Combined oral contraceptive use and obesity in women with polycystic ovary syndrome. A meta-analysis of randomized clinical trials.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogenous endocrine condition and combined oral contraceptives (COCs) have been demonstrated to be the first-line treatment to women who do not intend to become pregnant. The combination of COCs and PCOS may or may not amplify the risks of cardiovascular events. OBJECTIVE: To investigate whether surrogates for obesity may be influenced by the use of COCs containing different formulations in women with PCOS. METHOD: From January 2024 a literature search was conducted in Google Scholar and Pubmed databases using PCOS, COC, and obesity terms. Hand search of randomized clinical trials in the references of obtained manuscripts was also performed. After the exclusion of reviews and articles that did not fulfill eligibility criteria, compared the results obtained before and after the use of COCs in 13 randomized clinical trials (RCTs). Random-effects model was used to estimate the standardized mean differences (SMD) and standard errors (SE). Risk of bias was examined using the Rob2 tool. RESULT: Thirteen heterogeneous RCTs reported no difference in waist circumference with the use of different COC formulations (p = 0.714). On the contrary, body fat mass increased with the use of pill (p = 0.013). Waist triglyceride index and lipid accumulation product tended to be higher after the use of COCs (p = 0.073 and p = 0.064, respectively). CONCLUSION: Combined oral contraceptives with different formulations might increase fat mass accumulation in women with PCOS. Lipids may also be increased in PCOS users. Because some concerns about the quality and heterogeneity identified in various RCTs, caution should be taken before a definitive conclusion regarding the use of COCs and obesity.

El papel del estetrol en la anticoncepción: una revisión integral / The role of estetrol in contraception: a comprehensive review

Esta revisión narrativa explora el papel potencial del estetrol (E4), un esteroide estrogénico natural, en la anticoncepción, analizando sus propiedades farmacológicas, su efectividad y su seguridad. Se revisaron estudios preclínicos, ensayos clínicos y evaluaciones de seguridad del E4 como anticonceptivo oral combinado (AOC). Se investigó el impacto en parámetros endocrinos, metabólicos y hemostáticos, así como su tolerabilidad. En los resultados, el E4 tiene menor afinidad por el receptor de estrógeno-α de membrana, pero mantiene la actividad agonista en los receptores nucleares. E4/DRSP (drospirenona) demostró ser un AOC eficaz, con ciclos de sangrado regulares y predecibles en la mayoría de las mujeres. La tolerabilidad fue favorable, con eventos adversos leves o moderados y bajas tasas de interrupción. El sangrado fue el evento adverso más común, y se reportaron casos raros de migrañas con aura, trombosis venosa profunda, hiperpotasemia y depresión. E4/DRSP tuvo mínimo impacto en los parámetros lipídicos, hepáticos, de globulina fijadora de hormonas sexuales y de metabolismo de hidratos de carbono, y efecto neutral o mínimo en los parámetros hemostáticos. Se concluye que E4/DRSP parece ser una opción anticonceptiva eficaz y segura, con reducido riesgo trombótico y mínimo impacto en los parámetros endocrinos y metabólicos. Se requiere más investigación para confirmar su seguridad y eficacia a largo plazo.

This narrative review explores the potential role of estetrol (E4), a natural estrogenic steroid, in contraception, analyzing its pharmacological properties, effectiveness, and safety. Preclinical studies, clinical trials, and safety assessments of E4/DRSP (drospirenone) as a combined oral contraceptive (COC) were reviewed. The impact on endocrine, metabolic, and hemostatic parameters, as well as tolerability, was investigated. In results, E4 exhibits lower affinity for estrogen transmembrane receptor-α but maintains agonistic activity on nuclear receptors. E4/DRSP proved to be an effective COC with regular and predictable bleeding cycles in most women. Tolerability was favorable with mild or moderate adverse events and low discontinuation rates. Bleeding was the most common adverse event, and rare cases of aura migraines, deep vein thrombosis, hyperkalemia, and depression were reported. E4/DRSP had minimal impact on lipid, hepatic, sex hormone-binding globulin, and carbohydrate metabolism parameters, with a neutral or minimal effect on hemostatic parameters. The conclusion is that E4/DRSP seems to be an effective and safe contraceptive option, with reduced thrombotic risk and minimal impact on endocrine and metabolic parameters. Further research is needed to confirm long-term safety and efficacy.

Combined Oral Contraceptives: Association with Serum 25-Hydroxyvitamin D and Calcium and Bone Homeostasis.

