{"paper_id":"cd09a3d4-dacd-41f9-a278-283e17d96a02","body_text":"~ 173 ~ \nInternational Journal of Clinical Obstetrics and Gynaecology 2022; 6(1): 173-176 \n \nISSN (P): 2522-6614 \nISSN (E): 2522-6622 \n© Gynaecology Journal \nwww.gynaecologyjournal.com \n2022; 6(1): 173-176 \nReceived: 22-11-2021 \nAccepted: 24-12-2021 \n \nAnju \nAssociate Prof, Dept. of Obgy \nGMC, Patiala, Punjab, India \n \nParneet Kaur \nProf and Head, Dept. of Obgy \nGMC, Patiala, Punjab, India \n \nRajat Gupta \nMedical Student, GMC, Patiala, \nPunjab, India \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nCorresponding Author: \nAnju \nAssociate Prof, Dept. of Obgy \nGMC, Patiala, Punjab, India \n \nEvaluation of non-contraceptive benefits of LNG-IUS: A \nclinical study \n \nAnju, Parneet Kaur and Rajat Gupta \n \nDOI: https://doi.org/10.33545/gynae.2022.v6.i1c.1133 \n \nAbstract \nIntroduction: IUCDs are the most widely used and effective con traceptive methods and are safe . Huge \nvariety of IUCDs are available which include inert, copper containing, and medicated with levonorges trel \nor indomethacin.  LNG has been explored for its non -contraceptive benefits by various researchers and \nfound to be effective for women and adolescents as first line therapy with heavy menstrual bleeding and is \nassociated with improved dysmenorrhoea.so we did a two year perspective study in deptt of obs and gynae \nat GMC Patiala to assess the role of LNG -IUS IN various gynaecological indication otherthan \ncontraception. \nMaterial and Methods: Women with heavy menstrual period, dysmenorrhea or both who report ed in the \nOPD were examined, including breast and pelvic examination. USG was done to note various pathologies \nlike fibroid, endometriosis, endometrial hyperplasia, adenomyosis and functional ovarian cyst. This was \nfollowed by endometrial biopsy. After the biopsy report was available, decision for LNG-IUS insertion was \ntaken. LNG-IUS was inserted, under all sterile conditions without anaesthesia. After insertion, patient was \nfollowed up at 1-, 3-, 6- and 12-month interval for menstrual pattern change any co mplications compliance \non part of patient. \nResults: A total of 30 patients were enrolled over a period of two years. 28 patients were in the age group \n30-50 years and only 2 patients were post -menopausal. 56.6% had rural background, 43% were illiterate \nand 83.3% were multipara. In 50% of the women, the chief complaint was heavy menstrual bleeding with \ndysmenorrhea and 36% had heavy menstrual bleeding alone. 6.6% had dysmenorrhea alone and another \n10% reported with irregular bleeding.  According to PALM -COIEN classification, AUB-A was diagnosed \nin 16.6%, AUB-L in 30%, AUB -O in 40%, AUB -M in 3.3%, endometriosis in 13.3%. LNG -IUS was not \nused as contraception or HRT in any of the cases. \nOn post insertion follow up after one month, 90 percent had relief from heav y menstrual bleeding. At six-\nmonth follow-up, 23.3% reported spotting and 60% reported normal flow during periods.  After one year \n73.9% patient had normal flow and 13% patients achieved amenorrhoea. \nThe irregular bleeding or spotting was managed by giving supportive therapy in form of reassurance in \n30%, NSAIDS in 16.6%, and norethisterone in 46.6%. Ormeloxifene and OCPs were given in 3.3% each \nand response was satisfactory.  \nAt one year follow up it was seen that 76.6% patients continued with LNG IUS and f ound it comfortable \nwith enhanced quality of life. \nConclusion: LNG-IUS is a better choice for the management of endometrial hyperplasia simple or \ncomplex, with or without atypia, AUB, adenomyosis and endometriosis. LNG -IUS can be a good \nalternative to hysterectomy. \n \nKeywords: levonorgestrel intrauterine system, menstrual bleeding, endometriosis, endometrial hyperplasia \n \nIntroduction  \nIUCDs are the most widely used and effective contraceptive methods and are safe. Huge variety \nof IUCDs are available which in clude inert, copper containing, and medicated with \nlevonorgestrel or indomethacin. \nThe LNG -IUS (levonorgestrel releasing intrauterine system) was introduced by Schering -ox, \nFinland which released in vitro 20 micrograms of levonorgestrel per day. LNG -IUS contains 52 \nmg of levonorgestrel which is dispensed in polydimethylsiloxane frame which stays inside the \nuterus and very small amount is released in blood. Mechanism of action of LNG IUS is similar \nto LNG implant /minipills but with lower peak of serum lev els 0.1 to 0.4 ng/ml. 20 µg of LNG -\nIUS is released every 24hrs and it decreased to 11 µg /24hrs by end of 5 yrs. LNG thickens \ncervical mucus and suppresses endometrial proliferation creatin g hostile environment for sperm  \nsurvival by inhibiting motility and capacitation to prevent fertilisation. \n\n\nInternational Journal of Clinical Obstetrics and Gynaecology http://www.gynaecologyjournal.com \n~ 174 ~ \nIt produces endometrial thinning cum fragile superficial v essels \npreventing implantation [2]. \nLNG has been explored for its non -contraceptive benefits by \nvarious researchers and found to be effective for women and \nadolescents as first line therapy with heavy menstrual bleeding  \nand is associated with improved dysmenorrhoea [1]. It was found \nto be satisfactory, effective and economical alternative to \nmedical sur gical treatment of menorrhagia [2, 4, 5 ]. Associated \nmedical diseases in which LNG IUS can be used for treatment of \nHMB are obesity, severe anaemia, coagulopathies where surgery \nis either contraindicated, is high risk or is not affordable because \nof high cost [5, 6, 7, 8]. \nLNG has been associated with irregular spotting for up to \n6weeks after insertion and is associated with progress ive \namenorrhoea [11-15]. Irregular bleeding if associated is treated by \nvarious methods like cyclical progesterone or with ra loxifene or \nsimple reassurance [9, 13 ]. Other side effects  noticed with LNG  \nare anxious depressive disorders, sexual disorders, inc reased \nweight gain and pain [11, 12 ]. So, a study was conceptualised to \nevaluate various non contraceptive uses and its side effects like \nirregular spotting through first year of its use and its \nmanagement by different agents. \n \nAims and Objectives \n To evaluate LNG -IUS as a therapeutic alternative to \nhysterectomy in AUB, Endometriosis, Fibroid uterus.  \n To study side effects and their management. \n To find its continuation v/s discontinuation rates. \n \nMaterial and Methods  \nThe present study was undertaken in Department of Obstetrics \nand Gynaecology, GMC, Patiala for a period of two years from \n2017 to 2019 as a prospective interventional study. Consent for \nparticipation in the study was taken.  Women with heavy \nmenstrual period, dysmenorrhea or both who reported in the \nOPD were examined, including breast and pelvic examination. \nUSG was done to note various pathologies like fibroid, \nendometriosis, endometrial hyperplasia, adenomyosis and \nfunctional ovarian cyst. This was followed by endometrial \nbiopsy. After the biopsy report was available, decision for LNG -\nIUS insertion was taken. LNG-IUS was inserted, under all sterile \nconditions without anaesthesia. \nAfter insertion, patient was followed up at 1 -, 3 -, 6 - and 12 -\nmonth interval. The menstrual pattern was noted and USG \nrepeated to compare the changes with initial USG findings. For \nthe abnormal bleeding pattern following LNG -IUS, oral \nprogesterone v/s SERMs were compared. Exclusion criteria \nincluded pregnancy, DVT, STDs, liver disease, recent \ntrophoblastic disease, bacterial endocarditis, uterine pathologies \nobliterating uterine cavities. \n \nResults \nA total of 30 patients were enrolled over the period of two year, \nwho presented in Gynae OPD with chief c omplaint of heavy \nmenstrual period with/without dysmenorrhea. 