Double dosing ulipristal acetate emergency contraception for individuals with obesity: a randomised crossover trial.

IF 3.4 3区 医学 Q1 FAMILY STUDIES BMJ Sexual & Reproductive Health Pub Date : 2024-07-14 DOI:10.1136/bmjsrh-2024-202401
Alison Edelman, Jon D Hennebold, Kise Bond, Jeong Y Lim, Ganesh Cherala, Steven W Blue, Shawn P Kraft, David W Erikson, David Archer, Jeffery Jensen
{"title":"Double dosing ulipristal acetate emergency contraception for individuals with obesity: a randomised crossover trial.","authors":"Alison Edelman, Jon D Hennebold, Kise Bond, Jeong Y Lim, Ganesh Cherala, Steven W Blue, Shawn P Kraft, David W Erikson, David Archer, Jeffery Jensen","doi":"10.1136/bmjsrh-2024-202401","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To determine whether increasing the dose of ulipristal acetate (UPA)-containing emergency contraception (EC) improves pharmacodynamic outcomes in individuals with obesity.</p><p><strong>Study design: </strong>We enrolled healthy, regularly-cycling, confirmed ovulatory, reproductive-age individuals with body mass index (BMI) >30 kg/m<sup>2</sup> and weight >80 kg in a randomised crossover study. We monitored participants with transvaginal ultrasound and blood sampling for progesterone, luteinising hormone (LH), and estradiol every other day until a dominant follicle measuring >15 mm was visualised. At that point, participants received either oral UPA EC 30 mg or 60 mg and returned for daily monitoring up to 7 days. After a no treatment washout cycle, participants returned for a second monitored cycle and received the other UPA dose. Our primary outcome was the proportion of subjects with no follicle rupture 5 days post-dosing (yes/no). For reference, we also enrolled a control group with BMI <25 kg/m<sup>2</sup> and weight <80 kg who received UPA EC 30 mg during a single cycle. We also obtained blood samples for pharmacokinetic parameters for UPA and its active metabolite, <i>N</i>-monodemethyl-UPA (NDM-UPA) as an optional substudy.</p><p><strong>Results: </strong>We enrolled a total of 52 participants with BMI >30 kg/m<sup>2</sup> and 12 controls, with the following cycles completed: 12 controls, 49 UPA 30 mg, and 46 UPA 60 mg. The entire cohort demographics were a mean (SD) age of 29.8 (3.4) years and BMI by group: controls 22.5 (1.4) kg/m<sup>2</sup>, group 1 37.9 (6.7) kg/m<sup>2</sup>, and group 2 39.3 (5.4) kg/m<sup>2</sup>. All 12 (100%) of controls had a delay of at least 5 days for follicle rupture. Among the high BMI group, dosing groups (UPA EC 30 mg vs 60 mg) were similar in the proportion of cycles without follicle rupture over 5 days post-UPA dosing (UPA 30 mg: 47/49 (96%), UPA 60 mg: 42/46 (91%), Fisher's exact test p=0.43). However, after excluding cycles where dosing occurred too late (after LH surge), a delay of at least 5 days occurred in all participants at both doses. The 60 mg UPA dose resulted in a twofold increase in maximum observed concentration and the area under the curve of both UPA and NDM-UPA levels compared with 30 mg.</p><p><strong>Conclusion: </strong>A standard 30 mg dose of UPA is sufficient to delay ovulation regardless of BMI or weight. Results of our study do not support dose adjustment for body size.</p>","PeriodicalId":9219,"journal":{"name":"BMJ Sexual & Reproductive Health","volume":" ","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMJ Sexual & Reproductive Health","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/bmjsrh-2024-202401","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"FAMILY STUDIES","Score":null,"Total":0}
引用次数: 0

Abstract

Objective: To determine whether increasing the dose of ulipristal acetate (UPA)-containing emergency contraception (EC) improves pharmacodynamic outcomes in individuals with obesity.

Study design: We enrolled healthy, regularly-cycling, confirmed ovulatory, reproductive-age individuals with body mass index (BMI) >30 kg/m2 and weight >80 kg in a randomised crossover study. We monitored participants with transvaginal ultrasound and blood sampling for progesterone, luteinising hormone (LH), and estradiol every other day until a dominant follicle measuring >15 mm was visualised. At that point, participants received either oral UPA EC 30 mg or 60 mg and returned for daily monitoring up to 7 days. After a no treatment washout cycle, participants returned for a second monitored cycle and received the other UPA dose. Our primary outcome was the proportion of subjects with no follicle rupture 5 days post-dosing (yes/no). For reference, we also enrolled a control group with BMI <25 kg/m2 and weight <80 kg who received UPA EC 30 mg during a single cycle. We also obtained blood samples for pharmacokinetic parameters for UPA and its active metabolite, N-monodemethyl-UPA (NDM-UPA) as an optional substudy.

