Impact of long-term hormone replacement therapy on in vivo and in vitro markers of lipid oxidation.
Postmenopausal hormone replacement therapy (HRT) with estrogen has been suggested to inhibit oxidation of low-density lipoprotein (LDL) in vitro, but progestins may oppose this effect. We studied whether estrogen HRT and combined HRT with estrogen and progestin differ in their ability to resist in vivo and in vitro oxidation of lipids. Study group included 15 women on oestradiol valerate (mean age 56 years, treatment duration 10.5 years) and 15 women on combined HRT with oestradiol valerate and levonorgestrel (mean age 58 years, treatment duration 11.3 years). In addition to lipid and apolipoprotein concentrations, the lagtime of LDL to oxidation, the rate of the propagation phase and the maximum concentration of conjugated dienes were recorded as indices of LDL susceptibility to copper-induced oxidation in vitro. As an in vivo marker of oxidative stress we measured 24-h excretion of urinary 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha). All measurements were done after long-term HRT (baseline), after 4 weeks pause and again 3 weeks after reintroduction of HRT. High-density lipoprotein (HDL) cholesterol and apolipoprotein AI concentrations were significantly higher and LDL to HDL ratio significantly lower after long-term oestradiol valerate therapy than after combined therapy. Simultaneously, the triglyceride and lipoprotein (a) levels were higher in the estrogen group. Susceptibility of LDL to oxidation and the level of 8-iso-PGF2alpha were similar in both groups at all measurement points, and treatment group was not a statistically significant determinant of these markers at baseline. According to these results, estrogen and combined HRT do not differ in their abilities to oppose LDL oxidation in vitro or systemic oxidative stress in vivo, but have differential effects on blood lipids.
Rontu
Riikka
R
Laboratory of Atherosclerosis Genetics, Tampere University Hospital, Centre for Laboratory Medicine, FinnMedi 2, P.O. Box 2000, FIN-33521 Tampere, Finland. riikka.malin@csc.fi
Solakivi
Tiina
T
Teisala
Klaus
K
Lehtimäki
Terho
T
Punnonen
Reijo
R
Jokela
Hannu
H
D001053:Apolipoproteins / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D017698:Postmenopause; D013997:Time Factors
D001053:Apolipoproteins; D015415:Biomarkers; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C075750:8-epi-prostaglandin F2alpha; D004958:Estradiol; D016912:Levonorgestrel; D015237:Dinoprost