Circulating kisspeptin and anti-müllerian hormone levels, and insulin resistance in women with polycystic ovary syndrome: A systematic review, meta-analysis, and meta-regression

Abstract

Objective: This systematic review and meta-analysis aimed to summarize the available evidence regarding circulating kisspeptin and anti-müllerian hormone (AMH) and the homeostasis model assessment of insulin resistance (HOMA-IR) index in adolescents and women with and without polycystic ovary syndrome (PCOS).Method: We performed a comprehensive literature search in Medline, Embase, Cochrane, Scopus, and Web of Science for studies evaluating circulating kisspeptin levels in women with and without PCOS published until September 24th, 2020. Coprimary outcomes were the HOMA-IR index and AMH. The quality of included studies was assessed using the Newcastle-Ottawa Scale. Random-effects models were used to estimate outcomes, and effects reported as mean difference (MD) or standardized MD (SMD) and their 95% confidence interval (CI). The systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42020205030. Results: We evaluated 18 studies including, 1,282 PCOS cases and 977 controls. Participants with PCOS were younger (MD=-2.38 years, 95%CI -4.32 to -0.44), with higher BMI (MD=1.16, 95% CI 0.54 to 1.78), waist-to-hip ratio (MD=0.04, 95%CI 0.02 to 0.05), circulating kisspeptin (SMD=1.15, 95%CI 0.68 to 1.62), luteinizing hormone (SMD=1.29, 95%CI 0.76 to 1.83), AMH (SMD=0.97, 95%CI 0.60 to 1,34), total testosterone (SMD=2.48, 95%CI 1.73 to 3.23), free testosterone (SMD=1.37, 95%CI 0.56 to 2.17), and dehydroepiandrosterone sulfate (SMD=0.72, 95%CI 0.32 to 1.13) levels, and Ferriman-Galweg score (SMD = 5.08, 95%CI 2.76 to 7.39), and lower sex hormone-binding globulin level (SMD=-1.34, 95%CI -2.15 to -0.52). Besides, participants with PCOS had higher HOMA-IR index (SMD=0.76, 95%CI 0.35 to 1.17), and circulating insulin (SMD=0.75, 95%CI 0.30 to 1.19), leptin (SMD=2.82, 95%CI 1.35 to 4.29), and triglycerides (SMD=2.15, 95%CI 1.08 to 3.23) levels than participants without the syndrome. The meta-regression did not identify significant factors influencing circulating kisspeptin. Conclusion:Patients with PCOS showed higher kisspeptin, LH, insulin, AMH, and androgen levels and HOMA-IR index, and lower sex hormone-binding globulin levels than those without the syndrome.

Neuroendocrine Determinants of Polycystic Ovary Syndrome

“…Liu et al [ 37 ] have proposed a broader hypothesis in that kisspeptin can be regarded as an independent biomarker of PCOS. This proposition was made on the basis of a large meta-analysis (1282 participants: 699 patients and 583 controls) which noted that serum kisspeptin levels were higher in patients with PCOS compared to non-PCOS patients.…”

Advances in Neuroendocrine Research on Polycystic Ovary Syndrome: New Hope for Treatment Decoding the Link between Hormones and the Brain

“…Out of 12 studies in patients with PCOS, eight showed significantly higher serum levels of kisspeptin. Pérez-López et al 23 broadening hypothesis states that kisspeptin can be viewed as a separate PCOS biomarker. This claim was based on a comprehensive meta-analysis that included 1282 people, including 699 patients and 583 controls, and found that blood kisspeptin levels were greater in PCOS patients than in non-PCOS patients.…”

The role of gonadotropin‐releasing hormone neurons in polycystic ovary syndrome

“…128,[131][132][133] In addition, KNDy neurons are considered to at least partly mediate sex steroid negative feedback on GnRH secretion. 129,132,134 Women with PCOS appear to have elevated circulating kisspeptin levels (standardized mean difference 1.15 with 95% confidence interval 0.68-1.62) 135 ; the source of this kisspeptin is unknown but is unlikely to be the brain. Women with PCOS may be more likely to harbor the GG genotype of the kisspeptin gene polymorphism rs4889.…”