Manejo das irregularidades menstruais secundárias ao uso de contraceptivos ­ análise das recomendações atuais / Management of menstrual irregularities secondary to contraceptive use ­ analysis of current recommendations

As irregularidades menstruais representam uma série de desordens na quantida- de, duração, frequência ou regularidade do sangramento uterino. Entre suas cau- sas destaca-se o sangramento secundário ao uso de anticoncepcionais, uma razão frequente de descontinuidade dos contraceptivos, podendo aumentar as taxas de gestações não planejadas. Boa parte dos contraceptivos pode levar a mudanças no padrão de sangramento uterino, e a abordagem inicial do sangramentos irregula- res inclui a avaliação de outras possíveis causas, o reforço do uso correto da medi- cação, a tranquilização da paciente quanto à benignidade do quadro e à tendência a melhora com a continuidade do uso. Os anti-inflamatórios podem ser usados como estratégia inicial, e, não havendo resposta satisfatória, há alternativas espe- cíficas para cada método. Este trabalho visa identificar as recomendações atuais sobre o manejo do sangramento anormal decorrente de contraceptivos, por meio de revisão narrativa de estudos publicados sobre o tema nos últimos vinte anos.

Abnormal uterine bleeding represents a series of disorders in the amount, du- ration, frequency and or regularity of uterine bleeding. Among its causes, uterine bleeding secondary to the use of contraceptives stands out as a frequent reason for contraceptive discontinuity, which could lead to unplanned pregnancies. Most contraceptives can cause changes in the pattern of uterine bleeding, and the ini- tial approach of the abnormal bleeding includes assessing other possible cau- ses, reinforcing the correct use of medication, and reassuring the patient about the benignity of the condition and the tendency to improve with the continuity of the treatment. Anti-inflammatory drugs can be used as an initial strategy, and, if there is no satisfactory answer, there are specific alternatives for each contracep- tive method. This work aims to identify them current recommendations on the management of abnormal bleeding resulting from contraceptives use, through a narrative review of studies published on the subject in the last twenty years.

Risk of thromboembolism in patients with COVID-19 who are using hormonal contraception.

