Identification of Women With Severe Insulin Resistant Syndromes of Genetic Origin Among Patients With "Classic" Polycystic Ovary Syndrome (PCOS) (ANDROLIPO)

Diagnostic case-control study (1 case for 2 controls). Inclusion of patients with severe insulin resistance syndrome of genetic origin, then inclusion of controls: patients examined for PCOS in day hospital with matching age (+/- 5 years) and Body mass index (+/- 5kg/m2).

Study Overview

• Status: Not yet recruiting
• Conditions: Polycystic Ovary Syndrome; Familial Partial Lipodystrophy; LMNA (LaMin Nuclear A) Related Disorders
• Intervention / Treatment: Genetic: Genetic analysis; Other: Biological analysis; Other: imaging test; Other: Standard intervention

Detailed Description

Hyperandrogenism and/or menstrual cycle disorders are the leading cause of female infertility and are associated with cardiovascular comorbidities. The most common cause of hyperandrogenism is polycystic ovary syndrome (PCOS), which affects 10% of women. However, PCOS can also be the presenting symptom of rare, multisystemic conditions such as extreme insulin resistance (IR) syndromes, with or without lipodystrophy. Among these extreme IR syndromes, familial partial lipodystrophy type 2 (FPLD2), of genetic origin, requires early screening and management to prevent diabetes, hypertriglyceridemia, and cardiovascular complications, which occur in 50%, 68%, and 45% of women, respectively, as well as serious comorbidities in certain genetic forms (risk of sudden death). Associated metabolic complications are often difficult to control and necessitate the use of orphan drugs when standard treatments are insufficiently effective. Furthermore, family genetic counseling should be provided. Currently, there is a significant delay in the diagnosis of these rare and still poorly understood diseases. This diagnostic delay is associated with a delay in the screening and treatment of complications related to these diseases, with a risk of early cardiovascular morbidity and mortality that is difficult to assess at present due to the rarity of the disease.

The main objective is to identify the differences, in the insulin resistant profile, associated with the diagnosis of PCOS coupled with a severe insulin resistance syndrome, when compared to a diagnosis of "classic" PCOS.

The secondary objective is to describe the metabolic and hormonal phenotype of patients with familial partial lipodystrophy type 2 (FPLD2) and to compare it with that of women presenting a "classic" PCOS.

25 cases and 50 age- and BMI-matched controls will be included in the study. Up to 6 additional control patients could be included if a control patient becomes a case based on the results of the genetic analysis. Otherwise, these patients will not be included.

A maximum of 81 patients in total will be included.

• Study Type: Interventional
• Enrollment (Estimated): 81
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sophie LAMOTHE, Doctor; Phone Number: +33 0149282406; Email: sophie.lamothe@aphp.fr
• Study Contact Backup: Name: Camille VATIER, Doctor; Phone Number: +33 0149282406; Email: camille.vatier@aphp.fr

Study Locations

• France
  • Paris, France, 75012
    • Service Endocrinologie, Hôpital St Antoine
    • Contact: Sophie LAMOTHE, Doctor; Phone Number: +33 0149282406; Email: sophie.lamothe@aphp.fr
    • Contact: Camille VATIER, Doctor; Phone Number: +33 0149282406; Email: camille.vatier@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women aged ≥ 18 years and < 45 years ;
• Discontinuation of estrogen-progestin therapyfor at least 3 months ;
• Signed informed consent ;
• Social security affiliation.

Case (n=25):

- Patient with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene.

Control (n=50), :

- patient consulting for polycystic ovary syndrome (PCOS according to the Rotterdam criteria) in day hospital matched on age +/-5 years and BMI+/-5 kg/m2.

Exclusion Criteria:

• - Severe renal insufficiency (GFR < 30 ml/min) ;
• Hepato-cellular insufficiency (TP < 50%) ;
• Taking corticosteroids or antiretrovirals ;
• Menopausal women ;
• Taking estrogen-progestin therapy;
• Diabetic patients on insulin : type 1 diabetes or pancreatectomised patients
• Other known causes of hyperandrogenism (21-hydroxylase block, Cushing's syndrome, ovarian tumor).
• Pregnant woman
• Breastfeeding woman

