A prospective study on the effects on hemostasis of two oral contraceptives containing drospirenone in combination with either 30 or 20 microg ethinyl estradiol and a reference containing desogestrel and 30 microg ethinyl estradiol

PURPOSE: In this open-label, randomized study, we assessed the effects on hemostasis of two combined oral contraceptives containing drospirenone (DRSP) as progestogen component. METHODS: Three milligrams of DRSP, a progestogen with antimineralocorticoid activity, was combined with either 30 or 20 microg ethinyl estradiol (EE) (DRSP/30EE; DRSP/20EE) and compared with a preparation containing 150 microg desogestrel (DSG) and 30 microg ethinyl estradiol (DSG/30EE). A total of 75 healthy female volunteers aged 18-35 years were enrolled. The hemostasis variables were measured in the medication-free precycle (baseline); in the first, third and sixth treatment cycle; and in the follow-up phase. The target variables for comparison were the relative changes from baseline to Cycle 6. RESULTS: Data of 25 volunteers in each group were valid for the per-protocol evaluation. Most changes in hemostasis variables were similar in the three treatment groups. All procoagulatory variables and the anticoagulatory variable protein C antigen increased slightly, while protein S antigen and activity decreased. For fibrinogen and protein S activity, the changes were statistically significant: less pronounced with DRSP/20EE compared to DSG/30EE at Cycle 6. There were no statistically significant differences in the changes of antifibrinolytic variables, the global clotting tests and D-dimer. All pairwise comparisons of DRSP/30EE vs. DSG/30EE yielded nonsignificant results; however, there was a trend of a lower impact of DRSP/20EE on nearly all hemostatic parameters compared to the 30EE products. All three study treatments were safe and well tolerated by the volunteers and provided adequate contraceptive reliability. CONCLUSION: The changes in the hemostatic variables for DRSP/20EE were less pronounced compared to DSG/30EE and DRSP/30EE. The results were in accordance with previous reports on effects of similar OCs.     

Different oral contraceptives and voice quality--an observational study

The classical literature on endocrine effect on voice considers oral contraceptives (OCs) as a risk factor for voice. However, recent studies revealed no adverse effect of new-generation OCs on voice. It was also suggested that OCs could improve specific voice characteristics via different mechanisms. The aim of the present study was to evaluate the effect of OCs on voices of women who use different formulations containing drospirenone (n=10), desogestrel (n=9) and gestodene (n=10). Acoustic voice measures of the 29 women were evaluated twice during the menstrual cycle. Fundamental frequency, frequency as well as amplitude stability and noise characteristics were measured using a computerized voice analysis program. Results indicated that vocal stability and quality were similar in the three groups tested. Marginal differences were observed between the drospirenone group and the other two groups. This preliminary observational study indicates that although drospirenone was previously shown to reduce water retention, this effect was not found to directly influence voice characteristics of women who use OCs.     

The effects of seven monophasic oral contraceptive regimens on hemostatic variables: conclusions from a large randomized multicenter study

We investigated the effects of ethinylestradiol dose (50, 30 and 20 μg) and progestogen type [desogestrel (DSG), gestodene (GSD), levonorgestrel (LNG) and norgestimate (NGM)] in oral contraceptives on 24 hemostatic variables. In a multicenter, randomized, comparative study, 707 healthy, nonsmoking, nulliparous women were treated for six cycles with one of the seven monophasic oral contraceptives tested. Significantly greater increases in prothrombin fragment 1+2 and factor VII (activity and antigen), were found in the DSG, NGM and GSD groups compared to the LNG group. Similarly, significantly lower levels of protein S (free and total) and increased APC-sr (endogenous thrombin potential based) were found in the same groups compared with the LNG group. In addition, the estradiol dose (50 vs. 30 μg) significantly influenced these parameters. All changes were within the normal range and have not been associated with an increased risk of venous thromboembolic event (VTE). However, raised levels of these variables are associated with prothrombotic states such as pregnancy. The significance of the haemostatic changes found in this study in relation to VTE risk remains to be determined, but results of this study probably cannot explain the differences in risk of VTE between OCs containing different progestogens.     

