. The symptoms of endometriosis include \ndysmenorrhea, dyspareunia, and dyschezia, chronic pelvic pain, \nirregular uterine bleeding and/or infertility. Endometriosis represents \nDyspareunia Patients Control t-test p-value\nMean±SD 1.74±1.65 2.29±2.01\n1.526 0.221\nRange 0-7 0-7\nRecurrence\nNo 32(91.4%) 29(82.9%)\n1.148 0.284\nYes 3(8.6%) 6(17.1%)\nFrequency\nMild 1(33.3%) 1(16.7%)\n1.433 0.488\nModerate 2(66.7%) 5(83.3%)\nUse of pain killers\nNo pain 0(0.0%) 1(25%)\n5.065 0.079Mild 3(100%) 1(25%)\nModerate 0(0.0%) 4(50%)\nTable 3: Comparison between groups according to dyspareunia post treatment.\nThis table shows no statistically significant difference between groups according \nto dyspareunia.\nNon-menstrual pain Patients Control t-test p-value\nMean±SD 1.89±2.05 2.14±2.25\n0.249 0.619\nRange 0-8 0-9\nRecurrence\nNo 30(85.7%) 28(80.0%) 0.402 0.526\nYes 5(14.3%) 7(20.0%)\nFrequency\nMild 4(80%) 4(57.1%)\nModerate 1(20%) 1(14.3%)\nSevere 0(0%) 2(28.6%)\nUse of pain killers\nNo pain 4(80%) 2(28.6%)\n3.583 0.31\nMild 1(20%) 2(28.6%)\nModerate 0(0%) 1(14.3%)\nSevere 0(0%) 2(28.6%)\nTable 4: Comparison between groups according to non-menstrual pain post \ntreatment.\nAs regard table four, this table shows no statistically significant difference \nbetween groups according to non-menstrual pain.\nPatient group\nNRS\nPre Post\nMean Diff.\nPaired Sample t-test\nMean±SD Mean±SD t p-value\nDysmenorrhea 5.80±1.68 2.69±1.95 -3.11 19.765 <0.001\nDyspareunia 2.57±1.75 1.74±1.65 -0.83 2.938 0.039\nNon-menstrual pain 2.71±2.36 1.89±2.05 -0.82 2.465 0.041\nControl group\nNRS\nPre Post\nMean Diff.\nPaired Sample t-test\nMean±SD Mean±SD t p-value\nDysmenorrhea 5.60±1.52 4.66±2.17 0.94 4.91 0.022\nDyspareunia 2.37±1.99 2.29±2.01 0.09 0.902 0.373\nNon-menstrual pain 2.29±2.36 2.14±2.25 0.14 0.334 0.741\nTable 5: Difference between pre and post according to NRS in patients and \ncontrol group.\n\nAustin J Obstet Gynecol 4(4): id1082 (2017)  - Page - 04\nSwailum MB Austin Publishing Group\nSubmit your Manuscript | www.austinpublishinggroup.com\none of the most\nChallenging gynecologic conditions to manage, given its insidious \nonset, surgical diagnosis, association with pelvic pain and infertility \nraises clinical suspicion for this disorder. However, the substantial \noverlap of endometriosis symptoms with other conditions causing \npelvic pain, gynecologic and non-gynecologic, combined with the \nlimitation of pelvic examination in detecting endometriosis, makes \nclinical diagnosis challenging.\nFurthermore, the amount of endometriosis present does not \nnecessarily correlate with symptoms, and therefore, the usefulness of \navailable staging systems is limited.\nMany studies have been established in the past few years \nto determine the efficacy of oral contraceptive in treatment of \nendometriosis associated pain for example Harada and colleagues \nwho Evaluate the efficacy of a low-dose oral contraceptive pill for \ndysmenorrhea associated with endometriosis, a Placebo-controlled, \ndouble-blind, randomized trial held in 2008 and was sited in Japan \nover one hundred patients. After four cycles Total dysmenorrhea \nscores assessed by the verbal rating scale were significantly decreased \nat the end of treatment in both groups dysmenorrhea in the OCP \ngroup was significantly milder than in the placebo group [3]. Another \nstudy by Harada and colleagues in 2011, which evaluate the efficacy \nof a low-dose oral contraceptive pills for primary dysmenorrhea, a \nPlacebo-controlled, double-blind, randomized trial sited in Japan over \none hundred fifteen patients for four cycles and found that reduction \nin total dysmenorrhea score and verbal rating scale and Visual Analog \nScale (VAS) before and after treatment was significantly higher in \nthe OCP group than in the placebo group, no serious adverse events \noccurred [4].\nAlso a systemic review by Cochrane Collaboration was done \nin 2009to assess the effects of the Oral Contraceptive Pill (OCP) \nin comparison to other treatments for painful symptoms of \nendometriosis in women of reproductive age, and found that only \none study met the inclusion criteria, in which a total of 57 women \nwere allocated to two groups to compare an OCP to a GnRH analogue \nover treatment period of six months, the result shows no evidence \nof a difference in outcomes between the Oral Contraceptive Pill \n(OCP) studied and GnRH analogue was as effective as a GnRH \nanalogue in treating for endometriosis-associated painful symptoms \nof endometriosis [5].