Brazilian Guideline on Menopausal Cardiovascular Health ­ 2024 / Guía Brasileña de Salud Cardiovascular en el Climaterio y la Menopausia ­ 2024 / Diretriz Brasileira sobre a Saúde Cardiovascular no Climatério e na Menopausa ­ 2024

Women, who represent approximately half of the global population according to estimates as of January 2024, may experience signs and symptoms of menopause for at least one-third of their lives, during which they have a higher risk of cardiovascular morbidity and mortality. The effects of menopausal hormone therapy (MHT) on the progression of atherosclerosis and cardiovascular disease (CVD) events vary depending on the age at which MHT is initiated and the time since menopause until its initiation. Beneficial effects on CVD outcomes and all-cause mortality have been observed when MHT was initiated before the age of 60 or within 10 years after menopause. The decision regarding the initiation, dose, regimen, and duration of MHT should be made individually after discussing the benefits and risks with each patient. For primary prevention of postmenopausal chronic conditions, the combined use of estrogen and progestogen is not recommended in asymptomatic women, nor is the use of estrogen alone in hysterectomized women. Hormone-dependent neoplasms contraindicate MHT. For the treatment of genitourinary syndrome of menopause, vaginal estrogen therapy may be used in patients with known cardiovascular risk factors or established CVD. For women with contraindications to MHT or who refuse it, non-hormonal therapies with proven efficacy (antidepressants, gabapentin, and fezolinetant) may improve vasomotor symptoms. Compounded hormonal implants, or "bioidentical" and "compounded" hormones, and "hormone modulation" are not recommended due to lack of scientific evidence of their effectiveness and safety.

Mujeres, que representan aproximadamente la mitad de la población mundial según estimaciones de enero de 2024, pueden experimentar signos y síntomas de la menopausia durante al menos un tercio de sus vidas, durante los cuales tienen un mayor riesgo de morbilidad y mortalidad cardiovascular. Los efectos de la terapia hormonal de la menopausia (THM) en la progresión de la aterosclerosis y los eventos de enfermedad cardiovascular (ECV) varían según la edad en que se inicia la THM y el tiempo transcurrido desde la menopausia hasta su inicio. Se han observado efectos beneficiosos en los resultados de ECV y la mortalidad por todas las causas cuando la THM se inició antes de los 60 años o dentro de los 10 años posteriores a la menopausia. La decisión sobre la iniciación, dosis, régimen y duración de la THM debe tomarse individualmente después de discutir los beneficios y riesgos con cada paciente. Para la prevención primaria de condiciones crónicas en la posmenopausia, no se recomienda el uso combinado de estrógeno y progestágeno en mujeres asintomáticas, ni el uso de estrógeno solo en mujeres histerectomizadas. Las neoplasias dependientes de hormonas contraindican la THM. Para el tratamiento del síndrome genitourinario de la menopausia, se puede usar terapia estrogénica vaginal en pacientes con factores de riesgo cardiovascular conocidos o ECV establecida. Para mujeres con contraindicaciones a la THM o que la rechazan, las terapias no hormonales con eficacia demostrada (antidepresivos, gabapentina y fezolinetant) pueden mejorar los síntomas vasomotores. Los implantes hormonales compuestos, o hormonas "bioidénticas" y "compuestas", y la "modulación hormonal" no se recomiendan debido a la falta de evidencia científica sobre su efectividad y seguridad.

As mulheres, que representam cerca de metade da população mundial segundo estimativas de janeiro de 2024, podem sofrer com sinais e sintomas da menopausa durante pelo menos um terço de suas vidas, quando apresentam maiores risco e morbimortalidade cardiovasculares. Os efeitos da terapia hormonal da menopausa (THM) na progressão de eventos de aterosclerose e doença cardiovascular (DCV) variam de acordo com a idade em que a THM é iniciada e o tempo desde a menopausa até esse início. Efeitos benéficos nos resultados de DCV e na mortalidade por todas as causas ocorreram quando a THM foi iniciada antes dos 60 anos de idade ou nos 10 anos que se seguiram à menopausa. A decisão sobre o início, a dose, o regime e a duração da THM deve ser tomada individualmente após discussão sobre benefícios e riscos com cada paciente. Para a prevenção primária de condições crônicas na pós-menopausa, não se recomendam o uso combinado de estrogênio e progestagênio em mulheres assintomáticas nem o uso de estrogênio sozinho em mulheres histerectomizadas. Neoplasias hormônio-dependentes contraindicam a THM. Para tratamento da síndrome geniturinária da menopausa, pode-se utilizar terapia estrogênica por via vaginal em pacientes com fatores de risco cardiovascular conhecidos ou DCV estabelecida. Para mulheres com contraindicação à THM ou que a recusam, terapias não hormonais com eficácia comprovada (antidepressivos, gabapentina e fezolinetante) podem melhorar os sintomas vasomotores. Os implantes hormonais manipulados, ou hormônios "bioidênticos" "manipulados", e a 'modulação hormonal' não são recomendados pela falta de evidência científica de sua eficácia e segurança.

