Combined Oral Contraceptives Group Research Articles

The effects of dienogest and combined oral contraceptives on protein S-specific activity in endometriosis patients

ObjectiveOne serious side effect of combined oral contraceptives (COCs) is venous thromboembolism. Reduced activity in activated protein C-related coagulation pathways is attributable to low protein S activity in one-third of Japanese patients with deep vein thrombosis. Herer, we quantified the behavior of protein S-specific activity in response to dienogest (DNG) and COCs using the protein S-specific activity assay system to explore its potential utility as a thrombosis marker. Study DesignThis was a prospective cohort study. Female patients aged 20 – 49 years who were starting drug treatment for endometriosis using DNG or COCs were enrolled. Blood samples were taken before treatment and at the first, third, and sixth months of treatment. To analyze the primary endpoints, changes in total protein S antigen levels, total protein S activity, and protein S-specific activity from baseline to each time point were estimated using a linear mixed-effects model. All statistical analyses were performed in the SAS software version 9.4 (SAS Institute, Cary, NC). A two-sided P < 0.05 was considered statistically significant. Results64 patients took DNG and 34 patients took COCs. Protein S-specific activity did not change significantly from baseline in the six months after treatment started in either group. In the DNG group, total protein S activity and total protein S antigen levels increased slightly from baseline levels after the treatment. The means for total protein S activity and total protein S antigen levels in the COC group remained within reference limits, but they both decreased markedly in the first month and stayed low. Protein S-specific activity in four women remaind below the reference limit throughout the whole study period, suggesting they may have potential protein S deficiencies. ConclusionThe effects of DNG on protein S were negligible, though both total protein S activity and antigen levels decreased soon after COC treatment began and remained low. As there was no VTE event during the study, further studies with larger numbers of patients will be needed to confirm that protein S-specific activity can be a surrogate maker of VTE risk.

Metabolomic study combined with the low-level light therapy of Chinese acupuncture points and combined oral contraceptives in treatment of primary dysmenorrhea: A prospective, multicenter, randomized controlled study

ObjectiveTo compare the changes of metabolites between Low-level light therapy (LLLT) and combined oral contraceptive (COC) after treatment of primary dysmenorrhea (PD), and to compare and analyze the biological and biochemical effects of the two treatments by analyzing the differences in metabolite profiles. MethodsA multicenter, double-blind, prospective, parallel, randomized controlled study was conducted on 69 women aged 16–35 years old with PD who were randomly divided into COC treatment group or LLLT treatment group. Low-level light therapy with light-emitting diodes (LED) was applied on two acupoints named “Guanyuan” (CV4) and “Qihai” (CV6). After 12 weeks of treatment intervention, blood samples were collected before and after treatment for metabolomic analysis. We used UPLC-MS/MS analysis to compare the differences in metabolite changes between LLLT and COC before and after treatment. Results76 differential metabolites were detected in the LLLT group, and 92 differential metabolites were detected in the COC group, which were up-regulated or down-regulated (p < 0.001). Prostaglandin D2 (PG D2) was down-regulated and biliverdin was up-regulated after LLLT treatment, 4a-Hydroxytetrahydrobiopterin, Prostaglandin D2, 5-Hydroxy-l-tryptophan, Cholic acid were down-regulated and cortisol was up-regulated after COC treatment, and the differences were statistically significant. Cortisol and testosterone glucuronide in LLLT group were significantly lower than those in COC group. The metabolic pathways affected were glycerophospholipid metabolism, linoleic acid metabolism and arachidonic acid metabolism in the LLLT group, and glycerophospholipid metabolism, folate biosynthesis, arachidonic-acid-metabolism, and tryptophan metabolism in the COC group. The differential metabolic pathway were linoleic acid metabolism, steroid hormone biosynthesis, and alpha-Linolenic acid metabolism after the comparison of LLLT with COC. ConclusionLLLT and COC might relieve dysmenorrhea by down-regulating PGD2, and LLLT might also relieve dysmenorrhea by up-regulating biliverdin. The level of cortisol and testosterone glucuronide after LLLT treatment was lower than that after COC treatment, which might lead to the difference in the clinical efficacy of the two treatments for dysmenorrhea.

