{"paper_id":"3ce4f181-cc00-4ac2-a171-d2fab03cc966","body_text":"COMMUNICA TION\nDe novo postmenopausal endometriosis during tibolone\ntreatment: a case report and review of the literature\nBerna Dilbaz & Y esim Bayoglu Tekin & Serdar Dilbaz &\nAli Haberal\nReceived: 29 August 2007 / Accepted: 15 October 2007 / Published online: 30 November 2007\n# Springer-V erlag 2007\nAbstract Endometriosis is uncommon before puberty and\nafter menopause as it is an estrogen-dependent disease. A\ncase is presented of postmenopausal endometriosis encoun-\ntered in a patient who had received tibolone (Livial, Organon,\nCambridge, UK) 1 year before the diagnosis of the adnexal\nmass for 3 months for relief from vasomotor symptoms and\nhad the medication stopped because of fibrocystic disease of\nthe breast. Transvaginal ultrasonography showed homoge-\nneous cystic adnexal mass of 36×26 mm with no internal\nechoes in the right ovary. Laparoscopic right salpingooophor-\nectomy was performed and the histopathological examination\nof the cyst showed an endometriotic cyst. Most of the cases\nwith postmenopausal endometriosis are associated with the\nuse of hormone replacement therapy (HRT). However,\ntibolone is recommended in hormone replacement therapy\nof postmenopausal symptomatic women who have a past\nhistory of hormone-dependent tumors such as endometriosis.\nThere is restricted data in the literature about tibolone use and\nrecurrence or de novo formation of endometriosis.\nKeywords Postmenopausal endometriosis . Tibolone . HRT\nIntroduction\nEndometriosis is defined as the growth of endometrial tis-\nsue outside the uterus. This condition is an estrogen-\ndependent disease and occurs in approximately 10% of the\nwomen of reproductive age [ 1]. Endometriosis is uncom-\nmon before puberty and after menopause [ 2].\nIndeed the lesions regress after menopause or ovariecto-\nmy. Women who were diagnosed to have endometriosis in\nthe postmenopausal period are estimated to be only 2 –4%\nof the disease population [ 3]. Postmenopausal endometri-\nosis can occur with a wide spectrum of symptoms besides\nthe presence of asymptomatic masses including abdominal\npain, bleeding and intestinal or urinary tract obstruction [ 4].\nWe report a case of postmenopausal de novo endometriosis\nafter use of tibolone in a patient with no past history of\nendometriosis or adnexal mass.\nCase report\nA 56-year-old woman, gravida 3, para 3, body mass index\n26 kg/m\n2 presented with ongoing pelvic pain for the last\nyear. She had not experienced infertility, dysmenorrhea, or\ndyspareunia during her reproductive years. Her three\npregnancies resulted in normal vaginal deliveries at term.\nShe had regular flow until hypermenorrhea occurred in the\npremenopausal period; menopause ensued at 51 years of\nage. For the last 5 years she had attended the Menopause\nClinic for follow-up visits, and annual physical examina-\ntion, pelvic sonography, and cervical smear screening\ncarried out as a part of a routine protocol revealed no patho-\nlogical findings.\nOne year before the diagnosis of the adnexal mass, she\nhad received tibolone (Livial, Organon, Cambridge, UK)\nfor 3 months for relief from vasomotor symptoms, but the\nmedication was discontinued because of fibrocystic disease\nof the breast. She was taking antihypertensive drugs at the\ntime. A fullness presumed to be a right adnexal mass was\nGynecol Surg (2008) 5:235 –237\nDOI 10.1007/s10397-007-0355-9\nB. Dilbaz : Y . B. Tekin: S. Dilbaz : A. Haberal\nObstetrics and Gynecology, Ministry of Health Ankara,\nEtlik Maternity and Women’s Health Teaching and Research Hospital,\nEtlik, Ankara, Turkey\nS. Dilbaz ( *)\nMithatpasa Caddesi 59/3,\n06420 K ızılay, Ankara, Turkey\ne-mail: sdilbaz@hotmail.com\n\npalpated during bimanual vaginal examination. She was\nreferred to the Endoscopic Surgery Unit. Transvaginal\nultrasonography showed a homogeneous cystic adnexal\nmass of 36×26 mm with no internal echoes in the right\novary and an endometrial thickness of 10 mm was measured.\nA saline sonohysterography was performed showing a\nsubmucous leiomyoma of 17×15 mm. Serum concentra-\ntions of the tumor markers were as follows: CA-125=\n12.3 U/ml, CA 19-9=41.82 U/ml. Laparoscopy and\nhysteroscopy were performed on May 2007. During\nobservation of the peritoneal cavity, a 5-cm right ovarian\ncyst adherent to the fossae ovarica and the posterior wall of\nthe uterus was observed; otherwise the pelvic and perito-\nneal cavity was normal. After taking peritoneal washings\nfor cytological examination, right salpingooophorectomy\nwas performed in addition to hysteroscopic resection of the\nsubmucous leiomyoma 2.5 cm diameter that was located at\nthe left cornual side. The histopathological examination of\nthe cyst showed an endometriotic cyst.\nDiscussion\nEndometriosis is commonly a disease of the reproductive\nages associated with pelvic pain, dysmenorrhea, and\ninfertility. As endometriosis is an estrogen-dependent\ndisease, it is rarely seen after menopause. Most of the cases\nof postmenopausal endometriosis are associated with use of\nHRT, and the majority of the recent reports were cases with\nknown endometriosis that recurred in the postmenopausal\nperiod after estrogen replacement therapy.