An observational study in Polycystic Ovary Syndrome and Hypothalamic Amenorrhea, sponsored by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal. Completed at 1 site in Spain. Open to female participants aged 18 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-16.
Sponsored by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal · Observational
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:
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.
956 studies on the registry are indexed under Polycystic Ovary Syndrome; 176 are open to participants now.
This study's enrollment of 50 is below the median of 118 across 223 observational studies indexed under Polycystic Ovary Syndrome.
Browse Polycystic Ovary Syndrome studies →Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal is the lead sponsor of 83 studies on the registry; 22 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Patients with exercise-associated functional amenorrhea and polycystic ovary syndrome will be consecutively recruited from our Reproductive Endocrinolgy clinic. Those premenopausal adult women are referred to clinic because of symptoms of functional androgen excess such as hirsutism or menstrual dysfunction.
The control group (Groups IV and V) will include healthy female volunteers recruited - contemporarily with the recruitment of patients - from the hospital's staff and overweight or obese women seeking medical attention in our department.
Inclusion Criteria
Group I
Group II:
Group III:
Group IV:
Group V:
Exclusion Criteria (Groups I-V)
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
10 women with exercise-associated hypothalamic amenorrhea
Diagnostic Test: Anthropometric and physical examination · Diagnostic Test: Indirect calorimetry, accelerometer and seven-day dietary recall · Diagnostic Test: Biochemical, hormonal and metabolic phenotyping · Diagnostic Test: Sonographic studies · Diagnostic Test: 24-hour Ambulatory blood pressure monitoring · Procedure: Percutaneous biopsy · Diagnostic Test: Cardiovascular autonomic function studies · Diagnostic Test: Oral smear and feces specimen
5 lean women with hyperandrogenic polycystic ovary syndrome. 5 women with weight excess and hyperandrogenic polycystic ovary syndrome.
Diagnostic Test: Anthropometric and physical examination · Diagnostic Test: Indirect calorimetry, accelerometer and seven-day dietary recall · Diagnostic Test: Biochemical, hormonal and metabolic phenotyping · Diagnostic Test: Sonographic studies · Diagnostic Test: 24-hour Ambulatory blood pressure monitoring · Procedure: Percutaneous biopsy · Diagnostic Test: Cardiovascular autonomic function studies · Diagnostic Test: Oral smear and feces specimen
5 lean women with non-hyperandrogenic polycystic ovary syndrome 5 women with weight excess and non-hyperandrogenic polycystic ovary syndrome
Diagnostic Test: Anthropometric and physical examination · Diagnostic Test: Indirect calorimetry, accelerometer and seven-day dietary recall · Diagnostic Test: Biochemical, hormonal and metabolic phenotyping · Diagnostic Test: Sonographic studies · Diagnostic Test: 24-hour Ambulatory blood pressure monitoring · Procedure: Percutaneous biopsy · Diagnostic Test: Cardiovascular autonomic function studies · Diagnostic Test: Oral smear and feces specimen
10 women who exercise as intensively as women with exercise-associated hypothalamic amenorrhea but with normal ovulatory cycles.
Diagnostic Test: Anthropometric and physical examination · Diagnostic Test: Indirect calorimetry, accelerometer and seven-day dietary recall · Diagnostic Test: Biochemical, hormonal and metabolic phenotyping · Diagnostic Test: Sonographic studies · Diagnostic Test: 24-hour Ambulatory blood pressure monitoring · Procedure: Percutaneous biopsy · Diagnostic Test: Cardiovascular autonomic function studies · Diagnostic Test: Oral smear and feces specimen
10 women matched by age and body mass index with women with polycystic ovary syndrome who do not perform physical activity on a regular basis
Diagnostic Test: Anthropometric and physical examination · Diagnostic Test: Indirect calorimetry, accelerometer and seven-day dietary recall · Diagnostic Test: Biochemical, hormonal and metabolic phenotyping · Diagnostic Test: Sonographic studies · Diagnostic Test: 24-hour Ambulatory blood pressure monitoring · Procedure: Percutaneous biopsy · Diagnostic Test: Cardiovascular autonomic function studies · Diagnostic Test: Oral smear and feces specimen
* Weight and height. * Waist-to-hip ratio. * Body composition: Bioelectrical impedance and \[Dual energy X-ray absorptiometry (DEXA)\].
