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1.
Maturitas ; 130: 32-37, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31706433

RESUMO

INTRODUCTION: It is unclear how aging and menopause-induced lipid changes contribute to the elevated cardiovascular risk in menopausal women. We examined the association between lipid profiles and menopausal status and duration of menopause in the Longitudinal Study of Adult Health (ELSA-Brasil). METHODS: This is a cross-sectional analysis of baseline data from women in the ELSA-Brasil, stratified by duration of menopause into 5 groups: pre-menopause, <2 years, 2-5.9 years, 6-9.9 years and ≥10 years of menopause, excluding menopause <40 years or of non-natural cause; also excluded were women using lipid-lowering drugs or hormone replacement. Comparisons were performed using ANOVA with Bonferroni correction. Associations of menopause categories and time since menopause with lipid variables obtained by vertical auto-profile were tested using multiple linear regression. RESULTS: From 1916 women, postmenopausal groups had unadjusted higher total cholesterol, LDL-c, real LDL-c, IDL-c, VLDL-c, triglycerides, non-HDL-c, VLDL3-c, triglyceride-rich lipoprotein remnants (TRL-c) and buoyant LDL-c concentrations than pre-menopausal women, with no difference among postmenopausal groups. In multiple linear regression, duration of menopause <2 years was significantly associated with TRL-c [7.21 mg/dL (95% CI 3.59-10.84)] and VLDL3-c [2.43 mg/dL (95%CI 1.02-3.83)]. No associations of menopausal categories with HDL-c or LDL-c subfractions were found, and nor were associations of time since menopause with lipid subfractions. CONCLUSIONS: In a large sample of Brazilian women, deterioration of the lipid profile following menopause was confirmed, which could contribute to the increased cardiovascular risk. Our findings suggest a postmenopausal elevation in triglyceride-rich lipoprotein remnants. How lipoprotein subfractions change after the onset of menopause warrants investigation in studies with appropriate designs.


Assuntos
Pós-Menopausa/sangue , Pré-Menopausa/sangue , Adulto , Idoso , Brasil , LDL-Colesterol/sangue , VLDL-Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Metabolismo dos Lipídeos , Lipoproteínas/sangue , Estudos Longitudinais , Pessoa de Meia-Idade , Pós-Menopausa/fisiologia , Pré-Menopausa/fisiologia , Fatores de Tempo , Triglicerídeos/sangue
2.
J Med Life ; 12(3): 296-300, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31666834

RESUMO

During menstruation, endometrial hemostasis is achieved by platelet aggregation, fibrin deposition, and thrombus formation that interact with local endocrine and immunological factors which cause termination of menstrual bleeding. Interactions between steroidal sex hormones and platelet functions are not well understood. The aim of this study was to evaluate the effect of platelet function during the menstrual cycle and luteal phase in women of reproductive age. The cross-sectional study on women of reproductive age included 44 healthy women. Platelet function was assessed by PFA-100TM analyzer with collagen/epinephrine and collagen/ADP cartridges during the menstrual cycle and luteal phase. There were no significant differences in platelet function between menstruation and ovulatory phase. Platelet activity in Arab collagen/epinephrine cartridge increased during menstruation compared to non-Arab ethnic subjects and no significant differences in platelet function were found when using collagen/ADP cartridge. This study suggested modulation in platelet functions during menstruation and luteal phase in women of reproductive age. Further studies, including a large number of subjects, platelet genetic and progesterone factors change in platelet clotting associated to menstrual cycle should be conducted.


Assuntos
Plaquetas/fisiologia , Menstruação/fisiologia , Ovulação/fisiologia , Adulto , Colágeno/farmacologia , Estudos Transversais , Epinefrina/farmacologia , Feminino , Humanos , Pré-Menopausa/fisiologia
3.
Presse Med ; 48(11 Pt 1): 1244-1248, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31732361

RESUMO

Before menopause, women are protected from the risk of hypertension and atherosclerosis by endogenous estrogens. Estrogens have a vasoprotective role, while progesterone seems to have a neutral effect. Exogenous estrogens used in menopausal treatment have vascular effects. These effects depend of type, dose and administration type, and with age and atherosclerosis stages. Synthetic progestins have varying clinical effects. Each drug must be evaluated separately.


