Gonadotropin-Releasing Hormone Agonist Combined With a Levonorgestrel-Releasing Intrauterine System or Letrozole for Fertility-Preserving Treatment of Endometrial Carcinoma and Complex Atypical Hyperplasia in Young Women

2017 ◽  
Vol 27 (6) ◽  
pp. 1178-1182 ◽  
Author(s):  
Huimei Zhou ◽  
Dongyan Cao ◽  
Jiaxin Yang ◽  
Keng Shen ◽  
Jinghe Lang
Keyword(s):  
Endometrial Carcinoma ◽  
Young Women ◽  
Gonadotropin Releasing Hormone ◽  
Atypical Hyperplasia ◽  
Endometrioid Adenocarcinoma ◽  
Releasing Hormone ◽  
Gonadotropin Releasing Hormone Agonist ◽  
Intramuscular Injections ◽  
Well Differentiated

ObjectivesThe 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).MethodsWe 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.ResultsAfter 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.ConclusionsBoth 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.

Gonadotropin-Releasing Hormone Agonist for the Prevention of Chemotherapy-Induced Ovarian Failure in Patients With Lymphoma: 1-Year Follow-Up of a Prospective Randomized Trial

2013 ◽  
Vol 31 (7) ◽  
pp. 903-909 ◽  
Author(s):  
Isabelle Demeestere ◽  
Pauline Brice ◽  
Fedro A. Peccatori ◽  
Alain Kentos ◽  
Isabelle Gaillard ◽  
...  
Keyword(s):  
Ovarian Function ◽  
Alkylating Agents ◽  
Prospective Trial ◽  
Young Patients ◽  
Ovarian Failure ◽  
Gonadotropin Releasing Hormone ◽  
Control Group ◽  
Releasing Hormone ◽  
Gonadotropin Releasing Hormone Agonist

Purpose To assess the efficacy of gonadotropin-releasing hormone agonist (GnRHa) in preventing chemotherapy-induced ovarian failure in patients treated for Hodgkin or non-Hodgkin lymphoma within the setting of a multicenter, randomized, prospective trial. Patients and Methods Patients age 18 to 45 years were randomly assigned to receive either the GnRHa triptorelin plus norethisterone (GnRHa group) or norethisterone alone (control group) concomitantly with alkylating agents containing chemotherapy. The primary end point was the premature ovarian failure (POF) rate (follicle-stimulating hormone [FSH] ≥ 40 IU/L) after 1 year of follow-up. Results Eighty-four of 129 randomly assigned patients completed the 1-year follow-up. The mean FSH values were higher in the control group than in the GnRHa group during chemotherapy; however, this difference was no longer observed after 6 months of follow-up. After 1 year, 20% and 19% of patients in the GnRHa and control groups, respectively, exhibited POF (P = 1.00). More than half of patients in each group completely restored their ovarian function (FSH < 10 IU/L), but the anti–Müllerian hormone values were higher in the GnRHa group than in the control group (1.4 ± 0.35 v 0.5 ± 0.15 ng/mL, respectively; P = .040). The occurrence of adverse events was similar in both groups with the exception of metrorrhagia, which was more frequently observed in the control group than the GnRHa group (38.4% v 15.6%, respectively; P = .024). Conclusion Approximately 20% of patients in both groups exhibited POF after 1 year of follow-up. Triptorelin was not associated with a significant decreased risk of POF in young patients treated for lymphoma but may provide protection of the ovarian reserve.

No Evidence for the Benefit of Gonadotropin-Releasing Hormone Agonist in Preserving Ovarian Function and Fertility in Lymphoma Survivors Treated With Chemotherapy: Final Long-Term Report of a Prospective Randomized Trial

2016 ◽  
Vol 34 (22) ◽  
pp. 2568-2574 ◽  
Author(s):  
Isabelle Demeestere ◽  
Pauline Brice ◽  
Fedro A. Peccatori ◽  
Alain Kentos ◽  
Jehan Dupuis ◽  
...  
Keyword(s):  
Ovarian Reserve ◽  
Ovarian Function ◽  
Follicle Stimulating Hormone ◽  
Gonadotropin Releasing Hormone ◽  
Control Group ◽  
Releasing Hormone ◽  
Gonadotropin Releasing Hormone Agonist ◽  
Stimulating Hormone