\nWe carried out an RCT to evaluate the efficacy of continues \nuse of low dose OCPs for the treatment of different types of pain \nassociated with endometriosis. Study was held from February 2016 to \nDecember, the study patients were recruited from women attending \noutpatient clinic at (Ain-Shams University Maternity Hospital). \nSeventy women of reproductive age who complained of symptoms \nreferred to the diagnosis of endometriosis were randomly assigned as \npatient and placebo group those will receive (OCPs + NSAID’s) and \n(Tri-B tablets +NSAID’s) as a placebo in continues pattern for four \nsuccessive cycles, respectively.\nAfter four month of therapy, Pain was reassessed at the end of \ntreatment for each of the three symptoms. Also recurrence, frequency \nof pain and the use of pain killers were reassessed at end of treatment. \nThe numbers of women at trial entry and at the end of treatment \nwho had either no pain or any pain (mild, moderate or severe) were \ncalculated from the data presented. \nThe results demonstrated that continues uses of OCPs \nsignificantly reduce dysmenorrhea associated with endometriosis \ncompared with the placebo (2.69 ±1.95 p. value <0.001 for patient \ngroup vs. 4.66±2.17p.value 0.022 for placebo group). The recurrence \nof pain was higher in placebo group than in patient group (21 vs. 6 \npatients). Also the use of pain killer was higher in placebo group (15 \nvs. 10 in placebo group and patient group respectively), but there \nis statistically significant difference between pretreatment and post \ntreatment in both groups.\nDyspareunia score was also reduced after treatment (the pain \nscore reduced to 1.74±1.65, p. value= 0.039, while for placebo group \nthe pain score was 2.29±2.01, p value= 0.373). The recurrence and \nfrequency of pain was low in both groups (3 and 6 patient). Also \nthe use of pain killer was low in both groups. There is statistically \nsignificant difference between pretreatment and post treatment only \nin patient group.\nNon-menstrual pain was reduced after treatment for patient \ngroup (1.89±2.05p.value=0.041), while for placebo group there are \nslight reduction (2.14±2.25, p. value=0.741). The recurrence and \nfrequency of pain was low in both groups (5 and 7 patient). Also the \nuse of pain killer was low in both groups. The data shows statistically \nsignificant difference between pretreatment and post treatment only \nin patient group.\n Regarding safety, the incidence of irregular uterine bleeding \nand nausea was higher in the OCP group compared with the placebo \ngroup. No serious side effects were noticed during trial. \nThese results correspond well with the most widely accepted \npharmacologic theory that OCs prevent ovulation and suppress the \nprogesterone-driven proliferation of the secretory endometrium \nduring the luteal phase, thereby resulting in a decrease in the \nvolume of menstrual fluid and prostaglandin synthesis and decrease \nendometriosis associated pain.\nIn conclusion the present study clearly demonstrated that \ncontinues use of low dose OCPs are an effective treatment for pain \nassociated with endometriosis with few adverse effects in women \nwho did not wish to get pregnant in the near future. However longer \nstudies is recommended to evaluate the long term efficacy of oral \ncontraceptive pills in controlling pain of endometriosis as well as the \nrecurrence of pain after discontinuation of therapy.\nReferences\n1. Kodaman PH. Current Strategies for Endometriosis Management. Obstet \nGynecol Clin North Am. 2015; 42: 87-101.\n2. Al-Jefout M. Brief update on endometriosis treatment. Middle East Fertil Soc \nJ. 2011; 16: 167-174.\n3. Harada T, Momoeda M, Taketani Y, Hoshiai H, Terakawa N. Low-dose oral \ncontraceptive pill for dysmenorrhea associated with endometriosis: a placebo-\ncontrolled, double-blind, randomized trial. Fertil Steril. 2008; 90: 1583-1588.\n4. Harada T, Momoeda M, Terakawa N, Taketani Y. Evaluation of a low-dose \noral contraceptive pill for primary dysmenorrhea  : a placebo-controlled, \ndouble-blind, randomized trial. Fertil Steril. 2011; 95: 1928-1931.\n5. Davis LJ, Kennedy SS, Moore J, Prentice A. Modern combined oral \ncontraceptives for pain associated with endometriosis. Cochrane Database \nSyst Rev. 2009.","source_license":"CC0","license_restricted":false}