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ObjectiveTo evaluate overall and subgroup efficacy of an estetrol (E4) 15 mg drospirenone (DRSP) 3 mg oral contraceptive in a 24/4-day regimen.Study designWe pooled efficacy outcomes from 2 pivotal phase 3 contraceptive trials with E4/DRSP conducted in the United States/Canada and Europe/Russia. We assessed Pearl Index (PI; pregnancies per 100 participant-years) and 13-cycle life-table pregnancy rates in at-risk cycles (confirmed intercourse and no other contraceptive use) among participants 16 to 35 years. We calculated PI by age and further subcategorization (contraceptive history and body mass index [BMI]). We performed multivariable analysis using Cox regression to assess impact of potential confounding factors.ResultsAnalyses included 3027 participants, of whom 451 (14.9%) had a BMI ≥30 kg/m2. The pooled PI was 1.52 (95% confidence interval 1.04-2.16) and the 13-cycle life-table pregnancy rate was 1.28% (0.83%-1.73%). We calculated unadjusted pooled PI in participants 16 to 25 years and 26 to 35 years of 1.61 (0.94-2.57) and 1.43 (0.78-2.40), respectively; in new starters and switchers of 1.88 (1.09-3.00) and 1.24 (0.68-2.08), respectively; and by BMI

Background: Delivering contraceptive hormones through a transdermal patch or a vaginal ring might have advantages over the traditional oral route. Objectives: To compare the effectiveness, compliance, and side effect profile of oral and parenteral drug administration methods. Methods: We performed a systematic literature search in four medical databases—MEDLINE (via PubMed), Cochrane Library (CENTRAL), Embase, and Scopus—from inception to 20 November 2022. Randomized controlled trials assessing the efficacy, compliance, and adverse event profile of combined parenteral and oral hormonal contraceptives were included. Results: Our systematic search provided 3952 records; after duplicate removal, we screened 2707 duplicate-free records. A total of 13 eligible studies were identified after title, abstract, and full-text selection. We observed no significant difference in contraceptive efficacy (Pearl Index) between oral and parenteral drug administration (MD = −0.06, CI: −0.66–0.53; I2 = 0%). We found significant subgroup differences between parenteral methods in terms of compliance (χ2 = 4.32, p =0.038, I2 = 80%) and certain adverse events: breast discomfort (χ2 = 19.04, p =0.001, I2 = 80%), nausea (χ2 = 8.04, p =0.005, I2 = 75%), and vomiting (χ2 = 9.30, p =0.002; I2 = 72%). Conclusion: Both parenteral and oral contraceptives can be used as an effective contraceptive method, and the route of administration should be tailored to patient needs and adverse event occurrence. [ABSTRACT FROM AUTHOR]

Background: In recent years, new combined oral contraceptives (COCs) have become available, representing an advance in terms of individualization and compliance by users. Objective: To provide recommendations regarding COCs: formulations, use, efficacy, benefits and safety. Method: For these recommendations, we have used the modified Delphi methodology and carried out a systematic review of studies found in the literature and reviews performed in humans, published in English and Spanish in Pubmed, Medline and advanced medicine and computer networks until the year 2021, using the combination of terms: 'oral contraceptives', 'estroprogestins' and 'combined oral contraceptives'. Results: Regarding the estrogen component, initially switching from mestranol (the pro-drug of ethinylestradiol) to ethinylestradiol (EE) and then reducing the EE dose helped reduce side effects and associated adverse events. Natural estradiol and estradiol valerate are already available and represent a valid alternative to EE. The use of more potent 19-nortestosterone-derived progestins, in order to lower the dose and then the appearance of non-androgenic progestins with different endocrine and metabolic characteristics, has made it possible to individualize the prescription of COC according to the profile of each woman. Conclusion: Advances in the provision of new COCs have improved the risk/benefit ratio by increasing benefits and reducing risks. Currently, the challenge is to tailor contraceptives to individual needs in terms of safety, efficacy, and protection of female reproductive health. [ABSTRACT FROM AUTHOR]

IntroductionEstrogens used in women's healthcare have been associated with increased risks of venous thromboembolism (VTE) and breast cancer. Estetrol (E4), an estrogen produced by the human fetal liver, has recently been approved for the first time as a new estrogenic component of a novel combined oral contraceptive (E4/drospirenone [DRSP]) for over a decade. In phase 3 studies, E4/DRSP showed good contraceptive efficacy, a predictable bleeding pattern, and a favorable safety and tolerability profile.Areas coveredThis narrative review discusses E4's pharmacological characteristics, mode of action, and the results of preclinical and clinical studies for contraception, as well as for menopause and oncology.Expert opinionExtensive studies have elucidated the properties of E4 that underlie its favorable safety profile. While classical estrogens (such as estradiol) exert their actions via both activation of nuclear and membrane estrogen receptor α (ERα), E4 presents a specific profile of ERα activation: E4 binds and activates nuclear ERα but does not induce the activation of membrane ERα signaling pathways in specific tissues. E4 has a small effect on normal breast tissue proliferation and minimally affects hepatic parameters. This distinct profile of ERα activation, uncoupling nuclear and membrane activation, is unique.

ObjectivesTo assess the contraceptive efficacy, bleeding pattern and safety of a combined oral contraceptive containing estetrol (E4) 15 mg and drospirenone (DRSP) 3 mg.DesignMulticenter, open-label, phase 3 trial.SettingSixty-nine sites in Europe and Russia.PopulationSexually active women aged 18-50 years with regular menstrual cycles and body mass index ≤35 kg/m2 .MethodsE4/DRSP was administered in a 24 active/4 placebo regimen for up to 13 cycles. Visits were scheduled during Cycles 2, 4, 7 and 10 and after completing treatment during which adverse events (AEs) were collected. Participants recorded medication intake, vaginal bleeding/spotting, use of other contraceptive methods and sexual intercourse on a daily diary.Main outcome measuresPearl Index (PI) for women 18-35 years (overall and method-failure), bleeding pattern and AEs.ResultsA total of 1553 women aged 18-50 years, including 1353 from 18 to 35 years old, received the study medication. PI was 0.47 pregnancies/100 woman-years (95% CI 0.15-1.11); method failure PI was 0.29 pregnancies/100 woman-years (95% CI 0.06-0.83). Scheduled bleeding/spotting occurred in 91.9-94.4% of women over Cycles 1 to 12 and lasted a median of 4-5 days per cycle. The percentage of women with unscheduled bleeding/spotting episodes decreased from 23.5% in Cycle 1 to

