Efficacy and safety of the combination of estetrol 15 mg/drospirenone 3 mg in a cyclic regimen for the treatment of endometriosis-associated pain and objective gynecological findings: a multicenter, placebo-controlled, double-blind, randomized study
To evaluate the efficacy and safety of 24-week cyclic administration of estetrol (E4) (15 mg)/drospirenone (DRSP) (3 mg) in Japanese patients with endometriosis. A 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Twenty-five study centers in Japan. A total of...
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| Veröffentlicht in: | Fertility and sterility 2024-11, Vol.122 (5), p.894-901 |
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| creator | Harada, Tasuku Kobayashi, Takao Hirakawa, Akihiro Takayanagi, Toshiaki Nogami, Masayoshi Mochiyama, Takayuki Hirayama, Masashi Foidart, Jean-Michel Osuga, Yutaka |
| description | To evaluate the efficacy and safety of 24-week cyclic administration of estetrol (E4) (15 mg)/drospirenone (DRSP) (3 mg) in Japanese patients with endometriosis.
A 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study.
Twenty-five study centers in Japan.
A total of 162 Japanese women diagnosed with endometriosis.
Participants were randomly allocated to the E4/DRSP group or the placebo group. In the E4/DRSP group, participants were orally administered one tablet containing E4 (15 mg) and DRSP (3 mg) daily for 24 days, followed by one placebo tablet for 4 days for a hormone-free interval, constituting a 1-cycle regimen. One placebo tablet was administered once daily for 28 days to participants in the placebo group. The treatments were continued for six cycles (24 weeks) throughout the confirmatory period.
Changes in visual analogue scale (VAS) scores for the most severe pelvic pain (lower abdominal and back pain) from baseline to six treatment cycles at the end of the confirmatory study period.
Estetrol/drospirenone showed changes in the mean VAS scores for the most severe pelvic pain (−33.2 mm) from baseline to the end of the 6-cycle treatment. The between-group difference was significant (−8.5 mm; 2-sided 95% confidence interval, −16.1 to −0.9 mm), showing superiority to placebo. The responder rates, ≥30% and ≥50% reductions in the VAS scores from baseline, were higher in the E4/DRSP group than in the placebo group: 53.2% vs. 29.6% and 36.4% vs. 12.3%. Objective gynecological findings (induration of the cul-de-sac, pelvic tenderness, and limited uterine mobility) were significantly improved by E4/DRSP treatment, and the proportions of stable and worsened participants were significantly lower than in the placebo group. Estetrol/drospirenone decreased the size of endometriomas and improved quality of life, on the basis of quality of life–related questionnaires and global impression scores. No safety concerns were observed with E4/DRSP treatment. Few differences were observed in the proportion of participants with hemostasis parameters outside the reference range between the E4/DRSP and placebo groups.
Estetrol/drospirenone effectively treats endometriosis-associated pain and improves gynecological findings. Estetrol/drospirenone may be a safe, new option for endometriosis treatment with a potentially decreased risk of thromboembolic events.
jRCT2011210027.
