RESUMO
OBJECTIVE: This study aimed to evaluate the efficacy and safety of oral ultra-low-dose continuous combination of 17ß-estradiol (17ß-E2) and norethisterone acetate (NETA) in postmenopausal Brazilian women. METHODS: Postmenopausal women (age 45-60 years) with amenorrhea >12 months and intact uterus, with moderate to severe vasomotor symptoms, were included. The vasomotor symptoms and endometrial bleeding were evaluated by a daily diary for 24 weeks, and the women were assessed at baseline and endpoint. RESULTS: A total of 118 women were included. The group treated with 0.5 mg 17ß-E2/0.1 mg NETA (n = 58) showed a percentage reduction of 77.1% in the frequency of vasomotor symptoms versus 49.9% in the placebo group (n = 60) (p = 0.0001). The severity score showed a reduction in the treatment group when compared to the placebo (p < 0.0001). The adverse events were comparable between the groups; however, in the 0.5 mg 17ß-E2/0.1 mg NETA group there were more complaints of vaginal bleeding; despite that, in most cycles in both treatment groups, more than 80% of women experienced amenorrhea. CONCLUSIONS: The combination of 0.5 mg 17ß-E2/0.1 mg NETA in a continuous combination regimen was shown to be effective in reducing the frequency and severity of vasomotor symptoms in Brazilian postmenopausal women.
Assuntos
Estradiol , Noretindrona , Feminino , Humanos , Pessoa de Meia-Idade , Amenorreia , Brasil , Método Duplo-Cego , Estradiol/efeitos adversos , Terapia de Reposição de Estrogênios , Noretindrona/efeitos adversos , Acetato de Noretindrona/efeitos adversos , Pós-MenopausaAssuntos
Humanos , Feminino , Anticoncepcionais Pós-Coito/farmacologia , Contraceptivos Hormonais/administração & dosagem , Contraceptivos Hormonais/efeitos adversos , Contraceptivos Hormonais/uso terapêutico , Contraceptivos Hormonais/farmacologia , Progestinas , Progesterona , Testosterona , Protocolos Clínicos , Levanogestrel , Acetato de Medroxiprogesterona , Desogestrel , Medição de Risco , Contraindicações de Medicamentos , Eficácia de Contraceptivos , NoretindronaRESUMO
The Wobbler mouse has been proposed as an experimental model of the sporadic form of amyotrophic lateral sclerosis (ALS). The administration of natural progesterone (PROG) to Wobbler mice attenuates neuropathology, inhibits oxidative stress, enhances the expression of genes involved in motoneuron function, increases survival and restores axonal transport. However, current pharmacological treatments for ALS patients are still partially effective. This encouraged us to investigate if the synthetic progestin norethindrone (NOR), showing higher potency than PROG and used for birth control and hormone therapy might also afford neuroprotection. Two-month-old Wobbler mice (wr/wr) were left untreated or received either a 20â¯mg pellet of PROG or a 1â¯mg pellet of NOR for 18 days. Untreated control NFR/NFR mice (background strain for Wobbler) were also employed. Wobblers showed typical clinical and spinal cord abnormalities, while these abnormalities were normalized with PROG treatment. Surprisingly, we found that NOR did not increase immunoreactivity and gene expression for choline-acetyltransferase, drastically decreased GFAPâ¯+â¯astrogliosis, favored proinflammatory mediators, promoted the inflammatory phenotype of IBA1+ microglia, increased the receptor for advanced glycation end products (RAGE) mRNA and protein expression and the activity of nitric oxide synthase (NOS)/NADPH diaphorase in the cervical spinal cord. Additionally, NOR treatment produced atrophy of the thymus. The combined negative effects of NOR on clinical assessments (forelimb atrophy and rotarod performance) suggest a detrimental effect on muscle trophism and motor function. These findings reinforce the evidence that the type of progestin used for contraception, endometriosis or replacement therapy, may condition the outcome of preclinical and clinical studies targeting neurodegenerative diseases.
