Overview
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).
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.
Eligibility
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
