背景:他汀类药物是具有多效作用的降脂药。专家建议,除了改善与多囊卵巢综合征(PCOS)相关的血脂异常,他汀类药物还可以发挥其他有益的代谢和内分泌作用,比如降低睾丸激素水平。这是2011年首次发布的Cochrane评论的更新。
目的:评估他汀类药物治疗未积极尝试受孕的PCOS患者的疗效和安全性。
方法:我们搜索了Cochrane妇科和生育组的专业注册,中部,MEDLINE,Embase,PsycINFO,CINAHLs,以及2022年11月7日正在进行的四项试验登记。我们还手工搜索了相关会议记录和相关试验的参考列表,以获得任何其他研究,我们联系了该领域的专家进行进一步的研究。
方法:我们纳入了随机对照试验(RCT),该试验评估了他汀类药物治疗对未积极尝试受孕的PCOS女性的影响。合格的比较是他汀类药物与安慰剂或不治疗,他汀类药物加另一种药物与单独的另一种药物相比,和他汀类药物对抗另一种药物。我们使用ReviewManager5进行统计分析,并使用GRADE方法评估证据的确定性。
方法:我们使用标准Cochrane方法。我们的主要结果是月经规律的恢复和自发排卵的恢复。我们的次要结果是临床和生理指标,包括多毛症,痤疮严重程度,睾酮水平,和不良事件。
结果:六个RCT符合纳入标准。他们包括396名患有PCOS的女性,她们接受了六周的治疗,三个月,或六个月的治疗;374名妇女完成了研究。三项研究评估了辛伐他汀的作用,三项研究评估了阿托伐他汀的作用。我们总结了以下比较的研究结果。他汀类药物与安慰剂(3个随机对照试验)一项试验测量月经规律的恢复作为月经周期的天数。我们不确定他汀类药物与安慰剂相比是否缩短了月经周期的平均长度(平均差(MD)-2.00天,95%置信区间(CI)-24.86至20.86;37名参与者;非常低的确定性证据)。没有研究报告自发排卵恢复,改善多毛症,或改善痤疮。我们不确定他汀类药物与安慰剂相比是否在六周后降低睾丸激素水平(MD0.06,95%CI-0.72至0.84;1个RCT,20名参与者;确定性非常低的证据),3个月后(MD-0.53,95%CI-1.61至0.54;2项随机对照试验,64名参与者;确定性非常低的证据),或6个月后(MD0.10,95%CI-0.43至0.63;1个RCT,28名参与者;非常低的确定性证据)两项研究记录了不良事件,两组间均无显著差异。他汀类药物加二甲双胍与单独的二甲双胍(1个RCT)在该比较中包括的单个RCT测量月经规律的恢复为每6个月的自发月经次数。我们不确定他汀类药物加二甲双胍与二甲双胍相比是否能改善月经规律的恢复(MD0.60次月经,95%CI0.08至1.12;69名参与者;非常低的确定性证据)。该研究没有报告自发排卵的恢复。我们不确定他汀类药物加二甲双胍与单独使用二甲双胍相比是否可以改善多毛症,使用Ferriman-Gallwey评分(MD-0.16,95%CI-0.91至0.59;69名参与者;非常低的确定性证据),痤疮严重程度以0至3的量表(MD-0.31,95%CI-0.67至0.05;69名参与者;非常低的确定性证据),或睾酮水平(MD-0.03,95%CI-0.37至0.31;69名参与者;非常低的确定性证据)。该研究报告没有发生显著的不良事件。他汀类药物加口服避孕药与单独口服避孕药(1个RCT)比较该比较中包括的单个RCT没有报告月经规律或自发排卵的恢复。我们不确定他汀类药物加口服避孕药(OCP)是否比单独使用OCP改善多毛症(MD-0.12,95%CI-0.41至0.17;48名参与者;非常低的确定性证据)。该研究没有报告痤疮严重程度的改善。我们也不确定他汀类药物加OCP与单独OCP相比是否能降低睾酮水平,因为证据的确定性非常低(MD-0.82,95%CI-1.38~-0.26;48名参与者).该研究报告说,没有参与者出现明显的副作用。他汀类药物与二甲双胍(2个RCT)相比,与二甲双胍(每六个月自发月经数)相比,他汀类药物是否可以改善月经规律(MD0.50月经,95%CI-0.05至1.05;1个RCT,61名与会者,非常低的确定性证据)。没有研究报告自发排卵恢复。我们不确定他汀类药物与二甲双胍相比是否可以减少使用Ferriman-Gallwey评分测量的多毛症(MD-0.26,95%CI-0.97至0.45;1RCT,61名参与者;非常低的确定性证据),痤疮严重程度以0至3的等级测量(MD-0.18,95%CI-0.53至0.17;1RCT,61名参与者;非常低的确定性证据),或睾酮水平(MD-0.24,95%CI-0.58至0.10;1个RCT,61名参与者;非常低的确定性证据)。两项试验均报告未发生明显的不良事件。根据研究报告,他汀类药物与口服避孕药加氟他胺(1RCT)相比,没有参与者出现任何明显的副作用.没有其他主要结果的可用数据。
结论:本综述所有主要结果的证据的确定性非常低。由于证据有限,我们不确定他汀类药物是否与安慰剂相比,或他汀类药物加二甲双胍与单独二甲双胍相比,改善月经恢复规律。评估他汀类药物加OCP与单独OCP的试验均未报告我们的主要结局。没有其他研究报道自发排卵的恢复。我们不确定他汀类药物是否能改善多毛症,痤疮严重程度,或睾丸激素。所有测量不良事件的试验均报告两组间无显著差异。
Statins are lipid-lowering agents with pleiotropic actions. Experts have proposed that in addition to improving the dyslipidaemia associated with polycystic ovary syndrome (PCOS), statins may also exert other beneficial metabolic and endocrine effects, such as reducing testosterone levels. This is an update of a Cochrane Review first published in 2011.
