Allen Connor Luke, Banerjee Saikat, Karoshi Mahantesh, Humaidan Peter, Tahmasebi Farshad
Department of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia.
Western Health, Melbourne, Australia.
Arch Gynecol Obstet. 2025 Jun;311(6):1511-1533. doi: 10.1007/s00404-025-07957-0. Epub 2025 Mar 11.
Alongside being contraceptives, progestins have been investigated as potential anti-inflammatory and analgesic therapies for use in painful gynaecological conditions. This review aims to synthesise evidence pertaining to the efficacy of progestins as analgesics for use in endometriosis, fibroids and pre-menstrual syndrome (PMS).
We conducted a systematic review of the extant literature investigating the analgesic efficacy of progestins compared to any comparator interventions for individuals with the three specified gynaecological conditions. The search was carried out across the PubMed and CENTRAL databases on 7 April 2024 for randomised control trials (RCTs) published in the peer-reviewed literature from 2000 onwards. Data pertaining to analgesic efficacy, assessed by changes in pain indices/scores before and after treatment, were synthesised narratively. Data pertaining to adverse effect frequency and changes in bone mineral density (BMD) were also synthesised narratively. Risk of bias was assessed using the Cochrane risk of bias 2 tool.
The primary search identified 1220 potentially eligible RCTs of which 21 were ultimately included; 19 RCTs related to endometriosis, two related to fibroids and zero related to PMS. Quality assessment identified nine studies to be at a low risk of bias, nine studies with some concerns surrounding bias and three studies to be at a high risk of bias. The included studies represented a total of 2745 participants of whom 1317 were treated with a progestin and 1428 received a comparator intervention. In 18 of the 19 studies concerning endometriosis, progestins produced a statistically significant reduction in pain, further, in five instances progestins were more efficacious in reducing pain than comparator interventions. In both studies on fibroids, progestins produced significant reductions in pain, however, statistically significant differences compared to comparator interventions were not demonstrated. The most frequently cited adverse effect of progestins was spotting/irregular bleeding whilst those receiving comparator interventions most often reported hot flushes; cited in 12 and seven studies respectively. Five studies assessed the impact of progestins and comparators on BMD. Three studies found progestins significantly reduced BMD, however, in these instances reductions were significantly lower than those produced by comparator interventions and in two studies were not statistically significant after 12 months of follow-up.
Our review demonstrates the potential scope for the use of progestins as analgesics in the management of pain associated with endometriosis. Further research will need to be conducted to identify their efficacy in the management of pain associated with fibroids and PMS.
除了作为避孕药具外，孕激素已被研究作为用于治疗妇科疼痛疾病的潜在抗炎和镇痛疗法。本综述旨在综合有关孕激素作为子宫内膜异位症、子宫肌瘤和经前综合征（PMS）镇痛剂疗效的证据。
我们对现有文献进行了系统综述，研究孕激素与任何对照干预措施相比，对患有上述三种特定妇科疾病的个体的镇痛效果。于2024年4月7日在PubMed和CENTRAL数据库中进行检索，查找2000年以来发表在同行评审文献中的随机对照试验（RCT）。通过治疗前后疼痛指数/评分的变化评估的镇痛效果相关数据进行了叙述性综合。与不良反应频率和骨密度（BMD）变化相关的数据也进行了叙述性综合。使用Cochrane偏倚风险2工具评估偏倚风险。
初步检索确定了1220项潜在符合条件的RCT，最终纳入21项；19项RCT与子宫内膜异位症相关，2项与子宫肌瘤相关，0项与PMS相关。质量评估确定9项研究偏倚风险较低，9项研究存在一些偏倚问题，3项研究偏倚风险较高。纳入的研究共有2745名参与者，其中1317名接受孕激素治疗，1428名接受对照干预。在19项关于子宫内膜异位症的研究中的18项中，孕激素使疼痛在统计学上显著减轻，此外，在5例中，孕激素在减轻疼痛方面比对照干预更有效。在两项关于子宫肌瘤的研究中，孕激素均使疼痛显著减轻，然而，与对照干预相比未显示出统计学上的显著差异。孕激素最常被提及的不良反应是点滴出血/不规则出血，而接受对照干预的人最常报告潮热；分别在12项和7项研究中被提及。5项研究评估了孕激素和对照药物对骨密度的影响。3项研究发现孕激素显著降低了骨密度，然而，在这些情况下，降低幅度明显低于对照干预产生的幅度，并且在两项研究中，随访12个月后差异无统计学意义。
我们的综述表明，孕激素作为镇痛剂用于治疗与子宫内膜异位症相关的疼痛具有潜在的应用范围。需要进一步研究以确定其在治疗与子宫肌瘤和经前综合征相关疼痛方面的疗效。
