RESUMO
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 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.
Assuntos
Estradiol/uso terapêutico , Terapia de Reposição de Estrogênios/métodos , Noretindrona/análogos & derivados , Norpregnenos/uso terapêutico , Pós-Menopausa , Qualidade de Vida , Afeto , Carbonato de Cálcio/uso terapêutico , Colecalciferol/uso terapêutico , Anticoncepcionais Orais Sintéticos/uso terapêutico , Suplementos Nutricionais , Método Duplo-Cego , Quimioterapia Combinada , Moduladores de Receptor Estrogênico/uso terapêutico , Estrogênios/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Noretindrona/uso terapêutico , Acetato de Noretindrona , Comportamento Sexual , Estatísticas não Paramétricas , Inquéritos e Questionários , Vitaminas/uso terapêuticoRESUMO
OBJECTIVE: To compare the effects of the abrupt discontinuation of postmenopausal hormone therapy (HT) and reduction of the daily dosage of the hormone on climacteric symptoms. METHODS: The study included Brazilian postmenopausal women who were using estrogen-progestogen hormone therapy in full doses previously prescribed for vasomotor symptoms. The patients were randomized to receive one of three treatments: placebo for 6 months; estradiol (E2) 1 mg/day + norethisterone acetate (NETA) 0.5 mg/day for 2 months, followed by placebo for 4 months; or E2 1 mg/day + NETA 0.5 mg/day for 4 months, followed by placebo for 2 months. The climacteric symptoms were assessed by the Blatt-Kupperman Menopausal Index at baseline and at 2, 4 and 6 months. Statistical evaluation was performed using the chi(2) or Fisher's test for categorical data, the Kruskal-Wallis test for numerical data, and ANOVA for time and group relationship with the Blatt-Kupperman Menopausal Index. RESULTS: We randomized 60 women (20 in each group), and 54 completed the study. It was observed that both the full Blatt-Kupperman Menopausal Index and the hot flush score did not change significantly in the HT group during low-dose therapy compared with baseline; however, the evaluation performed at 2 months after low-dose-HT cessation showed that the full Blatt-Kupperman Menopausal Index and the hot flush score were similar to those of the group who stopped HT abruptly and significantly higher than at baseline (hot flush scores: p < 0.001 for all three groups at months 2, 4 and 6, respectively, vs. baseline). CONCLUSION: Discontinuation of HT by reducing the daily dose of estrogen for a period of 2 or 4 months did not differ in its effect from that of abrupt cessation with regard to vasomotor symptoms.
Assuntos
Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios/métodos , Fogachos/epidemiologia , Feminino , Fogachos/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Noretindrona/administração & dosagem , Noretindrona/análogos & derivados , Acetato de Noretindrona , Placebos , Fatores de TempoRESUMO
STUDY OBJECTIVE: To compare in a regular non-clinical trial experience the efficacy, acceptability, and continuation rates of an injectable contraceptive containing 50 mg norethisterone enanthate plus 5mg estradiol valerate (IC) and an oral contraceptive containing 0.15 mg levonorgestrel plus 0.03 mg ethinyl estradiol (OC), among adolescent users. DESIGN: A total of 251 adolescents ages 14-19 were followed during 12 months. The IC group (124 subjects) was studied for 1044 cycles and the OC group (127 subjects) was studied for 1368 cycles. The users were not assigned in a random selection. Information was collected from clinical records. Groups were compared using Pearson chi-square, odds ratio (95% confidence interval), t-test, and proportion difference test. RESULTS: The IC group had significant differences in baseline social risk, confidence, psychiatric problems, consumption of alcohol, and number of sexual partners. At 12 months, the IC group showed significant decrease in weight and increase in hypermenorrhea. In the OC group, dysmenorrhea decreased, and hypomenorrhea and regular cycles were significantly more frequent. One pregnancy occurred in the OC group (Pearl Index: 0.88). Final continuation rates at 12 months were 41.9% and 37.8% for IC and OC, respectively. CONCLUSIONS: The monthly injectable is a recommended contraceptive option for adolescents, especially for those facing psychosocial risk factors.