To assess the efficacy and safety of statin therapy in women with PCOS who are not actively trying to conceive.
We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHLs, and four ongoing trials registers on 7 November 2022. We also handsearched relevant conference proceedings and the reference lists of relevant trials for any additional studies, and we contacted experts in the field for any further ongoing studies.
We included randomised controlled trials (RCTs) that evaluated the effects of statin therapy in women with PCOS not actively trying to conceive. Eligible comparisons were statin versus placebo or no treatment, statin plus another agent versus the other agent alone, and statin versus another agent. We performed statistical analysis using Review Manager 5, and we assessed the certainty of the evidence using GRADE methods.
We used standard Cochrane methodology. Our primary outcomes were resumption of menstrual regularity and resumption of spontaneous ovulation. Our secondary outcomes were clinical and physiological measures including hirsutism, acne severity, testosterone levels, and adverse events.
Six RCTs fulfilled the criteria for inclusion. They included 396 women with PCOS who received six weeks, three months, or six months of treatment; 374 women completed the studies. Three studies evaluated the effects of simvastatin and three studies evaluated the effects of atorvastatin. We summarised the results of the studies under the following comparisons. Statins versus placebo (3 RCTs) One trial measured resumption of menstrual regularity as menstrual cycle length in days. We are uncertain if statins compared with placebo shorten the mean length of the menstrual cycle (mean difference (MD) -2.00 days, 95% confidence interval (CI) -24.86 to 20.86; 37 participants; very low-certainty evidence). No studies reported resumption of spontaneous ovulation, improvement in
hirsutism, or improvement in acne. We are uncertain if statins compared with placebo reduce testosterone levels after six weeks (MD 0.06, 95% CI -0.72 to 0.84; 1 RCT, 20 participants; very low-certainty evidence), after 3 months (MD -0.53, 95% CI -1.61 to 0.54; 2 RCTs, 64 participants; very low-certainty evidence), or after 6 months (MD 0.10, 95% CI -0.43 to 0.63; 1 RCT, 28 participants; very low-certainty evidence) Two studies recorded adverse events, and neither reported significant differences between the groups. Statins plus metformin versus metformin alone (1 RCT) The single RCT included in this comparison measured resumption of menstrual regularity as the number of spontaneous menses per six months. We are uncertain if statins plus metformin compared with metformin improves resumption of menstrual regularity (MD 0.60 menses, 95% CI 0.08 to 1.12; 69 participants; very low-certainty evidence). The study did not report resumption of spontaneous ovulation. We are uncertain if statins plus metformin compared with metformin alone improves
hirsutism measured using the Ferriman-Gallwey score (MD -0.16, 95% CI -0.91 to 0.59; 69 participants; very low-certainty evidence), acne severity measured on a scale of 0 to 3 (MD -0.31, 95% CI -0.67 to 0.05; 69 participants; very low-certainty evidence), or testosterone levels (MD -0.03, 95% CI -0.37 to 0.31; 69 participants; very low-certainty evidence). The study reported that no significant adverse events occurred. Statins plus oral contraceptive pill versus oral contraceptive pill alone (1 RCT) The single RCT included in this comparison did not report resumption of menstrual regularity or spontaneous ovulation. We are uncertain if statins plus the oral contraceptive pill (OCP) improves
hirsutism compared with OCP alone (MD -0.12, 95% CI -0.41 to 0.17; 48 participants; very low-certainty evidence). The study did not report improvement in acne severity. We are also uncertain if statins plus OCP compared with OCP alone reduces testosterone levels, because the certainty of the evidence was very low (MD -0.82, 95% CI -1.38 to -0.26; 48 participants). The study reported that no participants experienced significant side effects. Statins versus metformin (2 RCTs) We are uncertain if statins improve menstrual regularity compared with metformin (number of spontaneous menses per six months) compared to metformin (MD 0.50 menses, 95% CI -0.05 to 1.05; 1 RCT, 61 participants, very low-certainty evidence). No studies reported resumption of spontaneous ovulation. We are uncertain if statins compared with metformin reduce
hirsutism measured using the Ferriman-Gallwey score (MD -0.26, 95% CI -0.97 to 0.45; 1 RCT, 61 participants; very low-certainty evidence), acne severity measured on a scale of 0 to 3 (MD -0.18, 95% CI -0.53 to 0.17; 1 RCT, 61 participants; very low-certainty evidence), or testosterone levels (MD -0.24, 95% CI -0.58 to 0.10; 1 RCT, 61 participants; very low-certainty evidence). Both trials reported that no significant adverse events had occurred. Statins versus oral contraceptive pill plus flutamide (1 RCT) According to the study report, no participants experienced any significant side effects. There were no available data for any other main outcomes.
The evidence for all main outcomes of this review was of very low certainty. Due to the limited evidence, we are uncertain if statins compared with placebo, or statins plus metformin compared with metformin alone, improve resumption of menstrual regularity. The trial evaluating statin plus OCP versus OCP alone reported neither of our primary outcomes. No other studies reported resumption of spontaneous ovulation. We are uncertain if statins improve
hirsutism, acne severity, or testosterone. All trials that measured adverse events reported no significant differences between the groups.