{"paper_id":"93ba82a2-71eb-4008-b57a-cf1246c4e49a","body_text":"American Medical Journal 1 (1): 23-26, 2010 \nISSN 1949-0070 \n© 2010 Science Publications \n23 \n \nA Comparative Study between Norethisterone Progestogens and Dydrogesterone \nin the Treatment of Dysfunctional Uterine Bleeding  \n \nNabila K. Yaaqoub  \nDepartment of Gynaecology and Obstetrics, Faculty of Medicine, \nUniversity of Tikrit, P.O. Box 42, Tikrit Salahuddin, Iraq  \n \nAbstract: Problem statement:  To compare the effects of both Norethisterone Prog estongens and \nDydrogesterone in the treatment of Dysfunctional Ut erine bleeding Design: A prospective study. \nSetting: Tikrit Teaching Hospital, Iraq.  Approach:  About 200 patients presented with abnormal \nuterine bleeding and diagnosed as dysfunctional ute rine bleeding were included in this study. Group A \n(study group): Include 100 patients were treated wi th norethisterone progestogens. Group B (control \ngroup): Include 100 patients were treated with dydr ogesterone the response of the patients were \nassessed by regularity of menstrual cycle.  Results:  About 75 patients had regular cycle while 25 \npatients still had irregular bleeding regarding fir st group. 46 patients had regular cycle while25 pat ients \nstill had irregular bleeding regarding second group , decrease in severity of bleeding and resumption o f \nregular cycle were more apparent with Norethiserone  drug.  Conclusion/Recommendations:  Both \nnorethisterone progestogens and dydrogesterone can be used in the treatment of dysfunctional uterine \nbleeding. Norethisterone progertogens showed higher  rates of regular resumption of menses than \nDydrogesterone and I recommended to use Norethisert one in the treatment of other problems like \nregulate ovulation in infertile woman. \n \nKey words: Norethisterone progestogens, dydogestrone dysfuncti on uterine bleeding, menorrhagia, \nanovulatory cycle, menstruation \n \nINTRODUCTION \n \nDysfunctional Uterine Bleeding (DUB):  Is best define \nas abnormal bleeding from the uterus in the absence  of \norganic disease of the genital tract and applies to  any \nabnormal uterine bleeding, including disturbances o f \nthe menstrual cycle, regular and irregular uterine \nbleeding and alterations in the amount or duration of \nmenstrual loss, but most commonly implies excessive  \nregular menstrual bleeding or essential menorrhagia  \n(Van, 1995a). \n DUB is a group of disorders characterized by \ndysfunction of uterus, ovary, pituitary, hypothalam us or \nother part of the reproductive system, which result s in \nabnormal or excessive uterine bleeding and the \ndiagnosis is usually made by exclusion of organic \ndisease of the genital tract (Davey, 1995). \n Abnormal uterine bleeding in general due to \norganic and non organic causes, the organic causes due \nto sub mucous fibroid, Adenomyosis, endometrial and  \nend cervical polyp, pelvic inflammatory disease and  \nmalignanet disease (Stuartc, 2000). \n \nClassification of DUB:   \nPrimary:  Due to primary dysfunction in the uterus, \novary, pituitary, hypothalamus or higher centers. \nSecondary:  To either: \n \n• Intrauterine contraceptive device or administration  \nof sex hormones for contraception or other \npurposes \n• Organic disease outside the reproductive system \n(Jacobs, 1995) \n \n Twelve percent of all gynecological problems are \ndue to menorrhagia and the commonest cause for \nhysterectomy (Charles, 1999). \n The duration of menstrual blood loss varies \nnormally in different women from 2-7 days with a \nmean of 5 days, but any menstruation lasting 8 days  or \nlonger should be regarded as excessive (Van, 1995b) . \n The best measure of the amount of menstruation is \nthe total Menstrual Blood Loss (MBL), which is \nestimated from the total hemoglobin extracted from all \ntampons, towels and other material used during \nmenstruation and measured objectively by alkaline \nhaematin or other standard method (Hallberg, 1995).  \n DUB can occur at any age; though it’s an etiology \nand management vary greatly in different age groups  so \nan understanding of the effect of age and parity on  \nmanagement and on the risk of missed uterine \npathology is important (Van, 1995b). \n\nAm. Med. J. 1 (1): 23-26, 2010 \n \n24 \n The years immediately following the menarche are \ncharacterized by irregular menstrual cycles and lon g \ncycles due to immaturity of the hypothalamus and \npituitary and menstrual cycles may be a novulatory,  the \nmiddle years of reproductive life in normal women a re \ncharacterized by regular menstrual cycles and regul ar \novulation, in premenopausal years menstrual cycles \noften become irregular again due to the decreased \nnumber of ovarian follicles and their increased \nresistance to gonadotrophin stimulation, this resul ts in a \nprogressive increase in corpus lustrum insufficienc y or \nanovulatory cycles and eventually in cessation of \nmenstruation (Suther Land, 1995). \n History and examination are important in the \ndiagnosis of DUB, a full blood count is an essentia l \ninvestigation in a patient with abnormal bleeding, \nthyroid function tests to exclude thyroid diseases,  mid-\nluteal progesterone level test is performed when pa tient \nhas a regular cycle only, a level greater than 30 nmol L\n−1 \nis indicative of ovulation, prolactin level because  \nincrease level result in an ovulation that cause ab normal \nuterine bleeding, coagulation screen is important i f a \nbleeding disorder is suspected, serum androgens may be \nelevated in patients with polycystic ovarian syndro me \n(Geeta, 2000). \n Transvaginal ultrasound is an excellent tool for \nevaluating pelvic structures and pathology, new \ndevelopments with Doppler ultrasound will provide \ninformation on pelvic vascularity while 3-D ultraso und \nwill aid the diagnosis of congenital uterine \nabnormalities. \n Hysteroscopy is the gold standard procedure as it \nprovides visualization of entire uterine cavity, is  ideally \nperformed during the proliferative phase of the \nmenstrual cycle when the endometrium is at its thin nest \n(Jane, 2000). \n In acute situation the main priorities of treatmen t \ninvolve, correction of anemia and arresting ongoing  \nbleeding. \n Progestogens are mainly indicated in patients with  \nanovulatory bleeding, to reverse the effects of est rogen-\nmediated endometrial proliferation and induce \nendometrial maturation. \n Others Drugs can be used in DUB like combined \noral contraceptives, danzol, gonadotrophin releasin g \nhormone analogues like buserelin and goserelin and \nlevenorgestral-releasing intra-uterine contraceptiv e \ndevice (mirena). \n Other agents like antifibrinolytics like tranexami c \nacid and non-steroidal anti-inflammation agents lik e \nmefenamic acid can also arrest bleeding (Jane, 2000 ). \n Dilatation and curettage can reduce bleeding in 75 -\n80% of cases in acute situation, endometrial resect ion \nand ablation by diathermy and laser can reduce \nbleeding in 40% and finally hysterectomy as option for \npatients who have not responded to medical therapy or \nto more conservative surgical options. \n Both laparoscopic myolysis and embolization \ntechniques have been reported to be successful mode s \nof treatment (Farn, 2000). \n Primolut N can be used in dysfunctional bleeding, \nprimary and secondary amenorrhea, premenstrual \nsyndrone, mastopathy and endometriosis. \n In rare cases nausea may occur, it’s contraindicat ed \nin pregnancy, sever disturbances of liver function,  \ndubin-johuson syndrome, previous or existing liver \ntumors. \n A history of jaundice or severe pruritus during \npregnancy, a history of herpes of pregnancy and \nthrombo-embolic processes.  \n If migrainous headaches or unusual severe \nheadaches, sudden disturbances of vision or hearing , \nunusual pains or swelling of the legs, stabbing pai ns on \nbreathing, significant rise in blood pressure, onse t of \njaundice or itching or hepatitis there is should be  \ndiscontinuation of the drug.  \n Recent investigations have confirmed that \nnorethisterone is partly metabolized to ethinylestr adiol \nit’s c-19 derivative that cause more androgenic sid e-\neffects such as acne and greasy skin than C21 \nderivatives (Aladin and Yousif, 1990). \n \nDydrogesterone (duphaston):  Is C21 derivatives \ncause less androgenic side-effects but more \npsychological distress such as anxiety, appear to h ave \nless effect than C19 derivatives on lipoprotein \n(Whitehead, 1999). \n \nMATERIALS AND METHODS \n \n This study was conducted on women attending \ngynecological unit in Tikrit teaching hospital over  a \nperiod of one year from October 2008 to October 200 9, \nit is a prospective study. \n The total number of women included in this study \nwere 225, 25 women withdrew from the study due to \nintolerance of the side effects of the drugs, 200 w omen \nwere the total patients included in this study, 100  were \ncontrols and 100 were the study group. \n None of those patients were treated with ant \nbleeding agents in the previous 3 weeks. \n A full history was obtained from each woman and \na full physical examination was performed, the pati ents \nwere divided into 2 groups: \n \n• Group A (Study group): Include 100 patients were \ntreated with norethisterone progestogens \n\nAm. Med. J. 1 (1): 23-26, 2010 \n \n25 \n• Group B (control group): Include 100 patients were \ntreated with dydrogesterone \n \n The patients in both groups were diagnosed as \ndysfunctional uterine bleeding after exclude the or ganic \npathology by careful history taken from the patient s \nabout the attach of bleeding, severity, duration an d \nassociated symptoms, any associated gynecological \nproblems including dysmenorrheal, infertility, \nmenopausal symptoms, any symptoms suggestive of \nbleeding disorder or myxoedema. \n History of administration of sex hormones, \nintrauterine contraceptive device, history of hepar in or \nwayfaring using, pelvic inflammatory disease and \norganic pathology outside the reproductive system l ike \nhemorrhoid, anal fissure that causing bleeding per \nrectum or haematuria due to renal stone for example  \nand miss diagnosed as vaginal bleeding. \n General, pelvic and abdominal examination are \nessential, general examination for stigma of system ic \ndiseases like hirsutisum, strait, thyroid enlargement,skin \npigment changes for echymosis, petechi, examination  \nof lymph nodes, liver and spleen. \n Inspection of vulva for bleeding, infection and \nspeculum examination of vagina and cervix were \nessential for exclude any pathology. \n Ultrasound examination was performed for both \ngroups to exclude pelvic mass or possible pregnancy  \ncomplications, fibroids, ovarian cyst, endometrial polyp \nand measurement of endometrial thickness. \n Also Baseline Hemoglobin (Hb) was done for both \ngroups as a part of assessment of the severity of t he \nbleeding. \n All patients were in reproductive age group betwee n \n20-45 years old and all were married, from the ethi cal \npoint of view all patients were asked if they would like to \nparticipate in the study and a full explanation abo ut the \nnature and side effects of the drugs, if the patien t \npresented with sever uterine bleeding can be arrest ed by \nlarge doses of progestogens, norethisterone acetate  \n(primolut N) 20-30 mg daily is given until bleeding stops \n(within 24-48 h) and for not