Assuntos
Anticoncepcionais Orais Combinados/administração & dosagem , Estradiol/análogos & derivados , Adesão à Medicação , Noretindrona/análogos & derivados , Adolescente , Instituições de Assistência Ambulatorial , Anticoncepcionais Orais Combinados/efeitos adversos , Esquema de Medicação , Combinação de Medicamentos , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Etinilestradiol/administração & dosagem , Etinilestradiol/efeitos adversos , Feminino , Humanos , Injeções Intramusculares , Levanogestrel/administração & dosagem , Levanogestrel/efeitos adversos , Noretindrona/administração & dosagem , Noretindrona/efeitos adversos , Satisfação do Paciente , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: The contraceptive effect of the progestogen norethisterone (NET) and its main metabolites 5alpha-NET and 3beta,5alpha-NET has been demonstrated in several species, and most studies have focused on the effects of these compounds in the uterus. We previously reported that 5alpha-NET inhibits the progesterone (P(4))-induced acrosome reaction in pig and mouse spermatozoa and induces severe morphological damage in two-cell fertilized mouse oocytes. STUDY DESIGN: The main goal of this study was to analyze the possible role of P(4) receptor (PR) in the effects of NET and 5alpha-NET on the oocyte fertilization process. Different steroid treatments were used with or without cumulus-enclosed oocytes. RESULTS: It was demonstrated that NET increases the percentage of fertilized oocytes in the same manner as P(4) does, while 5alpha-NET reduces the percentage of fertilized oocytes. This effect was not reversed by P(4) in the same concentrations. CONCLUSION: A possible molecular mechanism for the effects of 5alpha-NET may be through a PR localized in the oocyte plasma membrane.
Assuntos
Anticoncepcionais Orais Sintéticos/farmacologia , Fertilização/efeitos dos fármacos , Noretindrona/farmacologia , Oócitos/metabolismo , Receptores de Progesterona/efeitos dos fármacos , Reação Acrossômica , Animais , Feminino , Fertilização/fisiologia , Fertilização in vitro , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Noretindrona/análogos & derivados , Distribuição Aleatória , Receptores de Progesterona/metabolismoRESUMO
OBJECTIVE: To evaluate the correlation between homocysteine levels and carotid vascular resistance in menopausal women submitted to estrogen and estrogen-progestogen therapy. METHODS: Eighty-six women with a mean age of 52 years were enrolled in a prospective, randomized, double-blind, 6-month study. Patients were allocated to use one of three oral therapies: placebo (n = 26), micronized estradiol 2 mg/day (n = 30) or micronized estradiol 2 mg/day plus norethisterone acetate 1 mg/day (n = 30). Evaluation of homocysteine levels and Doppler sonography of the common carotid artery, used to calculate pulsatility index (PI), were carried out prior to initiating therapy and at the end of the study. The correlation between these two parameters was evaluated using Pearson's coefficient of correlation. RESULTS: There was a significant reduction in homocysteine levels in the groups treated with estrogen alone or estrogen combined with norethisterone. PI was significantly lower only in users of estrogen alone; however, no significant correlation was found between homocysteine measurements and PI. CONCLUSION: No significant correlation was found between homocysteine levels and carotid vascular resistance following hormone therapy.
Assuntos
Artéria Carótida Primitiva/fisiologia , Estradiol/administração & dosagem , Homocisteína/sangue , Menopausa , Noretindrona/análogos & derivados , Artéria Carótida Primitiva/diagnóstico por imagem , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Noretindrona/administração & dosagem , Acetato de Noretindrona , Placebos , Estudos Prospectivos , Fluxo Pulsátil , Ultrassonografia , Resistência VascularRESUMO
OBJECTIVE: This study aimed to evaluate the effects of monophasic estrogen-progestogen therapy on the sexuality and climacteric symptoms of postmenopausal women. PATIENTS AND METHODS: A prospective, randomised, double-blind, crossover, placebo-controlled, single-centre study was carried out over a total of 12 consecutive months in 40 postmenopausal women with an intact uterus who had no contraindications to hormone therapy. Patients received 17beta-estradiol 2mg in combination with norethisterone acetate 1mg (Cliane) daily for 6 months or one placebo tablet daily for 6 months. The tablets were identical in appearance. After 6 months, the groups were crossed over and the patients were followed up for another 6 months. The groups were homogenous with respect to age, height, bodyweight, body mass index and race. For the statistical analysis, the group receiving hormone therapy was referred to as group A and the placebo group was designated group B, irrespective of the placebo/hormone therapy sequence. RESULTS: In group A there were fewer hot flashes (F=22.85, p<0.01) and an improvement in sexual interest (F=5.55, p<0.05). The sequence in which the medication was received resulted in a statistically significant difference with respect to dyspareunia (F=9.65, p<0.01) and satisfaction with the duration of penetration (F=6.58, p<0.05). In the intrapatient analysis of variation with respect to orgasmic capability and the presence of dialogue with partner regarding the couple's sexual life, whether the placebo was taken prior to or following hormone therapy was significant (F=17.12, p<0.001 and F=7.10, p<0.05, respectively). CONCLUSIONS: Monophasic estrogen-progestogen therapy has a beneficial effect on sexuality and on hot flashes in postmenopausal women.