Background: In recent years, new combined oral contraceptives (COCs) have become available, representing an advance in terms of individualization and compliance by users.Objective: To provide recommendations regarding COCs: formulations, use, efficacy, benefits and safety.Method: For these recommendations, we have used the modified Delphi methodology and carried out a systematic review of studies found in the literature and reviews performed in humans, published in English and Spanish in Pubmed, Medline and advanced medicine and computer networks until the year 2021, using the combination of terms: ‘oral contraceptives’, ‘estroprogestins’ and ‘combined oral contraceptives’.Results: Regarding the estrogen component, initially switching from mestranol (the pro-drug of ethinylestradiol) to ethinylestradiol (EE) and then reducing the EE dose helped reduce side effects and associated adverse events. Natural estradiol and estradiol valerate are already available and represent a valid alternative to EE. The use of more potent 19-nortestosterone-derived progestins, in order to lower the dose and then the appearance of non-androgenic progestins with different endocrine and metabolic characteristics, has made it possible to individualize the prescription of COC according to the profile of each woman.Conclusion: Advances in the provision of new COCs have improved the risk/benefit ratio by increasing benefits and reducing risks. Currently, the challenge is to tailor contraceptives to individual needs in terms of safety, efficacy, and protection of female reproductive health.

ObjectivesTo assess the contraceptive efficacy, bleeding pattern and safety of a combined oral contraceptive containing estetrol (E4) 15 mg and drospirenone (DRSP) 3 mg.DesignMulticenter, open-label, phase 3 trial.SettingSixty-nine sites in Europe and Russia.PopulationSexually active women aged 18-50 years with regular menstrual cycles and body mass index ≤35 kg/m2 .MethodsE4/DRSP was administered in a 24 active/4 placebo regimen for up to 13 cycles. Visits were scheduled during Cycles 2, 4, 7 and 10 and after completing treatment during which adverse events (AEs) were collected. Participants recorded medication intake, vaginal bleeding/spotting, use of other contraceptive methods and sexual intercourse on a daily diary.Main outcome measuresPearl Index (PI) for women 18-35 years (overall and method-failure), bleeding pattern and AEs.ResultsA total of 1553 women aged 18-50 years, including 1353 from 18 to 35 years old, received the study medication. PI was 0.47 pregnancies/100 woman-years (95% CI 0.15-1.11); method failure PI was 0.29 pregnancies/100 woman-years (95% CI 0.06-0.83). Scheduled bleeding/spotting occurred in 91.9-94.4% of women over Cycles 1 to 12 and lasted a median of 4-5 days per cycle. The percentage of women with unscheduled bleeding/spotting episodes decreased from 23.5% in Cycle 1 to

Objective: To compare between different combined oral contraceptive pills (COCPs) as part of the update of the International Evidence-Based Guidelines on the Assessment and Management of polycystic ovary syndrome (PCOS). Design: A systematic review and meta-analysis was performed, Prospero CRD42022345640. Methods: MEDLINE, EMBASE, All EBM, CINAHL, and PsycINFO was searched on July, 8, 2022, for studies including women with PCOS, comparing 2 different COCPs in randomized controlled trials. Results: A total of 1660 studies were identified, and 19 randomized controlled trials (RCTs) were included. Fourth-generation COCP resulted in lower body mass index (BMI) (mean difference [MD] 1.17 kg/m² [95% confidence interval {CI} 0.33; 2.02]) and testosterone (MD 0.60 nmol/L [95% CI 0.13; 1.07]) compared with third-generation agents, but no difference was seen in hirsutism. Ethinyl estradiol (EE)/cyproterone acetate (CPA) was better in reducing hirsutism as well as biochemical hyperandrogenism (testosterone [MD 0.38 nmol/L {95% CI 0.33-0.43}]) and BMI (MD 0.62 kg/m² [95% CI 0.05-1.20]) compared with conventional COCPs. There was no difference in hirsutism between high and low EE doses. No evidence regarding natural estrogens in COCP was identified. Conclusion: With current evidence, combined regimens containing an antiandrogen (EE/CPA) may be better compared with conventional COCPs in reducing hyperandrogenism, but EE/CPA will not be recommended as a first-line COCP treatment by the pending PCOS guideline update, due to higher venous thrombotic events (VTE) risk in the general population. Later-generation progestins offer theoretical benefits, but better evidence on clinical outcomes is needed in women with PCOS. [ABSTRACT FROM AUTHOR]

Objective: To evaluate overall and subgroup efficacy of an estetrol (E4) 15 mg drospirenone (DRSP) 3 mg oral contraceptive in a 24/4-day regimen.Study Design: We pooled efficacy outcomes from 2 pivotal phase 3 contraceptive trials with E4/DRSP conducted in the United States/Canada and Europe/Russia. We assessed Pearl Index (PI; pregnancies per 100 participant-years) and 13-cycle life-table pregnancy rates in at-risk cycles (confirmed intercourse and no other contraceptive use) among participants 16 to 35 years. We calculated PI by age and further subcategorization (contraceptive history and body mass index [BMI]). We performed multivariable analysis using Cox regression to assess impact of potential confounding factors.Results: Analyses included 3027 participants, of whom 451 (14.9%) had a BMI ≥30 kg/m2. The pooled PI was 1.52 (95% confidence interval 1.04-2.16) and the 13-cycle life-table pregnancy rate was 1.28% (0.83%-1.73%). We calculated unadjusted pooled PI in participants 16 to 25 years and 26 to 35 years of 1.61 (0.94-2.57) and 1.43 (0.78-2.40), respectively; in new starters and switchers of 1.88 (1.09-3.00) and 1.24 (0.68-2.08), respectively; and by BMI <25 kg/m2, 25 to 29.9 kg/m2, and ≥30 kg/m2 of 1.14 (0.64-1.88), 2.19 (1.05-4.03), and 2.27 (0.83-4.94), respectively. In multivariable analysis, we found associations of prior pregnancy (hazard ratio [HR] 3.61[1.56-8.38]), Black race (HR 4.61[1.97-10.80]), age 16 to 25 years (HR 2.37[1.09-5.15]) and compliance <99% of expected pills (HR 4.21[2.04-8.66]) with conception.Conclusion: E4/DRSP is an effective oral contraceptive overall and across subgroups stratified by age, contraceptive history, and BMI. Other than compliance, predictors of contraceptive failure are nonmodifiable.Implications Statement: Pooled results from two phase 3 trials demonstrate high contraceptive efficacy of the novel estetrol-drospirenone oral contraceptive. Several non-modifiable risk factors, including prior pregnancy, race, and age, are associated with higher pregnancy risk. Additional research is needed to better understand predictors of combined oral contraceptive failure. [ABSTRACT FROM AUTHOR]