Background: Use of combined oral contraceptives (COCs) has been found to increase serum 25-hydroxyvitamin D [25(OH)D] but effects on calcium and bone homeostasis are unclear. Materials and Methods: Serum 25(OH)D, parathyroid hormone (PTH), alkaline phosphatase (ALK) and estradiol, dietary intake of bone-related nutrients and foods, bone mineral density (BMD), and body fat were compared in adult women (20-35 years; body mass index 21.5 ± 2.3 kg/m2) users (+COC, n = 32) and nonusers (-COC, n = 20) of COC. Biochemical markers were measured by automated assays. BMD at total body (TB), lumbar spine (LS), femoral neck (FN) and trochanter (TR), and body fat, were measured by dual-energy X-ray absorptiometry. Dietary intake was assessed by a food frequency questionnaire. Results: Intake of calcium, dairy foods, and fruits and vegetables, were adequate and did not differ by COC. Mean 25(OH)D was 35% higher in +COC (110.4 ± 27.3 nmol/L, 44.2 ± 1.8 ng/mL) compared with -COC (81.7 ± 22.8 nmol/L, 32.7 ± 2.3 ng/mL; p < 0.001). Mean PTH, ALK, and estradiol were 28%, 12%, and 62% lower, respectively, in +COC compared with -COC (p ≤ 0.05). Mean BMD z-scores (all sites) were adequate and did not differ by COC. There were no correlations between 25(OH)D and dietary, biochemical, and body composition variables. PTH was inversely correlated with TR-BMD z-score in -COC (r = -0.47; p = 0.04), and ALK was inversely correlated with TB-, TR-, and LS-BMD z-scores in -COC (r ≤ -0.43; p ≤ 0.04), but not in +COC. Conclusions: Increased serum 25(OH)D with COC use was paralleled by expected physiologic adjustments in calcium and bone homeostasis, and adequate bone mass status, in nonobese young adult women consuming bone-healthy diets.

Contraindicated use of modern contraceptives among mothers from a Pelotas Birth Cohort

ABSTRACT OBJECTIVE To describe the prevalence of contraindicated use of combined hormonal contraceptives, progesterone-only contraceptives, and intrauterine devices in mothers participating in the 2015 Pelotas Birth Cohort according to the WHO medical eligibility criteria. METHODS The biological mothers of children belonging to the 2015 Pelotas birth cohort who attended the 48-month follow-up were studied. The 48-month follow-up data were collected from January 1, 2019, to December 31, 2019. Contraindicated use of modern contraceptives was considered to occur when these women presented at least one of the contraindications for the use of modern contraceptives and were using these methods. The prevalence of contraindicated use was calculated according to each independent variable and their respective 95% confidence intervals (95%CI). RESULTS The analyzed sample consisted of 3,053 women who used any modern contraceptive method. The prevalence of contraindicated use of modern contraceptives totaled 25.9% (95%CI: 24.4-27.5). Combined hormonal contraceptives showed the highest prevalence of contraindicated use (52.1%; 95%CI: 49.3-54.8). The prevalence of contraindicated use of modern contraceptives methods was greater in women with family income between one and three minimum wages, a 25-30 kg/m2 body mass index, indication by a gynecologist for the used method, and purchasing the contraceptive method at a pharmacy. The higher the women's education, the lower the prevalence of inappropriate use of modern contraceptives. CONCLUSION In total, one in four women used modern contraceptives despite showing at least one contraindication. Policies regarding women's reproductive health should be strengthened.

Eficacia y seguridad del uso extendido de anticonceptivos orales combinados / Efficacy and safety of extended use of combined oral contraceptives

Los anticonceptivos orales combinados constituyen hoy en día uno de los métodos anticonceptivos más populares a nivel mundial. Su composición consiste en una combinación de análogos de hormonas sexuales femeninas que se administran en bajas dosis diarias, manteniendo constante su concentración sanguínea y evitando de esta forma los cambios en el eje endócrino que estimulan la ovulación. Con el objetivo de recrear los procesos fisiológicos, la mayoría de las formulaciones comprenden un intervalo de 4 a 7 días libres de hormonas en el cual se genera el sangrado por deprivación.A partir de una viñeta clínica en la que una paciente sana desea posponer su hemorragia por deprivación, y tras realizar una búsqueda bibliográfica que prioriza las investigaciones más recientes y de mejor calidad, la autora revisa la evidencia sobre el uso de hormonas sin intervalo libre, especialmente su efectos sobre la eficacia y la incidencia de efectos adversos. (AU)

Nowadays, combined oral contraceptives are one of the most popular contraceptive methods worldwide. Its composition consists of a combination of similar female sex hormones administered in low daily doses, keeping their blood concentration constant and thus avoiding changes in the endocrine axis that stimulate ovulation. In order to recreate physiological processes, most formulations include an interval of 4 to 7 hormone-free days in which withdrawal bleeding occurs.Starting from a clinical vignette in which a healthy patient desires to postpone her withdrawal bleeding, and after conducting a bibliographic search that prioritizes the most recent and best-quality research, the author reviews the evidence about the use of hormones without free interval, especially their effects on efficacy and the incidence of adverse effects. (AU)

Combined Oral Contraceptive Use and the Risk of Cervical Cancer: Literature Review.