Assuntos
Aterosclerose/prevenção & controle , Estrogênios/farmacologia , Estrogênios/fisiologia , Hipertensão/prevenção & controle , Pré-Menopausa , Progestinas/farmacologia , Artérias/efeitos dos fármacos , Artérias/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Terapia de Reposição de Estrogênios , Etinilestradiol/farmacocinética , Etinilestradiol/farmacologia , Feminino , Humanos , Menopausa/fisiologia , Pré-Menopausa/fisiologia , Progesterona/fisiologia , Moduladores Seletivos de Receptor Estrogênico/farmacologia
4.
Reprod Biol Endocrinol ; 17(1): 67, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31420039

RESUMO

Polycystic ovary syndrome (PCOS) is a prevalent hormonal disorder of premenopausal women worldwide and is characterized by reproductive, endocrine, and metabolic abnormalities. The clinical manifestations of PCOS include oligomenorrhea or amenorrhea, hyperandrogenism, ovarian polycystic changes, and infertility. Women with PCOS are at an increased risk of suffering from type 2 diabetes; me\tabolic syndrome; cardiovascular events, such as hypertension, dyslipidemia; gynecological diseases, including infertility, endometrial dysplasia, endometrial cancer, and ovarian malignant tumors; pregnancy complications, such as premature birth, low birthweight, and eclampsia; and emotional and mental disorders in the future. Although numerous studies have focused on PCOS, the underlying pathophysiological mechanisms of this disease remain unclear. Mitochondria play a key role in energy production, and mitochondrial dysfunction at the cellular level can affect systemic metabolic balance. The recent wide acceptance of functional mitochondrial disorders as a correlated factor of numerous diseases has led to the presupposition that abnormal mitochondrial metabolic markers are associated with PCOS. Studies conducted in the past few years have confirmed that increased oxidative stress is associated with the progression and related complications of PCOS and have proven the relationship between other mitochondrial dysfunctions and PCOS. Thus, this review aims to summarize and discuss previous and recent findings concerning the relationship between mitochondrial dysfunction and PCOS.


Assuntos
Mitocôndrias/fisiologia , Ovário/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Pré-Menopausa/fisiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Infertilidade/metabolismo , Infertilidade/fisiopatologia , Mitocôndrias/metabolismo , Ovário/metabolismo , Ovário/patologia , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/metabolismo , Pré-Menopausa/metabolismo , Fatores de Risco
5.
Biomed Res Int ; 2019: 8598152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31011581

RESUMO

Objective: To create a prediction model including clinical variables for the prediction of premalignant/malignant endometrial pathology in premenopausal women with abnormal uterine bleeding (AUB). Methods: This is an observational retrospective study including 240 premenopausal women with AUB referred to diagnostic hysteroscopy. Based on the presence of endometrial hyperplasia (EH) or cancer (EC), the women were divided into cases (EH/EC) and controls (no EH/EC). Univariate, stepwise logistic regression and ROC curve analysis were performed. Results: 12 women had EH/EC (5%). Stepwise logistic regression analysis showed that EH/EC associated significantly with BMI ≥ 30 (OR=7.70, 95% CI 1.90 to 31.17), diabetes (OR=9.71, 95% CI 1.63 to 57.81), and a thickened endometrium (OR=1.20, 95% CI 1.08 to 1.34, criterion > 11 mm). The AUC was 0.854 (95% confidence intervals 0.803 to 0.896, p<0.0001). Considering the pretest probability for EH/EC of 5%, the prediction model with a positive likelihood ratio of 8.14 showed a posttest probability of 30%. The simultaneous presence of two or three risk factors was significantly more common in women with EH/EC than controls (50% vs. 6.6 and 25% vs. 0%, respectively, p<0.0001). Conclusion: When premenopausal vaginal bleeding occurs in diabetic obese women with ET > 11 mm, the percentage of premalignant/malignant endometrial pathology increases by 25%. It is likely that the simultaneous presence of several risk factors is necessary to significantly increase the probability of endometrial pathology.