Assuntos
Estradiol/uso terapêutico , Terapia de Reposição Hormonal , Noretindrona/análogos & derivados , Pós-Menopausa/efeitos dos fármacos , Adulto , Estudos Cross-Over , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Fogachos/tratamento farmacológico , Humanos , Libido/efeitos dos fármacos , Pessoa de Meia-Idade , Noretindrona/uso terapêutico , Acetato de Noretindrona , Satisfação Pessoal , Pós-Menopausa/fisiologia , Congêneres da Progesterona/uso terapêuticoRESUMO
BACKGROUND: Arterial hypertension and postmenopausal reduction of estrogen levels may be involved in modifications of the stiffness of large arteries. OBJECTIVES: To evaluate the pulse-wave velocity (PWV) and indirectly the arterial stiffness in hypertensive postmenopausal women submitted to hormone therapy with estradiol alone or combined with norethisterone acetate. SUBJECTS: Forty-five hypertensive postmenopausal women were double-blindly, randomly assigned to three arms of treatment: placebo (group I); estradiol 2 mg/day (group II); or estradiol 2 mg/day and norethisterone acetate 1 mg/day (group III). METHODS: Arterial stiffness was assessed from PWV measurements of the common carotid and femoral arteries (CF-PWV) and the common carotid and radial arteries (CR-PWV) obtained using the automatic Complior(R) device, taken at baseline and after 12 weeks of treatment. RESULTS: After the 12-week treatment, values of CF-PWV and CR-PWV were not significantly different (p = 0.910 and p = 0.736, respectively) among the groups. Systolic blood pressure showed a positive correlation with CF-PWV in groups II and III (p = 0.02 and p < 0.001, respectively). CONCLUSIONS: PWV and arterial stiffness in postmenopausal hypertensive women did not reduce over a 12-week treatment with estradiol alone compared with the same period of treatment with estradiol combined with norethisterone acetate.
Assuntos
Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Estradiol/farmacologia , Hipertensão/fisiopatologia , Noretindrona/análogos & derivados , Pós-Menopausa/efeitos dos fármacos , Pulso Arterial , Pressão Sanguínea/efeitos dos fármacos , Artérias Carótidas/fisiopatologia , Método Duplo-Cego , Combinação de Medicamentos , Estradiol/administração & dosagem , Feminino , Humanos , Hipertensão/sangue , Pessoa de Meia-Idade , Noretindrona/administração & dosagem , Noretindrona/farmacologia , Acetato de Noretindrona , Placebos , Pós-Menopausa/sangue , Resistência Vascular/efeitos dos fármacosRESUMO
OBJECTIVE: The objective of this descriptive study was to compare bone mineral density (BMD) between users of two kinds of once-a-month combined injectable contraceptives (CICs) and control subjects. SUBJECTS AND METHODS: This cross-sectional descriptive study included 97 women aged between 20 and 45 years using CICs containing either 25 mg of medroxyprogesterone acetate and 5 mg of estradiol cypionate for 12-82 months or 50 mg of norethindrone enanthate and 5 mg of estradiol valerate for 12-60 months, matched by age (+/-1 year) and body mass index (BMI; kg/m(2)) (+/-1) with users of the TCu 380A intrauterine device as control subjects. BMD was evaluated at the midshaft of the ulna and at the distal section of the radius of the nondominant forearm using double X-ray absorptiometry. RESULTS: There was no difference in BMD between users of either CIC and nonusers at either section of the forearm studied. There was also no difference in BMD between users of the two CICs at either section of the forearm. CONCLUSIONS: Women aged between 20 and 45 years, currently using one of these two kinds of CICs, presented BMDs similar to those of control subjects paired by age and BMI.