Cervical cancer (CC) is caused by persistent infection of human papillomavirus of high oncogenic risk (hr-HPV); however, several cofactors are important in its carcinogenesis, such as smoking, multiparity, and prolonged use of oral hormonal contraceptives (COCs). Worldwide, 16% of women use COCs, whereas in Brazil this rate is of ∼ 30%. The safety and adverse effects of COCs are widely discussed in the literature, including the increase in carcinogenic risk. Due to the existence of several drugs, combinations, and dosages of COCs, it is hard to have uniform information in epidemiological studies. Our objective was to perform a narrative review on the role of COCs use in the carcinogenesis of cervical cancer. Several populational studies have suggested an increase in the incidence of cervical cancer for those who have used COCs for > 5 years, but other available studies reach controversial and contradictory results regarding the action of COCs in the development of CC.

O câncer cervical (CC) é causado pela infecção persistente pelo papilomavírus humano de alto risco oncogênico (hr-HPV); entretanto, vários cofatores são importantes na sua carcinogênese, como tabagismo, multiparidade e uso prolongado de contraceptivos hormonais orais (COCs). No mundo, 16% das mulheres usam AOCs, enquanto no Brasil essa taxa é de ∼ 30%. A segurança e os efeitos adversos dos COCs são amplamente discutidos na literatura, incluindo o aumento do risco carcinogênico. Devido à existência de várias drogas, combinações e dosagens de COCs, é difícil ter informações uniformes em estudos epidemiológicos. Nosso objetivo foi realizar uma revisão narrativa sobre o papel do uso de COCs na carcinogênese do câncer cervical. Vários estudos populacionais têm sugerido aumento da incidência de câncer de colo uterino para aquelas que usam COCs há mais de 5 anos, mas outros estudos disponíveis chegam a resultados controversos e contraditórios quanto à ação dos COCs no desenvolvimento do CCU.

Bone impact after two years of low-dose oral contraceptive use during adolescence.

OBJECTIVE: Data regarding the use and effect of hormonal contraceptives on bone mass acquisition during adolescence are contradictory. The present study was designed to evaluate bone metabolism in two groups of healthy adolescents using combined oral contraceptives (COC). METHODS: A total of 168 adolescents were recruited from 2014 to 2020 in a non-randomized clinical trial and divided into three groups. The COC1 group used 20 µg Ethinylestradiol (EE)/150 µg Desogestrel and the COC2 group used 30 µg EE/3 mg Drospirenone over a period of two years. These groups were compared to a control group of adolescent non-COC users. The adolescents were submitted to bone densitometry by dual-energy X-ray absorptiometry and measurement of bone biomarkers, bone alkaline phosphatase (BAP), and osteocalcin (OC) at baseline and 24 months after inclusion in the study. The three groups studied were compared at the different time points by ANOVA, followed by Bonferroni's multiple comparison test. RESULTS: Incorporation of bone mass was greater in non-users at all sites analyzed (4.85 g in lumbar Bone mineral content (BMC)) when compared to adolescents of the COC1 and COC2 groups, with a respective increase of 2.15 g and loss of 0.43g in lumbar BMC (P = 0.001). When comparing subtotal BMC, the control increased 100.83 g, COC 1 increased 21.46 g, and COC 2 presented a reduction of 1.47 g (P = 0.005). The values of bone markers after 24 months are similar for BAP, being 30.51 U/L (± 11.6) for the control group, 34.95 U/L (± 10.8) for COC1, and 30.29 U/L for COC 2 (± 11.5) (P = 0.377). However, when we analyzed OC, we observed for control, COC 1, and COC 2 groups, respectively, 13.59 ng/mL (± 7.3), 6.44 ng/mL (± 4.6), and 9.48 ng/mL (± 5.9), with P = 0.003. Despite loss to follow-up occurring in the three groups, there were no significant differences between the variables in adolescents at baseline who remained in the study during the 24-month follow-up and those who were excluded or lost to follow-up. CONCLUSION: Bone mass acquisition was compromised in healthy adolescents using combined hormonal contraceptives when compared to controls. This negative impact seems to be more pronounced in the group that used contraceptives containing 30 µg EE. CLINICAL TRIAL REGISTRATION: http://www.ensaiosclinicos.gov.br, RBR-5h9b3c. "Low-dose combined oral contraceptive use is associated with lower bone mass in adolescents".

Impact of COVID-19 on the prescription of contraceptives in a city in São Paulo.