Assuntos
Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/patologia , Lesões Pré-Cancerosas/patologia , Doenças Uterinas/patologia , Hemorragia Uterina/patologia , Adulto , Endométrio/patologia , Feminino , Humanos , Histeroscopia/métodos , Pessoa de Meia-Idade , Pós-Menopausa/fisiologia , Pré-Menopausa/fisiologia , Estudos Retrospectivos , Fatores de Risco
6.
Int J Sports Med ; 40(4): 245-252, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30836390

RESUMO

The early vascular adaptation to indoor cycling, a popular activity at many fitness centres, is incompletely evaluated. Forty two healthy women (21-45 years) underwent measurements of arterial wall properties and geometry as well as a maximal bicycle exercise test before and after a 3 months period during which 21 of the women joined indoor cycling classes at a gym 2-3 times per week, while 21 women served as time controls. Peak work load increased by in average 16% (p<0.001) and ascending aortic diameter by 4% (p<0.01) in the exercise group, while unchanged in control group. The exercise intervention had no significant influence on the local intima-media thickness, blood pressure or the pulse pressure wave configuration while the carotid artery distensibility (p<0.05) was higher after the intervention. There was a positive correlation between change in (Δ) peak work load and Δ-diameter of tubular ascending aorta (r=0.42, p<0.01) in the exercise group. In conclusion, after only 3 months of bicycle exercise training, signs of central arterial remodelling were seen in premenopausal women, which was associated to improvement in exercise capacity.


Assuntos
Adaptação Fisiológica , Ciclismo/fisiologia , Vasos Sanguíneos/fisiologia , Pré-Menopausa/fisiologia , Adulto , Aorta/anatomia & histologia , Aorta/fisiologia , Pressão Sanguínea , Artéria Braquial/fisiologia , Artéria Carótida Primitiva/fisiologia , Espessura Intima-Media Carotídea , Teste de Esforço , Feminino , Frequência Cardíaca , Humanos , Pessoa de Meia-Idade , Pulso Arterial , Remodelação Vascular , Adulto Jovem
7.
Nutrients ; 11(3)2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30841631

RESUMO

The Mediterranean diet (MD) has been associated with an improvement in health and an increase in longevity. Certain components of a MD can play a role in the prevention of osteoporosis and/or hip fracture. We investigated the association between the degree of adherence to a MD and bone mineral density (BMD) measured in several bone areas in a population of Spanish premenopausal women. We analyzed 442 premenopausal women aged 42.73 ± 6.67 years. Bone measurements were obtained using quantitative bone ultrasound (QUS) for the phalanx, dual energy X-ray absorptiometry (DXA) for the lumbar spine, Ward's triangle, trochanter, and hip, and peripheral quantitative computed tomography (pQCT) for the non-dominant distal forearm. MD adherence was evaluated with MedDietScore. Amplitude-dependent speed of sound (Ad-SOS), BMD, and volumetric bone mineral density (vBMD) (total, trabecular, and cortical bone density) were positively associated with higher adherence to the MD (p < 0.05). Adherence to the MD was significantly associated with QUS, BMD, and vBMD in multiple regression analysis; QUS: Ad-SOS (m/s) ß = 0.099 (p = 0.030); BMD (g/cm²): femur neck ß = 0.114 (p = 0.010) and Ward's triangle ß = 0.125 (p = 0.006); vBMD (mg/cm³): total density ß = 0.119 (p = 0.036), trabecular density ß = 0.120 (p = 0.035), and cortical density ß = 0.122 (p = 0.032). We conclude that the adherence to the MD was positively associated with better bone mass in Spanish premenopausal women.


Assuntos
Densidade Óssea/fisiologia , Dieta Mediterrânea/estatística & dados numéricos , Cooperação do Paciente/estatística & dados numéricos , Pré-Menopausa/fisiologia , Absorciometria de Fóton , Adulto , Osso Esponjoso/diagnóstico por imagem , Estudos Transversais , Dieta Mediterrânea/psicologia , Feminino , Antebraço/diagnóstico por imagem , Humanos , Vértebras Lombares/diagnóstico por imagem , Pessoa de Meia-Idade , Pré-Menopausa/psicologia , Espanha , Tomografia Computadorizada por Raios X
8.
Osteoporos Int ; 30(5): 1059-1069, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30719548

