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.

Does the use of oral contraceptives or hormone replacement therapy offer protection against the formation or rupture of intracranial aneurysms in women?: a systematic review and meta-analysis

SUMMARY OBJECTIVE: The aim of this study was to carry out a systematic review of the literature with meta-analysis to evaluate the effect of using oral contraceptive and hormone replacement therapy as a protective factor in the formation of intracranial aneurysms and subarachnoid hemorrhage. METHODS: This is a systematic review of the literature with meta-analysis, using PubMed and Embase as databases and the PRISMA method. Case-control and cohort studies published until December 2022 were included in this review. RESULTS: Four studies were included in this review; three of which were eligible for meta-analysis. Regarding the use of oral contraceptive and the development of subarachnoid hemorrhage, there was a lower risk of aneurysm rupture with an odds ratio 0.65 (confidence interval 0.5-0.85). In the analysis of patients using hormone replacement therapy and developing subarachnoid hemorrhage, there was also a lower risk of aneurysm rupture with an OR 0.54 (CI 0.39-0.74). Only one article analyzed the formation of intracranial aneurysm and the use of hormone replacement therapy and oral contraceptive, and there was a protective effect with the use of these medications. oral contraceptive: OR 2.1 (CI 1.2-3.8) and hormone replacement therapy: OR 3.1 (CI 1.5-6.2). CONCLUSION: The use of hormone replacement therapy and oral contraceptive has a protective effect in intracranial aneurysm rupture and formation.

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.

Síndrome de ovario poliquístico / Polycystic ovary syndrome

El síndrome de ovario poliquísticos (SOP) representa una de las endocrinopatías más frecuentes en la mujer y es la principal causa de hiperandrogenismo (HA). Se trata de un trastorno complejo, multifactorial, poligénico con influencias ambientales. Aunque se han propuestos diferentes criterios para su diagnóstico, se prefiere el uso del más abarcativo (Criterio de Rotterdam) con la presencia de 2 de 3 de los siguientes: 1) HA clínico o bioquímico, 2) oligoanovulación crónica (OA), 3) poliquistosis ovárica por ecografía, excluyendo otras etiologías. Es frecuente su asociación con comorbilidades metabólicas (obesidad, diabetes 2, dislipidemia, apnea del sueño, etc.) y trastornos reproductivos (hiperplasia endometrial e infertilidad), sobre todo en los fenotipos clásicos, con HA y OA. El tratamiento estará orientado a las características clínicas de cada paciente y al deseo reproductivo. La pérdida de peso en aquellas con sobrepeso u obesidad o ambos factores puede restaurar los ciclos menstruales y disminuir el riesgo metabólico y representa la primera línea de tratamiento. Los anticonceptivos orales (ACO) son el tratamiento farmacológico de elección ya que atenúan las manifestaciones de HA y ofrecen protección endometrial. En las pacientes con oligoanovulación que buscan embarazo, el citrato de clomifeno es el tratamiento aconsejado en primera instancia. La metformina podría usarse en aquellas con intolerancia a la glucosa o diabetes 2 y también como segunda línea de tratamiento para restaurar los ciclos e inducir la ovulación. (AU)

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women, the main cause of hyperandrogenism (HA). It is a complex, multifactorial polygenic disorder with environmental influences. Although there have been proposed different criteria for diagnosis, using the most comprehensive (Criteria Rotterdam) with the presence of 2 of 3 of the following is preferred: 1) HA clinical or biochemical, 2) oligo-anovulation chronic (OA), 3) polycystic ovaries by ultrasound, excluding other etiologies. It is frequently associated with metabolic comorbidities (obesity, type 2 diabetes, dyslipidemia, sleep apnea, etc.) and reproductive disorders (endometrial hyperplasia and infertility), especially in the classical phenotypes, with HA and OA. The treatment will be oriented to the clinical characteristics of each patient and reproductive desire. Weight loss in those who are overweight and / or obesity can restore menstrual cycles and decrease metabolic risk and represents the first line of treatment. Oral contraceptives (OC) are the pharmacological treatment of choice as it attenuates the manifestations of HA and offer endometrial protection. In patients seeking pregnancy with oligo-anovulation, clomiphene citrate would be used at first instance. Metformin may be used in those with impaired glucose tolerance or type 2 diabetes and also as a second-line treatment to restore cycles and induce ovulation. (AU)

Modulation of Toll Like Receptor-2 on sebaceous gland by the treatment of adult female acne.