28 patients were \nin the age group 30 -50 years and only 2 patients were post -\nmenopausal. 56.6% had rural background, 43% were illiterate \nand 83.3% were multipara. (Table No 1). \n \nTable 1: Demographic characteristics \n \nAge (in years) No. of patients Percentage \n30 TO 40 10 33.3 \n41 TO 50 18 60 \n51 TO 60 2 6.6 \nEducation Status   \nIlleterate 13 43 \nmatric 6 20 \ngraduate and above 11 36 \nRural/Urban   \nRural 17 56.6 \nUrban 13 43.3 \nParity   \nPrimipara 5 16.6 \nMultipara 25 83.3 \n \nIn 50% of the women, the chief complaint was heavy menstrual \nbleeding with dysmenorrhea and 36% had heavy menstrual \nbleeding alone. 6.6% had dysmenorrhea alone and another 10% \nreported with irregular bleeding. 16.6% of women we re obese \nwith BMI >30 and 25% had diabetes, hypertension or both with \ndistribution as shown in the table. 6.6% of women had heart \ndisease and gall stones each. 3.3% had IITP, spine surgery, \nhistory of myomectomy, hypothyroidism, bronchial asthma and \nbreast surgery. (Table No 2)  \n \nTable 2: Medical/Surgical Comorbidities in patients \n \nMedical condition No of patients %age \nBMI>30 5 16.6 \nDiabetes 3 10 \nHypertension 4 13.3 \nDiabetes and hypertension 2 6.6 \nGallstones 2 6.6 \nITP 1 3.3 \nBronchial asthma 1 3.3 \nHeart disease 2 6.6 \nSpine surgery 1 3.3 \nDiagnostic laparopscoy for endometriosis 1 3.3 \nBreast surgery 2 6.6 \n \n76% reported with moderate anaemia and 6.6% with severe \nanaemia. USG findings revealed adenomyosis in 16.6 %, \nfunctional ovarian cyst in 13.3% wit h most commonly \nassociated finding of fibroids in 30% of the patients. \nEndometrial thickness was more than 8mm in 66.6% of pts.  The \nutero-cervical length was >7 cm in 16.6% and 8cm in 30%, 9cm \nin another 30% and >10 cm in 13.3%. Uterine cavity was regular \nin 93.3% of patients. Histopathological findings are as shown in \nthe Table No 3. \n \nTable 3: Endometrial Histopathlogy \n \nHistopathology No of \npatients \n% \nage \nProliferative phase 10 33.3 \nSecretary phase 9 30 \nDisordered proliferative phase 4 13.3 \nSimple endometrial hyperplasia without atypia 5 16.6 \nComplex endometrial hyperplasia without atypia 1 3.3 \nAdenocarcinoma well differentiated with squamoid \ndifferentiation 1 3.3 \n \n\nInternational Journal of Clinical Obstetrics and Gynaecology http://www.gynaecologyjournal.com \n~ 175 ~ \nAccording to PALM -COIEN classification, AUB -A was \ndiagnosed in 16.6%, AUB -L in 30%, A UB-O in 40%, AUB -M \nin 3.3%, endometriosis in 13.3%.  (Table no.4) LNG -IUS was \nnot used as contraception or HRT in any of the cases. \n \nTable 4: Final diagnosis \n \nIndication for insertion No of patients %age \nAUB -A 5 16.6 \nAUB -L 9 30 \nAUB-M 1 3.3 \nAUB -O 12 40 \nEndometrosis 4 13.3 \n \nOn post insertion follow up after one month,  90 percent had \nrelief from heavy menstrual bleeding (60% reported spotting,  \n23.3% reported moderate flow but not heavy flow,3.3% each \nreported amenorrhoea and normal flow). Rest 10% stil l had \nheavy flow.  At six -month follow-up, 23.3 % reported spotting \nand 60% reported normal flow during periods.  