Effect of four oral contraceptives on hemostatic parameters

This is the first double-blind, controlled, randomized study comparing the effect of different estrogen components in oral contraceptives (OCs) on hemostasis variables. Four groups of 25 women each were treated for six cycles with monophasic combinations containing 21 tablets with either 30 microg ethinylestradiol (EE) + 2 mg dienogest (DNG) (30EE/DNG), 20 microg EE + 2 mg DNG (20EE/DNG), 10 microg EE + 2 mg estradiol valerate (EV) + 2 mg DNG (EE/EV/DNG) or 20 microg EE + 100 microg levonorgestrel (LNG) (EE/LNG). Blood samples were taken on Days 21-26 of the control cycle and on Days 18-21 of the first, third and sixth treatment cycle. Treatment with all four OCs caused an increase in levels of fibrinogen, prothrombin fragment 1+2, D-dimer, plasminogen, plasmin-antiplasmin complex and an increase in protein C activity, a decrease in antithrombin activity, tissue-plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI), and a slight decrease in the sensitivity to activated protein C, but no significant change in that of the thrombin-antithrombin complex. In users of the DNG-containing OCs, the reduction in total and free protein S, and in t-PA and PAI was dependent on the EE dose, while factor VII activity was elevated, but not significantly different from EE/LNG. The results are in agreement with those of previous studies. The effects of EE/EV/DNG on total and free protein S and on t-PA and PAI were lower than those of 20EE/DNG, suggesting that the impact of 2 mg EV on several hemostasis variables is less than that of 10 microg EE. The results show an antagonistic effect of LNG on the EE-induced rise of factor VII activity and fragment 1+2 and on the EE-dependent reduction of total and free protein S.     

Treating acne with oral contraceptives: use of lower doses

Oral contraceptives (OCs) have been shown to effectively treat acne. Clinical trials of various doses of ethinyl estradiol (EE) combined with progestins such as levonorgestrel, desogestrel, norgestimate, gestodene, cyproterone acetate and drospirenone in monophasic, triphasic and combiphasic formulations used to treat acne in women are reviewed here. Open-label and comparative studies beginning in the 1980s were the first to demonstrate objective and subjective reductions in the incidence of acne, severity of existing acne and seborrhea. Placebo-controlled trials have corroborated these findings with a trend toward effective acne treatment with declining doses of EE. Significant reductions in total, inflammatory and noninflammatory lesions compared with placebo have been demonstrated with an OC containing the low dose of 20 microg of EE. Collectively, these findings support the use of low-dose OCs for the treatment of acne.     

Long-term effects of combined oral contraceptives on markers of endothelial function and lipids in healthy premenopausal women

The aim of this prospective cross-over study was to investigate the effect of two low-dosed oral contraceptives on markers of endothelial function and plasma lipids. Twelve healthy, nonsmoking women (mean age: 21.7 years) were recruited from the family planning clinic of the university hospital Zurich. For 6 months the participants received a treatment with two contraceptive pills containing 30 microg ethinyl estradiol/150 microg levonorgestrel (three cycles) and 30 microg ethinyl estradiol/75 microg gestodene (three cycles). Plasma levels of endothelin-1, nitric oxide, cholesterol, and HDL were measurement before and during treatment with both oral contraceptive treatments.No significant changes in the plasma levels of nitric oxide and endothelin-1, both important regulators of the vascular tone, were observed during oral contraceptive use. A significant negative correlation was found between nitric oxide and endothelin-1 and nitric oxide and cholesterol. There was a positive correlation between endothelin-1 and cholesterol. In conclusion, the investigated contraceptive pills did not cause major changes in circulating nitric oxide and endothelin-1 plasma levels.     