Prophylactic low-molecular-weight heparin in women with thrombophilia undergoing in vitro fertilization.

OBJECTIVE: To verify whether low-molecular-weight heparin (LMWH) could increase pregnancy rates and/or decrease abortion rates in women with thrombophilia undergoing assisted reproduction cycles. METHODS: Cross-sectional study with patients undergoing in vitro fertilization (IVF) (N = 104). Women without thrombophilia (control group, n = 20), women with thrombophilia who did not receive LMWH (untreated group, n = 30), and women with thrombophilia, treated with daily enoxaparin from the day of embryo transfer until week 36 of gestation (treated group, n = 54). All women underwent controlled ovarian hyperstimulation. IVF was performed by intracytoplasmic sperm injection, and embryos were transferred on day 3. Pregnancy was detected by ß-human chorionic gonadotropin (biochemical pregnancy) and fetal heartbeat at week 5 to 6. Ongoing pregnancy was determined by ultrasound on week 12. RESULTS: Patients in the untreated thrombophilia group presented with significantly lower ongoing pregnancy rates and live birth rates and significantly higher early pregnancy loss and abortion rates when compared with the control and the treated thrombophilia groups. CONCLUSIONS: In women with diagnosed coagulation disorders, use of LMWH is important to avoid miscarriages.

Best Laboratory Screening in Diagnosing Secondary Osteoporosis and Fracture Risk Assessment Tool and the National Osteoporosis Guideline Group Performance in Determining Clinical Risk: A Cross-Sectional Evaluation of the Bone Health in Postmenopausal Brazilian Women.

BACKGROUND: Identifying postmenopausal women with a high risk of having osteoporosis and fractures is a current challenge. This study aimed to assess the diagnostic performance of biochemical tests in identifying secondary osteoporosis and the fracture risk assessment tool (FRAX) in identifying fracture risk. METHODS: Data from biochemical tests and bone densitometry of postmenopausal women were analyzed. Additionally, the FRAX result was obtained and the patients were classified according to the National Osteoporosis Guideline Group (NOGG). RESULTS: A total of 646 women were evaluated, of whom 201 (31.1%) had osteoporosis or a previous frailty fracture. These women had statistically different parathyroid hormone (PTH) and alkaline phosphatase serum levels (p<0.01 and p=0.02, respectively) than those without osteoporosis or fracture. However, those at high risk had a higher prevalence of hypovitaminosis D (46% vs. 36%) and hypocalciuria (17% vs. 9%). The FRAX showed an area under the curve of 0.757 (p<0.01) and 0.788 (p<0.01) for identifying women at risk for "major fractures" and "hip," respectively. The NOGG categorization had a sensitivity of 19% to identify high-risk women, a specificity of 91.3% for low-risk women, with a positive predictive value of 57.4% and a negative predictive value of 64.6%. CONCLUSIONS: The evaluation of PTH, 25-hydroxy-vitamin D, serum calcium, and 24-hr urinary calcium proved adequate for initial osteoporosis screening. The FRAX tool has a regular ability to screen women at risk for fracture, and the NOGG method has high specificity to identify those at low risk.

Effects of ultra-low dose hormone therapy on biochemical bone turnover markers in postmenopausal women: A randomized, placebo-controlled, double-blind trial.