BACKGROUND: The novel coronavirus disease (COVID-19) has led to significant mortality and morbidity, including a high incidence of related thrombotic events. There has been concern regarding hormonal contraception use during the COVID-19 pandemic, as this is an independent risk factor for thrombosis, particularly with estrogen-containing formulations. However, higher estrogen levels may be protective against severe COVID-19 disease. Evidence for risks of hormonal contraception use during the COVID-19 pandemic is sparse. We therefore conducted a living systematic review that will be updated as new data emerge on the risk of thromboembolism with hormonal contraception use in patients with COVID-19. OBJECTIVES: To determine if use of hormonal contraception increases risk of venous and arterial thromboembolism in women with COVID-19. To determine if use of hormonal contraception increases other markers of COVID-19 severity including hospitalization in the intensive care unit, acute respiratory distress syndrome, intubation, and mortality. A secondary objective is to maintain the currency of the evidence, using a living systematic review approach. SEARCH METHODS: ⁠⁠⁠⁠⁠⁠We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, Global Health, and Scopus from inception to search update in March 2022. For the living systematic review, we monitored the literature monthly. SELECTION CRITERIA: We included all published and ongoing studies of patients with COVID-19 comparing outcomes of those on hormonal contraception versus those not on hormonal contraception. This included case series and non-randomized studies of interventions (NRSI). DATA COLLECTION AND ANALYSIS: One review author extracted study data and this was checked by a second author. Two authors individually assessed risk of bias for the comparative studies using the ROBINS-I tool and a third author helped reconcile differences. For the living systematic review, we will publish updates to our synthesis every six months. In the event that we identify a study with a more rigorous study design than the current included evidence prior to the planned six-month update, we will expedite the synthesis publication. MAIN RESULTS: We included three comparative NRSIs with 314,704 participants total and two case series describing 13 patients. The three NRSIs had serious to critical risk of bias in several domains and low study quality. Only one NRSI ascertained current use of contraceptives based on patient report; the other two used diagnostic codes within medical records to assess hormonal contraception use, but did not confirm current use nor indication for use. None of the NRSIs included thromboembolism as an outcome. Studies were not similar enough in terms of their outcomes, interventions, and study populations to combine with meta-analyses. We therefore narratively synthesized all included studies. Based on results from one NRSI, there may be little to no effect of combined hormonal contraception use on odds of mortality for COVID-19 positive patients (odds ratio (OR) 1.00, 95% confidence interval (CI) 0.41 to 2.40; 1 study, 18,892 participants; very low-certainty evidence). Two NRSIs examined hospitalization rates for hormonal contraception users versus non-users. Based on results from one NRSI, the odds of hospitalization for COVID-19 positive combined hormonal contraception users may be slightly decreased compared with non-users for patients with body mass index (BMI) under 35 kg/m2 (OR 0.79, 95% CI 0.64 to 0.97; 1 study, 295,689 participants; very low-certainty evidence). According to results of the other NRSI assessing use of any type of hormonal contraception, there may be little to no effect on hospitalization rates for COVID-19 positive individuals (OR 0.99, 95% CI 0.68 to 1.44; 1 study, 123 participants; very low-certainty evidence). We included two case series because no comparative studies directly assessed thromboembolism as an outcome. In a case series of six pediatric COVID-19 positive patients with pulmonary embolism, one (older than 15 years of age) was using combined hormonal contraception. In a second case series of seven COVID-19 positive patients with cerebral venous thrombosis, one was using oral contraceptives. One comparative study and one case series reported on intubation rates, but the evidence for both is very uncertain. In the comparative study of 123 COVID-19 positive patients (N = 44 using hormonal contraception and N = 79 not using hormonal contraception), no patients in either group required intubation. In the case series of seven individuals with cerebral venous thromboembolism, one oral contraceptive user and one non-user required intubation. AUTHORS' CONCLUSIONS: There are no comparative studies assessing risk of thromboembolism in COVID-19 patients who use hormonal contraception, which was the primary objective of this review. Very little evidence exists examining the risk of increased COVID-19 disease severity for combined hormonal contraception users compared to non-users of hormonal contraception, and the evidence that does exist is of very low certainty. The odds of hospitalization for COVID-19 positive users of combined hormonal contraceptives may be slightly decreased compared with those of hormonal contraceptive non-users, but the evidence is very uncertain as this is based on one study restricted to patients with BMI under 35 kg/m2. There may be little to no effect of combined hormonal contraception use on odds of intubation or mortality among COVID-19 positive patients, and little to no effect of using any type of hormonal contraception on odds of hospitalization and intubation for COVID-19 patients. At a minimum, we noted no large effect for risk of increased COVID-19 disease severity among hormonal contraception users. We specifically noted gaps in pertinent data collection regarding hormonal contraception use such as formulation, hormone doses, and duration or timing of contraceptive use. Differing estrogens may have different thrombogenic potential given differing potency, so it would be important to know if a formulation contained, for example, ethinyl estradiol versus estradiol valerate. Additionally, we downgraded several studies for risk of bias because information on the timing of contraceptive use relative to COVID-19 infection and method adherence were not ascertained. No studies reported indication for hormonal contraceptive use, which is important as individuals who use hormonal management for medical conditions like heavy menstrual bleeding might have different risk profiles compared to individuals using hormones for contraception. Future studies should focus on including pertinent confounders like age, obesity, history of prior venous thromboembolism, risk factors for venous thromboembolism, and recent pregnancy.

Fatores de risco cardiovascular, saberes e práticas de cuidado de mulheres: possibilidade para rever hábitos / Factores de riesgo cardiovascular, conocimientos y prácticas de cuidado de las mujeres: posibilidad de revisar hábitos / Cardiovascular risk factors, knowledge and care practices of women: possibility to review habits

Resumo Objetivo investigar fatores de risco para doenças cardiovasculares e compreender as práticas de cuidado de mulheres. Método paralelo convergente misto. A etapa quantitativa foi transversal descritiva com formulário abordando características demográficas, socioeconômicas, fatores de risco cardiovascular, hábitos de vida e saúde, participaram 289 mulheres e aplicou-se estatística descritiva. A etapa qualitativa foi fundamentada na pesquisa participativa, exploratória descritiva, mediante entrevista semiestruturada, técnica de criatividade e sensibilidade e narrativas, com 30 mulheres. Resultados identificaram-se fatores como sedentarismo (60,9%), uso do anticoncepcional (57,9%), estresse (60,6%), depressão (40,1%), obesidade (38,8%), hipertensão arterial (33,6%), consumo de bebida alcoólica (29,8%), cigarro (16,6%), dislipidemia (25,6%) e diabetes (10,0%). Quanto aos saberes e práticas de cuidado, as participantes mencionaram os fatores, porém algumas relataram realizar os cuidados, e outras não, mesmo reconhecendo os riscos. Assim, compartilharam a falta de tempo para realizar exercícios físicos, dificuldades para cuidar da alimentação e aderir ao tratamento anti-hipertensivo e, ainda, relataram sentirem-se estressadas. Conclusão e implicações para a prática identificaram-se fatores modificáveis e as mulheres possuíam conhecimento acerca destes, entretanto divergiam sobre os cuidados, demonstrando a importância de ações voltadas a essa população.

