Obstetrics and Gynecology International 3 Table 1: Age, weight, and serum levels of total cholesterol, coenzyme Q10, α-tocopherol, and γ-tocopherol, the ratios of coenzyme Q10/cholesterol and α-tocopherol/cholesterol in women who used the contraceptive pill, vaginal ring, or transdermal patch and control subjects. Variables Age (y) Weight (lb) Total Cholesterol (mmol/L) TAOC (n = 5) (mmol Trolox equi./L) Coenzyme Q10 (μmol/L) α-Tocopherol (μmol/L) γ-Tocopherol (μmol/L) CoQ10/Cholesterol (pmol/μmol) α-Toco/Cholesterol (nmol/μmol) Contraceptive Nonusers Group 1 (n = 40) 35.8 ± 7.1 146 ± 15 4.86 ± 1.5 1.33 ± 1.2 0.69 ± 0.2a,b 14.2 ± 3.0a,b 2.66 ± 1.2 143.0 ± 47c 2.9 ± 0.6 Pill Group 2 (n = 15) 31.9 ± 5.6 138 ± 13 4.30 ± 0.8 1.00 ± 0.41b 0.44 ± 0.1b 10.9 ± 2.1 2.92 ± 0.72 102.3 ± 26 2.5 ± 0.5 Contraceptive users Ring Group 3 (n = 5) 33.5 ± 3.5 124 ± 10 4.54 ± 09 0.85 ± 0.05 0.39 ± 0.1 10.9 ± 2.6 3.28 ± 1.9 85.9 ± 16 2.4 ± 0.6 Patch Group 4 (n = 10) 30.1 ± 7.6 138 ± 19 4.54 ± 0.9 0.65 ± 0.04 0.30 ± 0.1 10.2 ± 1.6 3.01 ± 0.7 66.0 ± 20 2.6 ± 0.4 Values are mean ± SD. aP < .001, group 1 versus 2, 4; and bP < .05, group 1 versus 3; group 2 versus 4; and cP < .05, group 1 versus 2, 3, 4, by Student’s t-test. than might be expected based solely on the amount of EE delivered [7]. Exposure to EE was previously reported to be highest for patients using the transdermal patch. The mean area-under-the curve was 3.4 times higher in the patch group than in the NuvaRing and 1.6 times higher than in the OC group [7]. It may be suggested that the greater bioavailability of EE reported with the transdermal patch may be responsible for the greatest lowering eﬀect on serum CoQ10 levels and TAOC observed in our study. Vaginal administration of contraceptive hormones allows low, steady, and continuous dosing and results in stable serum EE levels. The beneﬁts of this low, precise dosing include lower systemic exposure to EE and a low incidence of estrogen-related side eﬀects. Minimizing exposure to EE is desirable as it reduces estrogen-related side eﬀects. NuvaRing is a monthly contraceptive vaginal ring. It works by releasing a continuous low dose of estrogen and progestin, on average 0.120 mg of etonogestrel and 0.015 mg of ethinyl estradiol per day over the period of use. NuvaRing has been shown to produce a mean serum EE concentrations of 19 pg/ml and maximum serum concentrations of 35 pg/ml [6, 7, 11]. Estrogen levels from the contraceptive vaginal ring (NuvaRing) are the lowest in any combined hormonal con- traception currently available, and peak levels of ethinyl E2 are signiﬁcantly lower in NuvaRing users than transdermal patch or oral contraceptive users [7, 11, 12]. Lastly, OC users have the greatest degree of variation in ethinyl E2 serum concentrations [7]. The present three-way comparison in this study of diﬀerent hormonal contraceptives with diﬀerent routes of administration and antioxidant status has not been previ- ously reported [6, 7]. We previously described the eﬀects of menopause and hormonal replacement therapy on decreased serum CoQ10 and α-tocopherol levels [9]. In this study, we examined the inﬂuence of diﬀerent hormonal methods on lipid-soluble antioxidants in hormonal users. CoQ10 is regarded as one of the most important antioxi- dants. CoQ10 can be obtained from dietary sources of meat, ﬁsh, vegetables, and fruits. A typical Western diet provides 3 to 5 mg of CoQ10 daily, of which approximately two- thirds are derived from meat and poultry [13]. Tissues with high energy requirements, such as the heart, kidney, liver, and skeletal muscle contain high amounts of CoQ10 [14]. α-Tocopherol is generally considered the most potent antioxidant in the active tocopherols [15]. Vitamin E can be obtained from dietary sources of almonds, egg yolks, leafy vegetables, sunﬂower seeds, vegetable oils, and wheat germ. CoQ10 and α-tocopherol are lipid-soluble free radical scavengers located in cell membranes capable of neutralizing oxygen free radicals. Oxidative stress is implicated in the pathogenesis of many diseases [2, 3, 16]. The reduction-oxidation (redox) state constitutes a potential mechanism for the regulation of many metabolic processes through modulation of signaling pathways. Oxidative reactions are an essential part of several biological systems and can have toxic eﬀects depending on a critical balance between the oxidative stimulus and the antioxidant defense mechanisms available [1]. The imbalance between excessive redox generation and decreased antioxidant capacity leads to oxidative stress [16, 17]. It has been reported that an imbalance in the production of oxygen free radicals and the natural protective antioxidants can lead to oxidative stress-induced cell damage as a result of the excessive oxidation of lipids, nucleic acids, and proteins, and consequent apoptosis and cell loss [2, 3]. Antioxidants work cooperatively in biological systems and it is important to be able to correlate antioxidant measurements with antioxidant defenses and disease prevention. It is therefore recommended to study “total antioxidant capacity”, rather than monitoring individual antioxidant levels, which may be less aﬀected by dietary habits; [18, 19] hence the measurement of TAOC in our study. There has been increasing interest in measuring the protective antioxidant activity of a variety of biological ﬂuids and tissues. Most assays of TAOC utilize in vitro models of oxidative stress to which biological samples are exposed and the time to onset or the extent of oxidation is