Effects of Glucagon-like Peptide-1 (GLP-1) Agonist in Neuro-reproductive Function in Obese Adolescent Females With Polycystic Ovary Syndrome (PCOS)

NCT07169136 | Recruiting DMC FDA Drug

• 1 other identifier: 25-014
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The prevalence of childhood obesity in the United States has more than tripled in the past four decades affecting one in every five adolescent girls and is disproportionally higher among racial and/or ethnic minorities. Normal puberty onset and progression is dependent on normal hypothalamic-pituitary-gonadal (HPG) axis which is affected by whole body metabolism. Gonadotropin-releasing hormone (GnRH) and gonadotropins, LH and FSH, are released in a pulsatile manner for appropriate sex steroids production and gonadal function. Proper pulsatility in the GnRH system is disrupted by a significant change in energy balance such as in obesity. Polycystic Ovary Syndrome (PCOS) is the most common neuroendocrine dysfunction in women of reproductive age. Glucagon-like peptide-1 (GL-1), a peptide hormone secreted by the intestinal enteroendocrine L-cells following glucose and fat intake, stimulates insulin release by the pancreas in response to glucose, decreases gastric emptying and inhibits glucagon secretion. GLP-1 receptors are present in the hypothalamic nuclei and pituitary gland; and it is thought that GLP-1 may directly stimulate GnRH secretion and partially regulate reproduction. In animal studies, GLP-1 was found to stimulate GnRH secretion, to regulate kisspeptin (Kiss-1) mRNA and GnRH mRAN expression. GLP-1 receptor agonists are FDA-approved to treat adults and adolescents with obesity. Although the impact of GLP-1 receptor agonists in reproductive health has been investigated in preclinical trials, and in men with obesity and functional hypogonadism, no studies to date have investigated the impact of GLP-1 receptor agonists in female neuroendocrine function, particularly in youth. The goal of this proposal is to gather critical preliminary data to investigate, in a group of obese adolescent females with PCOS, the impact of GLP-1 agonist administration in addition to lifestyle modifications on the neuroendocrine rhythms - LH frequency and amplitude (principal); body composition, adiposity; and carbohydrate metabolism and insulin sensitivity. To accomplish these aims, we will recruit a cohort of up to 20 adolescents ages 12-18 years, at least 2 years post-menarche, with obesity, PCOS, by NIH criteria, without carbohydrate intolerance and in otherwise good health. Research volunteers will be advised on lifestyle modifications of diet and exercise as per routine, and a GLP-1 agonist will be started according to the product's label as per FDA guidelines in children with obesity. Medication will be titrated to maximal therapeutic dose, as per routine clinical practice. Participants will be treated for a total of 16 weeks. Neuroendocrine rhythms pre- and post-treatment will be compared.

Conditions

Polycystic Ovarian Syndrome in Adolescent Females; Obesity (Disorder)

Keywords

PCOS; Obesity; Adolescent Female; irregular menstrual cycles

Outcome Measures

Primary Outcomes (5)

• Change in LH pulse frequency after 4 months of GLP-1 agonist use.

  LH will be obtained every 20 minutes overnight. LH will be measured using a chemiluminescence assay. Pulse frequency will be calculated using mathematical deconvolution analysis.

  Blood sampling will occur at study enrollment and then 4 months post intervention.

• Change in average levels of LH and FSH after 4 months of GLP-1 agonist use.

  LH and FSH will be measured using a chemiluminescence assay.

  Blood sampling will occur at study enrollment and then 4 months post intervention.

• Change in average levels of Total testosterone and Estradiol after 4 months of GLP-1 agonist use.

  Total testosterone and estradiol will be measured by liquid chromatography-mass spectrometry

  Blood sampling will occur at study enrollment and then 4 months post intervention.

• Change in average levels of progesterone after 4 months of GLP-1 agonist use.

  Progesterone will be measured using immunoassay.

  Blood sampling will occur at study enrollment and then 4 months post intervention.

• Change in LH amplitude.

  LH will be obtained every 20 minutes overnight. LH will be measured using a chemiluminescence assay. Pulse amplitude will be calculated using mathematical deconvolution analysis.

  Blood sampling will occur at study enrollment and then 4 months post intervention.

