Inhibiting Kiss1 Neurons with Kappa Opioid Receptor Agonists to Treat Polycystic Ovary Syndrome and Vasomotor Symptoms

2021 ◽  
Author(s):  
Elizabeth A McCarthy ◽  
Daniel Dischino ◽  
Caroline Maguire ◽  
Silvia Leon ◽  
Rajae Talbi ◽  
...  
Keyword(s):  
Body Temperature ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Chronic Administration ◽  
Vasomotor Symptoms ◽  
Reproductive State ◽  
Ovary Syndrome ◽  
Receptor Agonists ◽  
Kappa Receptor ◽  
Kndy Neurons

Abstract Context Recent evidence suggests that vasomotor symptoms (VMS) or hot flashes in the postmenopausal reproductive state and polycystic ovary syndrome (PCOS) in the premenopausal reproductive state emanate from the hyperactivity of Kiss1 neurons in the hypothalamic infundibular/arcuate nucleus (KNDy neurons). Objective We demonstrate in 2 murine models simulating menopause and PCOS that a peripherally-restricted kappa receptor agonist (PRKA) inhibits hyperactive KNDy neurons (accessible from outside the blood brain barrier) and impedes their down-stream effects. Design Case/control. Setting Academic medical center. Participants Mice. Interventions Administration of peripherally-restricted kappa receptor agonists and frequent blood sampling to determine hormone release, and body temperature. Main Outcome Measures LH pulse parameters and body temperature. Results First, chronic administration of a PRKA to OVX mice with experimentally-induced hyperactivity of KNDy neurons reduces the animals’ elevated body temperature, mean plasma LH level, and mean peak LH per pulse. Second, chronic administration of a PRKA to a murine model of PCOS, having elevated plasma testosterone levels and irregular ovarian cycles, suppresses circulating levels of LH and testosterone and restores normal ovarian cyclicity. Conclusion The inhibition of Kiss1 neuronal activity by activation of kappa receptors shows promise as a novel therapeutic approach to treat both VMS and PCOS in humans.

The chronic administration of cabergoline normalizes androgen secretion and improves menstrual cyclicity in women with polycystic ovary syndrome

1996 ◽  
Vol 66 (4) ◽  
pp. 527-532 ◽  
Author(s):  
Anna Maria Paoletti ◽  
Angelo Cagnacci ◽  
Gian Franco Depau ◽  
Marisa Orrù ◽  
Silvia Ajossa ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Chronic Administration ◽  
Ovary Syndrome ◽  
Androgen Secretion

scholarly journals Obesity, Polycystic Ovary Syndrome, and Infertility: A New Avenue for GLP-1 Receptor Agonists

2020 ◽  
Vol 105 (8) ◽  
pp. e2695-e2709 ◽  
Author(s):  
Hellas Cena ◽  
Luca Chiovato ◽  
Rossella E Nappi
Keyword(s):  
Weight Loss ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Therapeutic Option ◽  
Evidence Synthesis ◽  
Treatment Options ◽  
Obese Women ◽  
Ovary Syndrome ◽  
Receptor Agonists ◽  
Increased Risk

Abstract Context Obesity is responsible for an increased risk of sub-fecundity and infertility. Obese women show poorer reproductive outcomes regardless of the mode of conception, and higher body mass index (BMI) is associated with poorer fertility prognosis. Polycystic ovary syndrome (PCOS) is one of the leading causes of infertility, and many women with PCOS are also overweight or obese. Evidence Acquisition The aim of the present narrative review is to describe the mechanisms responsible for the development of infertility and PCOS in women with obesity/overweight, with a focus on the emerging role of glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) as a therapeutic option for obese women with PCOS. Evidence synthesis Weight reduction represents the most significant factor affecting fertility and pregnancy outcomes. Current experimental and clinical evidence suggests the presence of an underlying pathophysiological link between obesity, GLP-1 kinetic alterations, and PCOS pathogenesis. Based on the positive results in patients affected by obesity, with or without diabetes, the administration of GLP-1 RA (mainly liraglutide) alone or in combination with metformin has been investigated in women with obesity and PCOS. Several studies demonstrated significant weight loss and testosterone reduction, with mixed results relative to improvements in insulin resistance parameters and menstrual patterns. Conclusions The weight loss effects of GLP-1 RA offer a unique opportunity to expand the treatment options available to PCOS patients.

scholarly journals Overview of the Role of Glucagon like Peptide-1 Receptor Agonists in the Management of Polycystic Ovary Syndrome

