Effects of estrogen-only therapy on LDL oxidation in women with hysterectomy: does paraoxonase genotype play a role?
OBJECTIVE
This study investigated the effects of estrogen-only therapy on lipid profile (through susceptibility of low density lipoproteins to oxidation) and on oxidant-antioxidant parameters in surgical menopausal women. PON genotypes are also evaluated considering that they may be associated with the personal differences observed in antioxidant effects induced by estrogen.


METHODS
Thirty women who had undergone hysterectomy+bilateral ovariectomy in the last 3 years, with causes other than malignancy were included and given estrogen-only (Premarin-Wyeth Inc. 0.625 mg/day/6 months, equine conjugated estrogen). Blood samples were collected at baseline, first and sixth month of treatment. Serum (total antioxidant activity-TAO and PON activity), erythrocyte (TBARS and catalase activity), LDL and Cu2+ induced ox-LDL (TBARS and diene levels) samples were evaluated and PON1 192 polymorphisms were determined by PCR amplification & restriction enzyme digestion.


RESULTS
At the sixth month, a higher TAO activity (p=0.016) and a lower eTBARS (p=0.028) were detected compared to the basal values. LDL and Cu induced ox-LDL TBARS levels at the sixth month of treatment were significantly (p=0.012 and 0.026, respectively) lower compared to the pretreatment values. Baseline eTBARS (p=0.007), LDL TBARS (p=0.044) and eCAT (p=0.033) activities were significantly higher in homozygote Q allele carriers compared to subjects with R allele. LDL TBARS and Cu2+ induced ox-LDLTBARS of QQ subjects (p=0.018 and 0.050) as well as LDL TBARS of QR subjects (p=0.044) showed a significant decrease with estrogen-only treatment.


CONCLUSIONS
Our study drives the attention to PON polymorphism in postmenopausal women who have risk for atherosclerosis. Although our data is limited, this study is the first that focuses on the role of PON genotypes in antiatherosclerotic effects of estrogen-only and provides important points for further studies.
Akçay
Yasemin D
YD
Ege University, Faculty of Medicine, Department of Biochemistry, Bornova Izmir 35100, Turkey.
Sagin
Ferhan G
FG
Sendağ
Fatih
F
Oztekin
Kemal
K
Sozmen
Eser Y
EY
D000975:Antioxidants / Q000378:metabolism*; D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics* / Q000517:prevention & control; D002374:Catalase / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood / Q000378:metabolism*; D004912:Erythrocytes / Q000737:chemistry / Q000201:enzymology; D015914:Estrogen Replacement Therapy / Q000379:methods*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D005260:Female; D005838:Genotype; D006801:Humans; D007044:Hysterectomy; D008875:Middle Aged; D015999:Multivariate Analysis; D010052:Ovariectomy; D010084:Oxidation-Reduction; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D000975:Antioxidants; D008078:Cholesterol, LDL; D004966:Estrogens, Conjugated (USP); D017392:Thiobarbituric Acid Reactive Substances; D002374:Catalase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human