Resumen Objetivo investigar los factores de riesgo para enfermedades cardiovasculares y comprender las prácticas de atención brindadas a las mujeres. Método paralelo convergente mixto. La etapa cuantitativa fue transversal transcriptiva con formulario abordando características demográficas, socioeconómicas, factores de riesgo cardiovascular, hábitos de vida y salud. Participaron 289 mujeres y se aplicó estadística descriptiva. La etapa cualitativa fue fundamentada en la investigación participativa, exploratoria descriptiva, mediante entrevista semiestructurada, técnica de creatividad y sensibilidad y narrativas, con 30 mujeres. Resultados se identificaron factores como sedentarismo (60,9%), uso de anticonceptivos (57,9%), estrés (60,6%), depresión (40,1%), obesidad (38,8%), hipertensión arterial (33,6%), consumo de bebidas alcohólicas (29,8%), tabaquismo (16,6%), dislipidemia (25,6%) y diabetes (10,0%). En cuanto a los conocimientos y prácticas de cuidado, las participantes mencionaron los factores, sin embargo, algunas reportaron realizar el cuidado y otras no, inclusive reconociendo los riesgos. Así, compartieron la falta de tiempo para la realización de actividades físicas, dificultades para cuidar su alimentación y la adherencia al tratamiento antihipertensivo e, inclusive, refirieron sentirse estresadas. Conclusión e implicaciones para la práctica se identificaron factores modificables y las mujeres tenían conocimiento sobre ellos, sin embargo, divergieron sobre el cuidado, demostrando la importancia de las acciones dirigidas a esta población.

Abstract Objective to investigate risk factors for cardiovascular disease and understand the care practices of women. Method mixed convergent parallel. The quantitative stage was descriptive transversal with a form addressing demographic characteristics, socioeconomic, cardiovascular risk factors, lifestyle and health habits; 289 women participated and descriptive statistics were applied. The qualitative step was based on participatory research, exploratory descriptive, through semi-structured interviews, creativity and sensitivity technique and narratives, with 30 women. Results factors were identified as sedentarism (60.9%), use of contraceptives (57.9%), stress (60.6%), depression (40.1%), obesity (38.8%), high blood pressure (33.6%), alcohol consumption (29.8%), smoking (16.6%), dyslipidemia (25.6%), and diabetes (10.0%). As for knowledge and care practices, the participants mentioned the factors, but some reported performing the care, and others did not, even though they recognized the risks. Thus, they shared the lack of time to perform physical exercises, difficulties to take care of the diet and adhere to antihypertensive treatment, and also reported feeling stressed. Conclusion and implications for practice modifiable factors were identified and women had knowledge about these, however, they differed on the care, demonstrating the importance of actions aimed at this population.

Effect of combined contraceptive pill on immune cell of ovarian endometriotic tissue.

BACKGROUND: Dysregulation of immune response is associated with development of endometriosis. The study aim was to evaluate effect of combined oral contraceptive pills (COCs) consisting of ethinyl estradiol (EE) and desogestrel on the expression of macrophage, natural killer cells, and regulatory T cells of ovarian endometriotic cysts. METHODS: Endometriotic cyst wall tissues were collected from women with endometriosis who were treated (n = 22) with COCs (one table per day of EE 0.03 mg and desogestrel 0.15 mg administered for 28 to 35 days before surgery) or untreated (n = 22). The tissues were collected from endometriotic cyst wall during laparoscopic or laparotomy ovarian cystectomy. Immunohistochemistry for anti-CD68, anti-CD56, and anti-forkhead-winged helix transcription factor (FoxP3), a marker for macrophages, natural killer cells, and regulatory T cells, respectively, were investigated. RESULTS: The median (interquartile range [IQR]) number of anti-CD68 positive cells in the COC group was significantly lower than in the untreated group (12.7; 4.9-19.3) versus 45.7 (26.0-70.7), p < 0.001). Tissue infiltration of anti-CD56 positive cells in endometriotic cyst was significantly higher after the treatment when compared with tissue from untreated group (42.9, 27.4-68.9 versus 25.3 (14.1-37.3; p = 0.009). The number of regulatory T cells was also significantly increased in the COC group (6.3, 2.8-15.5) versus 0 (0-1.8; p < 0.001). CONCLUSIONS: The effects of COC, containing EE 0.30 mg with desogestrel 0.15 mg, on the immune system was demonstrated by a significant decrease in the number of macrophages and an increase in natural killer and regulatory T cells.