OBJECTIVE: In the beginning of the pandemic, measures, such as social distancing, lockdown strategies, and restrictions on mobility, as well as the fear of transiting through health facilities, raised concerns about the impact of COVID-19 on women's ability to continue using contraceptives. METHODS: This is a retrospective cohort study, which evaluated reports of medication distribution spreadsheets in Bauru - SP, from January 2019 to June 2021. RESULTS: Our study showed that the municipal dispensation of contraceptives in the SUS was markedly impacted by the COVID-19 pandemic, suffering reductions that can impact on an increase in unplanned pregnancy rates. It is possible to note a significant decrease in the distribution of combined oral contraceptives (44.18%), combined injectable contraceptives (47.58% reduction), and medroxyprogesterone acetate (13.98%). This fact may be associated with the reduction in offers of face-to-face consultations in gynecology, due to the social isolation necessary at the time of the pandemic. CONCLUSION: Ensuring access to contraceptives during health emergencies should be a public health policy priority. Thus, it is essential to draw up strategic plans to encourage full access to reproductive planning services even in times of health emergency, so that the occurrence of unplanned pregnancies can be adequately prevented.

Exposure to levonorgestrel-based birth control pill in early life and its persistent effects in zebrafish.

The consumption of progestins has increased considerably in recent decades, as has their disposal into the environment. These substances can negatively affect the reproduction, physiology, and behavior of non-target organisms, such as fish. We aimed to evaluate the effects of exposure to environmentally relevant concentrations of levonorgestrel-control birth based (1.3, 13.3, 133, and 1330 ng/L) on the development and behavior of zebrafish (Danio rerio) in terms of mortality, hatching, spontaneous movement, and larval and adult behavioral tests. Exposure caused anxiogenic-like behavior in larvae, which persisted in adults, as demonstrated by the light-dark test. In contrast, it caused anxiolytic-like behavior in the novel tank test. There was a high mortality rate at all tested concentrations and increases in the hormone cortisol at 13.3 ng/L that affected the sex ratio. These changes may lead to an ecological imbalance, emphasizing the risk of early exposure to progestins in the environment.

Effect of two combinations of low-dose oral contraceptives on adolescent bone mass: A clinical trial with 2 years follow-up.

INTRODUCTION: Most contraceptive combinations can interfere with the processes of bone formation and resorption. AIM: The aim of this study was to evaluate the effect of 2 combinations of low-dose oral hormonal contraceptives (20 µg ethinyl estradiol [EE]/150 mg desogestrel [COC1] or 30 µg EE/3 mg drospirenone [COC2]) on bone mass acquisition in adolescents over 2 years by means of bone densitometry and measurement of biomarkers of bone remodeling. METHODS: Parallel-group, non-randomized controlled clinical trial of 127 adolescents divided into a control group and 2 groups receiving either COC1 or COC2. The participants were submitted to anthropometric assessment and evaluation of secondary sexual characteristics (Tanner criteria) and bone age. Bone densitometry by dual-energy X-ray absorptiometry and measurement of bone biomarkers (bone alkaline phosphatase, osteocalcin, and C-terminal telopeptide) were performed at baseline and after 24 months. RESULTS: No significant differences in the variables analyzed were observed between COC1 or COC2 users and the control group at baseline. After 24 months, non-users had incorporated more bone mass (content and density) than either group of contraceptive users. This negative impact was more pronounced in the COC2 group than in the COC1 group. A significant reduction in the percentage values of bone alkaline phosphatase and osteocalcin was observed in users of oral contraceptives. CONCLUSION: Bone mass acquisition was compromised in adolescent users of combined hormonal contraceptives. The negative impact was more pronounced in adolescents using contraceptives that contain 30 µg EE/3 mg drospirenone.

Effects of Physical Exercise on Lipid and Inflammatory Profile of Women Using Combined Oral Contraceptive: A Cross-Over Study

Abstract Background: The use of combined oral contraceptives (COC) is a risk factor for atherosclerotic disease, and physical exercise can minimize this condition. Objective: To verify if high intensity interval training (HIIT) promotes changes in the lipid and inflammatory profile of women using COC. Methods: Sequential crossover study with women aged 20-30 years, classified as irregularly active by the international physical activity questionnaire (IPAQ), when using COC. A physical-clinical assessment was performed with anthropometric measurements, VO2max, and analysis of lipid and inflammatory profile. Participants were divided into 2 groups: the initial intervention group (GII), which began practicing HIIT for 2 months, and the posterior intervention group (GIP), which remained inactive for the same period. The GII and GIP would then alternate their conditions. The collected data was divided into: Initial moment (IM), post-exercise moment (PEM) and post-inactivity (PIM). The statistical analyses were performed using the Statistical Package for the Social Sciences, adopting a significance level of p <0.05 . Results: Twelve women were evaluated. After crossing the GII and GIP data, there was a difference in the C-reactive protein values between the IM of 4 (1.6-6.3 mg/dL) vs. PEM 2 (1.5-5 mg/dL); as well as between the PEM vs. the PIM= 4 (1.5-5.8 mg/dL), with a p -value = 0.04 in the comparisons. There was no change between the "moments" of the lipid profile, although it was possible to notice a reduction in resting HR and an increase in indirect VO2max. Conclusion: The HIIT program was able to reduce the inflammatory profile, but it did not alter the lipid profile of irregularly active women using COC.