Introduction: Contraceptives containing ethinylestradiol (EE) induce changes in the coagulation system and are associated with a risk of venous thromboembolism. However, studies comparing the effects of combined oral contraceptives containing EE and low-potency estrogens (ie, estradiol [E2 ] and estradiol valerate [EV]) on coagulation biomarkers are limited. This study represents secondary outcomes of a randomized trial comparing combined oral contraceptives containing EV + dienogest (DNG), EE + DNG, and DNG alone on selected coagulation biomarkers. We could compare the specific effects of the different estrogen components owing to the inclusion of preparations containing the same progestin.Material and Methods: We enrolled 59 healthy, 18- to 35-year-old, non-smoking women, of whom three discontinued. The participants were randomly allocated to 9 weeks of continuous treatment with EV 2 mg + DNG 2-3 mg (n = 20), EE 0.03 mg + DNG 2 mg (n = 20), or DNG 2 mg (n = 19). Blood samples were collected at baseline and after 9 weeks. We assessed coagulation in vitro by thrombin generation using the Calibrated Automated Thrombogram. Thrombin generation was evaluated by lag time, time to thrombin peak, thrombin peak, and endogenous thrombin potential in response to tissue factor (1 pm). In vivo coagulation assessment was based on levels of prothrombin fragment 1 + 2 (F1 + 2) (thrombin generation) and D-dimer (fibrin turnover).Clinical Trial Registration: NCT02352090.Results: Lag time and time to thrombin peak remained unaltered after exposure to EV + DNG, whereas EE + DNG shortened both lag time (mean percentage change -24%, 95% confidence interval [CI] -32% to -15%; p < 0.01) and time to thrombin peak (-26%, 95% CI -37% to -16%; p < 0.01). EV + DNG induced lower thrombin peak and endogenous thrombin potential than EE + DNG (peak; +45%, 95% CI 22%-67% vs +147%,95% CI 96%-198%; p < 0.01, and endogenous thrombin potential; +26%, 95% CI 15%-38% vs +64%, 95% CI 51%-76%; p < 0.01). Median F1 + 2 levels remained unchanged with EV + DNG (p = 0.22) but increased within normal ranges with EE + DNG (from 152 pmol/L, 95% CI 127-206] pmol/L to 194 pmol/L, 95% CI 149-250 pmol/L, p = 0.04). The within-group change in D-dimer levels was not significant in any of the groups. DNG alone did not affect these biomarkers.Conclusions: Both in vitro and in vivo thrombin generation was lower after exposure to EV + DNG compared with EE + DNG. The lower thrombin generation measures after treatment with EV + DNG indicate less enhancement of coagulation potential and suggest that EV may be favorable to EE as a component of combined oral contraceptives. [ABSTRACT FROM AUTHOR]

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) was declared the cause of a global pandemic in early 2020. Patients with COVID-19 are at high risk for thrombotic occlusions of the arteries and veins. There are many ways that explain the high risk of thrombosis in COVID-19, they are conditionally divided into two main categories: mechanisms in which the renin-angiotensinaldosterone system is involved and mechanisms that affect the regulation of the immune response. It is assumed that the uncomplicated course of the disease is characterized by endothelial dysfunction, but if the process progresses with a pronounced immune response, plasma coagulation factors may also be involved, which significantly increases the risks of thromboembolic complications. The use of combined hormonal contraception (CHC) in the current conditions raises a number of concerns. According to some researchers, disorders of the hemostasis system observed in patients with COVID-19 may worsen while taking CHC and increase the risk of thromboembolic complications, which is especially important in severe disease with prolonged immobilization. However, with the use of CHC, the increase in thrombotic risks is explained primarily by changes in the plasma component of the hemostasis sys tem. At first glance, the recommendations to stop hormone therapy with confirmed COVID-19 seem logical, but they are based only on the procoagulant activity of estrogens, and not on real evidence. In patients with COVID-19, the increase in coagulation is associ ated with massive damage to the vascular endothelium (the so-called «external» coagulation pathway) and the immune response, and not with a primary increase in the level of coagulation factors per se. At the same time, stopping the intake of estrogens deprives the patient of their important protective effect. Thus, it became necessary to develop clinical guidelines for the management of women using contraception in the context of the COVID-19 pandemic.

Context: Limited studies have compared the effects of combined oral contraceptives (COCs) containing natural estrogens and synthetic ethinylestradiol (EE) on reproductive hormones. Objective: To compare estradiol valerate (EV) + dienogest (DNG), EE + DNG, and DNG alone (active control) on levels of follicle stimulating hormone (FSH), luteinizing hormone, anti-Müllerian hormone (AMH), ovarian steroids, sex hormone binding globulin (SHBG), and the free androgen index (FAI). Methods: This spin-off study from a randomized trial enrolled 59 healthy, 18 to 35-year-old ovulatory women, outpatients at Helsinki and Oulu University Hospitals, Finland, who were randomized to EV 2 mg + DNG 2-3 mg (n = 20); EE 0.03 mg + DNG 2 mg (n = 20); and DNG 2 mg (n = 19) for 9 weeks. Blood samples were drawn at baseline, and at 5 and 9 weeks. Age and BMI were comparable between groups; 3 women discontinued. Results: EV + DNG suppressed FSH by -27% (-51% to -3%) (median [95% CI]) vs EE + DNG, -64% (-78 to -51), P = 0.04, but AMH levels decreased similarly by -9% (-18 to -0.1) vs -13% (-28 to 0.2), P = 0.38, respectively. EV + DNG increased SHBG levels by 56% (30% to 82%) and EE + DNG by 385% (313% to 423%), P < 0.001. Total testosterone decreased by 16% (-27% to -5%) in the EV + DNG group but it did not decrease in the EE + DNG group, whereas the FAI decreased by -39% (-54% to -25%) vs -72% (-78% to -67%), P < 0.001. DNG alone did not induce changes in any of these parameters. Conclusion: Compared with EE + DNG, treatment with EV + DNG resulted in milder pituitary downregulation and reduced induction of hepatic SHBG synthesis--potentially carrying more beneficial health effects. [ABSTRACT FROM AUTHOR]