Assuntos
Densidade Óssea , Anticoncepcionais Femininos/administração & dosagem , Absorciometria de Fóton , Adulto , Índice de Massa Corporal , Estudos Transversais , Estradiol/administração & dosagem , Estradiol/análogos & derivados , Feminino , Humanos , Injeções , Acetato de Medroxiprogesterona/administração & dosagem , Noretindrona/administração & dosagem , Noretindrona/análogos & derivados , Rádio (Anatomia) , UlnaRESUMO
PURPOSE: This prospective observational study evaluated the bleeding patterns of adolescents receiving a monthly injectable contraceptive containing norethisterone enanthate 50 mg plus estradiol valerate 5 mg. MATERIALS AND METHODS: The study enrolled 73 volunteers aged between 14 and 19 years; of these patients, 38 (52%) recorded their menstrual cycles during 1 year. RESULTS: After 1 year of using the contraceptive, most of the 38 women (71.1%) had adequate menstrual patterns (two to four bleeding episodes; none lasting 10 days or longer; with a range of bleeding-free intervals not exceeding 17 days), 23.7% reported prolonged bleeding episodes, 2.6% had irregular bleeding and 2.6% had amenorrhea. Only 1 of the 38 teenagers is known to have discontinued the method due to bleeding. Among these 38 adolescents, dissatisfaction with bleeding patterns was not a frequent reason given for discontinuation of the monthly injectable contraceptive.
Assuntos
Anticoncepcionais Femininos/administração & dosagem , Estradiol/análogos & derivados , Menstruação/efeitos dos fármacos , Noretindrona/análogos & derivados , Adolescente , Adulto , Anticoncepcionais Femininos/efeitos adversos , Combinação de Medicamentos , Estradiol/administração & dosagem , Feminino , Humanos , Injeções Intramusculares , Distúrbios Menstruais/induzido quimicamente , Noretindrona/administração & dosagem , Cooperação do Paciente , Estudos ProspectivosRESUMO
OBJECTIVE: To evaluate changes in mammographic density and (99m)Tc-sestamibi scintimammographic uptake in postmenopausal women on hormone replacement therapy (HRT). METHODS: Seventy-five postmenopausal women were prospectively studied and allocated into three groups: 50 women were randomized to either Group 1 (G1, n=25), which received 2mg of 17beta-oestradiol continuously combined with 1mg of norethisterone acetate (E2/NETA, Kliogest, Medley) or Group 2 (G2), which received 2.5mg/day of tibolone (Livial, Organon). The remaining 25 women, who were asymptomatic and had no desire to undergo HRT, constituted the control group (G3). Each patient was submitted to both mammography and scintimammography at baseline and after six months. Mammographic density was evaluated by using the BI-RADS classification system. The classification system of Barros et al. was used in the interpretation of scintimammography. For statistical analysis, the Chi-square test, ANOVA and Pearson's correlation were used. RESULTS: At six months, increased mammographic density was observed in 48% of G1, 12% of G2 and 16% of G3 patients (p<0.001). The increase in sestamibi uptake was 56% in G1, 28% in G2 and 24% in G3 (p<0.001). Increases in both density and uptake were significantly higher in the group on E2/NETA than among tibolone users and the controls. CONCLUSION: In postmenopausal women, HRT with E2/NETA was associated with increased mammographic density and increased (99m)Tc-sestamibi scintimammographic uptakes, suggesting greater mithochondrial activity in the cells of the mammary duct. This was not observed in users of 2.5 mg of tibolone, demonstrating that the effects on the breast were reduced. The same was observed in the control group.