Secondary Outcomes (2)

• Body composition will be measured by dual x-ray absorptiometry (DXA) scan.

  At enrollment and 4 months post intervention.

• Carbohydrate metabolism and insulin sensitivity will be analyzed.

  Sampling will occur at enrollement and 4 months post intervention.

Study Arms (1)

Females ages 12 to 18 years, at least 2 years post-menarche, with obesity and PCOS..

Females ages 12 to 18 years, at least 2 years post-menarche, with obesity (BMI equal to or more than the 95th percentile for age) and with PCOS, by NIH criteria: oligomenorrhea (menstrual cycles \<21 or \>35 days) \[4\] and hyperandrogenism (testosterone level or free androgen index (FAI) \> refence range for tanner stage) and in good overall health. FAI is calculated as total testosterone\*100/sex hormone binding globulin.

Drug: GLP-1 Receptor Agonists

Interventions

GLP-1 Receptor Agonists DRUG

Weekly subcutaneous Semaglutide.

Females ages 12 to 18 years, at least 2 years post-menarche, with obesity and PCOS..

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Adolescent females with Obesity and PCOS.

You may qualify if:

• Diagnosed with PCOS, by NIH criteria: oligomenorrhea (menstrual cycles \<21 or \>35 days) and hyperandrogenism (testosterone level or free androgen index (FAI) \> refence range for tanner stage) and in good overall health
• Obesity (equal to or more than the 95th percentile)
• Females ages 12 to 18 years, at least 2 years post-menarche
• Participants has persistent symptoms of PCOS and obesity despite lifestyle modifications for at least 4 months.

You may not qualify if:

• Has abnormal thyroid function tests at Screening.
• Has suspected or known Diabetes mellitus, impaired fasting glucose, or elevated hemoglobin A1c.
• Has non-classic congenital adrenal hyperplasia.
• Has hyperprolactinemia.
• Has a known history or family history of medullary thyroid carcinoma or MEN2 and history of pancreatitis
• Participants receiving prior treatment with metformin, GLP-1 agonists, oral contraception pills, progesterone, or other insulin sensitizers for at least 6 weeks prior to Screening.
• Is currently pregnant or has been pregnant.

Sponsors & Collaborators

• Nemours Children's Clinic: lead

Study Sites (1)

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

RECRUITING

Related Publications (4)

• McCartney CR, Campbell RE. Abnormal GnRH Pulsatility in Polycystic Ovary Syndrome: Recent Insights. Curr Opin Endocr Metab Res. 2020 Jun;12:78-84. doi: 10.1016/j.coemr.2020.04.005. Epub 2020 Apr 23.

  PMID: 32676541 BACKGROUND

• Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985 Jul;28(7):412-9. doi: 10.1007/BF00280883.

  PMID: 3899825 BACKGROUND

• Ruffing KM, Koltun KJ, De Souza MJ, Williams NI. Moderate Weight Loss is associated with Reductions in LH Pulse Frequency and Increases in 24-hour Cortisol with no change in Perceived Stress in Young Ovulatory Women. Physiol Behav. 2022 Oct 1;254:113885. doi: 10.1016/j.physbeh.2022.113885. Epub 2022 Jun 16.

  PMID: 35718216 BACKGROUND

• McCartney CR, Prendergast KA, Blank SK, Helm KD, Chhabra S, Marshall JC. Maturation of luteinizing hormone (gonadotropin-releasing hormone) secretion across puberty: evidence for altered regulation in obese peripubertal girls. J Clin Endocrinol Metab. 2009 Jan;94(1):56-66. doi: 10.1210/jc.2008-1252. Epub 2008 Oct 28.

  PMID: 18957503 BACKGROUND

MeSH Terms

Conditions

Obesity; Menstruation Disturbances

Interventions

Glucagon-Like Peptide-1 Receptor Agonists

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Intervention Hierarchy (Ancestors)

Hypoglycemic Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Central Study Contacts

Camila Pereira-Eshraghi, MD. MS.

CONTACT

1 + 904-408-7895; camila.pereira-eshraghi@nemours.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD.

Study Record Dates

• First Submitted: August 19, 2025
• First Posted: September 11, 2025
• Study Start: September 11, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 16, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

US (1)