Renin-Angiotensin-Aldosterone System in Women Using Combined Oral Contraceptive: A Systematic Review.

OBJECTIVE: To describe the effects of combined oral contraceptives (COC) on the renin-angiotensin-aldosterone system (RAAS). DATA SOURCES: This is a systematic review according to the criteria of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), registered in PROSPERO under the ID: CRD42020200019. Searches were performed between August 2020 and December 2021, in the following databases: Medline via Pubmed, Cochrane Central Library, Scientific Electronic Library Online, and Latin American and Caribbean Literature in Health Sciences via Virtual Health Library. The effects of the combined oral contraceptive on plasma renin activity values, plasma renin values, angiotensinogen values- also known as plasma renin substrate- angiotensin, and/or aldosterone values. STUDY SELECTION: A total of 877 studies were selected and, of these, 10 articles met the eligibility criteria and were included in this review. DATA COLLECTION: Data were combined through qualitative synthesis and included in a spreadsheet previously prepared by the authors. DATA SYNTHESIS: The collected samples ranged from 18 to 137 participants, totaling 501 women aged between 18 and 49 years throughout all studies. The studies showed increased activity of plasma renin, plasma renin substrate, angiotensin II, and aldosterone in this population. CONCLUSION: The findings of this study suggest that the COC promotes greater activation of the RAAS. Supporting the idea that its use is related to an increased risk of cardiovascular events, including systemic arterial hypertension.

OBJETIVO: Descrever os efeitos do contraceptivo oral combinado (COC) no sistema renina-angiotensina-aldosterona (SRAA). FONTES DOS DADOS: Trata-se de uma revisão sistemática de acordo com os critérios do Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), registrada no PROSPERO sob ID: CRD42020200019. As buscas foram realizadas entre agosto de 2020 e dezembro de 2021 nas bases de dados: Medline via Pubmed, Biblioteca Cochrane Central, Scientific Electronic Library Online, e Literatura Latino-americana e do Caribe em Ciências da Saúde via Biblioteca Virtual em Saúde. Consultado os artigos sobre os efeitos do contraceptivo oral combinado nos valores da atividade da renina plasmática, valores plasmáticos da renina, valores do angiotensinogênio ­ também conhecido como substrato da renina plasmática ­, valores da angiotensina e/ou aldosterona. SELEçãO DOS ESTUDOS: Foram selecionados 877 estudos e, destes, 10 artigos preencheram os critérios de elegibilidade e foram incluídos nesta revisão. COLETA DE DADOS: Os dados foram combinados por meio de síntese qualitativa e inclusos em uma planilha elaborada previamente pelos autores. SíNTESE DOS DADOS: As amostras coletadas variavam entre 18 e 137 participantes, totalizando 501 mulheres com idade entre 18 e 49 anos em todos os estudos. Os estudos apresentaram aumento da atividade da renina plasmática, do substrato da renina plasmática, da angiotensina II e da aldosterona nessa população. CONCLUSãO: Os achados deste estudo sugerem que o COC promove maior ativação do SRAA. Apoiando a ideia de que o seu uso esteja relacionado ao aumento do risco de eventos cardiovasculares, incluindo a hipertensão arterial sistêmica.

Vaginal States: Detection of Conversion Processes in Women Using Contraception and Characterization of Vaginal Lactobacillus Species.

BACKGROUND: The vaginal microenvironment, regulated by an immune system, can be protected or altered by many factors, including contraceptive methods. OBJECTIVE: The objective of this study is to evaluate the impact of contraceptive methods on the basic vaginal states (BVSs) and to identify culturable vaginal Lactobacillus species. METHODS: This is a prospective, consecutive, longitudinal, and descriptive study. The vaginal contents of 208 women were sampled prior to initiating contraception and six months later. The BVSs were established using the balance of vaginal content (BAVACO) methodology that evaluates microbiota and vaginal inflammatory reaction (VIR). Lactobacillus species were characterized by biochemical tests and mass spectrometry. The following contraceptive methods were evaluated: combined oral contraceptive pill (COCP), condom (CON) and rhythm method (RHYT). McNemar's test was used. RESULTS: Of the 208 women, 171 attended both examinations. In the COCP group (n=127), 83 vaginal contents maintained a normal microbiota, 1 sample became dysbiotic, and 37/43 dysbiotic microbiota samples reverted to normal (p<0.0001). A conversion to BVS with VIR was detected in the CON group (n=31) (p=0.001). The RHYT group (n=13) maintained its initial BVSs. The predominant Lactobacillus species found were L. crispatus and L. gasseri, with a trend toward a positive association between L. crispatus and COCP (OR=2.82; p=0.058). CONCLUSION: Hormone administration corrected the dysbiosis and preserved a normal BVS. The CON increased the VIR. The protection of the microbiota observed in the rhythm method probably responds to a systemic hormonal influence. The trend toward a positive association between COCP and L. crispatus, with its protective properties, evidenced an effective hormonal relationship.

