RESUMEN
BACKGROUND: Postmenopausal dyspareunia and vulvar pain are common complaints, affecting about 60% of women within a few years after hormone levels begin to decline (such as estrogen and androgen). Atrophic changes mainly located in the vulvar vestibule and vulnerability to vulvovaginal infections in postmenopause could be predisposing factors to the development of vulvar burning/pain and introital dyspareunia (vestibulodynia secondary to atrophy). Tibolone is the most effective and safe alternative for treating menopausal symptoms. The role of Lactobacilli and lactoferrin shows its effectiveness in the treatment of vaginal microbiota dysbiosis. The aim of the present study was to assess the efficacy of the combination of tibolone and an oral-specific Lactobacilli mixture in combination with bovine lactoferrin as synergistic therapy for the treatment of vestibulodynia related to atrophy. METHODS: In this study, we included 35 postmenopausal women with at least 1 year of amenorrhea, affected by vulvar burning/pain and introital dyspareunia. All participants received treatment with open-label, oral Tibolone 2.5 mg and Lactobacilli mixture (5 × 109 CFU per capsule) in combination with bovine lactoferrin (Respecta®). Each product was taken once daily for 90 days. RESULTS: After 90 d of therapy with TIB+ Respecta®, in 30 women that completed the treatment, there was a statistically significant decrease from the baseline in the mean of the Visual Analog Scale for vulvar burning/pain and a reduction in scores in the pain evaluation test. CONCLUSIONS: This study provides evidence that the combination of TIB+ Respecta® was effective in reducing symptoms related to vestibular pain and hypersensitivity in a postmenopausal setting.
Asunto(s)
Lactobacillus , Lactoferrina , Norpregnenos , Posmenopausia , Femenino , Humanos , Lactoferrina/administración & dosificación , Persona de Mediana Edad , Norpregnenos/administración & dosificación , Vulvodinia/tratamiento farmacológico , Vulvodinia/terapia , Probióticos/administración & dosificación , Resultado del Tratamiento , Dispareunia/tratamiento farmacológico , Dispareunia/terapia , Vulva/microbiologíaRESUMEN
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
Gestodene (GES) is widely used in human therapy and animal husbandry and is frequently detected in aquatic environments. Although GES adversely affects aquatic organisms at trace levels, its effects on the reproductive biology of fish remain inconclusive. In this study, female zebrafish (Danio rerio) were exposed to environmentally relevant levels of GES for the evaluation of the effects of GES on the reproductive system by using endpoints including gene expression, plasma steroid concentrations, histological and morphological analyses, copulatory behavior, and reproductive output. Adult female zebrafish exposed to environmentally relevant concentrations of GES (4.0, 40.2, and 372.7 ng/L) for 60 d demonstrated stagnant ovarian oocyte development, evidenced by an increase in the percentage of perinuclear and atretic oocytes and a decrease in the percentage of late vitellogenic oocytes. GES-exposed females were less attractive to males and had lower copulatory intimacy than females in control. Consequently, spawning (44.3-49.2 %) and egg fertilization rates (27.9-32.0 %) were decreased. The decreased survival of fertilized eggs and hatching rates were accompanied by increased malformations. These negative effects were associated with abnormal transcriptional levels of gonadal steroid hormones, which were regulated by genes (Hsd17ß3, Hsd11ß2, Hsd20ß, Cyp19a1a, and Cyp11b). Overall, our findings suggest that GES impairs the reproductive system of zebrafish, which may threaten population stability.
Asunto(s)
Norpregnenos , Contaminantes Químicos del Agua , Pez Cebra , Animales , Masculino , Humanos , Femenino , Pez Cebra/metabolismo , Ovario , Hormonas Esteroides Gonadales/metabolismo , Reproducción , Contaminantes Químicos del Agua/metabolismo , GónadasRESUMEN
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
Gonadal hormone deprivation (GHD) and decline such as menopause and bilateral oophorectomy are associated with an increased risk of neurodegeneration. Yet, hormone therapies (HTs) show varying efficacy, influenced by factors such as sex, drug type, and timing of treatment relative to hormone decline. We hypothesize that the molecular environment of the brain undergoes a transition following GHD, impacting the effectiveness of HTs. Using a GHD model in mice treated with Tibolone, we conducted proteomic analysis and identified a reprogrammed response to Tibolone, a compound that stimulates estrogenic, progestogenic, and androgenic pathways. Through a comprehensive network pharmacological workflow, we identified a reprogrammed response to Tibolone, particularly within "Pathways of Neurodegeneration", as well as interconnected pathways including "cellular respiration", "carbon metabolism", and "cellular homeostasis". Analysis revealed 23 proteins whose Tibolone response depended on GHD and/or sex, implicating critical processes like oxidative phosphorylation and calcium signalling. Our findings suggest the therapeutic efficacy of HTs may depend on these variables, suggesting a need for greater precision medicine considerations whilst highlighting the need to uncover underlying mechanisms.
