A pilot study of gonadotropin-releasing hormone agonist combined with aromatase inhibitor as fertility-sparing treatment in obese patients with endometrial cancer

Zhang, Zhibo; Huang, Huifang; Feng, Fengzhi; Wang, Jinhui; Cheng, Ninghai

doi:10.3802/jgo.2019.30.e61

Cited by 25 publications

(22 citation statements)

References 20 publications

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“…After a median follow-up of four years, no recurrence was observed. The pregnancy rate was 50% and the life birth rate was 75% [ 74 ]. Tock et al, retrospectively, analyzed 18 women younger than 41 years with grade 1 EC (39%) or AEH (50%), who received endometrial resection and, subsequently, a GnRH agonist for three months.…”

Section: Resultsmentioning

confidence: 99%

“…Estrogen withdrawal by the GnRH-agonist induced reversible medical castration, which has been used in combination with systemic or local progestogen application as a fertility sparing treatment for AEH and early EC [ 69 , 70 , 71 , 72 , 73 , 76 ]. Alternatively, GnRH agonists were combined with aromatase inhibitors for more intensive suppression of estrogens [ 73 , 74 , 76 ] or given alone after complete endometrial resection [ 75 ]. In these small series, complete response rates of about 70% (54–100%) were observed for early EC.…”

Section: Discussionmentioning

confidence: 99%

“…Pregnancy rates were about 50%. A relevant number of patients had progression during therapy or relapsed after complete remission [ 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 ]. Estrogen withdrawal through reversible medical castration by GnRH analogs alone or in combination with a LNG-IUD or an aromatase inhibitor seems to be preferable in obese patients [ 76 ] ( Table 1 ).…”

Section: Discussionmentioning

confidence: 99%

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The Role of Gonadotropin-Releasing Hormone (GnRH) in Endometrial Cancer

Emons

Gründker

2021

Cells

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Endometrial cancer (EC) is one of the most common gynecological malignancies. Gonadotropin releasing hormone (GnRH) is a decapeptide first described to be secreted by the hypothalamus to regulate pituitary gonadotropin secretion. In this systematic review, we analyze and summarize the data indicating that most EC express GnRH and its receptor (GnRH-R) as part of an autocrine system regulating proliferation, the cell cycle, and apoptosis. We analyze the available data on the expression and function of GnRH-II, its putative receptor, and its signal transduction. GnRH-I and GnRH-II agonists, and antagonists as well as cytotoxic GnRH-I analogs, have been shown to inhibit proliferation and to induce apoptosis in human EC cell lines in pre-clinical models. Treatment with conventional doses of GnRH-agonists that suppress pituitary gonadotropin secretion and ovarian estrogen production has become part of fertility preserving therapy of early EC or its pre-cancer (atypical endometrial hyperplasia). Conventional doses of GnRH-agonists had marginal activity in advanced or recurrent EC. Higher doses or more potent analogs including GnRH-II antagonists have not yet been used clinically. The cytotoxic GnRH-analog Zoptarelin Doxorubicin has shown encouraging activity in a phase II trial in patients with advanced or recurrent EC, which expressed GnRH-R. In a phase III trial in patients with EC of unknown GnRH-R expression, the cytotoxic GnRH doxorubicin conjugate was not superior to free doxorubicin. Further well-designed clinical trials exploiting the GnRH-system in EC might be useful.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Role of Gonadotropin-Releasing Hormone (GnRH) in Endometrial Cancer

Emons

Gründker

2021

Cells

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“…Obese patients are hyperestrogenic and suppressing the production of endogenous estrogen may be an effective alternative. A recent pilot study of a GnRH agonist combined with an aromatase inhibitor in fertility-sparing treatment of 6 obese women with grade 1 EC reported a complete response in all women at 3–6 months, and a pregnancy and live birth rate of 50% and 75% respectively [ 72 ]. A prospective observation study of LNG-IUD for 1 year plus a GnRH analogue for 6 months in patients aged <40 years with stage 1A EC showed results comparable to studies using MPA and MA, with a complete remission rate of 57% and a recurrence rate of 25% [ 73 ].…”

