- Full estradiol suppression with GnRH antagonists alone can result in hypoestrogenic side effects, such as the loss of bone mineral density (BMD)1,2
- A reduction in BMD of approximately 2% is considered clinically meaningful.3,4 A BMD reduction of 3% or more needs to be monitored carefully3,4
- UF is an estrogen-driven disease and as per the theory, initially proposed by Barbieri et al, the focus should be on maintaining hormone levels within an optimal level.2 These optimal levels are required to ensure that the estrogen levels are not too high so that there is not good enough UF control for the patient’s needs; but conversely that they are not too low that would result in hypoestrogenic effects, such as BMD. The use of add-back therapy, for example, allows the maintenance of these levels within the optimal range, which in turn results in the adequate and important balance between efficacy and safety 2,5,6
- The Summary of Product Characteristics for any available GnRH antagonist clearly shows the relative incidence and risk of any clinically-meaningful BMD loss observed in the respective Phase 3 trials7,8
1. Osuga Y et al. Obs & Gynecol 2019; 133(3): 423-433.
2. Barbieri RL. Am J Obstet Gynecol 1992;166:740–745.
3. Cummings SR, Bates D, Black DM. Clinical use of bone densitometry: scientific review. JAMA. 2002 Oct 16;288(15):1889–97.
4. Pepe J, Body J-J, Hadji P, McCloskey E, Meier C, Obermayer-Pietsch B, et al. Osteoporosis in premenopausal women: A clinical narrative review by the ECTS and the IOF. J Clin Endocrinol Metab. 2020 Aug 1;105(8):2487–506.
5. Elsharoud A et al. Drugs of the Future 2019; 44(2): 131-143.
6. Donnez J & Dolmans MM. J Clin Med 2021; 10: 1085.
7. Relugolix Summary of Product Characteristics. https://www.ema.europa.eu/en/documents/product-information/ryeqo-epar-product-information_en.pdf
8. Linzagolix Summary of Product Characteristics. https://www.ema.europa.eu/en/medicines/human/EPAR/yselty