OBJECTIVE: Evaluate the effects of ultra-low-dose hormone therapy (Ultra-LD HT) with 17ß-estradiol 0.5 mg and norethisterone acetate 0.1 mg (E2 0.5/NETA 0.1) versus placebo on bone turnover markers (BTM) in postmenopausal women. STUDY DESIGN: A multicenter, double-blind, randomized, placebo-controlled study was performed with 107 participants who received one tablet daily of E2 0.5/NETA 0.1 or placebo for 24-weeks. Bone formation markers-N-terminal propeptide of type I procollagen (PINP) and Bone-specific alkaline phosphatase (BSAP), and bone resorption markers-C-telopeptide of type I collagen (CTX-I) and N-telopeptide crosslinked of type I collagen (NTX) were assessed before and at 12 and 24-weeks of treatment. RESULTS: Women treated with E2 0.5/NETA 0.1 had a significant reduction in the PINP marker from baseline (58.49 ± 21.12 µg/L) to week 12 (48.31 ± 20.99 µg/L) and week 24 (39.16 ± 16.50 µg/L). Placebo group, the PINP marker did not differ significantly. The analysis of the BSAP indicated a significant increase in the placebo group (13.8 ± 5.09 µg/L and 16.29 ± 4.3 µg/L, at baseline and week 24, respectively), whereas in the treatment group the values did not change. The analysis of the NTX marker showed a significant reduction only in the treatment group (43.21 ± 15.26 nM/mM and 33.89 ± 14.9 nM/mM, at baseline and week 24, respectively). CTX-I had a significant decrease in the treatment group from baseline (0.3 ± 0.16 ng/L) to week 12 (0.21 ± 0.14 ng/L) and week 24 (0.21 ± 0.12 ng/L). CONCLUSION: Women receiving E2 0.5/NETA 0.1 experienced reductions in bone resorption and formation markers, an expected effect during the anti-resorptive therapy, suggesting a protective bone effect with the Ultra-LD HT.

Performance of the Fracture Risk Assessment Tool Associated with Muscle Mass Measurements and Handgrip to Screen for the Risk of Osteoporosis in Young Postmenopausal Women.

OBJECTIVE: To evaluate the improvement in screening accuracy of the Fracture Risk Assessment Tool (FRAX) for the risk of developing osteoporosis among young postmenopausal women by associating with it clinical muscle mass measures. METHODS: A sample of postmenopausal women was submitted to calcaneal quantitative ultrasound (QUS), application of the FRAX questionnaire, and screening for the risk of developing sarcopenia at a health fair held in the city of São Bernardo do Campo in 2019. The sample also underwent anthropometric measurements, muscle mass, walking speed and handgrip tests. A major osteoporotic fracture (MOF) risk ≥ 8.5% on the FRAX, a classification of medium risk on the clinical guideline of the National Osteoporosis Guideline Group (NOGG), and a QUS T-score ≤ -1.8 sd were considered risks of having low bone mass, and QUS T-score ≤ -2.5sd, risk of having fractures. RESULTS: In total, 198 women were evaluated, with a median age of 64 ± 7.7 years, median body mass index (BMI) of 27.3 ± 5.3 kg/m2 and median QUS T-score of -1.3 ± 1.3 sd. The accuracy of the FRAX with a MOF risk ≥ 8.5% to identify women with T-scores ≤ -1.8 sd was poor, with an area under the curve (AUC) of 0.604 (95% confidence interval [95%CI]: 0.509-0.694) for women under 65 years of age, and of 0.642 (95%CI: 0.571-0.709) when age was not considered. Including data on muscle mass in the statistical analysis led to a significant improvement for the group of women under 65 years of age, with an AUC of 0,705 (95%CI: 0.612-0.786). The ability of the high-risk NOGG tool to identify T-scores ≤ -1.8 sd was limited. CONCLUSION: Clinical muscle mass measurements increased the accuracy of the FRAX to screen for osteoporosis in women aged under 65 years.

