RESUMEN
OBJECTIVE: This study aimed to investigate the association of hormone replacement therapy (HRT) use, type, duration and age of commencement with myocardial infarction (MI) and stroke in postmenopausal Korean women. METHODS: This nested case-control study used data from the National Health Insurance Service database to analyze 2017 data from women aged ≥50 years and diagnosed with natural menopause between 2004 and 2007. Among 356,160 eligible women, 36,446 used HRT for ≥1 year and 319,714 did not (controls). These two groups were matched 1:1 for statistical analysis. Type and duration were categorized into three categories. RESULTS: Women who started estrogen-progestogen therapy (EPT) or estrogen therapy (ET) in their 50s, or EPT or tibolone in their ≥60s exhibited a lower stroke risk than controls. MI risk was lower among women who used tibolone - regardless of duration - or EPT or ET for 1-3 years than among controls. Stroke risk was lower with tibolone use for ≥5 years or with EPT or ET use for 1-3 years or ≥5 years than non-users. CONCLUSION: Our study may support the beneficial effect of HRT by showing that Korean postmenopausal women who used HRT at a relatively younger and healthier age had a relative benefit for MI and stroke.
Asunto(s)
Terapia de Reemplazo de Estrógeno , Infarto del Miocardio , Norpregnenos , Posmenopausia , Accidente Cerebrovascular , Humanos , Femenino , Infarto del Miocardio/epidemiología , Persona de Mediana Edad , República de Corea/epidemiología , Estudios de Casos y Controles , Accidente Cerebrovascular/epidemiología , Norpregnenos/efectos adversos , Terapia de Reemplazo de Estrógeno/efectos adversos , Anciano , Factores de Edad , Bases de Datos Factuales , Factores de Riesgo , Terapia de Reemplazo de Hormonas/efectos adversosRESUMEN
We compared the efficacy of 4 mg drospirenone (DRSP) progestin-only pills (POPs) versus combined oral contraceptive pills (COCs) containing 0.02 mg of ethinyl estradiol (EE) and 0.075 mg of gestodene (GS) in ovulation inhibition and inducing unfavorable cervical mucus changes using a delayed-starting approach. This randomized controlled trial involved 36 participants aged 18-45 years. The major outcomes included ovulation inhibition assessed using the Hoogland and Skouby score, and cervical mucus permeability, assessed using the modified World Health Organization score. The results demonstrated ovulation inhibition rates of 77.8% for the EE/GS group and 88.9% for the DRSP group. The risk ratio and absolute risk reduction were 0.50 (95% confidence interval [CI]: 0.10, 2.40) and - 0.11 (95% CI: - 0.35, 0.13), respectively, satisfying the 20% non-inferiority margin threshold. The median time to achieve unfavorable cervical mucus changes was comparable between the DRSP (3 days, interquartile range [IQR]: 6 days) and EE/GS (3.5 days, IQR: 4 days) groups. However, the DRSP group had a higher incidence of unscheduled vaginal bleeding (55.56% vs. 11.11%; p = 0.005). DRSP-only pills, initiated on days 7-9 of the menstrual cycle, were non-inferior to EE/GS pills in ovulation inhibition. However, they exhibited delayed unfavorable cervical mucus changes compared to the standard two-day backup recommendation.Clinical trial registration: Thai Clinical Trials Registry (TCTR20220819001) https://www.thaiclinicaltrials.org/show/TCTR20220819001 .
Asunto(s)
Androstenos , Anticonceptivos Orales Combinados , Etinilestradiol , Inhibición de la Ovulación , Humanos , Femenino , Adulto , Etinilestradiol/administración & dosificación , Androstenos/administración & dosificación , Androstenos/efectos adversos , Adulto Joven , Adolescente , Anticonceptivos Orales Combinados/administración & dosificación , Inhibición de la Ovulación/efectos de los fármacos , Método Simple Ciego , Persona de Mediana Edad , Norpregnenos/administración & dosificación , Norpregnenos/efectos adversos , Ovulación/efectos de los fármacos , Moco del Cuello Uterino/efectos de los fármacosRESUMEN
IMPORTANCE: Menopausal hormone therapy (HT) includes a wide variety of hormonal compounds, and its effect on blood pressure is still uncertain. OBJECTIVE: The aim of this study was to assess evidence regarding the effect of HT on blood pressure in postmenopausal women and its association with arterial hypertension. EVIDENCE REVIEW: This systematic review and meta-analysis included randomized clinical trials and prospective observational studies. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and the incidence of hypertension were assessed. All stages were independently performed by two reviewers. For blood pressure outcome, standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated as effect measures. Heterogeneity was assessed using the I2 statistic. The results are presented based on the HT type. The incidence of hypertension was compared using descriptive analyses. FINDINGS: Eleven studies were included with 81,041 women evaluated, of which 29,812 used HT. The meta-analysis, conducted with 8 studies and 1,718 women, showed an increase in SBP with the use of oral conjugated equine estrogens plus progestogen (SMD = 0.60 mm Hg, 95% CI = 0.19 to 1.01). However, oral or transdermal use of estradiol plus progestogen (SMD = -2.00 mm Hg, 95% CI = -7.26 to 3.27), estradiol alone, and tibolone did not show any significant effect. No significant effect on DBP was observed for any formulation. Women who used oral estrogen plus progestogen had a higher risk of incident hypertension than those who never used it. CONCLUSIONS AND RELEVANCE: The effect of HT on blood pressure is influenced by the formulation used, especially the type of estrogen. The combined formulations of conjugated equine estrogens plus progestogen increased SBP and the risk of hypertension, which was not observed among estradiol plus progestogen, estradiol alone, and tibolone users.