Energy availability assessment.
* 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.
* 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.
A\&D TM2430EX oscillometric devices (A\&D Company Limited, Tokyo, Japan).
Subcutaneous fat tissue and muscle tissue for proteomics an gene expression studies.
Parasympathetic and sympathetic responses to deep breathing, Valsalva's maneuver and orthostatism.
Microbiome studies.
Adipokine and myokine signaling identification
Time frame: Up to 5 years
Circulating adipokine profile
At fasting and after an oral glucose challenge: Circulating concentrations of Leptin, Adiponectin, Chemerin, Lipocalin-2, Adipsin, Plasminogen Activator Inhibitor (PAI)-1, Monocyte Chemoattractant Protein (MCP)-1, and Soluble Leptin Receptor by multianalyte profiling on the Luminex Magpix system (Luminex Technologies, Austin, USA.).
Time frame: Up to 5 years
Appetite regulation hormonal profile
At fasting and after an oral glucose challenge: Circulating concentrations of Amylin, C-Peptide, Ghrelin, Gastric Inhibitory Peptide (GIP), Glucagon-Like Peptide (GLP)-1, Glucagon, IL-6, Insulin, Pancreatic Polypeptide (PP), Peptide YY, Tumor Necrosis Factor (TNF)-α by multianalyte profiling on the Luminex Magpix system (Luminex Technologies, Austin, USA.).
Time frame: Up to 5 years
Association between body mass index and sex steroids
Body mass index in in kg/m\^2. Sex steroids (including circulating total testosterone, estradiol, androstenedione, dehydroepiandrosterone-sulphate and estrone) measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Free testosterone will be calculated from total testosterone and sex hormone binding globulin levels.
Time frame: Up to 5 years
Association between percentage of fat mass with respect to total body weight and sex steroids
Fat mass% by bioelectric impedanciometry and DEXA. Sex steroids (including circulating total testosterone, estradiol, androstenedione, dehydroepiandrosterone-sulphate and estrone) measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Free testosterone will be calculated from total testosterone and sex hormone binding globulin levels.
Time frame: Up to 5 years
Association between percentage of lean mass with respect to total body weight and sex steroids
Lean mass% by bioelectric impedanciometry and DEXA. Sex steroids (including circulating total testosterone, estradiol, androstenedione, dehydroepiandrosterone-sulphate and estrone) measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Free testosterone will be calculated from total testosterone and sex hormone binding globulin levels.
Time frame: Up to 5 years
Association between body fat depots and sex steroids
Adipose tissue depots will be estimated using a Toshiba Nemio XG SSA-580A Diagnostic Ultrasound System. Minimum sc and preperitoneal fat thicknesses will be measured at the level of the xyphoid process. Maximum sc fat thickness will be measured at the level of the umbilicus. Intraperitoneal fat thickness will be measured placing a probe transversally in the midline of abdomen, 2 cm above the umbilicus. Three measures of ip fat thickness will be obtained: the distance from the fascia of rectus abdominis muscle to the vertebral column, the distance from the peritoneum to the vertebral column, and the distance from the linea alba to the vertebral column. Perirenal fat thickness will be estimated as the distance from the perirenal fascia to the renal surface. Sex steroids will be measured as previously described.
Time frame: Up to 5 years
Association between body composition, sex steroids, and insulin resistance.
Fat mass, lean mass and body fat depots will be measured as previously described. Fasting glucose and insulin levels will be used for calculating the homeostasis model assessment of insulin resistance (HOMA-IR), and the composite insulin sensitivity index will be estimated from the glucose and insulin concentrations measured during the oral glucose tolerance test. Sex steroids will be measured as previously described.