Does a single application of contraceptive cause pathological changes in bitches? / [Uma única aplicação de anticoncepcional causa alterações patológicas em cadelas?]

O presente trabalho objetivou avaliar os efeitos da administração em dose única de progestágenos em fêmeas caninas hígidas, as quais nunca haviam recebido tais fármacos. Foram selecionadas 20 cadelas, que foram examinadas clinicamente e por meio de exames complementares. Nessas cadelas, foi aplicado medroxiprogesterona por via subcutânea. Noventa dias após, as fêmeas foram esterilizadas cirurgicamente, sendo os tecidos reprodutivos encaminhados para histopatologia. Foi possível verificar que, aos 30 dias, 12 animais (60%) apresentaram hiperplasia mamária. Aos 90 dias, 18 animais (90%) apresentavam sinais de hiperplasia endometrial cística, tendo cinco (27,77%) destes animais apresentado conteúdo purulento no lúmen uterino. No exame microscópico, apenas uma fêmea não demonstrou alterações patológicas, sendo a única que recebeu o contraceptivo na fase correta (anestro). As demais fêmeas apresentaram alterações que variaram entre alterações circulatórias a hiperplasia endometrial cística grave. Assim, foi possível concluir que uma única aplicação de anticoncepcional em fêmeas hígidas pode causar complicações leves a graves.(AU)

Estro-progestin Contraceptives and Risk of Cervical Cancer: A Debated Issue.

Steroid contraceptive hormones may promote human papilloma virus (HPV) - DNA integration into the host genome, may bind to specific HPV-DNA sequences within transcriptional regulatory regions, and may modulate cell apoptosis. Most epidemiological studies, reported in this narrative review, have shown that oral contraception is associated with a 1.5-3.3-fold higher relative risk of cervical carcer, but only in users for >5 years and especially in HPV-positive women. The relative risk declines with increasing time since last use and is not different from that of never users after >10 years. Ten-year oral contraceptive use from the age of 20 years is associated with an increase in the cumulative incidence of invasive cervical cancer at the age of 50 years of approximately 1 case per 1,000. Oral contraception has a very small negative impact on the absolute risk of cancer of the uterine cervix.

Migraine start, course and features over the cycle of combined hormonal contraceptive users with menstrual migraine - temporal relation to bleeding and hormone withdrawal: a prospective diary-based study.

BACKGROUND: Many studies have described the features of menstrually-related migraines (MRM) in the natural cycle and the efficacy of prevention. MRM in combined hormonal contraceptive (CHC) users has scarcely been researched. Estrogen and progestin withdrawal in CHC users are both more abrupt and from higher hormone levels compared with the natural cycle. An advantage for prevention of MRM in CHC users is that the hormone withdrawal is predictable. It is unknown, whether the attacks during the hormone-free interval are associated with the hormone withdrawal or onset of bleeding. Improved understanding of this relation might contribute to better define and shorten the time interval for prevention. METHODS: For this prospective diary-based trial we collected migraine and bleeding data from CHC users with MRM in at least two of three cycles. We analyzed frequency of migraines over the whole CHC cycle. During the hormone-free phase the relation between onset of migraine and onset of bleeding was studied. We compared pain intensity and identified prolonged-migraine attacks during hormone use and the hormone-free phase. RESULTS: During the hormone-free interval the number of migraine days and the pain score/migraine day were significantly higher in comparison with the mean during hormone use. The prevalence of migraine attacks was fourfold on hormone-free days 3-6. Migraine typically started on days 1-4. Migraine in relation to bleeding mostly occurred on days - 1 to + 4. In 78% of the cycles the first migraine day occurred during bleeding days 1 ± 2 and 48% started on days - 1 and day 1. The predictability of the first bleeding day was very high. CONCLUSION: The day of hormone-withdrawal migraine and the first bleeding day are highly predictable in CHC users. Migraine onset is mostly day - 1 and 1 of the bleeding and on days 1-4 of the hormone-free interval. Migraine attacks of CHC users in the hormone-free interval are severe and long lasting. Further trials are necessary to investigate if this knowledge can be used to optimise prevention.