Results: We enrolled a total of 52 participants with BMI >30 kg/m2 and 12 controls, with the following cycles completed: 12 controls, 49 UPA 30 mg, and 46 UPA 60 mg. The entire cohort demographics were a mean (SD) age of 29.8 (3.4) years and BMI by group: controls 22.5 (1.4) kg/m2, group 1 37.9 (6.7) kg/m2, and group 2 39.3 (5.4) kg/m2. All 12 (100%) of controls had a delay of at least 5 days for follicle rupture. Among the high BMI group, dosing groups (UPA EC 30 mg vs 60 mg) were similar in the proportion of cycles without follicle rupture over 5 days post-UPA dosing (UPA 30 mg: 47/49 (96%), UPA 60 mg: 42/46 (91%), Fisher's exact test p=0.43). However, after excluding cycles where dosing occurred too late (after LH surge), a delay of at least 5 days occurred in all participants at both doses. The 60 mg UPA dose resulted in a twofold increase in maximum observed concentration and the area under the curve of both UPA and NDM-UPA levels compared with 30 mg.

Conclusion: A standard 30 mg dose of UPA is sufficient to delay ovulation regardless of BMI or weight. Results of our study do not support dose adjustment for body size.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
针对肥胖症患者的双剂量醋酸乌利司他紧急避孕药:随机交叉试验。
研究目的研究设计:研究设计:我们在一项随机交叉研究中招募了健康、定期周期性排卵、身体质量指数(BMI)大于 30 kg/m2、体重大于 80 kg 的育龄人士。我们每隔一天通过经阴道超声波和抽血检测孕酮、黄体生成素(LH)和雌二醇对参与者进行监测,直到观察到一个直径大于 15 毫米的优势卵泡。此时,参与者口服 UPA EC 30 毫克或 60 毫克,并接受长达 7 天的每日监测。在一个无治疗冲洗周期后,受试者返回进行第二个监测周期,并接受另一剂量的 UPA 治疗。我们的主要结果是用药后 5 天没有卵泡破裂的受试者比例(是/否)。作为参考,我们还招募了一个对照组,其 BMI 为 2,体重为 N-单甲基-UPA(NDM-UPA),作为可选的子研究:我们共招募了 52 名体重指数大于 30 kg/m2 的参与者和 12 名对照组,完成了以下周期的研究:对照组 12 人,UPA 30 毫克组 49 人,UPA 60 毫克组 46 人。整个组群的人口统计学特征为:平均(标清)年龄 29.8(3.4)岁,各组的 BMI 分别为:对照组 22.5(1.4)kg/m2,第 1 组 37.9(6.7)kg/m2,第 2 组 39.3(5.4)kg/m2。所有 12 个对照组(100%)的卵泡破裂都延迟了至少 5 天。在高体重指数组中,用药组(UPA EC 30 毫克与 60 毫克)在 UPA 用药后 5 天内无卵泡破裂的周期比例相似(UPA 30 毫克:47/49(96%);UPA EC 60 毫克:47/49(96%)):47/49 (96%),UPA 60 mg:费雪精确检验 p=0.43)。然而,在排除用药过晚(LH激增后)的周期后,所有参与者在两种剂量下都出现了至少 5 天的延迟。与 30 毫克相比,60 毫克 UPA 剂量导致 UPA 和 NDM-UPA 水平的最大观察浓度和曲线下面积增加了两倍:结论:无论体重指数或体重如何,30 毫克标准剂量的 UPA 都足以延迟排卵。我们的研究结果不支持根据体型调整剂量。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
BMJ Sexual & Reproductive Health
BMJ Sexual & Reproductive Health Medicine-Reproductive Medicine
CiteScore
5.10
自引率
6.10%
发文量
38
期刊介绍: BMJ Sexual & Reproductive Health is a multiprofessional journal that promotes sexual and reproductive health and wellbeing, and best contraceptive practice, worldwide. It publishes research, debate and comment to inform policy and practice, and recognises the importance of professional-patient partnership.
期刊最新文献
Shifting discourses, changing interests? How the language of sexual and reproductive health has evolved in the past 50 years. "That's not how abortions happen": a qualitative study exploring how young adults navigate abortion misinformation in the post-Roe era. Attitudes towards the regulation and provision of abortion among healthcare professionals in Britain: cross-sectional survey data from the SACHA Study. Reported side effects from hormonal contraceptives among those seeking abortion care versus contraceptive services. The post-Roe potential of mifepristone and misoprostol in the United States.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1