Asunto(s)
Norpregnenos , Animales , Norpregnenos/farmacología , Femenino , Ratones , Proteómica/métodos , Moduladores de los Receptores de Estrógeno/farmacología , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/tratamiento farmacológico , Ratones Endogámicos C57BL , Masculino , Ovariectomía , Hormonas Gonadales/metabolismo , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/patologíaRESUMEN
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
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
IMPORTANCE: Menopause hormone therapy (MHT) effectively alleviates menopausal symptoms. However, it is generally not recommended for breast cancer survivors, although the scientific evidence is scarce. OBJECTIVE: This study aimed to establish eligibility criteria for use of the MHT in breast cancer survivors based on a systematic review and meta-analysis of the literature. EVIDENCE REVIEW: We conducted exhaustive literature searches until June 2022 in MEDLINE, The Cochrane Library, and EMBASE, using a tailored strategy with a combination of controlled vocabulary and search terms related to breast cancer survivors and MHT. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and assessed the risk of bias using the Cochrane and Risk of Bias in Non-randomized Studies - of Interventions tools. The quality of the evidence was graded according to grading quality of evidence and strength of recommendations criteria (A, high; B, moderate; C, low; and D, very low). We categorized MHT use into four levels: category 1 (no restrictions on use), category 2 (the benefits outweigh the risks), category 3 (the risks generally outweigh the benefits), and category 4 (MHT should not be used). FINDINGS: A total of 12 studies met the eligibility criteria. Analysis of the three randomized clinical trials using combined MHT or tibolone revealed no significant differences concerning tumor recurrence (relative risk [RR], 1.46; 95% CI, 0.99-2.24). A combined analysis of randomized clinical trials, prospective, and retrospective trials found no elevated risk of recurrence (RR, 0.85; 95% CI, 0.54-1.33) or death (RR, 0.91; 95% CI, 0.38-2.19). The eligibility criteria for patients with hormone receptor (HR)-positive tumors fell into categories 3B and 3C for combined MHT or estrogen alone and 4A for tibolone. For HR-negative tumors, the category was 2B and 2C. CONCLUSIONS AND RELEVANCE: Our findings suggest that MHT could be a viable treatment alternative for breast cancer survivors experiencing menopausal symptoms, especially those with HR-negative tumors. Personalized management is recommended for each peri/postmenopausal woman facing a diminished quality of life because of menopause symptoms. Further randomized trials are needed before considering changes to current standards of care.
Asunto(s)
Neoplasias de la Mama , Supervivientes de Cáncer , Menopausia , Humanos , Femenino , Terapia de Reemplazo de Estrógeno , Terapia de Reemplazo de Hormonas , Persona de Mediana Edad , Determinación de la Elegibilidad , Norpregnenos/uso terapéuticoRESUMEN
Abstract Objective To analyze the effects of estrogen alone or in combination with progestogens and tibolone (TIB) on the expression of the extracellular matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), of perlecan, and of heparanase (HPSE) of the vascular walls of the carotid arteries. Methods A total of 30 250-day-old ovariectomized Wistar rats were orally treated for 5 weeks with: a) 1 mg/kg of estradiol benzoate (EB); b) EB + 0.2 mg/kg of medroxyprogesterone acetate (MPA); c) EB + 0.2mg/kg of norethisterone acetate (NETA); d) EB + 2 mg/kg of dydrogesterone (DI); e) 1 mg/kg of TIB; f) placebo (CTR). Following treatment, the expression of mRNA for MMP-2, MMP-9, and HPSE was analyzed by realtime polymerase chain-reaction (PCR), and the expression of MMP-2, of MMP-9, of tissue inhibitor of metalloproteinase 2 (TIMP-2), and of perlecan was quantified by immunohistochemistry in the carotid arteries. Results The groups showed significant differences on mRNA HPSE expression (p = 0.048), which was higher in the EB, EB + MPA, and TIB groups. There was no statistically significant difference in mRNA MMP-2 or MMP-9 expression. The immunohistochemical expression of MMP-2, of TIMP-2, of MMP-9, of HPSE, and of perlecan showed no differences between groups. Conclusion Estradiol alone or associated with MPA and TIB treatment can increase mRNA HSPE expression of the walls of the carotid arteries in ovariectomized rats.