Effects of Hormonal Contraceptives on Mood: A Focus on Emotion Recognition and Reactivity, Reward Processing, and Stress Response.

PURPOSE OF REVIEW: We review recent research investigating the relationship of hormonal contraceptives and mood with a focus on relevant underlying mechanisms, such as emotion recognition and reactivity, reward processing, and stress response. RECENT FINDINGS: Adverse effects of hormonal contraceptives (HCs) on mood seem most consistent in women with a history of depressive symptoms and/or previous negative experience with HC-intake. Current evidence supports a negativity bias in emotion recognition and reactivity in HC-users, although inconsistent to some extent. Some data, however, do indicate a trend towards a blunted reward response and a potential dysregulation of the stress response in some HC-users. HC-effects on psychological and neurophysiological mechanisms underlying mood are likely context-dependent. We provide suggestions on how to address some of the contributing factors to this variability in future studies, such as HC-dose, timing, administration-mode, and individual risk. A better understanding of how and when HCs affect mood is critical to provide adequate contraceptive choices to women worldwide.

Efectos adversos del implante anticonceptivo subdérmico en adolescentes / Adverse effects of the subdermal contraceptive implant in adolescents

Introducción: Los anticonceptivos subdérmicos deben ser seguros, con efectos colaterales mínimos, reversibles y de larga duración, sin embargo, se ha observado que ocasionan efectos adversos, fundamentalmente en los primeros meses de su uso. Objetivos: Describir efectos adversos, junto a antecedentes personales en adolescentes a quienes se realizó implante anticonceptivo subdérmico. Métodos: Se realizó un estudio descriptivo en 120 adolescentes a las que se les colocó implante subdérmico como método anticonceptivo. Fueron estudiadas las variables efectos adversos, edad y antecedente obstétrico. Resultados: El 36,6 por ciento de las pacientes tenía antecedentes de abortos provocados, y el 5 por ciento era menor de 15 años. Los efectos adversos más frecuentes fueron el aumento de peso (23,3 por ciento a los 6 meses y 21,6 por ciento al año), la cefalea (18,3 por ciento a los 6 meses y 8,3 por ciento al año) y la mastalgia (12,5 por ciento a los 6 meses y 15 por ciento al año). En el patrón de sangrado, se presentaron, sangrado infrecuente (36 por ciento a los 6 meses y 43,3 por ciento al año) y amenorrea (27,5 por ciento a los 6 meses y 35 por ciento al año). Conclusiones: Más de un tercio de las pacientes tenían abortos previos; los efectos adversos más frecuentes fueron: aumento de peso, cefalea y mastalgia, tanto a los 6 meses como al año y en el patrón de sangrado, el sangrado infrecuente y la amenorrea(AU)

Introduction: Subdermal contraceptives must be safe, with minimal side effects, reversible and long lasting, however, it has been observed that they cause adverse effects, mainly in the first months of its use. Objectives: To describe adverse effects, together with personal history in adolescents who underwent a subdermal contraceptive implant. Methods: A descriptive study was conducted in 120 adolescents who were placed as a subdermal implant as a contraceptive method. The variables adverse effects, age and obstetric history were studied. Results: 36.6 percent of the patients had a history of induced abortions, and 5 percent were younger than 15 years. The most frequent adverse effects were weight gain (23.3 percent at 6 months and 21.6 percent per year), headache (18.3 percent at 6 months and 8.3 percent per year) and mastalgia (12.5 percent at 6 months and 15 percent at year). In the pattern of bleeding, infrequent bleeding occurred (36 percent at 6 months and 43.3 percent per year) and amenorrhea (27.5 percent at 6 months and 35 percent per year). Conclusions: More than a third of the patients had previous abortions; The most frequent adverse effects were: weight gain, headache and mastalgia, both at 6 months and 1 year and in the pattern of bleeding, infrequent bleeding and amenorrhea(AU)