Asunto(s)
Presión Sanguínea , Terapia de Reemplazo de Estrógeno , Hipertensión , Posmenopausia , Humanos , Femenino , Hipertensión/tratamiento farmacológico , Presión Sanguínea/efectos de los fármacos , Terapia de Reemplazo de Estrógeno/métodos , Progestinas/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Estrógenos Conjugados (USP)/administración & dosificación , Persona de Mediana Edad , Estradiol/administración & dosificación , Norpregnenos/efectos adversos , Norpregnenos/administración & dosificación , Estrógenos/administración & dosificaciónRESUMEN
OBJECTIVE: To explore the risk of breast cancer associated with menopausal hormone therapy (MHT), including the various progestogens used today. METHODS: The study included postmenopausal women over 40 years from the National Health Insurance Database in South Korea (2011-2014) who either used MHT for over 6 months (MHT group) or never used MHT (non-MHT group) and were matched 1:1 based on several variables using propensity score matching. Both groups were followed until 2020. RESULTS: The non-MHT and MHT groups comprised 153 736 women each. In Cox proportional hazard analysis with time-dependent covariates, MHT was associated with an increased risk of breast cancer (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.15-1.3). Tibolone, estradiol valerate (EV)/medroxyprogesterone acetate (MPA), EV/norethisterone acetate (NETA), conjugated equine estrogen (CEE), EV, estradiol hemihydrate (EH), CEE/micronized progesterone (MP), CEE/MPA, EV/MP, EV/MPA, and EH/MP did not increase the risk of breast cancer compared with the non-MHT group. However, EH/drospirenone (DRSP) (HR 1.51, 95% CI 1.38-1.66), EH/NETA (HR 1.66, 95% CI 1.34-2.06), EH/dydrogesterone (DYD) (HR 1.37, 95% CI 1.12-1.68), and EV/cyproterone acetate (CPA) (HR 1.74, 95% CI 1.54-1.96) increased the risk of breast cancer compared with the non-MHT group. CONCLUSIONS: MHT was linked to increased breast cancer risk, but not all MHTs. Specific combined therapies (EH/DRSP, EH/DYD, EH/NETA, and EV/CPA) were associated with higher risk, whereas estrogen alone and tibolone were not.
Asunto(s)
Neoplasias de la Mama , Terapia de Reemplazo de Estrógeno , Progestinas , Humanos , Femenino , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/inducido químicamente , Persona de Mediana Edad , República de Corea/epidemiología , Anciano , Terapia de Reemplazo de Estrógeno/efectos adversos , Terapia de Reemplazo de Estrógeno/estadística & datos numéricos , Progestinas/efectos adversos , Progestinas/administración & dosificación , Estudios de Cohortes , Modelos de Riesgos Proporcionales , Norpregnenos/efectos adversos , Adulto , Posmenopausia , Menopausia , Estradiol/efectos adversos , Factores de Riesgo , Terapia de Reemplazo de Hormonas/efectos adversos , Terapia de Reemplazo de Hormonas/estadística & datos numéricos , Acetato de Medroxiprogesterona/efectos adversos , Acetato de Medroxiprogesterona/administración & dosificación , Noretindrona/efectos adversos , Noretindrona/administración & dosificación , Noretindrona/análogos & derivadosRESUMEN
OBJECTIVE: To evaluate the association between menopausal hormonal therapy (MHT) and the risk of cardiovascular disease (CVD), according to various regimens, dosages, routes of administration and starting ages of MHT. DESIGN: A population-based cohort study using the Korean National Health Insurance Services database. SETTING: Nationwide health insurance database. POPULATION: Women who reported entering menopause at an age of ≥40 years with no history of CVD in the national health examination. METHODS: The study population comprised 1 120 705 subjects enrolled between 2002 and 2019, categorised according to MHT status (MHT group, n = 319 007; non-MHT group, n = 801 698). MAIN OUTCOME MEASURES: Incidence of CVD (a composite of myocardial infarction and stroke). RESULTS: The incidence of CVD was 59 266 (7.4%) in the non-MHT group and 17 674 (5.5%) in the MHT group. After adjusting for confounding factors, an increased risk of CVD was observed with the administration of tibolone (hazard ratio, HR 1.143, 95% CI 1.117-1.170), oral estrogen (HR 1.246, 95% CI 1.198-1.295) or transdermal estrogen (HR 1.289, 95% CI 1.066-1.558), compared with the non-MHT group; the risk was based on an increased risk of stroke. The risk trends were consistent regardless of the age of starting MHT or the physicians' specialty. Among tibolone users, a longer period from entering menopause to taking tibolone and the use of any dosage (1.25 or 2.5 mg) were linked with a higher risk of CVD, compared with non-MHT users. CONCLUSIONS: This nationwide cohort study demonstrated an increased risk of CVD, driven mainly by an increased risk of stroke, among tibolone and oral or transdermal estrogen users, compared with that of non-MHT users.