Assuntos
Modelos Animais de Doenças , Neurônios Motores/efeitos dos fármacos , Doenças Neurodegenerativas/tratamento farmacológico , Neuroproteção/efeitos dos fármacos , Noretindrona/farmacologia , Progesterona/farmacologia , Progestinas/farmacologia , Animais , Anticoncepcionais Orais Sintéticos/farmacologia , Camundongos , Neurônios Motores/patologiaAssuntos
Humanos , Feminino , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Terapia de Reposição Hormonal , Disfunções Sexuais Fisiológicas/terapia , Educação Sexual/métodos , Testosterona/uso terapêutico , Neurotransmissores , Sexualidade , Disfunções Sexuais Psicogênicas/terapia , Estrogênios/uso terapêutico , Noretindrona/uso terapêuticoRESUMO
A 23-year-old East Indian woman with no significant medical history, except a depot-norethisterone enanthate injection taken 3 weeks prior to admission, presented with a gradually worsening headache for the past 5 days. She had no fever, vomiting, neck stiffness, focal weakness or rash, and examination was unremarkable with no focal neurological deficits. Vasculitic, thrombophilia and sepsis screens were normal. A brain CT scan showed a left parietal lobe venous infarct, secondary to a venous dural sinus thrombosis, with MRI and Magnetic Resonance Venogram (MRV) confirming a signal void. She was diagnosed to have multiple cerebral venous sinus thrombosis due to norethisterone enanthate. She made a complete recovery following treatment with mannitol, dexamethasone and anticoagulants. A follow-up brain MRI done at 6 months was normal.
Assuntos
Anticoncepcionais Femininos/efeitos adversos , Noretindrona/análogos & derivados , Trombose dos Seios Intracranianos/induzido quimicamente , Anticoagulantes/uso terapêutico , Feminino , Cefaleia/etiologia , Heparina/uso terapêutico , Humanos , Injeções Intramusculares , Imageamento por Ressonância Magnética , Noretindrona/efeitos adversos , Lobo Parietal/diagnóstico por imagem , Trombose dos Seios Intracranianos/tratamento farmacológico , Adulto JovemRESUMO
OBJECTIVE: To evaluate the influence of estrogen therapy and estrogen-progestin therapy on homocysteine and C-reactive protein levels in postmenopausal women. METHODS: In total, 99 postmenopausal women were included in this double-blind, randomized clinical trial and divided into three groups: Group A used estrogen therapy alone (2.0 mg of 17ß-estradiol), Group B received estrogen-progestin therapy (2.0 mg of 17 ß-estradiol +1.0 mg of norethisterone acetate) and Group C received a placebo (control). The length of treatment was six months. Serum measurements of homocysteine and C-reactive protein were carried out prior to the onset of treatment and following six months of therapy. RESULTS: After six months of treatment, there was a 20.7% reduction in homocysteine levels and a 100.5% increase in C-reactive protein levels in the group of women who used estrogen therapy. With respect to the estrogen-progestin group, there was a 12.2% decrease in homocysteine levels and a 93.5% increase in C-reactive protein levels. CONCLUSION: Our data suggested that hormone therapy (unopposed estrogen or estrogen associated with progestin) may have a positive influence on decreasing cardiovascular risk due to a significant reduction in homocysteine levels.
Assuntos
Proteína C-Reativa/metabolismo , Terapia de Reposição de Estrogênios/métodos , Estrogênios/uso terapêutico , Homocisteína/sangue , Pós-Menopausa/sangue , Progestinas/uso terapêutico , Fatores Etários , Brasil , Doenças Cardiovasculares/prevenção & controle , Método Duplo-Cego , Combinação de Medicamentos , Estradiol/administração & dosagem , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Noretindrona/administração & dosagem , Noretindrona/análogos & derivados , Acetato de Noretindrona , Pacientes Desistentes do Tratamento , Estudos ProspectivosRESUMO
OBJECTIVE: To evaluate the influence of estrogen therapy and estrogen-progestin therapy on homocysteine and C-reactive protein levels in postmenopausal women. METHODS: In total, 99 postmenopausal women were included in this double-blind, randomized clinical trial and divided into three groups: Group A used estrogen therapy alone (2.0 mg of 17β-estradiol), Group B received estrogen-progestin therapy (2.0 mg of 17 β-estradiol +1.0 mg of norethisterone acetate) and Group C received a placebo (control). The length of treatment was six months. Serum measurements of homocysteine and C-reactive protein were carried out prior to the onset of treatment and following six months of therapy. RESULTS: After six months of treatment, there was a 20.7% reduction in homocysteine levels and a 100.5% increase in C-reactive protein levels in the group of women who used estrogen therapy. With respect to the estrogen-progestin group, there was a 12.2% decrease in homocysteine levels and a 93.5% increase in C-reactive protein levels. CONCLUSION: Our data suggested that hormone therapy (unopposed estrogen or estrogen associated with progestin) may have a positive influence on decreasing cardiovascular risk due to a significant reduction in homocysteine levels. .
