Purpose: To assess estrogen-related changes in the redox status of the brain and liver proteins as well as the systemic oxidative stress in ovarectomised (OVX) rats Methods: Twelve-week-old, sexually mature female Sprague–Dawley rats (200-250g) were randomly divided into four groups: The following treatment combinations were administrated daily to all in 0.05 ml 96% ethanol solution by gastric gavage. (1) Sham operation (2) OVX rats (3) OVX rats [0.02 mg/kg/day of 17?-estradiol (E2) and 0.01 mg/kg/day of norethisterone acetate] (4) OVX rats [E2 (0.01 mg/kg/day) and drospirenon (0.02 mg/kg/day)]. Estrogen levels were determined using routine clinical-chemistry methods. We also measured protein oxidation parameters such as protein carbonyl (PCO), total thiol (T-SH) and the other oxidative stress markers malondialdehyde (MDA) and glutathione (GSH). Results: Ovariectomy resulted in abnormal elevation of plasma and tissue oxidative stress markers and changes in redox status of the proteins in tissue dependent manner. Supplementation of various estrogens combinations partially alleviated these abnormalities and restored redox homeostasis of proteins after the ovariectomy. Among the studied protein oxidation parameters, plasma and tissue PCO levels of the OVX rats were higher than those of the control groups (P < 0.01). Hormone replacement therapies (HRT) caused a decrease in PCO and MDA in both plasma and tissue of the OVX rats (P < 0.01). HRT in OVX rats decreased plasma MDA and increased liver and brain GSH (P < 0.01). Liver MDA levels of the Drospirenon-treated rats were lower than in the norethisterone acetate group (P < 0.01). On the other hand, Drospirenon increases brain GSH s more effectively than norethisterone acetate (P < 0.01). After bilateral oopherectomy, plasma and tissue T-SH levels decreased in the OVX group compared with control (P < 0.01). Norethisterone acetate increased plasma T-SH more effectively than Drospirenon (P < 0.05) Conclusions: The study showed the extent of oxidative protein damage (OPD) in this model of estrogen deficiency. The protective effect of estrogens against tissue specific OPD suggests that estrogens play an important role within the antioxidant defense systems in plasma, liver and brain. The exact molecular mechanisms leading to these findings are not yet completely known. Meanwhile, hormone replacement therapy for the prevention of OPD in a tissue specific manner may be required.

Oxidized low-density lipoproteins (oxLDL) are involved in initiation of atherosclerosis. Paraoxonase 1 (PON1), the isoenzyme of PON, is located on high-density lipoprotein (HDL) and protects against the oxidative modification of both HDL and LDL by hydrolysing lipid peroxides. Postmenopausal women have a higher risk of cardiovascular events compared with premenopausal women. The aim of this clinical study was to evaluate the effects of hormone replacement therapy (HRT) on oxLDL and PON1 activity in menopausal status. The subjects included 45 healthy postmenopausal women, aged 43 to 57 years, and 30 premenopausal women with regular cycles, aged 31 to 40 years. None of the participating women had a history of hypertension, diabetes mellitus or medications known to affect the cardiovascular system. Twenty five of the postmenopausal women received conjugated estrogens at dose of 0.625 mg/day per oral (P.O.) and medroxyprogesterone acetate (MPA) (1 mg/d P.O.) for 10 days. Twenty of the postmenopausal women received 17-beta estradiol (2 mg/day) and norethysterone acetate (NETA) (5 mg/day P.O.) for 10 days. Fasting blood samples were taken from premenopausal women (baseline) and postmenopausal women after HRT of 6 months to determine serum malondialdehyde (MDA), oxLDL, and PON1 activity. After 6-month therapy, MDA and oxLDL levels showed a statistically significant reduction in the treated groups versus baseline (p < 0.05), whereas PON1 activities were increased (p < 0.05). Increase in oxidative status may be one of the factors leading to reduction in PON1 activity and increased oxLDL in menapouse. HRT may be effective on oxidative stress and lipoprotein metabolism in apparrently healthy postmenopausal women.hormone replacement therapy; paraoxonase; oxidized low-density lipoprotein (oxLDL); malondialdehyde (MDA); oxidative stress

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There is lack of studies in literature about the long-term effects of hormone replacement therapies and cholesterol levels on mood scores in menopause. In the present study we have investigated whether serum lipid levels affect mood scores in menopause and evaluated the long-term effects of the combined hormone replacement regimens (HRT) on depressive symptoms in postmenopausal women. In this prospective-randomized, placebo-controlled, double-blind study, 286 women in menopause were divided into four groups according to therapeutic regimens they received; 1) Conjugated equine estrogen (CEE) of 0.625 mg plus medroxyprogesterone acetate (MPA) of 2.5 mg (n = 79), 2) CEE (0.625 mg) plus MPA of 5 mg (n = 77), 3) tibolone of 2.5 mg (a selective tissue estrogenic activity regulator) (n = 76), and 4) Calcium (Ca) of 1,000 mg (n = 54). Beck Depression Inventory (BDI), and serum levels of lipoprotein lipids were assessed before and after 12-months of treatment with oral continuous HRT and Ca supplementation. BDI scores in the study groups were not correlated with lipid profiles. We compared two subgroups of patients with initial BDI scores 0-14 (normal mood scores) in order to asses for the possible relation between the lipid profile and mood. Following treatment, first subgroup had increased scores to 15-30 (mildly depressed women, n = 27) and the second subgroup preserved BDI scores of 0-14 (normal mood scores, n = 23). Serum levels of total cholesterol, high-density lipoprotein, lowdensity lipoprotein and body mass index were found to be similar between these two groups. BDI scores decreased significantly in all HRT groups after 12 months of treatment, compared to Ca group ( p < 0.05). We did not observe any correlation between BDI scores and lipid profiles before and following continuous HRT or Ca supplementation. Continuous combined hormone replacement regimens, CEE + MPA and tibolone, have superior long-term effects on mood scores in menopause and should be considered during