Asunto(s)
Enfermedades Cardiovasculares , Terapia de Reemplazo de Estrógeno , Norpregnenos , Posmenopausia , Humanos , Femenino , Persona de Mediana Edad , República de Corea/epidemiología , Enfermedades Cardiovasculares/epidemiología , Terapia de Reemplazo de Estrógeno/efectos adversos , Terapia de Reemplazo de Estrógeno/estadística & datos numéricos , Norpregnenos/efectos adversos , Estudios de Cohortes , Incidencia , Adulto , Anciano , Estrógenos/efectos adversos , Estrógenos/administración & dosificación , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/inducido químicamente , Factores de Riesgo , Factores de Riesgo de Enfermedad Cardiaca , Bases de Datos FactualesRESUMEN
The safety profile of hormone replacement therapy (HRT) on breast is still controversial. Tibolone is an option of treatment for climacteric syndrome of postmenopausal women. Its risk profile on breast is debated. This is an updated narrative review focusing on the impact of tibolone on breast. Particularly, we will report data from major preclinical and clinical studies regarding the effects of the use of this compound on breast tissue and breast density. Moreover, we will analyze and discuss the most relevant findings of the principal studies evaluating the relationship between tibolone and breast cancer risk. Our purpose is making all clinicians who are particularly involved in women's health more aware of the effects of this compound on breast and, thus, more experienced in the management of menopausal symptoms with this drug. According to the available literature, tibolone seems to be characterized by an interesting safety profile on breast tissue.
Asunto(s)
Neoplasias de la Mama , Moduladores de los Receptores de Estrógeno , Femenino , Humanos , Moduladores de los Receptores de Estrógeno/efectos adversos , Norpregnenos/efectos adversos , Terapia de Reemplazo de Hormonas/efectos adversos , Neoplasias de la Mama/inducido químicamente , Neoplasias de la Mama/tratamiento farmacológicoRESUMEN
We aimed to compare low-level light therapy with oral contraceptive pills for pain relief and serum levels of nitric oxide and prostaglandin E2 in patients with primary dysmenorrhoea. This was a randomised, active comparator-controlled, multicentre study. In total, 156 patients were randomised to receive either low-level light therapy with light-emitting diodes (LED) applying on two acupoints, namely, conception vessel 4 (CV4) and CV6 or conventional treatment with oral Marvelon, 30 µg of ethinyl estradiol and 150 µg of desogestrel (DSG/EE), for three consecutive menstrual cycles. The main outcome was the proportion of patients who achieved 33% or more decrease in pain scores measured using the visual analogue scale, which was deemed as efficient rate. Absolute changes in visual analogue scale scores, serum levels of nitric oxide (assessed by nitrites and nitrates reflecting nitric oxide metabolism) and prostaglandin E2 (measured by enzyme-linked immunosorbent assay) were the secondary outcomes. A total of 135 patients completed the study (73 in the light therapy group and 62 in the DSG/EE group). The efficient rate at the end of treatment was comparable between the groups (73.6% vs. 85.7%, χ2 = 2.994, p = 0.084). A more significant reduction in pain scores was observed in the DSG/EE group (39.25% vs. 59.52%, p < 0.001). Serum levels of prostaglandin E2 significantly decreased from baseline but did not differ between groups (- 109.57 ± 3.99 pg/mL vs. - 118.11 ± 12.93 pg/mL, p = 0.51). Nitric oxide concentration remained stable in both groups. Low-level light therapy with LED-based device applied on acupuncture points CV4 and CV6 demonstrated a similar level of dysmenorrhoea pain reduction to DSG/EE combined contraceptive. Both treatment modalities achieved clinically meaningful levels of pain reduction. Registration on ClinicalTrials.gov: TRN: NCT03953716, Date: April 04, 2019.