Correlation between Serum Sialic Acid, Serum Lipids, Cardiac Troponin I and Myoglobin among Women on Combined Oral Contraceptives

Background: Women using combined oral contraceptives have an increased risk of developing cardiovascular disease. While the utility of biomarkers such as serum lipids have been well evaluated, serum sialic acid, which has shown some promise as a marker of cardiovascular disease progression has been poorly studied. This study aimed to determine the correlation between sialic acid and lipid profile as risk factors of cardiovascular disease in women on combined oral contraceptives. Materials and Methods: This was a cross-sectional study involving 143 women on combined oral contraceptive pill as the study group and 100 age and sex matched healthy controls. Serum levels of Total Sialic Acid (TSA), lipids, and some cardiac biomarkers (Myoglobin, Creatine Kinase-MB and Troponin-I) were measured, summarized as mean (±SD) and compared. Correlation between serum level of sialic acid and each of the measured serum lipid component was subsequently determined using correlation analysis. Results: Sialic acid (1.070±0.117 vs 0.837±0.272), Total cholesterol (3.944±0.918 vs 3.106±0.635), Low density lipoprotein cholesterol (2.408±1.085 vs 1.088±0.392), High density lipoprotein cholesterol (1.049±0.421 vs 0.902±0.542) &amp; Triglycerides (1.620±0.703 vs 1.052±0.514) were all significantly (P&lt;0.05) higher in the combined oral contraceptive group than controls respectively. Sialic acid demonstrated a weak but positive correlation with Myoglobin (r= +0.403), Creatine kinase-MB (r= +0.441) and Troponin-I (r= +0.424). While TGs and sialic acid were shown to have a very weakly positive association (r= +0.089), TC, LDL-C, and HDL-C all had very weakly negative correlations (r= -0.136, -0.146, and -0.006, respectively). Conclusion: Combined oral contraceptives use confers an artherogenic lipid profile imparting a positive cardiovascular disease risk. Although sialic acid is significantly higher among combined oral contraceptive users and shows a positive relationship with cardiac biomarkers, it correlates poorly with serum lipids suggesting its limited utility as a CVD marker.

Effect of prolonged use of hormonal contraception on ovarian reserve

Background and Objective: Contraception is widely used throughout the world, with 62% of reproductive-aged women. This trial was established to assess the effect of prolonged use of hormonal contraception (HC) on ovarian reserve. Methods: This retrospective randomized controlled trial was performed on 150 healthy females aged (20-35) years with normal menstrual history had at least one offspring after spontaneous pregnancy. Participants were subdivided into equal three groups: first group (study group): used the injectable progesterone for more than four years continuously, second group (study group): used combined oral contraceptive (COC) for more than four years continuously, control group: didn’t use HC (as intrauterine device, natural and non-users of any contraception). Results: Ovarian volume (OV) and antral follicle count (AFC) were significantly decreased in COC group than control group. There was a significant negative correlation between body mass index and OV was found. There was an insignificant correlation between age, gravidity, parity, BMI, usage duration and both AFC, AMH among group 3 controls. Conclusion: The prolonged use of HC in COC group had a significant negative effect on volume of ovary and AFC with no effect on AMH. A significant negative correlation between age and AMH was found among COC users.

Long-term treatment of endometriosis-related pain among women seeking hormonal contraception

Objective To evaluate the different effects of a progestin-only contraceptive with desogestrel (DSG) vs combined oral contraceptives (COCs) for a first line long-term treatment of endometriosis-related pain among patients seeking hormonal contraception. Methods An observational retrospective cohort study was conducted in collaboration with a local outpatient clinic for endometriosis among a group of nulliparous young women (n = 216) with endometriosis-related pain and seeking contraception. The cohort was subdivided into a group (n = 73) treated as first line by DSG and another group (n = 75) treated by a COC. During the study, clinical symptoms, side effects and possible changes in OC type use were recorded. Results No significant difference was found between the two groups in terms of clinical characteristics and pain scores before treatment. After 6 months both treatments were effective in reducing endometriosis-related pain, and those treated with DSG showed lower levels of dysmenorrhea, dyspareunia and nonmenstrual pelvic pain than COCs group (p < .01). After 12 months, in DSG Group some patients (15%) switched from DSG to a COC for breakthrough bleeding, whereas in COC Group 48% of patients switched to another type of COC for reduced efficacy on pain and/or for side effects. After 3 years of OC treatment, in DSG Group 79% of patients maintained the same therapy, whereas in COC Group only 14% continued the same COC type, 37% switched to another COC and 47% to DSG. Conclusions A progestin-only contraceptive with DSG is a valid option for long term management of endometriosis-related pain in patients seeking hormonal contraception.