RESUMO

Analyses using the largest Korean cohort of adrenal incidentaloma (AI) revealed that subtle cortisol excess in premenopausal women and reduced dehydroepiandrosterone-sulfate (DHEA-S) in postmenopausal women and men are associated with bone mineral density (BMD) reduction in Asian patients with subclinical hypercortisolism (SH). INTRODUCTION: Few studies evaluated bone metabolism in Asians with SH. We investigated associations of cortisol and DHEA-S, an adrenal androgen, with BMD in Asians with AI, with or without SH. METHODS: We used cross-sectional data of a prospective multicenter study from Korea. We measured BMD, bone turnover markers, cortisol levels after 1-mg dexamethasone suppression test (1-mg DST), DHEA-S, and baseline cortisol to DHEA-S ratio (cort/DHEA-S) in 109 AI patients with SH (18 premenopausal, 38 postmenopausal women, and 53 men) and 686 with non-functional AI (NFAI; 59 premenopausal, 199 postmenopausal women, and 428 men). RESULTS: Pre- and postmenopausal women, but not men, with SH had lower BMDs at lumbar spine (LS) than those with NFAI (P = 0.008~0.016). Premenopausal women with SH also had lower BMDs at the hip than those with NFAI (P = 0.009~0.012). After adjusting for confounders, cortisol levels after 1-mg DST demonstrated inverse associations with BMDs at all skeletal sites only in premenopausal women (ß = - 0.042~- 0.033, P = 0.019~0.040). DHEA-S had positive associations with LS BMD in postmenopausal women (ß = 0.096, P = 0.001) and men (ß = 0.029, P = 0.038). The cort/DHEA-S had inverse associations with LS BMD in postmenopausal women (ß = - 0.081, P = 0.004) and men (ß = - 0.029, P = 0.011). These inverse associations of cort/DHEA-S remained significant after adjusting for cortisol levels after 1-mg DST (ß = - 0.079~- 0.026, P = 0.006~0.029). In postmenopausal women, the odds ratios of lower BMD by DHEA-S and cort/DHEA-S was 0.26 (95% CI, 0.08-0.82) and 3.40 (95% CI, 1.12-10.33), respectively. CONCLUSION: Subtle cortisol excess in premenopausal women and reduced DHEA-S in postmenopausal women and men may contribute to BMD reduction in Asians with SH.


Assuntos
Neoplasias das Glândulas Suprarrenais/sangue , Densidade Óssea/fisiologia , Síndrome de Cushing/sangue , Sulfato de Desidroepiandrosterona/sangue , Hidrocortisona/sangue , Neoplasias das Glândulas Suprarrenais/fisiopatologia , Adulto , Idoso , Biomarcadores/sangue , Remodelação Óssea/fisiologia , Estudos Transversais , Síndrome de Cushing/fisiopatologia , Feminino , Colo do Fêmur/fisiopatologia , Humanos , Hidrocortisona/fisiologia , Achados Incidentais , Vértebras Lombares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/fisiopatologia , Pós-Menopausa/sangue , Pós-Menopausa/fisiologia , Pré-Menopausa/sangue , Pré-Menopausa/fisiologia
9.
Eur J Epidemiol ; 34(3): 235-246, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30721378

RESUMO

Early menopause is associated with an increased risk of subsequent cardiovascular disease (CVD). Few studies have investigated the converse. We examined whether premenopausal CVD events are associated with early age at menopause. We pooled the individual data of 177,131 women from nine studies. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRR) and 95% confidence intervals (CI) for the associations between age at onset of premenopausal CVD events-including coronary heart disease (CHD) and stroke-and age at natural menopause. Altogether 1561 (0.9%) premenopausal participants reported CVD events (including 1130 CHD and 469 stroke) at a mean age of 41.3 years. Compared with women without any premenopausal CVD events, women who experienced a first CVD event before age 35 years had a twofold risk of menopause before age 45 years (early menopause); adjusted RRR (95% CI) of 1.92 (1.17, 3.14) for any CVD, 1.86 (1.01, 3.43) for CHD and 2.17 (1.43, 3.30) for stroke. Women who experienced a first premenopausal CVD event after age 40 years underwent a natural menopause at the expected age (around 51 years). These associations were robust to adjustment for smoking status, BMI, educational level, race/ethnicity, age at menarche, parity, hypertension and family history of CVD. For premenopausal women, a first CVD event before age 35 years is associated with a doubling of the risk of an early menopause, while a first CVD event occurred after 35 years indicates a normal menopause at around 51 years. Shared genetic and environmental factors (such as smoking), as well as compromised vasculature following CVD events, may contribute to this outcome.


