Combined Oral Contraceptive Use and the Risk of Cervical Cancer: Literature Review / Uso de anticoncepcional oral combinado e o risco de câncer cervical: Revisão da literatura

Abstract 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.

Resumo 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.

The attention-emotion interaction in healthy female participants on oral contraceptives during 1-week escitalopram intake.

Previous findings in healthy humans suggest that selective serotonin reuptake inhibitors (SSRIs) modulate emotional processing via earlier changes in attention. However, many previous studies have provided inconsistent findings. One possible reason for such inconsistencies is that these studies did not control for the influence of either sex or sex hormone fluctuations. To address this inconsistency, we administered 20 mg escitalopram or placebo for seven consecutive days in a randomized, double-blind, placebo-controlled design to sixty healthy female participants with a minimum of 3 months oral contraceptive (OC) intake. Participants performed a modified version of an emotional flanker task before drug administration, after a single dose, after 1 week of SSRI intake, and after a 1-month wash-out period. Supported by Bayesian analyses, our results do not suggest a modulatory effect of escitalopram on behavioral measures of early attentional-emotional interaction in female individuals with regular OC use. While the specific conditions of our task may be a contributing factor, it is also possible that a practice effect in a healthy sample may mask the effects of escitalopram on the attentional-emotional interplay. Consequently, 1 week of escitalopram administration may not modulate attention toward negative emotional distractors outside the focus of attention in healthy female participants taking OCs. While further research in naturally cycling females and patient samples is needed, our results represent a valuable contribution toward the preclinical investigation of antidepressant treatment.

Effects of orally administered hormonal contraceptives on the musculoskeletal system of healthy premenopausal women-A systematic review.

Introduction: The musculoskeletal system (MSK) is one of the extragonadal target tissues of sex hormones: osteoblasts and osteocytes express estrogen receptors, while in fibroblasts of the anterior cruciate ligament (ACL) and myocytes of the vastus lateralis muscle (MVL), estrogen and progesterone receptors can be detected by immunoassay. Indeed, upon binding of sex hormones to the extragonadal receptors, the MSK seems to respond to varying levels of sex hormones with structural adaptation. Hormonal contraceptives can affect the musculoskeletal system; however, there is a lack of high-quality studies, and no recommendation for female athletes exists. Material and Methods: This is a systematic review of publications on the effects of oral hormonal contraceptives on the biomechanical properties of tendons, muscles and ligaments, muscle strength, and soft tissue regeneration. A systematic database search was performed using MESH keywords and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology in Pubmed and Cochrane to identify studies investigating the influence of oral hormonal contraceptives on muscles, tendons, and ligaments of healthy, adult, premenopausal women. The risk of bias in the studies included was assessed by two independent researchers using the ROBINS-I Tool. Results: Nine comparative studies were identified that met the inclusion criteria. Endpoints were muscle strength and biomechanical tissue properties. No significant influence of oral hormonal contraceptives on muscle strength was found, although general muscle growth and Type I fiber growth were found to be significantly increased in a dose-dependent manner. There was a negative effect on regeneration of muscle strength after exercise. The stiffness of tendons remained unchanged, while their size adaptation to load increased. Conclusion: The anabolic effect could be beneficial for specific sports, whereas reduced muscle regeneration could be disadvantageous for women exercising with high-performance demands. The different effects on tendons and ligaments and the functional consequences of altered ligament and muscle stiffness, especially with regard to synthetic hormones, should be further investigated.

Sex Hormones and Gender Role Relate to Gray Matter Volumes in Sexually Dimorphic Brain Areas.

The present study investigates the relationship of circulating sex hormone levels and gender role to gray matter volumes in sexually dimorphic brain areas and explores, whether these relationships are modulated by biological sex (as assigned at birth based on sexual anatomy) or oral contraceptive (OC) use. It was hypothesized that testosterone and masculinity relate positively to gray matter volumes in areas that are typically larger in men, like the hippocampus or cerebellum, while estradiol/progesterone and femininity relate positively to gray matter volumes in the frontal cortex. To that end, high resolution structural MRI scans, sex hormone levels and gender role self-assessments were obtained in a large sample 89 men, 89 naturally cycling (NC) women, and 60 OC users. Men showed larger regional gray matter volumes than women in the cerebellum and bilateral clusters spanning the putamen and parts of the hippocampi/parahippocampi and fusiform gyri. In accordance with our hypotheses, a significant positive association of testosterone to hippocampal volumes was observed in women irrespective of OC use. Participant's self-reported femininity was significantly positively associated with gray matter volumes in the left middle frontal gyrus (MFG) in men. In addition several differences between OC-users and NC women were identified.

