Study question: How should premature/primary ovarian insufficiency (POI) be diagnosed and managed, based on the best available evidence from published literature?

Summary answer: The current guideline provides 145 recommendations on symptoms, diagnosis, causation, sequelae and treatment of POI.

What is known already: Premature ovarian insufficiency (POI) presents a significant challenge to women's health, with far-reaching implications, both physically and emotionally. The potential implications include adverse effects on quality of life; fertility; and bone, cardiovascular and cognitive health. Although hormone therapy (HT) can mitigate some of these effects, many questions still remain regarding the optimal management of POI.

Study design, size, duration: The guideline was developed according to the structured methodology for development of ESHRE guidelines. Key questions were determined by a group of experts and informed by a scoping survey of women and health care professionals. Literature searches and assessment were then performed. Papers published up to January 30th, 2024, and written in English were included in the guideline. An integrity review was conducted for the randomised controlled trials (RCTs) on POI included in the guideline.

Participants/materials, setting, methods: Based on the collected evidence, recommendations were formulated and discussed within the guideline development group until consensus was reached. Women with lived experience of POI informed the recommendations in general, and particularly on those on provision of care. A stakeholder review was organised after finalisation of the draft. The final version was approved by the guideline development group and the ESHRE Executive Committee.

Main results and the role of chance: New data indicate a higher prevalence of POI, 3.5%, than was previously thought. This guideline aims to help health care professionals to apply best practice care for women with POI. The recent update of the POI guideline covers 40 clinical questions on diagnosis of the condition, the different sequelae, including bone, cardiovascular, neurological and sexual function, fertility and general well-being, and treatment options, including hormone therapy. The list of clinical questions was expanded from the previous iteration of the guideline (2015) based on the scoping survey and appreciation of emerging knowledge of POI. Questions were added on the role of anti-Müllerian hormone (AMH) in the diagnosis of POI, fertility preservation, muscle health, and specific considerations for HT in iatrogenic POI. Additionally, the topic on complementary treatments was extended with specific focus on non-hormonal treatments and lifestyle management options. Significant changes from the previous 2015 guideline include the recommendations that only one elevated FSH >25 IU is required for diagnosis of POI and guidance that AMH testing, repeat FSH measurement and/or AMH may be required where there is diagnostic uncertainty. Recommendations were also updated regarding genetic testing, estrogen doses and regimens, use of the combined oral contraceptive and testosterone therapy. Women with lived experience of POI informed the recommendations on provision of care.

Limitations, reasons for caution: The guideline describes different management options, but it must be acknowledged that for most of these options, supporting evidence is limited for POI.

Wider implications of the findings: The guideline provides health care professionals with clear advice on best practice in POI care, based on the best evidence currently available. In addition, a list of research recommendations is provided to guide further studies in POI.