Сравнение эффективности применения инозитолов и комбинированных оральных контрацептивов для коррекции метаболических, эндокринных и клинических параметров пациенток с синдромом поликистозных яичников

The use of a combination of myoinositol and D-chiroinositol in a ratio of 5:1 (MI/DCI 5:1), manganese and folic acid appears promising for the correction of androgen-dependent dermopathy, regulation of the menstrual cycle, restoration of ovulation in patients planning pregnancy, as well as for improving endocrine and metabolic parameters, carbohydrate and lipid metabolism in patients with polycystic ovary syndrome (PCOS). Objective. To compare the effects of combined oral contraceptives (COCs) and combination of MI/DCI 5:1, manganese and folic acid on endocrine, metabolic and clinical parameters in patients with PCOS. Patients and methods. A prospective open-label clinical trial included 129 patients with PCOS. Patients in group 1 (A, n = 63) were prescribed COCs with antiandrogenic activity containing ethinyl estradiol 20 μg/drospirenone 3 mg; patients in group 2 (B, n = 66) were prescribed the combination of MI/DCI 5:1, manganese and folic acid for 6 months. Lifestyle modifications were also recommended for all patients: physical activity and diet therapy. Results. Low serum androgen levels were observed in both groups. The use of COCs resulted in a more significant reduction in hirsutism according to the Ferriman-Gallwey score and clinical manifestations of acne. Administration of the combination of MI/DCI 5:1 showed good results in improving carbohydrate and lipid metabolism in patients with PCOS. Thus, in group B there was a significant reduction in glucose levels (4.9 ± 0.3 vs. 5.2 ± 0.5 mmol/L, p &lt; 0.01) and fasting insulin (12.1 ± 5.3 vs. 22.2 ± 4.9 mmol/L, p &lt; 0.01), HOMA and CARO indices. No changes in carbohydrate metabolism were observed during COCs administration, but there was an increase in cholesterol levels (6.0 ± 0.7 vs. 5.7 ± 0.5 mmol/L, p &lt; 0.05), low-density lipoproteins (LDL) (3.9 ± 0.4 vs. 3.5 ± 0.6 mmol/L, p &lt; 0.05), and atherogenic coefficient (AC). Lipid profile parameters in group B improved significantly from baseline by reducing cholesterol (5.1 ± 0.6 vs. 5.6 ± 0.6 mmol/L, p &lt; 0.05), triglycerides (1.5 ± 0.4 vs. 1.8 ± 0.3 mmol/L, p &lt; 0.05), and LDL (2.7 ± 0.5 vs. 3.6 ± 0.8 mmol/L, p &lt; 0.01). Diet therapy and administration of the combination of MI/DCI 5:1, manganese and folic acid resulted in a 4.4% decrease in waist circumference and a 4.8% decrease in body mass index (BMI). In contrast, the COCs group showed a 2.1% increase in waist circumference and a 4.7% increase in BMI, which may be related to an increased appetite. In group B, the regularity of menstrual cycle in patients with PCOS was also analyzed. After 6 months of therapy, a regular cycle was observed in 40% of patients vs. 11% of patients at baseline with a mean duration of 33.3 ± 9.4 days (p &lt; 0.05). Conclusion. Lifestyle modification with the combination of MI/DCI 5:1, manganese and folic acid is effective for the correction of endocrine, metabolic, and clinical profile in patients with PCOS and appears to be a promising new alternative to COCs regardless of reproductive planning. Key words: polycystic ovary syndrome, myoinositol, D-chiroinositol, hyperandrogenism, insulin resistance, hirsutism, acne

The Effect of Combined Oral Contraceptive Pills on Beclin-1 and LC3B Transcript Levels in Ovarian Endometrioma.

Background Autophagy is likely altered in patients with endometriosis. Ovarian steroid hormones seem to affect this changing of the autophagic process. Objective To study the effect of combined oral contraceptive (COC) pills on the expression of autophagic-related gene BECN1 and LC3B in the ectopic and eutopic endometria of patients with endometriosis. Material and Methods. The present quasiexperimental study recruited 36 women (18–45 years old) with endometrioma and nonendometrioma who were scheduled for surgery. Patients with endometrioma were randomly assigned to either a no-treatment group (n = 12) or a COC group (n = 12). The COC group was prescribed a daily oral pill composed of 3 mg drospirenone and 0.03 mg ethinyl estradiol for 6 weeks before surgery. The control group (n = 12) was composed of women without endometrioma. Ectopic endometriotic and endometrium tissues were collected from the no-treatment and COC groups, whereas the only endometrium was collected from the control group. These tissues were used for real-time PCR to measure the expression of the BECN1 and LC3B genes. Results The baseline demographic data were not different among the three groups. The BECN1 gene expression in endometrium tissue in the COC group was significantly less than that in the no-treatment and control groups (P = 0.011 and 0.029, respectively). No significant difference of endometriotic cyst BECN1 and LC3B gene expression was found between COC and no treatment. Conclusions Oral COC pills for 6 weeks continuously before surgery decreased the eutopic endometrial expression (mRNA) of the BECN1 gene compared to those from healthy normal women and nontreated patients with an endometriotic cyst. The change in the expression of autophagy-related genes was more distinct in eutopic than ectopic endometria. This trial is registered with TCTR20170720002. Registered and enrolled the first patient on 20 July 2017.