Effects of different hormonal contraceptives in women's blood pressure values / Efectos de los distintos anticonceptivos hormonales en los valores de presión arterial de la mujer / Efeitos dos diferentes anticoncepcionais hormonais nos valores de pressão arterial da mulher

ABSTRACT Objective: To identify evidence in the literature of the relationship between the use of different hormonal contraceptive methods and alterations in women's blood pressure values. Method: This is an integrative literature review, consisting of ten scientific articles published in PubMed and BVS, between 2012 and 2016, selected by keywords, available fully and free of charge, in English, Portuguese, or Spanish. Results: The articles showed that exogenous estrogen helps in the activation of the renin-angiotensin-aldosterone system causing hypertensive effects even in small doses; and that combined use with drospirenone reduces these effects. Routes of administration without passage through the liver and use of isolated progestin showed promising results in reducing the effects on blood pressure. Conclusion: There is evidence in the literature of pressure alterations associated with different hormonal contraceptives and that personal history of morbidities are to be considered in an attempt to reduce the effects on the cardiovascular system.

RESUMEN Objetivo: Identificar en la literatura evidencias sobre la relación entre el uso de distintos métodos anticonceptivos hormonales y las alteraciones en los valores de presión arterial en mujeres. Método: Se trata de la revisión integrativa de la literatura, constituida por diez artículos científicos publicados en PubMed y BVS, entre 2012 y 2016, seleccionados por medio de palabras-clave, disponibles en su totalidad, gratuitos, en inglés, en portugués o en español. Resultados: Los artículos han enseñado que el estrógeno exógeno aporta en la activación del sistema renina-angiotensina-aldosterona causando efectos hipertensivos aunque en pequeñas dosificaciones; y que el uso combinado con la drospirenona reduce esos efectos. Vías de administración sin pasaje por el hígado y el uso del progestágeno aislado han enseñado resultados promisores en la reducción de los efectos sobre la presión. Conclusión: Hay evidencias en la literatura de alteraciones presóricas asociadas a distintos anticonceptivos hormonales y de que antecedentes personales de morbilidades deben ser considerados en el intento de reducir los efectos sobre el sistema cardiovascular.

RESUMO Objetivo: Identificar na literatura evidências sobre a relação entre o uso de diferentes métodos anticoncepcionais hormonais e as alterações nos valores de pressão arterial em mulheres. Método: Trata-se de revisão integrativa da literatura, constituída por dez artigos científicos publicados no PubMed e BVS, entre 2012 e 2016, selecionados por meio de palavras-chave, disponíveis na íntegra, gratuitos, em inglês, português ou espanhol. Resultados: Os artigos mostraram que o estrogênio exógeno contribui na ativação do sistema renina-angiotensina-aldosterona causando efeitos hipertensores mesmo em pequenas dosagens; e que o uso combinado com a drospirenona reduz esses efeitos. Vias de administração sem passagem pelo fígado e uso do progestágeno isolado mostraram resultados promissores na redução dos efeitos sobre a pressão. Conclusão: Há evidências na literatura de alterações pressóricas associadas a diferentes anticoncepcionais hormonais e de que antecedentes pessoais de morbidades devem ser considerados na tentativa de reduzir os efeitos sobre o sistema cardiovascular.

Oral contraceptive-related transverse sinus thrombosis as an initial manifestation of antiphospholipid syndrome in the absence of systemic lupus erythematosus.

