Comparative efficacy of exercise, diet and/or pharmacological interventions on BMI, ovulation, and hormonal profile in reproductive-aged women with overweight or obesity: a systematic review and network meta-analysis

• Published in: Human reproduction update 2024-07, Vol.30 (4), p.472-487
• Main Authors: Ruiz-González, David, Cavero-Redondo, Iván, Hernández-Martínez, Alba, Baena-Raya, Andrés, Martínez-Forte, Sonia, Altmäe, Signe, Fernández-Alonso, Ana M, Soriano-Maldonado, Alberto
• Format: Article
• Language: English
• Subjects: Adult; Body Mass Index; Diet; Exercise; Female; Humans; Medicin och hälsovetenskap; Network Meta-Analysis; Obesity - blood; Obesity - complications; Obesity - diet therapy; Obesity - therapy; Overweight - blood; Overweight - complications; Overweight - diet therapy; Overweight - therapy; Ovulation - drug effects; Review
• ISSN: 1355-4786; 1460-2369; 1460-2369
• DOI: 10.1093/humupd/dmae008

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. 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. 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. 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 (stand