Eficacia y seguridad de la combinación de estetrol 15 mg/drospirenon |
| doi_str_mv | 10.1016/j.fertnstert.2024.07.011 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3079956802</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0015028224006046</els_id><sourcerecordid>3079956802</sourcerecordid><originalsourceid>FETCH-LOGICAL-c299t-674ce01d3924811498daead6ddcbd9090c2697cdf0d29545b3e1875c7facdcd3</originalsourceid><addsrcrecordid>eNqFUU1v1DAUjBCIbgt_AfnIYbO1821uUJWCVIlL75bz_By8cuzFdiqFf84Np1vgyMWWRvNm5r0pCsLogVHWXR8PGkNyMeX3UNGqOdD-QBl7UexY23Zl27X1y2JHKWtLWg3VRXEZ45FS2rG-el1c1JxmuOe74tet1gYkrEQ6RaLUmFbiNUnfkYCfR-NkMt5tEGa7FLwlrCXzdK2CjycT0HmHpM4IMY5IAitYAyTgZGZ0RPvwpJUCypSB9KTklJ-zlvHRxFLG6MHIhIqc5KaRg_jxiJDMI5JpdQje-imntEQbp4yb4ofsNC82GciSGPbkZCXg6EvwbstoUe2J8stosRxtHtqTIDdX8zPbxLSo9U3xSksb8e3zf1U8fL59uPlS3n-7-3rz8b6EivNUdn0DSJmqedUMjDV8UBKl6pSCUXHKKVQd70FpqireNu1YIxv6FnotQYGqr4r3Z9lT8D-WfEMxmwhorXTolyhq2nPedgOtMnU4UyGfNgbU4hTMLMMqGBVb7-Io_vUutt4F7UXuPY--e3ZZxhnV38E_RWfCpzMB86qPBoOIYNABqlwhJKG8-b_Lb25dy_g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3079956802</pqid></control><display><type>article</type><title>Efficacy and safety of the combination of estetrol 15 mg/drospirenone 3 mg in a cyclic regimen for the treatment of endometriosis-associated pain and objective gynecological findings: a multicenter, placebo-controlled, double-blind, randomized study</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Harada, Tasuku ; Kobayashi, Takao ; Hirakawa, Akihiro ; Takayanagi, Toshiaki ; Nogami, Masayoshi ; Mochiyama, Takayuki ; Hirayama, Masashi ; Foidart, Jean-Michel ; Osuga, Yutaka</creator><creatorcontrib>Harada, Tasuku ; Kobayashi, Takao ; Hirakawa, Akihiro ; Takayanagi, Toshiaki ; Nogami, Masayoshi ; Mochiyama, Takayuki ; Hirayama, Masashi ; Foidart, Jean-Michel ; Osuga, Yutaka</creatorcontrib><description>To evaluate the efficacy and safety of 24-week cyclic administration of estetrol (E4) (15 mg)/drospirenone (DRSP) (3 mg) in Japanese patients with endometriosis.
A 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study.
Twenty-five study centers in Japan.
A total of 162 Japanese women diagnosed with endometriosis.
Participants were randomly allocated to the E4/DRSP group or the placebo group. In the E4/DRSP group, participants were orally administered one tablet containing E4 (15 mg) and DRSP (3 mg) daily for 24 days, followed by one placebo tablet for 4 days for a hormone-free interval, constituting a 1-cycle regimen. One placebo tablet was administered once daily for 28 days to participants in the placebo group. The treatments were continued for six cycles (24 weeks) throughout the confirmatory period.
Changes in visual analogue scale (VAS) scores for the most severe pelvic pain (lower abdominal and back pain) from baseline to six treatment cycles at the end of the confirmatory study period.
Estetrol/drospirenone showed changes in the mean VAS scores for the most severe pelvic pain (−33.2 mm) from baseline to the end of the 6-cycle treatment. The between-group difference was significant (−8.5 mm; 2-sided 95% confidence interval, −16.1 to −0.9 mm), showing superiority to placebo. The responder rates, ≥30% and ≥50% reductions in the VAS scores from baseline, were higher in the E4/DRSP group than in the placebo group: 53.2% vs. 29.6% and 36.4% vs. 12.3%. Objective gynecological findings (induration of the cul-de-sac, pelvic tenderness, and limited uterine mobility) were significantly improved by E4/DRSP treatment, and the proportions of stable and worsened participants were significantly lower than in the placebo group. Estetrol/drospirenone decreased the size of endometriomas and improved quality of life, on the basis of quality of life–related questionnaires and global impression scores. No safety concerns were observed with E4/DRSP treatment. Few differences were observed in the proportion of participants with hemostasis parameters outside the reference range between the E4/DRSP and placebo groups.