O uso da pílula anticoncepcional e as alterações das principais vias metabólicas / The use of contraceptive pill and alterations of main metabolic pathways

As pílulas anticoncepcionais são esteroides que visam impedir a gravidez indesejada e regular distúrbios menstruais. Acessíveis em grande variedade no mercado e no SUS, são o método contraceptivo mais aceito pelas mulheres, entretanto trazem diversos efeitos colaterais. O objetivo deste trabalho foi analisar como a pílula anticoncepcional pode alterar as principais vias metabólicas femininas. Trata-se de uma revisão bibliográfica nas bases de dados SciELO, BVS e PubMed, com foco nas correlações entre o uso da pílula anticoncepcional e as alterações metabólicas. Os anticoncepcionais orais atuam na inibição da biossíntese de androgênios e estimulação da SHBG, o que reduz o efeito anabólico proteico. Também promovem o acréscimo dos níveis de LDL-colesterol, colesterol total, PCR-us e dímero D, e alterações na sensibilidade da insulina, no metabolismo do zinco e na hemostasia. Apesar de existirem recomendações que preconizam o uso de outros métodos contraceptivos e estudos que demonstram a satisfação feminina ao trocar os anticoncepcionais orais pelos LARCs, a pílula ainda é a mais utilizada pelas mulheres.(AU)

Contraceptive pills are steroids that prevent unwanted pregnancy and regular menstrual disorders. Accessible in a great variety in market and SUS, they are the contraceptive method most accepted by women, however, they bring several side effects. The objective of this study was analyze how the contraceptive pill can alter the main female metabolic pathways. This is a literature review in the SciELO, BVS and PubMed databases, focusing on the correlations between the use of contraceptive pill and metabolic alterations. Oral contraceptives act to inhibit androgen biosynthesis and stimulate SHBG, which reduces the protein anabolic effect. They also bring about high levels of LDL cholesterol, total cholesterol, CRP, D-dimer, changes in insulin, absence of zinc metabolism and hemostasis. Although there are recommendations that recommend the use of other contraceptive methods and studies that demonstrate the satisfaction of women in exchanging oral contraceptives with LARCs, the pill is still the most used by women.(AU)

Contraceptive utilization and counseling among breast cancer survivors.

PURPOSE: To explore contraceptive counseling and utilization among breast cancer survivors. METHODS: We enrolled reproductive-aged women with a history of breast cancer for a cross-sectional study. Participants were recruited via the Athena Breast Health Network and via the Young Survival Coalition's social media postings. Descriptive statistics were calculated to understand utilization of and feelings about contraceptive methods before, during, and after breast cancer treatment. RESULTS: Data presented here are from an online survey of 150 breast cancer survivors who completed the survey. Seventy-one percent (n = 105) of respondents reported being sexually active and not pregnant during their primary cancer treatment (surgery, chemotherapy, and/or radiation). Of these, 90% (n = 94) reported using any form of contraceptive, and the most common method was condoms (n = 55, 52%). Respondents reported that safety concerns had the biggest influence on their contraception method choice. Sixty-one percent (n = 92) reported receiving contraceptive counseling by their oncologist either before or after treatment; however, 49% (n = 45) of those did not receive a specific recommendation for a contraceptive method. Of respondents who reported receiving contraceptive counseling from their gynecologist, 44% (n = 35) reported that their gynecologist specifically recommended a copper intrauterine device (IUD). The majority of respondents (n = 76, 52%) wanted their oncologist to discuss contraceptive options with them and preferred to receive this counseling at the time of diagnosis (n = 81, 57%). CONCLUSIONS: Breast cancer survivors in this study remained sexually active across the cancer care continuum and predominantly used condoms as their contraceptive method during treatment. Breast cancer patients would prefer contraceptive counseling from their oncologist at the time of their cancer diagnosis. IMPLICATION FOR CANCER SURVIVORS: Education efforts in the future should focus on initiatives to improve comprehensive contraceptive counseling at the time of diagnosis by an oncologist.

A Population-Based, Case-Control Evaluation of the Association Between Hormonal Contraceptives and Idiopathic Intracranial Hypertension.

