Fatores de risco para osteoporose em mulheres na pós-menopausa do sudeste brasileiro

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos da isoflavona sobre os sintomas climatéricos e o perfil lipídico na mulher em menopausa

OBJETIVO: avaliar os efeitos da isoflavona, do gérmen da soja, sobre os sintomas climatéricos e o perfil lipídico na mulher em menopausa. MÉTODOS: foi conduzido estudo prospectivo, com 50 mulheres em menopausa, divididas em: G1, usuárias de isoflavona (60 mg/dia) (n=25), e G2, placebo (n=25). Os critérios de inclusão foram FSH >40 mUI/mL e presença de fogachos. Foram excluídas as vegetarianas, fumantes, asiáticas, portadoras de doenças gastrointestinais e usuárias de terapia de reposição hormonal. No seguimento, de seis meses, foram obtidos o índice menopausal de Kupperman (IMK), o perfil hormonal e o lipídico. Na análise estatística, empregaram-se ANOVA, o teste t pareado e as provas não paramétricas de Wilcoxon e Mann-Whitney. RESULTADOS: os valores medianos do IMK, inicialmente iguais entre os grupos (IMK = 20), reduziram-se nas usuárias de isoflavona aos 2 e 4 meses (IMK = 14 e 9, respectivamente) e no grupo controle, apenas aos 2 meses (IMK = 15) (p<0,01). Ao final do estudo, a isoflavona foi superior ao placebo na redução dos fogachos (44% versus 12%, respectivamente). Aos seis meses, verificou-se que os valores médios de estradiol foram superiores no G1 quando comparados ao G2 (18,0 ± 6,7 versus 12,3 ± 3,8 ng/dL) (p<0,05), sem alterações no FSH e LH. Entre as usuárias de isoflavona, houve redução de 11,8% no LDL (de 151,5 ± 39,2 para 133,6 ± 26,4 mg/dL) e elevação de 27,3% no HDL (de 44,0 ± 11,3 para 56,0 ± 11,9 mg/dL) (p<0,05). CONCLUSÕES: a isoflavona, do gérmen da soja, induziu efeitos favoráveis sobre os sintomas climatéricos e o perfil lipídico, revelando-se opção interessante como terapêutica alternativa para mulheres em menopausa.

Métodos para abandono do tabagismo e tratamento da dependência da nicotina

O tabagismo está relacionado a 30% das mortes por câncer. É fator de risco para desenvolver carcinomas do aparelho respiratório, esôfago, estômago, pâncreas, cérvix uterina, rim e bexiga. A nicotina induz tolerância e dependência pela ação nas vias dopaminérgicas centrais, levando às sensações de prazer e recompensa mediadas pelo sistema límbico. É estimulante do sistema nervoso central (SNC), aumenta o estado de alerta e reduz o apetite. A diminuição de 50% no consumo da nicotina pode desencadear sintomas de abstinência nos indivíduos dependentes: ansiedade, irritabilidade, distúrbios do sono, aumento do apetite, alterações cognitivas e fissura pelo cigarro. O aconselhamento médico é fundamental para o sucesso no abandono do fumo. A farmacoterapia da dependência de nicotina divide-se em: primeira linha (bupropiona e terapia de reposição da nicotina), e segunda linha (clonidina e nortriptilina). A bupropiona é um antidepressivo não-tricíclico que age inibindo a recaptação de dopamina, cujas contra-indicações são: epilepsia, distúrbios alimentares, hipertensão arterial não-controlada, abstinência recente do álcool e uso de inibidores da monoaminoxidase (MAO). A terapia de reposição de nicotina pode ser feita com adesivos e gomas de mascar. Os efeitos da acupuntura no abandono do fumo ainda não estão completamente esclarecidos. As estratégias de interrupção abrupta ou redução gradual do fumo têm a mesma probabilidade de sucesso.

Influence of estrogen deficiency and its treatment with alendronate and estrogen on bone density around osseointegrated implants: radiographic study in female rats

Objective. This study evaluated the influence of estrogen deficiency and its treatment on bone density around integrated implants.Study design. Implants were placed in female rat tibiae. The animals were assigned to 5 groups: control, sham, ovariectomy, estrogen, and alendronate. The control group was humanely killed to confirm integration of the implant. The others were submitted to ovariectomy or sham surgery. Bone density was measured by digital radiographs at 6 points on sides of the implant.Results. The analysis of radiographic bone density revealed estrogen privation had a negative impact only in the cancellous bone. The estrogen group differed significantly ( P <.05) from the ovariectomy and alendronate groups. The alendronate group presented the highest density for all evaluated regions.Conclusion. Ovariectomy caused a decrease in the radiographic bone density in the cancellous region. Estrogen replacement therapy and alendronate were effective treatments in preventing bone mass loss around integrated implants.