Asunto(s)
Anticonceptivos Orales Combinados , Terapia por Luz de Baja Intensidad , Anticonceptivos Orales Combinados/efectos adversos , Desogestrel/efectos adversos , Desogestrel/uso terapéutico , Dismenorrea/tratamiento farmacológico , Dismenorrea/radioterapia , Etinilestradiol/efectos adversos , Etinilestradiol/uso terapéutico , Femenino , Humanos , Óxido Nítrico , Norpregnenos/efectos adversos , Estudios Prospectivos , Prostaglandinas , Resultado del TratamientoRESUMEN
Inconsistencies exist with regard to influence of tibolone treatment on the lipid profile. The reasons for these inconsistencies might derive from several factors, i.e., differences in baseline variables, intervention duration, participants' health status or baseline body mass index (BMI). To address these inconsistencies, based on a systematic search in Scopus, PubMed/Medline, Web of Science, and Embase for papers published until 21 December 2020, we conducted the current dose-response meta-analysis of randomized controlled trials (RCTs) to determine the impact of tibolone treatment on the lipid profile. The overall findings were derived from 26 RCTs. Tibolone administration decreased total cholesterol (TC) (weighted mean difference, WMD: -18.55 mg/dL, CI: -25.95 to -11.16, P < 0.001), high-density lipoprotein-cholesterol (HDL-C) (WMD: -9.42 mg/dL, CI: -11.83 to -7.01, P < 0.001) and triglyceride (TG) (WMD: -21.43 mg/dL, CI: -27.15 to -15.70, P < 0.001) levels. A significant reduction in LDL-C occurred when tibolone was prescribed for ≤ 26 weeks (WMD: -7.64 mg/dL, 95% CI: -14.58 to -0.70, P = 0.031) versus > 26 weeks (WMD: -8.84 mg/dL, 95% CI: -29.98, 12.29, P = 0.412). The decrease in TG (WMD: -22.64 mg/dL) and TC (-18.55 mg/dL) concentrations was more pronounced in patients with BMI ≥ 25 kg/m2versus BMI < 25 kg/m2. This systematic review and meta-analysis discovered that tibolone decreases TC, HDL-C and TG levels. LDL-C concentrations are significantly reduced when tibolone administration lasts for ≤ 26 weeks.
Asunto(s)
Lípidos/sangre , Norpregnenos/efectos adversos , Relación Dosis-Respuesta a Droga , Terapia de Reemplazo de Estrógeno/efectos adversos , Femenino , Humanos , Norpregnenos/farmacología , Norpregnenos/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: To assess the risks of breast cancer associated with different types and durations of hormone replacement therapy (HRT). DESIGN: Two nested case-control studies. SETTING: UK general practices contributing to QResearch or Clinical Practice Research Datalink (CPRD), linked to hospital, mortality, social deprivation, and cancer registry (QResearch only) data. PARTICIPANTS: 98 611 women aged 50-79 with a primary diagnosis of breast cancer between 1998 and 2018, matched by age, general practice, and index date to 457 498 female controls. MAIN OUTCOME MEASURES: Breast cancer diagnosis from general practice, mortality, hospital, or cancer registry records. Odds ratios for HRT types, adjusted for personal characteristics, smoking status, alcohol consumption, comorbidities, family history, and other prescribed drugs. Separate results from QResearch or CPRD were combined. RESULTS: Overall, 33 703 (34%) women with a diagnosis of breast cancer and 134 391 (31%) controls had used HRT prior to one year before the index date. Compared with never use, in recent users (<5 years) with long term use (≥5 years), oestrogen only therapy and combined oestrogen and progestogen therapy were both associated with increased risks of breast cancer (adjusted odds ratio 1.15 (95% confidence interval 1.09 to 1.21) and 1.79 (1.73 to 1.85), respectively). For combined progestogens, the increased risk was highest for norethisterone (1.88, 1.79 to 1.99) and lowest for dydrogesterone (1.24, 1.03 to 1.48). Past long term use of oestrogen only therapy and past short term (<5 years) use of oestrogen-progestogen were not associated with increased risk. The risk associated with past long term oestrogen-progestogen use, however, remained increased (1.16, 1.11 to 1.21). In recent oestrogen only users, between three (in younger women) and eight (in older women) extra cases per 10 000 women years would be expected, and in oestrogen-progestogen users between nine and 36 extra cases per 10 000 women years. For past oestrogen-progestogen users, the results would suggest between two and eight extra cases per 10 000 women years. CONCLUSION: This study has produced new generalisable estimates of the increased risks of breast cancer associated with use of different hormone replacement preparations in the UK. The levels of risks varied between types of HRT, with higher risks for combined treatments and for longer duration of use.
Asunto(s)
Neoplasias de la Mama/epidemiología , Terapia de Reemplazo de Hormonas/estadística & datos numéricos , Anciano , Estudios de Casos y Controles , Bases de Datos Factuales , Estrógenos/administración & dosificación , Estrógenos/efectos adversos , Femenino , Terapia de Reemplazo de Hormonas/efectos adversos , Humanos , Incidencia , Persona de Mediana Edad , Norpregnenos/administración & dosificación , Norpregnenos/efectos adversos , Progestinas/administración & dosificación , Progestinas/efectos adversos , Medición de RiesgoRESUMEN
Tibolone (TIB), a selective tissue estrogenic activity regulator (STEAR) in clinical use by postmenopausal women, activates hormonal receptors in a tissue-specific manner. Estrogenic activity is present mostly in the brain, vagina, and bone, while the inactive forms predominate in the endometrium and breast. Conflicting literature on TIB's actions has been observed. While it has benefits for vasomotor symptoms, bone demineralization, and sexual health, a higher relative risk of hormone-sensitive cancer has been reported. In the brain, TIB can improve mood and cognition, neuroinflammation, and reactive gliosis. This review aims to discuss the systemic effects of TIB on peri- and post-menopausal women and its role in the brain. We suggest that TIB is a hormonal therapy with promising neuroprotective properties.