Study funding/competing interest(s): The guideline was developed and funded by ESHRE, American Society for Reproductive Medicine (ASRM), Centre for Research Excellence in Women's Health in Repoduction Life (CRE-WHiRL) and International Menopause Society (IMS), covering expenses associated with the guideline meetings, literature searches and dissemination of the guideline. The guideline group members did not receive payments. N.P. declared grants from Bayer Pharma (research and consultancy), and NIHR - research POISE; consulting fees from Abbott, Astellas, Bayer, Besins, Lawley, Mithra, Theramex, Viatris; honoraria from Astellas, Bayer, Besins, Gedeon Richter, Theramex, Viatris; support for attending meetings and/or travel from Astellas, Bayer, Theramex, Viatris; President, International Menopause Society, Medical Advisory Committee member, British Menopause Society, Patron Daisy Network. A.J.V. declared grants from Amgen Australia, Australian NHMRC, and Australian MRFF; consulting fees from IQ Fertility; honoraria from the Australasian Menopause Society; participation on a Data Safety Monitoring Board or Advisory Board of Astellas; Board Member of the International Menopause Society (2020 to current) and Past president of the Australasian Menopause Society (2017-2019); R.A.A. declared grants from Roche (Research support, to institution), and participation on a Data Safety Monitoring Board of Bayer. M.C. declared grants from NHI; payments or honoraria from Up-to-Date (as editor/reviewer); Board Member of American Society of Reproductive Medicine, and of American Gynecological and Obstetrical Society. M.D. declared (NIHR - HTA Reference Number: NIHR133461; NIHR - HTA Reference Number: NIHR128757; Action Medical Research and Borne: GN2818); consulting fees from a small personal medical practice, support for attending meetings and/or travel from ESHRE, Bayer and UCLH special Trustees; Participation on the Advisory Board from the British Menopause Society, UKSTORE project, the Progress Educational Trust, and the Turner Syndrome Support Society UK; Leadership or fiduciary roles in the British Fertility Society (Trustee), Elizabeth Garrett Anderson Hospital Charity (chair of Trustees), and the Essex Wynter charitable trust (Trustee). C.E. declared being Chair of a SIG from the Royal Australian College of General Practitioners Integrative Medicine Specific Interest Group and Program Lead for Next Practice Western Sydney Integrative Health. C.H.G. declared grants from Novo Nordisk Foundation (Nos. NNF15OC0016474 and NNF20OC0060610), sygesikringen danmark (No 2022-0189), and the Independent Research Fund Denmark (Nos. 0134-00406 and 0134-00130B); consulting fees from Novo Nordisk, Merck, and Astra Zeneca. S.K. declared grants from Roche diagnostics. A.K. declared grants from NIH R01 5R01HD101475; consulting fees as Medical Reviewer for Flo and for Healthline; honoraria as Medical Consultant for Summus; support for attending meetings from the Reproductive Scientist Development Program; Society for Reproductive Investigation Council Member and Society for Assisted Reproduction Registry / Validation Chair; R.N. declared consulting fees from Astellas, Bayer Pharma, Besins Healthcare, Fidia, Theramex; honoraria from Abbott, Astellas, Exeltis, Fidia, Gedeon Richter, Merck & Co, Novo Nordisk, Shionogi Limited, Theramex, Viatris; payment for expert testimony from Vichy Laboratories; Participation in Data Safety Monitoring Board of Advisory board from Astellas and Bayer Healthcare; President elect of the International Menopause Society (IMS). H.T. declared a grant from NHMRC Centre for Research Excellence for women's health in reproductive life. A.B. declared being chair of the Daisy Network Charity. The other authors have no conflicts of interest to declare.

研究问题：如何根据已发表文献的最佳证据诊断和治疗卵巢功能不全（POI）？

概要回答：目前的指南提供了145条关于POI的症状、诊断、病因、后遗症和治疗的建议。

已知情况：卵巢功能不全（POI）对女性健康构成重大挑战，对身体和情感都有深远影响。潜在的影响包括对生活质量的不利影响；生育能力;以及骨骼、心血管和认知健康。虽然激素治疗（HT）可以减轻这些影响，但关于POI的最佳管理仍然存在许多问题。

研究设计、规模、持续时间：该指南是根据制定ESHRE指南的结构化方法制定的。关键问题由一组专家确定，并由对妇女和保健专业人员进行的范围调查提供信息。然后进行文献检索和评估。2024年1月30日前发表的英文论文纳入指南。对指南中纳入的POI随机对照试验（rct）进行了完整性评价。

参与者/材料、环境、方法：根据收集到的证据，指南制定小组制定并讨论建议，直至达成共识。有POI生活经验的妇女一般地介绍了建议，特别是关于提供护理的建议。在草案定稿后，组织了一次利益相关者审查。指南制定小组和ESHRE执行委员会批准了最终版本。

主要结果和偶然性的作用：新数据表明POI的患病率为3.5%，比之前认为的要高。本指南旨在帮助保健专业人员对患有POI的妇女实施最佳做法护理。最近更新的POI指南涵盖了40个临床问题，涉及该病的诊断、不同的后遗症，包括骨骼、心血管、神经和性功能、生育和一般健康，以及治疗选择，包括激素治疗。根据范围调查和对POI新兴知识的欣赏，临床问题列表从指南的前一次迭代（2015年）扩展。对抗<s:1>勒氏杆菌激素（AMH）在POI诊断中的作用、生育能力保存、肌肉健康以及在医源性POI中对HT的具体考虑提出了疑问。此外，关于补充治疗的主题扩展到具体关注非激素治疗和生活方式管理选择。与2015年之前的指南相比，重大的变化包括建议诊断POI只需要一次FSH升高-25IU，并指导在诊断不确定的情况下可能需要AMH检测、重复FSH测量和/或AMH。还更新了关于基因检测、雌激素剂量和方案、使用口服避孕药和睾酮联合疗法的建议。有POI生活经验的妇女提供了关于提供护理的建议。