BACKGROUND: Cerebral venous sinus thrombosis is a rare and potentially life-threatening neurologic manifestation of antiphospholipid syndrome. Oral contraceptive pills (OCP) may increase the risk of vascular events, even in people without family history of venous thrombosis. CASE PRESENTATION: A 31-year-old woman with four weeks of constant headache and history of taking OCP for one year has been selected for this study. The results of magnetic resonance imaging (MRI) of brain and venography confirmed a diagnosis of cerebral venous sinus thrombosis. The serum anticardiolipin and antiphospholipid antibodies were elevated and a definitive diagnosis of antiphospholipid syndrome was made. CONCLUSION: The present report demonstrates the importance of screening for antiphospholipid antibodies in patients presenting with cerebral venous sinus thrombosis despite history of taking OCP.

Prevalencia de prescripción conjunta incorrecta de fármacos anticonvulsivantes y anticonceptivos hormonales, Colombia, 2014 / Prevalence of prescription errors in the concomitant use of anticonvulsants and hormonal contraceptive drugs, Colombia, 2014

Determinar la prevalencia de prescripción conjunta de fármacos antiepilépticos para identificar formulación incorrecta que podría afectar la efectividad de los anticonceptivos hormonales en un grupo de mujeres afiliadas al Sistema General de Seguridad Social en Salud de Colombia.Materiales y métodos: estudio de corte transversal, en el que se seleccionaron registros de mujeres de 15 a 45 años que recibían al menos un fármaco antiepiléptico, entre el 1 y el 31 de marzo de 2014, en una base de datos poblacional de dispensación de medicamentos de un operador logístico en Colombia, para población perteneciente al régimen contributivo y subsidiado en el Sistema General de Seguridad Social en Salud de Colombia. Se evaluaron el tipo de anticonceptivo hormonal y de fármaco antiepiléptico, y la frecuencia de prescripción concomitante de formulación incorrecta de uso combinado de medicamentos. Se utilizó estadística descriptiva.Resultados: de un total de 2092 pacientes usuarias de fármacos antiepilépticos, se identificaron 89 (4,3 %) casos que tenían por lo menos un antiepiléptico y un anticonceptivo simultáneamente. En 48 mujeres (54 %) se encontró formulación incorrecta de métodos de planificación, como el uso de fármacos antiepilépticos inductores enzimáticos e inyectables combinados (20 casos), el uso de anticonceptivos orales combinados de bajas dosis de estrógenos (16 casos), de progestinas orales (10 casos), y el uso de antiepilépticos no inductores enzimáticos y anticonceptivos orales combinados y dosis altas de estrógenos (2 casos).Conclusiones: un importante número de mujeres usuarias de medicamentos antiepilépticos utiliza métodos hormonales de anticoncepción, y cerca de la mitad de ellas tenían una prescripción anticonceptiva incorrecta, lo que podría resultar en embarazos no deseados o incremento del riesgo de enfermedad tromboembólica...

To determine the prevalence of simultaneous prescription of antiepileptic drugs and identify wrong prescriptions that may affect the effectiveness of hormonal contraceptives in a group of women covered under the Colombian General Social Security System in Health.Materials and methods: Cross-sectional study based on records of women between 15 and 45 years of age who received at least one antiepileptic drug from March 1st to 31st 2014, included in database of a logistic operator for medication distribution for a population belonging to the Contributory and Subsidized regimes in the Colombian social security system. The evaluation included the type of hormonal contraceptive and of the anticonvulsant medication, and the frequency of concomitant prescription and of incorrect prescription of combined use of medications. Descriptive statistics were used.Results: Out of a total number of 2092 female users of antiepileptic drugs, there were 89 (4.3%) cases identified with concomitant use of at least one anticonvulsant and one contraceptive. Incorrect prescription of contraceptive methods was identified in 48 cases (54%), including the concomitant use of enzymatic-inducing anticonvulsants and combined hormonal injectable contraceptives (20 cases) or the use of combined low-dose oestrogen oral contraceptives (16 cases) or oral progestins (10 cases) and the use of non enzyme-inducing antiepileptic drugs and combined oral contraceptives, and high-dose oestrogens (2 cases).Conclusions: An important number of female users of anticonvulsants used hormonal contraception and almost half of them had an incorrect contraceptive prescription, creating a risk of undesired pregnancies or increasing the risk of thromboembolic disease...