Resumo Objetivo Analisar os efeitos do estrogênio isolado ou em combinação com progestogênios e tibolona (TIB) na expressão das metaloproteinases 2 e 9 da matriz extracelular (MMP-2 e MMP-9), da perlecan e da heparanase (HPSE) das paredes vasculares das artérias carótidas. Métodos Trinta ratas Wistar ovariectomizadas com 250 dias de idade foram tratadas oralmente por 5 semanas com: a) 1 mg/kg de benzoato de estradiol (EB); b) EB + 0,2 mg/kg de acetato de medroxiprogesterona (MPA); c) EB + 0,2mg/kg de acetato de noretisterona (NETA); d) EB + 2 mg/kg de didrogesterona (DI); e) 1 mg/kg de TIB; f) placebo (CTR). Após o tratamento, a expressão de mRNA para MMP-2, MMP- 9, e HPSE foi analisada por reação em cadeia da polimerase (RCP) em tempo real, e a expressão de MMP-2, MMP-9, inibidor tecidual de metaloproteinase 2 (TIMP-2), e de perlecan foi quantificado por imunohistoquímica em artérias carótidas. Resultados Os grupos apresentaram diferenças significativas na expressão do mRNA HPSE (p = 0,048), sendo maiores nos grupos EB, EB + MPA e TIB. Não houve diferença estatisticamente significativa nas expressões de mRNA MMP-2 ou MMP-9. A expressão imunohistoquímica de MMP-2, TIMP-2, MMP-9, HPSE e perlecan não mostrou diferenças entre os grupos. Conclusão O estradiol isolado ou associado ao tratamento com MPA e TIB pode aumentar a expressão de mRNA HSPE nas paredes das artérias carótidas em ratas ovariectomizadas.
Asunto(s)
Animales , Femenino , Ratas , Progestinas/farmacología , Arterias Carótidas/enzimología , Liasa de Heparina/efectos de los fármacos , Estradiol/análogos & derivados , Agentes Anticonceptivos Hormonales/farmacología , Norpregnenos/farmacología , Progestinas/administración & dosificación , Ovariectomía , Arterias Carótidas/efectos de los fármacos , Terapia de Reemplazo de Estrógeno , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Administración Oral , Ratas Wistar , Liasa de Heparina/genética , Liasa de Heparina/metabolismo , Proteoglicanos de Heparán Sulfato/genética , Proteoglicanos de Heparán Sulfato/metabolismo , Metaloproteinasa 2 de la Matriz/efectos de los fármacos , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/efectos de los fármacos , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Modelos Animales , Estradiol/administración & dosificación , Estradiol/farmacología , Agentes Anticonceptivos Hormonales/administración & dosificación , Norpregnenos/administración & dosificaciónRESUMEN
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
OBJETIVO: Avaliar o efeito da terapia hormonal com tibolona, em três períodos de tempo diferentes, sobre o tecido mamário de ratas castradas. MÉTODO: Foram utilizadas 60 ratas Wistar adultas e virgens, submetidas à ooforectomia. Após 21 dias de pós-operatório (PO), confirmado o hipoestrogenismo, os animais foram divididos aleatoriamente em 6 grupos: tibolona 1 (n=10) recebeu tibolona 1 mg/dia por 23 dias, tibolona 2 (n=10), por 59 dias, tibolona 3 (n=10), por 118 dias; os subgrupos controle 1 (n=8), controle 2 (n=7) e controle 3 (n=10) receberam a água destilada por 23, 59 e 118 dias, respectivamente. Após o tratamento, foram ressecados seis pares de mamas, destinados à análise histológica pela coloração de hematoxilina e eosina (HE); o procedimento seguiu de eutanásia. Os parâmetros histológicos avaliados foram: hiperplasia epitelial e atividade secretora (AS). As variáveis foram submetidas à análise estatística, adotando-se como significante p<0,05. RESULTADOS: Foram observadas alterações histológicas em 20/55 ratas, sendo: hiperplasia epitelial leve (HEB1) em 7/55, hiperplasia epitelial moderada (HEB2) em 5/55, hiperplasia alvéolo-nodular (HAN) em 7/55, atipia sem proliferação epitelial em 1/55, não sendo encontrada hiperplasia severa (HEB3). Encontrou-se AS em 31/55 das ratas. A AS foi significativamente maior no grupo tibolona (T), em todos os tempos avaliados (p=0,001). As alterações histológicas analisadas não foram significantes comparando (p>0,05) os grupos controle (C) e T. A variável tempo de exposição à droga não apresentou significância, quando comparados os três períodos avaliados. CONCLUSÃO: Não foi verificada relação entre as alterações histológicas e a terapêutica com tibolona em curto, médio e longo prazo. .