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Encéfalo/efectos de los fármacos , Moduladores de los Receptores de Estrógeno/farmacología , Menopausia/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Norpregnenos/farmacología , Encéfalo/inmunología , Encéfalo/metabolismo , Moduladores de los Receptores de Estrógeno/efectos adversos , Femenino , Humanos , Menopausia/inmunología , Menopausia/metabolismo , Norpregnenos/efectos adversosRESUMEN
Tibolon is the only therapeutic approach to climacteric symptoms, prevention of osteoporosis and urogenital atrophy with the same efficacy as hormone replacement therapy. Tibolon has more positive effects on sexuality and mood changes in menopausal women. It decreases the mammographic density. Its safety for breast cancer is the same as for only estrogen therapy and better than for estrogen-gestagen therapy. Tibolon is the first choice for postmenopausal women with mood and sexuality disorders, women with mastodynia and high mammographic density.
Asunto(s)
Moduladores de los Receptores de Estrógeno , Norpregnenos , Osteoporosis , Neoplasias de la Mama/inducido químicamente , Clima , Moduladores de los Receptores de Estrógeno/efectos adversos , Moduladores de los Receptores de Estrógeno/uso terapéutico , Estrógenos , Femenino , Humanos , Menopausia , Norpregnenos/efectos adversos , Norpregnenos/uso terapéutico , Osteoporosis/prevención & control , ProgestinasRESUMEN
INTRODUCTION AND HYPOTHESIS: The impact of estradiol-based hormone therapy (HT) on the incidence of stress urinary incontinence (SUI) is unknown. Therefore, we compared the use of such HT regimens and tibolone in women with and without SUI. METHODS: The women with a history of SUI operation (N = 15,002) were identified from the Finnish National Hospital Discharge Register, and the control women without such an operation (N = 44,389) from the Finnish Central Population Register. The use of HT was traced from the National Drug Reimbursement Register, and the odd ratios (ORs) with 95% confidence intervals (95% CIs) for SUI were calculated by using the conditional logistic regression analysis. RESULTS: The cases had used any HT more often than the controls. The use of systemic estradiol-only or estradiol-progestin therapy was accompanied by an increased SUI risk (OR 3.8, 95% CI: 3.6-4.0 and OR 2.7, 95% CI: 2.6-2.9 respectively). The use of estradiol with noretisterone acetate showed a higher risk of increase than that with medroxyprogesterone acetate. Age over 55 years at the initiation of systemic HT was accompanied by a higher SUI risk increase than that under 55 years of age. The use of tibolone, an estradiol + levonorgestrel-releasing intrauterine device, or vaginal estradiol also increased the risk. CONCLUSIONS: The use of HT regimens may predispose to the de novo development or worsening of pre-existing SUI. Thus, caution is needed when these regimens are prescribed to women with mild stress-related urine leakage or with established SUI risk factors.
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Estradiol/efectos adversos , Terapia de Reemplazo de Estrógeno/efectos adversos , Estrógenos/efectos adversos , Norpregnenos/efectos adversos , Incontinencia Urinaria de Esfuerzo/epidemiología , Terapia de Reemplazo de Estrógeno/métodos , Femenino , Finlandia/epidemiología , Humanos , Persona de Mediana Edad , Posmenopausia/efectos de los fármacos , Sistema de Registros , Factores de Riesgo , Incontinencia Urinaria de Esfuerzo/inducido químicamenteRESUMEN
We describe the association of rapid progression of keratoconus in a 49-year-old woman on selective tissue estrogenic activity regulator (STEAR) therapy for endometriosis. Approximately 4 months after initiation of therapy with STEAR therapy and 3 months after ovariectomy, Scheimpflug images showed a massive increase in the previously stable ectasia. During this period, the maximum increase in the keratometry values was 2.7 diopters (D) in the right eye and 3.8 D in the left eye. Corneal crosslinking (CXL) was performed in both eyes. This resulted in excessive flattening of 5.5 D in the right eye and 6.1 D in the left eye at 9 months postoperatively. Patients having STEAR therapy must be monitored closely for corneal changes.
