The role of Kisspeptin levels in polycystic ovary syndrome: a systematic review and meta-analysis

Rodrigues, Nicole Paloma de Assis; Laganà, Antonio Simone; Zaia, Victor; Vitagliano, Amerigo; Barbosa, Caio Parente; Oliveira, Renato de; Trevisan, Camila Martins; Montagna, Erik

doi:10.1007/s00404-019-05307-5

Cited by 14 publications

(11 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In women with normal ovaries, high AMH has an inhibitory effect on antral follicle development while low serum AMH is associated with ovulation, pregnancy rate and greater live birth rates [64]. AMH levels are related to increased fasting glucose and insulin levels , testosterone, and BMI in PCOS patients [65]. AMH values higher than 5.1 ng/mL are considered a surrogate marker of hyperandrogenism since positively correlates with total testosterone, 17-hydroxyprogesterone, and LH [66].…”

Section: Discussionmentioning

confidence: 99%

“…AMH values higher than 5.1 ng/mL are considered a surrogate marker of hyperandrogenism since positively correlates with total testosterone, 17-hydroxyprogesterone, and LH [66]. AMH levels are highest when patients have all three major characteristics of PCOS (menstrual disorders, hyperandrogenism, and ultrasound evidence of polycystic ovaries) [65,67].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Pérez‐López

Ornat

López‐Baena

et al. 2021

European Journal of Obstetrics & Gynecology and Reproductiv

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Pérez‐López

Ornat

López‐Baena

et al. 2021

European Journal of Obstetrics & Gynecology and Reproductiv

View full text Add to dashboard Cite

show abstract

“…A series of studies have recently recommended that the KISS1 might get involved in folliculogensis and controlling the maturation of follicles in mammals [ 8 , 11 , 42 ]. In humans, the level of Kisspeptin is higher in polycystic ovarian syndrome patients than control group, suggesting that the Kisspeptin may be a potential biomarker for the diagnosis of polycystic ovarian syndrome [ 43 ]. It is widely known that E2 is mainly synthetized and produced in GCs [ 44 , 45 ], and the survival and proliferation of GCs directly stimulate the synthesis of E2 [ 46 , 47 ] and facilitate the follicular maturation [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

STAT4 targets KISS1 to promote the apoptosis of ovarian granulosa cells

et al. 2020

View full text Add to dashboard Cite

Background In mammals, it is known that the estradiol-17β (E2) is mainly synthetized in ovarian granulosa cells (GCs), and the excessive apoptosis of GCs induces the follicular atresia. Many studies have implicated the essential role of KISS1, with the pro-synthetic effect of E2 and the anti-apoptotic effect on GCs, in the mammalian folliculogenesis, and several STAT4 potential binding sites were previously predicted on the promoter of KISS1 in pigs. However, the biological effects of STAT4 on GCs and the molecular regulation between STAT4 and KISS1 remained largely unknown. Methods Using the porcine GCs as the cellular model, the overexpression plasmid, small interfering RNA, 5′-deletion and luciferase assay were applied to investigate the molecular mechanisms for STAT4 regulating the expression of KISS1. Results In this study, the STAT4 negatively regulated the mRNA and protein levels of KISS1 in porcine GCs, and the mRNA level of STAT4 was observed to significantly decrease from immature to mature follicles, which was inversed with that of KISS1. The relative luciferase activity of KISS1 promoter was significantly increased with deletion of the fourth potential binding site (− 305/− 295), and ChIP further confirmed that the STAT4 bound at − 305/− 295 region of KISS1. Besides, the STAT4 significantly regulated the mRNA levels of PDK1, FOXO3 and TSC2 of PI3K signaling pathway to promote the cell apoptosis and the percentage of cells at G0/G1 phase of cell cycle in GCs. Alternatively, the STAT4 significantly decreased the mRNA levels of CYP17, 3B-HSD, 17B-33 HSD, ESR1, and ESR2, as well as the concentration of E2 in GCs. Furthermore, interfering with the expression of STAT4 was observed to significantly stimulate the pro-synthetic effect of E2 and anti-apoptotic effect of KISS1 in GCs. Conclusions Collectively, the STAT4 might directly target at − 305/− 295 region of KISS1 to negatively regulate the transcription of KISS1, promote the cell apoptosis via PI3K signaling pathway, suppress the synthesis of E2 through the estrogen signaling pathway in porcine GCs. These proposed works could provide useful insight in further investigations on the molecular functionalities of STAT4 and KISS1 in the folliculogenesis of mammals.

show abstract

“…Heterogeneity was tested with τ 2 and I 2 statistics [28], considering values between 50 and 75% moderate, and high if >75%. In addition, a meta-analysis of studies which also presented precocious thelarche (PT) com- pared to CPP was performed, and the KP level related to patient age as previously reported [29]. The Egger test [30], the Baujat plot [31], and the radial plot [27] were used to detect sources of heterogeneity.…”

Section: Discussionmentioning

confidence: 99%

Kisspeptin Levels in Girls with Precocious Puberty: A Systematic Review and Meta-Analysis

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background/Aims: Kisspeptin (KP) is a key player in the regulation of the release of gonadotropin-releasing hormone (GnRH), which increases the secretion of gonadotropin during puberty to establish reproductive function and regulate the hypothalamic-pituitary-gonadal axis. Premature activation of GnRH secretion leads to idiopathic/central gonadotropin-dependent precocious puberty (CPP). We aimed to compare the blood KP concentrations in girls with CPP and healthy controls. Methods: A systematic review and meta-analysis was performed. We searched MEDLINE, EMBASE, The Cochrane Library, and SciELO. Random-effects model and standardized mean difference (SMD) were used. Heterogeneity was assessed through I2. Meta-regression considered patient age, KP fraction, and analytical method for KP measurement. Results: The 11 studies included comprised 316 CPP patients and 251 controls. Higher KP levels in the CPP group were found (SMD 1.53; CI 95% = 0.56–2.51). Subgroup analysis revealed association with patient age (p = 0.048), indicating a positive correlation between elevation in KP concentration and age in CPP group. A group of patients with precocious thelarche (PT) from 5 of the included studies comprising 121 patients showed higher levels of KP (1.10; −0.25–2.45: CI 95%) and high heterogeneity (I2 = 91%). The CPP/PT ratio for KP level indicates KP 36% higher on CPP than PT patients. Conclusions: A consistent difference in KP levels between girls with CPP and controls was identified. While there are important limitations in KP assays which argue against its use as a diagnostic tool, the KP levels in CPP versus control and PT children are consistent with the predicted mechanisms and pathophysiology of CPP.

show abstract

The role of Kisspeptin levels in polycystic ovary syndrome: a systematic review and meta-analysis

Cited by 14 publications

References 42 publications

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

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

STAT4 targets KISS1 to promote the apoptosis of ovarian granulosa cells

Kisspeptin Levels in Girls with Precocious Puberty: A Systematic Review and Meta-Analysis

Contact Info

Product

Resources

About