\nThe recurrent disease is more severe than the primary\ndisease in some cases [ 5–9]. However, HRT has been\nreported to be associated with development of de novo\nendometriosis in a hysterectomized postmenopausal patient\n[10]. A case of cutaneous endometriosis was reported in a\npostmenopausal woman receiving hormonal replacement,\nhighlighting the possibility of growth of extrauterine endo-\nmetrial tissue during exposure to exogenous estrogen [ 11].\nTibolone [(7_,17_)-17-hydroxy-7-methyl-19-norpropen-\n5(10)-en-20-yn-3-one] is a steroid that exhibits weak estro-\ngenic, progestogenic, and androgenic activity and has been\nshown to have a beneficial effect on climacteric vasomotor\nsymptoms and on depressed mood [ 12]. Combined estro-\ngenic, androgenic, and progestogenic activities exert a posi-\ntive synergistic effect on certain target organs, e.g., the\nhypothalamic-pituitary axis, and antagonistic or comple-\nmentary effects on others, e.g., endometrium. The effect of\ntibolone on endometrium is inhibitory as progestogenic-\nandrogenic activity is dominant. Tibolone, being anon-bleeding\nform of hormone replacement therapy, is recommended in\npostmenopausal symptomatic women who had hormone-\ndependent tumors such as endometriosis in the past [13]. The\ndrug is used to treat the vasomotor symptoms of women with\nendometriosis, as it is presumed to show minimal stimulative\neffect on ectopic endometrial tissue [ 14]. However, Davies\net al. reported a postmenopausal case that showed exacer-\nbation of adenomyosis while receiving tibolone [ 15].\nOur patient had no known history of endometriosis and\nher symptoms began after she had received tibolone for\nhormonal replacement; the adnexal mass was determined\nafter the treatment. There is restricted data in the literature\nabout tibolone use and recurrence or de novo formation of\nendometriosis. Most report the beneficial effect of the drug\nfor treatment of endometriosis [ 16] and its safety for\ntreatment of residual endometriosis after menopause [ 17].\nExogenous estrogen supplement therapy and endoge-\nnous production of estrogens by conversion of androgens\nare blamed for the proliferation of endometrial lesions\nduring the postmenopausal period. Endometriotic lesions\ncontain estrogen and aromatase receptors.\nAromatase is an enzyme that acts as a catalyzer in\nconversion of androgens to estrogens [ 18]. The presence of\naromatase receptors may explain the stimulation of the\ngrowth of endometriotic lesions by local estrogen produced\nthrough conversion from androgens in patients who have\npostmenopausal endometriosis without any estrogen use. In\ngeneral, postmenopausal endometriosis is considered as\nrecurrence of the previous disease. Goodman et al. [ 7] also\nproposed that endometrial metaplasia may develop under\nthe influence of estrogen in spite of the concomitant use of\nprogestogen. All of these hypotheses may explain the\ndevelopment of an endometriotic cyst during the meno-\npausal period in patients without a previous history of\nendometriosis. Moreover, a series of 123 women with\nendometriosis who had definitive surgery (total abdominal\nhysterectomy with bilateral salpingooophorectomy) were\nfollowed-up to evaluate the effect of HRT regimens\n(estrogen only, cyclic estrogen/progestin, continuous com-\nbined estrogen/progestin) and no HRT on disease recur-\nrence [ 19]. There was only one case (2%) of recurrent\nendometriosis in the estrogen-only group.\nThe etiology and pathophysiology of endometriosis is\nnot well understood or well documented. Furthermore\npostmenopausal development of endometriosis still remains\na mystery as in some cases it occurs with HRT mostly as a\nrecurrent disease or sometimes as a de nova formation and\nrarely without any exogenous hormone treatment. Investi-\ngation of large series is required for a better understanding\nof this condition. In conclusion, endometriosis should be\nconsidered in postmenopausal women who present with\npelvic pain and adnexal mass while receiving HRT.\n236 Gynecol Surg (2008) 5:235 –237\n\nReferences\n1. Crosignani P , Olive D, Bergqvist A, Luciano A (2006) Advances\nin the management of endometriosis: an update for clinicians.\nHuman Reprod Update 12(2):179 –189\n2. Barbieri RL (1990) Etiology and epidemiology of endometriosis.\nAm J Obstet Gynecol 162:565 –567\n3. Punnonen R, Klemi PJ, Nikkanen V (1980) Postmenopausal\nendometriosis. Eur J Obstet Gynecol Reprod Biol 11(3):195 –200\n4. Kempers RD, Dockerty MB, Hunt AB, Symmonds RE (1960)\nSignificant postmenopausal endometriosis. Surg Gynecol Obstet\n111:348–356\n5. Lam AM, French M, Charnock FM (1992) Bilateral ureteric\nobstruction due to recurrent endometriosis associated with\nhormone replacement therapy. Aust NZ J Obstet Gynaecol\n32:83–84\n6. Deval B, Rafii A, Dachez MF, Kermanash R, Levardon M (2002)\nSigmoid endometriosis in a post menopausal woman. Am J Obstet\nGynecol 187:1723 –1725\n7. Goodman HM, Kredentser D, Deligdisch L (1989) Postmeno-\npausal endometriosis associated with hormone replacement\ntherapy. A case report. J Reprod Med 34(3):231 –233\n8. Goh JT, Hall BA (1992) Postmenopausal endometrioma and\nhormonal replacement therapy. Aust NZ J Obstet Gynaecol 32\n(4):384–385\n9. Bellina JH, Schenck D (2000) Large postmenopausal ovarian\nendometrioma. Obstet Gynecol 96:846\n10. 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