After one year \n73.9% patient had normal flow and 13% patients achieved \namenorrhoea. The irregular bleeding or spotting was managed \nby giving supp ortive therapy in form of reassurance in 30%, \nNSAIDS in 16.6%, and norethisterone in 46.6%. Ormeloxifene \nand OCPs were given in 3.3% each and response was \nsatisfactory. Repeat biopsy after 6 months was done in a patient \nof endometroid carcinoma with squamo us differentiation stage \n1a which came out to be same with improvement in symptoms. \nLater patient was lost to follow up. Dysmenorrhoea was reported \nby 17 patients and 12 got a relief from dysmenorrhoea. \nAt one year follow up it was seen that 76.6% patients  continued \nwith LNG IUS and found it comfortable with enhanced quality \nof life as 6.6% opted for hysterectomy as they continued to have \nheavy bleeding and pain. One of these patients was having \nfibroid uterus as well. Another 6.6% of patients got it remove d \nas they were not satisfied with its use and switched to alternative \nmedicine. In three patients it got expelled spontaneously which \nwas noticed on repeat USG. \n \nDiscussion \nPerimenopausal age group of women is surrounded by plethora \nof menstrual problems f or which earlier hysterectomy was the \nonly answer but as the physiology and pathology became clearer \nwith advancing research there came many options to treat these \nproblems. Most of the women in developing and developed \ncountries, who suffer from AUB opt f or hysterectomy because \nof the loss of working hours, money, costly healthcare and \nassociated morbidity with AUB. Various medical and surgical \nmethods available for heavy menstrual bleeding are like \nProstaglandin synthetase inhibitors, anti -fibrinolytic ag ents, \nOCPs and endometrial ablation (Trans cervical resection of \nendometrium or thermal balloon ablati on), have just 20 -50% \nefficacy [2]. LNG appears to be a boon for women with heavy \nmenstrual bleeding provided they are adequately counselled [4]. \nIn our study, 90% of the patients got relieved of heavy menstrual \nflow within one month of its use and similar trends were noticed \nby other authors [2, 4, 5, 7, 12, 15]. (Table No 5).\n \nTable 5: Comparison of Results with various studies \n \nAuthor & Study Decrease in Blood Loss Decrease in Dysmenorrhea Continuation rate Hysterectomy \nBeatty and Blumenthal 2009 86-97% - 90% - \nGallos et al. 2013 84% - - - \nUma Pandey 2016 80% - 80% 20% \nGARG And SONI A 2016 93% 76% 90% 6% \nBenipal et al. 2018 85% - 98% 1.92 \nBeckert V et al. 2019 54% - - - \nChen Ba et al. 2019 74.7% - - - \nMargatho D et al. 2020 - Vas score decreased - - \nPresent Study 90% 70% 76.6% 6.6% \n \nLNG-IUS when compared with oral progesterone’s is a better \nfirst line management in endometrial hyperplasia becaus e of \n94% regression rate as compared to 84% [3, 7]. Mandel Baum et \nal., RS et al . compared the effects of LNG -IUS with systemic \nprogesterone in complex atypical endometrial hyperplasia in 245 \nwomen and found (78.7% vs 46.7%) higher rate of complete \nresponse and lower progression rate to cancer in  LNG-IUS \ngroup (4.5% vs 15.7%) [9]. \nEndometriosis is a significant problem affecting 5.7% of women \nof reproductive age group causing chronic pelvic pain, \ndyspareunia, infertility and dysmenorrhea, affecting the qual ity \nof their life. The hypoestrogenic effects of medical treatment \nlike Depot Medroxyprogesterone acetate, Danazol, \ngonadotrophin realising hormone analogues affected the \ncompliance of the patients and higher discontinuation rate. This \nled to the use of LN G-IUS as an alternative. In our study, 17 \npatients who came with dysmenorrhea and heavy menstrual \nbleeding and diagnosed on USG as adenomyosis and \nendometriosis, 12 patients were relieved of dysmenorrhea within \n6 months of LNG -IUS insertion