Atherogenic and cardiovascular risks of women on combined oral contraceptives: A comparative study.

Although combined oral contraceptive (COC) is commonly used in sub-Saharan Africa, data on its cardiovascular disease risk remains scanty. The study aimed to determine serial serum lipid profiles and cardiovascular disease risks among COC-users. This is a prospective, comparative multicentered study conducted at four health facilities in Nigeria. Participants were new users of contraceptives; 120 each of women initiating COCs (group I) and those initiating other forms of nonhormonal contraceptives (group II) were recruited and monitored over a 6-month period. Serial lipid profile, blood pressure, and atherogenic risk for cardiovascular diseases were measured at recruitment (start) and scheduled follow-up clinic visits at 3 months and 6 months for all participants. Statistical analysis was performed with SPSS (version 21.0) and P value < 0.05 was considered significant. In all, 225 participants (111 COC-users, 114 nonCOC-users) that completed the study were aged 18 to 49 years. There was a statistically significant increase in the diastolic blood pressure (P = 0.001), Low Density Lipoprotein- Cholesterol (P = 0.038) and higher atherogenic risk (P = 0.001) among COC-users compared to nonCOC-users. The serial total serum cholesterol, triglyceride, High Density Lipoprotein, systolic blood pressure, and body mass index were higher among COC-users but were not statistically significant compared to nonCOC-users. Alterations in lipid profile and increased short-term atherogenic risk for cardiovascular disease were reported among the COC-users in this study. Serial lipid profile and atherogenic risk assessment for cardiovascular diseases are recommended for monitoring of COC-users.

Ethinyl estradiol vs estradiol valerate in combined oral contraceptives – Effect on glucose tolerance: A randomized, controlled clinical trial

ObjectiveTo compare the effects of two formulations of combined oral contraceptives (COCs), estradiol valerate (EV) and ethinyl estradiol (EE) combined with dienogest (DNG), and DNG-only, on glucose tolerance. Study DesignWe performed a randomized, controlled 9-week clinical trial. Inclusion criteria were: age 18–35 years, regular menstrual cycle (28 ± 7 days), no polycystic ovaries, non-smoking, no contraindications for COC use and a 2-month wash-out from hormonal contraceptive use. The women were randomized to EV + DNG (n = 20), EE + DNG (n = 20), and DNG-only (n = 19), and evaluated at baseline, at 4–5 weeks and 8–9 weeks of treatment. Study medications were used continuously for 63 days. Primary outcome measure was change in the whole-body insulin sensitivity index (Matsuda index) derived from the oral glucose tolerance test (OGTT) over the treatment period. Secondary outcome measures were area under curves (AUC) of glucose and insulin, homeostatic model assessment – insulin resistance (HOMA-IR) and Insulin Sensitivity Index (ISI). ResultsFifty-nine women enrolled, and 56 women completed the study. The Matsuda index changed from baseline as follows (mean percentage change, mean change [95%CI]): DNG-only −12%, −1.45 [95%CI −3.22–0.325] P = 0.10; EV + DNG + 2.7%, −0.10 [−1.34 to 1.14] P = 0.86; EE + DNG −5.5%, −1.02 [−2.51 to 0.46] P = 0.16, comparing the groups P = 0.27. There were no clinically significant differences in glucose tolerance between the COC groups, but the DNG-only group showed an improvement in the 2-h glucose levels (5.5 [95%CI 5.0–6.0] to 4.7 mmol/l [4.2–5.2], P = 0.001). ConclusionWe found no clinically significant differences between EV and EE combined with DNG and DNG-only on glucose tolerance in healthy, young, normal-weight women, indicating that these preparations appear close to neutral regarding glucose metabolism when used continuously for nine weeks. ImplicationsCombinations of both ethinyl estradiol and natural estradiol (estradiol valerate) with dienogest (DNG), as well as DNG-only, seem metabolically safe in young and healthy women in short-term continuous use.

Bone mass in women with premature ovarian insufficiency: a comparative study between hormone therapy and combined oral contraceptives.