Assuntos
Mama/efeitos dos fármacos , Estradiol/farmacologia , Moduladores de Receptor Estrogênico/farmacologia , Terapia de Reposição de Estrogênios/métodos , Noretindrona/análogos & derivados , Norpregnenos/farmacologia , Mama/diagnóstico por imagem , Distribuição de Qui-Quadrado , Estradiol/administração & dosagem , Moduladores de Receptor Estrogênico/administração & dosagem , Feminino , Seguimentos , Humanos , Mamografia , Pessoa de Meia-Idade , Noretindrona/administração & dosagem , Noretindrona/farmacologia , Acetato de Noretindrona , Norpregnenos/administração & dosagem , Pós-Menopausa , Estudos Prospectivos , CintilografiaRESUMO
The contra gestational effects of norethisterone and its main metabolites, 5alpha-NET and 3beta5alpha-NET, has been demonstrated in several species. However, the focus has been mainly on their effects in the uterus. We previously reported that 5alpha-NET inhibits the progesterone-induced AR in pig spermatozoa and induces severe morphological damage to fertilized mouse oocytes. In the present study, we analysed the effects of these compounds on the fertilization process in vitro. Oocytes and spermatozoa were obtained from Balb/c female and C57BL/6J male mice, respectively. Both, the AR assays and the fertilization experiments were performed under different steroid treatment schemes using progesterone as a control. Results showed that norethisterone induced the AR, while 5alpha-NET reduced the percentage of spermatozoa that had undergone progesterone-induced AR. Both 17beta-estradiol and 3beta5alpha-NET induced the AR in a considerably lower percentage of spermatozoa than progesterone. In addition, when 5alpha-NET was added to the medium simultaneously with progesterone at the moment of fertilization, the percentage of fertilized oocytes (two-cell stage) decreased by as much as 77% as compared with the control progesterone-treated group. All results suggest that these compounds can have important effects on the fertilization process.
Assuntos
Reação Acrossômica/efeitos dos fármacos , Fertilização/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Animais , Estradiol/farmacologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Noretindrona/análogos & derivados , Noretindrona/farmacologiaRESUMO
OBJECTIVE: The present study was undertaken to assess the impact, effectiveness and safety of a monophasic hormone replacement treatment (HRT) for continuous use with regards to the clinical effects, bleeding patterns and lipid profile of menopausal women in four Latin American countries. DESIGN: Three hundred and six postmenopausal women with natural menopause and uterus present were recruited. This was a multicentre prospective, clinical trial; the participating countries were Brazil (BR), Colombia (CO), Mexico (MX) and Argentina (AR). The study period was 12 months. The HRT regime was formulated in tablets containing 2 mg estradiol E2 and 1mg norethisterone acetate (NETA); one visit every 3 months was solicited. METHODS: HRT was given as one tablet every day without interruption for 1 year. Climacteric complaints, side-effects, reason for discontinuation, bleeding patterns, lipid profile at baseline and 12 months of treatment were documented. RESULTS: There were no significant differences between the four populations on clinical measurements. Thirty-four women discontinued, 13 for bleeding problems. The five most common side-effects were mastalgia, bleeding problems, headache, pelvic pain and nausea. 44.8% of women experienced scanty vaginal bleeding during the first 3 months of therapy. Ninety seven percent of women had amenorrhea at the end of the study in MX, BR and AR, and 100% in CO. Body weight was constant during the study, and no correlation was found between body weight and total days with bleeding. The Kupperman index score was used to evaluate the climacteric complaints, and the score decreased from a mean of 25.4 to 5.1 at 12-months visit. Total cholesterol levels were significantly reduced in BR and CO (P < 0.05) between baseline and the final sample; serum triglycerides remained unchanged, HDL-cholesterol was significantly increased in MX (P < 0.05), and LDL-cholesterol was significantly reduced in CO (P < 0.05). The results of this 1-year study emphasize that a continuous combined HRT regimen with 2 mg E2/1 mg NETA is an attractive alternative for postmenopausal women who are at least 1 year after their menopause and optimally 2 years after their menopause. Although the combination of 2 mg E2 with 1 mg NETA in a continuous combined therapy scheme has been in use in the Nordic countries for over a decade and in Latin America for the last 6 years, there have been no previous published reports on its effectivity in Latin American women. This publication reports the experience in a group of 306 Latin American women, and it is the first Latin American publication with this formulation.