Estetrol/drospirenone effectively treats endometriosis-associated pain and improves gynecological findings. Estetrol/drospirenone may be a safe, new option for endometriosis treatment with a potentially decreased risk of thromboembolic events.
jRCT2011210027.
Eficacia y seguridad de la combinación de estetrol 15 mg/drospirenona 3 mg en un régimen cíclico para el tratamiento del dolor asociado a la endometriosis y hallazgos ginecológicos objetivos: un estudio aleatorizado, doble ciego, multicéntrico y controlado con placebo
Evaluar la eficacia y seguridad de la administración cíclica de 24 semanas de estetrol (E4) (15 mg) /drospirenona (DRSP) (3 mg) en pacientes japonesas con endometriosis.
Estudio de grupos paralelos, multicéntrico, aleatorizado, doble ciego, controlado con placebo, de 24 semanas de duración.
Veinticinco centros de estudio en Japón.
Un total de 162 mujeres japonesas diagnosticadas con endometriosis.
Los participantes fueron asignados aleatoriamente al grupo E4/DRSP o al grupo placebo. En el grupo E4/DRSP, a los participantes se les administró por vía oral una tableta que contenía E4 (15 mg) y DRSP (3 mg) al día durante 24 días, seguida de una tableta de placebo durante 4 días durante un intervalo libre de hormonas, lo que constituye un ciclo de 1 régimen. Se administró una tableta de placebo una vez al día durante 28 días a los participantes del grupo de placebo. Los tratamientos continuaron durante seis ciclos (24 semanas) durante todo el período de confirmación.
Cambios en las puntuaciones de la escala visual analógica (EVA) para el dolor pélvico más grave (dolor abdominal y de espalda) desde el inicio hasta seis ciclos de tratamiento al final del período del estudio confirmatorio.
El estetrol/drospirenona mostró cambios en las puntuaciones EVA medias para el dolor pélvico más intenso (-33.2 mm) desde el inicio hasta el final del tratamiento de 6 ciclos. La diferencia entre los grupos fue significativa (-8.5 mm; intervalo de confianza bilateral del 95%, -16.1 a -0.9 mm), demostrando superioridad sobre el placebo. Las tasas de respuesta, reducciones de ≥30% y ≥50% en las puntuaciones EVA desde el inicio, fueron mayores en el grupo E4/DRSP que en el grupo de placebo: 53,2% frente a 29,6% y 36,4% frente a 12,3%. Los hallazgos ginecológicos objetivos (endurecimiento del cul-de-sac, sensibilidad pélvica y movilidad uterina limitada) mejoraron significativamente con el tratamiento con E4/DRSP, y las proporciones de participantes estables y empeoradas fueron significativamente menores que en el grupo de placebo. El estetrol/drospirenona disminuyó el tamaño de los endometriomas y mejoró la calidad de vida, según cuestionarios relacionados con la calidad de vida y puntuaciones de impresión global. No se observaron problemas de seguridad en el tratamiento con E4/DRSP. Se observaron pocas diferencias en la proporción de participantes con parámetros de hemostasia fuera del rango de referencia entre los grupos E4/DRSP y placebo.