The aim of the study was to evaluate whether combined oral contraceptives (COCs) can be used as hormone therapy (HT) to preserve bone mineral density (BMD) in women with premature ovarian insufficiency (POI). An observational study of women with POI comparing the use of COC (ethinylestradiol 30 μg + levonorgestrel, continuously) with: low-dose HT (continuous conjugated estrogen 0.625 mg plus medroxyprogesterone or continuous estradiol [E2] 1 mg + norethisterone), high-dose HT (continuous conjugated estrogen 1.25 mg + medroxyprogesterone or continuous E2 2 mg + norethisterone), tibolone 2.5 mg, or no treatment. Bone density scans were performed every 2 ± 1 years. The difference between final and initial (delta) BMD values was calculated for the lumbar spine, total femur, and femoral neck. Generalized estimating equations were used to analyze the effect of treatment over time. Variables without normal distribution were transformed into ranks. Overall, 420 scans (210 deltas) of 119 women were analyzed. The women were 30.3 ± 9.2 years old (mean ± SD). BMD deltas at the lumbar spine and total femur were grater in the COC and high-dose HT groups. At the lumbar spine, the differences between two scans were greater in the COC group when compared to low-dose HT group: -0.043 (95% CI -0.062 to -0.024), untreated: -0.056 (-0.080 to -0.032), and tibolone: -0.050 (-0.094 to -0.006) groups. Total femur BMD decreases and the delta were lower in the low-dose HT group -0.038 (-0.052 to -0.024) when compared to COC. Continuous COC was associated with increased BMD in women with POI compared to low-dose HT, with similar improvement in the COC and high-dose HT groups. : Video Summary:http://links.lww.com/MENO/A620.

Effect of pretreatment with combined oral contraceptives on outcomes of assisted reproductive technology for women with polycystic ovary syndrome: a meta-analysis.

To evaluate the effect of pretreatment with combined oral contraceptives (COC) on outcomes in women with polycystic ovary syndrome (PCOS) who underwent assisted reproductive technology for subfertility. Two authors independently searched MEDLINE, EMBASE, and the Cochran Library to identify and review articles published from October 1995 until December 2018 according to selection criteria. Outcomes are expressed as mean difference and odds ratio (OR) in a meta-analysis model. A total of seven studies were included in this meta-analysis: one randomized controlled study and two prospective and four retrospective cohort studies. Meta-analysis showed that the COC pretreatment did not affect rate of clinical pregnancy (OR = 0.93, 95% confidence interval CI 0.65-1.34, I2 = 76%) or ovarian hyperstimulation syndrome (OR = 0.90, 95% CI 0.57-1.44, I2 = 0%). However, the rate of miscarriage in the COC group was significantly higher (OR = 1.33, 95% CI 1.02-1.72, I2 = 9%) and the rate of cumulative live birth was significantly lower compared with the control group (OR = 0.72, 95% CI 0.54-0.98, I2 = 55%). Subgroup analysis showed higher rates of miscarriage and lower rates of cumulative live birth in studies with a gonadotropin-releasing hormone (GnRH) antagonist protocol (OR = 1.69, 95% CI 1.17-2.44, I2 = 0% and OR = 0.38, 95% CI 0.29-0.50, respectively). Pretreatment with COC in women with PCOS before assisted reproductive technology may have an adverse effect on clinical outcomes, especially with a GnRH antagonist protocol.

Combined oral contraceptive in female mice causes hyperinsulinemia due to β-cell hypersecretion and reduction in insulin clearance

Oral contraception is the most commonly used interventional method in the world. However, several women employ the continuous use of these hormones to avoid pre- and menstruation discomforts. Some studies indicate that oral contraceptives are associated with disturbances in glycemia and the effects of the use of a continuous regime are poorly elucidated. Herein, we evaluated the effects of the continuous administration of a combined oral contraceptive (COC) composed by ethinyl estradiol (EE) and drospirenone (DRSP) on glucose homeostasis in female mice. Adult Swiss mice received 0.6 μg EE and 60 μg DRSP (COC group) or vehicle [control (CTL)] daily by gavage for 35 days. COC treatment had no effect on body weight or adiposity, but increased uterus weight and induced hepatomegaly. Importantly, COC females displayed normal glycemia and glucose tolerance, but hyperinsulinemia and lower plasma C-peptide/insulin ratio, indicating reduced insulin clearance. Furthermore, COC mice displayed reduced protein content of the β subunit of the insulin receptor (IRβ) in the liver. Additionally, pancreatic islets isolated from COC mice secreted more insulin in response to increasing glucose concentrations. This effect was associated with the activity of steroid hormones, since INS-1E cells incubated with EE plus DRSP also secreted more insulin. Therefore, we provide the first evidence that the continuous administration of EE and DRSP lead to hyperinsulinemia, due to enhancement of insulin secretion and the reduction of insulin degradation, which possibly lead to the down-regulation of hepatic IRβ. These findings suggest that the continuous administration of COC could cause insulin resistance with the prolongation of treatment.