Iñaki Lete,1 Jesus Novalbos,2 Esther de la Viuda,3 Felix Lugo,4 Mercedes Herrero,5 Marian Obiol,6 Josep Perelló,7 Rafael Sanchez-Borrego8 1Unit of Clinical Management of Obstetrics and Gynaecology, Araba University Hospital, Vitoria, Spain; 2Medical Department, Theramex SLU, Madrid, Spain; 3Gynaecology and Obstetrics Department, University Hospital of Guadalajara, Guadalajara, Spain; 4Intimate Health Unit Diatros Woman´s Clinic, Barcelona, Spain; 5Gynaecology Department Gine4, HM Hospitals, Madrid, Spain; 6Reproductive and Sexual Health Centre Fuente De San Luis, Valencia, Spain; 7Gynaecology and Obstetrics Department, Sant Pau Hospital, Barcelona, Spain; 8DIATROS, Woman’s Clinic, Barcelona, SpainCorrespondence: Iñaki LeteUnit of Clinical Management of Obstetrics and Gynaecology. Araba University Hospital, Jose Atxotegi s/n, Vitoria, 01009, SpainTel +34 945007204Email luisignacio.letelasa@osakidetza.netObjective: To know the contraceptive behaviour of Spanish women who use combined oral contraception (COC) during the period of lockdown due to COVID-19.Methods: Cross-sectional, descriptive study of a sample of Spanish women who use COC based on a survey conducted through social networks using the online platform Survey Monkey. The survey was conducted during the period of home confinement.Results: A total of 1407 women answered the survey and 937 were valid for the analysis. A total of 675 women (71.8%) were confined all day at home. During confinement 96,6% of women continued to use the COC, 53.5% responded that their sexual activity decreased during this time and 54% that their physical activity had decreased. A significant percentage of women (10.3%) recognized a worsening of premenstrual symptoms.Conclusion: Despite the lockdown and the decrease in the frequency of sexual intercourse, the Spanish women who use COC did not abandon its use during the period of time analysed.Keywords: COVID-19, confinement, combined oral contraception, discontinuation, premenstrual symptoms

Objective: To evaluate the effects of estetrol 15 mg/drospirenone 3 mg on ovarian function.Study Design: Single-center, randomized, open-label, parallel study in healthy young women with proven ovulatory cycles. Participants received either estetrol 15 mg/drospirenone 3 mg (E4/DRSP) (n = 41) or ethinylestradiol 20 µg/drospirenone 3 mg (EE/DRSP) (n = 41) in a 24/4-day regimen for 3 consecutive cycles. Follicular size and endometrial thickness were measured by transvaginal ultrasound every 3 days in cycles 1 and 3. Blood was sampled for hormone analysis. Ovarian function expressed as Hoogland score was based on follicular size, serum estradiol (E2) and progesterone (P) concentrations. Ovulation was defined as a ruptured follicle-like structure >13 mm with serum E2 concentrations >100 pmol/L and serum P concentrations >5 nmol/L. We assessed return of ovulation after treatment cessation, and safety throughout the study.Results: None of the participants ovulated with E4/DRSP use, while one participant ovulated once and one participant ovulated twice during EE/DRSP treatment. Most participants had a Hoogland score of 1 (no ovarian activity) in cycle 1 (85.0% and 82.9% of participants on E4/DRSP and EE/DRSP, respectively) and in cycle 3 (65.8% and 83.8%, respectively). E4/DRSP suppressed follicle-stimulating hormone and luteinizing hormone to a lesser extent than EE/DRSP, whereas both treatments comparably suppressed E2 and P and endometrial thickness. Return of ovulation occurred, on average, 15.5 days after E4/DRSP treatment discontinuation. E4/DRSP was safe and well-tolerated.Conclusions: E4 15 mg/DRSP 3 mg results in adequate ovulation inhibition and ovarian function suppression, comparable to a marketed combined oral contraceptive containing EE/DRSP.Implications Statement: Treatment with E4 15 mg/DRSP 3 mg showed complete ovulation inhibition, despite less suppression of follicle-stimulating hormone and luteinizing hormone compared to EE/DRSP. If it becomes commercially available, E4/DRSP, containing a naturally occurring estrogen, should be as effective as EE/DRSP. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effect on endocrine and metabolic parameters of a new combined oral contraceptive (COC) containing estetrol (E4) and drospirenone (DRSP).Study Design: Randomized, open-label, controlled, 3-arm, parallel study. Healthy subjects received either E4 15 mg/DRSP 3 mg (E4/DRSP) (n = 38), or ethinylestradiol (EE) 30 µg/levonorgestrel (LNG) 150 µg (n = 29), or EE 20 µg/DRSP 3 mg (n = 31) for 6 treatment cycles. Median percentage change from baseline to cycle 3 and to cycle 6 were evaluated for endocrine parameters, liver proteins, lipid profile, and carbohydrate metabolism.Results: At cycle 6, E4/DRSP treatment had less effect on gonadotropins (follicle stimulating hormone [FSH] +30.5%, luteinizing hormone [LH] -7.5%) compared to EE/LNG (FSH -84.0%, LH -92.0%) and EE/DRSP (FSH -64.0%, LH -90.0%). With E4/DRSP increases in total cortisol (+26.0%) and cortisol binding globulin ([CBG] (+40.0%) were less compared to EE/LNG (cortisol +109.0%, CBG +152.0%) and EE/DRSP (cortisol +107.0%, CBG +140.0%). Liver proteins, except CRP, increased, but the effect was less pronounced with E4/DRSP for angiotensinogen (+75.0%) compared to EE/LNG (+170.0%) and EE/DRSP (+206.5%) and for sex hormone binding globulin ([SHBG] +55.0%), compared to EE/LNG (+74.0%) and EE/DRSP (+251.0%). E4/DRSP had minimal impact on lipid parameters; the largest effect was observed for triglycerides (+24.0%), which was less compared to EE/LNG (+28.0%) and EE/DRSP (+65.5%). E4/DRSP had no effect on carbohydrate metabolism.Conclusions: E4/DRSP treatment has limited effects on endocrine and metabolic parameters. The effects on gonadotropins, cortisol, CBG, angiotensinogen, SHBG and triglycerides were less pronounced compared to EE-containing products.Implications Statement: Combining E4 15 mg with DRSP 3 mg resulted in a COC with a different metabolic profile in comparison to EE-containing products. The clinical relevance of these findings needs to be further assessed, using clinical endpoints to establish the safety profile of this new COC. [ABSTRACT FROM AUTHOR]