El estetrol/drospirenona trata eficazmente el dolor asociado a la endometriosis y mejora los hallazgos ginecológicos. El estetrol/drospirenona puede ser una nueva opción segura para el tratamiento de la endometriosis con un riesgo potencialmente reducido de eventos tromboembólicos.</description><identifier>ISSN: 0015-0282</identifier><identifier>ISSN: 1556-5653</identifier><identifier>EISSN: 1556-5653</identifier><identifier>DOI: 10.1016/j.fertnstert.2024.07.011</identifier><identifier>PMID: 39002879</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Androstenes - administration & dosage ; Androstenes - adverse effects ; Androstenes - therapeutic use ; Double-Blind Method ; drospirenone ; Drug Administration Schedule ; Drug Combinations ; endometriosis ; Endometriosis - complications ; Endometriosis - diagnosis ; Endometriosis - drug therapy ; Estetrol ; Estetrol - administration & dosage ; Estetrol - adverse effects ; estrogen-progestin combination ; Female ; Humans ; Japan ; pain alleviation ; Pain Measurement ; Pelvic Pain - diagnosis ; Pelvic Pain - drug therapy ; Pelvic Pain - etiology ; Treatment Outcome ; Young Adult</subject><ispartof>Fertility and sterility, 2024-11, Vol.122 (5), p.894-901</ispartof><rights>2024 The Authors</rights><rights>Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c299t-674ce01d3924811498daead6ddcbd9090c2697cdf0d29545b3e1875c7facdcd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.fertnstert.2024.07.011$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>315,781,785,3551,27926,27927,45997</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39002879$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Harada, Tasuku</creatorcontrib><creatorcontrib>Kobayashi, Takao</creatorcontrib><creatorcontrib>Hirakawa, Akihiro</creatorcontrib><creatorcontrib>Takayanagi, Toshiaki</creatorcontrib><creatorcontrib>Nogami, Masayoshi</creatorcontrib><creatorcontrib>Mochiyama, Takayuki</creatorcontrib><creatorcontrib>Hirayama, Masashi</creatorcontrib><creatorcontrib>Foidart, Jean-Michel</creatorcontrib><creatorcontrib>Osuga, Yutaka</creatorcontrib><title>Efficacy and safety of the combination of estetrol 15 mg/drospirenone 3 mg in a cyclic regimen for the treatment of endometriosis-associated pain and objective gynecological findings: a multicenter, placebo-controlled, double-blind, randomized study</title><title>Fertility and sterility</title><addtitle>Fertil Steril</addtitle><description>To evaluate the efficacy and safety of 24-week cyclic administration of estetrol (E4) (15 mg)/drospirenone (DRSP) (3 mg) in Japanese patients with endometriosis.
A 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study.
Twenty-five study centers in Japan.
A total of 162 Japanese women diagnosed with endometriosis.
Participants were randomly allocated to the E4/DRSP group or the placebo group. In the E4/DRSP group, participants were orally administered one tablet containing E4 (15 mg) and DRSP (3 mg) daily for 24 days, followed by one placebo tablet for 4 days for a hormone-free interval, constituting a 1-cycle regimen. One placebo tablet was administered once daily for 28 days to participants in the placebo group. The treatments were continued for six cycles (24 weeks) throughout the confirmatory period.
Changes in visual analogue scale (VAS) scores for the most severe pelvic pain (lower abdominal and back pain) from baseline to six treatment cycles at the end of the confirmatory study period.
Estetrol/drospirenone showed changes in the mean VAS scores for the most severe pelvic pain (−33.2 mm) from baseline to the end of the 6-cycle treatment. The between-group difference was significant (−8.5 mm; 2-sided 95% confidence interval, −16.1 to −0.9 mm), showing superiority to placebo. The responder rates, ≥30% and ≥50% reductions in the VAS scores from baseline, were higher in the E4/DRSP group than in the placebo group: 53.2% vs. 29.6% and 36.4% vs. 12.3%. Objective gynecological findings (induration of the cul-de-sac, pelvic tenderness, and limited uterine mobility) were significantly improved by E4/DRSP treatment, and the proportions of stable and worsened participants were significantly lower than in the placebo group. Estetrol/drospirenone decreased the size of endometriomas and improved quality of life, on the basis of quality of life–related questionnaires and global impression scores. No safety concerns were observed with E4/DRSP treatment. Few differences were observed in the proportion of participants with hemostasis parameters outside the reference range between the E4/DRSP and placebo groups.
Estetrol/drospirenone effectively treats endometriosis-associated pain and improves gynecological findings. Estetrol/drospirenone may be a safe, new option for endometriosis treatment with a potentially decreased risk of thromboembolic events.
jRCT2011210027.
