Ultra-low-dose continuous combined estradiol and dydrogesterone in postmenopausal women: A pooled safety and tolerability analysis

Objective: To assess the safety and tolerability of ultra-low dose estradiol and dydrogesterone (E0.5 mg/D2.5 mg) among postmenopausal women. Methods: This pooled analysis of data from three clinical studies assessed the effects of continuous combined ultra-low-dose estradiol and dydrogesterone amon...

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Main Authors: Tetiana Tatarchuk, John C. Stevenson, Qi Yu, Elke Kahler, Marcelo Graziano Custodio, Mulan Ren, Rossella E. Nappi, Viktoriya Karpova, Tommaso Simoncini
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Gynecological Endocrinology
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Online Access:https://www.tandfonline.com/doi/10.1080/09513590.2024.2375577
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author Tetiana Tatarchuk
John C. Stevenson
Qi Yu
Elke Kahler
Marcelo Graziano Custodio
Mulan Ren
Rossella E. Nappi
Viktoriya Karpova
Tommaso Simoncini
author_facet Tetiana Tatarchuk
John C. Stevenson
Qi Yu
Elke Kahler
Marcelo Graziano Custodio
Mulan Ren
Rossella E. Nappi
Viktoriya Karpova
Tommaso Simoncini
author_sort Tetiana Tatarchuk
collection DOAJ
description Objective: To assess the safety and tolerability of ultra-low dose estradiol and dydrogesterone (E0.5 mg/D2.5 mg) among postmenopausal women. Methods: This pooled analysis of data from three clinical studies assessed the effects of continuous combined ultra-low-dose estradiol and dydrogesterone among postmenopausal women. Participants received E0.5 mg/D2.5 mg or placebo for 13 weeks (double-blind, randomized, European study), E0.5 mg/D2.5 mg or placebo for 12 weeks (double-blind, randomized, Chinese study), or E0.5 mg/D2.5 mg for 52 weeks (open-label, European study). Safety outcomes included treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), treatment discontinuation due to a TEAE, and adverse events of special interest (AESIs). Results: Overall, 1027 women were included in the pooled analysis (E0.5 mg/D2.5 mg, n = 736; placebo, n = 291). Mean treatment exposure was 288.9 days in the E0.5 mg/D2.5 mg group and 86.6 days in the placebo group. The proportion of women experiencing ≥1 TEAE was similar in the E0.5 mg/D2.5 mg and placebo groups (50.1% vs 49.5%, respectively). TESAEs occurred in 12 (1.6%) women receiving E0.5 mg/D2.5 mg and 9 (3.1%) women receiving placebo. Discontinuation of study treatment was infrequent in both groups (E0.5 mg/D2.5 mg: 1.5%; placebo: 2.4%). The occurrence of breast pain was more common in the E0.5 mg/D2.5 mg group than in the placebo group (2.0% vs 0.3%) as was uterine hemorrhage (6.5% vs 2.4%). The incidence of acne, hypertrichoses and weight increased was similar between groups. Conclusions: Across three studies, ultra-low-dose estradiol plus dydrogesterone was well tolerated among postmenopausal women, with no increase in TEAEs or TESAEs compared with placebo.