OBJETIVO: Avaliar a melhora da precisão da Fracture Risk Assessment Tool (Ferramenta de Avaliação do Risco de Fraturas, FRAX, em inglês) no rastreio do risco de desenvolver osteoporose em mulheres jovens pós-menopáusicas com a associação de medidas clínicas de massa muscular e preensão manual. MéTODOS: Uma amostra de mulheres pós-menopáusicas foi submetida a ultrassom quantitativo (USQ) de calcâneo, à aplicação do questionário FRAX, e rastreadas quanto ao risco de desenvolver sarcopenia em uma feira de saúde realizada em 2019 em São Bernardo do Campo. Além disso, a amostra também foi submetida a antropometria, e a testes de massa muscular, velocidade de marcha, e preensão manual. Um risco de grandes fraturas osteoporóticas (GFOs) ≥ 8,5% no FRAX, classificação de médio risco nas diretrizes clínicas do National Osteoporosis Guideline Group (NOGG), e T-score no USQ ≤ -1,8 dp foram considerados riscos de ter baixa massa óssea, e T-score no QUS ≤ -2,5 sd, risco de ter fraturas. RESULTADOS: Ao todo, 198 mulheres foram avaliadas, com idade média de 64 ± 7,7 anos, índice de massa corporal (IMC) médio de 27,3 ± 5,3 kg/m2, e T-score médio no USQ de -1,3 ± 1,3 sd. A precisão do FRAX com um risco de GFO ≥ 8,5% para identificar mulheres com T-score ≤ -1,8 dp foi precária, com uma área sob a curva (ASC) de 0,604 (intervalo de confiança de 95% [IC95%]: 0,509­0,694), para mulheres menores de 65 anos de idade, e de 0,642 (IC95%: 0,571­0,709) quando a idade não foi considerada. A inclusão de dados da massa muscular na análise estatística levou a uma melhora significativa no grupo menor de 65 anos de idade, com uma ASC de 0,705 (IC95%: 0,612­0,786). A habilidade da ferramenta NOGG de alto risco para identificar T-scores ≤ -1,8 dp foi limitada. CONCLUSãO: As medidas clínicas da massa muscular aumentaram a precisão do FRAX no rastreio de osteoporose em mulheres menores de 65 anos de idade.

Performance of the Fracture Risk Assessment Tool Associated with Muscle Mass Measurements and Handgrip to Screen for the Risk of Osteoporosis in Young Postmenopausal Women / Desempenho da ferramenta de avaliação de risco de fraturas associada à medida de massa muscular e à preensão manual no rastreio de risco de osteoporose em mulheres jovens pós-menopáusicas

Abstract Objective To evaluate the improvement in screening accuracy of the Fracture Risk Assessment Tool (FRAX) for the risk of developing osteoporosis among young postmenopausal women by associating with it clinical muscle mass measures. Methods A sample of postmenopausal women was submitted to calcaneal quantitative ultrasound (QUS), application of the FRAX questionnaire, and screening for the risk of developing sarcopenia at a health fair held in the city of São Bernardo do Campo in 2019. The sample also underwent anthropometric measurements, muscle mass, walking speed and handgrip tests. A major osteoporotic fracture (MOF) risk ≥ 8.5% on the FRAX, a classification of medium risk on the clinical guideline of the National Osteoporosis Guideline Group (NOGG), and a QUS T-score ≤ -1.8 sd were considered risks of having low bone mass, and QUS T-score ≤ -2.5sd, risk of having fractures. Results In total, 198 women were evaluated, with a median age of 64±7.7 years, median body mass index (BMI) of 27.3±5.3 kg/m2 and median QUS T-score of -1.3±1.3 sd. The accuracy of the FRAX with a MOF risk ≥ 8.5% to identify women with T-scores ≤ -1.8 sd was poor, with an area under the curve (AUC) of 0.604 (95% confidence interval [95%CI]: 0.509-0.694) for women under 65 years of age, and of 0.642 (95%CI: 0.571-0.709) when age was not considered. Including data on muscle mass in the statistical analysis led to a significant improvement for the group of women under 65 years of age, with an AUC of 0,705 (95%CI: 0.612-0.786). The ability of the high-risk NOGG tool to identify T-scores ≤ -1.8 sd was limited. Conclusion Clinical muscle mass measurements increased the accuracy of the FRAX to screen for osteoporosis in women aged under 65 years.

Resumo Objetivo Avaliar a melhora da precisão da Fracture Risk Assessment Tool (Ferramenta de Avaliação do Risco de Fraturas, FRAX, em inglês) no rastreio do risco de desenvolver osteoporose em mulheres jovens pós-menopáusicas com a associação de medidas clínicas de massa muscular e preensão manual. Métodos Uma amostra de mulheres pós-menopáusicas foi submetida a ultrassom quantitativo (USQ) de calcâneo, à aplicação do questionário FRAX, e rastreadas quanto ao risco de desenvolver sarcopenia em uma feira de saúde realizada em 2019 em São Bernardo do Campo. Alémdisso, a amostra tambémfoi submetida a antropometria, e a testes de massa muscular, velocidade de marcha, e preensão manual. Um risco de grandes fraturas osteoporóticas (GFOs) ≥ 8,5% no FRAX, classificação de médio risco nas diretrizes clínicas do National Osteoporosis Guideline Group (NOGG), e T-score no USQ ≤ -1,8 dp foram considerados riscos de ter baixa massa óssea, e T-score no QUS ≤ -2,5 sd, risco de ter fraturas. Resultados Ao todo, 198 mulheres foram avaliadas, com idade média de 64±7,7 anos, índice de massa corporal (IMC) médio de 27,3±5,3 kg/m2, e T-score médio no USQ de -1,3±1,3 sd. A precisão do FRAX comumrisco de GFO≥ 8,5% para identificar mulheres com T-score ≤ -1,8 dp foi precária, com uma área sob a curva (ASC) de 0,604 (intervalo de confiança de 95% [IC95%]: 0,509-0,694), para mulheres menores de 65 anos de idade, e de 0,642 (IC95%: 0,571-0,709) quando a idade não foi considerada. A inclusão de dados da massa muscular na análise estatística levou a uma melhora significativa no grupo menor de 65 anos de idade, com uma ASC de 0,705 (IC95%: 0,612-0,786). A habilidade da ferramenta NOGG de alto risco para identificar T-scores ≤ -1,8 dp foi limitada. Conclusão As medidas clínicas da massa muscular aumentaram a precisão do FRAX no rastreio de osteoporose em mulheres menores de 65 anos de idade.

