-
Current Medicinal Chemistry Jan 2024Kisspeptin was initially known as metastin for its role in suppressing metastasis in melanoma and breast cancer. Later, based on its ability to stimulate GPR54, its...
BACKGROUND
Kisspeptin was initially known as metastin for its role in suppressing metastasis in melanoma and breast cancer. Later, based on its ability to stimulate GPR54, its importance in maintaining an intact hypothalamic-pituitary-ovarian axis was recognised, which is the basis for the widespread application of the drug in several conditions such as secondary amenorrhea, regulation of puberty onset, ovarian function, trophoblast invasion, fertility regulation, parturition, and lactation. This systematic study aims to evaluate the current status of kisspentin in clinical trials.
METHODS
The keywords 'kisspeptin' or 'metastin' were used in the clinicaltrials.gov website and Clinical Trial Registry of India (CTRI) to find eligible clinical trials or records carried out without time constraints until February 26, 2023.
RESULTS
A total of 33 records were identified through clinical trial databases. All records were screened, and four trials were rejected as they failed to meet the inclusion criteria. Finally, 29 (87.9%) reports of interventional clinical trials with kisspeptin were reviewed.
CONCLUSION
Kisspeptin can be viewed as a multipurpose drug with considerably fewer side effects due to its effects simulating normal physiological processes in our body.
PubMed: 38265397
DOI: 10.2174/0109298673251224230919093656 -
The Journal of Maternal-fetal &... Dec 2023A highly accurate serum marker for predicting viable pregnancy needs to be developed. Recent studies have demonstrated that kisspeptin is a potential biomarker for this...
OBJECTIVE
A highly accurate serum marker for predicting viable pregnancy needs to be developed. Recent studies have demonstrated that kisspeptin is a potential biomarker for this purpose.
METHODS
This systematic review evaluated the available data in the literature on the role of kisspeptin as a miscarriage biomarker. A literature search was conducted in the PubMed/Medline, Embase, Web of Science, and Scopus databases using the following keywords: (kisspeptin) AND (miscarriage OR pregnancy loss OR spontaneous abortion OR reproductive failure).
RESULTS
Seven case-control studies were selected for the systematic review. The included papers described the potential role of kisspeptin as a putative biomarker of pregnancy loss. Furthermore, two studies reported that changes in kisspeptin levels may be associated with unexplained infertility and low rates of embryo implantation in women undergoing assisted reproductive technology.
CONCLUSION
Kisspeptin might be used as a potential biomarker of pregnancy viability in the near future. However, studies with better evidence are needed to establish the applicability of kisspeptin as a diagnostic and prognostic tool.
Topics: Pregnancy; Female; Humans; Abortion, Spontaneous; Kisspeptins; Infertility; Reproductive Techniques, Assisted; Biomarkers; Pregnancy Rate; Live Birth; Fertilization in Vitro
PubMed: 37015836
DOI: 10.1080/14767058.2023.2197097 -
Reproductive Sciences (Thousand Oaks,... Dec 2022The objective of this study is to investigate whether kisspeptin levels in early pregnancy have a better diagnostic value on early pregnancy outcome as compared with... (Meta-Analysis)
Meta-Analysis Review
The objective of this study is to investigate whether kisspeptin levels in early pregnancy have a better diagnostic value on early pregnancy outcome as compared with human chorionic gonadotropin (hCG). This study was a systematic review and meta-analysis aiming to investigate the diagnostic value of kisspeptin levels on early pregnancy outcome. The primary outcome was miscarriage or viable intrauterine pregnancy. Five studies were included for systematic review, and three studies were included for meta-analysis. Meta-analysis showed kisspeptin levels had a good diagnostic value with the area under the curve (AUC) 0.902 (0.866, 0.937) when kisspeptin was measured after 6 weeks of gestation. Sensitivity analysis demonstrated kisspeptin levels had a diagnostic value with AUC = 0.881 (0.855, 0.906). hCG levels had a diagnostic value with AUC = 0.834 (0.785, 0.883), which was inferior to the diagnostic value of kisspeptin (mean difference = 0.09 (0.02, 0.16)). Kisspeptin measurement has a potential for comparable or even higher accuracy than hCG in differentiating between miscarriage and viable intrauterine pregnancy after 6 weeks of gestation.
