Premature ovarian insufficiency: the need for evidence on the effectiveness of hormonal therapy

Abstract

Premature ovarian insufficiency (POI) – the loss of ovarian function before the age of 40 years, a decade before natural menopause – is a life-changing diagnosis for women. POI causes significant short-term and long-term morbidity related to estrogen deficiency. The condition is managed by providing exogenous estrogen replacement, usually as the oral contraceptive pill or hormone therapy. These preparations have different estrogen formulations and may have differing benefits and risks. At present, there are no robust data to inform clinical recommendations and women’s decision-making about treatment that they may be taking for many years. The POISE study (Premature Ovarian Insufficiency Study of Effectiveness of hormonal therapy) has been designed to determine whether hormone therapy is superior to combined oral contraceptives on important clinical outcomes and patient-reported symptoms, based on the hypothesis that hormone therapy provides more physiological continuous hormone supplementation with natural estrogens. The study is an open and pragmatic, parallel, randomized controlled trial. The primary outcome is absolute bone mineral density assessed by dual-energy X-ray absorptiometry of the lumbar spine after 2 years of treatment. The study will also investigate cardiovascular markers, symptom relief and acceptability of treatment, and will continue to collect long-term data on fractures and cardiovascular events. Results will inform future guidance on management of POI.

早发性卵巢功能不全：需要激素治疗有效性的证据 摘要

早发性卵巢功能不全（POI）—40岁之前出现卵巢功能衰退, 比自然绝经提前至少10年—是一个会改变女性生活的诊断。POI可导致显著的与雌激素缺乏相关的短期和长期发病率。通过提供外源性雌激素, 通常为口服避孕药或激素治疗来控制这种情况。这些药品具有不同的雌激素制剂, 可能具有不同的益处和风险。目前还没有可靠的数据为临床建议以及给女性可能会应用多年的治疗决策来提供信息。POISE研究（早发性卵巢功能不全激素替代治疗有效性的研究）基于激素替代应用天然雌激素治疗提供了更多的生理连续性激素补充的假设, 旨在确定激素替代治疗在重要临床结果和症状方面是否优于复合口服避孕药。这项研究是一项开放性、实用、平行、随机对照试验。主要指标是在治疗2年后, 通过双能X线骨密度仪评估腰椎的绝对骨密度。该研究还将研究心血管标志物、症状缓解和治疗的可接受性, 并将继续收集有关骨折和心血管事件的长期数据。结果将为POI管理的未来指导提供信息。

Keywords:

• Premature ovarian insufficiency
• hormone therapy
• reproductive health
• bone health
• cardiovascular health

Potential conflict of interest

The authors report no conflict of interest.

Additional information

Funding

This project is funded by National Institute for Health Research (NIHR) HTA Programme [project reference NIHR128757]. The views expressed are those of the authors and not necessarily those of the National Institute of Health Research or the Department of Health and Social Care.