title: Association between vascular health and ovarian ageing in type 1 diabetes mellitus.
abstract: Is vascular health associated with ovarian reserve status using type 1 diabetes mellitus (DM-1) as a model for vascular compromise?
  
  
  
  No conclusive evidence for an association between vascular health and ovarian ageing was found in women with DM-1.
  
  
  
  The mechanism behind advanced ovarian ageing has not yet been elucidated. We hypothesize that vascular impairment precedes ovarian ageing. DM-1 is hallmarked by premature vascular complications that may consequently play a role in the rate of primordial follicle decline.
  
  
  
  A cross-sectional, patient-control study was performed in 150 premenopausal, regular cycling women with DM-1, as well as a reference population of 177 healthy, fertile women.
  
  
  
  In a single-study visit, an inventory of both ovarian reserve and vascular status was carried out in the DM-1 group. A transvaginal ultrasound to calculate the antral follicle count (AFC) and blood sampling for anti-Müllerian hormone (AMH), lipids, C-reactive protein and HbA1c measurements were performed. Furthermore, vascular screening including measurements of blood pressure, flow-mediated dilation, peripheral arterial tonometry, pulse wave velocity, pulse wave analysis and intima-media thickness was carried out. The relative decrease in serum AMH levels in women with DM-1 compared with healthy references was investigated.
  
  
  
  Systolic blood pressure was negatively correlated with both serum AMH (P= 0.006) and AFC (P= 0.004) in the DM-1 group. A non-linear relationship between HDL-cholesterol and serum AMH was found (P= 0.0001). No associations were detected between other vascular risk factors or vascular function tests and serum AMH or AFC in women with DM-1. With regard to the comparison of AMH levels between women with and without DM-1, mean AMH levels were 2.5 ± 1.9 ng/ml and 3.0 ± 2.8 ng/ml, respectively. After adjustment for confounders the difference in AMH levels between both groups appeared non-significant (fold change: 0.92, 95% confidence interval: 0.68-1.23).
  
  
  
  The use of different AMH assays and the cross-sectional design may limit the interpretation of this study.
  
  
  
  The lack of evident association between vascular health and ovarian ageing may be the result of an insufficient vascular compromise in the relatively young, DM-1 group.
  
  
  
  No external funding was received for conducting or publishing this study. F.Y., W.S., A.F., F.L.J.V., M.J.C.E. and H.W.d.V. have nothing to disclose. F.J.M.B. has received fees and grant support from the following companies: Ferring, Gedeon Richter, Merck Serono, Medical Specialties Distributors and Roche.
  
  
  
  Not applicable.
authors.affiliation: Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands f.yarde@umcutrecht.nl.
authors.forename: F
authors.initials: F
authors.lastname: Yarde
authors.affiliation: Department of Vascular Medicine, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: Spiering
authors.affiliation: Birth Center, University Medical Center Utrecht, PO Box 85090, 3508 AB Utrecht, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Franx
authors.affiliation: Department of Vascular Medicine, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: F L J
authors.initials: FL
authors.lastname: Visseren
authors.affiliation: Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: M J C
authors.initials: MJ
authors.lastname: Eijkemans
authors.affiliation: Department of Internal Medicine, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: H W
authors.initials: HW
authors.lastname: de Valk
authors.affiliation: Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: F J M
authors.initials: FJ
authors.lastname: Broekmans
mesh_terms: D054304:Anti-Mullerian Hormone / Q000097:blood; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000378:metabolism; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000473:pathology; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000097:blood; D065851:Ovarian Reserve; D010053:Ovary / Q000473:pathology*; D014652:Vascular Diseases / Q000150:complications*
chemical_list: D054304:Anti-Mullerian Hormone; D002097:C-Reactive Protein; D006442:Glycated Hemoglobin; D008055:Lipids; C517652:hemoglobin A1c protein, human
keywords: anti-Müllerian hormone; cardiovascular disease; ovarian reserve; type 1 diabetes mellitus; vascular risk factors