GnRH Antagonists with or without Add-Back Therapy: A New Alternative in the Management of Endometriosis?

Abstract

To evaluate the effectiveness of a new class of medical drugs, namely oral gonadotropin-releasing hormone (GnRH) antagonists, in the management of premenopausal women with endometriosis-associated pelvic pain. We reviewed the most relevant papers (n = 27) on the efficacy of new medical alternatives (oral GnRH antagonists) as therapy for endometriosis. We first briefly summarized the concept of progesterone resistance and established that oral contraceptives and progestogens work well in two-thirds of women suffering from endometriosis. Since clinical evidence shows that estrogens play a critical role in the pathogenesis of the disease, lowering their levels with oral GnRH antagonists may well prove effective, especially in women who fail to respond to progestogens. There is a need for reliable long-term oral treatment capable of managing endometriosis symptoms, taking into consideration both the main symptoms and phenotype of the disease. Published studies reviewed and discussed here confirm the efficacy of GnRH antagonists. There is a place for GnRH antagonists in the management of symptomatic endometriosis. Novel algorithms that take into account the different phenotypes are proposed.

Pathogenesis of Endometriosis: New Insights into Prospective Therapies

“…GnRH antagonists block GnRH receptors and thereby cause the suppression of follicle-stimulating hormone and luteinizing hormone in a dose-dependent manner. Donnez and Dolmans previously reviewed the results of different studies on the outcomes of linzagolix, relugolix, and elagolix treatment of symptomatic endometriosis, concluding that these drugs may constitute a promising new treatment option [ 52 ].…”

Endometriosis: An Inflammatory Disease That Requires New Therapeutic Options

“…Indeed, due to progesterone resistance, 33% of women suffering from endometriosis are poor responders to oral contraceptives and progestogens, and their percentage climbs even higher in women with deep nodular endometriosis. Donnez and Dolmans reviewed the most important papers reporting the results from clinical trials on three potentially useful oral GnRH antagonists: elagolix, linzagolix, and relugolix [6]. These studies confirmed that GnRH antagonists suppress ovarian function in a dose-dependent manner, allowing the modulation of estrogen levels which, according to the threshold hypothesis, may provide relief from endometriosis-associated symptoms while reducing side effects such as hot flushes and bone mineral density loss.…”

“…Of course, lowering the estrogen levels may well prove effective, especially in women who failed to respond to progestins. Donnez and Dolmans [6] evaluated in their review the effectiveness of a new class of drugs, the gonadotropin-releasing hormone (GnRH) antagonists in the management of premenopausal women with endometriosis-associated pelvic pain. There is a need for long-term oral treatments capable of managing symptoms while taking into account both the main symptoms (pain and/or infertility) and the lesion phenotypes.…”

Salvia miltiorrhiza-Containing Chinese Herbal Medicine Combined With GnRH Agonist for Postoperative Treatment of Endometriosis: A Systematic Review and meta-Analysis

“…Nonetheless, the long-term use of GnRH-a causes adverse effects such as vasomotor symptoms, insomnia, and bone density loss ( Sauerbrun-Cutler and Alvero, 2019 ). Although add-back treatment is commonly used to alleviate side effects, its efficacy remains inadequate ( Donnez and Dolmans, 2021 ).…”