The effect of oestrogen and alendronate therapies on postmenopausal bone loss around osseointegrated titanium implants

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of 17 beta-estradiol and alendronate on the removal torque of osseointegrated titanium implants in ovariectomized rats

Background: This study investigated the influence of estrogen deficiency and its treatment with estrogen and alendronate on the removal torque of osseointegrated titanium implants.Methods: Fifty-eight female Wistar rats received a titanium implant in the tibia metaphysis. After 60 days, which was needed for implant osseointegration, the animals were randomly divided into five groups: control (CTLE; N = 10), sham surgery (SHAM; N = 12), ovariectomy (OVX; N = 12), ovariectomy followed by hormone replacement (EST; N = 12), and ovariectomy followed by treatment with alendronate (ALE; N = 12). The CTLE group was sacrificed to confirm osseointegration, whereas the remaining groups were submitted to sham surgery or ovariectomy according to their designations. After 90 days, these animals were also sacrificed. Densitometry of femur and lumbar vertebrae was performed by dual-energy x-ray absorptiometry (DXA) to confirm systemic impairment of the animals. All implants were subjected to removal torque.Results: Densitometric analysis of the femur and lumbar vertebrae confirmed a systemic impairment of the animals, disclosing lower values of bone mineral density for OVX. Analysis of the removal torque of the implants showed statistically lower values (P <0.05) for the OVX group in relation to the other groups. However, the group treated with alendronate (ALE group) presented significantly higher torque values compared to the others.Conclusion: According to this study, estrogen deficiency was observed to have a negative influence on the removal torque of osseointegrated implants, whereas treatment with alendronate

Implants of polyanionic collagen matrix in bone defects of ovariectomized rats

In recent years, there has been a great interest in the development of biomaterials that could be used in the repair of bone defects. Collagen matrix (CM) has the advantage that it can be modified chemically to improve its mechanical properties. The aim of the present study was to evaluate the effect of three-dimensional membranes of native or anionic (submitted to alkaline treatment for 48 or 96 h) collagen matrix on the consolidation of osteoporosis bone fractures resulting from the gonadal hormone alterations caused by ovariectomy in rats subjected to hormone replacement therapy. The animals received the implants 4 months after ovariectomy and were sacrificed 8 weeks after implantation of the membranes into 4-mm wide bone defects created in the distal third of the femur with a surgical bur. Macroscopic analysis revealed the absence of pathological alterations in the implanted areas, suggesting that the material was biocompatible. Microscopic analysis showed a lower amount of bone ingrowth in the areas receiving the native membrane compared to the bone defects filled with the anionic membranes. In ovariectomized animals receiving anionic membranes, a delay in bone regeneration was observed mainly in animals not subjected to hormone replacement therapy. We conclude that anionic membranes treated with alkaline solution for 48 and 96 h presented better results in terms of bone ingrowth.

La última palabra en dosis mínima

In this article we rewiewed the indications of the low-dose hormone replacement therapy in post menopausal women. We evaluate the effects of this therapy on menopausal symptoms bone metabolism, cardiovascular risk and endometrial cancer. The low-dose hormone replacement therapy is satisfactory to relief menopausal symptoms and improves lipid profile preventing atherosclerosis. It does not increase the risk of hyperplasia or endometrial cancer when is associate with progestagens. The low dose hormone replacement therapy is also associate to improve bone mineral density but to have better comprehension about the effective action of the low dose hormone replacement therapy on bone, more studies evaluating the risk of fractures are necessary.

Síndrome do climatério

The climateric is characterized by progressive hipoestrogenism and by tissue and functional alterations that leads the women to aging. The diagnosis approach needs to consider the symptoms originated by estrogenic deficiency and by the more prevalent chronic diseases in this lifetime, for instance, among others, the cardiovascular and osteoporosis diseases, witch need a systematic screening. The therapeutic management must consider the proposition of healthy life habits and, when indicated, pharmacological treatment for estrogenic deficiency or for anothers comorbidities existent. The estroprogestative hormonal therapeutic is a valuable tool to provide health and better quality of life, once obeyed the individualized criterion of the cases, doses, hormonal composition and mainly of the opportunity of intervention. There are nonhormonal alternatives to treat the menopausal symptoms, as the antidepressives and phytoestrogens. It's also advised to combine with regular physical activities and adequate calcium intake. © Copyright Moreira Jr. Editora. Todos os direitos reservados.