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Endometriosis/tratamiento farmacológico , Moduladores de los Receptores de Estrógeno/efectos adversos , Queratocono/inducido químicamente , Queratocono/diagnóstico , Norpregnenos/efectos adversos , Colágeno/metabolismo , Sustancia Propia/metabolismo , Topografía de la Córnea , Reactivos de Enlaces Cruzados , Progresión de la Enfermedad , Femenino , Humanos , Queratocono/tratamiento farmacológico , Persona de Mediana Edad , Ovariectomía , Fármacos Fotosensibilizantes/uso terapéutico , Riboflavina/uso terapéutico , Rayos Ultravioleta , Agudeza VisualRESUMEN
La definición de sangrado ginecológico anormal durante terapia hormonal de la menopausia es aquel sangrado no programado durante el uso de la terapia. Este artículo es un pauteo que describe: 1) cuándo diagnosticar unsangrado anormal, ya que difiere según el tipo de esquema hormonal utilizado; 2) eldiagnóstico diferencial del origen del sangrado anormal; 3) los métodos de evaluación para diagnosticar el origen del sangrado. Se destacan los aspectos principales para el diagnóstico diferencial entre patología orgánica versus disrupción endometrial debida al tratamiento hormonal. Además, se describen los ajustes posibles para resolver el sangrado cuando éste se debe a disrupción del endometrio.
Abnormal bleeding related to menopausal hormone therapy is defined as unscheduled bleeding during the use of the therapy. This article outlines when to diagnose an abnormal bleeding -as this differs according to the type of hormonal scheme used-, the differential diagnosis of the origin of abnormal bleeding, and the methods of evaluation to assess the origin of the bleeding. The main aspects are highlighted on the differentiation of organic pathology versus disruption of the endometrium due to treatment. Also, treatment adjustments to resolve bleeding when it is due to disruption of the endometrium are outlined.
Asunto(s)
Humanos , Femenino , Hemorragia Uterina/etiología , Menopausia , Terapia de Reemplazo de Estrógeno/efectos adversos , Moduladores de los Receptores de Estrógeno/efectos adversos , Norpregnenos/efectos adversos , Pólipos/complicaciones , Pólipos/diagnóstico , Neoplasias Endometriales/complicaciones , Neoplasias Endometriales/diagnóstico , Moduladores de los Receptores de Estrógeno/uso terapéutico , Diagnóstico Diferencial , Hiperplasia Endometrial/complicaciones , Hiperplasia Endometrial/diagnóstico , Endometrio/diagnóstico por imagen , Metrorragia/etiología , Norpregnenos/uso terapéuticoRESUMEN
OBJECTIVES: To synthesize knowledge on cancer risks related to hormonal contraception and to propose recommendations on contraception during treatment and after cancer. METHODS: A systematic review of the literature about hormonal contraception and cancer was conducted on PubMed/Medline and the Cochrane Library. RESULTS: Overall, there is no increase in cancer (all types together) incidence or mortality among hormonal contraceptive users. Estroprogestin combined contraceptive use is associated with an increased risk of breast cancer (during use), and with a reduced risk of endometrial, ovarian, lymphatic or hematopoietic cancers that persist after discontinuation, and a decreased risk of colorectal cancer. Information on cancer risk is part of the systematic information given to patients wishing contraception. However, these data will not influence its prescription, considering the positive risk/benefit balance in women without specific cancer risk factor. Contraception is required during and after cancer treatment in every non-menopausal woman at cancer diagnosis. Specific thromboembolic, immunologic or vomiting risks due to the oncological context should be taken into account before the contraceptive choice. All hormonal contraceptives are contra-indicated after breast cancer, regardless of the delay since treatment, hormone receptor status and histological subtype. There is no data in the literature to limit hormonal or non-hormonal contraceptive use after colorectal or thyroid cancer. There was insufficient data in the literature to propose recommendations on contraceptive choice after cervical cancer, melanoma, lung cancer, tumor of the central nervous system, or after thoracic irradiation. If an emergency contraception is needed in a woman previously treated for a hormone-sensitive cancer, a non-hormonal copper intrauterine device should be preferred. CONCLUSIONS: Information on cancer risk is part of the patient's information but does not influence the prescription of contraception in the absence of any specific risk factor. Contraception should be proposed in every woman treated or previously treated for cancer. The whole context should be taken into account to choose a tailored contraception.