Plasma Renin in Women Using and not Using Combined Oral Contraceptive

Abstract Backgroud: Recent studies show that women on combined oral contraceptives (COC) present abnormal fasting lipid profile, increased postprandial lipemia, plasma C-reactive protein (CRP) and blood pressure (BP) compared to women not on combined oral contraceptives. Plasma renin is one of the factors responsible for abnormal BP. Objectives: To assess plasma renin levels in women using or not using COC, the correlation between renin and CRP, as well as divergences in lipid profile. Methods: A cross-sectional study with apparently healthy women aged 20 to 30, eutrophic, irregularly active, and with fasting triglycerides < 150 mg/dL. The sample was stratified into two groups: the No Combined Oral Contraceptive Group (NCOCG), comprised of women who did not use any type of hormone contraceptive, and the Combined Oral Contraceptive Group (COCG) comprised of women on low-dose COC for at least one year. After a 12-hour fast, 5 ml of blood was collected for renin dosing and PCR. Data were analyzed by the t-Test and bidirectional Mann-Whitney Test, both with significance < 0.05. Results: We evaluated 44 women equally distributed between the groups, age 23 ± 1.2 years, BMI 21.0 ± 3.2 kg/m2. Median and interquartile deviation of renin in the NCOCG and the COCG were, respectively, 0.5 (0.1-1.0) and 3.0 (2-6) (p < 0.01). A positive correlation between PCR and renin (p < 0.01 and r = 0.68) was found. Conclusion: The plasma renin levels of women using COC were higher, with a strong correlation with CRP.

Combined oral contraception: is there a resource for increased use?

Combined oral contraceptives (COCs) are a highly effective method for preventing unintended pregnancy, but unfortunately, the resource of their contraceptive and therapeutic potential is not used enough, and global unintended pregnancies account for about 40%. The reasons for the lack of proper distribution of COCs are insufficient awareness of the beneficial properties of contraception, along with exaggerated fears of the adverse effects of hormone intake both among women and among doctors. This problem can only be overcome by providing adequate information to health professionals regarding the accumulated data and bringing this information to potential users. The review examines the risks of possible complications, as well as the preventive and therapeutic benefits of some COCs. The COC group is represented by preparations, which properties may differ significantly due to the different dose of the estrogen component and the qualitative characteristics of the progestins. Despite the launch of new combination drugs, COCs deserve high attention. Their efficacy and safety is confirmed by the long practical administration.

Elevation of Oxidized Lipoprotein of Low Density in Users of Combined Oral Contraceptives

BackgroundThe use of combined oral contraceptive (COC) has been related to changes in glycemic, lipid metabolism, increased oxidative stress, and systemic blood pressure, which could suggest a higher oxidation of low-density lipoprotein cholesterol (LDL-cholesterol) in women on use of COC.ObjectiveTo test the hypothesis that there is a difference in the plasma values of oxidized LDL among women who use and do not use COC, as well as to evaluate the correlation between it and the lipid profile and high-sensitivity C-reactive protein (hs-CRP).MethodsForty-two women with ages between 18 and 35 years old, who were eutrophic, irregularly active, with triglycerides < 150 mg/dL, blood glucose < 100 mg/dL, and who used or did not use COC were selected. These women were allocated in the COC group, formed by 21 women on COC use for at least 1 year; and a control group (CG), consisting of 21 women who had not used any type of hormonal contraceptive for at least 1 year. A significance level of 5% was adopted for statistical analyses.ResultsIt was observed that GCOC showed higher values of oxidized LDL than the CG, respectively 384 mU/mL versus 283 mU/mL (p < 0.01). A positive correlation between oxidized LDL and LDL-cholesterol (r = 0.3, p < 0.05), with total cholesterol (r = 0.47, p < 0.01) and with triglycerides (r = 0.32, p < 0.03) was observed, and there was no correlation with the hs-CRP. In the categorized analysis of oxidized LDL, 71.4% of GCOC women, and 28.6% of the CG remained above the established cutoff point.ConclusionWomen who use COC have higher plasma levels of oxidized LDL, and there is a positive correlation between oxidized LDL and other lipid variables.

