TY - JOUR
T1 - Tolerability and safety of the estetrol/drospirenone combined oral contraceptive
T2 - Pooled analysis of two multicenter, open-label phase 3 trials
AU - Chen, Melissa J.
AU - Jensen, Jeffrey T.
AU - Kaunitz, Andrew M.
AU - Achilles, Sharon L.
AU - Zatik, János
AU - Weyers, Steven
AU - Piltonen, Terhi
AU - Suturina, Larisa
AU - Apolikhina, Inna
AU - Bouchard, Celine
AU - Archer, David F.
AU - Jost, Maud
AU - Foidart, Jean Michel
AU - Creinin, Mitchell
N1 - Publisher Copyright:
© 2022
PY - 2022/12
Y1 - 2022/12
N2 - Objectives: To evaluate tolerability and safety of estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg oral contraceptive using pooled data from two, multicenter, phase 3 trials. Study design: The two trials enrolled participants aged 16−50 years with a body mass index ≤35.0 kg/m2 to use E4/DRSP in a 24/4-day regimen for up to 13 cycles. We pooled data from participants who used at least one E4/DRSP dose and had a follow-up assessment to analyze adverse events (AEs), vital signs, and laboratory parameters, including serum lipids, glucose, glycated hemoglobin, and potassium. We consolidated similar Medical Dictionary for Regulatory Activities preferred terms into groupings. Results: Of 3725 participants enrolled, we included 3417 in the analyses of whom 1786 (52.3%) reported ≥1 AE. Most participants with reported AEs had AEs that investigators rated as mild or moderate (n = 1665, 93.2%); of participants reporting AEs, 1105 (61.9%) did so during cycles 1 to 3. In total, 981 (28.7%) participants experienced ≥1 treatment-related AE, most frequently related to bleeding complaints (n = 323, 9.5%), breast pain or tenderness (n = 136, 4.0%), acne (n = 113, 3.3%), and mood disturbance (n = 111, 3.2%). Discontinuation due to treatment-related AEs occurred in 272 participants (8.0%), with only bleeding complaints (n = 97, 2.8%) and mood disturbance (n = 38, 1.1%) at rates exceeding 1%. Three participants experienced serious AEs, which the site investigators considered treatment-related: one venous thromboembolism, one worsening of depression, and one ectopic pregnancy. We found no clinically relevant changes in weight, blood pressure, heart rate, or laboratory parameters during treatment. Conclusions: E4/DRSP is associated with a favorable tolerability and safety profile. Implications statement: Pooling data allowed for a robust assessment of tolerability and safety, including relatively infrequent events. Other than bleeding complaints and mood disturbance, no adverse event resulted in E4/DRSP discontinuation at rates >1%. Post-marketing surveillance studies are needed to evaluate long-term safety of the E4/DRSP COC and population-based venous thromboembolism risks.
AB - Objectives: To evaluate tolerability and safety of estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg oral contraceptive using pooled data from two, multicenter, phase 3 trials. Study design: The two trials enrolled participants aged 16−50 years with a body mass index ≤35.0 kg/m2 to use E4/DRSP in a 24/4-day regimen for up to 13 cycles. We pooled data from participants who used at least one E4/DRSP dose and had a follow-up assessment to analyze adverse events (AEs), vital signs, and laboratory parameters, including serum lipids, glucose, glycated hemoglobin, and potassium. We consolidated similar Medical Dictionary for Regulatory Activities preferred terms into groupings. Results: Of 3725 participants enrolled, we included 3417 in the analyses of whom 1786 (52.3%) reported ≥1 AE. Most participants with reported AEs had AEs that investigators rated as mild or moderate (n = 1665, 93.2%); of participants reporting AEs, 1105 (61.9%) did so during cycles 1 to 3. In total, 981 (28.7%) participants experienced ≥1 treatment-related AE, most frequently related to bleeding complaints (n = 323, 9.5%), breast pain or tenderness (n = 136, 4.0%), acne (n = 113, 3.3%), and mood disturbance (n = 111, 3.2%). Discontinuation due to treatment-related AEs occurred in 272 participants (8.0%), with only bleeding complaints (n = 97, 2.8%) and mood disturbance (n = 38, 1.1%) at rates exceeding 1%. Three participants experienced serious AEs, which the site investigators considered treatment-related: one venous thromboembolism, one worsening of depression, and one ectopic pregnancy. We found no clinically relevant changes in weight, blood pressure, heart rate, or laboratory parameters during treatment. Conclusions: E4/DRSP is associated with a favorable tolerability and safety profile. Implications statement: Pooling data allowed for a robust assessment of tolerability and safety, including relatively infrequent events. Other than bleeding complaints and mood disturbance, no adverse event resulted in E4/DRSP discontinuation at rates >1%. Post-marketing surveillance studies are needed to evaluate long-term safety of the E4/DRSP COC and population-based venous thromboembolism risks.
KW - Combined Oral Contraceptive
KW - Drospirenone
KW - E4
KW - Estetrol
KW - Oral Contraception
KW - Safety
KW - Tolerability
UR - http://www.scopus.com/inward/record.url?scp=85141507660&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85141507660&partnerID=8YFLogxK
U2 - 10.1016/j.contraception.2022.10.004
DO - 10.1016/j.contraception.2022.10.004
M3 - Article
C2 - 36257374
AN - SCOPUS:85141507660
SN - 0010-7824
VL - 116
SP - 44
EP - 50
JO - Contraception
JF - Contraception
ER -