Topics: Female; Pregnancy; Humans; Kisspeptins; Chorionic Gonadotropin; Abortion, Spontaneous; Pregnancy Outcome; Pregnancy Trimester, First
PubMed: 35212930
DOI: 10.1007/s43032-022-00856-8 -
Gynecological Endocrinology : the... Dec 2021There are contradictory data concerning kisspeptin in gravids with preeclampsia and gestational hypertension (GH). (Meta-Analysis)
Meta-Analysis
BACKGROUND
There are contradictory data concerning kisspeptin in gravids with preeclampsia and gestational hypertension (GH).
OBJECTIVE
To conduct a meta-analysis of studies comparing maternal kisspeptin levels in gravids with and without preeclampsia or GH.
MATERIAL AND METHODS
We searched PubMed, LILACS, and CNKI list of articles up to 20 August 2021, without language limitations, comparing circulating maternal kisspeptin levels, and maternal and neonatal outcomes in gravids with and without preeclampsia or GH. Meta-analyzed results are reported as standardized mean differences (SMD), and their 95% confidence interval (CI).
RESULTS
Seven studies with a low-to-moderate risk of bias were eligible for meta-analysis. Gravids with preeclampsia or GH displayed significantly lower circulating kisspeptin levels (SMD, -0.68, 95% CI, -1.04 to -0.32), lower gestational ages at delivery (SMD, -2.22, 95% CI, -3.25 to -1.18), and birth weight (SMD, -2.16, 95% CI, -3.15 to -1.17), and significantly higher body mass indices (MD, 0.56, 95% CI, 0.24-0.88), systolic (SMD, 2.87, 95% CI, 2.22-3.53), and diastolic blood pressures (SMD, 2.57, 95% CI, 2.19-2.95).
CONCLUSION
Gravids with preeclampsia or GH had lower kisspeptin levels as compared to normotensive controls.
Topics: Female; Humans; Kisspeptins; Pre-Eclampsia; Pregnancy
PubMed: 34779331
DOI: 10.1080/09513590.2021.2004396 -
Hormone Research in Paediatrics 2020Kisspeptin (KP) is a key player in the regulation of the release of gonadotropin-releasing hormone (GnRH), which increases the secretion of gonadotropin during puberty... (Meta-Analysis)
Meta-Analysis
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.
Topics: Case-Control Studies; Child; Female; Humans; Kisspeptins; Puberty, Precocious
PubMed: 33887744
DOI: 10.1159/000515660 -
European Journal of Obstetrics,... May 2021This systematic review and meta-analysis aimed to summarize the available evidence regarding circulating kisspeptin and anti-müllerian hormone (AMH) and the homeostasis... (Meta-Analysis)
Meta-Analysis
Circulating kisspeptin and anti-müllerian hormone levels, and insulin resistance in women with polycystic ovary syndrome: A systematic review, meta-analysis, and meta-regression.
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. 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.
RESULTS
We 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.
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.
Topics: Adolescent; Anti-Mullerian Hormone; Female; Humans; Insulin Resistance; Kisspeptins; Polycystic Ovary Syndrome
PubMed: 33744505
DOI: 10.1016/j.ejogrb.2021.03.007 -
Reproductive Sciences (Thousand Oaks,... Feb 2020Polycystic ovary syndrome (PCOS) affects 6% to 20% of reproductive age women and is the most frequent cause of anovulatory infertility. Its physiopathology may result in...
Polycystic ovary syndrome (PCOS) affects 6% to 20% of reproductive age women and is the most frequent cause of anovulatory infertility. Its physiopathology may result in part from hypothalamic alterations in the pulsatile secretion of gonadotropin-releasing hormone (GnRH). The neuropeptide kisspeptin participates in the mechanism through stimulation of the hormone's production. The purpose of this study was to review the articles which compared kisspeptin levels in women with PCOS with those of controls. A systematic review of observational studies was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations. The selected studies encompassed a population of patients with PCOS and controls, whose serum kisspeptin levels were evaluated. The studies were retrieved from the Medline, Cochrane, and Embase databases, and four of them were chosen for the review. In most studies, the serum kisspeptin levels were higher in women with PCOS than in controls notwithstanding the BMI. One of the articles showed that circulating plasma levels of kisspeptin were significantly higher in women with PCOS whose BMI was lower than 25 than in obese and overweight women. Our data suggest a higher concentration of serum kisspeptin in women with PCOS irrespective of their BMI. Further experimental and clinical studies are needed to ascertain the role of kisspeptin in PCOS.
