lhrh--ala(6)-gly(10)-ethylamide- and Endometrial-Neoplasms

To critically examine the possible association between hormonal treatment of endometriosis and ovarian cancer.. The malignant potential of endometriosis has been suggested by several clinical studies. Although controversial, ovarian carcinoma of the endometrioid and clear cell subtypes has been associated with endometriosis, particularly among subjects with a longstanding disease. Furthermore, a significantly higher frequency of endometriosis has been found in patients undergoing surgery for endometrioid, clear cell, and mixed subtypes of ovarian carcinoma, as compared with the other subtypes. Changes in the genomic material in endometriotic implants were observed by many investigators in chromosomes 1, 5, 6, 7, 16, and 22 by several methods (fluorescent in situ hybridization, comparative genomic hybridization, and others). Because hormonal ablative treatments may suppress the normal, eukaryotic cells more than the aneuploid cells bearing chromosomal aberrations, it may increase the rate of dyskaryotic cells in the endometriotic implants, possibly augmenting the risk of malignant transformation. A recent published association between Danazol and ovarian cancer suggests that such a theoretical risk may occur.. The hormonal ablative treatment of endometriosis may increase the risk of malignant transformation in the endometriotic implants by causing a negative selection and increasing the rate of dyskaryosis and loss of heterozygosity.

Topics: Danazol; Endometrial Neoplasms; Endometriosis; Estrogen Antagonists; Female; Gonadotropin-Releasing Hormone; Health; Humans; Loss of Heterozygosity; Patients; Progestins

Gonadotropin-releasing hormone (GnRH) analogue has beneficial effects on the size and symptoms of endometriosis and uterine leiomyomas as a result of suppressing ovarian steroidogenesis. GnRH analogues are also the preferred treatment for advanced and even metastatic or recurred carcinomas originated from the reproductive tract. The original rationale for a GnRH analogue in the treatment was to block the endogenous gonadotropin and thereby steroid hormone secretion which was thought to stimulate tumor growth. However, more than 80% of ovarian and endometrial cancers express receptors for GnRH, and the analogues inhibit proliferation of the GnRH receptor-bearing tumor cells both in vivo and in vitro, supporting evidence for a direct antiproliferative effect. These receptors could be used for targeted chemotherapy (by tumoricidal agents linked to GnRH analogues) to improve antitumor effects and reduce side effects compared with conventional systemic chemotherapy. In addition to the anticancer action, GnRH analogues act to protect the gonads during radiation and/or chemotherapy by preferentially steering cells into cell cycle arrest with a decline in responsibility to the chemotherapy and radiation. In women who wish to maintain potential fertility, GnRH analogue therapy is successful in preventing the most critical postoperative complication, adhesion formation. The additional unrecognized benefits may add to the advantage of GnRH analogues in cancer management in gynecology.

Topics: Endometrial Neoplasms; Female; Gonadotropin-Releasing Hormone; Humans; Ovarian Neoplasms

The aim of this study was to evaluate the efficacy and safety with gonadotropin-releasing hormone agonist (GnRHa) combined with a levonorgestrel-releasing intrauterine system or an aromatase inhibitor (letrozole) in young women with well-differentiated early endometrial carcinoma (EC) and complex atypical hyperplasia (CAH).. We performed a retrospective analysis including the clinical characteristics of 29 patients younger than 45 years with early well-differentiated endometrioid adenocarcinoma of the uterus (EC) or CAH who were treated at the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, from January 2012 to April 2016. Eighteen patients were treated with the combination of intramuscular injections of GnRHa every 4 weeks with the levonorgestrel intrauterine hormonal system (Mirena® Bayer Health Care Pharmaceutical Inc, Wayne, NY) was inserted. Eleven patients were treated with the combination of intramuscular injections of GnRHa every 4 weeks with oral letrozole 2.5 mg daily. The patients underwent follow-up with endometrial sampling by hysteroscopy and curettage for endometrial response every 3 months.. After a median follow-up of 18.7 months (range, 5.6-54.9 months), 15 women (88.2%) in the EC group and 12 women (100%) in the CAH group had complete response (CR) after GnRHa combination treatment. Among the women who achieved CR, 1 woman (8.3%) with CAH and 1 woman (5.9%) with EC had recurrence after CR, and they finally underwent a hysterectomy. Time to CR was similar in the 2 groups (4.5 ± 1.9 months in the CAH group vs 5.0 ± 2.9 months in the EC group). Ten women (34.5%) had CR after the first 3 months, 8 women (27.6%) had CR after 6 months, and 9 women (31.0%) had CR after 9 months.. Both GnRHa with the levonorgestrel-releasing intrauterine system and GnRHa with letrozole are alternative treatments for women with CAH and EC who desire fertility preservation. A larger multicenter trial of the fertility-preserving treatment is warranted.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Carcinoma, Endometrioid; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Fertility Preservation; Gonadotropin-Releasing Hormone; Humans; Intrauterine Devices, Medicated; Letrozole; Levonorgestrel; Nitriles; Retrospective Studies; Triazoles; Young Adult