Asunto(s)
Anticonceptivos Femeninos/efectos adversos , Anticonceptivos Hormonales Orales/efectos adversos , Neoplasias/epidemiología , Neoplasias/terapia , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/etiología , Anticoncepción Postcoital , Combinación de Medicamentos , Etinilestradiol/efectos adversos , Femenino , Francia , Humanos , Dispositivos Intrauterinos de Cobre , MEDLINE , Neoplasias/inducido químicamente , Norpregnenos/efectos adversos , Factores de RiesgoRESUMEN
Venous thromboembolism and arterial ischemic events are the main deleterious diseases associated with the use of combined hormonal contraceptives (CHC). Even though their composition has been substantially improved, the vascular risk persists with the most recent CHCs use. If the vascular risk associated with CHCs containing 50µg EE is significantly higher than with those containing less than 50µg, there is no evidence that the CHCs containing either 30 or 20µg of EE induce different venous risks. CHC containing gestodene, desogestrel, drospirenone or cyproterone acetate are associated with a higher risk of venous thrombosis compared with levonorgestrel-containing CHCs. CHC containing norgestimate are associated with similar venous thrombosis risk than CHC containing levonorgestrel. Venous thrombosis risk of non-oral routes of administration of CHC appears to be equivalent to the risk of CHC containing gestodene or desogestrel, but this result is based on a small number of epidemiological studies. Before prescribing a CHC, it is important to determine all vascular risk factors. Family history of ischemic arterial event or venous thromboembolism disease should be routinely sought before any CHC prescription. All CHCs are contraindicated in women with biological thrombophilia, in women with combined vascular risk factors, in women with first-degree family history of arterial or venous event (under age 50) as well as in women suffering of migraine with aura. Progestin-only contraceptives are not associated with vascular risk (arterial or venous) outside of medroxyprogesterone acetate. In women with higher vascular risk, progestin-only contraceptives (administered by oral, sous-cutaneous or intra-uterine routes) can be prescribed.
Asunto(s)
Anticonceptivos Hormonales Orales/efectos adversos , Enfermedades Vasculares/inducido químicamente , Tromboembolia Venosa/inducido químicamente , Androstenos/efectos adversos , Anticonceptivos Femeninos/administración & dosificación , Anticonceptivos Femeninos/efectos adversos , Anticonceptivos Orales Combinados/efectos adversos , Acetato de Ciproterona/efectos adversos , Desogestrel/efectos adversos , Femenino , Francia , Humanos , Levonorgestrel/efectos adversos , Norpregnenos/efectos adversos , Progestinas , Factores de Riesgo , Tromboembolia Venosa/epidemiologíaRESUMEN
There are several possible mechanisms by which combined oral contraceptives (COC) use increase venous thromboembolism (VTE) risk. Melodene® is a monophasic COC containing the third-generation progestin Gestodene (GSD), which is associated with increased risk of VTE. Therefore, the aim of this study was to investigate the possible alterations in viscoelastic parameters of whole blood and plasma clots along with the biophysical characteristics of erythrocytes and specifically fibrin fibers in females using a COC containing GSD. GSD appeared to have a significant impact on the biophysical characteristics of fibrin fiber networks. When GSD is combined with ethinylestradiol the viscoelastic properties of whole blood clots tend to become more prothrombotic. The alterations to and aggregation of erythrocytes accompanied with spontaneous formation of a fibrin "blanket" provides a possible mechanism for the increased occurrence of "red" clots, which can lead to occlusions in the vascular system. Thus, the increased risk of VTE associated with these COCs can be attributed to these erythrocyte-and-fibrin-rich-clots occluding venous vessels. However, our findings also propose that these changes to the biophysical properties of both erythrocytes and fibrin, specifically spontaneous expansion of deformed fibrin networks, can also occlude vessels in the microcirculation, which could have lasting, subclinical complications for female users. We recommend that a thorough risk assessment, with specific focus on coagulation and other factors affecting fibrin formation, be done for each female before prescribing a GSD-containing COC. Females that "qualify" then need to be monitored on a regular basis to lower the risk of thrombotic events. RESEARCH HIGHLIGHTS: Gestodene in combination with ethinyl estradiol significantly impacts the biophysical characteristics of erythrocytes and fibrin fiber networks. These changes, specifically spontaneous expansion of deformed fibrin networks, can occlude vessels in the microcirculation, which could have lasting, subclinical complications for the female user. The changes observed for specifically erythrocytes and fibrin show that the hormone formulation investigated contribute to a thrombogenic profile for female users.