Topics: Animals; Female; Humans; Kisspeptins; Observational Studies as Topic; Polycystic Ovary Syndrome
PubMed: 31919796
DOI: 10.1007/s43032-019-00085-6 -
Archives of Gynecology and Obstetrics Nov 2019Polycystic ovarian syndrome (PCOS) is a complex and not fully elucidated pathology. This prevalent endocrinopathy affects patients in reproductive age, impacts on... (Meta-Analysis)
Meta-Analysis
PURPOSE
Polycystic ovarian syndrome (PCOS) is a complex and not fully elucidated pathology. This prevalent endocrinopathy affects patients in reproductive age, impacts on estrogen-dependent diseases, as well as in infertility. In this context, Kisspeptin (KP) may be considered a potential biomarker for PCOS diagnosis and follow-up. Here, we aimed to verify the levels of KP in obese and non-obese patients with PCOS, their relationship with other hormones, in comparison to healthy controls.
METHODS
A systematic review and meta-analysis were performed according to the PRISMA guidelines. We searched MEDLINE, EMBASE, PsycINFO, Global Health, The Cochrane Library, Health Technology Assessment Database, and Web of Science for eligible studies. A random effects model meta-analysis of standardized mean difference (SMD) was conducted and the I was used to assess heterogeneity. Meta-regression was conducted through mixed-effects model.
RESULTS
A total of 12 studies were included, comprising 660 PCOS patients and 600 controls. The KP levels were lower in the control group (0.76: 0.17-1.35; 95% CI). In the subgroup analyses, patients were divided in non-overweight/obese (BMI < 25) and overweight/obese (BMI ≥ 25) groups. The meta-regression revealed a difference between the obese and non-obese groups (z = 2.81; p = 0.0050).
CONCLUSIONS
PCOS patients showed higher KP levels than control, and obese non-PCOS patients also showed altered KP levels. All studies had poor descriptions of sample collection, pre-analytical and analytical procedures, which is critical considering structural characteristics of the KP molecule.
Topics: Adult; Biomarkers; Female; Humans; Kisspeptins; Polycystic Ovary Syndrome; Risk Assessment
PubMed: 31584133
DOI: 10.1007/s00404-019-05307-5 -
Reproductive Biomedicine Online Oct 2019A close association between Kisspeptin-1 (KISS-1) and reproductive physiology has been reported, but the results on circulatory KISS-1 are ambiguous in patients with... (Meta-Analysis)
Meta-Analysis
RESEARCH QUESTION
A close association between Kisspeptin-1 (KISS-1) and reproductive physiology has been reported, but the results on circulatory KISS-1 are ambiguous in patients with polycystic ovary syndrome (PCOS). A systematic review and meta-analysis were conducted to evaluate the association between KISS-1 and PCOS, and to test its diagnostic test accuracy (DTA) through DTA meta-analysis.
DESIGN
Relevant studies were identified by searching PubMed and other databases in addition to manual searching of cross-references. Random-effects model was used to obtain standardized mean differences (SMD), pooled correlation coefficients and summary of DTA. Meta-regression and sub-group analyses were conducted to explore heterogeneity. The presence of publication bias was tested using funnel plot analysis.
RESULTS
This meta-analysis finally included 12 studies. Compared with controls, women with PCOS showed significantly increased circulatory KISS-1 levels (SMD = 0.47; P = 0.002). Meta-analysis of correlations showed positive associations between KISS-1 and anti-Müllerian hormone (AMH) (P = 0.03), testosterone (P < 0.001) and dehydroepiandrosterone (P = 0.004). The pooled diagnostic odds ratio and area under curve were 13.71 and 0.835, respectively. A one-study leave-out sensitivity analysis indicated that no single study had a significant influence on the overall outcome, suggesting the robustness of this meta-analysis.
CONCLUSIONS
This meta-analysis showed significantly increased KISS-1 level in PCOS, and its association with AMH reflects its role in reproductive physiology. In our DTA meta-analysis, KISS-1 showed good accuracy for PCOS detection. Further large-scale studies are required to establish its validity.
Topics: Anti-Mullerian Hormone; Case-Control Studies; Diagnostic Techniques, Endocrine; Diagnostic Tests, Routine; Female; Humans; Kisspeptins; Polycystic Ovary Syndrome; Predictive Value of Tests; Reproducibility of Results; Testosterone
PubMed: 31515170
DOI: 10.1016/j.rbmo.2019.04.018