Objective: To 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 Design: We 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).Results: Fifty-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).Conclusion: We 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.Implications: Combinations 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. [ABSTRACT FROM AUTHOR]

Background: Family planning is one important consulting encountered daily in the medical profession. Choosing the contraception method among others should be based on both patients' and physician's choices. Multiple options of contraception now are available in the markets, each one has its unique pros and cons. So, profound knowledge about each type is mandatory to help the patients in that regard. Objectives: We aimed to review the literature reviewing contraception methods, their mechanism of action, side effects, efficacy, and contraindications. Methodology: PubMed database was used for article selection, gathered papers had undergone a thorough review. Conclusion: Against the common belief that there is a perfect contraceptive method, each patient has their perfect match instead. Taking into consideration efficacy, reversibility, side effects, accessibility, and usage complexity would, certainly, contribute to the determination of the method of choice. Compliance is a key factor that must be addressed and shed light on with patients during a consultation session where proper education showed better outcomes in compliance. [ABSTRACT FROM AUTHOR]

Introduction: The study was conducted to assess the safety and efficacy of a combined oral contraceptive, YAZ, containing 3 mg drospirenone/20 μg ethinyl estradiol administered in a 24/4 regimen.Methods: This was a single-arm, open-label, interventional, post-authorization safety surveillance study of YAZ across 6 treatment cycles. Primary objective was assessing its safety profile in Chinese women. Secondary objectives included assessing contraceptive efficacy, cycle control, and bleeding patterns among subjects with and without preceding abortion, along with efficacy in moderate acne vulgaris. Subgroup analyses included assessing efficacy in the dysmenorrhea group using a visual analog scale. All variables were analyzed by descriptive statistical methods.Results: Of 1921 women treated with YAZ (mean age: 29.9 ± 5.5 years), 12.9% reported adverse drug reactions. Most frequently reported adverse events were nausea (2.6%), breast pain (2.3%), and breast swelling (1.3%). Unintended pregnancy rate (adjusted Pearl Index) was 0.3 (n = 2 pregnancies, 95% confidence interval 0.1-1.2). Incidence of overall withdrawal bleeding (cycle 2-cycle 5) was 93.3%-95.2%, of which 87.8%-95.1% in post-abortion subjects and 94.0%-95.3% in subjects without preceding abortion. Intra-cyclic bleeding (cycle 2-cycle 6) decreased in the overall population (from 14.9 to 5.5%), post-abortion subgroup (32.4% to 6.9%), and in subjects without preceding abortion (12.4% to 5.3%). Incidence of onset of withdrawal bleeding < 7 days among abnormal uterine bleeding patients at baseline was 85.2% and 87.2% at cycles 2 and 5, respectively, and incidence of intra-cyclic bleeding was 23.5% and 8.0% at cycles 1 and 6, respectively. Mean percent change in total acne lesion count from baseline to cycle 6 was - 79.9% ,and mean change in pain severity due to dysmenorrhea was - 31.2 mm at cycle 6 when compared with baseline.Conclusion: The 24/4 YAZ regimen showed good safety profile, contraceptive reliability, good cycle control along with subgroup of patients. Improvements in dysmenorrhea and acne were also observed. No events of venous thromboembolism/arterial thromboembolism were reported.Trial Registration: ClinicalTrials.gov identifier, NCT02710708; Center for Drug Evaluation (CDE), China Food and Drug Administration (CFDA) number: CTR20160203. [ABSTRACT FROM AUTHOR]

The article presents the latest data on the risks of complications development on the background of the use of combined oral contraceptives, as well as the treatment effects of the use of hormonal contraceptives.

The paper presents a review of accumulated data relating to major definitions in diagnostics and therapy of the premenstrual syndrome and own experience represented by case histories. Various therapeutic approaches from the point of view of evidencebased medicine are highlighted.

Objective: The combined oral contraceptive pill is the most preferred contraceptive method worldwide. Despite high life-time prevalence of infertility of 16-26%, scarce data about concerns of future fertility among COC users are available. We aimed to study whether COC usage induces concerns about fertility. Methods: Online questionnaire-based survey included 1283 current COC users and 1006 past users. The questionnaire covered knowledge and concerns of various aspects of fertility with respect to COC usage. Results: Significantly, more current users (66%) than past users (52%) had considered whether or not COC usage could affect future fertility (OR = 1.6, 95% CI 1.3-1.9). Nearly 50% of both groups believed COC usage could impair conception rates after discontinuation. Furthermore, 28% current vs. 19% past users believed COC could diminish the ovarian reserve more permanently. Conversely, 14% current and 11% past users believed that lack of ovulation could 'spare' the eggs (OR = 0.9, 95% CI 0.7-1.3). Significantly fewer current users (22%) vs. past users (35%) had heard, primarily by female friends, that a short break of 1-2 months during long-term COC usage was healthy, (OR 0.72, 95%CI = 0.56-0.92). Conclusions: Health care professionals prescribing hormonal contraception should be aware of misapprehensions and concerns of fertility among users of COC. [ABSTRACT FROM AUTHOR]

Biological role of magnesium in the human body is proved and very well-known. The pathogenesis of obstetrics and gynecology pathology shows that, next to magnesium, pyridoxine plays a key role. An effective strategy for prevention premature delivery, preeclampsia and eclampsia is proved to be timely magnesium sulfate application. We also have facts about its neuroprotective effect on the fetus. However the possibility of overdosage and serious side effects lead to a restricted usage of magnesium sulfate. To minimize the risk of overdosage, its necessary to follow the standard protocols, to make independent crosscheck and to monitor the condition of the patient. Its also reasonable to take magnesium sulfateorally - apart from better bioavailability,overdosage won’t cause serious side effects. Organic magnesium sulfate for magnesium deficiency control and associated symptoms is also justified for premenstrual syndrome (PMS), when COC (Combined Oral Contraceptives) and HRT (hormonal replacement therapy) is prescribed for women undergoing menopause. Magnesium citrate is more preferable because citrate-anion facilitates high bioavailability of magnesium, its also necessary in Krebs cycle and it turns into carbon dioxide and water. Due to this citrate is a perfect transporter of magnesium to the cells.

