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International Angiology 2003 September;22(3):222-8


lingua: Inglese

Influence of the hormonal changes during the normal menstrual cycle in healthy young women on soluble adhesion molecules, plasma homocysteine, free radical markers and lipoprotein fractions

Elhadd T. A. 1, Neary R. 2, Abdu T. A. M. 1, Kennedy G. 3, Hill A. 3, McLaren M. 3, Akber M. 1, Belch J. J. F. 3, Clayton R. N. 1

1 Department of Medicine, North Staffordshire Hospital, Stoke-on-Trent, UK 2 Department of Clinical Biochemistry, North Staffordshire Hospital, Stoke-on-Trent, UK 3 Section of Vascular Medicine and Biology, University Department of Medicine Ninewells Hospital and Medical School, Dundee,UK


Aim. ­Female sex hor­mones are known to exert a pro­tec­tive role on the vas­cu­lar endo­the­lial func­tion, but the exact mech­a­nisms of such pro­tec­tion is not known. We aimed to study the pos­sible reg­u­la­to­ry role of the ­female sex hor­mones chang­es dur­ing the nor­mal men­stru­al cycle on sol­u­ble adhe­sion mole­cules E-selec­tin and ICAM-1, plas­ma homo­cy­teine, free rad­i­cal mark­ers and lipop­ro­teins in ­healthy young women.
Meth­ods. Experi­men­tal ­design: a cross sec­tion­al study of ­healthy ­female vol­un­teers stud­ied dur­ing a sin­gle nor­mal men­stru­al cycle at 3 spe­cif­ic time ­points. Set­ting: North Staf­ford­shire Hos­pi­tals NHS Trust. Sub­jects: 20 ­healthy young men­stru­at­ing women, aged (mean±SEM) 34±1 years, with nor­mal men­stru­a­tion, ­defined as a men­stru­al cycle of 21-35 days were stud­ied at 3 time ­points of the same men­stru­al cycle. First in the early fol­lic­u­lar phase (M-phase), at mid-fol­lic­u­lar phase (F-phase), and dur­ing the ­luteal phase (L-phase). Inter­ven­tion: none. Meas­ure­ment: serum lev­els of sol­u­ble E-selec­tin, ICAM-1, plas­ma homo­cys­teine, vita­min E and mal­on­di­al­de­hyde (MDA), as well as lip­o­pro­tein frac­tions were meas­ured at each time ­points.
­Results. The mean per­cent­age ­change for E-selec­tin ­between the M-phase and L-phase, F-phase and L-phase were 6% and 4%, respec­tive­ly, p<0.005, p<0.066. Lev­els of ICAM-1, vita­min E and mal­on­di­al­de­hyde did not vary ­through the cycle. Homo­cys­teine was not dif­fer­ent ­between M-phase and F-phase (10.39±0.68 μmol/l vs 10.33±0.65), nor ­between M-phase and L-phase (10.39±0.68 vs 9.77±0.75 μmol/l). ­Although the mean per­cent­age ­decrease in homo­cys­teine ­between F- and L-phas­es was sig­nif­i­cant (5.36±0.53%, p=0.029), the abso­lute ­decrease in con­cen­tra­tions was not (p=0.07). There were no cycli­cal chang­es in total, LDL, HDL cho­les­te­rol, tri­gly­ce­rides, apo A-I, apo B or Lp(a). Using a lin­e­ar regres­sion model, after cor­rec­tion for age, smok­ing, body mass index (BMI) and waist/hip ratio (WHR), oes­tro­gen lev­els were the only pre­dic­tor of E-selec­tin dur­ing the L-phase p<0.005. There were no sig­nif­i­cant cor­re­la­tions ­between oes­tro­gen with lip­ids, apol­i­pop­ro­teins or homo­cys­teine. There was an inter­est­ing sig­nif­i­cant uni­var­i­ate cor­re­la­tion ­between homo­cys­teine with low-den­sity-lip­o­pro­tein (LDL) cho­les­te­rol and apo B through­out all phas­es of the cycle, which per­sist­ed after cor­rec­tion for the ­effects of age, BMI, WHR and smok­ing his­to­ry. Mul­ti­ple regres­sion anal­y­sis with all these fac­tors ­showed homo­cys­teine to be a sig­nif­i­cant pre­dic­tor of apo B con­cen­tra­tion dur­ing M (p=0.030) and L-phas­es (p=0.023) of the cycle and of LDL cho­les­te­rol in the M-phase (p=0.033).
Con­clu­sion. ­Female sex hor­mones may have small, ­though sig­nif­i­cant mod­ulat­ing role on E-selec­tin and homo­cys­teine metab­olism in ­healthy pre­men­o­pau­sal women. Fur­ther­more, the cor­re­la­tion ­between homo­cys­teine, LDL and apo B lev­els sug­gests that induc­tion of cho­les­te­rol syn­the­sis by homo­cys­teine, shown pre­vi­ous­ly in vitro, may be of rel­e­vance in vivo.

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