Eficacia y seguridad de la combinación de estetrol 15 mg/drospirenona 3 mg en un régimen cíclico para el tratamiento del dolor asociado a la endometriosis y hallazgos ginecológicos objetivos: un estudio aleatorizado, doble ciego, multicéntrico y controlado con placebo
Evaluar la eficacia y seguridad de la administración cíclica de 24 semanas de estetrol (E4) (15 mg) /drospirenona (DRSP) (3 mg) en pacientes japonesas con endometriosis.
Estudio de grupos paralelos, multicéntrico, aleatorizado, doble ciego, controlado con placebo, de 24 semanas de duración.
Veinticinco centros de estudio en Japón.
Un total de 162 mujeres japonesas diagnosticadas con endometriosis.
Los participantes fueron asignados aleatoriamente al grupo E4/DRSP o al grupo placebo. En el grupo E4/DRSP, a los participantes se les administró por vía oral una tableta que contenía E4 (15 mg) y DRSP (3 mg) al día durante 24 días, seguida de una tableta de placebo durante 4 días durante un intervalo libre de hormonas, lo que constituye un ciclo de 1 régimen. Se administró una tableta de placebo una vez al día durante 28 días a los participantes del grupo de placebo. Los tratamientos continuaron durante seis ciclos (24 semanas) durante todo el período de confirmación.
Cambios en las puntuaciones de la escala visual analógica (EVA) para el dolor pélvico más grave (dolor abdominal y de espalda) desde el inicio hasta seis ciclos de tratamiento al final del período del estudio confirmatorio.
El estetrol/drospirenona mostró cambios en las puntuaciones EVA medias para el dolor pélvico más intenso (-33.2 mm) desde el inicio hasta el final del tratamiento de 6 ciclos. La diferencia entre los grupos fue significativa (-8.5 mm; intervalo de confianza bilateral del 95%, -16.1 a -0.9 mm), demostrando superioridad sobre el placebo. Las tasas de respuesta, reducciones de ≥30% y ≥50% en las puntuaciones EVA desde el inicio, fueron mayores en el grupo E4/DRSP que en el grupo de placebo: 53,2% frente a 29,6% y 36,4% frente a 12,3%. Los hallazgos ginecológicos objetivos (endurecimiento del cul-de-sac, sensibilidad pélvica y movilidad uterina limitada) mejoraron significativamente con el tratamiento con E4/DRSP, y las proporciones de participantes estables y empeoradas fueron significativamente menores que en el grupo de placebo. El estetrol/drospirenona disminuyó el tamaño de los endometriomas y mejoró la calidad de vida, según cuestionarios relacionados con la calidad de vida y puntuaciones de impresión global. No se observaron problemas de seguridad en el tratamiento con E4/DRSP. Se observaron pocas diferencias en la proporción de participantes con parámetros de hemostasia fuera del rango de referencia entre los grupos E4/DRSP y placebo.