more than 3 days, then  the \nprogestogens may continued at lower dose for 21 days, if \nnot sever bleeding, norethisterone acetate 5 mg dai ly \nfrom the 5th-25th day of cycle and continued for a \nminimum of 3 cycles, this protocol for the first gr oup \n(Group A). \n The protocol for the second group (Group B),the \nbleeding can be arrested by given 10 mg \ndydrogesterone (duphaston) one Tablet daily 3 times  \nover 10 days, then continued at lower dose for 21 d ays, \nif not sever bleeding dydrogesterone 10 mg daily fr om \n5th-25th day of cycle and continued for a minimum o f \n3 cycles. \nTable 1: Character of patient  \nGroups Study group Control group \nNumber of patients  100 100 \nAge (mean ± SD) 28±3.5 27.5±3.8 \n \nTable 2: Response  of patient according to type of drugs   \nEffects R/(primolut N) R/(duphaston) Total \nStop bleeding with  75   46  121 \nregular cycle \nNot stop bleeding   25   54  79 \nTotal  100  100  200 \n \n For both groups we gave one Tablet primolut N or \ndydrogesterone 2 times daily from the 19th-26th day  of \ncycle as prophylactic dose after we control the ble eding \nto prevent recurrence of dysfunctional bleeding for  at \nleast 3 cycles. \n \nRESULTS \n \n The all patients involve in this study were marrie d \nand in reproductive age group (20-45), so both grou ps \nwere matched for the age and it was founded that th ere \nis no significant difference between mean age of bo th \ngroup. \n \nGroup A (study group):  Mean age ± SD = 28±3.5 (SD \n(Standard deviation) \n \nGroup B (control group): 27.5±3.8 when applying t-\ntest: \n \nT = 1.86, so p<0.05 \n \n No significant difference between both groups \nregarding the age as in Table 1. \n In the study group which is on primolut N there is  \n75 patients had regular cycle with arrest bleeding within \na period of treatment, while 25 patients still had \nirregular cycle with no control bleeding. \n In the control group which is on duphaston there i s \n46 patients had regular cycle with arrest bleeding,  while \n54 patients still had irregular cycle with no contr ol \nbleeding as in Table 2: \n \nChi-Square (X \n2) = 18.4 \n \ndf = Degree of freedom \n \np>0.05 (probability) = Level of significant \n \n There is a very significant difference between bot h \ngroups according to the type of treatment.  \n \nDISCUSSION \n \n The most common cause of abnormal uterine \nbleeding in premenopausal woman is estrogenized an \novulation (Steve, 2003). \n Menorrhagia affects approximately 15-20% of \nwomen presenting with abnormal uterine bleeding and  \n\nAm. Med. J. 1 (1): 23-26, 2010 \n \n26 \ncause significant social inconvenience as well as t he \npotential for significant anemia (James, 2003). \n Unfortunately, there is no simple clinical way to \nquantities the amount of blood lost during a menstr ual \nperiod, counting the number of sanitary protective’ s \nused in a menstrual cycle has proven to be inaccura te \nbased on differences in personal hygiene and cultur al \nback grounds, when accurately quantities, blood loo se \nduring an entire normal adulatory menstrual cycle i s \napproximately 60-80 mL\n−1, this amount of blood loose \nwill not cause a decrease in hemoglobin in women \nconsuming normal balanced diet (Beth, 2003). \n As described by Arthur (2003), dysfunctional \nuterine bleeding unrelated to mechanical factors, \niatrogenic causes, infectious agents, cancer or \npregnancy. \n They’re no one particular pattern of bleeding that  \nunequivocally defines dysfunctional uterine bleedin g \n(Arthur, 2003). \n All women in our study were in the reproductive \nage group and there is no significant difference be tween \nstudy and control groups regarding age as in Table 1. \n About 75 patients were putted on primolut N \nTablet had regular cycle and stop their bleeding