White, brown, and bone marrow adipose tissue behavior in DHEA-induced PCOS mice.

METHODS: Thirty-one female C57BL/6J mice were divided into four groups: two were treated with subcutaneous dehydroepiandrosterone (DHEA) implants and divided into normal and hypercaloric diet (HFD). Two were control and divided into normal and HFD. Presence of insulin resistance, growth, and adipocyte markers expression of white and brown adipose tissues and growth and inflammatory cytokines expression of bone marrow adipose tissue were evaluated. RESULTS: Hypercaloric diet groups presented higher total weight gain and huge growth in all fat sites, except bone marrow. They also demonstrated greater expression of adipocyte markers in sites of white adipose tissue. DHEA + HFD group showed more insulin intolerance than all other groups. DHEA shows to abrogate AdipoQ expression in all fatty tissues. CONCLUSIONS: DHEA alone does not influence adipose tissue growth, but contributes to increased insulin resistance and influences the expression of adipokines. Proximal MAT showed different behavior from the other fat depot.

Bleeding Pattern and Management of Unexpected Bleeding/Spotting with an Extended Regimen of a Combination of Ethinylestradiol 20 mcg and Drospirenone 3 mg.

OBJECTIVE: To compare the bleeding pattern in women using ethinylestradiol 20 mcg/drospirenone 3 mg (EE 20 mcg/DRSP 3 mg) in a 24/4-day cyclic regimen with an extended regimen. Unexpected bleeding/spotting in the extended regimen group was managed by allowing a 4-day hormone-free interval (HFI). METHODS: This was a randomized, prospective, open-label, multicenter study. Participants (N = 348) were randomized to receive EE 20 mcg/DRSP 3 mg in either an extended regimen (EE/DRSPes group) or a 24/4-day cyclic regimen (EE/DRSP24/4 group) and followed for 168 days. In the EE/DRSPes group, a 4-day HFI was allowed whenever unexpected bleeding/spotting persisted for ≥7 consecutive days. The participants assessed their bleeding daily as "no bleeding," "spotting," or "light," "moderate," or "heavy" bleeding according to a predefined scale. RESULTS: EE/DRSPes group experienced fewer days of bleeding than those using a 24/4 cyclic regimen (P < 0.001). After 168 days, 57.5% of women in the EE/DRSPes group achieved complete amenorrhea (i.e., neither bleeding nor spotting) and 73.9% achieved "no bleeding" (i.e., no bleeding with or without spotting) during the final 28-day interval of the study period. Women in the extended group who instituted the 4-day HFI experienced a 94.1% rate of successful management of unexpected bleeding/spotting. CONCLUSION: The use of EE 20 mcg/DRSP 3 mg in an extended regimen resulted in high rates of amenorrhea and "no bleeding". Unexpected bleeding/spotting in the EE/DRSPes group could be managed effectively with a 4-day HFI. CLINICAL TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN57661673): http://www.controlled-trials.com/isrctn/pf/57661673.

The Effect of Testosterone Replacement on Intramedullary, Inguinal and Visceral Fat in Ovariectomized Rats.