PURPOSE: To determine if the use of oral contraceptive pills (OCP) and other hormonal contraceptives are associated with a higher incidence of idiopathic intracranial hypertension (IIH). DESIGN: Retrospective, population-based, case-control study. METHODS: Setting: Female IIH patients evaluated between January 1, 1990, and December 31, 2016 were identified using the Rochester Epidemiology Project (REP), a record-linkage system of medical records for all patient-physician encounters among Olmsted County, Minnesota, residents. STUDY POPULATION: Fifty-three female residents of Olmsted County diagnosed with IIH between 15 and 45 years of age. The use of OCPs and other hormonal contraceptives was compared to controls matched for age, sex, and body mass index. Interventions/Exposures: Hormonal contraceptives. MAIN OUTCOME MEASURE: Odds of developing IIH. RESULTS: Of the 53 women diagnosed with IIH between 15 and 45 years of age, 11 (20.8%) had used hormonal contraceptives within ≤30 days of the date of IIH diagnosis, in contrast to 30 (31.3%) among the control patients. The odds ratio of hormonal contraceptive use and IIH was 0.55 (95% conficence interval [CI]: 0.24-1.23, P = .146). The odds ratio of OCP use was 0.52 (95% CI: 0.20-1.34, P = .174). CONCLUSIONS: OCP and other hormonal contraceptives were not significantly associated with a higher incidence of IIH, arguing against the need for women with IIH to discontinue their use.

Ethinylestradiol and Levonorgestrel as Active Agents in Normal Skin, and Pathological Conditions Induced by UVB Exposure: In Vitro and In Ovo Assessments.

The link between melanoma development and the use of oral combined contraceptives is not fully elucidated, and the data concerning this issue are scarce and controversial. In the present study, we show that the components of oral contraceptives, ethinylestradiol (EE), levonorgestrel (LNG), and their combination (EE + LNG) ± UVB (ultraviolet B radiation) induced differential effects on healthy (human keratinocytes, fibroblasts, and primary epidermal melanocytes, and murine epidermis cells) and melanoma cells (human-A375 and murine-B164A5), as follows: (i) at low doses (1 µM), the hormones were devoid of significant toxicity on healthy cells, but in melanoma cells, they triggered cell death via apoptosis; (ii) higher doses (10 µM) were associated with cytotoxicity in all cells, the most affected being the melanoma cells; (iii) UVB irradiation proved to be toxic for all types of cells; (iv) UVB irradiation + hormonal stimulation led to a synergistic cytotoxicity in the case of human melanoma cells-A375 and improved viability rates of healthy and B164A5 cells. A weak irritant potential exerted by EE and EE + LNG (10 µM) was assessed by the means of a chick chorioallantoic membrane assay. Further studies are required to elucidate the hormones' cell type-dependent antimelanoma effect and the role played by melanin in this context.

Combined Hormonal Contraceptive Use and Risk of Breast Cancer in a Population of Women With a Family History.

BACKGROUND: We estimated the association between combined hormonal contraceptive (CHC) use and breast cancer (BC) incidence in a well-selected population of women at familial risk of BC at the Modena Family Cancer Clinic. MATERIALS AND METHODS: We performed a retrospective cohort study by reviewing the data from 2527 women (4.5% BRCA mutation carriers, 72.2% high risk, and 23.3% intermediate risk using the Modena criteria and the Tyrer-Cuzick model). RESULTS: We did not find any specific feature of breast cancer (infiltration, hormone receptor and HER2 status, onset before age 35 years, multiple diagnoses) in the CHC users (P > .05). Only 2.0% of women used a preparation with ≥ 50 µg of ethinylestradiol (EE). The use of CHCs was not associated with an increased risk of breast cancer (cumulative hazard: never used, 0.17; CHC users, 0.20; P = .998), regardless of the duration of use (cumulative hazard: never used, 0.17, used < 5 years, 0.20; used 5-10 years, 0.14; used > 10 years, 0.25; P = .414). This was confirmed for the different risk groups when interacted in a Cox proportional hazard regression model. The EE dose did not influence the risk of BC (cumulative hazard, 2.37; 95% confidence interval, 0.53-10.1; never used, 0.18; EE < 20 µg used, 0.04; EE ≥ 20 µg used, 0.16; P = .259). The types of progestins used might influence the risk, with some, such as gestodene (P = .028) and cyproterone acetate (P = .031), associated with an even greater reduced risk. CONCLUSIONS: CHC use does not increase the risk of BC in a population of women with a family history, encouraging CHC use in this group of women.