Sexual Dysfunction in Two Types of Hormonal Contraception: Combined Oral Contraceptives versus Depot Medroxyprogesterone Acetate

Background & aim: Sexual health is an essential element of quality of life, affecting both physical and psychological domains. Hormones used in contraceptive methods have contradictory effects on sexual function. In this study, we aimed to compare sexual function in women using combined oral contraceptives (COC) and depot medroxyprogesterone acetate (DMPA), referred to healthcare centers affiliated to Shahid Beheshti University of Medical Sciences in Tehran, Iran in 2013. Methods: This descriptive, comparative study was performed on 240 women (n=120 per group), selected through multistage sampling in Tehran, Iran. A questionnaire consisting of three parts, General Health Questionnaire (GHQ-28), demographic characteristics, and Female Sexual Function Index (FSFI), was completed through interviews. For data analysis, descriptive statistics were calculated, and independent t-test, Mann-Whitney test, Chi-square, and Fisher's exact test were performed, using SPPS version 16. P-value less than 0.05 was considered statistically significant. Results: The mean age at marriage in women using DMPA was lower than those using COC (18.55±3.61 vs. 19.92±3.98 years). Based on the findings, the menstrual status in the majority of DMPA users was irregular (46.7% in DMPA group vs. 8.3% in COC group). The difference in sexual function between the COC and DMPA groups was significant. Sexual arousal and lubrication were more favorable in the COC group in comparison with the DMPA group; also, pain in this group was lower than the DMPA group. Scores of total sexual function (27.35±5.22 in DMPA group vs. 29.15±6.13 in COC group), sexual arousal (4.11±0.90 in DMPA group vs. 4.51±1.39 in COC group), and vaginal lubrication (4.82±1.30 in DMPA group vs. 5.26±1.35 in COC group) were lower in the DMPA group, compared to the COC group. Pain scores (4.91±1.25 in DMPA group vs. 5.28±1.19 in COC group) were higher in the DMPA group in comparison with the COC group (p <0.05). Conclusion: Sexual dysfunction seems to be more prevalent among DMPA users. Therefore, healthcare providers should pay particular attention to sexual function and contraceptive methods. Also, we recommend further research to determine the best way to inform women about the potential risks and benefits of hormonal contraception.

The effect of a drospirenone-containing combined oral contraceptive on female sexual function: a prospective randomised study

Objectives: The study investigated the effects on female sexual function of a progestogen-containing combined oral contraceptives (COCs) with an antiandrogenic profile taken in a continuous regimen.Methods: In this prospective randomised single-institution study, 80 healthy women with a monogamous partner and an active sexual life were randomised into two groups for a period of 3 months. Women in the exposed group (n = 40) took a COCs containing 30 μg ethinylestradiol (EE) and 3 mg drospirenone (DRSP) in a 21/7 regimen. Women in the control group (n = 40) used either a barrier contraceptive method (BCM) or a natural family planning method (NFPM). Participants were asked to complete a set of validated questionnaires to assess sociodemographic variables and measure Female Sexual Function Index (FSFI).Results: The total FSFI score (p < 0.0001), as well as the desire (p = 0.04) and arousal (p = 0.03) scores, were significantly lower in the COCs group after 3 months of hormonal contraceptive use compared with baseline. Women using BCM or NFPM showed an improvement in total FSFI score (p = 0.02). Hormonal contraception with DRSP increased the likelihood of worse sexual function in the desire (odds ratio [OR] 2.47; 95% confidence interval [CI] 1.22, 4.98; p = 0.01) and arousal domains (OR 2.85; 95%CI 1.34, 5.93; p = 0.005) and in total FSFI score (OR 2.01; 95%CI 1.45, 2.79; p < 0.001). The results remained statistically significant even after adjustment for smoking status.Conclusions: The study found evidence that women taking a combined EE/DRSP COCs for 3 months may have a worsening of sexual function as measured by FSFI.

The CORALIE study: improving patient education to help new users better understand their oral contraceptive

Objectives: Combined oral contraceptives (COCs) are the most widely used contraceptive method in Europe. Paradoxically, rates of unintended pregnancy and abortion are still remarkably high. A lack of knowledge about COCs is often reported to lead to poor adherence, suggesting an unmet need for adequate contraceptive counselling. Our objective was to investigate the impact on the knowledge level of users of a structured approach to deliver contraceptive information for a first COC prescription.Methods: The Oral Contraception Project to Optimise Patient Information (CORALIE) is a multicentre, prospective, randomised study conducted in France between March 2009 and January 2013. The intervention involved providing either an ‘essential information’ checklist or unstructured counselling to new COC users. The outcome measure was a questionnaire that assessed whether the information provided to the new user by the gynaecologist had been correctly understood.Results: One hundred gynaecologists and an expert committee used the Delphi method to develop an ‘essential information’ checklist, after which 161 gynaecologists were randomised to two groups. Group I (n = 81) used the checklist with 324 new COC users and group II (n = 80) delivered unstructured information to 307 new COC users. The average score for understanding the information delivered during the visit was significantly higher in women in group I than in the women in group II, even after adjustment for age and previous history of pregnancy: 16.48/20 vs 14.27/20 (p < 0.0001).Conclusion: Delivering structured information for a first COC prescription is beneficial for understanding contraception. Our tool could ultimately contribute to increased adherence and should be investigated in a prospective study of long-term outcomes.