Effect of dienogest-containing oral contraceptives on lipid metabolism

In a double-blind, controlled, randomized, four-arm, bicentric clinical study, the effect of four oral contraceptives (OCs) on lipid metabolism was investigated. Four groups composed of 25 volunteers each (mean age 26.1 +/- 4.5 years; body mass index 21.9 +/- 2.8 kg/m(2)) were treated for six cycles with monophasic combinations containing 21 tablets with either 30 microg ethinyl estradiol (EE) + 2 mg dienogest (DNG) (30 EE/DNG), 20 microg EE + 2 mg DNG (20 EE/DNG), 10 microg EE + 2 mg estradiol valerate (EV) + 2 mg DNG (EE/EV/DNG), or 20 microg EE + 100 microg levonorgestrel (LNG; EE/LNG). The study was completed by 91 women. Blood samples were taken by venipuncture after at least 12 h fasting on Days 21-26 of the control cycle and Days 18-21 of the first, third, and sixth treatment cycle. There were clear differences between the effects of EE/LNG and the formulations containing estrogens and DNG. Although EE/LNG did not change the triglycerides levels, a significant increase was observed during treatment with the DNG-containing preparations. Although EE/LNG significantly reduced HDL-CH and HDL(2)-CH, there was a nonsignificant increase with the DNG-containing OCs. No change was observed in the levels of HDL(3)-CH. A significant rise in apolipoprotein A1 occurred during intake with the three DNG-containing formulations, but not with EE/LNG. In contrast to the women treated with combinations of estrogens and DNG, apolipoprotein B rose significantly in the women in the EE/LNG group. Lipoprotein (a) was significantly reduced by 30 EE/DNG and EE/LNG and remained unaltered with 20 EE/DNG and EE/EV/DNG. Altogether, the changes in lipid metabolism caused by the DNG-containing formulations appeared to be more favorable than those observed with EE/LNG. In OCs with DNG, the EE dose does not seem to play a major role with respect to the effect on lipids.     

Study of low-density lipoprotein receptor regulation by oral (steroid) contraceptives: desogestrel, levonorgestrel and ethinyl estradiol in JEG-3 cell line and placental tissue

BACKGROUND: The aim of this study was to compare in vitro the role of two oral contraceptives, desogestrel (a less androgenic derivative of levonorgestrel) and levonorgestrel--alone and in combination with ethinyl estradiol--on low-density lipoprotein (LDL) receptor regulation by assessing receptor protein expression and functional effectiveness. STUDY DESIGN: Placental tissue and cultured placental cells (JEG-3) were used to study the expression and endocytotic activity of LDL receptor protein. The expression of the receptor was assessed by immunocytochemistry and immunoblot assays with and without contraceptive challenge. Functioning activity of LDL receptor was studied by measuring the rate of uptake of LDL by placental cells. Quantification of LDL was based on the total cholesterol content of the lipoprotein. RESULTS: A combination of desogestrel (20 ng/mL of incubation medium) and ethinyl estradiol (10 ng/mL of incubation medium) maintained the LDL receptor at high level of expression and functioning mode. In contrast, the double-blind preparation of levonorgestrel (20 ng/mL) and ethinyl estradiol (10 ng/mL) had shown much lower expression as well as receptor-mediated LDL uptake. The concentration of contraceptives used in this study was similar to the prevailing concentration of oral contraceptives in clinical use. CONCLUSION: Higher expression of LDL receptor and enhanced rate of LDL uptake by the receptor protein projects the possibility that there might be less atherosclerosis-related disorders from the combination of desogestrol and ethinyl estradiol.     

Primary dysmenorrhea treatment with a desogestrel-containing low-dose oral contraceptive

This randomized, double-blind, placebo-controlled exploratory study examined the efficacy and safety of a low-dose oral contraceptive (Mircette®), desogestrel/ethinyl estradiol [DSG/EE] and ethinyl estradiol [EE]) in relieving the symptoms of dysmenorrhea. Twenty-three clinics in the United States enrolled 77 women (age ≤32 years) with primary dysmenorrhea documented for at least four consecutive cycles. Forty participants received DSG/EE&EE and 37 received placebo for four consecutive 28-day cycles. The intensity of menstrual-related distress was measured with the Menstrual Distress Questionnaire (MDQ). Patient diaries were used to assess number of school/work days missed as well as the use of rescue medication. Participants receiving DSG/EE&EE recorded reduced menstrual pain severity, lower total MDQ scores, and significantly less menstrual cramping. No significant change in bloating, anxiety, loneliness, weight gain, or acne was reported. The DSG/EE&EE formulation shows promise for the treatment of primary dysmenorrhea and was well tolerated by the participants in this study.     

The effects of two monophasic oral contraceptives containing 30 mcg of ethinyl estradiol and either 2 mg of chlormadinone acetate or 0.15 mg of desogestrel on lipid, hormone and metabolic parameters

Background

This study was conducted to compare the effects of two monophasic oral contraceptives (OCs) containing ethinyl estradiol (EE) 30 mcg+either chlormadinone acetate (CMA) 2 mg (Belara^®) or 0.15 mg desogestrel (Marvelon^®) on lipid, hormone and other relevant metabolic parameters.

