Risk factors for persistent cervical intraepithelial neoplasia grades 1 and 2: managed by watchful waiting.

OBJECTIVE: : This study examines risk factors for persistent cervical intraepithelial neoplasia (CIN) and examines whether human papillomavirus (HPV) testing predicts persistent lesions. MATERIALS AND METHODS: : Women with histologically diagnosed CIN 1 or CIN 2 (n = 206) were followed up every 3 months without treatment. Human papillomavirus genotyping, plasma levels of ascorbic acid, and red blood cell folate levels were obtained. Cervical biopsy at 12 months determined the presence of CIN. Relative risk (RR) was estimated by log-linked binomial regression models. RESULTS: : At 12 months, 70% of CIN 1 versus 54% of CIN 2 lesions spontaneously regressed (p < .001). Levels of folate or ascorbic acid were not associated with persistent CIN at 12 months. Compared with HPV-negative women, those with multiple HPV types (RRs ranged from 1.68 to 2.17 at each follow-up visit) or high-risk types (RRs range = 1.74-2.09) were at increased risk for persistent CIN; women with HPV-16/18 had the highest risk (RRs range = 1.91-2.21). Persistent infection with a high-risk type was also associated with persistent CIN (RRs range = 1.50-2.35). Typing for high-risk HPVs at 6 months only had a sensitivity of 46% in predicting persistence of any lesions at 12 months. CONCLUSIONS: : Spontaneous regression of CIN 1 and 2 occurs frequently within 12 months. Human papillomavirus infection is the major risk factor for persistent CIN. However, HPV testing cannot reliably predict persistence of any lesion.

Effects of menstrual cycle and oral contraceptive use on serum levels of lipid-soluble antioxidants.

OBJECTIVE: The purpose of this study was to examine the influence of menstrual cycle and oral contraceptive use on serum levels of lipid-soluble antioxidants. STUDY DESIGN: In this cross-section study, nonfasting blood samples were collected twice from 10 healthy premenopausal women during the follicular phase (between days 8 and 11) and the luteal phase (between days 18 and 22) of their same menstrual cycle. In addition, blood samples from 15 premenopausal women who used oral contraceptive for at least 6 months and 40 women who did not use oral contraceptive were collected randomly at any day of the menstrual cycle. Serum levels of coenzyme Q10, alpha-tocopherol, gamma-tocopherol, beta-carotene, alpha-carotene, and lycopene were determined using high pressure liquid chromatography. RESULTS: Serum coenzyme Q10 and alpha-tocopherol levels were significantly lower during the follicular phase compared with the luteal phase of the same menstrual cycle (P < .05). Oral contraceptive use also significantly decreased coenzyme Q10 and alpha-tocopherol (P < .001). Other antioxidant levels were comparable. CONCLUSION: Alterations in coenzyme Q10 and alpha-tocopherol levels during the menstrual cycle and in oral contraceptive users should be taken into consideration, concerning the future antioxidant research in premenopausal women. Further studies are needed to investigate the potential role of endogenous and exogenous ovarian hormones on oxidative stress in women.

Effects of menopause and hormone replacement therapy on serum levels of coenzyme Q10 and other lipid-soluble antioxidants.

The present study examines the influence of menopause and hormone replacement therapy (HRT) on serum levels of coenzyme Q(10) and other lipid-soluble antioxidants in normal women. Serum levels of coenzyme Q(10), alpha-tocopherol, gamma-tocopherol, beta-carotene and lycopene in 50 premenopausal women (not using oral contraceptives), 33 healthy postmenopausal and 15 postmenopausal women on HRT ("Prempo"; combination of 0.625 mg conjugated estrogen and 2.5 mg medroxyprogesterone acetate) were measured by high-pressure liquid chromatography. Lipid profiles were also analyzed. Significantly higher serum coenzyme Q(10) and alpha-tocopherol levels were detected in postmenopausal compared with premenopausal women (P < 0.05, and < 0.001); whereas, in postmenopausal subjects on HRT, we detected a significant decrease in coenzyme Q(10) and gamma-tocopherol levels (P < 0.001, and < 0.05) and increased alpha-tocopherol levels (P < 0.05). Serum levels of beta-carotene, lycopene, LDL, HDL, cholesterol and triglyceride were comparable among the study groups. Coenzyme Q(10) is postulated to be involved in preventing cardiovascular disease (CVD) because of its bioenergetics role in the mitochondrial respiratory chain and its antioxidant properties at the mitochondrial and extramitochondrial levels. The decrease in serum concentrations of coenzyme Q(10), produced by HRT, may promote oxygen free radical-induced membrane damage and may, thus alter cardiovascular risk in postmenopausal women. HRT-induced reductions in lipid-soluble antioxidant(s) levels, and its potential consequences on CVD, needs to be further investigated.

Effects of oral, vaginal, and transdermal hormonal contraception on serum levels of coenzyme q(10), vitamin e, and total antioxidant activity.