Assuntos
Doenças Cardiovasculares/epidemiologia , Menopausa/fisiologia , Pré-Menopausa/fisiologia , Adulto , Idade de Início , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco
10.
Breast Cancer Res Treat ; 175(2): 479-485, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30796655

RESUMO

PURPOSE: The role of non-genetic factors as modifiers of TP53-related hereditary breast cancer (BC) risk is debated. In this regard, little is known about the impact of germline TP53 mutations on BC in sub-Saharan Africa, where the disease often presents in non-contraceptive multiparous premenopausal women with extended history of breastfeeding. Herein, we report the germline TP53 mutations found in a series of 92 Sudanese premenopausal BC patients characterized for reproductive history. METHODS: The entire TP53 coding sequence, including intron-exon boundaries and UTRs, was analyzed via DHPLC and direct sequencing, and the association of TP53 genotypes with BC risk and with individual lifetime exposures to reproductive factors was investigated with statistical tools. RESULTS: The germline TP53 mutation spectrum comprised 20 variants, 15 in the non-coding and 5 in the coding region. The latter included a deleterious missense mutation, c.817C>T (p.Arg273Cys), in a unique patient, and the common and functionally relevant coding polymorphism at amino acid 72 [Pro72Arg (rs1042522)]. The non-coding mutations included c.919+1G>A, a known deleterious splice site mutation, also in a unique patient. Notably, the 2 carriers of deleterious TP53 mutations clustered in the subset of cases with stronger reproductive history relative to childbearing age. When analyzed in comparison to population controls, the codon 72 polymorphism did not reveal associations with BC. CONCLUSIONS: Our study suggests that the codon 72 Arg>Pro polymorphism is not implicated in premenopausal BC susceptibility, whereas multiparity and breastfeeding might be BC risk factors for carriers of deleterious TP53 mutations.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Reprodução/genética , Proteína Supressora de Tumor p53/genética , Adulto , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/fisiopatologia , Feminino , Testes Genéticos , Genótipo , Mutação em Linhagem Germinativa/genética , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Paridade/genética , Gravidez , Pré-Menopausa/genética , Pré-Menopausa/fisiologia , Reprodução/fisiologia , História Reprodutiva , Sudão/epidemiologia
11.
Hum Mol Genet ; 28(8): 1392-1401, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30649302

RESUMO

Anti-Müllerian hormone (AMH) is required for sexual differentiation in the fetus, and in adult females AMH is produced by growing ovarian follicles. Consequently, AMH levels are correlated with ovarian reserve, declining towards menopause when the oocyte pool is exhausted. A previous genome-wide association study identified three genetic variants in and around the AMH gene that explained 25% of variation in AMH levels in adolescent males but did not identify any genetic associations reaching genome-wide significance in adolescent females. To explore the role of genetic variation in determining AMH levels in women of late reproductive age, we carried out a genome-wide meta-analysis in 3344 pre-menopausal women from five cohorts (median age 44-48 years at blood draw). A single genetic variant, rs16991615, previously associated with age at menopause, reached genome-wide significance at P = 3.48 × 10-10, with a per allele difference in age-adjusted inverse normal AMH of 0.26 standard deviations (SD) (95% confidence interval (CI) [0.18,0.34]). We investigated whether genetic determinants of female reproductive lifespan were more generally associated with pre-menopausal AMH levels. Genetically-predicted age at menarche had no robust association but genetically-predicted age at menopause was associated with lower AMH levels by 0.18 SD (95% CI [0.14,0.21]) in age-adjusted inverse normal AMH per one-year earlier age at menopause. Our findings provide genetic support for the well-established use of AMH as a marker of ovarian reserve.


Assuntos
Hormônio Antimülleriano/genética , Pré-Menopausa/fisiologia , Adulto , Fatores Etários , Hormônio Antimülleriano/sangue , Hormônio Antimülleriano/fisiologia , Sequência de Bases , Feminino , Expressão Gênica , Regulação da Expressão Gênica/genética , Estudos de Associação Genética/métodos , Variação Genética/genética , Estudo de Associação Genômica Ampla/métodos , Haplótipos , Humanos , Longevidade , Menarca/genética , Pessoa de Meia-Idade , Mitocôndrias/genética , Folículo Ovariano , Ovário , Polimorfismo de Nucleotídeo Único/genética , Pré-Menopausa/genética , Reprodução/genética , Análise de Sequência de DNA , Transcriptoma/genética
12.
Medicina (Kaunas) ; 55(1)2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30669665