OBJECTIVE: To assess the effect of tibolone on mammary tissue of castrated rats over 3 different periods of time. METHODS: Sixty virgin female Wistar rats were submitted to oophorectomy. Twenty-one days after surgery, with hypoestrogenism confirmed, the experimental rats were randomly assigned to six groups: Tibolone 1 (n=10) received tibolone 1 mg/day for 23 days, tibolone 2 (n=10) for 59 days and tibolone 3 (n=10) for 118 days. The groups control 1 (n=8), control 2 (n=7) and control 2 (n=10) received distilled water for 23, 59 and 118 days, respectively. After treatment, all six pairs of mammary glands were removed and stained with hematoxylin and eosin (HE) for histological analysis after euthanasia. The histological parameters evaluated were: epithelial cell proliferation and secretory activity. The variables were analyzed statistically, with the level of significance set at 0.05. RESULTS: Histological changes were observed in 20/55 rats, mild epithelial hyperplasia in 7/55, moderate epithelial hyperplasia in 5/55, alveolar-nodular hyperplasia in 7/55, atypia without epithelial proliferation in 1/55, and no cases of severe epithelial hyperplasia were found. Secretory activity was observed in 31/55 rats. The secretory activity was significantly higher in the tibolone groups compared to control at all the time points assessed (p=0,001). The histological changes were did not show significance when the control and tibolone groups were compared. The time of exposure to tibolone did not show significance when the three different periods of evaluation were compared. CONCLUSION: No relation between histological modification and tibolone treatment was verified after short-, medium- and long-term treatment. .
Asunto(s)
Animales , Femenino , Ratas , Moduladores de los Receptores de Estrógeno/farmacología , Glándulas Mamarias Animales/efectos de los fármacos , Norpregnenos/farmacología , Distribución Aleatoria , Ratas Wistar , Factores de TiempoRESUMEN
<p><b>BACKGROUND</b>As a Chinese Traditional Medicine product, Kuntai capsule could improve the peri-menopausal symptoms in postmenopausal women. But it is still not clear whether Kuntai capsule has a good effect on alleviating peri-menopausal symptoms induced by gonadotropin releasing hormone agonist (GnRH-a) treatment. The purpose of this study was to investigate the clinical effectiveness and safety of Kuntai capsule, on peri-menopausal symptoms in endometriosis (EMS) patients, with postoperative GnRH-a treatment.</p><p><b>METHODS</b>Ninety EMS ovarian cyst women with postoperative GnRH-a administration were enrolled in the study, and were randomly divided into Kuntai group, Tibolone group, or blank Control group. The therapeutic strategy in Kuntai group was 4 Kuntai capsules tid,po for 12 weeks after the first GnRH-a injection, while Tibolone 2.5 mg qd, po for 12 weeks in Tibolone group. There was no drug addition in Control group. Climacteric complaints were evaluated by Kupperman menopausal index (KMI) and hot flash/sweating score. Liver and renal functions, lipid profile, serum sex hormone levels and endometrial thickness were measured, and the frequency of adverse events in Kuntai and Tibolone groups was recorded.