The biologic properties of adenomyosis and the effects of therapeutic agents on adenomyosis were evaluated with immunohistochemistry, terminal deoxy-nucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method, transmission electron microscopy, and analysis of genomic abnormality. In the adenomyotic endometrium, estrogen receptor (ER) expression was more intense than in the eutopic endometrium during the secretory phase, and bcl-2 was constantly expressed throughout the menstrual cycle. The expression of ER and bcl-2 was weaker in the adenomyotic endometrium treated with danazol than in that treated with gonadotro-pin-releasing hormone agonist (GnRHa), whereas bcl-2 phosphorylated on serine-87 was more intensely expressed in danazol-treated adenomyotic endometrium than in the GnRHa-treated one. The number of TUNEL-positive cells increased in the adenomyotic endometrium treated with danazol or GnRHa. Ultrastructurally, most of the adenomyotic endometrial cells treated with danazol underwent postapoptotic necrosis and formed a cluster of dead cells. In contrast, cells treated with GnRHa underwent typical apoptosis and were sparsely distributed in the adenomyotic endometrium. Analysis of several cancer-related genes showed no microsatellite instability or loss of heterozygosity in adenomyotic tissues. Therefore, we conclude that the occurrence of adenomyosis is correlated to bcl-2 expression regulated by estrogen and ER rather than genetic mutation.

Topics: Adenomyoma; Adult; Apoptosis; bcl-2-Associated X Protein; Danazol; DNA, Neoplasm; Endometrial Neoplasms; Estrogen Antagonists; Fas Ligand Protein; fas Receptor; Female; Gonadotropin-Releasing Hormone; Humans; Membrane Glycoproteins; Menstrual Cycle; Middle Aged; Phosphorylation; Proto-Oncogene Proteins c-bcl-2; Receptors, Estrogen; Receptors, Progesterone

Endometriosis affects a 10 % of women during their reproductive years. Unequoral statistics concerning the incidence of adenomyosis are not available although a combined occurrence of both diseases is found in a 20 % of cases. The risk that malignancy arises from endometrioid tissue typical for endometriosis is between a 0.3-1 %. 75 % of these malignancies are ovarian cancer in conjunction with pre-existing ovarian endometriosis; less frequently extraovarian malignancies are found. The development of malignancy of adenomyosis is very rarely reported. In this report we present the case of a 35 year old patient who suffered from both, endometriosis and adenomyosis and who underwent a therapy using GnRH analogues. After five months and before the completion of the therapy a hysterectomy with conservation of the ovaries was performed at the request of the patient (carcinophobia). The histology confirmed the diagnosis of adenomyosis and demonstrated the unexpected finding of an endometrium carcinoma. This latter arose from a complex atypical hyperplasia surrounded by hypoplastic endometrium. There is some evidence that suggests a slightly elevated risk of breast and ovarian cancer as well as haematological malignancies amongst patients with endometriosis. However, there does not appear to be an increased risk of endometrial carcinoma. Adipositas leads to an increased risk for the development of endometrial carcinoma due to the increased conversion of testosterone to estrone in fat. The peripheral synthesis of estrone is unaffected by GnRHa-therapy. A progesterone containing HRT should be added to a GnRHa-therapy in overweight patients to prevent the development of endometrial hyperplasia and/or carcinoma. In conclusion a careful indication has to be made for GnRHa-therapy in overweight patients and before and during the therapy high resolution ultrasound scan should be performed to evaluate the endometrium in those patients.

Topics: Adult; Endometrial Neoplasms; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Hysterectomy; Treatment Outcome