Assuntos
Anticoncepcionais Orais Sintéticos/uso terapêutico , Estradiol/uso terapêutico , Terapia de Reposição de Estrogênios , Menopausa , Noretindrona/análogos & derivados , Noretindrona/uso terapêutico , Administração Oral , Adulto , Ansiedade/tratamento farmacológico , Anticoncepcionais Orais Sintéticos/efeitos adversos , Depressão/tratamento farmacológico , Tontura/tratamento farmacológico , Estradiol/efeitos adversos , Terapia de Reposição de Estrogênios/efeitos adversos , Feminino , Cefaleia/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Fogachos/tratamento farmacológico , Humanos , América Latina , Lipídeos/sangue , Pessoa de Meia-Idade , Debilidade Muscular/tratamento farmacológico , Noretindrona/efeitos adversos , Acetato de Noretindrona , Parestesia/tratamento farmacológico , Estudos ProspectivosRESUMO
The aim of this study was to evaluate the effect of hormone replacement therapy (HRT) on the expression of Ki-67, bcl-2 and c-erb.B2 in endometrial polyps during menopause. Sixteen patients using HRT and 24 untreated controls with endometrial polyps were enrolled in this study. Polypectomy was carried out by hysteroscopy. The presence of c-erb.B2, bcl-2 and Ki-67 expression was determined by immunohistochemistry. HRT was found to decrease Ki-67 and bcl-2 expression in endometrial polyps without affecting the c-erb.B2 staining reaction. HRT may cause endometrial polyp involution by decreasing proliferation and stimulating apoptosis.
Assuntos
Neoplasias do Endométrio/metabolismo , Terapia de Reposição de Estrogênios , Noretindrona/análogos & derivados , Pólipos/metabolismo , Administração Cutânea , Administração Oral , Idoso , Estudos de Casos e Controles , Estradiol/farmacologia , Estrogênios Conjugados (USP)/farmacologia , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Acetato de Medroxiprogesterona/farmacologia , Menopausa , Pessoa de Meia-Idade , Noretindrona/farmacologia , Acetato de Noretindrona , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptor ErbB-2/metabolismo , Estudos RetrospectivosRESUMO
OBJECTIVE: To compare the short-term effects of oral hormone replacement therapy (HRT) and placebo on carotid and uterine vascular impedance. METHODS: 80 postmenopausal women selected from the outpatient clinic of the Hospital Leonor Mendes de Barros in São Paulo, Brazil, were randomized to oral HRT (estradiol 2 mg/norethisterone acetate 1 mg-Kliogest(r)) or placebo. Carotid and uterine arteries pulsatility indices (PIs) were assessed by color Doppler at baseline, after 4 and 12 weeks of treatment. Seventy-six women completed the trial, 38 in each group. RESULTS: The carotid PI did not decrease significantly in either group. In the uterine arteries, the drop in PI was steeper and greater for HRT women. Drops occurred despite the supposed counteracting effect of norethisterone acetate. In placebo group, there was no significant difference between 4 and 12 weeks of treatment compared with the baseline. The results did not change when analyzed in a real treatment approach. CONCLUSION: Oral continuous HRT are effective at 12 weeks in reducing impedance to flow in uterine, but not in carotid circulation. These results suggest that the effects of HRT vary by vascular site, and do not have a detectable short-term vascular effect in the carotid area.
Assuntos
Artérias Carótidas/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Terapia de Reposição Hormonal , Noretindrona/análogos & derivados , Análise de Variância , Brasil , Artérias Carótidas/diagnóstico por imagem , Método Duplo-Cego , Endométrio/irrigação sanguínea , Endométrio/diagnóstico por imagem , Estradiol/sangue , Estradiol/farmacologia , Estradiol/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Noretindrona/farmacologia , Noretindrona/uso terapêutico , Acetato de Noretindrona , Pacientes Ambulatoriais , Placebos , Pós-Menopausa/efeitos dos fármacos , Pós-Menopausa/metabolismo , Fatores de Tempo , Ultrassonografia Doppler Dupla/métodosRESUMO
The objectives of this study were to compare effects of medroxyprogesterone acetate 25 mg + estradiol cypionate 5 mg (Cyclofem) and norethisterone enanthate (NET-EN) upon the menstrual pattern and determine changes in lipoprotein parameters after 12 months of use. One-hundred females were included and 87 (45 with Cyclofem and 42 with NET-EN) women completing 12 months were evaluated. Menstrual changes were the leading complaint among users. At the end of 12 months, 20/45 (44.4%) and 18/41 (43.9%) Cyclofem and NET-EN users, respectively, had normal menstrual pattern. Irregular and infrequent bleeding were the two most important changes that occurred. The discontinuation rate at 12 months due to menstrual disturbances did not show any significant differences between the two preparations, but showed lower incidence compared to other studies. Total cholesterol, high-density, low-density and very low-density lipoprotein cholesterol and triglyceride levels decreased at 12 months in both groups and these changes were statistically significant.
Assuntos
Anticoncepcionais Femininos/efeitos adversos , Anticoncepcionais Orais Combinados/efeitos adversos , Estradiol/análogos & derivados , Estradiol/efeitos adversos , Lipídeos/sangue , Acetato de Medroxiprogesterona/efeitos adversos , Distúrbios Menstruais/induzido quimicamente , Noretindrona/análogos & derivados , Noretindrona/efeitos adversos , Adolescente , Adulto , Colesterol/metabolismo , Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Orais Combinados/administração & dosagem , Combinação de Medicamentos , Estradiol/administração & dosagem , Feminino , Humanos , Injeções Intramusculares , Acetato de Medroxiprogesterona/administração & dosagem , Distúrbios Menstruais/prevenção & controle , Pessoa de Meia-Idade , Noretindrona/administração & dosagemRESUMO
The steroid 17 alpha-ethynyl-19-nor-4-androsten-17 beta-ol, 3-one (Norethisterone; NET) and its 5 alpha-dihydro (5 alpha-NET), 3 alpha- and 3 beta-tetrahydro derivatives (3 alpha,5 alpha- and 3 beta,5 alpha-NET), were comparatively studied by the ab initio quantum mechanics theory. Additionally, 5 alpha-androstan-3 beta,17 beta-diol (ADIOL) was also studied. The Hartree-Fock method and the 6-31G(*) basis set were used to obtain the lowest energy conformation, geometries, electronic structure and physicochemical properties of the steroids. The results showed bond distances and valence angles similar among all steroids, but some differences in dihedral angles in the A-B-ring system were observed. The electronic structure analysis showed that NET has both frontier orbitals that is, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) located at the C4-C5 pi-bond. In A-ring reduced derivatives, the HOMO was found at the 17 beta-OH and ethynyl groups. In the case of 5 alpha-NET, the LUMO was confined to the A-ring and its C3 carbonyl group while the two NET tetrahydro-reduced derivatives showed the LUMO at the 17 beta-OH and ethynyl groups. The energy changes of the rotational barrier of the 17 beta-OH group suggest that its movement is somewhat restricted by the 17 alpha-ethynyl group. Interestingly both groups at C17 form a single electrostatic potential with high electronic density. On the other side, the 19-nor condition increases the A-ring mobility. However, the 3 beta-OH group of 3 beta,5 alpha-NET may rotate without significant energy differences as compared to the same group in ADIOL. The electronic structure of NET and its A-ring reduced derivatives explains in some extent their interaction with androgen and progesterone receptors as well as their selectivity for the estrogen alpha-receptor.
Assuntos
Noretindrona/química , Congêneres da Progesterona/química , Sítios de Ligação/fisiologia , Eletrônica , Isomerismo , Conformação Molecular , Estrutura Molecular , Noretindrona/análogos & derivadosRESUMO
OBJECTIVE: This randomized, double-blind, multicenter study was planned to compare the efficacy and tolerance of a novel oral regimen containing estradiol (2.0 mg) sequentially combined with trimegestone, at a daily dose of either 0.25 mg or 0.5 mg, with a standard hormone replacement therapy containing estradiol and norethisterone acetate (E2 + NETA) in the treatment of climacteric symptoms. METHODS: The study was conducted over 13 cycles, each of 28 days, and involved 487 subjects, of whom 349 completed the study. RESULTS: All three treatments were equally effective in alleviating hot flushes and showed a progressive and significant reduction in the value of the Kupperman index. The treatments diminished equally effectively urogenital signs and symptoms. All treatments were well tolerated and the incidences of adverse events associated with each treatment were similar across the treatment groups. The duration of expected withdrawal bleeding was shorter in the estradiol + trimegestone 0.5 mg group than in the estradiol + trimegestone 0.25 mg or E2 + NETA group. CONCLUSION: All treatments were effective and well tolerated, providing significant relief from climacteric symptoms. Treatment with estradiol + trimegestone 0.5 mg provided the most favorable bleeding pattern.