Prolonged use of gonadotropin-releasing hormone agonist and tibolone as add-back therapy for the treatment of endometrial hyperplasia

Αγοραστός, Θεόδωρος; Vaitsi, Violetta; Paschopoulos, Minas; Vakiani, Andromache; Zournatzi-Koiou, Vassiliki; Saravelos, H.; Kostopoulou, Evanthia; Constantinidis, Theodoros C.; Dinas, Konstantinos; Vavilis, Dimitrios; Lolis, D.; Bontis, J.

doi:10.1016/j.maturitas.2003.08.008

Cited by 19 publications

(9 citation statements)

References 19 publications

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“…11,12 Nu me ro us stu di es ha ve shown that to ac hi e ve add-back tre atment of en do met ri o sis, the use of ti bo lo ne in cre a se the bo ne mi ne ral den sity, re du ces an ti-es tro ge nic si de-ef fects, however do es not af fect the de ve lopment of en do met ri o sis fo ci. [24][25][26] In the me no pa u sal pe ri od, the use of ti bo lo ne has be en shown to in du ce en do met ri al at rophy. 27 Et tin ger et al, in ves ti ga ted the en do met ri al ef fects of ti bo lo ne in 3519 post-me no pa u sal pa ti ents, and they emp ha si zed the neg li gib le ef fect of ti bo lo ne on en do met ri al pro li fe ra ti on for ma ti on in the first three ye ars of its use.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Efficiency of Tibolone in a Rat Endometriosis Model

Şimşek¹,

Ceyhan²,

Üstün³

et al. 2011

Turkiye Klinikleri J Med Sci

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A AB BS S T TR RA AC CT T O Ob b j je ec c t ti i v ve e: : This study ai med to eva lu a te the the ra pe u tic ef fi ci ency of ti bo lo ne in an ex pe ri men tal rat mo del of in tra-ab do mi nal en do met ri o sis. M Ma a t te e r ri i a al l a an nd d M Me et t h ho od ds s: : In this ex pe rimen tal study, in tra-ab do mi nal en do met ri o sis was in du ced in 30 fe ma le rats sur gi cally. Fo ur we eks af ter this pro ce du re, la pa ro tomy was per for med again. The di men si ons of the en do met ri o sis fo ci were re cor ded and right af ter, the ope ra ti on was comp le ted. Rats we re ran domly di vi ded in to thre e gro ups and sub se qu ently, the tre at ment was star ted. In the first gro up (n= 8), a sing le do se of 1 cc 0.9% NaCl was in jec ted sub cu ta ne o usly. In the se cond gro up (n= 8), in tra mus cu lar in jec ti on of 1 mg le up ro lid ace ta te was ad mi nis te red. In the third gro up (n= 8), 1 mg/kg/day of ti bo lo ne was gi ven by ga va ge. At the end of 4-we eks of drug ad mi nis tra ti on, la pa ro tomy was per for med to all rats. The di men si ons of the en do met ri o sis fo ci we re re cor ded. Af ter wards, all the rats we re sac ri fi ced. The dif fe ren ces in the are as of en do met ri o tic imp lants and ad he si on sco res we re com pa red bet we en the gro ups. R Re e s su ul lt ts s: : The di men si ons of the en do met ri o sis fo ci in the gro ups tre a ted with le up ro lid (p< 0.05) and ti bo lo ne (p< 0.05) we re sig ni fi cantly di mi nis hed compared to that of the con trol gro up. No sta tis ti cally sig ni fi cant dif fe ren ces we re fo und bet we en the tre at ment gro ups. C Co on nc c l lu u s si i o on n: : In a rat en do met ri o sis mo del, ti bo lo ne has a si mi lar ef fi ci ency as that of le up ro lid ace ta te, an agent used for con ven ti o nal me di cal tre at ment of en do met ri o sis. With its an dro ge nic and pro ges ta ge nic charac te ris tics, ti bo lo ne de ser ves at ten ti on as an al ter na ti ve agent in the me di cal tre at ment of en domet ri o sis in hu man. K Ke ey y W Wo or rd ds s: : Rats; endometriosis; gonadotropin-releasing hormone; tibolone Ö ÖZ ZE ET T A Am ma aç ç: : Bu ça lış ma da ka rın içi en do met ri o zis li de ney sel sı çan mo de lin de ti bo lon un te ra pö tik et kin li ği nin de ğer len di ril me si amaç lan dı. G Ge e r re eç ç v ve e Y Yö ön n t te em m l le er r: : Bu de ney sel ça lış ma da, 30 di şi sı çan -da ka rın içi cer ra hi en do met ri o zis mey da na ge ti ril di. Bu iş lem den dört haf ta son ra tekrar la pa ro tomi ya pıl dı. En do met ri o zis odak la rı nın bo yut la rı kay de dil di he men ar dın dan ope ras yon ta mam lan dı. Sı çan lar rast ge le üç gru ba ay rıl dı ve da ha son ra te da vi baş lan dı. Bi rin ci gru ba (n= 8), NaCl 1 cc %0.9 tek doz ola rak cilt al tı na en jek te edil di. İkin ci gru ba (n= 8), le up ro lid ase tat 1 mg in tra mus kü ler ola rak uy gu lan dı. Üçün cü gru ba (n= 8), ti bo lon 1mg/kg/gün ola rak ga vaj ile ve ril di. Dört haf ta ilaç alı mı nın son ra s...

