GnRH Analogues as a Co-Treatment to Therapy in Women of Reproductive Age with Cancer and Fertility Preservation.

Evangelia Charmandari,Georgios Valsamakis,Nikolaos F. Vlahos,Irene Lambrinoudaki,Konstantinos Valtetsiotis

doi:10.3390/ijms23042287

Abstract

In this review, we analyzed existing literature regarding the use of Gonadotropin-releasing Hormone (GnRH) analogues (agonists, antagonists) as a co-treatment to chemotherapy and radiotherapy. There is a growing interest in their application as a prophylaxis to gonadotoxicity caused by chemotherapy and/or radiotherapy due to their ovarian suppressive effects, making them a potential option to treat infertility caused by such chemotherapy and/or radiotherapy. They could be used in conjunction with other fertility preservation options to synergistically maximize their effects. GnRH analogues may be a valuable prophylactic agent against chemotherapeutic infertility by inhibiting rapid cellular turnover on growing follicles that contain types of cells unintentionally targeted during anti-cancer treatments. These could create a prepubertal-like effect in adult women, limiting the gonadotoxicity to the lower levels that young girls have. The use of GnRH agonists was found to be effective in hematological and breast cancer treatment whereas for ovarian endometrial and cervical cancers the evidence is still limited. Studies on GnRH antagonists, as well as the combination of both agonists and antagonists, were limited. GnRH antagonists have a similar protective effect to that of agonists as they preserve or at least alleviate the follicle degradation during chemo-radiation treatment. Their use may be preferred in cases where treatment is imminent (as their effects are almost immediate) and whenever the GnRH agonist-induced flare-up effect may be contra-indicated. The combination treatment of agonists and antagonists has primarily been studied in animal models so far, especially rats. Factors that may play a role in determining their efficacy as a chemoprotective agent that limits gonadal damage, include the type and stage of cancer, the use of alkylating agents, age of patient and prior ovarian reserve. The data for the use of GnRH antagonist alone or in combination with GnRH agonist is still very limited. Moreover, studies evaluating the impact of this treatment on the ovarian reserve as measured by Anti-Müllerian Hormone (AMH) levels are still sparse. Further studies with strict criteria regarding ovarian reserve and fertility outcomes are needed to confirm or reject their role as a gonadal protecting agent during chemo-radiation treatments.

Highlights

The incidence of cancer in women of a reproductive age remains high
Depending on age and treatment choices, 15–50% of pre-menopausal women may be expected to develop premature ovarian failure (POF) [5]. This is true especially when chemotherapy is administered for breast cancer and Hodgkin’s Lymphoma (HL) [6,7], though it is encountered in the treatment of other malignancies such as ovarian and endometrial cancer [8]
We searched for the phrase “fertility preservation” in combination with: “woman reproductive age” (288 combined results), “Hodgkin’s lymphoma” (52), “gynecological cancer” (31), “breast cancer” (593), “Anti-Müllerian Hormone (AMH)” (150), “Gonadotropin-releasing Hormone (GnRH) agonists” (53) and

Summary

Introduction

The incidence of cancer in women of a reproductive age remains high. In 2020, breast cancer became the leading type of cancer worldwide, with 2.3 million new cases and685,000 deaths [1]. The incidence of cancer in women of a reproductive age remains high. In Australia, the cancer incidence rate for women under 40 was 64.7 per. The International Agency for the Research of Cancer estimates that globally in 2020 there were about 1,380,000 new cancer cases in women under 45 with a 52.2 per. Depending on age and treatment choices, 15–50% of pre-menopausal women may be expected to develop premature ovarian failure (POF) [5]. This is true especially when chemotherapy is administered for breast cancer and Hodgkin’s Lymphoma (HL) [6,7], though it is encountered in the treatment of other malignancies such as ovarian and endometrial cancer [8]. Infertility is an important long-term effect of cancer treatment, especially given the fact that surviving cancer does not seem to drop the desire for childbearing and may increase value placed on familial bonds, though anxieties about potential infertility remain [9,10]

Methods

Results

Conclusion