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

Faustino R Pérez-López,Lía Ornat,María T López-Baena,Javier Santabárbara,Ricardo Savirón-Cornudella,Gonzalo R Pérez-Roncero

doi:10.1016/j.ejogrb.2021.03.007

Abstract

ObjectiveThis 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). MethodWe 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. Co-primary 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. ResultsWe evaluated 18 studies including, 1282 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 0.54–1.78), waist-to-hip ratio (MD = 0.04, 95 %CI 0.02 to 0.05), circulating kisspeptin (SMD = 1.15, 95 %CI 0.68–1.62), luteinizing hormone (SMD = 1.29, 95 %CI 0.76–1.83), AMH (SMD = 0.97, 95 %CI 0.60–1,34), total testosterone (SMD = 2.48, 95 %CI 1.73–3.23), free testosterone (SMD = 1.37, 95 %CI 0.56–2.17), and dehydroepiandrosterone sulphate (SMD = 0.72, 95 %CI 0.32–1.13) levels, and Ferriman-Gallwey score (SMD = 5.08, 95 %CI 2.76–7.39), 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 0.35–1.17), and circulating insulin (SMD = 0.75, 95 %CI 0.30–1.19), leptin (SMD = 2.82, 95 %CI 1.35–4.29), and triglycerides (SMD = 2.15, 95 %CI 1.08–3.23) levels than participants without the syndrome. The meta-regression did not identify significant factors influencing circulating kisspeptin. ConclusionPatients 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.

Highlights

Kisspeptins are a group of brain neuropeptides initially described as metastasis suppressors [1]
Adolescents and women with polycystic ovary syndrome (PCOS) have high kisspeptin levels associated with increased insulin, luteinizing hormone (LH), anti-müllerian hormone (AMH), total and free testosterone, and dehydroepiandrosterone sulfate (DHEA-S), and lower Sex hormone-binding globulin (SHBG) levels
The homeostasis model assessment of insulin resistance (HOMA-IR) index, and circulating insulin, leptin, and triglycerides are higher in patients with PCOS

Summary

Introduction

Kisspeptins are a group of brain neuropeptides initially described as metastasis suppressors [1]. The kisspeptin precursor has 145 amino acids that, by proteolysis, produce kisspeptin-54 ( know as metastin) that is considered the active product. Kisspeptin 13 and kisspeptin-14 are products from the degradation of kisspeptin-54 [2,3]. Kisspeptin is expressed in discrete brain regions, it is present in peripheral tissues like fat, liver, and pancreas [4]. Women with PCOS have an increased expression of kisspeptin receptors in granulosa lutein cells [6]. Clinical studies reported variable and heterogeneous results concerning circulating kisspeptin levels in women with PCOS [7,8]

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Discussion

Conclusion