Profile of estetrol, a promising native estrogen for oral contraception and the relief of climacteric symptoms of menopause

Gérard, Céline; Arnal, Jean-François; Jost, Maud; Douxfils, Jonathan; Lenfant, Françoise; Fontaine, Coralie; Archer, David F.; Reid, Robert L.; Løbo, Rogerio A.; Gaspard, Ulysse; Bennink, Herjan J.T. Coelingh; Creinin, Mitchell D.; Foidart, Jean-Michel

doi:10.1080/17512433.2022.2054413

Cited by 51 publications

(49 citation statements)

References 124 publications

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“…Currently available estrogens cause cardiovascular (CV) problems and are therefore not recommended for combination treatment with ADT [4] . However, the fetal estrogen E4 has been developed since 2001 as a natural estrogen with less of an effect on liver function and hemostasis and is therefore expected to be less harmful for the CV system [13] , [14] .…”

Section: Introductionmentioning

confidence: 99%

Estetrol Prevents Hot Flushes and Improves Quality of Life in Patients with Advanced Prostate Cancer Treated with Androgen Deprivation Therapy: The PCombi Study

Zimmerman¹,

Frydenberg²,

Poppel³

et al. 2022

European Urology Open Science

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Section: Introductionmentioning

confidence: 99%

Estetrol Prevents Hot Flushes and Improves Quality of Life in Patients with Advanced Prostate Cancer Treated with Androgen Deprivation Therapy: The PCombi Study

Zimmerman¹,

Frydenberg²,

Poppel³

et al. 2022

European Urology Open Science

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“…E4/DRSP is a COC containing E4, an estrogen produced in the human fetal liver [ 37 ] and manufactured for clinical use from a plant source [ 38 , 39 , 40 ]. E4/DRSP has a 24/4-day treatment regimen, with 24 tablets containing DRSP 3 mg combined with E4 15 mg (as monohydrate) followed by 4 inactive pills.…”

Section: Results—overview Of Bleeding Patterns Of Most Recently Marke...mentioning

confidence: 99%

“…E4/DRSP has a 24/4-day treatment regimen, with 24 tablets containing DRSP 3 mg combined with E4 15 mg (as monohydrate) followed by 4 inactive pills. E4/DRSP is globally registered (first approval 2021) [ 39 , 40 ].…”

Section: Results—overview Of Bleeding Patterns Of Most Recently Marke...mentioning

confidence: 99%

Bleeding Patterns of Oral Contraceptives with a Cyclic Dosing Regimen: An Overview

Archer

Mansour²,

Foidart

2022

JCM

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Bleeding irregularities are one of the major reasons for discontinuation of oral contraceptives (OCs), and therefore clinicians need to set expectations during consultations. In this review we provide an overview of bleeding data of recently marketed cyclic combined OCs (COCs) and one progestin-only pill (POP). We evaluated data from phase 3 trials (≥12 months) used to gain regulatory approval. Overall, each type of OC has its own specific bleeding pattern. These patterns however were assessed by using different bleeding definitions, which hampers comparisons between products. In COCs, the estrogen balances the effects of the progestin on the endometrium, resulting in a regular bleeding pattern. However, this balance seems lost if a too low dose of ethinylestradiol (EE) (e.g., 10 µg in EE/norethindrone acetate 1 mg) is used in an attempt to lower the risk of venous thromboembolism. Replacement of EE by 17β-estradiol (E2) or E2 valerate could lead to suboptimal bleeding profile due to destabilization of the endometrium. Replacement of EE with estetrol (E4) 15 mg in the combination with drospirenone (DRSP) 3 mg is associated with a predictable and regular scheduled bleeding profile, while the POP containing DRSP 4 mg in a 24/4 regimen is associated with a higher rate of unscheduled and absence of scheduled bleeding than combined products.

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“…The structure of E4 differs from the other natural estrogens estrone (E1), estradiol (E2) and estriol (E3), by an additional alphahydroxy (OH) group at position 15 of the molecule (Figure 2). In contrast to other estrogens, E4 does not bind to SHBG and has no active metabolites in human hepatocytes (53,54). The activity of cytochrome P-450 is not inhibited by E4, whereas E2 and also the synthetic estrogen EE, interfere with liver CYP P-450 enzymes.…”

Section: High-dose Estetrolmentioning

confidence: 97%

Maintaining bone health by estrogen therapy in patients with advanced prostate cancer: a narrative review

Bennink

Krijgh

Egberts³

et al. 2022

Endocrine Connections

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The purpose of androgen deprivation therapy (ADT) in prostate cancer (PCa), using luteinizing hormone-releasing hormone agonists (LHRHa) or gonadotrophin releasing-hormone antagonists, is to suppress the levels of testosterone. Since testosterone is the precursor of estradiol (E2), one of the major undesired effects of ADT is the concomitant loss of E2, causing among others an increase in bone turnover and bone loss, and an increased risk of osteoporosis and fractures. Therefore, the guidelines for ADT indicate to combine ADT routinely with bone-sparing agents such as bisphophonates, denosumab or selective estrogen receptor modulators. However, these compounds may have side effects and some require inconvenient parenteral administration. (Co-)treatment with estrogens is an alternative approach to prevent bone loss, and at the same time avoid other side effects caused by the loss of estrogens, which is the topic explored in the present narrative review. Estrogens investigated in PCa patients include parenteral or transdermal E2, diethylstilbestrol (DES), and ethinylestradiol (EE) as monotherapy, or high-dose estetrol (HDE4) combined with ADT. Cardiovascular adverse events have been reported with parenteral E2, DES and EE. Encouraging effects on bone parameters have been obtained with transdermal E2 (tE2) and HDE4, in the tE2 development program (PATCH study), and in the LHRHa/HDE4 co-treatment study (PCombi), respectively. Confirmation of the beneficial effects of estrogen therapy with tE2 or HDE4 on bone health in patients with advanced PCa is needed, with special emphasis on bone mass and fracture rate.

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Profile of estetrol, a promising native estrogen for oral contraception and the relief of climacteric symptoms of menopause

Cited by 51 publications

References 124 publications

Estetrol Prevents Hot Flushes and Improves Quality of Life in Patients with Advanced Prostate Cancer Treated with Androgen Deprivation Therapy: The PCombi Study

Estetrol Prevents Hot Flushes and Improves Quality of Life in Patients with Advanced Prostate Cancer Treated with Androgen Deprivation Therapy: The PCombi Study

Bleeding Patterns of Oral Contraceptives with a Cyclic Dosing Regimen: An Overview

Maintaining bone health by estrogen therapy in patients with advanced prostate cancer: a narrative review

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