Study design

Markers of lipid and carbohydrate metabolism, and reproductive hormone levels, were measured in 45 subjects randomly assigned to 6 months of treatment with one of the two OCs. The cortisol response to adrenocorticotrophic hormone (ACTH) stimulation was also evaluated.

Results

In both treatment groups, triglycerides, high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) AI and Apo AII levels increased; low-density lipoprotein cholesterol (LDL-C) and the LDL-C/HDL-C ratio decreased; and total cholesterol and lipoprotein(a) were unchanged during treatment. Effects on HDL-C, Apo AI, LDL-C and the LDL-C/HDL-C ratio were more evident in the EE 30 mcg+CMA 2 mg group. Follicle-stimulating hormone, luteinizing hormone and androgen levels decreased and sex hormone-binding globulin levels increased in both groups. Both OCs increased basal cortisol levels and cortisol response to ACTH. Oral contraceptive did not have a clinically significant impact on carbohydrate metabolism.

Conclusions

Both low-dose monophasic OCs had comparable effects on lipid, hormone and metabolic parameters during six cycles of treatment in healthy female subjects. There was some evidence of a beneficial effect on atherogenic cardiovascular risk markers, which was slightly more pronounced with EE 30 mcg+CMA 2 mg.     

Effects of transdermal and oral contraceptives on estrogen-sensitive hepatic proteins

OBJECTIVE: The purpose of this study was to evaluate the effects of the contraceptive patch and an oral contraceptive (OC) on serum concentrations of estrogen-sensitive hepatic proteins, ethinyl estradiol (EE) and levonorgestrel (LNG). METHODS: Twenty-four women were randomized to receive three cycles of a contraceptive patch that delivers EE 20 microg/day and norelgestromin 150 microg/day or an OC that contains EE 35 microg and norgestimate 250 microg. Blood samples were taken at baseline and at the end of Cycle 3. Serum levels of sex-hormone-binding globulin (SHBG), thyroxine-binding globulin (TBG), corticosteroid-binding globulin (CBG) and C-reactive protein (CRP) were quantified by immunoassay methods. EE and LNG levels in patch users were measured by radioimmunoassay (RIA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. The paired t test and Student's t test were used for statistical analysis. RESULTS: Nineteen women completed the study (patch, n=10; OC, n=9). Treatment with both the patch and OC resulted in significant increases from baseline in SHBG, TBG and CBG. The increase in CRP was significant in the patch group and approached significance in the OC group. The increases in SHBG and TBG observed with the patch were significantly greater than those associated with the OC. By way of RIA and LC-MS/MS assay methods, the patch was associated with mean EE levels of 114 and 111 pg/mL, respectively. CONCLUSIONS: The serum concentrations of estrogen-sensitive hepatic proteins and EE associated with the patch suggest that this new contraceptive system may have relatively large net estrogen effects.     

Serum resistin levels in women taking combined oral contraceptives containing desogestrel or gestodene

Resistin is a hormone secreted by adipose tissue that could be involved in the development of insulin resistance. Previous studies confirmed that endogenous sex steroids may influence serum resistin concentration in women. The aim of our study was to investigate the influence of combined oral contraceptives containing desogestrel or gestodene on circulating levels of resistin. Fifty-three women were enrolled in the study. Thirteen patients received 20 μg ethinylestradiol/150 μg desogestrel, 15 women were treated with 20 μg ethinylestradiol/75 μg gestodene, 11 with 30 μg ethinylestradiol/150 μg desogestrel and 14 with 30 μg ethinylestradiol/75 μg gestodene. Blood samples for estimation of serum resistin and insulin levels were drawn before administration of oral contraceptive and after 6 cycles of therapy. We found that serum resistin level remained unchanged in women receiving ethinylestradiol/desogestrel and was reduced in women treated with formulations containing gestodene. We conclude that ethinylestradiol combined with desogestrel or gestodene is unlikely to induce insulin resistance through resistin pathway.     