Résumé: Chez les adolescents, la santé sexuelle et reproductive est un aspect important des soins de santé complets. Le présent document de principes fournit des conseils afin de sélectionner des contraceptifs à l'intention des adolescentes et de leur en prescrire, y compris les contraceptifs hormonaux courants (pilule, timbre, anneau et progestatif injectable) et les contraceptifs réversibles à longue durée d'action (CRLDA). Tel qu'on les utilise habituellement, les CRLDA, qui incluent les implants sous-cutanés (non offerts au Canada) et les contraceptifs intra-utérins, sont beaucoup plus efficaces que les contraceptifs hormonaux. Le présent document de principes recommande les CRLDA comme contraception de première intention chez les adolescentes canadiennes, tout en soulignant que les dispensateurs de soins doivent collaborer avec les jeunes dans le choix d'un moyen de contraception que celles-ci trouvent acceptable, sécuritaire, efficace et pratique. Des stratégies sont proposées pour éliminer les obstacles à l'adoption et au maintien de la contraception. [ABSTRACT FROM AUTHOR]

Sexual and reproductive health is an important component of comprehensive health care for youth. This statement provides guidance for selecting and prescribing contraceptives for youth, including commonly prescribed hormonal contraceptives—the pill, patch, ring and injectable progestin—and long-acting reversible contraceptives (LARCs). LARCs, including subdermal implants (which are not available in Canada) and intrauterine contraceptives (IUCs), are substantially more effective during typical use than hormonal contraceptives. This statement endorses LARCs as the first-line option for contraception for Canadian youth, while emphasizing that providers must collaborate with youth to select a contraceptive method that is acceptable, safe, effective and practical for them. Strategies that eliminate obstacles to initiating and continuing contraception are provided. [ABSTRACT FROM AUTHOR]

Objectives: Meniere's disease is caused by an augmented endolymph pressure in the inner ear; symptoms are vertigo, fluctuating hearing loss and tinnitus. Exacerbations has been noted during premenstrual phase. The study aims to evaluate the effects of a 20 μm Ethinylestradiol (EE) and 3 mg Drospirenone (DRSP) oral contraceptive (20 μmEE/3mgDRSP) in continuous regimen, associated with rehabilitation therapy on Meniere's disease.Study Design: This non-randomized controlled study was performed from October 2015 to October 2017. Forty-two premenopausal women affected by MD with severe distress in the premenstrual phase were enrolled. Sixteen women constituted the study group (Group A), and twenty women constituted the control group (Group B). Group A underwent EE/DRSP therapy and rehabilitation and Group B underwent rehabilitation therapy alone. Stabilometry and the Dizziness Handicap Inventory questionnaire were used to measure vestibular function and distress related to the disease, respectively, at baseline (T0), 3 months (T1) and 6 months (T2).Results: At T0, both groups had large, similar areas of stabilometric ellipses (p = NS) that reduced more in Group A than in Group B, at T1 and T2 (p < 0.001). High scores of the DHI (cut-off ≤54) were observed at T0 in both groups (A 66.8 ± 2.8 vs B 65.5 ± 3.6; p = NS). At T1, a gradual improvement in both groups was observed, manly in Group A (A 45.1 ± 3.6 vs B 62.4 ± 4.1; p < 0.001). At T2, the DHI scores were significantly lower in Group A (39.2 ± 3.8) compared to Group B (68.8 ± 3.6) (p < 0.001).Conclusions: DRSP could be effective in reducing the fluid overload typical of the premenstrual phase, improving symptoms of MD. The results support the efficacy of EE/DRSP usage associated with rehabilitation therapy on premenstrual exacerbation of MD. [ABSTRACT FROM AUTHOR]

This article is a review of continuous use of oral contraception.

Purpose: To evaluate scheduled and unscheduled bleeding and spotting over 1 year of treatment with 91-day extended-regimen combined oral contraception (COC) providing continuous lowdose ethinyl estradiol (EE) in place of the traditional 7-day hormone-free interval (HFI). Patients and methods: This post hoc analysis of a multicenter, open-label, 1-year, Phase 3 study of extended-regimen COC with 30 μg EE/150 μg levonorgestrel (LNG) for 84 days and EE 10 μg for 7 days included 799 sexually active, adult women who completed at least one 91-day cycle of therapy. Subjects recorded bleeding and spotting episodes daily using electronic diaries. Logistic regression analyses are reported as ORs with 95% CIs. Results: There was a 10% increase (OR =1.102; 95% CI: 1.006-1.206) in the likelihood of reporting no scheduled bleeding for each additional 91-day cycle completed. From the third 91-day cycle, more than one fifth of women reported no scheduled bleeding (third cycle =23% [121/533]; fourth cycle =22% [97/446]). Among women who reported no scheduled bleeding at Cycle 1 (136/758 [18%]), $45% showed sustained lack of scheduled bleeding in later cycles. There were increases of 53% (OR =1.531; 95% CI: 1.393-1.683) and 31% (OR =1.307; 95% CI: 1.205-1.418) in the likelihood of reporting 0 to #6 days vs .6 days of unscheduled bleeding and spotting, respectively, for each additional 91-day cycle. By Cycle 2, more than 80% of women reported no unscheduled bleeding or #6 days of unscheduled bleeding during each 91-day cycle. Conclusion: Improved cycle control with decreased bleeding over time was shown during extended-regimen COC with 30 μg EE/150 μg LNG for 84 days and continuous low-dose EE instead of the traditional 7-day HFI. Women considering this regimen should be informed that those who complete at least one 91-day COC cycle will likely experience less bleeding/ spotting in future cycles. [ABSTRACT FROM AUTHOR]

