Prolonged use of gonadotropin-releasing hormone agonist and tibolone as add-back therapy for the treatment of endometrial hyperplasia.
OBJECTIVE
To investigate the response of the various hyperplastic disorders of the endometrium to a prolonged treatment with leuprolide acetate, a gonadotropin-releasing hormone agonist (GnRH-a), plus tibolone, as add-back therapy, and further to study if the tibolone addition reduces the hypoestrogenic actions of the GnRH-analogue.


METHODS
We treated 26 women with histologically confirmed simple (n = 9), complex (n = 15) or atypical (n = 2) endometrial hyperplasia (EH) for 12 months with monthly injections of 1Ampulle/3.75 mg of leuprolide acetate, followed by tibolone, 2.5mg per day per os. Every woman underwent a hysteroscopic evaluation and biopsy of the endometrium after 3 (in cases with atypical EH), 6 and 12 months of treatment, as well as after 12 and 24 months of follow-up. The clinical, paraclinical and laboratory course of the disease was followed-up by using of a climacteric scoring system and by testing of various parameters.


RESULTS
The histopathologic evaluation of the endometria revealed regression of EH in all women after 12 months of treatment, however, during the first 2 years of follow-up EH reappeared in four women (4/21, 19%). Bone mineral density and serum parameters did not show significant changes during treatment, whereas only a mild suffering from hypoestrogenic side-effects was noted.


CONCLUSIONS
It seems that the combined GnRH-a/tibolone treatment in women with EH is a potent alternative, so far as the endometrial status and the clinical course of the disease are concerned, whereas tibolone appears to act sufficiently as add-back therapy to prolonged GnRH-a treatment. The probability of relapse of the disease during the follow-up period makes the close monitoring of the endometrium after cessation of the treatment absolutely necessary.
Agorastos
Theodoros
T
Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Hippokrateion Hospital, Greece. agorast@med.auth.gr
Vaitsi
Violetta
V
Paschopoulos
Minas
M
Vakiani
Andromache
A
Zournatzi-Koiou
Vassiliki
V
Saravelos
Haris
H
Kostopoulou
Evanthia
E
Constantinidis
Theodoros
T
Dinas
Konstantinos
K
Vavilis
Dimitrios
D
Lolis
Dimitrios
D
Bontis
John
J
D000328:Adult; D004359:Drug Therapy, Combination; D004714:Endometrial Hyperplasia / Q000188:drug therapy* / Q000473:pathology; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D007267:Injections; D016729:Leuprolide / Q000008:administration & dosage*; D008875:Middle Aged; D009652:Norpregnenes / Q000008:administration & dosage*; D016896:Treatment Outcome
D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; D007987:Gonadotropin-Releasing Hormone; D016729:Leuprolide; C027385:tibolone