An open label, comparative study of the effects of a dose-reduced oral contraceptive containing 20 microg ethinyl estradiol and 100 microg levonorgestrel on hemostatic, lipids, and carbohydrate metabolism variables

In this open label, randomized study we compared the influence of a dose-reduced oral contraceptive containing 20 microg ethinyl estradiol (EE) and 100 microg levonorgestrel (20 EE) with a reference preparation containing 30 microg EE and 150 microg levonorgestrel (30 EE) on hemostatic, lipids, and carbohydrate metabolism variables. Data from 48 volunteers were obtained. The direction of the change (increase or decrease) in most of the hemostatic variables were similar in both treatment groups. In particular, prothrombin fragment 1 + 2 increased during treatment, reaching a median percent change of 40% in the 20 EE group and of 17% in the 30 EE group after one year. D-Dimer fibrin split products remained virtually unchanged, with no change at Cycle 13. The median HDL2 cholesterol levels decreased by 26% in the 20 EE group and by 39.8% in 30 EE group (p = 0.0045 for group difference) after one year. The median one year change for LDL cholesterol was 3.23% in the 20 EE group, compared to 25% in the 30 EE group, for VLDL 11.1% compared to 38.8%, respectively, and for total triglycerides 10.0% compared to 37.5%, respectively. The median absolute change for the area under the curve (AUC)(0-3h) for glucose at treatment Cycle 13 was 41.25 mmol/L x min in the 20 EE group and 73.50 mmol/L x min in the 30 EE group. The AUC(0-3h) insulin at treatment Cycle 13 decreased in the 20 EE group by 1635.0 pmolL x min and increased in the 30 EE group by 11797.5 pmolL x min (p = 0.0491 for group difference). Both study treatments were safe and well tolerated by the volunteers.In conclusion, the balanced one-third dose reduction in this new oral contraceptive evoked similar effects on the hemostatic variables, but favorable results for the lipid and carbohydrate profiles.     

Efficacy of second versus third generation oral contraceptives in the treatment of hirsutism

OBJECTIVE: To compare second versus third generation combination oral contraceptives (OCs) in the treatment of hirsutism. METHODS: Women with hirsutism, as defined by a minimum Ferriman-Gallwey score of 10, were randomized in a double-blind fashion to receive an OC containing either ethinyl estradiol/desogestrel or ethinyl estradiol/levonorgestrel for 9 months of treatment. Ferriman-Gallwey scores, androgen levels and sex hormone-binding globulin were measured at baseline and every 3 months for the duration of the study. Hormones were measured in duplicate by radioimmunoassay. RESULTS: Of the 47 women enrolled, 24 were randomized to ethinyl estradiol/desogestrel and 23 were randomized to ethinyl estradiol/levonorgestrel. Mean sex hormone-binding globulin increased significantly in subjects using the desogestrel-containing contraceptive compared with the levonorgestrel-containing contraceptive. Ten subjects completed the 9 months of treatment in the levonorgestrel group and 11 completed the study in the desogestrel group. Mean free testosterone and 3alpha-androstanediol glucuronide decreased significantly in the group receiving ethinyl estradiol/desogestrel but not in the ethinyl estradiol/levonorgestrel group. Mean Ferriman-Gallwey scores decreased significantly in both treatment groups. Improvement in mean Ferriman-Gallwey score was 35.7 +/- 38.1% (p < 0.001) for the ethinyl estradiol/desogestrel arm and 33.4 +/- 27.3% (p < 0.001) for the ethinyl estradiol/levonorgestrel arm. There were no statistically significant differences found in the improvement of Ferriman-Gallwey scores between the two treatment arms, although the power to detect a difference was limited by the small sample size. CONCLUSIONS: Treatment of hirsute women with third generation OCs containing desogestrel results in a significant increase in sex hormone-binding globulin and decrease in free testosterone and 3alpha-androstanediol glucuronide. Both second and third generation OCs were clinically effective in treating hirsutism.     

