BACKGROUND The increasing prevalence of obesity worldwide poses a significant threat to reproductive function owing, in part, to hormonal disturbances caused by negative feedback between excess adiposity and the hypothalamic-pituitary-ovarian axis. Consequently, finding the most appropriate strategies to lose weight and improve ovulation in women with overweight or obesity is a clinically relevant matter that needs to be investigated. A comprehensive comparison of the independent and combined efficacy of lifestyle and/or pharmacological interventions on BMI, ovulation, and hormonal profile in women with overweight or obesity at risk of anovulatory infertility would facilitate improving fertility strategies in this population. OBJECTIVE AND RATIONALE This study aimed to evaluate the comparative efficacy of exercise, diet, and pharmacological interventions on BMI, ovulation, and hormonal profile in reproductive-aged women with overweight or obesity. SEARCH METHODS A systematic review was performed by searching PubMed, Scopus, Web of Science, PsycINFO, and Cochrane Library up to 14 December 2023, for randomized controlled trials assessing the effects of exercise, diet and/or pharmacological interventions (i.e. weight-lowering drugs or ovulation inducers) on BMI, ovulation, and/or hormonal profile in reproductive-aged women with overweight or obesity. We performed frequentist random-effect network meta-analyses and rated the certainty of the evidence. The primary outcomes were BMI and ovulation rate, and the secondary outcomes were serum reproductive hormone levels (gonadotrophins, androgens, or oestrogens). We performed sensitivity analyses, including the studies that only involved women with PCOS. OUTCOMES Among 1190 records screened, 148 full texts were assessed for eligibility resulting in 95 trials (9910 women), of which 53% presented a high or unclear risk of bias. The network meta-analyses revealed that, compared to control: diet combined with weight-lowering drugs (mean difference (MD) -2.61 kg/m2; 95% CI -3.04 to -2.19; τ2 = 0.22) and adding exercise (MD -2.35 kg/m2; 95% CI -2.81 to -1.89; τ2 = 0.22) led to the greatest decrease in BMI; exercise combined with diet and ovulation inducers (risk ratio (RR) 7.15; 95% CI 1.94-26.40; τ2 = 0.07) and exercise combined with diet and weight-lowering drugs (RR 4.80; 95% CI 1.67-13.84; τ2 = 0.07) produced the highest increase in ovulation rate; and exercise combined with diet and weight-lowering drugs was the most effective strategy in reducing testosterone levels (standardized mean difference (SMD) -2.91; 95% CI -4.07 to -1.74; τ2 = 2.25), the third most effective strategy in increasing sex hormone-binding globulin levels (SMD 2.37; 95% CI 0.99-3.76; τ2 = 2.48), and it was coupled with being ranked first in terms of free androgen index reduction (SMD -1.59; 95% CI -3.18 to 0.01; τ2 = 1.91). The surface under the cumulative ranking curve scores suggested that: diet combined with weight-lowering drugs is the strategy most likely (94%) to produce the highest BMI reduction; and exercise combined with diet and ovulation inducers is the strategy most likely (89%) to produce the highest ovulation rate improvement. The sensitivity analyses, which exclusively included studies involving women diagnosed with PCOS, were consistent with the results presented above. WIDER IMPLICATIONS Overall, the findings of this network meta-analysis indicate that the combination of exercise, diet, and pharmacological interventions is effective for weight loss, improving ovulation, and normalizing the androgen levels of women with overweight or obesity. Although higher quality studies are needed, these results support that the optimal treatment strategy for women with overweight or obesity wishing to conceive must consider exercise, diet, and pharmacological interventions during the shared decision-making process.

中文翻译：

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运动、饮食和/或药物干预对超重或肥胖育龄妇女 BMI、排卵和荷尔蒙状况的疗效比较：系统评价和网络荟萃分析。


背景 全球肥胖患病率的上升对生殖功能构成重大威胁，部分原因是过度肥胖与下丘脑-垂体-卵巢轴之间的负反馈引起的荷尔蒙紊乱。因此，找到最合适的策略来减轻超重或肥胖女性的体重和改善排卵是一个需要调查的临床相关问题。全面比较生活方式和/或药物干预对有无排卵性不孕风险的超重或肥胖女性 BMI、排卵和荷尔蒙水平的独立和综合疗效，将有助于改善该人群的生育策略。目的和基本原理 本研究旨在评估运动、饮食和药物干预对超重或肥胖育龄妇女 BMI、排卵和荷尔蒙水平的比较疗效。检索方法 通过检索 PubMed、Scopus、Web of Science、PsycINFO 和 Cochrane 图书馆进行系统评价，检索截至 2023 年 12 月 14 日，评估运动、饮食和/或药物干预（即 减重药物或诱导排卵剂）对超重或肥胖育龄妇女的 BMI、排卵和/或荷尔蒙状况的影响。我们进行了频率随机效应网络meta分析，并对证据质量进行了评级。主要结局是 BMI 和排卵率，次要结局是血清生殖激素水平（促性腺激素、雄激素或雌激素）。我们进行了敏感性分析，包括仅涉及PCOS女性的研究。 结果 在筛选的 1190 条记录中，对 148 篇全文进行了合格性评估，导致 95 项试验（9910 名女性），其中 53% 存在高或不明确的偏倚风险。网状荟萃分析显示，与对照组相比：饮食联合减肥药物（平均差 （MD） -2.61 kg/m2;95% CI -3.04 至 -2.19;τ2 = 0.22）和增加运动（MD -2.35 kg/m2;95% CI -2.81 至 -1.89;τ2 = 0.22）导致 BMI 下降幅度最大;运动联合饮食和诱导排卵剂（风险比 （RR）7.15;95% CI 1.94-26.40;τ2 = 0.07）和运动联合饮食和减重药物（RR 4.80;95% CI 1.67-13.84;τ2 = 0.07）产生的排卵率增加最高;运动联合饮食和减重药物是降低睾酮水平的最有效策略（标准化均数差 （SMD）-2.91;95% CI -4.07 至 -1.74;τ2 = 2.25），是增加性激素结合球蛋白水平的第三大有效策略（SMD 2.37;95% CI 0.99-3.76;τ2 = 2.48），并且在游离雄激素指数降低方面排名第一（SMD -1.59;95% CI -3.18 至 0.01;τ2 = 1.91）。累积排名曲线分数下的表面表明： 饮食联合减肥药物是最有可能产生最高 BMI 降低的策略 （94%）;运动结合饮食和诱导排卵剂是最有可能 （89%） 产生最高排卵率改善的策略。敏感性分析仅包括涉及被诊断患有 PCOS 的女性的研究，与上述结果一致。 更广泛的影响 总体而言，这项网络荟萃分析的结果表明，运动、饮食和药物干预的结合可有效减轻体重、改善排卵并使超重或肥胖女性的雄激素水平正常化。尽管需要更高质量的研究，但这些结果支持希望怀孕的超重或肥胖女性的最佳治疗策略必须在共同决策过程中考虑运动、饮食和药物干预。