goserelin and Endometrial-Hyperplasia

The results of conservative treatment of 121 patients with endometrial atypical hyperplasia (EAH) and early endometrial cancer (EC) with preservation of fertility are presented. In EAH (n = 56) for 6 months the intrauterine spiral Mirena was used. The effectiveness was 91%, the recurrence rate 16%, pregnancies occurred in 16% of patients. In EC (n = 65) hormone therapy was conducted for 6 months using the intrauterine spiral Mirena and zoladex. The effectiveness was 79%, recurrence rate 22%, pregnancies occurred in 24% of patients. Based on our data and on the results of other studies, the benefits and risks of hormone therapy alone for EAH and EC are discussed in women of reproductive age.

Topics: Adult; Antineoplastic Agents, Hormonal; Drug Administration Schedule; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Goserelin; Humans; Levonorgestrel; Neoplasm Recurrence, Local; Precancerous Conditions; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Rate; Treatment Outcome

STUDY-PLAN: an open study aimed at evaluating the results of a short term therapy (3 months) with Goserelin depot as a medical treatment of premenopausal dysfunctional uterine bleeding.. 60 premenopausal women (aged 36-50) with dysfunctional uterine bleeding, presenting simple endometrial hyperplasia.. after the treatment, spontaneous menstrual bleeding recurred in 57/60 patients, while 3/60 (5%) patients remained amenorrheal during the whole period of follow-up, showing a postmenopausal hormonal pattern. In the first post-therapy menstrual cycle all the 57 patients had a bleeding score < 100; patients relapsing during the second, third and fourth cycle were respectively 2/54 (3.7%), 5/48 (10.7%) and 17/38 (44.7%). The fourth post-therapy cycle was delayed 6-9 months after the last injection of Goserelin. Both the mean blood loss and the mean duration of bleeding were significantly reduced in all post-therapy cycles. Eleven patients were anaemic before therapy (Hb < 12 g%); Goserelin treatment resulted in a normalization of the hematological parameters. At the end of treatment a small area of hyperplasia persisted in only 4/60 patients (6.7%). Localised or diffused hyperplasia were found respectively in 5/54 (9.3%) and in 1/54 patients (1.9%) at three months, and in 5/48 (10.4%) and 4/48 (8.3%) at a six-month follow-up. Side effects were infrequent.. the long symptom-free period and the low incidence of side effects indicates Goserelin depot as a valuable medical treatment for dysfunctional uterine bleeding.

Topics: Adult; Delayed-Action Preparations; Dose-Response Relationship, Drug; Endometrial Hyperplasia; Female; Goserelin; Humans; Menorrhagia; Metrorrhagia; Middle Aged; Premenopause

Cyclic or irregular uterine bleeding is common in perimenarchal and perimenopausal women with or without endometrial hyperplasia. The disturbance often requires surgical treatment because of its negative effects on both blood loss and abnormal endometrial growth including the development of endometrial cancer. The endometrium is often overstimulated during the perimenopausal period when estrogen/progesterone production is unbalanced. A therapeutical approach with gonadotropin-releasing hormone agonist (GnRHa) was proposed in a depot formulation (Zoladex) that induces a sustained and reversible ovarian suppression. To avoid the risk of osteoporosis and to obtain adequate endometrial proliferation and differentiation during ovarian suppression, transdermal 17-beta-estradiol and oral progestin were administered. Results of 20 cases versus 20 controls showed a reduction of metrorrhagia, a normalization of hemoglobin plasma concentration, and an adequate proliferation and secretory differentiation of the endometrium of patients with abnormal endometrial growth. Abnormal uterine bleeding is mainly due to uterine fibrosis and an inadequate estrogen and/or progesterone production or to a disordered estrogen transport from blood into the endometrium. In premenopausal women, endometrial hyperplasia may be part of a continuum that is ultimately manifested in the histological and biological pattern of endometrial carcinoma. The regression of endometrial hyperplasia obtained by using the therapeutic regimen mentioned above represents a preventive measure for endometrial cancer. Finally the normalization of blood loss offers a good medical alternative to surgery for patients with DUB.

Topics: Adult; Delayed-Action Preparations; Endometrial Hyperplasia; Endometrium; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Humans; Laminin; Luteinizing Hormone; Metrorrhagia; Middle Aged; Progesterone

Our aim was to summarize our and foreign experience in the field of diagnosis, progression and modern treatment of precancer of the endometrium-the atypical glandular hyperplasia.. We researched 750 cases with glandular and atypical glandular hyperplasia for 10 years period (2000-2010). The hyperplasia were followed up for progression from glandular hyperplasia into atypical glandular hyperplasia and early endometrial cancer. The hyperplasias were evaluated with or without progestagen hormonal therapy. All patients were treated by D&C before and after the hormonal treatment.. The main symptom in all patients was the postmenopausal bleeding (72% from the cases). In 90% of the patients (675) there was obesity. Exogenous use of estrogens was found in 30% (225) of the patients. The cases with complex hyperplasia in 12% (65/525) progressed into atypical glandular hyperplasia and in 4% (21/525) progressed into endometrial cancer. The patients with atypical glandular hyperplasia in 60% (90/150) progressed into endometrial cancer. Remission was observed in 70% of the patients (194/278) with glandular hyperplasia and progestagen treatment. The remission was detected by the golden standart (D&C). The patients without hormonal treatment and with complex glandular hyperplasia have in 15% (37/247) remission. Except with progestagen therapy, we have also 15 patients treated with GnRh-analogs (Zoladex a 3.6 mg) for 3-6 months. For them we have 80% (12/15) remission.. The glandular hyperplasia without atypical cells can be influenced by the hormonal treatment with progestagens and GnRh-analogs. Nevertheless this hormonal treatment--before and after we have to perform D&C and to follow up patients by ultrasound measuring the endometrial thickness. If the fertility plans of the patients are over and if they are in postmenopause with histological result from D&C-atypical glandular hyperplasia--we have to treat them more radically with simple total hysterectomy.