</p><p><b>RESULTS</b>(1) Before GnRH-a therapy, the baseline parameter results were comparable in the three groups (P > 0.05). (2) After GnRH-a therapy, KMI and hot flash/sweating scores in all the three groups increased significantly (P < 0.05). At the 4 th week after GnRH-a therapy, KMI and hot flash/sweating score results were as follows: Control group > Kuntai group > Tibolone group (P < 0.05); at the 8 th and 12 th week after GnRH-a therapy, KMI and hot flash/sweating score in Control group were significantly higher than the other two groups (P < 0.05), and no significant difference was identified between Kuntai and Tibolone group (P > 0.05). (3) No statistical change took place in the liver and renal functions and lipid profile in all the three groups after the treatment (P > 0.05). (4) The posttherapeutic serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) level and endometrial thickness decreased significantly in all the three groups (P < 0.05). After therapy, serum E2 level in Tibolone group was obviously higher than the other two groups (P < 0.05), while FSH and LH levels were obviously lower (P < 0.05). (5) The incidence of vaginal bleeding, breast distending pain in Tibolne group was obviously higher than Kuntai group (P < 0. 05).</p><p><b>CONCLUSIONS</b>Kuntai capsule is effective on the peri-menopausal symptoms induced by postoperative GnRH-a administration to EMS patients, although its clinical effect might be a few weeks later than Tibolone. Kuntai capsule might be a little safer than Tibolone tablet.</p>
Asunto(s)
Adulto , Femenino , Humanos , Adulto Joven , Método Doble Ciego , Medicamentos Herbarios Chinos , Usos Terapéuticos , Endometriosis , Quimioterapia , Endometrio , Patología , Hormona Liberadora de Gonadotropina , Goserelina , Usos Terapéuticos , Norpregnenos , Usos TerapéuticosRESUMEN
This study taking gestodene (GEST) as a model, investigated the factors affecting reservoir-type intravaginal ring (IVR)'s drug release. This paper reported a gestodene intravaginal ring of reservoir design, comprising a gestodene silicone elastomer core encased in a non-medicated silicone sheath, separately manufactured by reaction injection moulding at 80 degrees C and heating vulcanization at 130 degrees C is reported. The test investigated the factors affecting drug release through a single variable method, taking the drug release rates of 21 days as standards. When changing the thickness of the controlling sheath outside, the ratio of the first day of drug release and mean daily release (MDR), named the relatively burst effect, is closing to 1 with the thickness of controlling sheath increasing, while the 1.25 mm sheath corresponding to 1.04 controlled the burst release effectively; a positive correlation (r = 0.992 2) existed between the average drug release (Q/t) and drug loading (A) within a certain range. The C6-165 controlling sheath with high solubility of GEST is easier to achieve controlled release of the drug; GEST crystalline power is more effective to implement controlled release of drugs among difficent states of the drug. A 1/4 fractional segment core gives a relatively burst effect of 1.76, while the 1/1 and 1/2 are 1.93 and 1.87 separately, at the same drug loading, concluding that use of a fractional segment core would allow development of a suitable GEST reservoir IVR. In summary, GEST reservoir-type IVR could be adjusted by the thickness of controlling sheath, the loading of drug, the material properties of controlling sheath, the dispersion state of drug, the additive composition and structure of intravaginal ring, to control the drug release behavior and achieve the desired drug release rate.