The use of the transdermal contraceptive patch is associated with greater bioavailability of ethinyl estradiol (EE) compared with contraceptive vaginal ring or oral contraceptives (OC). We compared the influences of three contraceptive methods (OC, vaginal ring, and transdermal patch) on serum levels of coenzyme Q(10), alpha-tocopherol, gamma-tocopherol and total antioxidant capacity in premenopausal women. Blood samples from 30 premenopausal women who used hormonal contraception for at least 4 months were collected. Forty subjects who did not use any contraception were studied as control. Serum levels of coenzyme Q(10), alpha-tocopherol and gamma-tocopherol were measured by high-pressure liquid chromatography. Serum samples were also assayed for total antioxidant capacity (TAOC). Serum levels of coenzyme Q(10) and alpha-tocopherol were found to be significantly lower (P < .05) in all three contraceptive users compared with controls. Contraceptive patch users had the lowest levels of coenzyme Q(10) levels compared with normal subjects. Serum TAOC levels were significantly lower (P < .05) among the contraceptive user groups. Alterations in coenzyme Q(10) and alpha-tocopherol induced by hormonal contraception and the potential effect(s) of exogenous ovarian hormones should be taken into consideration in future antioxidant research.

Plasma uric acid levels in women with cervical intraepithelial neoplasia.

The objective of this study was to determine the association of plasma levels of uric acid, an endogenous antioxidant, in women with cervical intraepithelial neoplasia (CIN), while controlling for the confounding effects of human papillomavirus (HPV) infection, age, smoking, and use of oral contraception. Plasma-reduced and oxidized uric acid levels were determined in 650 women by high-performance liquid chromatography, employing electrochemical technique. The findings demonstrated that 1) plasma-reduced uric acid (PRUA) levels in women with CIN (n = 311) were significantly lower (P < 0.05) compared with women in a control group (n = 339); 2) according to multiple logistic regression analysis, PRUA levels were negatively (P = 0.0113) and HPV infection were positively associated (P < 0.0001) with CIN, after controlling for the confounding effects of the studied factors; 3) according to multiple regression analysis, there was a 31% decrease in CIN risk for each incremental increase of 1mg/dl of PRUA; and 4) according to polychotomous logistic regression analysis, independent of HPV infection, PRUA level was inversely associated with the histopathological graded severity of CIN. We have previously reported decreased plasma levels of exogenous antioxidants, for example, vitamins C and E, in women with CIN independent of HPV infection. The data suggest that plasma deficiencies of several antioxidants in HPV-infected uterine cervical tissue may create an oxidative environment that renders the tissue susceptible to free radical damage. It may be speculated that chronic free radical-induced tissue damage in the context of persistent HPV infection may be involved in the pathogenesis of CIN.

Lipid-soluble antioxidants and pregnancy: maternal serum levels of coenzyme Q10, alpha-tocopherol and gamma-tocopherol in preeclampsia and normal pregnancy.

It has been hypothesized that in preeclampsia, the antioxidant-deficient state may facilitate increased attacks of free radicals, which may result in endothelial cell damage. The purpose of this study was to investigate the association of three lipid-soluble antioxidants, coenzyme Q10, alpha-tocopherol and gamma-tocopherol, with preeclampsia and normal pregnancy. Serum levels of all three antioxidants in 42 women with normal pregnancies, 25 with mild preeclampsia and 28 with severe preeclampsia were measured by high-pressure liquid chromatography. A significant decrease was observed in serum levels of coenzyme Q10 and alpha-tocopherol (p < 0.001 for each by the Kruskal-Wallis rank test) in women with preeclampsia compared to levels in normal pregnancy. gamma-Tocopherol levels were comparable among the different groups. Logistic regression analysis revealed significant association between grades of preeclampsia and both serum coenzyme Q10 and alpha-tocopherol levels (p = 0.000 and 0.030, respectively). Coenzyme Q10 and alpha-tocopherol are potent antioxidants, and the decreased levels of these two antioxidants in preeclampsia may alter the normal redox balance, thereby reducing the ability of antioxidant defenses to protect against free radical damage. This could be a factor in the endothelial cell damage observed in preeclampsia.

Alpha-tocopherol and alpha-tocopheryl quinone levels in cervical intraepithelial neoplasia and cervical cancer.

OBJECTIVE: alpha-Tocopherol is a potent antioxidant that protects cell membranes against oxidative damage. Red blood cell alpha-tocopherol levels reflect membrane alpha-tocopherol concentrations, and altered levels may suggest membrane damage. The objective of this study was to determine the levels of alpha-tocopherol and alpha-tocopheryl quinone, the oxidized product of alpha-tocopherol, in plasma and red blood cells that were obtained from control subjects and patients with cervical intraepithelial neoplasia and cervical cancer. STUDY DESIGN: In this cross-sectional study, 72 women, (32 African American and 40 Hispanic) were recruited. Among these subjects, 37 women had cervical intraepithelial neoplasia; 14 women had cervical cancer, and 21 women were considered control subjects, who had normal Papanicolaou test results. alpha-Tocopherol and alpha-tocopheryl quinone levels were determined in red blood cell and plasma by high-pressure liquid chromatography. RESULTS: Plasma levels of alpha-tocopherol and alpha-tocopheryl quinone were decreased significantly (P=.012 and=.005, respectively, by Kruskal-Wallis test) in study groups compared with the control group; red blood cell levels of alpha-tocopherol and alpha-tocopheryl quinone were not altered significantly. CONCLUSION: The lower alpha-tocopherol level that was observed in this study is consistent with our previous reports of decreased antioxidant concentrations and increased oxidative stress in women with cervical intraepithelial neoplasia. Unaltered red blood cell alpha-tocopherol and alpha-tocopheryl quinone levels suggest undamaged cell membrane. Further studies are needed to investigate the potential role of oxidative stress in cervical intraepithelial neoplasia.