Profile of Reproductive Issues Associated with Different Sickle Cell Disease Genotypes / Perfil reprodutivo associado aos diferentes genótipos da doença falciforme

Abstract Purpose To describe the reproductive variables associated with different sickle cell disease (SCD) genotypes and the influence of contraceptive methods on acute painful episodes among the women with the homozygous hemoglobin S (HbSS) genotype. Methods A cross-sectional study was conducted between September of 2015 and April of 2016 on 158 women afflicted with SCD admitted to a hematology center in the Northeast of Brazil. The reproduction-associated variables of different SCD genotypes were assessed using the analysis of variance (ANOVA) test to compare means, and the Kruskal-Wallis test to compare medians. The association between the contraceptive method and the acute painful episodes was evaluated by the Chi-square test. Results Themean age of women with SCD was 28.3 years and 86.6% were mixed or of African-American ethnicity. With respect to the genotypes, 134 women (84.8%) had HbSS genotype, 12 women (7.6%) had hemoglobin SC (HbSC) disease genotype, and 12 (7.6%) were identified with hemoglobinopathy S-beta (S-β) thalassemia. The mean age of HbSS diagnosis was lower than that of HbSC disease, the less severe formof SCD (p < 0.001). The mean age ofmenarche was 14.8 ± 1.8 years for HbSS and 12.7 ± 1.5 years for HbSC (p < 0.001). Among women with HbSS who used progestin-only contraception, 16.6% had more than 4 acute painful episodes per year. There was no statistically significant difference when compared with other contraceptive methods. Conclusion With respect to reproduction-associated variables, only the age of the menarche showed delay in HbSS when compared with HbSC. The contraceptive method used was not associated with the frequency of acute painful episodes among the HbSS women.

Resumo Objetivo Descrever as variáveis reprodutivas em diferentes genótipos da doença falciforme (DF) e a influência dos métodos contraceptivos na frequência das crises álgicas em mulheres com homozigose da hemoglobina S (HbSS). Métodos Estudo de corte transversal realizado entre setembro de 2015 e abril de 2016 com 158 mulheres com DF atendidas em um centro de hematologia no Nordeste do Brasil. As variáveis reprodutivas dos diferentes genótipos da DF foram avaliadas utilizando-se o teste de análise de variância (ANOVA) para comparação de médias e o teste de Kruskal-Wallis para comparação de medianas. A associação entre o método contraceptivo e a frequência das crises álgicas foi avaliada pelo teste Qui-quadrado. Resultados A idade média das mulheres com DF foi de 28,3 anos e 86,6% eram afrodescentes. Em relação aos genótipos, 134 mulheres (84,8%) tinham genótipo HbSS, 12 mulheres (7,6%) tinham genótipo para doença da hemoglobina SC (HbSC) e 12 (7,6%) foram identificadas com beta talassemia (S-β). A idade média do diagnóstico de HbSS foi menor do que a da HbSC, sendo esta a forma menos grave da DF (p < 0,001). A idade média da menarca foi de 14,8 ± 1,8 anos para HbSS e de 12,7 ± 1,5 anos para HbSC (p < 0,001). Entre as mulheres com HbSS que fizeram contracepção com progesterona isolada, 16,6% apresentaram mais de 4 episódios de crises álgicas agudas por ano. Não houve diferença estatisticamente significativa quando comparado com outros métodos anticoncepcionais. Conclusão Em relação às variáveis reprodutivas, apenas a idade da menarca apresentou atraso no HbSS em relação ao HbSC. O método anticoncepcional utilizado não foi associado à frequência de crises álgicas entre as mulheres com HbSS.

Progesterone-based compounds affect immune responses and susceptibility to infections at diverse mucosal sites.

Over 100 million women worldwide are currently on progesterone-based contraceptives to improve their health outcomes through reduced maternal mortality and family planning. In addition to their role in reproduction, progesterone-based compounds modulate immune responses throughout the body, particularly at mucosal sites. By binding to receptors located in immune cells, including natural killer cells, macrophages, dendritic cells, and T cells, as well in non-immune cells, such as epithelial and endothelial cells, progesterone-based compounds alter cellular signaling and activity to affect the outcome of infections at diverse mucosal sites, including the genital, gastrointestinal, and respiratory tracts. As the use of progesterone-based compounds, in the form of contraceptives and hormone-based therapies, continue to increase worldwide, greater consideration should be given to how the immunomodulatory effects these compounds alter the outcome of diseases at mucosal sites beyond the reproductive tract, which has profound implications for women's health.