El estetrol/drospirenona trata eficazmente el dolor asociado a la endometriosis y mejora los hallazgos ginecológicos. El estetrol/drospirenona puede ser una nueva opción segura para el tratamiento de la endometriosis con un riesgo potencialmente reducido de eventos tromboembólicos.</description><subject>Adult</subject><subject>Androstenes - administration & dosage</subject><subject>Androstenes - adverse effects</subject><subject>Androstenes - therapeutic use</subject><subject>Double-Blind Method</subject><subject>drospirenone</subject><subject>Drug Administration Schedule</subject><subject>Drug Combinations</subject><subject>endometriosis</subject><subject>Endometriosis - complications</subject><subject>Endometriosis - diagnosis</subject><subject>Endometriosis - drug therapy</subject><subject>Estetrol</subject><subject>Estetrol - administration & dosage</subject><subject>Estetrol - adverse effects</subject><subject>estrogen-progestin combination</subject><subject>Female</subject><subject>Humans</subject><subject>Japan</subject><subject>pain alleviation</subject><subject>Pain Measurement</subject><subject>Pelvic Pain - diagnosis</subject><subject>Pelvic Pain - drug therapy</subject><subject>Pelvic Pain - etiology</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>0015-0282</issn><issn>1556-5653</issn><issn>1556-5653</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUU1v1DAUjBCIbgt_AfnIYbO1821uUJWCVIlL75bz_By8cuzFdiqFf84Np1vgyMWWRvNm5r0pCsLogVHWXR8PGkNyMeX3UNGqOdD-QBl7UexY23Zl27X1y2JHKWtLWg3VRXEZ45FS2rG-el1c1JxmuOe74tet1gYkrEQ6RaLUmFbiNUnfkYCfR-NkMt5tEGa7FLwlrCXzdK2CjycT0HmHpM4IMY5IAitYAyTgZGZ0RPvwpJUCypSB9KTklJ-zlvHRxFLG6MHIhIqc5KaRg_jxiJDMI5JpdQje-imntEQbp4yb4ofsNC82GciSGPbkZCXg6EvwbstoUe2J8stosRxtHtqTIDdX8zPbxLSo9U3xSksb8e3zf1U8fL59uPlS3n-7-3rz8b6EivNUdn0DSJmqedUMjDV8UBKl6pSCUXHKKVQd70FpqireNu1YIxv6FnotQYGqr4r3Z9lT8D-WfEMxmwhorXTolyhq2nPedgOtMnU4UyGfNgbU4hTMLMMqGBVb7-Io_vUutt4F7UXuPY--e3ZZxhnV38E_RWfCpzMB86qPBoOIYNABqlwhJKG8-b_Lb25dy_g</recordid><startdate>202411</startdate><enddate>202411</enddate><creator>Harada, Tasuku</creator><creator>Kobayashi, Takao</creator><creator>Hirakawa, Akihiro</creator><creator>Takayanagi, Toshiaki</creator><creator>Nogami, Masayoshi</creator><creator>Mochiyama, Takayuki</creator><creator>Hirayama, Masashi</creator><creator>Foidart, Jean-Michel</creator><creator>Osuga, Yutaka</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202411</creationdate><title>Efficacy and safety of the combination of estetrol 15 mg/drospirenone 3 mg in a cyclic regimen for the treatment of endometriosis-associated pain and objective gynecological findings: a multicenter, placebo-controlled, double-blind, randomized study</title><author>Harada, Tasuku ; Kobayashi, Takao ; Hirakawa, Akihiro ; Takayanagi, Toshiaki ; Nogami, Masayoshi ; Mochiyama, Takayuki ; Hirayama, Masashi ; Foidart, Jean-Michel ; Osuga, Yutaka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c299t-674ce01d3924811498daead6ddcbd9090c2697cdf0d29545b3e1875c7facdcd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Androstenes - administration & dosage</topic><topic>Androstenes - adverse effects</topic><topic>Androstenes - therapeutic use</topic><topic>Double-Blind Method</topic><topic>drospirenone</topic><topic>Drug Administration Schedule</topic><topic>Drug Combinations</topic><topic>endometriosis</topic><topic>Endometriosis - complications</topic><topic>Endometriosis - diagnosis</topic><topic>Endometriosis - drug therapy</topic><topic>Estetrol</topic><topic>Estetrol - administration & dosage</topic><topic>Estetrol - adverse effects</topic><topic>estrogen-progestin combination</topic><topic>Female</topic><topic>Humans</topic><topic>Japan</topic><topic>pain alleviation</topic><topic>Pain Measurement</topic><topic>Pelvic Pain - diagnosis</topic><topic>Pelvic Pain - drug therapy</topic><topic>Pelvic Pain - etiology</topic><topic>Treatment