wh ile \n25 patients still had irregular bleeding, which is \nconsistent with the findings of Davey (1995). \n About 46 patients were putted on duphastone \nTablet had regular cycle and stop their bleeding wh ile \n54 patients still had irregular bleeding, which is \nconsistent with findings of Charles (1999). \n So there is a significant difference between both \ngroups according to the type of treatment which is \nconsistent with findings of Matthew (2003). \n \nCONCLUSION \n \n• Both norethisterone progestogens and \ndydrogesterone can be used in the treatment of \ndysfunctional uterine bleeding \n• Norethisterone progestogens were more effective \nin the treatment of dysfunctional uterine bleeding \nthan dydrogesterone \n \nREFERENCES \n \nAladin, A.S.  and Z. Yousif, 1990. Iraqi Drug Guide . \n1st Edn., John Wiley and Sons, \n pp: 168-170. \nArthur, F., 2003. Hormones and Abnormal Uterine \nBleeding. Danforth’s Obstetrics and Gynecology. \n9th   Edn.,  Lippincott   Williams  and  Wilkins,  \nISBN: 0-3452-5430-1, pp: 645-646.  \nBeth, Y., 2003. Abnormal Uterine Bleeding . Danforth’s \nObstetrics and Gynecology. 9th Edn., Lippincott \nWilliams   and  Wilkins,  ISBN: 0-7817-3730-3, \npp: 643-644. \nCharles, R., 1999. Dysfunctional Uterine Bleeding. \nDewhursts Text Book of Obstetrics and \nGynecology for Post Graduates. 6th Edn., John \nWiley and Sons, ISBN: 0766526511, pp: 409-411. \nDavey, D.A., 1995. Dysfunctional Uterine Bleeding. \nDewhursts Text Book of Obstetrics and \nGynecology for Post Graduates. 5th Edn., John \nWiley and Sons, USA., pp: 590-593. \nFarn, R., 2000. Abnormal Uterine Bleeding. \nGynecology by 10 Teachers. 17th Edn., Oxford \nUniversity Press, Oxford, pp: 54-55. \nGeeta, N., 2000. Abnormal Uterine Bleeding. \nGynecology by 10 Teachers. 17th Edn., Oxford \nUniversity Press, Oxford, ISBN: 13: 978-0-340-\n81664-2, pp: 48-51. \nHallberg, L., 1995. Normal and Abnormal \nMenstruation . Dewhursts Text book of Obstetrics \nand Gynecology for post Graduates. 5th Edn., John \nWiley and Sons, ISBN: 085542652, pp: 590-595. \nJacobs, A.J., 1995. Incidence of Missed Organic \nDisease. Dewhursts Text Book of Obstetrics and \nGynecology for Post Graduates. 5th Edn., John \nWiley and Sons, ISBN: 085542652, pp: 590-592. \nJane, E., 2000. Abnormal Uterine Bleeding. \nGynecology by 10 Teachers. 17th Edn., Oxford \nUniversity Press, ISBN: 13: 978-0-340-81564-2, \npp: 51-54. \nJames, R., 2003. Abnormal Uterine Bleeding. \nDanforth’s Obstetrics and Gynecology. 9th Edn., \nLippincott Williams and Wilkins, ISBN: 0-5643-\n3830-2, pp: 649-650. \nMatthew, C., 2003. Endocrine Disorders. Berek and \nNovak’s Gynecology. 14th Edn., Lippincott \nWilliams and Wilkins, pp: 1076-1080. \nSuther Land, M., 1995. Incidence and Effects of Age  \nand Parity. Dewhursts Text book of Obstetrics and \nGynecology for post Graduates. 5th Edn., John \nWiley and Sons, ISBN: 085542652, pp: 592-594. \nStuartc, C., 2000. Disorders of the Menstrual Cycle . \nGynecology by 10 Teachers. 17th Edn., John \nWiley and Sons,  ISBN:   0665426511, pp: 48-50. \nSteve, N., 2003. Abnormal Uterine Bleeding. \nDanforth’s Obstetrics and Gynecology. 9th Edn., \nLippincott Williams and Wilkins, pp: 48-50. \nVan, E., 1995a. Blood Loss. Dewhursts Text Book of \nObstetrics and Gynecology for post Graduates. 5th \nEdn., John Wiley and Sons, pp: 591-594. \nVan, E., 1995b. Definition and Classification of \nDysfunctional Uterine Bleeding: Dewhursts Text \nBook of Obstetrics and Gynecology for Post \nGraduates. 5th Edn., John Wiley and Sons, USA., \nISBN: 085542652, pp: 590-591. \nWhitehead, M.I., 1999. Menopanse. Dewhurst’s Text \nbook of Obstetrics and Gynecology for post \nGraduates. 6th Edn., John Wiley and Sons, USA., \nISBN: 0765426511, pp: 453-454.","source_license":"CC0","license_restricted":false}