RESUMO

Background and objectives: Regular exercise may stimulate bone formation and reduce the loss of bone mass in premenopausal women. This study aims to evaluate the effect of high-impact physical activity (Zumba®) and low-impact physical activity (Aquagym) on bone mass in inactive middle-aged women. Materials and methods: Fifty-five healthy inactive women (30⁻50 years old) were recruited in Spain in 2016 and were randomly allocated into one of three groups: High impact group (HIG: n = 15), low impact group (LIG: n = 12) and control group (CG: n = 28). HIG and LIG were recruited from Madrid and the CG from Toledo. HIG and LIG completed a 12-week intervention program with three 40' sessions per week of Zumba® or Aquagym; respectively. Dual energy X-ray absorptiometry (DXA) measured bone mineral content (BMC) and areal bone mineral density (aBMD) at total body less head (TBLH), lumbar spine and right hip. Results: Post-intervention adjusted data showed no significant differences in BMC between any of the groups nor in aBMD between HIG and LIG. Interestingly; significant differences for the HIG vs. CG were found in the change in total hip aBMD (1.76% vs. -0.44%), femoral neck aBMD (1.80% vs. -2.71%), and intertrochanter aBMD (2.03% vs. -0.50%). Moreover, significant differences for the LIG vs. CG were also found in the change in femoral neck aBMD (-0.54% vs. -2.71%). Conclusions: The regular practice of Zumba® and Aquagym might reduce the progressive deterioration of bone mass in inactive middle-aged women.


Assuntos
Densidade Óssea/fisiologia , Exercício/fisiologia , Osteogênese/fisiologia , Osteoporose/prevenção & controle , Pré-Menopausa/fisiologia , Absorciometria de Fóton , Adulto , Antropometria , Feminino , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/fisiologia , Quadril/diagnóstico por imagem , Quadril/fisiologia , Humanos , Perna (Membro)/diagnóstico por imagem , Perna (Membro)/fisiologia , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem , Espanha
13.
J Clin Endocrinol Metab ; 104(4): 1181-1186, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30608551

RESUMO

BACKGROUND: Although the 2017 Endocrine Society Guidelines for gender dysphoria stipulated that cross-sex hormone therapy (CHT) achieve gonadal steroid levels equivalent to those of a cisperson of the chosen sex, for transgender women (male-to-female gender dysphoria), current gonadal therapy is usually estradiol. Accumulated evidence indicates that normally ovulatory menstrual cycles are necessary for ciswomen's current fertility, as well as for later-life bone and cardiovascular health and the prevention of breast and endometrial cancers. EVIDENCE ACQUISITION: Extensive past clinical experience with transgender women's CHT using estradiol/estrogen combined with progesterone/medroxyprogesterone and pioneering the addition of spironolactone. Comprehensive progesterone physiology research plus a brief review of transgender women's literature to assess current therapy and clinical outcomes, including morbidity and mortality. PURPOSE: To emphasize that both ovarian hormones, progesterone as well as estradiol, are theoretically and clinically important for optimal transgender women's CHT. EVIDENCE SYNTHESIS: It is important to add progesterone to estradiol and an antiandrogen in transgender women's CHT. Progesterone may add the following: (i) more rapid feminization, (ii) decreased endogenous testosterone production, (iii) optimal breast maturation to Tanner stages 4/5, (iv) increased bone formation, (v) improved sleep and vasomotor symptom control, and (vi) cardiovascular health benefits. CONCLUSIONS: Evidence has accrued that normal progesterone (and ovulation), as well as physiological estradiol levels, is necessary during ciswomen's premenopausal menstrual cycles for current fertility and long-term health; transgender women deserve progesterone therapy and similar potential physiological benefits.