OBJECTIVE: The present article aims to evaluate the impact of testosterone treatment on the expansion of visceral, subcutaneous and intramedullary adipose tissue of ovariectomized rats and the visceral and subcutaneous fat expression of peroxisome proliferator-activated receptors (PPARs) gamma. METHODS: In total 48 female Wistar rats were castrated and randomly divided into 6 treatment groups: group E2 was submitted to estradiol 5 µg/day; group T, to testosterone 5 µg/day; group E2 + T, to estradiol 5 µg/day + testosterone 5 µg/day; group TT, to testosterone 30 µg/day; group E2 + TT, to estradiol 5 µg/day + testosterone 30 µg/day; and placebo was administered to group P. After 5 weeks, the rats were euthanized, the inguinal and visceral adipose tissues were harvested, weighted, and had their PPAR gamma expression evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The right femurs were harvested and histologically prepared to perform the number count of the intramedullary adipocytes. RESULTS: The expansion of visceral fat tissue was much higher in the TT group when compared with other treated groups (p < 0.001). The TT group also showed a higher expansion of inguinal fat (p < 0.01), and groups E2 + T and E2 + TT presented lower growth compared to the P group (p < 0.01). The number of femur intramedullary adipocytes only showed significant differences between groups TT and E2 + TT (p < 0.05). The expression of PPAR gamma showed no differences among the groups. CONCLUSION: The use of testosterone in high doses leads to an important expansion in both visceral and inguinal adipose tissues. Association with estradiol exerts an expansion-repressive effect on the visceral and inguinal adipose tissues.

OBJETIVO: Este artigo tem como objetivo avaliar o impacto do tratamento com testosterona na expansão dos tecidos adiposos visceral, subcutâneo e intramedular de ratas ovariectomizadas e a expressão de receptores ativados por proliferadores de peroxissoma (RAPPs) gama nas gorduras visceral e subcutânea. MéTODOS: No total, 48 ratas Wistar foram castradas e divididas aleatoriamente em 6 grupos de tratamento: o grupo E2 recebeu estradiol 5 µg/dia; o grupo T, testosterona 5 µg/dia; o grupo E2 + T, estradiol 5 µg/dia + testosterona 5 µg/dia; o grupo TT, testosterona 30 µg/dia; o grupo E2 + TT, estradiol 5 µg/dia + testosterona 30 µg/dia; e o grupo P recebeu placebo. Após 5 semanas, as ratas foram submetidas a eutanásia, o tecido adiposo inguinal e visceral foi coletado, pesado, e se avaliou a expressão dos RAPP gama por reação em cadeia da polimerase via transcriptase reversa quantitativa (RCP-TRq). Os ossos do fêmur direito foram colhidos e processados histologicamente para contagem de números de adipócitos intramedulares. RESULTADOS: A expansão do tecido adiposo visceral foi muito maior no grupo TT quando comparado a outros grupos tratados (p < 0,001). O grupo TT também apresentou maior expansão da gordura inguinal (p < 0,01), e os grupos E2 + T e E2 + TT apresentaram menor crescimento em relação ao grupo P (p < 0,01). O número de adipócitos intramedulares no fêmur mostrou apenas diferenças significativas entre os grupos TT e E2 + TT (p < 0,05). A expressão de RAPP gama não mostrou diferenças entre os grupos. CONCLUSãO: O uso de testosterona em altas doses leva a uma importante expansão nos tecidos adiposos visceral e inguinal. A associação com o estradiol exerce um efeito repressivo de expansão nos tecidos adiposos visceral e inguinal.

The effect of testosterone replacement on intramedullary, inguinal and visceral fat in ovariectomized rats / Efeito da reposição de testosterona na gordura intramedular, inguinal e visceral em ratas ovariectomizadas

Abstract Objective The present article aims to evaluate the impact of testosterone treatment on the expansion of visceral, subcutaneous and intramedullary adipose tissue of ovariectomized rats and the visceral and subcutaneous fat expression of peroxisome proliferator-activated receptors (PPARs) gamma. Methods In total 48 female Wistar rats were castrated and randomly divided into 6 treatment groups: group E2 was submitted to estradiol 5 μg/day; group T, to testosterone 5 μg/day; group E2+ T, to estradiol 5 μg/day + testosterone 5 μg/day; group TT, to testosterone 30 μg/day; group E2+ TT, to estradiol 5 μg/day+ testosterone 30 μg/day; and placebo was administered to group P. After 5 weeks, the rats were euthanized, the inguinal and visceral adipose tissues were harvested, weighted, and had their PPAR gamma expression evaluated by reverse transcription quantitative polymerase chain reaction (RTqPCR). The right femurs were harvested and histologically prepared to performthe number count of the intramedullary adipocytes. Results The expansion of visceral fat tissue was much higher in the TT group when compared with other treated groups (p < 0.001). The TT group also showed a higher expansion of inguinal fat (p < 0.01), and groups E2 +T and E2+ TT presented lower growth compared to the P group (p < 0.01). The number of femur intramedullary adipocytes only showed significant differences between groups TT and E2 + TT (p < 0.05). The expression of PPAR gamma showed no differences among the groups. Conclusion The use of testosterone in high doses leads to an important expansion in both visceral and inguinal adipose tissues. Association with estradiol exerts an expansion-repressive effect on the visceral and inguinal adipose tissues.