Efeito do raloxifeno sobre a densidade mamográfica em mulheres na pós-menopausa

PURPOSE: to evaluate changes in mammographic breast density in postmenopausal women using raloxifene. METHODS: in this clinical trial, 80 women (mean age=61.1 years) were studied prospectively. Forty patients received 60 mg/day raloxifene, and 40 women comprised the non-treated group (control), paired by age and time of menopause. The treated group was composed of patients with osteoporosis of the lumbar spine. Those with history of breast surgery and users of hormone therapy up to six months prior to the study were excluded. The breast density was assessed qualitatively (subjective) and quantitatively (objective) in two moments, initial and final, after a 6-month follow-up. The 320 mammograms (craniocaudal and oblique) were interpreted qualitatively by the Breast Imaging Reporting and Data System (BI-RADS) classification and quantitatively by digital scanning and computer-assisted segmentation. For statistical analysis t-test, Wilcoxon Mann-Whitney, Spearman correlation and the kappa index were used. RESULTS: on the initial statistical comparison, the groups were considered homogenous for the variables: analyzed age, time of menopause, parity, breast feeding, previous hormonal therapy and body mass index. Baseline breast density, by qualitative and quantitative methods, correlated negatively with the age in both groups (p<0.05). Concerning the other variables, there was no correlation. After six months, no alteration was observed in the mammographic breast density in 38 women of raloxifene group and 38 of the control group, by qualitative method. However, by quantitative method, no alteration was observed in 30 women of the raloxifene group and 27 controls (p>0.05). It was observed a weak agreement rate (kappa=0.25) between the BI-RADS classification and digital scanning/computer-assisted segmentation. CONCLUSIONS: in post-menopausal women with osteoporosis, submitted to raloxifene treatment for six months, no alterations were observed on the mammographic breast density.

Adjunctive antimicrobial photodynamic treatment of experimentally induced periodontitis in rats with ovariectomy

Background: The aim of this study is to compare antimicrobial photodynamic therapy (aPDT) as an adjunctive therapy to scaling and root planing (SRP) for the treatment of experimentally induced periodontitis in rats with ovariectomy (OVX) that are or are not treated with estrogen replacement. Methods: A total of 270 female rats were divided into three groups: 1) normal rats; 2) rats with OVX; and 3) rats with OVX with estrogen replacement. Periodontal disease was induced through the introduction of a cotton thread around the mandibular left first molar. After 7 days, the ligature was removed, and the rats were randomly divided into the following treatment groups: 1) SRP plus saline solution; 2) SRP plus low-level laser therapy (LLLT); and 3) SRP plus toluidine blue O irrigation followed by LLLT. Ten rats from each group were euthanized at days 7, 15, and 30 after dental treatment. Bone loss (BL) in the furcation region was evaluated using histometric and immunohistochemical analyses. Results: aPDT treatment resulted in reduced BL compared with SRP treatment at all time points. Additionally, rats treated with aPDT exhibited reduced numbers of tartrate-resistant acid-phosphatase-positive cells and more proliferating cell nuclear antigen-positive cells in all treatment groups regardless of estrogen status. Whereas rats treated with aPDT showed weak immunoreactivity to the receptor activator of nuclear factor-k B ligand at day 7 post-treatment, strong osteoprotegerin immunoreactivity was observed at day 15 post-treatment. Conclusion: aPDT is an effective adjunctive therapy for the treatment of periodontitis in rats with OVX that are or are not given estrogen replacement therapy.

Estrogenic and mutagenic activities of crotalaria pallida measured by recombinant yeast assay and ames test

Background: Crotalaria pallida Ailton is a plant belonging to the Fabaceae family, popularly known as rattle or rattlesnake and used in traditional medicine to treat swelling of the joints and as a vermifuge. Previous pharmacological studies have also reported anti-inflammatory, antimicrobial and antifungal activities. Nevertheless, scientific information regarding this species is scarce, and there are no reports related to its possible estrogenic and mutagenic effects. Thus, the purpose of the present study was to investigate the estrogenic potential of C. pallida leaves by means of the Recombinant Yeast Assay (RYA), seeking an alternative for estrogen replacement therapy during menopause; and to reflect on the safe use of natural products to assess the mutagenic activity of the crude extract from C. pallida leaves, the dichloromethane fraction and stigmasterol by means of the Ames test.Methods: The recombinant yeast assay with the strain BY4741 of Saccharomyces cerevisiae, was performed with the ethanolic extract, dichloromethane fraction and stigmasterol isolated from the leaves of C. pallida. Mutagenic activity was evaluated by the Salmonella/microsome assay (Ames test), using the Salmonella typhimurium tester strains TA100, TA98, TA97 and TA102, with (+S9) and without (-S9) metabolization, by the preincubation method.Results: All samples showed estrogenic activity, mainly stigmasterol. The ethanolic extract from C. pallida leaves showed mutagenic activity in the TA98 strain (-S9), whereas dichloromethane fraction and stigmasterol were found devoid of activity.Conclusion: Considering the excellent estrogenic activity performed by stigmasterol in the RYA associated with the absence of mutagenic activity when evaluated by the Ames test, stigmasterol becomes a strong candidate to be used in hormone replacement therapy during menopause. © 2013 Boldrin et al.; licensee BioMed Central Ltd.