2021 ◽  
pp. 312-318
Author(s):  
Asma Alshenqiti ◽  
Ghaida Almohammadi
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Premenopausal Women ◽  
Ovary Syndrome ◽  
Receptor Agonists ◽  
Long Term Effect ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects premenopausal women. It is a multifactorial disease that involves hyperandrogenism, ovulatory dysfunction, insulin resistance and genetic factors. Women with PCOS present with menstrual disorder, hirsutism, and obesity. Diagnosis of PCOS involves evidence of ovulation dysfunction, hyperandrogenism, either physical or biochemical, and ultrasonographic evaluation of the ovarian morphology. There is no single treatment for PCOS but rather it is a symptom-oriented management. Glucagon-like-peptide-1 receptor agonists (GLP-1 RAs) are insulin sensitizers usually involved in the management of PCOS. Aim: This article aims to review the evidence regarding the role GLP-1 RAs in the management of polycystic ovary syndrome. Conclusion: GLP-1 RAs found to improve PCOS outcomes in the form of increasing menstrual frequency, reducing androgens levels, higher pregnancy rates, weight reduction, and improving insulin resistance. Mild and transient adverse events were observed such as nausea, diarrhea, headache, insomnia and mild hypoglycemic events. However, long term studies are required to assess long term effect of GLP-1 RAs and its safety during pregnancy.

Effect of chronic administration of cabergoline on uterine perfusion in women with polycystic ovary syndrome

1999 ◽  
Vol 71 (2) ◽  
pp. 314-318 ◽  
Author(s):  
Silvia Ajossa ◽  
Anna Maria Paoletti ◽  
Stefano Guerriero ◽  
Stefano Floris ◽  
Marina Mannias ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Chronic Administration ◽  
Ovary Syndrome ◽  
Uterine Perfusion

GLP-1 receptor agonists in the treatment of polycystic ovary syndrome

2017 ◽  
Vol 10 (4) ◽  
pp. 401-408 ◽  
Author(s):  
Elizabeth Mary Lamos ◽  
Rana Malek ◽  
Stephen N. Davis
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Receptor Agonists

scholarly journals The Antiobesity Effect of GLP-1 Receptor Agonists Alone or in Combination with Metformin in Overweight /Obese Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Xiaorui Lyu ◽  
Taibiao Lyu ◽  
Xue Wang ◽  
Huijuan Zhu ◽  
Hui Pan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Weight Loss ◽  
Waist Circumference ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Ovary Syndrome ◽  
Receptor Agonists

Objectives. Both glucagon-like peptide-1 receptor agonists (GLP-1RAs) and metformin (MET) have markedly antiobesity effects in overweight/obese polycystic ovary syndrome (PCOS) patients. However, there was no literature to compare the antiobesity effects of these two medicines. Therefore, a systematic review and meta-analysis were conducted in our present study to evaluate the antiobesity effects of GLP-1RAs either as monotherapy or combined with MET in comparison with MET alone in overweight/obese PCOS patients. Methods. All randomized controlled trials (RCTs) which reported the efficacy of GLP-1RAs and MET in overweight/obese PCOS patients in Medline (from Pubmed), Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases were independently searched by two reviewers. The random-effect model was used to pool data extracted from the included literature. The weighted mean difference (WMD) and 95% confidence interval (CI) were used to present the meta-analysis results (PROSPERO registration number: CRD42020173199). Results. A total of eight eligible RCTs were finally enrolled in our meta-analysis from the 587 retrieved literature. The results showed that GLP-1RAs alone or combined with MET was associated with a greater weight loss (N = 318, WMD = −2.61, 95% CI: −3.51 to −1.72, P ≤ 0.001 , I2 = 77.5%), more obvious reduction of waist circumference (N = 276, WMD = −3.46, 95% CI: −4.36 to −2.56, P ≤ 0.001 , I2 = 0.0%), and body mass index (BMI) (N = 318, WMD = −0.93, 95% CI: −1.60 to −0.26, P = 0.007 , I2 = 84.9%) in overweight/obese PCOS patients when compared with MET alone. Further sensitivity analysis demonstrated that the meta-analysis results of the efficacy differences in terms of body weight, waist circumference, and BMI were relatively stable and reliable. Conclusion. Our meta-analysis demonstrated that the antiobesity effect of GLP-1RAs alone or combined with MET  was superior to MET  alone in terms of weight loss, the reduction of waist circumference, and BMI. More large-scale, high-quality RCTs are needed to further confirm these results in PCOS patients.

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