Asunto(s)
Administración Intravaginal , Anticonceptivos Femeninos , Dispositivos Anticonceptivos Femeninos , Preparaciones de Acción Retardada , Sistemas de Liberación de Medicamentos , Métodos , Norpregnenos , Química , Elastómeros de Silicona , Química , SolubilidadRESUMEN
El objetivo principal del tratamiento en la mujer con mioma uterino es el control de los síntomas asociados como sangrado uterino anormal, dolor o presión. Aunque el coste y los posibles efectos adversos del uso a largo plazo del tratamiento médico pueden limitar su uso durante un tiempo prolongado, esta alternativa debe contemplarse antes de la indicación de un tratamiento quirúrgico. En la actualidad disponemos de una gran variedad de fármacos que, aunque no son un tratamiento específico para los miomas, pueden ser usados para el control del sangrado a corto-medio plazo, pero aún no hemos encontrado ninguna alternativa que permita eliminar la necesidad de tratamientos invasivos, por lo que es necesario continuar con la investigación en este campo. Dada la heterogeneidad de los miomas y la falta de tratamientos efectivos en el control de su crecimiento, la identificación de las señales que estimulan la iniciación y el crecimiento de este abre las puertas al desarrollo de nuevas terapias. Es posible que en el futuro se puedan diferenciar clases de miomas por técnicas moleculares y así aplicar el tratamiento específico, que controle su desarrollo y los síntomas asociados a él (AU)
The main objective of treatment in women with uterine fibroids is the control of associated symptoms such as abnormal uterine bleeding, pain and pressure. Although the cost and potential adverse effects of the long-term use of medical treatment may limit its use for a long time, this alternative should be considered before indicating surgical treatment. At present, we have a considerable variety of drugs that, although not specific treatments for fibroids, may be used for the short to medium-term management of bleeding; however, we have still not found an alternative that eliminates the need for invasive treatments. Further research in this field is therefore warranted. Given the heterogeneity of fibroids and the lack of effective treatments in controlling their growth, the identification of signals that stimulate the onset and growth of these fibroids opens doors to the development of new therapies. In the future we may be able to differentiate classes of fibroids by molecular techniques and thereby implement specific treatments that control their development and their associated symptoms (AU)
Asunto(s)
Femenino , Humanos , Estrógenos/uso terapéutico , Leiomioma/complicaciones , Leiomioma/cirugía , Hemorragia Uterina/tratamiento farmacológico , Hemorragia Uterina/etiología , Neoplasias Uterinas/complicaciones , Neoplasias Uterinas/cirugía , Progestinas/uso terapéutico , Terapia Combinada , Anticonceptivos Femeninos/uso terapéutico , Anticonceptivos Orales Combinados/uso terapéutico , Anticonceptivos Hormonales Orales/uso terapéutico , Moduladores de los Receptores de Estrógeno/uso terapéutico , Histerectomía , Levonorgestrel/uso terapéutico , Norpregnenos/uso terapéutico , Progesterona/uso terapéutico , Resultado del TratamientoRESUMEN
PURPOSE: To verify the effects of tibolone administration on trabecular and cortical bone of ovariectomized female rats by computed radiography system (CRS). METHODS: The experiment was performed on two groups of rats previously ovariectomized, one received tibolone (OVX+T) while the other did not (OVX), those groups were compared to a control group (C) not ovariectomized. Tibolone administration (1mg/day) began thirty days after the ovariectomy and the treatment remained for five months. At last, the animals were euthanized and femurs and tibias collected. Computed radiographies of the bones were obtained and the digital images were used to determine the bone optical density and cortical thickness on every group. All results were statistically evaluated with significance set at P<0.05 percent. RESULTS: Tibolone administration was shown to be beneficial only in the densitometric analysis of the femoral head, performing higher optical density compared to OVX. No difference was found in cortical bone thickness. CONCLUSION: Ovariectomy caused bone loss in the analyzed regions and tibolone administered in high doses over a long period showed not to be fully beneficial, but preserved bone mass in the femoral head.
OBJETIVO: Verificar o efeito da administração de tibolona no tecido ósseo cortical e trabecular de ratas castradas através de radiografia computadorizada. MÉTODOS: O experimento foi realizado em dois grupos de ratas previamente ooforectomizadas, onde um grupo recebeu tibolona (OVX+T) e o outro não (OVX). Esses grupos foram comparados a um grupo controle (C) não ooforectomizado. A administração de tibolona (1mg/dia) começou trinta dias após a ooforectomia e o tratamento teve duração de cinco meses. No final, os animais foram mortos e fêmures e tibias coletados. As radiografias computadorizadas dos ossos foram obtidas e as imagens digitais usadas para determinar a densidade óssea e a espessura cortical em todos os grupos. Todos os resultados foram avaliados estatisticamente com significância estabelecida a 5 por cento. RESULTADOS: A administração de tibolona mostrou ser benéfica apenas para análise densitométrica da cabeça do fêmur, apresentando maiores valores de densidade comparada ao grupo OVX. Nenhuma diferença significativa foi encontrada para espessura óssea cortical. CONCLUSÃO: A ooforectomia ocasionou perda óssea nas regiões analisadas e a tibolona administrada, em dose elevada e durante um longo período, mostrou não ser totalmente benéfica, porém preservou a massa óssea na cabeça femoral.