Adult female acne is a chronic inflammatory, immune-mediated disease that affects the pilosebaceous unit in women in their 20s to 40s, and is considered different from acne vulgaris. Propionibacterium acnes is recognized by TLR-2, resulting in activation of this receptor and an inflammatory response through the NFκ B pathway. This therapeutic, interventional, open, randomized, evaluator-blinded and comparative trial included 38 adult women with moderate facial acne and 10 age-matched controls, all aged between 26 and 44 years. Two treatments were performed over six months: 15% azelaic acid gel (AA) bid (n = 18) and oral contraceptive (COC) drospirenone 3 mg/ethinylestradiol .02 mg (n = 20). Biopsies were taken at baseline (control, lesion, perilesional) and at the conclusion (lesion and perilesional) of the study to evaluate TLR-2 expression by immunohistochemistry. Lesion count and blind photographic evaluation were used for efficacy. The groups were homogeneous: 70% of lesions were located in the submandibular area, 95% of participants had inflammatory lesions; of these, 50% had persistent and 50% had late-onset acne. The mean ages were 33.7 ± 5.5 and 33.1 ± 5.3 years (COC and AA group, respectively). A moderate clinical improvement was observed in both groups. No difference in TLR-2 expression in the lesion or perilesional areas was observed; however, reduced TLR-2 expression was seen in the control group. A significant reduction in expression was observed after both treatments, with no difference between the groups. This finding suggests an anti-inflammatory effect of COCs and AA in adult female acne, via modulation of the TLR-2 receptor.

Influence of Dyslipidemia on the Quality of Sexual Life in Women in the Menacme using a Combined Oral Contraceptive / Influência da dislipidemia na qualidade de vida sexual de mulheres na menacme usando contraceptivos orais combinados

ABSTRACT Purpose: Female sexual dysfunction is a complex and common condition that affects women, and the relationship between sexual function and dyslipidemia is poorly studied. This study aims to assess this relationship in the reproductive life women in the menacme who use combined oral contraceptives (COCs) . Methods: A total of 49 healthy women who were sexually active received COC pills that contained ethinylestradiol 30 mcg (EE30) plus levonorgestrel 150 mcg (LNG150). The women were divided into two groups according to their lipid profiles. Dyslipidemia was defined as a high-density lipoprotein (HDL) level < 50 mg/dL or a low-density lipoprotein (LDL) level > 130 mg/dL. Sexual function was assessed using the Female Sexual Function Index (FSFI) Questionnaire. Lipid and lipoprotein parameters were obtained at baseline and after the sixth cycle. Results: After six cycles of the COCs, the total cholesterol and LDL cholesterol levels in the women with a LDL level > 130 mg/dL decreased by 14.7% and 22.1% respectively. In the women with a HDL level < 50 mg/dL at baseline, the HDL level increased by 15.5% at the end of the study. The arousal and orgasm domains and the FSFI total scores significantly increased in women with and without dyslipidemia. The desire and satisfaction domains increased only in the group without dyslipidemia at the end of the treatment period. Conclusions: The EE30/LNG150 formulation increased the sexual function and it was only positively correlated with the HDL cholesterol level. These data indicated a low correlation between sexual function and the changes in the lipid and lipoprotein metabolism.

RESUMO Objetivo: Disfunção sexual feminina é uma condição complexa acomete as mulheres, e a relação entre a função sexual e a dislipidemia é muito pouco estudada. Este estudo objetivou avaliar esta relação em mulheres na menacme que fazem uso de contraceptivos orais combinados (COCs). Métodos: Um total de 49 mulheres saudáveis com vida sexual ativa receberam pílulas anticoncepcionais contendo etinilestradiol 30 mcg (EE30) associado a levonorgestrel 150 mcg (LNG150). As mulheres foram divididas em dois grupos, de acordo com o perfil lipídico. Dislipidemia foi definida como nível de lipoproteína de alta densidade (HDL) < 50 mg/dL, ou nível de lipoproteína de baixa densidade (LDL) > 130 mg/dL. A função sexual feminina foi avaliada utilizando o questionário de Índice de Função Sexual Feminina (IFSF). O IFSF e os parâmetros lipídicos e lipoproteicos foram obtidos no início e após o sexto ciclo do estudo. Resultados: Após seis ciclos de uso dos COCs, as mulheres com LDL > 130 mg/dL, tiveram redução dos níveis de colesterol total e colesterol LDL de 14,7% e 22,1% respectivamente. Nas mulheres com níveis HDL < 50 mg/dL no momento basal, o nível de HDL aumentou 15,5% ao final do estudo. Os domínios de excitação, orgasmo e os escores totais do IFSF aumentaram significativamente nas mulheres com e sem dislipidemia. Os domínios de desejo e satisfação aumentaram no final do período de tratamento exclusivamente no grupo sem dislipidemia. Conclusões: A formulação EE30/LNG150 aumentou a função sexual das mulheres, sendo positivamente correlata somente com os níveis de colesterol HDL. Estes achados demonstram baixa correlação entre a função sexual e as alterações no metabolismo lipídico e lipoproteico.