Outcome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Harada, Tasuku</creatorcontrib><creatorcontrib>Kobayashi, Takao</creatorcontrib><creatorcontrib>Hirakawa, Akihiro</creatorcontrib><creatorcontrib>Takayanagi, Toshiaki</creatorcontrib><creatorcontrib>Nogami, Masayoshi</creatorcontrib><creatorcontrib>Mochiyama, Takayuki</creatorcontrib><creatorcontrib>Hirayama, Masashi</creatorcontrib><creatorcontrib>Foidart, Jean-Michel</creatorcontrib><creatorcontrib>Osuga, Yutaka</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Fertility and sterility</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Harada, Tasuku</au><au>Kobayashi, Takao</au><au>Hirakawa, Akihiro</au><au>Takayanagi, Toshiaki</au><au>Nogami, Masayoshi</au><au>Mochiyama, Takayuki</au><au>Hirayama, Masashi</au><au>Foidart, Jean-Michel</au><au>Osuga, Yutaka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy and safety of the combination of estetrol 15 mg/drospirenone 3 mg in a cyclic regimen for the treatment of endometriosis-associated pain and objective gynecological findings: a multicenter, placebo-controlled, double-blind, randomized study</atitle><jtitle>Fertility and sterility</jtitle><addtitle>Fertil Steril</addtitle><date>2024-11</date><risdate>2024</risdate><volume>122</volume><issue>5</issue><spage>894</spage><epage>901</epage><pages>894-901</pages><issn>0015-0282</issn><issn>1556-5653</issn><eissn>1556-5653</eissn><abstract>To evaluate the efficacy and safety of 24-week cyclic administration of estetrol (E4) (15 mg)/drospirenone (DRSP) (3 mg) in Japanese patients with endometriosis.
A 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study.
Twenty-five study centers in Japan.
A total of 162 Japanese women diagnosed with endometriosis.
Participants were randomly allocated to the E4/DRSP group or the placebo group. In the E4/DRSP group, participants were orally administered one tablet containing E4 (15 mg) and DRSP (3 mg) daily for 24 days, followed by one placebo tablet for 4 days for a hormone-free interval, constituting a 1-cycle regimen. One placebo tablet was administered once daily for 28 days to participants in the placebo group. The treatments were continued for six cycles (24 weeks) throughout the confirmatory period.
Changes in visual analogue scale (VAS) scores for the most severe pelvic pain (lower abdominal and back pain) from baseline to six treatment cycles at the end of the confirmatory study period.
Estetrol/drospirenone showed changes in the mean VAS scores for the most severe pelvic pain (−33.2 mm) from baseline to the end of the 6-cycle treatment. The between-group difference was significant (−8.5 mm; 2-sided 95% confidence interval, −16.1 to −0.9 mm), showing superiority to placebo. The responder rates, ≥30% and ≥50% reductions in the VAS scores from baseline, were higher in the E4/DRSP group than in the placebo group: 53.2% vs. 29.6% and 36.4% vs. 12.3%. Objective gynecological findings (induration of the cul-de-sac, pelvic tenderness, and limited uterine mobility) were significantly improved by E4/DRSP treatment, and the proportions of stable and worsened participants were significantly lower than in the placebo group. Estetrol/drospirenone decreased the size of endometriomas and improved quality of life, on the basis of quality of life–related questionnaires and global impression scores. No safety concerns were observed with E4/DRSP treatment. Few differences were observed in the proportion of participants with hemostasis parameters outside the reference range between the E4/DRSP and placebo groups.
Estetrol/drospirenone effectively treats endometriosis-associated pain and improves gynecological findings. Estetrol/drospirenone may be a safe, new option for endometriosis treatment with a potentially decreased risk of thromboembolic events.
jRCT2011210027.
Eficacia y seguridad de la combinación de estetrol 15 mg/drospirenona 3 mg en un régimen cíclico para el tratamiento del dolor asociado a la endometriosis y hallazgos ginecológicos objetivos: un estudio aleatorizado, doble ciego, multicéntrico y controlado con placebo
Evaluar la eficacia y seguridad de la administración cíclica de 24 semanas de estetrol (E4) (15 mg) /drospirenona (DRSP) (3 mg) en pacientes japonesas con endometriosis.