Purpose of Review: The review aims to summarize our current knowledge surrounding treatment strategies aimed at recovery of bone mass in energy-deficient women suffering from the Female Athlete Triad. Recent Findings: The independent and interactive contributions of energy status versus estrogen status on bone density, geometry, and strength have recently been reported, highlighting the importance of addressing both energy and estrogen in treatment strategies for bone health. This is supported by reports that have identified energy-related features (low body weight and BMI) and estrogen-related features (late age of menarche, oligo/amenorrhea) to be significant risk factors for low bone mineral density and bone stress injury in female athletes and exercising women. Summary: Nutritional therapy is the recommended first line of treatment to recover bone mass in energy-deficient female athletes and exercising women. If nutritional therapy fails after 12 months or if fractures or significant worsening in BMD occurs, pharmacological therapy may be considered in the form of transdermal estradiol with cyclic oral progestin (not COC). [ABSTRACT FROM AUTHOR]

Objectives: To compare user satisfaction and adverse events (AEs) with a levonorgestrel intrauterine system (LNG-IUS 8; average levonorgestrel release rate approximately 8 μg/24 h over the first year [total content 13.5 mg]) and a 30 μg ethinyl estradiol/3 mg drospirenone (EE/DRSP) combined oral contraceptive (COC) in a population of young women.Methods: Nulliparous and parous women (aged 18-29 years) with regular menstrual cycles (21-35 days) were randomised to LNG-IUS 8 or EE/DRSP for 18 months. The primary endpoint was the overall user satisfaction rate at month 18/end of study visit.Results: Overall, 279 women were randomised to LNG-IUS 8 with attempted placement and 281 women were randomised to EE/DRSP and took ≥1 pill; the mean age was 23.7 and 23.9 years, and 77.4% and 73.3% were nulliparous, respectively. At month 18/end of study, 82.1% and 81.9% of women, respectively, reported being 'very satisfied' or 'satisfied' with their treatment; however, significantly more LNG-IUS 8 users reported a preference to continue their treatment post-study (66.2% vs 48.8%; p = 0.0001). There were two pregnancies (one ectopic pregnancy, one spontaneous abortion) reported in the LNG-IUS 8 group and six (three live births, two spontaneous abortions, one induced abortion) in the EE/DRSP group.Conclusions: LNG-IUS 8 and EE/DRSP were associated with similarly high user satisfaction rates. However, LNG-IUS 8 users were significantly more likely to prefer to continue their contraceptive method post-study, indicating that a levonorgestrel intrauterine system is an appealing contraceptive option for young women. [ABSTRACT FROM AUTHOR]

Objectives: This observational, multicentre, prospective phase IV study examined change in health-related quality of life (QOL) from baseline to 6 months in women initiating combined oral contraception (COC) based on natural estrogen.Methods: Eligible women attending a baseline and 6-month gynaecology appointment belonged to one of three groups: group 1 used barrier contraception (condoms) and elected to continue this method; group 2 used condoms and elected to switch to COC based on natural estrogen; group 3 used COC based on ethinylestradiol and elected to switch to COC based on natural estrogen. The Spanish Society of Contraception (SEC)-QOL scale assessed health-related QOL. Secondary outcomes included symptoms of premenstrual syndrome, intermenstrual bleeding, duration and intensity of menstrual bleeding, contraception continuation rate, and tolerability.Results: A total of 857 women were enrolled and 785 completed the study. Group 2 (n = 224 completed) had significantly lower SEC-QOL global and dimension scores at baseline and significantly greater increases in SEC-QOL from baseline to 6 months compared with groups 1 (n = 72) and 3 (n = 489). Group 3 reported a similar SEC-QOL score to that of group 1 at baseline but showed significantly greater improvement in SEC-QOL global and psychological scores from baseline to 6 months. Among women receiving COC based on natural estrogen, the contraception continuation rate was 713/780 (91.4%); treatment-related adverse events were reported by 13/780 (1.7%).Conclusions: Improved SEC-QOL after 6 months was found in women who were dissatisfied with their current contraception at baseline and chose to switch to COC based on natural estrogen. [ABSTRACT FROM AUTHOR]

ObjectivesThe aim of our study was to investigate the knowledge, perceptions and attitudes of female Romanian university students, as possible future opinion leaders, about contraception and motherhood, by assessing their level of contraceptive use, opinions and knowledge with regard to combined oral contraceptives (COCs). MethodsA knowledge, attitudes and practice questionnaire was conducted among 1105 female university students aged 19 to 30 years. The participants were recruited from six faculties at universities in Iasi and Arad, Romania. The study protocol was approved by the university ethics committees. Statistical analyses included percentages, χ2tests and Fisher's exact test. ResultsTwo-thirds of respondents were in a relationship or married. Average age at first sexual intercourse was 18.6 years. Two out of three (69%) students identified themselves as sexually active. The same percentage showed a positive attitude towards contraception and stated that they used it. The most commonly used contraceptive methods were condoms, COCs and withdrawal. The students’ perceptions of the benefits and adverse effects of COCs were analysed. Half of the students had heard about extended COC regimens, but only 24% showed interest in using them regularly. A large proportion of pharmacy and non-medical students appeared to have poor knowledge about contraception and reproductive health, which generated misperceptions and negative attitudes. Two-thirds of the participants considered 25 to 29 years to be the optimal age for starting a family, and 85.5% intended to have children in the future. ConclusionsMedical students, but not pharmacy students, showed higher levels of knowledge. Improvement of students’ knowledge, perceptions and attitudes towards general contraceptive use, COCs and childbearing is needed. Evidence-based information is required to address poor knowledge about the physiology of reproduction, misconceptions relating to COCs, and the possibility of menstrual suppression using hormonal contraceptive methods. Compulsory reproductive health education for students is desirable. 摘要目的本研究的目的是通过对避孕药具使用水平、意见及复方口服避孕药的知识的评估调查罗马尼亚女大学生—可能为未来舆论领导者，对避孕和孕产的知识、认知和态度。 方法对年龄在19-30岁之间的1105名女大学生进行关于知识、态度及行为的问卷调查。调查者来自罗马尼亚雅西和阿拉德大学的6个学院。本研究得到大学伦理委员会批准。统计分析使用百分率、卡方检验和Fisher精确概率法。 结果三分之二的调查者有性生活或者已婚，初次性交的平均年龄是18.6岁，超过三分之二（69%）的学生认为她们自己性活跃，相同比例的学生对避孕持积极的态度并且表示使用避孕方法。最常使用的避孕方法是避孕套、复方口服避孕药和体外排精避孕。对学生们关于复方口服避孕药的益处和副作用的了解情况进行了分析。一半的学生听说过复方口服避孕药，仅24%规律使用。很大比例的药学和非医学专业的学生对避孕和生殖健康知识了解很少并产生错误的认识和消极态度。三分之二的调查者认为成家的最佳年龄是25-29岁，85.5%打算在将来要孩子。 结论除药学外的医学生知识水平较高，必需提高学生们对常规的避孕药具使用、复方口服避孕药及生育的知识、观念和态度。这就要求用循证的信息来解决生殖生理、避孕药的错误认识、使用复方口服避孕药月经抑制的可能性等知识上的不足。强制性的生殖健康教育对学生们来说是合适的。 [ABSTRACT FROM PUBLISHER]

