Estetrol-drospirenone combination oral contraceptive: North American phase 3 efficacy and safety results

Creinin, Mitchell D.; Westhoff, Carolyn; Bouchard, Céline; Chen, Melissa J.; Jensen, Jeffrey T.; Kaunitz, Andrew M.; Achilles, Sharon L.; Foidart, Jean Michel; Archer, David F.

doi:10.1016/j.contraception.2021.05.002

Cited by 51 publications

(68 citation statements)

References 29 publications

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“…Two studies are available by now, for a total of around 3400 women enrolled and followed for a period of 13 cycles. In the first study conducted in 1864 women aged 16 to 50 years old from North America, the PI was 2.65 in women aged 16 to 35 (54% of the undesired pregnancies due to method failure, with a method-failure PI of 1.43) [ 35 ]. In the second study, conducted in 1553 women from Europe and Russia between the ages of 18 and 50 years old, less pregnancies were reported, and the Pearl Index (PI) was 0.47 in the group aged 18 to 35 and 0.41 in the whole group, with a method-failure PI of 0.25 in the whole group.…”

Section: New Combined Hormonal Contraception With Estetrolmentioning

confidence: 99%

Estetrol: A New Choice for Contraception

Fruzzetti

Fidecicchi

Guevara

et al. 2021

JCM

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Estetrol (E4) is a natural estrogenic steroid that is normally produced by human fetal liver. Recent research has demonstrated that it is a potent, orally bioavailable, natural selective estrogen receptor modulator; it has a moderate affinity for both human estrogen receptor alpha (ERα) and ERβ, with a preference for ERα. Clinical studies have demonstrated possible use as an estrogen in combined oral contraceptives (COC). COCs containing E4 and drospirenone (DRSP) showed a high acceptability, tolerability, and user satisfaction also when compared to COCs containing ethinylestradiol (EE). E4/DRSP effectively inhibits ovulation, with a similar effect on endometrium thickness than that of EE-containing COCs. Low doses (15 mg) of E4 with DRSP (3 mg) showed promising results in term of bleeding pattern and cycle control, also when compared to other COCs containing synthetic estrogens. Moreover, the association has limited effects on serum lipids, liver, SHBG levels, and carbohydrate metabolism. This combination also could drive a lower risk of venous thromboembolism than EE-containing COCs. In this review, we will summarize the actual knowledge about the new E4-containing contraceptive. Further large-scale studies in the full target population are needed to provide more insights into the cardiovascular safety profile and user satisfaction of E4/DRSP.

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Section: New Combined Hormonal Contraception With Estetrolmentioning

confidence: 99%

Estetrol: A New Choice for Contraception

Fruzzetti

Fidecicchi

Guevara

et al. 2021

JCM

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“…16,17 To further evaluate the contraceptive efficacy and safety of E4/DRSP, two comparable pivotal phase 3 studies were conducted (E4 Freedom), one in Europe/Russia and the other in the USA/Canada. 18 This paper presents the results of the first study.…”

Section: Introductionmentioning

confidence: 99%

Estetrol‐Drospirenone combination oral contraceptive: a clinical study of contraceptive efficacy, bleeding pattern and safety in Europe and Russia

Gemzell‐Danielsson

Apter

Zatik³

et al. 2021

BJOG

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Objectives To assess the contraceptive efficacy, bleeding pattern and safety of a combined oral contraceptive containing estetrol (E4) 15 mg and drospirenone (DRSP) 3 mg. Design Multicenter, open‐label, phase 3 trial. Setting Sixty‐nine sites in Europe and Russia. Population Sexually active women aged 18–50 years with regular menstrual cycles and body mass index ≤35 kg/m2. Methods E4/DRSP was administered in a 24 active/4 placebo regimen for up to 13 cycles. Visits were scheduled during Cycles 2, 4, 7 and 10 and after completing treatment during which adverse events (AEs) were collected. Participants recorded medication intake, vaginal bleeding/spotting, use of other contraceptive methods and sexual intercourse on a daily diary. Main outcome measures Pearl Index (PI) for women 18–35 years (overall and method‐failure), bleeding pattern and AEs. Results A total of 1553 women aged 18–50 years, including 1353 from 18 to 35 years old, received the study medication. PI was 0.47 pregnancies/100 woman‐years (95% CI 0.15–1.11); method failure PI was 0.29 pregnancies/100 woman‐years (95% CI 0.06–0.83). Scheduled bleeding/spotting occurred in 91.9–94.4% of women over Cycles 1 to 12 and lasted a median of 4–5 days per cycle. The percentage of women with unscheduled bleeding/spotting episodes decreased from 23.5% in Cycle 1 to <16% from Cycle 6 onwards. The most common AEs were headache (7.7%), metrorrhagia (5.5%), vaginal haemorrhage (4.8%) and acne (4.2%). One treatment‐related serious AE was reported, a lower extremity venous thromboembolism. One‐hundred and forty‐one (9.1%) women discontinued study participation because of treatment‐related adverse events. Conclusion E4/DRSP provides effective contraception, a predictable bleeding pattern and a favourable safety profile. Tweetable abstract A phase 3 trial with E4/DRSP shows high contraceptive efficacy, a predictable bleeding pattern and favourable safety profile.

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“…The fixed-dose drospirenone/estetrol combination has a long half-life along with anti-androgenic and anti-mineralocorticoid properties. This novel combination demonstrates contraceptive effectiveness with a favorable bleeding profile and minimal effects on lipid profile (Creinin et al 2021 ; Gemzell-Danielsson et al 2022 ). It may cause irregular or painful periods, breast pain or tenderness, mood changes, and headache.…”

Section: Methodsmentioning

confidence: 99%

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

Kaykı-Mutlu

Aksoyalp

Wojnowski

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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The second year of the COVID-19 pandemic had no adverse effect on the number of new drug approvals by the US Food and Drug Administration (FDA). Quite the contrary, with a total of 50 new drugs, 2021 belongs to the most successful FDA years. We assign these new drugs to one of three levels of innovation: (1) first drug against a condition (“first-in-indication”), (2) first drug using a novel molecular mechanism (“first-in-class”), and (3) “next-in-class”, i.e., a drug using an already exploited molecular mechanism. We identify 21 first-in-class, 28 next-in-class, and only one first-in-indication drugs. By treatment area, the largest group is once again cancer drugs, many of which target specific genetic alterations. Every second drug approved in 2021 targets an orphan disease, half of them being cancers. Small molecules continue to dominate new drug approvals, followed by antibodies and non-antibody biopharmaceuticals. In 2021, the FDA continued to approve drugs without strong evidence of clinical effects, best exemplified by the aducanumab controversy.

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Estetrol-drospirenone combination oral contraceptive: North American phase 3 efficacy and safety results

Cited by 51 publications

References 29 publications

Estetrol: A New Choice for Contraception

Estetrol: A New Choice for Contraception

Estetrol‐Drospirenone combination oral contraceptive: a clinical study of contraceptive efficacy, bleeding pattern and safety in Europe and Russia

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

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