Estudio de grupos paralelos, multicéntrico, aleatorizado, doble ciego, controlado con placebo, de 24 semanas de duración.
Veinticinco centros de estudio en Japón.
Un total de 162 mujeres japonesas diagnosticadas con endometriosis.
Los participantes fueron asignados aleatoriamente al grupo E4/DRSP o al grupo placebo. En el grupo E4/DRSP, a los participantes se les administró por vía oral una tableta que contenía E4 (15 mg) y DRSP (3 mg) al día durante 24 días, seguida de una tableta de placebo durante 4 días durante un intervalo libre de hormonas, lo que constituye un ciclo de 1 régimen. Se administró una tableta de placebo una vez al día durante 28 días a los participantes del grupo de placebo. Los tratamientos continuaron durante seis ciclos (24 semanas) durante todo el período de confirmación.
Cambios en las puntuaciones de la escala visual analógica (EVA) para el dolor pélvico más grave (dolor abdominal y de espalda) desde el inicio hasta seis ciclos de tratamiento al final del período del estudio confirmatorio.
El estetrol/drospirenona mostró cambios en las puntuaciones EVA medias para el dolor pélvico más intenso (-33.2 mm) desde el inicio hasta el final del tratamiento de 6 ciclos. La diferencia entre los grupos fue significativa (-8.5 mm; intervalo de confianza bilateral del 95%, -16.1 a -0.9 mm), demostrando superioridad sobre el placebo. Las tasas de respuesta, reducciones de ≥30% y ≥50% en las puntuaciones EVA desde el inicio, fueron mayores en el grupo E4/DRSP que en el grupo de placebo: 53,2% frente a 29,6% y 36,4% frente a 12,3%. Los hallazgos ginecológicos objetivos (endurecimiento del cul-de-sac, sensibilidad pélvica y movilidad uterina limitada) mejoraron significativamente con el tratamiento con E4/DRSP, y las proporciones de participantes estables y empeoradas fueron significativamente menores que en el grupo de placebo. El estetrol/drospirenona disminuyó el tamaño de los endometriomas y mejoró la calidad de vida, según cuestionarios relacionados con la calidad de vida y puntuaciones de impresión global. No se observaron problemas de seguridad en el tratamiento con E4/DRSP. Se observaron pocas diferencias en la proporción de participantes con parámetros de hemostasia fuera del rango de referencia entre los grupos E4/DRSP y placebo.
El estetrol/drospirenona trata eficazmente el dolor asociado a la endometriosis y mejora los hallazgos ginecológicos. El estetrol/drospirenona puede ser una nueva opción segura para el tratamiento de la endometriosis con un riesgo potencialmente reducido de eventos tromboembólicos.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>39002879</pmid><doi>10.1016/j.fertnstert.2024.07.011</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0015-0282 |
| ispartof | Fertility and sterility, 2024-11, Vol.122 (5), p.894-901 |
| issn | 0015-0282 1556-5653 1556-5653 |
| language | eng |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Adult Androstenes - administration & dosage Androstenes - adverse effects Androstenes - therapeutic use Double-Blind Method drospirenone Drug Administration Schedule Drug Combinations endometriosis Endometriosis - complications Endometriosis - diagnosis Endometriosis - drug therapy Estetrol Estetrol - administration & dosage Estetrol - adverse effects estrogen-progestin combination Female Humans Japan pain alleviation Pain Measurement Pelvic Pain - diagnosis Pelvic Pain - drug therapy Pelvic Pain - etiology Treatment Outcome Young Adult |
| title | Efficacy and safety of the combination of estetrol 15 mg/drospirenone 3 mg in a cyclic regimen for the treatment of endometriosis-associated pain and objective gynecological findings: a multicenter, placebo-controlled, double-blind, randomized study |
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