Objective This study describes ovarian activity suppression of a 21/7-active low-dose combined oral contraceptive (COC) regimen that included only ethinyl estradiol (EE) during the traditional hormone-free interval (HFI) and two commercially available 28-day regimens, a 24/4 and a 21/7 regimen. Study design The randomized, open-label, parallel-group descriptive study was conducted at two US sites. Healthy, reproductive-aged women ( n = 146) were randomized to one of three groups for three consecutive 28-day cycles, as follows: treatment 1 ( n = 39 completed): 21/7-active COC [21 days of 150 mcg desogestrel (DSG)/20 mcg EE, followed by 7 days of 10 mcg EE (DSG/EE+7 days EE)], treatment 2 ( n = 39 completed): 24 days of 3 mg drospirenone (DRSP)/20 mcg EE, followed by 4 placebo (PBO)-pill days (DRSP/EE+4 days PBO) and treatment 3 ( n = 42 completed): 21 days of 100 mcg levonorgestrel (LNG)/20 mcg EE, followed by 7 PBO-pill days (LNG/EE+7 days PBO). The primary outcome was ovarian activity suppression assessed by transvaginal ultrasound and serum hormone concentrations and classified using the Hoogland and Skouby (H/S) method. Results Ovarian activity rate (H/S grade 4 or 5) was low for all three treatments: 0% [95% confidence interval (CI) 0–2.8] for DSG/EE+7 days EE, 1% (95% CI 0.2–5.2) for DRSP/EE+4 days PBO and 1% (95% CI 0–3.9) for LNG/EE+7 days PBO. All three treatments showed similar suppression of serum progesterone, 17β-estradiol, follicle-stimulating hormone and luteinizing hormone levels. Conclusions The 21/7-active low-dose COC regimen (DSG/EE+7 days EE) showed ovarian activity suppression that was similar to the 24/4 (DRSP/EE+4 days PBO) and 21/7 (LNG/EE+7 days PBO) regimens. Implications The 21/7-active low-dose COC regimen (DSG/EE+7 days EE) that included only EE during the traditional HFI showed suppression of ovarian follicular activity that was similar to the 24/4 (DRSP/EE+4 days PBO) and the 21/7 (LNG/EE+7 days PBO) comparator regimens. [ABSTRACT FROM AUTHOR]

Résumé: La contraception estro-progestative est le moyen de contraception le plus utilisé en France chez les femmes en âge de procréer. Suite au déremboursement des contraceptifs contenant un progestatif de 3e génération et suite au retrait provisoire du marché de Diane 35® et de ses génériques, quel est le retentissement de ces évènements sur notre pratique de prescription ? Quels arguments scientifiques peuvent appuyer notre pratique quotidienne ? Nous aborderons tout particulièrement les risques cardiovasculaires de la contraception estro-progestative. [ABSTRACT FROM AUTHOR]

Unlabelled: BACKGROUND; Combined oral contraceptives (COCs) reduce levels of androgen, especially testosterone (T), by inhibiting ovarian and adrenal androgen synthesis and by increasing levels of sex hormone-binding globulin (SHBG). Although this suppressive effect has been investigated by numerous studies over many years, to our knowledge no systematic review concerning this issue had been performed. This systematic review and meta-analysis was performed to evaluate the effect of COCs on concentrations of total T, free T and SHBG in healthy women and to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T and free T.Methods: A review of the literature was performed using database searches (MEDLINE, EMBASE and the Cochrane Central Register of Clinical Trials) and all publications (from inception date until July 2012) investigating the effect of COCs on androgen levels in healthy women were considered eligible for selection. Three reviewers were involved in study selection, data extraction and critical appraisal. For the meta-analysis, data on total T, free T and SHBG were extracted and combined using random effects analysis. Additional subgroup analyses were performed to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T or free T.Results: A total of 151 records were identified by systematic review and 42 studies with a total of 1495 healthy young women (age range: 18-40 years) were included in the meta-analysis. All included studies were experimental studies and 21 were non-comparative. Pooling of the results derived from all the included papers showed that total T levels significantly decreased during COC use [mean difference (MD) (95% confidence interval, CI) -0.49 nmol/l (-0.55, -0.42); P < 0.001]. Significantly lower levels of free T were also found [relative change (95% CI) 0.39 (0.35, 0.43); P < 0.001], with a mean decrease of 61%. On the contrary, SHBG concentrations significantly increased during all types of COC use [MD (95% CI) 99.08 nmol/l (86.43, 111.73); P < 0.001]. Subgroup analyses revealed that COCs containing 20-25 µg EE had similar effects on total and free T compared with COCs with 30-35 µg EE. In addition, suppressive effects on T levels were not different when comparing different types of progestins. However, subgroup analyses for the estrogen dose and the progestin type in relation to changes in SHBG levels did show significant differences: COCs containing second generation progestins and/or the lower estrogen doses (20-25 µg EE) were found to have less impact on SHBG concentrations.Conclusions: The current literature review and meta-analysis demonstrates that COCs decrease circulating levels of total T and free T and increase SBHG concentrations. Due to the SHBG increase, free T levels decrease twice as much as total T. The estrogen dose and progestin type of the COC do not influence the decline of total and free T, but both affect SHBG. The clinical implications of suppressed androgen levels during COC use remain to be elucidated. [ABSTRACT FROM AUTHOR]