Resumo Objetivo Este artigo tem como objetivo avaliar o impacto do tratamento com testosterona na expansão dos tecidos adiposos visceral, subcutâneo e intramedular de ratas ovariectomizadas e a expressão de receptores ativados por proliferadores de peroxissoma (RAPPs) gama nas gorduras visceral e subcutânea. Métodos No total, 48 ratas Wistar foram castradas e divididas aleatoriamente em 6 grupos de tratamento: o grupo E2 recebeu estradiol 5 μg/dia; o grupo T, testosterona 5 μg/dia; o grupo E2 + T, estradiol 5 μg/dia + testosterona 5 μg/dia; o grupo TT, testosterona 30 μg/dia; o grupo E2 + TT, estradiol 5 μg/dia + testosterona 30 μg/dia; e o grupo P recebeu placebo. Após 5 semanas, as ratas foram submetidas a eutanásia, o tecido adiposo inguinal e visceral foi coletado, pesado, e se avaliou a expressão dos RAPP gama por reação em cadeia da polimerase via transcriptase reversa quantitativa (RCP-TRq). Os ossos do fêmur direito foram colhidos e processados histologicamente para contagem de números de adipócitos intramedulares. Resultados A expansão do tecido adiposo visceral foi muito maior no grupo TT quando comparado a outros grupos tratados (p < 0,001). O grupo TT também apresentou maior expansão da gordura inguinal (p < 0,01), e os grupos E2 +T e E2 + TT apresentaram menor crescimento em relação ao grupo P (p < 0,01). O número de adipócitos intramedulares no fêmur mostrou apenas diferenças significativas entre os grupos TT e E2 + TT (p < 0,05). A expressão de RAPP gama não mostrou diferenças entre os grupos. Conclusão O uso de testosterona emaltas doses leva a uma importante expansão nos tecidos adiposos visceral e inguinal. A associação com o estradiol exerce um efeito repressivo de expansão nos tecidos adiposos visceral e inguinal.

Effect of Testosterone on Proliferation Markers and Apoptosis in Breasts of Ovariectomized Rats.

OBJECTIVE: To investigate the action of testosterone (T), isolated or associated with estradiol benzoate (EB), on the proliferation markers and apoptosis of breasts of ovariectomized rats. METHODS: A total of 48 castrated female Wistar rats were divided into 6 groups, and each of them were submitted to one of the following treatments for 5 weeks: 1) control; 2) EB 50 mcg/day + T 50 mcg/day; 3) T 50mcg/day; 4) EB 50 mcg + T 300 mcg/day; 5) T 300 mcg/day; and 6) EB 50 mcg/day. After the treatment, the mammary tissue was submitted to a histological analysis and immunoexpression evaluation of proliferation markers (proliferating cell nuclear antigen, PCNA) and apoptosis (caspase-3). RESULTS: There was a statistically significant difference among the groups regarding microcalcifications and secretory activity, with higher prevalence in the groups treated with EB. There was no difference among the groups regarding atrophy, but a higher prevalence of atrophy was found in the groups that received T versus those that received EB + T. There was a difference among the groups regarding the PCNA (p = 0.028), with higher expression in the group submitted to EB + T 300 mcg/day. Regarding caspase-3, there was no difference among the groups; however, in the group submitted to EB + T 300 mcg/day, the expression was higher than in the isolated T group. CONCLUSION: Isolated T did not have a proliferative effect on the mammary tissue, contrary to EB. Testosterone in combination with EB may or may not decrease the proliferation, depending on the dose of T.