cosistentent wi th findings of \nother authors. In adenomyosis, LNG -IUS causes decidualization \nand atrophy of endometrium. Decreased blood flow and \ndownregulation of oestrogen receptors in glandular and stromal \nendometrial tissue leads to atrophy and shrinkage of \nadenomyosis foci in the myometrium. This allows myometrium \nto contract better and decreases blood l oss and the size of the \nuterus [2, 5, 7, 17]. \nEndometrial hyperplasia may be simple or complex, with or \nwithout atypia, is another indication where LNG -IUS is being \nused with 100% response rate.  \nFertility preservation is the main requirement in endometrial \ncancers, LNG -IUS has been tried and lesion have regressed in \n70-75% cases of Stage 1A endometrioid endometrial cancer and \natypical hyperplasia [18]. In our study, we  had just one case of \nendometrial cancer who was not medically fit for hysterectomy, \nso LNG-IUS was given with dramatic decrease in blood loss and \nimprovement in general condition through 6 months post LNG -\nIUS. Histopathological findings were same on repea t biopsy and \nthere after that patient was lost to follow-up.  \nIn our study, 30% of patients had fibroid who reported with \nheavy menstrual bleeding and dysmenorrhea and found to have \nendometrial hyperplasia which might be associated with hyper \nestrogenic state. Uterine cavity was not distorted by fibroids and \nfibroid size did not exceed 3cm. LNG -IUS was given and only \none patient expelled it, another one patient discontinued it \nfollowing persistent heavy menstrual bleeding and another got it \n\nInternational Journal of Clinical Obstetrics and Gynaecology http://www.gynaecologyjournal.com \n~ 176 ~ \nremoved and unde rwent hysterectomy. Uma Pandey too \nreported 20% hysterectomy rate in her study. (Table no.5) \nLNG-IUS is usually well tolerated but its most common side \neffects are menstrual bleeding cycle change and spotting off and \non, maybe breakthrough bleeding. Most a uthors report decrease \nin number of bleeding days and improvement in symptoms from \n1st through 3 months of insertion [12, 13, 14, 15, 16]. The treatment of \nthis breakthrough bleeding by oral progesterone or by  SERMs \nwere not much different [13]. In our stu dy we found SERMs \ngiving better control than oral progesterone. \nOverall use of LNG -IUS was associated with good results with \nincrease in quality of life but it needed lots of persuation to go \nfor this method as it resembled CuT.  Various myths attached \nwith CuT affected the choice of LNG -IUS over hysterectomy. \nSecond was the cost factor which was a major hur dle in \nacceptance of the method . Third was the refusal for follow up \nvisits and repeat biopsy requirements as most pts want once and \nfor all treatment . Larger studies are required to further \nauthenticate its use for non contraceptive uses. \n \nConclusion \nIt is being concluded that LNG -IUS is a better choice for the \nmanagement of endometrial hyperplasia simple or complex, \nwith or without atypia, AUB, adenomyos is and endometriosis. \nLNG-IUS can be a good alternative to hysterectomy, and is akin \nto medical hysterectomy in present times, which is cost \neffective, time saving, does not require anaesthesia and \ndecreases morbidity. \n \nReferences \n1. Hoffman Schorage, Bradshaw Halvorson, Schaffer Corton. \nWilliams Gynecology.  3rd edition.  Abnormal Uterine \nBleeding, New York:  McGraw Hill education . 2016, \nP(195). \n2. Beatty MN, Blumenthal PD. The levonorgestrel -releasing \nintrauterine system: safety, efficacy, and patient \nacceptability. Therapeutics and clinical risk management. \n2009;5:561. \n3. 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