Assuntos
Feminino , Humanos , Pessoa de Meia-Idade , Proteína C-Reativa/metabolismo , Terapia de Reposição de Estrogênios/métodos , Estrogênios/uso terapêutico , Homocisteína/sangue , Pós-Menopausa/sangue , Progestinas/uso terapêutico , Fatores Etários , Brasil , Doenças Cardiovasculares/prevenção & controle , Método Duplo-Cego , Combinação de Medicamentos , Estradiol/administração & dosagem , Seguimentos , Estudos Longitudinais , Noretindrona/administração & dosagem , Noretindrona/análogos & derivados , Pacientes Desistentes do Tratamento , Estudos ProspectivosRESUMO
OBJECTIVE: This study aims to compare the effects of a soy-based dietary supplement, low-dose hormone therapy (HT), and placebo on the urogenital system in postmenopausal women. METHODS: In this double-blind, randomized, placebo-controlled trial, 60 healthy postmenopausal women aged 40 to 60 years (mean time since menopause, 4.1 y) were randomized into three groups: a soy dietary supplement group (90 mg of isoflavone), a low-dose HT group (1 mg of estradiol plus 0.5 mg of norethisterone), and a placebo group. Urinary, vaginal, and sexual complaints were evaluated using the urogenital subscale of the Menopause Rating Scale. Vaginal maturation value was calculated. Transvaginal sonography was performed to evaluate endometrial thickness. Genital bleeding pattern was assessed. Statistical analysis was performed using χ(2) test, Fisher's exact test, paired Student's t test, Kruskal-Wallis test, Kruskal-Wallis nonparametric test, and analysis of variance. For intergroup comparisons, Kruskal-Wallis nonparametric test (followed by Mann-Whitney U test) was used. RESULTS: Vaginal dryness improved significantly in the soy and HT groups (P = 0.04). Urinary and sexual symptoms did not change with treatment in the three groups. After 16 weeks of treatment, there was a significant increase in maturation value only in the HT group (P < 0.01). Vaginal pH decreased only in this group (P < 0.01). There were no statistically significant differences in endometrial thickness between the three groups, and the adverse effects evaluated were similar. CONCLUSIONS: This study shows that a soy-based dietary supplement used for 16 weeks fails to exert estrogenic action on the urogenital tract but improves vaginal dryness.
Assuntos
Suplementos Nutricionais , Estradiol/farmacologia , Isoflavonas/farmacologia , Noretindrona/farmacologia , Pós-Menopausa/efeitos dos fármacos , Proteínas de Soja/farmacologia , Sistema Urogenital/efeitos dos fármacos , Adulto , Método Duplo-Cego , Terapia de Reposição de Estrogênios/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Fitoterapia , Pós-Menopausa/fisiologia , Ultrassonografia , Sistema Urogenital/diagnóstico por imagem , Doenças Vaginais/tratamento farmacológicoRESUMO
OBJECTIVE: This study compared the effects of a continuous-combined regimen of low-dose hormone therapy (LD-HT) versus tibolone and supplemental calcium/vitamin D3 (control) on quality of life (QoL) in symptomatic postmenopausal women. DESIGN: This study was a prospective, randomised, double-blind, comparative trial with a control group. SETTING: The study was conducted in a climacteric outpatient clinic in the University Hospital of Federal University of Juiz de Fora, Brazil. POPULATION: A total of 174 postmenopausal women under 60 years of age who attended the climacteric outpatient clinic between June 2009 and June 2011 were recruited. These women complained of moderate or intense vasomotor symptoms and exhibited no contraindications for the use of hormone therapy. INTERVENTIONS: The patients were randomised into three groups: (1) daily treatment with 2.5mg tibolone (n=64), (2) 50mg calcium carbonate+200 IU vitamin D3 (Ca/Vit D3, n=54) or (3) 1mg oestradiol+0.5mg norethindrone acetate (E2/NETA, n=56) for 12 weeks. PRIMARY OUTCOME MEASURES: The primary outcome was the evaluation of QoL using the Women's Health Questionnaire (WHQ) in all subjects at baseline and after 4, 8 and 12 weeks of treatment. RESULTS: A total of 130 women in the following groups completed the study: tibolone (n=42), Ca/Vit D3 (n=44) and E2/NETA (n=44). An improved QoL based on the WHQ was observed at T0 (80.12±14.04, 77.73±15.3, 77.45±15.4) and T12 (57.0±15.5, 55.7±16.7, 58.4±12.6) for the tibolone, E2+NETA and Ca/Vit D3 groups, respectively (p values <0.05). The three groups exhibited significantly different scores at T12 for sexual behaviour and vasomotor symptoms. The tibolone group exhibited better sexual function compared with the E2/NETA and Ca/Vit D3 groups (4.2±26, 5.6±2.8, 5.4±2.8, respectively, p values <0.05). LD-HT was superior to tibolone and Ca/Vit D3 treatment for improvements in vasomotor symptoms (3.2±1.5, 4.0±1.8, 4.3±2.0, respectively, p values <0.05). Adverse effects were few and mild. CONCLUSIONS: An improved QoL was observed in the three study groups. Tibolone primarily improved sexual function, and E2/NETA exhibited a superior response for vasomotor symptoms.