两种单向复方口服避孕药对经前期综合征影响的研究

目的观察两种单向口服避孕药(OCs)优思明和妈富隆对育龄妇女经前期综合症(PMS)的影响。方法将自愿服用COC避孕的妇女随机分为两组,其中优思明(DRSP/EE)组47例,妈富隆(DSG/EE)组19例。两组均从月经周期第1天开始服药,1片/d,连续服用21天,之后停药7天。两组均连续服用6个周期(28天/周期)。两组对象在研究开始前及6个月经周期后各完成1份相同的经期不适问卷(MDQ)。计算服用避孕药前和服药6个周期后各组MDQ平均得分和平均得分的变化。结果①服药6个周期后,优思明组经前期水潴留和注意力损害评分、月经期水潴留评分比妈富隆组有显著性改善(P<0.05)。②优思明组服药6个周期后,经前期水潴留和消极情绪评分,月经期水潴留评分比服药前有显著性下降(P<0.05)。妈富隆组服药6个周期后,经前期消极情绪比服药前有显著性下降(P<0.05)。结论两种COC对PMS均有一定的改善作用;口服避孕药优思明比妈富隆对PMS的改善作用更加显著,这与DRSP抗盐皮质激素作用有关。     

230例孕妇口服避孕药止血的临床分析

目的探讨孕妇口服避孕药止血相关影响因素。方法研究对象随机选取在2010年1月至2012年6月期间在我医院就诊的人流、上环、取环术后阴道流血时间超过2周的妇女230例进行临床观察。结果 230例流血患者中有130例流血时间在14-20天,60例流血时间在21-35天,40例流血时间>35天。Cox比例风险回归模型统计分析后,表明口服避孕药止血影响因素有感染、不良分娩史、宫内残留、多次人工流产史,及女性内分泌紊乱等。结论妇科临床门诊对治疗口服避孕药止血的孕妇,其前提是要保证手术质量,手术操作规范,要求我们努力宣教生殖健康知识,及时处理术后不良反应。     

Gestodene: A review of its pharmacology,potency and tolerability in combined contraceptive preparations

Combined progestin–estrogen pills are an established and reliable contraceptive option used by women worldwide. Combined oral contraceptives (COCs) containing the progestins – gestodene, desogestrel or norgestimate – were developed to minimize androgenic side effects and are considered an effective, well-tolerated contraceptive option. Gestodene achieves contraceptive efficacy with the lowest dose of any progestin in a COC, and has an established and favorable short- and long-term tolerability profile. In this review we present an overview of the pharmacology, potency and tolerability of gestodene.     

Low-dose oral contraceptives: health consequences of discontinuation

Presently, the lowest effective estrogen dose available as a combination oral contraceptive (OC) in the United States is 20 μg of ethinyl estradiol (EE) with different progestins. Twenty micrograms of EE coupled with levonorgestrel results in fewer side effects and cycle control comparable with higher-dose pills. Differences between therapeutically equivalent and brand-name, low-dose oral contraceptives, with respect to the bioavailability of hormones, may interfere with contraceptive efficacy and increase breakthrough bleeding. One of the most common reasons why women discontinue OCs is increased breakthrough bleeding. Because after OC discontinuation most women switch to a less-effective method, or no method, of contraception, an increase in breakthrough bleeding could ultimately result in an increase in unintended pregnancy. Thus, substituting a therapeutically equivalent for a brand-name low-dose oral contraceptive may have significant clinical and economic effects on individual and public health.     

Reciprocal coordination of a combination oral contraceptive containing desogestrel+ethinyl estradiol on the expression of LOX-1 and LDLR in placental trophoblast cells

Background

The aim of this study was to assess the consistency of antiatherosclerotic potential of a combination oral contraceptive steroid (ethinyl estradiol+desogestrel) by rating its effect on the differential expression of the low-density lipoprotein receptor (LDLR) and lectin-like oxidized LDL (LOX-1) receptor.

Study Design

Cells from placental trophoblast cell line (JAR) and differentiated primary placental trophoblast cells isolated from term human placentae were used for this study. Expressions of LOX-1 and LDLR were assessed by immunoblot and immunocytochemistry assays. Differential effects of the constituent steroids in the combination of ethinyl estradiol and desogestrel were verified on the expression profile of the receptors.

Results

Desogestrel opposed the effect of ethinyl estradiol on LOX-1 expression, and when used in combination, the combination oral contraceptive reduced the expression of LOX-1 in contrast to LDLR. The characteristic change in the expressions of LOX-1 and LDLR showed an antiatherosclerotic improvisation at the unique combination of ethinyl estradiol (10 ng/mL) and desogestrel (20 ng/mL).

Conclusion

The aforesaid combination of ethinyl estradiol and desogestrel keeps LOX-1 and LDLR reciprocally expressed in antiatherosclerotic mode.