Time frame: Up to 5 years
Association between body composition, sex steroids, and lipids.
Fat mass, lean mass and body fat depots will be measured as previously described. Circulating HDL-cholesterol and phospholipid levels will be measured by enzymatic methods after precipitation of plasma with phosphotungstic acid and Mg2+. Total cholesterol and triglyceride levels will be determined by enzymatic methods. LDL-cholesterol concentrations will be estimated by Friedewald's equation. Circulating apolipoprotein (Apo) AI, Apo B100, and lipoprotein (a) levels will be determined by kinetic immunonephelometry. Sex steroids will be measured as previously described.
Time frame: Up to 5 years
Association between body composition, sex steroids, and office blood pressure.
Fat mass, lean mass and body fat depots will be measured as previously described. Office blood pressure will be determined as the mean of three manual sphygmomanometer readings in the sitting position. Sex steroids will be measured as previously described.
Time frame: Up to 5 years
Association between body composition, sex steroids, and ambulatory blood pressure monitoring parameters.
Fat mass, lean mass and body fat depots will be measured as previously described. Twenty-four-hour ambulatory blood pressure monitoring will be performed using an A\&D TM2430EX oscillometric device (A\&D Co., Ltd., Tokyo, Japan). The cuff (12 × 22 cm for lean participants, 14 × 30 cm for overweight or obese participants) will placed on the nondominant arm in every woman. The period from 0700 to 2300 h will be considered daytime, and from 2300 until 0700 h the next day will be considered nighttime, reflecting the usual sleeping habits of Spaniards. Systolic, diastolic, and mean blood pressure as well as heart rate will be measured every 20 min during daytime and every 30 min during nighttime. Sex steroids will be measured as previously described.
Time frame: Up to 5 years
Association between body composition, sex steroids, and cardiovascular autonomic function tests.
Fat mass, lean mass and body fat depots will be measured as previously described. Cardiovascular autonomic function will be assessed by the blood pressure and heart rate responses to active standing, and Ewing and Clarke's tests. Sex steroids will be measured as previously described.
Time frame: Up to 5 years
Association between body composition, sex steroids, and carotid intima-media thickness.
Fat mass, lean mass and body fat depots will be measured as previously described. Imaging will be conducted using a high-resolution 7.5-MHz phased-array transducer by the same trained operator in all the participants. Sex steroids will be measured as previously described.
Time frame: Up to 5 years
Association between body composition, sex steroids, and oxidative stress.
Fat mass, lean mass and body fat depots will be measured as previously described. Oxidative stress profile will be measured by enzymatic assays: Plasma thiobarbituric acid reactive substances, total antioxidant capacity, nitrotyrosine, protein carbonyl groups and erythrocyte glutathione peroxidase levels. Sex steroids will be measured as previously described.
Time frame: Up to 5 years
Association between body composition, sex steroids, and microbiome
Participants will be instructed to collect fecal and salivary samples. DNA samples wil be used for massive sequencing of 16S ribosomal DNA (rDNA) amplicons in a MiSeq platform (Illumina). The bacterial diversity will be estimated by using Shannon, Chao 1, Jaccard, and Sorensen indexes with their SDs. Taxonomic affiliations will be assigned by using the RDP\_classifier from the Ribosomal Database Project (RDP), and readings with RDP score value \<0.8 will be assigned to the upper taxonomic rank, leaving the last rank as unidentified. Sex steroids will be measured as previously described.
Time frame: Up to 5 years
Plan to share: Yes — The investigators will deposit any datasets and supplemental materials to a generalist repository. The investigators will refer to the deposited material as an item in the bibliography of any manuscript and number the reference appropriately within the text.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report, Analytic code
Time frame: Data will become available at the time of the first manuscript submission.
Access criteria: Public access
Ran from Jan 2020 to primary completion in Jun 2025, 64 months.
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Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal