RESUMO
Postmenopausal hyperandrogenism constitutes a very rare condition of tumoral or non-tumoral origin primarily residing either in the ovary or in the adrenal glands. We present herein two cases with this condition; one with abnormal postmenopausal genital bleeding and mild increase in facial hair, and the second with slow-developing hirsutism and virilization. Both cases shared a notorious increase in libido. The laboratory tests showed high levels of testosterone (>100 ng/ml). A normal value of dehydroepiandrosterone sulfate and a normal cortisol level at 9 am after 1 mg of dexamethasone administered at midnight (Nugent test) made an adrenal etiology very unlikely. On the other hand, a high level of inhibine B oriented to an ovarian source. Transvaginal sonography failed to demonstrate an ovarian tumor, but an abdominal and pelvic computed tomography scan or magnetic resonance imaging detected an ovarian tumor and normal adrenal glands. A laparoscopic oophorectomy was performed, and the histological study demonstrated a steroidal cell tumor in the first case and a Leydig cell tumor in the second.
Assuntos
Androgênios/metabolismo , Hiperandrogenismo , Tumor de Células de Leydig/diagnóstico , Neoplasias Ovarianas/diagnóstico , Pós-Menopausa , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Tumor de Células de Leydig/diagnóstico por imagem , Tumor de Células de Leydig/metabolismo , Tumor de Células de Leydig/patologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Ovariectomia , Tomografia Computadorizada por Raios XRESUMO
Women carriers of mutations in the genes BRCA1 and BRCA2 coding for tumor suppressor proteins are at high risk of developing breast and ovarian cancers. Hereditary breast and ovarian cancers due to BRCA pathogenic mutations occur at earlier ages: mean age 43 years at diagnosis of breast cancer for BRCA1 mutations; onset of ovarian cancer up to 10-21% by age 50 years. Preventive strategies are then defined in the reproductive years. The National Comprehensive Cancer Network (NCCN) guidelines define that BRCA1/2 genetic testing should begin with the affected cancer individual (BRCA1/2 full sequencing); then, family members should be tested for the specific gene mutation found. A woman known to be a carrier needs a strict specific surveillance strategy to achieve early diagnosis. The NCCN proposes breast imageneological surveillance beginning at age 25 years; ovarian surveillance beginning at age 30-35 years. Concomitantly, risk-reducing strategies should be analyzed: surgical or pharmacological. When prophylactic bilateral salpingo-oophorectomy is performed before menopause, estrogen replacement therapy could be required. For BRCA, we review the risks of cancer in mutations carriers, criteria for genetic testing, surveillance and risk-reduction strategies, and the safety of prescribing hormone therapy when needed.
Assuntos
Neoplasias da Mama/prevenção & controle , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença , Neoplasias Ovarianas/prevenção & controle , Neoplasias da Mama/genética , Terapia de Reposição de Estrogênios , Feminino , Triagem de Portadores Genéticos , Aconselhamento Genético , Humanos , Mutação , Neoplasias Ovarianas/genética , Medição de Risco , Fatores de Risco , Salpingo-OoforectomiaRESUMO
OBJECTIVE: Non-hormonal treatment for menopausal vasomotor symptoms (VMS) is needed in women in whom there are medical or personal concerns on the use of hormone therapy. This paper reviews conventional and phytochemical therapies available for the relief of VMS, on their mechanisms of action, their efficacy and safety concerns. METHODS: Medline was searched through Pubmed on the names of the diverse therapies analyzed, up to June 2011. The Cochrane Controlled Clinical Trials Register Database was searched for relevant trials that provided data on treatment of menopausal hot flushes. RESULTS: All non-estrogen treatments for VMS are less efficacious than estrogen treatment. Randomized trials with neuroendocrine agents show globally modest to moderate reduction of VMS and frequent bothersome adverse events. The variability of effects makes it possible to undergo treatment in search for individual response where estrogen treatment is contraindicated. The antidepressants that interact with cytochrome P450, inhibiting tamoxifen metabolism to endoxifen, interfere with tamoxifen therapy in breast cancer patients. Otherwise, botanical products containing isoflavones from soy bean or red clover have great variability in bioavailability, have a broader spectrum of action than estradiol, and have predominant estrogen receptor-b activity. The efficacy of phytoestrogens on VMS is similar to placebo. They should be avoided in women with breast cancer and, in particular, in women being treated with tamoxifen or aromatase inhibitors due to possible antagonism. Cimicifuga racemosa is not a phytoestrogen, has partial serotonin agonist action and has a modest effect on VMS. CONCLUSIONS: There are safe non-hormonal conventional treatments for menopausal VMS, although they are less efficacious than estrogens. The indication of phytochemicals is for women who make this choice on personal beliefs; long-term studies of larger groups of patients are needed to assess safety.
Assuntos
Fogachos/tratamento farmacológico , Menopausa/efeitos dos fármacos , Sudorese/efeitos dos fármacos , Sistema Vasomotor/efeitos dos fármacos , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Aminas/farmacologia , Aminas/uso terapêutico , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Cimicifuga , Clonidina/farmacologia , Clonidina/uso terapêutico , Ácidos Cicloexanocarboxílicos/farmacologia , Ácidos Cicloexanocarboxílicos/uso terapêutico , Feminino , Gabapentina , Humanos , Fitoestrógenos/farmacologia , Fitoestrógenos/uso terapêutico , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Pregabalina , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Sistema Vasomotor/fisiopatologia , Ácido gama-Aminobutírico/análogos & derivados , Ácido gama-Aminobutírico/farmacologia , Ácido gama-Aminobutírico/uso terapêuticoRESUMO
OBJECTIVE: Ethinylestradiol (EE) combined with the antiandrogenic progestin cyproterone acetate (CPA) is a possible treatment in polycystic ovary syndrome (PCOS). We investigated the impact of EE/CPA on lipid and carbohydrate metabolism in women with PCOS,who were otherwise healthy. METHOD: The 31 women were separated into two groups paired by body mass index (BMI): Group A (control, n = 15) were cycled with 10 mg medroxyprogesterone acetate (MPA) x 10 days (Provera, Pharmacia & Upjohn) every month for 3 months; Group B (n = 16) were treated with 35 microg EE/2 mg CPA (Diane 35, Schering) for 3 months. Metabolic and hormonal conditions were similar in both groups. RESULTS: Group A showed no change in any hormone or metabolic parameter. Group B showed a significant decrease in free androgen index (-81%) and increase in sex hormone binding globulin (+ 639%), a decrease in low density lipoprotein cholesterol (-14%) and total cholesterol/high density lipoprotein (HDL) cholesterol index (-19%), and increases in HDL cholesterol (+ 23%) and triglycerides (+ 82%) (p < 0.001). Fasting insulin increased in 18%, the glucose/insulin index worsened in 8%, and the plasma glucose disappearance worsened in 12%, with no statistical significance (p= 0.092, p=0.308 and p= 0.237, respectively). CONCLUSION: Treatment of PCOS with EE/CPA induces important favorable changes regarding hormone parameters associated with hyperandrogenism, significant favorable changes in lipid profile except for triglyceride increase, and no significant change in carbohydrate metabolism (measured by fasting insulin, glucose/insulin index and plasma glucose disappearance). MPA cycling does not change any of these parameters.
Assuntos
Acetato de Ciproterona/uso terapêutico , Etinilestradiol/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Administração Oral , Adulto , Androgênios/sangue , Glicemia/efeitos dos fármacos , Colesterol/sangue , HDL-Colesterol/sangue , HDL-Colesterol/efeitos dos fármacos , LDL-Colesterol/sangue , LDL-Colesterol/efeitos dos fármacos , Acetato de Ciproterona/administração & dosagem , Esquema de Medicação , Etinilestradiol/administração & dosagem , Feminino , Humanos , Síndrome do Ovário Policístico/sangue , Estudos Prospectivos , Globulina de Ligação a Hormônio Sexual/efeitos dos fármacos , Resultado do Tratamento , Triglicerídeos/sangueRESUMO
BACKGROUND: Phytoestrogens are a family of plant-derived compounds with weak estrogenic and antiestrogenic properties. The antioxidant capacity of phytoestrogens has been proposed as one of the important mechanisms that explain their health benefits. OBJECTIVE: To determine the in vitro potency of three phytoestrogens, ubiquitous in food, (biochanin A, daidzein and genistein) as antioxidants of low density lipoprotein (LDL) and to compare them with the well-established antioxidant actions of estradiol and quercetin, an ubiquitous flavonoid which is found in high concentration in onions, tea and berries. METHODS: LDL was isolated by ultracentrifugation from the plasma of ten healthy postmenopausal women who were not on hormone therapy. Aliquots containing 0.5 mg of protein were incubated for 4 h with CuSO4 15 micromol/l to induce oxidative stress and with one of the five compounds studied: estradiol, quercetin, biochanin A, daidzein, and genistein, in doses of 0, 5, 15, 50, 500, 1000 and 2000 micromol/l. In addition, we studied the combined effect of estradiol 1 micromol/l plus quercetin 1 micromol/l, comparing their antioxidant action with that of each compound separately. Malonaldehyde (MDE nmol/ mg protein) was measured as a marker of LDL oxidation. RESULTS: Estradiol and quercetin induced a dose-dependent decrease in MDE concentration (p < 0.01). Comparing the areas under the curve, the antioxidant effect of quercetin was 8 times higher than the one observed with estradiol (p < 0.01). A 50% decrease in MDE was reached by quercetin at a concentration of 3.4 micromol/l, estradiol at 29 micromol/l, genistein at 280 micromol/l, biochanin at 1312 mmol/l and daidzein at 8007 mmol/l. Estradiol 1 micromol/l and quercetin 1 micromol/l did not modify MDE generation separately, but, when incubated combined, there was a significant decrease of MDE (p < 0.02). CONCLUSION: The phytoestrogens studied showed a weak antioxidant activity in vitro. The flavonoid quercetin, in contrast, showed the most potent antioxidant activity in vitro, higher than estradiol. Estradiol and quercetin showed additive antioxidant activity. We speculate that different compounds with variable antioxidant effects could amplify their antioxidant capacity when acting combined.
Assuntos
Antioxidantes/farmacologia , LDL-Colesterol/sangue , Malondialdeído/sangue , Fitoestrógenos/farmacologia , Quercetina/farmacologia , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Estradiol/farmacologia , Feminino , Humanos , Técnicas In Vitro , Isoflavonas/farmacologia , Pessoa de Meia-Idade , Pós-Menopausa/fisiologiaRESUMO
Evidence that domestic dogs may act as reservoir hosts for cutaneous leishmaniasis in the Peruvian Andes is provided by the isolation, for the first time, from naturally infected dogs of parasites identified (by isoenzymes) as Leishmania peruviana. Leishmania parasites were isolated from nasal aspirates or biopsies from 5 (1.8%) of 279 asymptomatic dogs samples in endemic villages of the Peruvian Andes. In addition, Leishmania (Viannia) infections were identified in 15 (5.4%) of 276 nasal samples by the polymerase chain reaction (PCR) using subgenus-specific primers. Further circumstantial evidence for a reservoir role for dogs comes from the finding of a relatively high dog blood index among the sandfly vectors collected inside houses (29% for Lutzomyia peruensis and 17% for Lu. verrucarum). Possible wild mammal reservoir hosts for Andean cutaneous leishmaniasis were also detected in endemic villages. At least 8 species were identified among the 1266 small mammals trapped. Leishmania parasites were isolated from blood or skin biopsies taken from 2 (2.6%) of 78 Didelphis albiventris and 6 (1.2%) of 511 Phyllotis andinum. Three isolates were identified by isoenzymes as L. peruviana, and the other 5 were identified by PCR as Leishmania (Viannia) species. Leishmania (Viannia) infections were also identified by PCR directly on skin biopsies taken from 2 (2.8%) of 72 D. albiventris, 1 (0.2%) of 499 P. andinum, and 4 (2.6%) of 153 Akodon sp.
Assuntos
Vetores de Doenças , Doenças do Cão/parasitologia , Leishmaniose Cutânea/veterinária , Animais , Animais Domésticos/parasitologia , Antígenos/análise , Doenças do Cão/epidemiologia , Cães , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/parasitologia , Peru/epidemiologia , Psychodidae/imunologiaRESUMO
During May 1998, we conducted a case-control study of 357 participants from 60 households during an outbreak of acute bartonellosis in the Urubamba Valley, Peru, a region not previously considered endemic for this disease. Blood and insect specimens were collected and environmental assessments were done. Case-patients (n = 22) were defined by fever, anemia, and intra-erythrocytic coccobacilli seen in thin smears. Most case-patients were children (median age = 6.5 years). Case-patients more frequently reported sand fly bites than individuals of neighboring households (odds ratio [OR] = 5.8, 95% confidence interval [CI] = 1.2-39.2), or members from randomly selected households > or = 5 km away (OR = 8.5, 95% CI = 1.7-57.9). Bartonella bacilliformis isolated from blood was confirmed by nucleotide sequencing (citrate synthase [g/tA], 338 basepairs). Using bacterial isolation (n = 141) as the standard, sensitivity, specificity, and positive predictive value of thin smears were 36%, 96%, and 44%, respectively. Patients with clinical syndromes compatible with bartonellosis should be treated with appropriate antibiotics regardless of thin-smear results.
Assuntos
Infecções por Bartonella/epidemiologia , Bartonella/isolamento & purificação , Surtos de Doenças , Adolescente , Adulto , Infecções por Bartonella/diagnóstico , Infecções por Bartonella/fisiopatologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Peru/epidemiologia , Fatores de RiscoRESUMO
En el valle Sagrado de los Incas (Valle del Río Urubamba) encontramos una sola de Lutzomyia, nos referimos a la Lutzomyia suele compartir su habitat con el vector de la enfermedad de Carrión, la Lutzomyia verrucarum. Los aspectos entomológicos fueron levados a cabo, en Mayo de 1998. Las colectas entomológicas se realizaron utilizando trampas de luz CDC toda la noche y en capturas diurnas en las viviendas.Se muestra la importancia de Lutzomyia peruensis incriminándola epidemiológicamente y se detectó Bartonella bacilliformis mediante PCR y haciendo secuenciamiento de ADN. Se presenta también la estimación del riesgo entomólogico de transmisión de bartonelosis por Lutzomyia peruensis, mediante el índice de inoculación de Bartonella bacilliformis
Assuntos
Peru , Psychodidae , Infecções por BartonellaRESUMO
BACKGROUND: Estradiol (E2) has a potent antioxidant effect on low density lipoproteins (LDL) in vitro and in vivo, which could be important in explaining the cardioprotective effect of hormone replacement therapy (HRT) in post menopausal women. Estriol (E3), on the other hand, is a weak estrogen with low metabolic effects on different tissues, and at present no cardioprotective effect has been attributed to this steroid. AIM: To study the antioxidant effect of E3 on LDL and to compare it with the potent antioxidant action exhibited by E2. SUBJECTS AND METHODS: After LDL was isolated by ultra centrifugation from plasma of 12 healthy untreated post menopausal women, it was divided into aliquots containing 0.5 mg of LDL protein. Estriol and E2 in doses of 0, 1, 5, 15 and 50 microM were incubated with different aliquots of LDL. CuSO4 15 microM was added to each aliquot to induce an oxidative stress. The aliquots were then incubated during 4 hours at 37 degrees C. Malonaldehyde (MDA) was measured as a marker of LDL oxidation, and expressed as nM/mg protein. RESULTS: (mean +/- SD): Estriol induced a dose-dependent decrease in MDA concentration (baseline 62.8 +/- 21.7; 1 microM: 61.5 +/- 23.0; 5 microM: 52.9 +/- 20.3; 15 microM 43.5 +/- 20.1 and 50 microM: 31.0 +/- 17.6 nM/mg protein; F = 92.4; p < 0.0001), reaching a mean decrease of 50.7% at the highest dose tested. Estradiol has a similar dose-dependent decrease in MDA concentration (F = 60.2; p < 0.0001), revealing a more potent effect than E3 (p < 0.05), with a mean decrease of 67.4% at the highest dose tested. CONCLUSIONS: Our results demonstrate that estriol shows an important antioxidant action of LDL in vitro, although its effect is less potent than estradiol. These results raise the possibility that estriol could have a cardioprotective effect in post menopausal women, possibility that has not been yet demonstrated.
Assuntos
Antioxidantes/metabolismo , Estradiol/farmacologia , Estriol/farmacologia , Lipoproteínas LDL/sangue , Lipoproteínas LDL/efeitos dos fármacos , Pós-Menopausa/sangue , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Feminino , Humanos , Peroxidação de Lipídeos , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: To determine the relative bioavailability of the estrogenic components of a generic brand of conjugated estrogens marketed in Chile in comparison to that of Conpremin (Premarin in the United States). METHODS: A randomized cross-over study was conducted on 16 healthy postmenopausal women receiving single oral doses of either two Conpremin 0.625-mg tablets or two 0.625-mg tablets of the generic brand, with a 14-day wash-out interval between doses. A gas chromatography tandem mass spectrometry assay was used to determine estrogen components. RESULTS: The peak plasma concentrations of unconjugated and total estrone and equilin, unconjugated 17 beta-dihydroequilin and 17 beta-estradiol were higher and occurred earlier with the generic conjugated estrogens than with Conpremin. The 90% confidence limits for both variables lay outside the accepted bioequivalence limits of 80-125%. Additionally, no measurable plasma concentration of unconjugated delta 8,9-dehydroestrone or 17 beta-delta 8,9-dehydroestradiol was seen after administration of the generic conjugated estrogens. CONCLUSIONS: These pharmacokinetic results indicate that the generic tablets do not have the modified-release characteristics of Conpremin tablets. In addition, the absence of delta 8,9-dehydroestrone and 17 beta-delta 8,9-dehydroestradiol in the plasma indicates that the generic form is not compositionally equivalent to Conpremin.