Asunto(s)
Anticonceptivos Orales Combinados/efectos adversos , Norpregnenos/efectos adversos , Trombosis/etiología , Adulto , Coagulación Sanguínea/efectos de los fármacos , Eritrocitos/citología , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Femenino , Fibrina/metabolismo , Humanos , Trombosis/sangre , Trombosis/metabolismo , Adulto JovenRESUMEN
Importance: Women are at higher risk of drug-induced torsade de pointes (TdP) than men. Androgens are protective. Influence of oral contraception on drug-induced TdP and QT prolongation is controversial. Objective: To determine if the extent of sotalol-induced corrected QT (QTc) prolongation and specific T-wave morphological changes, which are biomarkers for the risk of drug-induced TdP, differ in patients according to the androgenic activity of the type of oral contraceptive (OCs) they take compared with patients who took no pills. Design, Setting, and Participants: A cohort of 498 healthy, nonmenopausal women received 80 mg of oral sotalol, a drug with known risk of drug-induced TdP, during this study in a clinical investigation center. The participants also took either no oral contraception or received OCs with different types of progestin: levonorgestrel (which has high androgenic potency), desogestrel or gestodene (which has intermediate androgenic potency), or drospirenone (which has antiandrogenic properties). Women were enrolled from February 2008 to February 2012, and data analysis took place from September 2014 to May 2018. Main Outcomes and Measures: Electrocardiographic changes 3 hours after sotalol administration. Results: A total of 137 women received levonorgestrel, 41 received desogestrel, 51 received gestodene, and 62 received drospirenone; another 207 received no OCs. Baseline QTc duration, plasma sotalol levels, and potassium levels did not significantly differ among groups. However, 3 hours after sotalol exposure, QTc prolongation was greater in women taking drospirenone (mean [SD] increase, 31.2 [12.6] milliseconds from baseline) than in women taking no OCs (mean [SD] increase, 24.6 [12.5] milliseconds; P = .005) or those taking levonorgestrel (mean [SD] increase, 24.2 [13.7] milliseconds; P = .005). The frequency of sotalol-induced T-wave alteration was higher in women taking drospirenone (n = 13 of 61 [21.0%]) than those taking levonorgestrel (n = 20 of 137 [14.6%]) or women taking no OCs (n = 24 of 207 [11.6%]; P = .01). Disproportionality analysis using the European pharmacovigilance database showed a higher reporting rate of OC-induced prolonged QT and ventricular arrhythmias in women taking drospirenone than levonorgestrel (drug-induced long QT syndrome: reporting odds ratio [ROR], 6.2 [95% CI, 1.3-30.8]; P = .01; ventricular arrhythmia: ROR, 3.3 [95% CI, 1.7-6.3]; P < .001). Conclusions and Relevance: Contraceptive pills are associated with variable drug-induced alterations of ventricular repolarization in healthy nonmenopausal women. Drospirenone, an antiandrogenic pill, was associated with increased sotalol-induced QTc prolongation, although absolute QTc prolongation was modest. This finding was supported by the European pharmacovigilance database, which showed a higher reporting rate of suspected OC-induced ventricular arrhythmias on drospirenone compared with levonorgestrel. More data are required on whether antiandrogenic OCs lead to clinically significant adverse events in patients taking QTc-prolonging drugs.
Asunto(s)
Antagonistas de Andrógenos/efectos adversos , Androstenos/efectos adversos , Síndrome de QT Prolongado/epidemiología , Sotalol/efectos adversos , Administración Oral , Adulto , Antagonistas de Andrógenos/administración & dosificación , Androstenos/administración & dosificación , Estudios de Cohortes , Anticonceptivos Femeninos/administración & dosificación , Anticonceptivos Femeninos/efectos adversos , Desogestrel/administración & dosificación , Desogestrel/efectos adversos , Europa (Continente) , Femenino , Humanos , Levonorgestrel/administración & dosificación , Levonorgestrel/efectos adversos , Modelos Logísticos , Síndrome de QT Prolongado/inducido químicamente , Norpregnenos/administración & dosificación , Norpregnenos/efectos adversos , Sotalol/administración & dosificación , Adulto JovenRESUMEN
Hypertriglyceridemia is the third most common cause of acute pancreatitis. Among the causes that lead to secondary hypertriglyceridemia, the use of contraceptive agents is the main reason to be assessed in young women. We report a case of a 31-year-old woman who had suffered two acute pancreatitis episodes secondary to hypertriglyceridemia. In the investigation, the previous medical team indicated a genetic screening before ruling out all secondary causes. LPL, apo CII and apo AV genes were negative for mutations. In the first appointment with us, the patient reported the use of a contraceptive agent for about 2 years. She was instructed to discontinue the drug. After one year of follow-up, her serum triglycerides are within the normal range and a copper intrauterine device was the method chosen by the patient for contraception.
Asunto(s)
Anticonceptivos Sintéticos Orales/efectos adversos , Estrógenos/efectos adversos , Etinilestradiol/efectos adversos , Hipertrigliceridemia/complicaciones , Norpregnenos/efectos adversos , Pancreatitis/etiología , Adulto , Humanos , Hipertrigliceridemia/inducido químicamenteRESUMEN
OBJECTIVES: Systemic sclerosis (SSc) is a chronic, autoimmune connective tissue disease with a female predominance. The reason for the female predilection in SSc may relate to the difference in hormones between the genders. There are no current data on the influence male-to-female sex transition may have in the development of SSc. We report three patients who developed SSc after initiating the transgender process, and review current literature in regards to transgender patients with connective tissue disease (CTD). METHODS: We describe the clinical features and disease course of three transgender patients who developed SSc after their transition from male-to-female, who presented to our centre. Two additional transgender cases de- scribed in the literature with CTD were included in this review. RESULTS: All three patients developed SSc after having started the hormonal therapy required to transition. Two patients had surgical procedures preceding their diagnosis of SSc. Antibody profile, time of onset and disease features differed among our patients. Hormonal therapies were continued in all patients and they received the standard therapy for SSc. One patient died from complications of her disease. Only two cases describing the development of CTD in transgender patients were identified in the literature and both of these patients were diagnosed with systemic lupus erythematosus (SLE). CONCLUSIONS: This case series suggests that the hormonal modification as part of gender transition may be relevant in development of SSc. No further conclusions can be drawn on the continuation or not of HT.