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spelling doaj-art-2a693e7feb49414b83fe22b7a3c445aa2025-08-20T02:39:22ZengTaylor & Francis GroupGynecological Endocrinology0951-35901473-07662024-12-0140110.1080/09513590.2024.2375577Ultra-low-dose continuous combined estradiol and dydrogesterone in postmenopausal women: A pooled safety and tolerability analysisTetiana Tatarchuk0John C. Stevenson1Qi Yu2Elke Kahler3Marcelo Graziano Custodio4Mulan Ren5Rossella E. Nappi6Viktoriya Karpova7Tommaso Simoncini8Department of Endocrine Gynaecology, National Institute of Pediatrics, Obstetrics and Gynecology of National Academy of Medical Science of Ukraine, Kyiv, UkraineNational Heart and Lung Institute, Royal Brompton Hospital and Imperial College London, London, UKGynecological Endocrinology and Reproductive Center, Peking Union Medical College Hospital, Beijing, ChinaGlobal Biometrics, Established Pharmaceuticals Division, Abbott Laboratories GmbH, Hannover, GermanGlobal Innovation and Development, Established Pharmaceuticals Division, Abbott Products Operations AG, Allschwil, SwitzerlandDepartment of Obstetrics and Gynecology, Zhongda Hospital, Southeast University, Nanjing, ChinaDepartment of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, ItalyEstablished Pharmaceuticals Division, Abbott Ukraine LLC, Kyiv, UkraineDivision of Obstetrics and Gynecology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyObjective: To assess the safety and tolerability of ultra-low dose estradiol and dydrogesterone (E0.5 mg/D2.5 mg) among postmenopausal women. Methods: This pooled analysis of data from three clinical studies assessed the effects of continuous combined ultra-low-dose estradiol and dydrogesterone among postmenopausal women. Participants received E0.5 mg/D2.5 mg or placebo for 13 weeks (double-blind, randomized, European study), E0.5 mg/D2.5 mg or placebo for 12 weeks (double-blind, randomized, Chinese study), or E0.5 mg/D2.5 mg for 52 weeks (open-label, European study). Safety outcomes included treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), treatment discontinuation due to a TEAE, and adverse events of special interest (AESIs). Results: Overall, 1027 women were included in the pooled analysis (E0.5 mg/D2.5 mg, n = 736; placebo, n = 291). Mean treatment exposure was 288.9 days in the E0.5 mg/D2.5 mg group and 86.6 days in the placebo group. The proportion of women experiencing ≥1 TEAE was similar in the E0.5 mg/D2.5 mg and placebo groups (50.1% vs 49.5%, respectively). TESAEs occurred in 12 (1.6%) women receiving E0.5 mg/D2.5 mg and 9 (3.1%) women receiving placebo. Discontinuation of study treatment was infrequent in both groups (E0.5 mg/D2.5 mg: 1.5%; placebo: 2.4%). The occurrence of breast pain was more common in the E0.5 mg/D2.5 mg group than in the placebo group (2.0% vs 0.3%) as was uterine hemorrhage (6.5% vs 2.4%). The incidence of acne, hypertrichoses and weight increased was similar between groups. Conclusions: Across three studies, ultra-low-dose estradiol plus dydrogesterone was well tolerated among postmenopausal women, with no increase in TEAEs or TESAEs compared with placebo.https://www.tandfonline.com/doi/10.1080/09513590.2024.2375577Ultra-low dose estradioldydrogesteronepostmenopausal womensafetytolerability
spellingShingle Tetiana Tatarchuk
John C. Stevenson
Qi Yu
Elke Kahler
Marcelo Graziano Custodio
Mulan Ren
Rossella E. Nappi
Viktoriya Karpova
Tommaso Simoncini
Ultra-low-dose continuous combined estradiol and dydrogesterone in postmenopausal women: A pooled safety and tolerability analysis
Gynecological Endocrinology
Ultra-low dose estradiol
dydrogesterone
postmenopausal women
safety
tolerability
title Ultra-low-dose continuous combined estradiol and dydrogesterone in postmenopausal women: A pooled safety and tolerability analysis
title_full Ultra-low-dose continuous combined estradiol and dydrogesterone in postmenopausal women: A pooled safety and tolerability analysis
title_fullStr Ultra-low-dose continuous combined estradiol and dydrogesterone in postmenopausal women: A pooled safety and tolerability analysis
title_full_unstemmed Ultra-low-dose continuous combined estradiol and dydrogesterone in postmenopausal women: A pooled safety and tolerability analysis
title_short Ultra-low-dose continuous combined estradiol and dydrogesterone in postmenopausal women: A pooled safety and tolerability analysis
title_sort ultra low dose continuous combined estradiol and dydrogesterone in postmenopausal women a pooled safety and tolerability analysis
topic Ultra-low dose estradiol
dydrogesterone
postmenopausal women
safety
tolerability
url https://www.tandfonline.com/doi/10.1080/09513590.2024.2375577
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