NCT03841981

Body Fat as Determinant of Female Gonadal Dysfunction

Amount, Distribution and Dysfunction of Body Fat as Determinants of Female Gonadal Dysfunction: From Functional Hypothalamic Amenorrhea to the Polycystic Ovary Syndrome

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 50 (estimated)
• Sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal · Academic / Other
• Sex: Female
• Age: 18 Years – 40 Years
• Healthy volunteers: Accepted

Summary

Reproduction requires from women enough energy depots to warrant an adequate nutritional supply to the fetus. Hence, adipose tissue is able to communicate with female hypothalamic-pituitary-ovary axis. The hypothesis of the project is that abnormalities in the quantity (absolute and relative to lean body mass), distribution and/or function of adipose tissue are associated with functional forms of female gonadal dysfunction in predisposed women, in a spectrum of anomalies that go from hypothalamic amenorrhea to the polycystic ovary syndrome (PCOS). To challenge this hypothesis, the investigators will study 5 groups of 10 women each: women with exercise-associated hypothalamic amenorrhea, women without ovulatory dysfunction that exercise equally, non-hyperandrogenic patients with PCOS, hyperandrogenic patients with PCOS, and healthy control women comparable to those with PCOS. The aims of the study will be: Primary objective: To identify novel signalling factors originating from adipose tissue and muscle using targeted and nontargeted evaluation of the proteome and of gene expression of superficial subcutaneous fat, deep subcutaneous fat (which mimics visceral adipose tissue) and skeletal muscle. Secondary objectives: 1. To study the serum adipokine profile - including those identified by the primary objective - and circulating gut hormones during fasting and after a glucose load in the 5 groups of women, and their associations with sexual hormones and body fat distribution. 2. To study body composition and body fat distribution in these women and their relationships with: 2.1, Sex steroid profiles. 2.2. Classic cardiovascular risk factors: carbohydrate metabolism, lipid profiles and blood pressure. 2.3 Markers of low-grade chronic inflammation. 2.4. Oxidative stress markers. 2.5. Cardiovascular autonomic function. 2.6. Surrogate markers of subclinical atherosclerosis. 2.7. Circulating concentrations of endocrine disruptors. 2.8. Oral and gut microbiome. The results will provide a better understanding of the mechanisms linking body energy depots with the female reproductive axis and, hopefully, the identification of potential biomarkers for the diagnosis and treatment of the disorders studied here.

Conditions

• Polycystic Ovary Syndrome
• Hypothalamic Amenorrhea

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Anthropometric and physical examination	* Weight and height. * Waist-to-hip ratio. * Body composition: Bioelectrical impedance and \[Dual energy X-ray absorptiometry (DEXA)\].
DIAGNOSTIC_TEST	Indirect calorimetry, accelerometer and seven-day dietary recall	Energy availability assessment.
DIAGNOSTIC_TEST	Biochemical, hormonal and metabolic phenotyping	* Lipid profile. * Oral glucose tolerance test: plasma glucose and insulin, insulin sensitivity indices, gastrointestinal hormones, adipokines, oxidative stress markers. * Sex steroid profile. * Hypothalamic-pituitary-adrenal axis study. * Ferrokinetic study. * Subclinical chronic inflammatory markers.
DIAGNOSTIC_TEST	Sonographic studies	* Polycystic ovarian morphology. * Carotid intima-media thickness. * Eco-FAT: Ultrasound measurements of adipose tissue depots including sc, preperitoneal, intraperitoneal (ip), mesenteric, and perirenal fat thickness.
DIAGNOSTIC_TEST	24-hour Ambulatory blood pressure monitoring	A\&D TM2430EX oscillometric devices (A\&D Company Limited, Tokyo, Japan).
PROCEDURE	Percutaneous biopsy	Subcutaneous fat tissue and muscle tissue for proteomics an gene expression studies.
DIAGNOSTIC_TEST	Cardiovascular autonomic function studies	Parasympathetic and sympathetic responses to deep breathing, Valsalva's maneuver and orthostatism.
DIAGNOSTIC_TEST	Oral smear and feces specimen	Microbiome studies.

Timeline

• Start date: 2020-01-31
• Primary completion: 2025-06-30
• Completion: 2025-12-31
• First posted: 2019-02-15
• Last updated: 2025-08-12

Locations

1 site across 1 country: Spain