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Section: Discussionmentioning

confidence: 99%

Therapeutic Efficiency of Tibolone in a Rat Endometriosis Model

Şimşek¹,

Ceyhan²,

Üstün³

et al. 2011

Turkiye Klinikleri J Med Sci

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“…After 2 years of follow-up, in four out of 21 patients (19%), endometrial hyperplasia recurred. Apart from mild hypoestrogenic side-effects, no significant change in bone mineral density was observed during the treatment (Agorastos et al 2004). Similarly, Perez-Medina et al (1999) after 5-years of follow-up, demonstrated recurrence in three out of 19 patients (16%) with atypical hyperplasia using a GnRH-agonist (triptorelin; 3.75 mg) for 6 months plus norethisterone acetate (weekly; 500 mg) for 3 months.…”

Section: Conservative Treatment In Endometrial Hyperplasiamentioning

confidence: 90%

“…In another series of 26 patients of mixed population, mean age 43.9 years (range 20-60 years), we introduced prolonged use (12 months of therapy) of GnRH-agonist (leuprolide acetate; 3.75 mg), followed by tibolone (daily; p.o. 2.5 mg) (Agorastos et al 2004). Hysteroscopy and endometrial biopsy were used for the clinical evaluation of the patients in 3, 6, 12 and 24 months, while 21 patients completed the follow-up.…”

Section: Conservative Treatment In Endometrial Hyperplasiamentioning

confidence: 99%

“…Thereafter, different regimens were used as a uterine-sparing treatment in endometrial hyperplasia of any type (with or without atypia), in premenopausal and postmenopausal women (Table I) (Gal et al 1983;Ferenczy and Gelfand 1989;Randall and Kurman 1997;Agorastos et al 1997;Perez-Medina et al 1999;Agorastos et al 2004;Tamaoka et al 2004;Agorastos et al 2005;Varma et al 2008). Gal et al (1983) showed 90% regression of hyperplasia with or without atypia in postmenopausal women treated by daily administration of 40 mg megestrol acetate (MA) (Gal et al 1983).…”

Section: Conservative Treatment In Endometrial Hyperplasiamentioning

confidence: 99%

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Conservative management of young patients with endometrial highly-differentiated adenocarcinoma

Kalogiannidis

Αγοραστός

2011

Journal of Obstetrics and Gynaecology

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Endometrial cancer is uncommon in young women. However, almost 5% of patients are younger than 40 years old. Progestins such as medroxyprogesterone acetate (MPA) and megestrol acetate (MA), have been used as a fertility-sparing approach in this group of patients, with different dose regimens of cyclic (14 days every month) or continuous therapy successfully used. According to the present data, the overall response rate was 73% in a median time of 4 months (range 1-15 months). Endometrial biopsy every 3 months was the common approach to evaluate the patient's response during the treatment. The relapse rate was 36% in a median follow-up time of 22 months (range 6-73 months). Overall, 40% of patients who responded to the treatment successfully, conceived. Half of the patients used assisted reproductive technology to achieve an immediate pregnancy. Although, there are no definite recommendations concerning the conservative management of young patients with early stage endometrial cancer, progestin agents may be used in a selected group of patients for fertility-sparing reasons. After childbearing is completed, hysterectomy remains the standard treatment.

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“…Prolonged use of GnRH analogue and tibolone as add-back therapy acted efficiently for the treatment of endometrial hyperplasia (Agorastos et al 2004). GnRH analogues seem to be suitable drugs for an efficacious and less toxic endocrine therapy for endometrial cancer (Fister et al 2007).…”

Section: Applications Of Gnrh Analogues To Uterine Related Diseasesmentioning

confidence: 99%

GnRH signaling in intrauterine tissues

Wu¹,

Wang²,

Huang³

et al. 2009

Reproduction

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Type I GnRH (GnRH-I, GNRH1) and type II GnRH (GnRH-II, GNRH2), each encoded by separate genes, have been identified in humans. The tissue distribution and functional regulation of GnRH-I and GnRH-II clearly differ despite their comparable cDNA and genomic structures. These hormones exert their effects by binding to cell surface transmembrane G protein coupled receptors and stimulating the Gq/11 subfamily of G proteins. The hypothalamus and pituitary are the main origin and target sites of GnRH, but numerous studies have demonstrated that extra-hypothalamic GnRH and extra-pituitary GnRH receptors exist in different reproductive tissues such as the ovary, endometrium, placenta, and endometrial cancer cells. In addition to endocrine regulation, GnRH is also known to act in an autocrine and paracrine manner to suppress cell proliferation and activate apoptosis in the endometrium and endometrial cancer cells through several mechanisms. Both GnRH-I and GnRH-II exhibit regulatory roles in tissue remodelling during embryo implantation and placentation, which suggests that these hormones may have important roles in embryo implantation and early pregnancy. The presence of varied GnRH and GnRH receptor systems demonstrate their different roles in distinct tissues using dissimilar mechanisms. These may result in the generation of new GnRH analogues used for several hormone-related diseases.

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Prolonged use of gonadotropin-releasing hormone agonist and tibolone as add-back therapy for the treatment of endometrial hyperplasia

Cited by 19 publications

References 19 publications

Therapeutic Efficiency of Tibolone in a Rat Endometriosis Model

Therapeutic Efficiency of Tibolone in a Rat Endometriosis Model

Conservative management of young patients with endometrial highly-differentiated adenocarcinoma

GnRH signaling in intrauterine tissues

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