Assuntos
Estradiol/administração & dosagem , Disforia de Gênero/tratamento farmacológico , Terapia de Reposição Hormonal/métodos , Progesterona/administração & dosagem , Pessoas Transgênero , Administração Oral , Relação Dose-Resposta a Droga , Quimioterapia Combinada/métodos , Estradiol/efeitos adversos , Estradiol/fisiologia , Medicina Baseada em Evidências/métodos , Feminino , Disforia de Gênero/fisiopatologia , Humanos , Masculino , Ciclo Menstrual/efeitos dos fármacos , Ciclo Menstrual/fisiologia , Ovulação/efeitos dos fármacos , Ovulação/fisiologia , Pré-Menopausa/efeitos dos fármacos , Pré-Menopausa/fisiologia , Progesterona/fisiologia , Embolia Pulmonar/induzido quimicamente , Embolia Pulmonar/epidemiologia , Adesivo Transdérmico/efeitos adversos , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/epidemiologia
14.
J Bone Miner Metab ; 37(1): 60-71, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29318392

RESUMO

Although evidence exists for a daily rhythm in bone metabolism, the contribution of factors such as melatonin levels, the light-dark cycle, and the sleep-wake cycle is difficult to differentiate given their highly correlated time courses. To examine these influences on bone resorption, we collected 48-h sequential urine samples under both ambulatory (8-h sleep:16-h wake) and constant routine (CR) (constant wake, posture, nutrition and dim light) conditions from 20 healthy premenopausal women. Urinary 6-sulphatoxymelatonin (aMT6s; ng/h) and the bone resorption marker amino-terminal cross-linked collagen I telopeptide (NTx; bone collagen equivalents nM/h) were assayed and fit by cosinor models to determine significant 24-h rhythms and acrophase. Most participants had significant 24-h aMT6s rhythms during both ambulatory and CR conditions (95 and 85%, respectively), but fewer had significant 24-h NTx rhythms (70 and 70%, respectively). Among individuals with significant rhythms, mean (± SD) aMT6s acrophase times were 3:57 ± 1:50 and 3:43 ± 1:25 h under ambulatory and CR conditions, respectively, and 23:44 ± 5:55 and 3:06 ± 5:15 h, respectively, for NTx. Mean 24-h levels of both aMT6s and NTx were significantly higher during CR compared with ambulatory conditions (p < 0.0001 and p = 0.03, respectively). Menstrual phase (follicular versus luteal) had no impact on aMT6s or NTx timing or 24-h levels. This study confirms an endogenous circadian rhythm in NTx with a night-time peak when measured under CR conditions, but also confirms that environmental factors such as the sleep-wake or light-dark cycles, posture or meal timing affects overall concentrations and peak timing under ambulatory conditions, the significance of which remains unclear.


Assuntos
Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Ritmo Circadiano/fisiologia , Melatonina/metabolismo , Pré-Menopausa/fisiologia , Adulto , Biomarcadores , Reabsorção Óssea/fisiopatologia , Colágeno Tipo I/metabolismo , Feminino , Humanos , Luz , Peptídeos/metabolismo
15.
J Clin Endocrinol Metab ; 104(2): 301-311, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30358874

RESUMO

Purpose: Menopause-related changes may affect regional but also morphological characteristics of adipose tissue. We sought to assess the clinical value of echogenicity of subcutaneous adipose tissue (SAT) and preperitoneal adipose tissue (pPAT) in postmenopausal women without cardiovascular disease. Methods: In 244 consecutively recruited postmenopausal women, subclinical atherosclerosis was assessed in the femoral and carotid arteries by intima-media thickness (IMT) and atheromatous plaques using high-resolution ultrasonography. In 41 women with a second visit (median follow-up 41.5 months), carotid atherosclerosis was re-evaluated. Images of SAT and pPAT were ultrasonographically acquired, and their echogenicity was evaluated by grayscale mean (GSMn) using a dedicated software. A control group of 20 healthy premenopausal women was used for comparisons in fat echogenicity. Results: SAT GSMn but not pPAT was higher in postmenopausal as compared with healthy premenopausal women and was independently associated with metabolic markers of adiposity including body mass index (BMI) and waist circumference (WC). SAT GSMn was associated with carotid IMT and the presence and number of atheromatous plaques [adjusted OR 2.44 and 2.32 per 1-SD increase in GSMn (95% CIs 1.55 to 3.93 and 1.55 to 3.45), respectively]. SAT GSMn conferred incremental value over traditional risk factors, insulin resistance, BMI, and WC for the detection of subclinical atherosclerosis. Increased baseline SAT GSMn was associated with increased rate of progression in carotid IMT. Conclusions: SAT echogenicity may serve as a qualitative marker of adiposity, conferring incremental clinical value over BMI and WC in postmenopausal women. Further investigation is warranted to assess the utility of ultrasonography-derived fat echogenicity as a screening method for morbid obesity.