Epidemiological Survey on the Perception of Adverse Effects in Women Using Contraceptive Methods in Brazil.

OBJECTIVE: The present study aimed to understand patient perception of the adverse effects of contraceptives to improve health care and adherence to treatment. METHODS: An online questionnaire was available for women in Brazil to respond to assess their perception of adverse effects and their relationship with contraceptive methods. RESULTS: Of all 536 women who responded, 346 (64.6%) reported current contraceptive use. One hundred and twenty-two (122-34.8%) women reported having already stopped using contraception because of the adverse effects. As for the contraceptive method used, the most frequent was the combined oral contraceptive (212-39.6%). When we calculated the relative risk for headache, there was a relative risk of 2.1282 (1.3425-3.3739; 95% CI), suggesting that the use of pills increases the risk of headache, as well as edema, in which a relative risk of 1.4435 (1.0177-2.0474; 95% CI) was observed. For low libido, the use of oral hormonal contraceptives was also shown to be a risk factor since its relative risk was 1.8805 (1.3527-2.6142; 95% CI). As for acne, the use of hormonal contraceptives proved to be a protective factor, with a relative risk of 0.3015 (0.1789-0.5082; 95% CI). CONCLUSION: The choice of a contraceptive method must always be individualized, and the patients must be equal participants in the process knowing the expected benefits and harms of each method and hormone, when present.

OBJETIVO: Este estudo é destinado a entender a percepção de pacientes sobre os efeitos adversos dos métodos contraceptivos para aprimorar o atendimento médico e a aderência das mulheres ao tratamento. MéTODOS: Um questionário online foi disponibilizado para que mulheres no Brasil respondessem a fim de avaliar a sua percepção em relação aos efeitos adversos e a associação desses aos métodos contraceptivos. RESULTADOS: Das 536 mulheres que responderam, 346 (64,5%) alegaram uso atual de método contraceptivo. Cento e vinte e duas (122­34,8%) mulheres disseram que já haviam parado o uso de métodos contraceptivos devido aos seus efeitos adversos. Quanto ao método contraceptivo em uso, o mais frequentemente utilizado foi o contraceptivo hormonal oral combinado (212­39,6%). Quando calculamos o risco relativo para cefaleia, foi encontrado um risco relativo de 2,1282 (1,3425­3,3739; 95% intervalo de confiança [IC]), sugerindo que o uso das pílulas aumenta o risco de ocorrência desse efeito adverso, bem como de edema, cujo risco relativo foi de 1,4435 (1,0177­2,0474; 95% IC). Em relação à redução da libido, o uso de contraceptivo hormonal oral combinado foi também considerado um fator de risco, pois seu risco relativo foi 1,8805 (1,3527­2,6142; 95% IC). No que se refere à acne, o uso de contraceptivos hormonais demonstrou ser um fator de proteção, com risco relativo de 0,3015 (0,1789­0,5082; 95% IC). CONCLUSãO: A escolha de um método contraceptivo deve sempre ser individualizada, e as pacientes devem participar igualmente nesse processo sabendo dos benefícios e malefícios esperados de cada método e hormônio, quando presente.

Pooled incidence of continuation and pregnancy rates of four contraceptive methods in young women: a meta-analysis.

BACKGROUND: Continuation rates of contraceptive methods in young women vary among studies, and there is scarce data regarding the pregnancy rate in this population. METHODS: Four independently systematic searches were performed in PUBMED, EMBASE, LILACS, and Cochrane databases from inception until January 2021 for oral contraceptive pill (OCP), copper IUD, levonorgestrel intrauterine system (LNG-IUS), and subdermal implant. Inclusion criteria were observational or RCT studies that reported continuation for at least 12 months and/or pregnancy rate of these contraceptives methods in girls aged 22 years old or younger. Two authors extracted data from the study design and the outcomes. Pooled proportions of each method were applied using the inverse variance in all calculations with LOGIT transformation, using the random-effects model. Cochrane collaboration tool and New Castle-Ottawa were used to assess the quality and bias of all included studies. GRADE criteria evaluated the quality of evidence. RESULTS: Continuation rate for OCP was 51% (95%CI 34%-68%), while for cooper IUD was 77% (95%CI 74%-80%), LNG-IUS 84% (95%CI 80%-87%), and implant 85% (95%CI 81%-88%). The pooled estimated pregnancy rate for OCP was 11% (95%CI 6%-20%), while for cooper IUD was 5% (95%CI 3%-7%), LNG-IUS 1.6% (95%CI 1.2%-2.3%), and implant 1.8% (95%CI 0.4%-8.4%). CONCLUSION: Long-acting contraceptive methods presented higher continuation rates and lower pregnancy rates when compared to OCPs.

