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The medical community is exploring a transformative approach to hormonal management with the introduction of relugolix and estetrol contraception. This novel concept aims to replace traditional progestins with oral GnRH antagonists to suppress ovarian function. Specifically, researchers propose a combination of 40 mg relugolix and a low dose of the fetal estrogen estetrol. This regimen potentially offers a seamless transition from adolescence to menopause while maintaining hormonal balance.
Initially, the use of oral GnRH antagonists was limited to treating specific conditions like uterine fibroids. However, the RE4Women (RE4W) concept expands this utility into the realm of lifelong endocrine management. By utilizing relugolix to inhibit ovulation, clinicians can eliminate the need for progestins. Consequently, this shift may address several side effects associated with traditional combined oral contraceptives.
One of the primary advantages of this new approach is the establishment of continuous amenorrhea. Furthermore, the regimen provides a smooth and symptomless transition from perimenopause to postmenopausal status. Notably, the absence of luteal progesterone and synthetic progestins is expected to significantly reduce the long-term incidence of breast cancer. Therefore, this strategy prioritizes both current comfort and future oncological safety.
Moreover, estetrol acts as a selective estrogen with unique properties. It maintains essential estrogenic functions, such as bone health and vasomotor stability, without causing excessive endometrial growth. Currently, two Phase 2 studies are assessing the optimal dose of estetrol in women aged 18-35 and 36-51 years. These trials will determine the efficacy of the combination in preventing breakthrough bleeding while ensuring effective contraception.
The RE4Women concept represents a paradigm shift in women's health. By combining a potent GnRH antagonist with a fetal estrogen, this approach targets a wide age demographic. Additionally, it addresses the limitations of current progestin-based methods. Ultimately, this life cycle endocrine management approach could redefine how physicians manage contraception and the menopausal transition.
Relugolix is a GnRH antagonist that directly inhibits the pituitary-ovarian axis, thereby preventing ovulation. In traditional pills, progestins perform this task. By using relugolix, the regimen achieves ovarian suppression without the metabolic or breast-related risks sometimes linked to progestins.
Estetrol is a natural fetal estrogen that exhibits selective tissue activity. It maintains bone density and manages hot flashes but has a significantly lower impact on the liver and breast tissue compared to ethinyl estradiol or estradiol valerate.
The approach targets women from adolescence through the perimenopausal transition. It is particularly beneficial for those seeking continuous amenorrhea and a reduced risk of hormone-related cancers during their reproductive and transition years.
Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice, diagnosis, or treatment. Always seek the advice of a qualified healthcare provider with any questions regarding a medical condition or new treatment. Refer to the latest local and national guidelines for clinical practice.
References
Coelingh Bennink HJT et al. A concept for a new approach to combined oral contraception from adolescence to perimenopause: Continuous use of the oral GnRH antagonist Relugolix and the fetal estrogen estetrol. Acta Obstet Gynecol Scand. 2026 Mar 07. doi: 10.1111/aogs.70182. PMID: 41793206.
Gérard C, et al. Estetrol: A New Choice for Contraception. Front Endocrinol (Lausanne). 2022;13:848324.
Bennink HJT, et al. Estetrol a promising native estrogen for oral contraception and the relief of menopausal symptoms. Climacteric. 2022;25(5):451-463.
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A new contraceptive concept (RE4W) combines Relugolix and Estetrol to replace progestins, offering amenorrhea and a smooth transition to menopause....
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