促性腺激素释放激素（GnRH）激动剂亮丙瑞林对患有严重多囊肝病的绝经前女性肝体积的影响。
完整摘要 · 中文译文
背景：多囊肝病（PLD）以多发肝囊肿为特征，有时可导致肝脏严重增大，并伴有相关的躯体及社会心理不适。治疗选择有限。女性是PLD的危险因素；雌激素补充会使PLD女性的肝脏体积增大，而绝经后多囊肝则缩小。因此，雌激素可能是治疗的一个靶点。 方法：在这项前瞻性、开放标签研究中，18-45岁患有严重PLD的绝经前女性按1：1随机分配至直接开始使用促性腺激素释放激素激动剂亮丙瑞林（n=6）组，或随机分配后18个月延迟开始使用亮丙瑞林的标准治疗（n=8）组。促性腺激素释放激素激动剂（11.25 mg注射剂，每3个月一次）可降低雌激素和孕激素水平，从而导致药物性绝经。主要结局为18个月时的肝脏生长速率。次要结局包括生活质量、绝经相关副作用和不良事件。由于出现了明显的副作用，在所有参与者达到第18个月时进行了期中分析。 结果：在直接开始使用亮丙瑞林的组中，半数参与者的肝脏体积仍在增加，中位肝脏生长速率与标准治疗组相比无显著差异（分别为4.04[-4.62至6.84]%/年 vs. 11.0[0.70-13.2]%/年，p=0.15）。重要的是，PLD相关生活质量并未因治疗而改善，而绝经相关副作用却很严重，导致一名参与者停止治 早期治疗。直接治疗组与标准治疗组的不良事件总数分别为38例和9例（p<0.001）。鉴于这些结果，该研究被提前终止。 结论：亮丙瑞林治疗未能逆转肝脏体积，而绝经相关副作用和不良事件相当明显。
完整摘要 · 英文原文
BACKGROUND: Polycystic liver disease (PLD) is characterized by multiple liver cysts, sometimes leading to severe liver enlargement, with associated physical and psychosocial complaints. Treatment options are limited. Female gender is a risk factor for PLD; estrogen supplementation increases liver size in women with PLD, whereas the polycystic liver decreases after menopause. Estrogens may therefore be a target for therapy. METHODS: In this prospective, open-label study, premenopausal women aged 18-45 years with severe PLD were randomized 1:1 to a direct start of the gonadotropin-releasing hormone agonist leuprorelin (n=6) or to standard care with delayed start of leuprorelin 18 months after randomization (n=8). The gonadotropin-releasing hormone agonist (11.25 mg injections once every 3 mo) leads to a reduction in estrogens and progesterone, and consequently to medically induced menopause. The primary outcome was liver growth rate at 18 months. Secondary outcomes comprised quality of life, menopausal side effects, and adverse events. An interim analysis was performed when all participants had reached month 18, as notable side effects were expressed. RESULTS: In the group with direct start of leuprorelin, liver volume still increased in half of the participants, with the median liver growth rate not significantly different from the standard care group (4.04 [-4.62 to 6.84] vs. 11.0 [0.70-13.2] %/year, respectively, p=0.15). Importantly, PLD-related quality of life did not improve with treatment, whereas menopausal side effects were severe, leading one participant to stop treatment early. The total number of adverse events in the direct versus standard care group was 38 versus 9, respectively (p<0.001). Because of these results, the study was terminated early. CONCLUSIONS: leuprorelin treatment did not reverse liver volume, while menopausal side effects and adverse events were substantial.