Topics: Antineoplastic Agents, Hormonal; Disease Progression; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Progestins

We studied local expression of insulin-like growth factor 1, insulin-like growth factor receptor, epithelial growth factor, transforming growth factor beta2, PCNA, TNF-alpha, type I TNF receptor, Fas, FasL, IFN-gamma, IL-1beta, IL-4, IL-6, IL-8, IL-10, and IL-12 genes in intact and hyperplastic endometrium. Endometrial hyperplasia was associated with reduced production of TNF-alpha (p<0.05), PCNA (p<0.05), and epithelial growth factor mRNA and enhanced production of Fas mRNA (p<0.01). The expression of TNF-R1, IL-1beta, and IL-12 genes decreased only in glandular cystic hyperplasia (p<0.05 for all genes), expression of insulin-like growth factor 1 gene decreased only in adenomatous hyperplasia (p<0.05). Dufaston therapy of glandular cystic hyperplasia and zoladex therapy of adenomatous hyperplasia normalized expression of Fas receptor, PCNA, and insulin-like growth factor 1 genes, while the expression of IFN-gamma and IL-6 genes, which was normal in hyperplasia, decreased (p<0.05). Zoladex therapy decreased the production of transforming growth factor beta2 (p<0.05) and IL-1beta (p<0.01) mRNA, dufaston therapy decreased production of TNF-alpha (p<0.05) and IL-4 mRNA (p<0.05). Hence, both apoptosis and proliferative activity were suppressed in endometrial hyperplasia, and hormone therapy created prerequisites for transition of the endometrium into the normal proliferation stage.

Topics: Apoptosis; Cell Proliferation; Cells, Cultured; Cytokines; Dydrogesterone; Endometrial Hyperplasia; Female; Gene Expression; Goserelin; Humans; RNA, Messenger

Correlations between local expression of insulin-like growth factor 1, insulin-like growth factor receptor, epithelial growth factor, transforming growth beta2 factor, PCNA, TNF-alpha, TNF receptor 1, Fas, FasL, IFN-gamma, IL-1beta, IL-4, IL-6, IL-8, IL-10, and IL-12 genes in intact and hyperplastic endometrium and in the endometrium after hormone therapy were analyzed. Numerous correlations at the proliferation and secretion stages of the menstrual cycle indicate balanced cytokine system. The number of correlations decreases in glandular cystic and more so in atypical hyperplasia, indicating imbalance in the cytokine system. Dufastone and zoladex therapy did not lead to recovery of this balance, but higher correlations between the expression of some factors of cell proliferation attest to the beginning of normalization of pathologically changed endometrium.

Topics: Antineoplastic Agents, Hormonal; Apoptosis; Cell Division; Cytokines; Deoxyribonucleases; Endometrial Hyperplasia; Endometrium; Epidermal Growth Factor; Female; Goserelin; Humans; Insulin-Like Growth Factor I; Menstrual Cycle; Proliferating Cell Nuclear Antigen; Receptor, IGF Type 1; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger

Glandular Hyperplasia is commonly associated with meno and/or metrorrhagia. We treated 84 patients suffering from meno and/or metrorrhagia associated with simple glandular hyperplasia with a gonadotropin releasing hormone agonist, goserelin, (Zoladex, ICI Pharmaceuticals, Macclesfield. Cheshire, England), available in a depot formulation. Subcutaneous administration of goserelin 3.6 mg was repeated every 28 days for 6 months. Within the first 4 weeks from the start of therapy 45% of the patients became amenorrhoeic, within 12 weeks 100%. Only 3 patients reported continued spotting. Hysteroscopic evaluation and biopsy have shown in the 84 evaluable patients, a positive result in 76 (90.4%), demonstrating the validity of the use of this analogue in this indication. In the future it would be of value to increase the period of treatment in selected cases as well as increasing the length of the follow-up period.

Topics: Adult; Delayed-Action Preparations; Endometrial Hyperplasia; Female; Follow-Up Studies; Goserelin; Humans; Hysteroscopy; Injections, Subcutaneous; Menorrhagia; Metrorrhagia; Middle Aged; Uterus

Nineteen patients with simple endometrial hyperplasia presenting metrorrhagia or menometrorrhagia were treated with 4 injections of Goserelin depot, one every 4 weeks. 12/19 patients were refractory after previous medical therapy. The treatment with Goserelin depot resulted in a complete remission of the symptoms, occurring within the first month of treatment and still present after a median follow-up of 12 months, and in the normalization of the histological profile. No patient experienced clinically relevant side effects.

Topics: Biopsy; Delayed-Action Preparations; Endometrial Hyperplasia; Endometrium; Female; Goserelin; Humans; Menorrhagia; Metrorrhagia