Maintaining physiological testosterone levels by adding dehydroepiandrosterone to combined oral contraceptives: I. Endocrine effects

ObjectiveTo determine whether adding dehydroepiandrosterone to combined oral contraceptives (COCs) maintains physiological levels of free testosterone. Study designA randomized, double-blind, placebo-controlled, two-way crossover study conducted in 81 healthy women (age range: 20–35 years; Body mass index (BMI) range: 18–35 kg/m2) using oral contraceptives. Androgens, sex hormone-binding globulin (SHBG), estradiol (E2) and estrone (E1) were measured, and free testosterone and the free testosterone index were calculated. Subjects discontinued oral contraceptive use for at least one menstrual cycle before being randomized to receive five cycles of ethinyl estradiol (EE) combined with either levonorgestrel (EE/LNG group) or drospirenone (EE/DRSP group) together with either dehydroepiandrosterone (DHEA) (50 mg/day orally) or placebo. Subsequently, all subjects crossed over to the other treatment arm for an additional five cycles. ResultsBoth COCs decreased the levels of all androgens measured. Significant decreases (p<.05) were found with EE/LNG and EE/DRSP for total testosterone (54.5% and 11.3%, respectively) and for free testosterone (66.8% and 75.6%, respectively). Adding DHEA to the COCs significantly increased all androgens compared to placebo. Moreover, including DHEA restored free testosterone levels to baseline values in both COC groups and total testosterone levels to baseline in the EE/LNG group and above baseline in the EE/DRSP group. SHBG concentrations were significantly higher with EE/DRSP compared to EE/LNG (p<.0001). The addition of DHEA did not affect the levels of SHBG. ConclusionsTaking COCs reduces total and free testosterone levels and increases SHBG concentrations. By coadministration with DHEA, physiological levels of total and free testosterone are restored while using EE/LNG. With EE/DRSP, only the free testosterone level is normalized by DHEA coadministration. ImplicationsA daily oral dose of 50-mg DHEA maintains physiological free and total testosterone levels in women who are using an EE/LNG-containing COC.

Efficacy and safety of the contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive in Chinese women: a 1-year randomised trial

Objectives: The aim of the study was to assess the efficacy and tolerability of the monthly vaginal ring (NuvaRing; 15 μg ethinylestradiol [EE] and 120 μg etonogestrel per day) compared with a monophasic (21/7) combined oral contraceptive (COC) containing 30 μg EE and 3 mg drospirenone in healthy Chinese women aged 18–40 years.Methods: This was a phase III, open-label, randomised multicentre trial conducted in China. Participants received NuvaRing or COC for 13 cycles (3 weeks of ring/pill treatment followed by a 1-week ring-free/pill-free period). Contraceptive efficacy was assessed by in-treatment pregnancies and expressed by the Pearl Index (PI; number of pregnancies/100 woman-years of use). Cycle control was assessed by unscheduled (breakthrough) and absence of scheduled (withdrawal) bleeding events. Safety and tolerability were assessed throughout the study.Results: Participants were randomised either to the NuvaRing (n = 732) or to the COC (n = 214); 588 (82.4%) and 182 (78.4%) participants, respectively, completed the study. There were 10 in-treatment pregnancies in the NuvaRing group (PI 1.92; 95% confidence interval [CI] 0.92, 3.53) and five in the COC group (PI 3.12; 95% CI 1.01, 7.29). Breakthrough bleeding/spotting ranged from 18.6% (Cycle 1) to 4.2% (Cycle 11) for NuvaRing and from 21.6% (Cycle 1) to 7.9% (Cycle 11) for COC. Absence of withdrawal bleeding ranged from 8.6% (Cycle 1) to 3.0% (Cycle 11) for NuvaRing and from 14.6% (Cycle 1) to 6.4% (Cycle 5) for COC. For NuvaRing and COC, respectively, 26.6% and 25.0% of participants had treatment-related adverse events, and 7.0% and 9.1% discontinued the study as a result.Conclusions: Once-monthly NuvaRing is efficacious and safe for use in Chinese women.