The renin-angiotensin system plays a major role in voiding dysfunction of ovariectomized rats

Aims: The renin-angiotensin system (RAS) plays a major role in cardiovascular diseases in postmenopausal women, but little is known about its importance to lower urinary tract symptoms. In this study we have used the model of ovariectomized (OVX) estrogen-deficient rats to investigate the role of RAS in functional and molecular alterations in the urethra and bladder. Main methods: Responses to contractile and relaxant agents in isolated urethra and bladder, as well as cystometry were evaluated in 4-month OVX Sprague-Dawley rats. Angiotensin-converting enzyme activity and Western blotting for AT1/AT2 receptors were examined. Key findings: Cystometric evaluations in OVX rats showed increases in basal pressure, capacity and micturition frequency, as well as decreased voiding pressure. Angiotensin II and phenylephrine produced greater urethral contractions in OVX compared with Sham group. Carbachol-induced bladder contractions were significantly reduced in OVX group. Relaxations of urethra and bladder to sodium nitroprusside and BAY 41-2272 were unaffected by OVX. Angiotensin-converting enzyme activity was 2.6-fold greater (p < 0.05) in urethral tissue of OVX group, whereas enzyme activity in plasma and bladder remained unchanged. Expressions of AT1 and AT2 receptors in the urethra were markedly higher in OVX group. In bladder, AT1 receptors were not detected, whereas AT2 receptor expression was unchanged between groups. 17β-Estradiol replacement (0.1 mg/kg, weekly) or losartan (30 mg/kg/day) largely attenuated most of the alterations seen in OVX group. Significance: Prolonged estrogen deprivation leads to voiding dysfunction and urethral hypercontractility that are associated with increased ACE activity and up-regulation of angiotensin AT1/AT2 receptor in the urethral tissue. © 2013 Elsevier Inc. All rights reserved.

Evaluation of Estrogenic Potential of Flavonoids Using a Recombinant Yeast Strain and MCF7/BUS Cell Proliferation Assay

Phytoestrogens are of interest because of their reported beneficial effects on many human maladies including cancer, neurodegeneration, cardiovascular disease and diabetes. Furthermore, there is a search for compounds with estrogenic activity that can replace estrogen in hormone replacement therapy during menopause, without the undesirable effects of estrogen, such as the elevation of breast cancer occurrence. Thus, the principal objective of this study was to assess the estrogenic activity of flavonoids with different hydroxylation patterns: quercetin, kaempferol, luteolin, fisetin, chrysin, galangin, flavone, 3-hydroxyflavone, 5-hydroxyflavone and 7-hydroxyflavone via two different in vitro assays, the recombinant yeast assay (RYA) and the MCF-7 proliferation assay (E-screen), since the most potent phytoestrogens are members of the flavonoid family. In these assays, kaempferol was the only compound that showed ERα-dependent transcriptional activation activity by RYA, showing 6.74±1.7 nM EEQ, besides acting as a full agonist for the stimulation of proliferation of MCF-7/BUS cells. The other compounds did not show detectable levels of interaction with ER under the conditions used in the RYA. However, in the E-screen assay, compounds such as galangin, luteolin and fisetin also stimulated the proliferation of MCF-7/BUS cells, acting as partial agonists. In the evaluation of antiestrogenicity, the compounds quercetin, chrysin and 3-hydroxyflavone significantly inhibited the cell proliferation induced by 17-β-estradiol in the E-screen assay, indicating that these compounds may act as estrogen receptor antagonists. Overall, it became clear in the assay results that the estrogenic activity of flavonoids was affected by small structural differences such as the number of hydroxyl groups, especially those on the B ring of the flavonoid. © 2013 Resende et al.

Efeito do consumo de iogurte de soja suplementado com isoflavonas e cálcio sobre o tecido ósseo de ratas maduras ovariectomizadas

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