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Case; Patient with a Lipodystrophy Familial Partial due to a known pathogenic variant of the LMNA gene	Genetic: Genetic analysis; Analyses of the insulin resistance and lipodystrophy gene panel revealed pathogenic or highly susceptible variants in control PCOS patients; Other: Biological analysis; Measurement of adipokines; Other: imaging test; DEXA (Dual-Energy X-ray Absorptiometry)
Other: Control; Patient consulting for polycystic ovary syndrome in day hospital matched on age +/-5 years and BMI+/-5 kg/m2	Other: Standard intervention; Standard intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of Insulinemia rate during an orally induced hyperglycemia	Measure of Insulinemia rate in order to compare the association between the profile of insulin secretion (Insulinemia , C-peptide and glycaemia) during an orally induced hyperglycemia and the known diagnosis of lipodystrophy linked to a mutation of the LMNA (FPLD2) gene.	Day 0
Measure of C-peptide rate during an orally induced hyperglycemia	Measure of C-peptide rate in order to compare the association between the profile of insulin secretion (Insulinemia, C-peptide and glycaemia) during an orally induced hyperglycemia and the known diagnosis of lipodystrophy linked to a mutation of the LMNA (FPLD2) gene.	Day 0
Measure of glycaemia rate during an orally induced hyperglycemia	Measure of glycaemia rate in order to compare the association between the profile of insulin secretion (Insulinemia, C-peptide and glycaemia) during an orally induced hyperglycemia and the known diagnosis of lipodystrophy linked to a mutation of the LMNA (FPLD2) gene.	Day 0
Research of mutation of the LMNA (FPLD2) gene	Research of mutation of the LMNA (FPLD2) gene in order to compare the association between the profile of insulin secretion (Insulinemia, C-peptide and glycaemia) during an orally induced hyperglycemia and the known diagnosis of lipodystrophy linked to a mutation of the LMNA (FPLD2) gene.	Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of BMI	Measure of BMI in order to determine fatty tissue distribution in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Measure of waist circumference	Measure of waist circumference in order to determine fatty tissue distribution in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Measure of hip circumference	Measure of hip circumference in order to determine fatty tissue distribution in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Measure of skin fold thickness	Measure of skin fold thickness in order to determine fatty tissue distribution in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Measure of the percentage of total body fat at DEXA	Measure of the percentage of total body fat at DEXA in order to determine fatty tissue distribution in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0 and up to 1 month
Measure of the android to gynoid ratio at DEXA	Measure of the android to gynoid ratio at DEXA in order to determine fatty tissue distribution in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0 and up to 1 month
Determine biological differences in concentration of fasting blood glucose	Determine biological differences in concentration of fasting blood glucose in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine biological differences in concentration of fasting blood insulin	Determine biological differences in concentration of fasting blood insulin in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine biological differences in concentration of ASAT/ALAT (Aspartate Aminotransferases) /ALAT(Alanine Aminotransferases)	Determine biological differences in concentration of ASAT/ALAT in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine biological differences in concentration of Gamma GT (Gamma-glutamyl transpeptidase)	Determine biological differences in concentration of Gamma GT in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine biological differences in concentration of leptinemia	Determine biological differences in concentration of leptinemia in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine biological differences in concentration of adiponectinemia	Determine biological differences of plasma total adiponectin hydroxyprogesterone in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine biological differences in concentration of triglyceridemia	Determine biological differences of concentration triglyceridemia in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine biological differences in concentration of HDL cholesterolemia	Determine biological differences of concentration HDL cholesterolemia in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine differences in hormonal concentrations of testosterone	Determine differences in hormonal concentrations of testosterone in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine differences in hormonal concentrations of FSH (Follicle-Stimulating Hormone)	Determine differences in hormonal concentrations of FSH in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine differences in hormonal concentrations of LH (Luteinizing Hormone)	Determine differences in hormonal concentrations of LH in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine differences in hormonal concentrations of AMH (Anti-Müllerian Hormone)	Determine differences in hormonal concentrations of AMH in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine differences in hormonal concentrations of cortisol	Determine differences in hormonal concentrations of androgens and steroids (cortisol measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine differences in hormonal concentrations of cortisone	Determine differences in hormonal concentrations of cortisone measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine differences in hormonal concentrations of pregnenolone	Determine differences in hormonal concentrations of pregnenolone, measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine differences in hormonal concentrations of 17-alpha hydroxypregnenolone	Determine differences in hormonal concentrations of 17-hydroxyprogesterone measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine differences in hormonal concentrations of 16-hydroxyprogesterone	Determine differences in hormonal concentrations of 16-hydroxyprogesterone measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine differences in hormonal concentrations of delta 4 androstenedione	Determine differences in hormonal concentrations of delta 4 androstenedione measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine differences in hormonal concentrations of 11 betahydroxyandrostenedione	Determine differences in hormonal concentrations of 11 betahydroxyandrostenedione measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine differences in hormonal concentrations of DHEA (Dehydroepiandrosterone)	Determine differences in hormonal concentrations of DHEA measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine differences in hormonal concentrations of 11-deoxycortisol	Determine differences in hormonal concentrations of 11-deoxycortisol measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine differences in hormonal concentrations of 21-deoxycortisol	Determine differences in hormonal concentrations of 21-deoxycortisol measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine differences in hormonal concentrations of testosterone	Determine differences in hormonal concentrations of testosterone measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine differences in hormonal concentrations of dihydrotestosterone	Determine differences in hormonal concentrations of dihydrotestosterone measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine differences in hormonal concentrations of corticosterone	Determine differences in hormonal concentrations of corticosterone, measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine differences in hormonal concentrations of 21-deoxycorticosterone	Determine differences in hormonal concentrations of 21-deoxycorticosterone measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine differences in hormonal concentrations of aldosterone	Determine differences in hormonal concentrations of aldosterone measured by mass spectometry in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0
Determine the follicular count on pelvic ultrasound or pelvic MRI	Determine the follicular count on pelvic ultrasound in patients with a lipodystrophic syndrome due to a known pathogenic variant of the LMNA gene compared to the control group	Day 0

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Sophie LAMOTHE, APHP

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: January 27, 2026
• First Submitted That Met QC Criteria: February 13, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 13, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Polycystic Ovary Syndrome; Familial Partial Lipodystrophy; LMNA related disorders
• Additional Relevant MeSH Terms: Laminopathies; Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genetic Diseases, Inborn; Metabolic Diseases; Genital Diseases, Female; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Skin Diseases; Ovarian Cysts; Cysts; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Skin Diseases, Metabolic; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Lipodystrophy; Polycystic Ovary Syndrome; Lipodystrophy, Familial Partial; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Public Health; Environment and Public Health; Health Services; Health Care Facilities Workforce and Services; Preventive Health Services; Genetic Techniques; Genetic Services; Diagnostic Services; Public Health Practice; Environmental Pollution; Environmental Monitoring; Environmental Exposure; Genetic Testing; Biological Oxygen Demand Analysis
• Other Study ID Numbers: APHP241600; IDRCB 2025-A02210-49 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No