Trombólise farmacomecânica na tromboembolia pulmonar aguda em vigência de sangramento / Pharmacomechanical thrombolysis in acute pulmonary thromboembolism in the presence of bleeding

INTRODUÇÃO: O tromboembolismo pulmonar (TEP) é uma das principais causas de morte cardiovascular no mundo. A base do tratamento é a terapia de anticoagulação. Nos casos de moderada a alta probabilidade de TEP com instabilidade hemodinâmica, disfunção grave do ventrículo direito a terapia trombolítica pode ser utilizada em até 14 dias do início dos sintomas. As principais contraindicações aos trombolíticos são: o acidente vascular encefálico (AVE) hemorrágico ou de origem indeterminada, AVE isquêmico há menos de 6 meses, discrasia sanguínea, traumatismo craniano grave há menos de 3 semanas, tumor de sistema nervoso central, sangramento ativo. Na impossibilidade de trombólise farmacológica poderia ser realizada a trombectomia cirúrgica ou, mais recentemente, a trombectomia farmacomecânica. RELATO DE CASO: Paciente do sexo feminino, 35 anos, procura o Pronto Socorro com queixa de dispneia progressiva de início há cerca de 21 dias da admissão. Associado ao quadro, afirma fadiga e edema assimétrico de membro inferior esquerdo. Nega febre, sintomas gripais, precordialgia ou síncope. Apresenta sangramento uterino anormal por miomatose uterina em tratamento com anticoncepcional oral combinado, em uso de ácido tranexâmico e vacinada contra COVID-19 há 2 meses. À admissão no Pronto Socorro, apresenta-se hipocorada, taquidispneica, com FC 134 bpm, PA 124x70mmHg, SatO2 82% em ar ambiente, sangramento vaginal ativo intenso. Sem alterações às auscultas cardíaca e pulmonar, apresentando edema +2/+4 em membro inferior esquerdo com empastamento de panturrilha ipslateral com Doppler revelando trombose venosa profunda extensa. À admissão, Hb 8,4, hipoxemia arterial (PaO2 = 64 mmHg) e BNP 2300, sem outras alterações dignas de nota. A angiotomografia do tórax apontou tromboembolismo pulmonar bilateral desde a bifurcação das artérias pulmonares até subíramos, dilatação do tronco pulmonar e de câmaras direitas do coração. Encaminhada ao laboratório de hemodinâmica onde realizou trombectomia farmacomecânica com sucesso e implante de filtro de veia cava. Evoluiu com melhora da dispneia e hipoxemia. Foram descartadas trombofilias como causas para o quadro. Reavaliada 12 dias após o procedimento mantendo disfunção ventricular direita importante, melhora da hipertensão arterial pulmonar (PSAP caiu de 82 para 48 mmHg) e segue em programação de abordagem cirúrgica da miomatose uterina. Em retorno ambulatorial, mantinha dispneia, porém aos grandes esforços.

Pharmacokinetics of oral levonorgestrel and ethinylestradiol in women after Roux-en-Y gastric bypass surgery.

BACKGROUND: Most patients undergoing Roux-en-Y gastric bypass (RYGB) are women in reproductive age. It is not known if bariatric surgery affects the pharmacokinetics of oral contraceptives. OBJECTIVES: The primary objective was to evaluate ethinylestradiol (EE) and levonorgestrel (LNG) absorption in women undergoing RYGB, compared with nonoperated controls matched by age and body mass index (BMI). A secondary objective was to assess whether the time since surgery and BMI in the postoperative period influenced the absorption parameters. SETTING: University hospital, Brazil. METHODS: This study was designed to compare the maximum plasma concentration (Cmax), the time to the peak plasma level (Tmax), the area under the curve (AUC0-8 and AUC0-∞) after a single dose of a combined oral contraceptive with 0.03 mg EE and 0.15 mg LNG among 20 women after RYGB and 20 controls. Blood samples were obtained for 8 hours. RESULTS: The mean LNG AUC0-8 and LNG AUC0-∞ were higher in RYGB group (P = .048 and P = .004, respectively). We found a positive correlation for LNG AUC0-8 (P = .045) and AUC0-∞ (P = .004) and the time since surgery, and we found a negative correlation for LNG Cmax (P = .018), AUC0-8 (P = .003), and AUC0-∞ (P = .001) and BMI. CONCLUSION: No significant differences were found in oral EE pharmacokinetics. The operated group showed higher mean LNG AUC0-8 and AUC0-∞ but it was not considered clinically significant. The present study suggests that RYGB may not affect EE and LNG absorption.

Drospirenone: a Latin American perspective for oestrogen-free oral contraception.

AIM: Combined hormonal contraceptives, despite their high efficacy, are associated with an increased relative risk of cardiovascular events. The contraceptive mechanism of action of combined pills depends fundamentally on their progestin component. METHODS: A narrative review was performed. RESULTS: The drospirenone-only pill, including this synthetic progestogen with antimineralocorticoid and antiandrogenic activity, has high contraceptive efficacy that has been demonstrated with a 24-day schedule of 4-day administration of hormone-free pills. Due to its safety profile, the drospirenone-only pill is suitable even in high-risk populations, such as women with high blood pressure, thromboembolism, smoking or dyslipidemia. CONCLUSION: Considering the increasing prevalence of these comorbidities in Latin America, the 4 mg drospirenone-only pill is suggested as one of the strategies of choice in the region for those women who choose oral contraceptives.

Perfil e fatores associados ao uso de anticoncepcionais orais combinados em mulheres férteis atendidas em um centro de planejamento familiar / Profile and factors associated with the use of combined oral contraceptives in fertile women attending a family planning center

Objetivo: Avaliar o perfil e os fatores associados ao uso de anticoncepcionais orais combinados (AOC) em regimes de pausa (intermitente) ou estendido (contínuo) em mulheres férteis atendidas em um centro de planejamento familiar. Métodos: Trata-se de um estudo transversal, realizado no Centro de Pesquisa e Assistência em Reprodução Humana (CEPARH), Salvador, Bahia. Resultados: Entre julho e setembro de 2017, 210 mulheres atendidas, consecutivamente, no CEPARH foram entrevistadas. Dessas, 69 (32,8%) fazem uso de algum AOC, das quais 32 (46,4%) utilizam-no em regimes estendidos. Mulheres que trabalham têm 1,89 vezes mais chances de usarem AOC do que as que não trabalham (IC95%: 1,04-3,42; p=0,039). Nenhuma diferença significativa foi observada nas características entre as que fazem uso de AOC em regime de pausa ou estendido (p>0,05). Conclusão: Os resultados indicam que mulheres que trabalham adiam a concepção e utilizam com mais frequência a pílula contraceptiva, independentemente da forma de administração (forma contínua ou intermitente). Ademais, não há nenhum fator que contribua, significativamente, para que as mulheres façam uso estendido das cartelas de AOC.

Objective To evaluate the profile and factors associated with the use of combined oral contraceptives (COC) in pause (intermittent) or extended (continuous) regimens in fertile women attended at a family planning center. Methods: This is a cross-sectional study, carried out at the Center for Research and Assistance in Human Reproduction (CEPARH), Salvador, Bahia. Results: Between July and September 2017, 210 women consecutively attended at CEPARH were interviewed. Of these, 69 (32.8%) make use of some COC, of which 32 (46.4%) use it in extended regimens. Women who work were 1.89 times more likely to use COC than those who do not work (95%CI: 1.04-3.42; p=0.039). No significant difference was observed in characteristics among those who use COC in a paused or extended regime (p>0.05). Conclusion: The results indicate that working women postpone conception and use the contraceptive pill more frequently, regardless of the form of administration (continuous or intermittent). Moreover, there is no factor that contributes, significantly, for women to make extended use of COC cards.

Endometriose: aspectos clínicos do diagnóstico ao tratamento / Endometriosis: clinical aspects from diagnosis to treatment

A suspeita clínica de endometriose geralmente envolve a história clínica da paciente e exame físico, abordando sua sintomatologia e história pessoal e familiar. Entretanto, a apresentação clínica da doença varia consideravelmente, sem características clínicas patognomônicas, fato que dificulta o seu diagnóstico. Um diagnóstico presuntivo de endometriose pode ser fortemente sugerido pela ultrassonografia transvaginal e pela ressonância magnética em casos de endometrioma ou endometriose infiltrativa profunda. No entanto, esses exames de imagem não possuem a sensibilidade e a especificidade necessárias quando se trata de endometriose peritoneal superficial. O biomarcador sérico mais utilizado na investigação da endometriose foi o CA-125, que não apresenta sensibilidade (70%-75%) suficiente para sua indicação na prática clínica. Portanto, apesar de seu risco e alto custo, a videolaparoscopia e a análise anatomopatológica subsequente ainda se apresentam como o procedimento padrão-ouro para o diagnóstico definitivo de endometriose. Assim, com o objetivo de demonstrar quais exames seriam necessários para o diagnóstico dessa doença, realizamos uma revisão sistemática da literatura, cujos dados estão descritos a seguir.(AU)