OBJETIVO: Investigar a ação da testosterona (T) isolada ou associada ao benzoato de estradiol (EB) na proliferação e apoptose de mamas de ratas ovariectomizadas. MéTODOS: Um total de 48 ratas Wistar castradas foram divididas em 6 grupos, e cada um foi submetido a um dos seguintes tratamentos durante 5 semanas: 1) controle; 2) BE 50 mcg/dia + T 50 mcg/dia; 3) T 50 mcg/dia; 4) BE 50 mcg + T 300 mcg/dia; e) T 300 mcg/dia; e f) BE 50 mcg/dia. Após o tratamento, o tecido mamário foi submetido a análise histológica e avaliação de imunoexpressão de marcadores de proliferação (antígeno nuclear de células proliferantes, PCNA) e apoptose (caspase-3). RESULTADOS: Houve diferença estatisticamente significante entre os grupos com relação às microcalcificações e à atividade secretora, com maior prevalência nos grupos tratados com BE. Não houve diferença entre os grupos quanto à atrofia, mas houve maior prevalência de atrofia nos grupos que receberam T versus os que receberam BE + T. Houve diferença entre os grupos quanto ao ANCP (p = 0,028), com maior expressão no grupo BE + T 300 mcg/dia. Com relação à caspase-3, não houve diferença entre os grupos, mas, no grupo BE + T 300 mcg/dia, a expressão foi maior do que no grupo de T isolada. CONCLUSãO: A T isolada não apresentou efeito proliferativo do tecido mamário, contrariamente ao EB. A T em associação ao EB pode diminuir ou não a proliferação, a depender da dose de T.

Effect of testosterone on proliferation markers and apoptosis in breasts of ovariectomized rats / Efeito da testosterona em marcadores de proliferação e apoptose em mamas de ratas ovariectomizadas

Abstract Objective To investigate the action of testosterone (T), isolated or associated with estradiol benzoate (EB), on the proliferation markers and apoptosis of breasts of ovariectomized rats. Methods A total of 48 castrated female Wistar rats were divided into 6 groups, and each of them were submitted to one of the following treatments for 5 weeks: 1) control; 2) EB 50 mcg/day + T 50 mcg/day; 3) T 50mcg/day; 4) EB 50 mcg +T 300 mcg/day; 5) T 300 mcg/day; and 6) EB 50 mcg/day. After the treatment, the mammary tissue was submitted to a histological analysis and immunoexpression evaluation of proliferation markers (proliferating cell nuclear antigen, PCNA) and apoptosis (caspase-3). Results There was a statistically significant difference among the groups regarding microcalcifications and secretory activity, with higher prevalence in the groups treated with EB. There was no difference among the groups regarding atrophy, but a higher prevalence of atrophy was found in the groups that received T versus those that received EB +T. There was a difference among the groups regarding the PCNA (p = 0.028), with higher expression in the group submitted to EB +T 300 mcg/day. Regarding caspase-3, there was no difference among the groups; however, in the group submitted to EB +T 300 mcg/day, the expression was higher than in the isolated T group. Conclusion Isolated T did not have a proliferative effect on the mammary tissue, contrary to EB. Testosterone in combination with EB may or may not decrease the proliferation, depending on the dose of T.

Resumo Objetivo Investigar a ação da testosterona (T) isolada ou associada ao benzoato de estradiol (EB) na proliferação e apoptose de mamas de ratas ovariectomizadas. Métodos Um total de 48 ratas Wistar castradas foram divididas em 6 grupos, e cada um foi submetido a um dos seguintes tratamentos durante 5 semanas: 1) controle; 2) BE 50 mcg/dia + T 50mcg/dia; 3) T 50 mcg/dia; 4) BE 50 mcg + T 300mcg/dia; e) T 300 mcg/dia; e f) BE 50 mcg/dia. Após o tratamento, o tecido mamário foi submetido a análise histológica e avaliação de imunoexpressão de marcadores de proliferação (antígeno nuclear de células proliferantes, PCNA) e apoptose (caspase-3). Resultados Houve diferença estatisticamente significante entre os grupos com relação às microcalcificações e à atividade secretora, com maior prevalência nos grupos tratados com BE. Não houve diferença entre os grupos quanto à atrofia, mas houve maior prevalência de atrofia nos grupos que receberam T versus os que receberam BE+ T. Houve diferença entre os grupos quanto ao ANCP (p= 0,028), com maior expressão no grupo BE+ T 300 mcg/dia. Com relação à caspase-3, não houve diferença entre os grupos, mas, no grupo BE+ T 300 mcg/dia, a expressão foi maior do que no grupo de T isolada. Conclusão A T isolada não apresentou efeito proliferativo do tecido mamário, contrariamente ao EB. A T em associação ao EB pode diminuir ou não a proliferação, a depender da dose de T.