Section: Fertility-sparing Managementmentioning

confidence: 99%

Fertility-sparing treatment in early endometrial cancer: current state and future strategies

et al. 2020

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Endometrial cancer (EC) is the fifth most common cancer in women worldwide. Global estimates show rising incidence rates in both developed and developing countries. Most women are diagnosed postmenopausal, but 14–25% of patients are premenopausal and 5% are under 40 years of age. Established risk factors include age and hyperestrogenic status associated with nulliparity, obesity, and metabolic syndrome. Standard treatment for EC, which involves total hysterectomy and bilateral salpingo-oophorectomy, has excellent survival outcomes, particularly for low-grade endometrioid tumors. However, it leads to permanent loss of fertility among women who wish to preserve their reproductive potential. With current trends of reproductive-age women delaying childbearing, rising EC incidence rates, and a growing epidemic of obesity, particularly in developed countries, research on conservative non-surgical treatment approaches remains a top priority. Fertility-sparing treatment predominantly involves the use of oral progestins and levonorgestrel-releasing intrauterine devices, which have been shown to be feasible and safe in women with early stage EC and minimal or no myometrial invasion. However, data on the efficacy and safety of conservative management strategies are primarily based on retrospective studies. Randomized clinical trials in younger women and high-risk obese patients are currently underway. Here, we have presented a comprehensive review of the current literature on conservative, fertility-sparing approaches, defining the optimal candidates and evaluating tumor characteristics, reproductive and oncologic outcomes, and ongoing clinical trials. We have also summarized current guidelines and recommendations based on the published literature.

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“…A gonadotropin-releasing hormone (GnRH) agonist combined with another agent also can be used. Several studies have reported the successful treatment of EC with a GnRH agonist along with an aromatase inhibitor or LNG-IUS [ 16 , 41 , 42 ]. Additionally, others have reported positive outcomes of treatment incorporating photodynamic therapy [ 13 ] and of hysteroscopic resection of the lesion combined with progestin [ 43 ] or a GnRH agonist [ 44 ].…”

Section: Treatment Efficacy and Primary Modalitymentioning

confidence: 99%

Fertility-sparing treatment in women with endometrial cancer

Won

Kim

Seong

2020

Clin Exp Reprod Med

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Endometrial cancer (EC) in young women tends to be early-stage and low-grade; therefore, such cases have good prognoses. Fertility-sparing treatment with progestin is a potential alternative to definitive treatment (i.e., total hysterectomy, bilateral salpingo-oophorectomy, pelvic washing, and/or lymphadenectomy) for selected patients. However, no evidence-based consensus or guidelines yet exist, and this topic is subject to much debate. Generally, the ideal candidates for fertility-sparing treatment have been suggested to be young women with grade 1 endometrioid adenocarcinoma confined to the endometrium. Magnetic resonance imaging should be performed to rule out myometrial invasion and extrauterine disease before initiating fertility-sparing treatment. Although various fertility-sparing treatment methods exist, including the levonorgestrel-intrauterine system, metformin, gonadotropin-releasing hormone agonists, photodynamic therapy, and hysteroscopic resection, the most common method is high-dose oral progestin (medroxyprogesterone acetate at 500–600 mg daily or megestrol acetate at 160 mg daily). During treatment, re-evaluation of the endometrium with dilation and curettage at 3 months is recommended. Although no consensus exists regarding the ideal duration of maintenance treatment after achieving regression, it is reasonable to consider maintaining the progestin therapy until pregnancy with individualization. According to the literature, the ovarian stimulation drugs used for fertility treatments appear safe. Hysterectomy should be performed after childbearing, and hysterectomy without oophorectomy can also be considered for young women. The available evidence suggests that fertility-sparing treatment is effective and does not appear to worsen the prognosis. If an eligible patient strongly desires fertility despite the risk of recurrence, the clinician should consider fertility-sparing treatment with close follow-up.

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A pilot study of gonadotropin-releasing hormone agonist combined with aromatase inhibitor as fertility-sparing treatment in obese patients with endometrial cancer

Cited by 25 publications

References 20 publications

The Role of Gonadotropin-Releasing Hormone (GnRH) in Endometrial Cancer

The Role of Gonadotropin-Releasing Hormone (GnRH) in Endometrial Cancer

Fertility-sparing treatment in early endometrial cancer: current state and future strategies

Fertility-sparing treatment in women with endometrial cancer

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