Purpose We have reported previously that after 1-year follow up, gonadotropin-releasing hormone agonist (GnRHa) did not prevent chemotherapy-induced premature ovarian failure (POF) in patients with lymphoma, but may provide protection of the ovarian reserve. Here, we report the final analysis of the cohort after 5 years of follow up. Patients and Methods A total of 129 patients with lymphoma were randomly assigned to receive either triptorelin plus norethisterone (GnRHa group) or norethisterone alone (control group) during chemotherapy. Ovarian function and fertility were reported after 2, 3, 4, and 5 to 7 years of follow up. The primary end point was POF, defined as at least one follicle-stimulating hormone value of > 40 IU/L after 2 years of follow up. Results Sixty-seven patients 26.21 ± 0.64 years of age had available data after a median follow-up time of 5.33 years in the GnRHa group and 5.58 years in the control group (P = .452). Multivariate logistic regression analysis showed a significantly increased risk of POF in patients according to age (P = .047), the conditioning regimen for hematopoietic stem cell transplant (P = .002), and the cumulative dose of cyclophosphamide > 5 g/m2 (P = .019), but not to the coadministration of GnRHa during chemotherapy (odds ratio, 0.702; P = .651). The ovarian reserve, evaluated using anti-Müllerian hormone and follicle-stimulating hormone levels, was similar in both groups. Fifty-three percent and 43% achieved pregnancy in the GnRHa and control groups, respectively (P = .467). Conclusion To the best of our knowledge, this is the first long-term analysis confirming that GnRHa is not efficient in preventing chemotherapy-induced POF in young patients with lymphoma and did not influence future pregnancy rate. These results reopen the debate about the drug’s benefit in that it should not be recommended as standard for fertility preservation in patients with lymphoma.

Fertility-Sparing Treatment of Early Endometrial Cancer and Complex Atypical Hyperplasia in Young Women of Childbearing Potential

2015 ◽  
Vol 25 (6) ◽  
pp. 1010-1014 ◽  
Author(s):  
Stanislav Mikhailovich Pronin ◽  
Olga Valerievna Novikova ◽  
Julia Yurievna Andreeva ◽  
Elena Grigorievna Novikova
Keyword(s):  
Endometrial Cancer ◽  
Young Women ◽  
Hormonal Therapy ◽  
Endometrial Hyperplasia ◽  
Endometrial Adenocarcinoma ◽  
Gonadotropin Releasing Hormone ◽  
Atypical Hyperplasia ◽  
Childbearing Potential ◽  
Atypical Endometrial Hyperplasia ◽  
Gonadotropin Releasing Hormone Agonist

ObjectiveTo evaluate oncologic and reproductive outcome with levonorgestrel-releasing intrauterine system combined with gonadotropin-releasing hormone agonist in women with grade 1 endometrial carcinoma, and the levonorgestrel monotherapy in women with complex atypical hyperplasia.Materials/MethodsA prospective study was conducted. We analyzed the clinical characteristics of 70 patients younger than 42 years (mean age, 33 years) with a diagnosis of complex atypical endometrial hyperplasia (AEH) or grade 1 endometrial adenocarcinoma who were treated with hormonal therapy at the Division of Gynecologic Oncology of P.A. Hertsen Moscow Cancer Research Institute from February 2009 to December 2012. Patients with complex AEH received monotherapy with levonorgestrel-releasing intrauterine system (Mirena, Shering, Finland; 52 mg). Patients with a diagnosis of grade 1 endometrial cancer were treated with levonorgestrel-releasing intrauterine system combined with gonadotropin-releasing hormone agonist (Zoladex; AstraZeneca UK Limited, UK; 3.6-mg depot). All the patients received hormonal therapy for a minimum of 6 months. Pretreatment evaluation consisted of transabdominal and transvaginal ultrasound in grayscale, color Doppler ultrasound, contrast-enhanced magnetic resonance imaging,cervical hysteroscopy, Pipelle endometrial biopsy, and morphological and immunohistochemical characteristics of the tissue.ResultsSeventy patients were included in study analyses. Twenty three (72%) of 32 patients with adenocarcinoma and 35 (92%) of 38 patients with AEH had complete remission, defined as the absence of any carcinoma or hyperplasia on endometrial sampling specimens. Among these cases, 2 patients with adenocarcinoma and 1 patient with AEH had recurrence after their complete response. Nine patients had persistent disease. Eight patients had 10 conceptions, resulting in 8 live births.ConclusionsThe suggested conservative treatment strategy can be considered as a valid therapeutic option for young women of childbearing potential with atypical endometrial hyperplasia and grade 1 endometrial adenocarcinoma who wish to preserve their fertility and thus may be recommended as an alternative to hysterectomy. Close follow-up during and after the treatment period is strictly required.

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