Asunto(s)
Animales , Femenino , Ratas , Densidad Ósea/efectos de los fármacos , Moduladores de los Receptores de Estrógeno/efectos adversos , Estrógenos/deficiencia , Fémur , Norpregnenos/efectos adversos , Ovariectomía/efectos adversos , Tibia , Modelos Animales de Enfermedad , Métodos Epidemiológicos , Moduladores de los Receptores de Estrógeno/administración & dosificación , Fémur/efectos de los fármacos , Fémur/patología , Procesamiento de Imagen Asistido por Computador , Norpregnenos/administración & dosificación , Ratas Wistar , Tibia/efectos de los fármacos , Tibia/patologíaRESUMEN
OBJECTIVES: This study was performed to assess the risk factors, histologic and clinical features of breast cancer in postmenopausal women receiving hormone therapy (HT). METHODS: We evaluated 40 breast cancer patients who received HT due to postmenopausal symptoms by reviewing their medical charts at Pusan National University Hospital. Research variables, including patients' history, type and duration of received HT, moment of cancer debut after starting HT, radiological characteristics of breast cancer stage, histologic type, tumor size, grade, lymph node metastasis, estrogen and progesterone receptor status and 5-year survival were investigated. RESULTS: In the risk factors of breast cancer patients, only one patient had familial history of breast cancer. No patient had smoking history. The average body mass index (BMI) was 23.2 kg/m2. Twelve patients (30%) had estrogen only therapy, 13 patients (32.5%) had combined estrogen and progesterone therapy, 10 patients (25%) had tibolone therapy and the others consecutively received combination therapy of the above regimens. The mean duration of treatment was 31 +/- 27.9 months (range 0.4-115 months). In the distribution of the cancer debut after starting HT, in 4 cases (10%) was within 1 year, 5 cases (12.5%) within 1-2 years, 10 cases (25%) within 2-3 years, 4 cases (10%) within 3-4 years, 1 case (2.5%) within 4-5 years, and 16 cases (40%) within more than 5 years. The average diameter of tumor size was 1.7 cm. In 92.5% of cases, the tumor was of ductal type. Tumor stage 0 and 1 appeared in 66% and grade I was present in 38% of investigated cases. Hormone receptor-positive breast cancers were 85% and 70% of patients had negative lymph node metastases. The 5-year survival rate was 92%. CONCLUSION: The breast cancers which emerged during HT in postmenopausal women had hormone receptor-positive tendency. The size and stage of these breast cancers were shown as small and low, and represented low-grade differentiation. Recurrences of disease were uncommon and we found favorable 5-year survival rates and good prognosis.
Asunto(s)
Femenino , Humanos , Índice de Masa Corporal , Mama , Neoplasias de la Mama , Estrógenos , Ganglios Linfáticos , Metástasis de la Neoplasia , Norpregnenos , Progesterona , Pronóstico , Receptores de Progesterona , Recurrencia , Factores de Riesgo , Humo , Fumar , Tasa de SupervivenciaRESUMEN
OBJECTIVES: To investigate the differences between the effect of tibolone and estradiol (E2)-based hormone therapy (HT) on bone mineral density (BMD) and serum lipid profiles in postmenopausal Korean women. MATERIALS AND METHODS: A retrospective study was conducted with 65 postmenopausal women receiving tibolone or E2-based hormone therapy in university hospital. BMD at lumbar spine (LS) and proximal femur was measured before and after 1 year of therapy and serum total cholesterol, triglyceride (TG) and high-density lipoprotein (HDL) was determined by enzymatic methods. RESULTS: BMD at LS increased after 1 year of tibolone (mean change: 3.0%) or E2-based HT (mean change: 1.6%), and the changes were significant (P=0.002 and 0.04, respectively). In E2 group, serum total cholesterol has decreased significantly after 1 year of therapy (P=0.02). Moreover, the change of HDL level was statistically significant in tibolone group compared to E2 group (P=0.01). The changes of levels of total cholesterol, TG and HDL has demonstrated negative relationship of BMD changes at femur neck and trochanter in tibolone group, whereas only the HDL changes were significantly related to the change of trochanter BMD in E2 group. CONCLUSIONS: Both tibolone and E2-based hormone therapy increased BMD at lumbar spine. The changes of serum lipid levels may be associated with the BMD changes in both groups although the relationships were different according to the regimen.