局限性，谨慎的原因：指南描述了不同的管理选择，但必须承认，对于大多数这些选择，支持POI的证据是有限的。

研究结果的更广泛影响：该指南根据目前可获得的最佳证据，为卫生保健专业人员提供了关于POI护理最佳实践的明确建议。此外，还提供了一系列研究建议，以指导POI的进一步研究。

研究经费/竞争利益：该指南由ESHRE、美国生殖医学学会（ASRM）、女性生殖健康卓越研究中心（CRE-WHiRL）和国际绝经学会（IMS）制定和资助，包括指南会议、文献检索和指南传播的相关费用。指导小组成员没有收到报酬。N.P.宣布了拜耳制药（研究和咨询）和NIHR-研究POISE的资助；雅培（Abbott）、安斯泰来（Astellas）、拜耳（Bayer）、贝欣（Besins）、劳利（Lawley）、密特拉（Mithra）、Theramex、Viatris的咨询费；来自安斯泰来、拜耳、贝辛斯、Gedeon Richter、Theramex、Viatris的酬金；支持参加会议和/或从安斯泰来、拜耳、Theramex、Viatris出差；国际更年期协会主席，英国更年期协会医学咨询委员会成员，赞助人黛西网络。A.J.V.宣布获得安进澳大利亚、澳大利亚NHMRC和澳大利亚MRFF的资助；IQ Fertility的咨询费；澳大利亚更年期协会的酬金；参与安斯泰来的数据安全监测委员会或咨询委员会；国际更年期协会董事会成员（2020年至今）和澳大利亚更年期协会前任主席（2017-2019）；R.A.A.宣布从罗氏公司获得资助（研究支持，给机构），并参与拜耳公司的数据安全监测委员会。M.C.宣布从NHI获得拨款；来自the-up的报酬或酬金（作为编辑/审稿人）；美国生殖医学学会和美国妇产科学会董事会成员。M.D.申报(NIHR-HTA参考号：NIHR133461；NIHR-HTA参考号：NIHR128757；行动医学研究与传播（GN2818）；小型个人医疗实践的咨询费，ESHRE、拜耳和UCLH特别受托人参加会议和/或旅行的支持；参与英国更年期协会、UKSTORE项目、进步教育信托基金和英国特纳综合征支持协会的咨询委员会；担任英国生育协会（受托人）、伊丽莎白·加勒特·安德森医院慈善机构（受托人主席）和埃塞克斯·温特慈善信托基金（受托人）的领导或受托人角色。C.E.宣布成为澳大利亚皇家全科医师学院综合医学特定兴趣小组和西悉尼综合健康下一步实践项目负责人的SIG主席。C.H.G.宣布获得诺和诺德基金会（No.NNF15OC0016474和NNF20OC0060610）、丹麦sygesikringen（No.2022-0189）和丹麦独立研究基金（No.0134-00406和0134-00130B）的资助；诺和诺德、默克和阿斯利康的咨询费。S.K.宣布获得罗氏诊断公司的资助。A.K.宣布NIH拨款R01 5R01HD101475；作为Flo和Healthline医学审稿人的咨询费；作为Summus医疗顾问的酬金；生殖科学家发展方案为出席会议提供支助；生殖调查学会理事会成员和辅助生殖学会登记/验证主席；R.N.宣布了来自安斯泰来、拜耳制药、贝辛医疗、Fidia、Theramex的咨询费；雅培、安斯泰来、Exeltis、Fidia、Gedeon Richter、默克、诺和诺德、盐野义有限公司、Theramex、Viatris的酬金；支付维希实验室专家证言的费用；参与来自安斯泰来和拜耳医疗保健的数据安全监测咨询委员会；国际更年期学会（IMS）候任主席。H.T.宣布从国家人口与生殖健康委员会卓越研究中心获得一笔关于妇女生殖健康的赠款。a。b。宣布成为黛西慈善网络的主席。其他作者没有利益冲突需要申报。