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Femenino , Humanos , Densidad Ósea , Colesterol , Estradiol , Fémur , Cuello Femoral , Lipoproteínas , Norpregnenos , Estudios Retrospectivos , Columna VertebralRESUMEN
OBJECTIVES: To describe prescription patterns by gynecologists for osteoporosis therapy and to compare with the prescription patterns by physicians of other medical specialties based on the data from the Health Insurance Review and Assessment Service. METHODS: A total of 28,568 prescription claims by gynecologists of 633,870 prescription claims by physicians with medications for osteoporosis alone or medications for other indications, including osteoporosis, were analyzed. The medications for osteoporosis alone were, selective estrogen receptor modulators (SERMs), calcitonin (injection or nasal spray), vitamin K2, ipriflavone, and fluoride. The medications for other indications including osteoporosis were estrogen, tibolone, testosterone, calcium, calcium-vitamin D complex, vitamin D, and oxymetholone. RESULTS: Anti-osteoporosis medications were prescribed by 4.7% of gynecologists. Calcium and vitamin D were the most commonly prescribed medications by gynecologists (60.7%), followed by hormones, including tibolone (44%). Bisphosphonates, including bisphosphonate complex, were prescribed by 27.5% of gynecologists and SERMs were prescribed by 3.6% of gynecologists. Amongst all prescribers, the percentage of gynecologists was highest for hormones (50.6%), followed by tibolone (31.0%). When both medications were combined, the percentage of gynecologists among prescribers was 81.6%. The combination rate of calcium with other anti-osteoporosis medications was highest in gynecologists among prescribers of medical specialties (34.1%). CONCLUSION: A very small percentage of gynecologists prescribed anti-osteoporosis medications, while calcium, vitamin D, and hormones, including tibolone, were commonly prescribed by gynecologists.
Asunto(s)
Calcitonina , Calcio , Difosfonatos , Estrógenos , Fluoruros , Seguro de Salud , Isoflavonas , Norpregnenos , Osteoporosis , Prescripciones , Moduladores Selectivos de los Receptores de Estrógeno , Testosterona , Vitamina D , Vitamina K 2RESUMEN
OBJECTIVES: To describe prescription patterns by gynecologists for osteoporosis therapy and to compare with the prescription patterns by physicians of other medical specialties based on the data from the Health Insurance Review and Assessment Service. METHODS: A total of 28,568 prescription claims by gynecologists of 633,870 prescription claims by physicians with medications for osteoporosis alone or medications for other indications, including osteoporosis, were analyzed. The medications for osteoporosis alone were, selective estrogen receptor modulators (SERMs), calcitonin (injection or nasal spray), vitamin K2, ipriflavone, and fluoride. The medications for other indications including osteoporosis were estrogen, tibolone, testosterone, calcium, calcium-vitamin D complex, vitamin D, and oxymetholone. RESULTS: Anti-osteoporosis medications were prescribed by 4.7% of gynecologists. Calcium and vitamin D were the most commonly prescribed medications by gynecologists (60.7%), followed by hormones, including tibolone (44%). Bisphosphonates, including bisphosphonate complex, were prescribed by 27.5% of gynecologists and SERMs were prescribed by 3.6% of gynecologists. Amongst all prescribers, the percentage of gynecologists was highest for hormones (50.6%), followed by tibolone (31.0%). When both medications were combined, the percentage of gynecologists among prescribers was 81.6%. The combination rate of calcium with other anti-osteoporosis medications was highest in gynecologists among prescribers of medical specialties (34.1%). CONCLUSION: A very small percentage of gynecologists prescribed anti-osteoporosis medications, while calcium, vitamin D, and hormones, including tibolone, were commonly prescribed by gynecologists.