Assuntos
Gordura Abdominal/diagnóstico por imagem , Obesidade Mórbida/diagnóstico por imagem , Adiposidade/fisiologia , Antropometria/métodos , Índice de Massa Corporal , Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Mediadores da Inflamação/sangue , Resistência à Insulina/fisiologia , Lipídeos/sangue , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Obesidade Mórbida/fisiopatologia , Pós-Menopausa/fisiologia , Pré-Menopausa/fisiologia , Gordura Subcutânea/diagnóstico por imagem , Ultrassonografia/métodos
16.
Am J Obstet Gynecol ; 220(1): 83.e1-83.e11, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30312584

RESUMO

BACKGROUND: Hysterectomy is a common surgical procedure, predominantly performed when women are between 30 and 50 years old. One in 3 women in Australia has had a hysterectomy by the time they are 60 years old, and 30% have both ovaries removed at the time of surgery. Given this high prevalence, it is important to understand the long-term effects of hysterectomy. In particular, women who have a hysterectomy/oophorectomy at younger ages are likely to be premenopausal or perimenopausal and may experience greater changes in hormone levels and a shortened reproductive lifespan than women who have a hysterectomy when they are older and postmenopausal. Use of menopausal hormone therapy after surgery may compensate for these hormonal changes. To inform clinical decisions about postsurgery management of women who have a hysterectomy prior to menopause (ie, average age at menopause 50 years), it is useful to compare women with a hysterectomy to women with no hysterectomy and to stratify the hysterectomy status by whether or not women have had a bilateral oophorectomy, or used menopausal hormone therapy. OBJECTIVE: We sought to investigate whether women who had a hysterectomy with ovarian conservation or a hysterectomy and bilateral oophorectomy before the age of 50 years were at a higher risk of premature all-cause mortality compared to women who did not have this surgery before the age of 50 years. We also sought to explore whether use of menopausal hormone therapy modified these associations. STUDY DESIGN: Women from the midcohort (born 1946 through 1951) of the Australian Longitudinal Study on Women's Health were included in our study sample (n = 13,541). Women who reported a hysterectomy (with and without both ovaries removed) before the age of 50 years were considered exposure at risk and compared with women who did not report these surgeries before age 50 years. To explore effect modification by use of menopausal hormone therapy we further stratified hysterectomy status by menopausal hormone therapy use. Risk of all-cause mortality was assessed using inverse-probability weighted Cox regression models. RESULTS: During a median follow-up of 21.5 years, there were 901 (6.7%) deaths in our study sample. Overall, there was no difference in all-cause mortality between women who reported a hysterectomy with ovarian conservation (hazard ratio, 0.86; 95% confidence interval, 0.72-1.02) or women who reported a hysterectomy and bilateral oophorectomy (hazard ratio, 1.02; 95% confidence interval, 0.78-1.34) and women with no hysterectomy. When stratified by menopausal hormone therapy use, women with hysterectomy and ovarian conservation before the age of 50 years were not at higher risk of all-cause mortality compared to no hysterectomy, regardless of menopausal hormone therapy use status. In contrast, among nonusers of menopausal hormone therapy only, women who reported a hysterectomy-bilateral oophorectomy before the age of 50 years were at a higher risk of death compared to women with no hysterectomy (hazard ratio, 1.81; 95% confidence interval, 1.01-3.25). CONCLUSION: Hysterectomy with ovarian conservation before the age of 50 years did not increase risk of all-cause mortality. Among nonmenopausal hormone therapy users only, hysterectomy and bilateral oophorectomy before the age of 50 years was associated with a higher risk of death.


Assuntos
Causas de Morte , Histerectomia/estatística & dados numéricos , Ovariectomia/estatística & dados numéricos , Pré-Menopausa/fisiologia , Adulto , Distribuição por Idade , Austrália , Feminino , Humanos , Histerectomia/métodos , Incidência , Estudos Longitudinais , Pessoa de Meia-Idade , Ovariectomia/métodos , Qualidade de Vida , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo
17.
BMJ Open ; 8(12): e023115, 2018 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-30580266

RESUMO

INTRODUCTION: BRCA1 mutation carriers have a significant lifetime risk of breast cancer, with their primary risk-reduction option being bilateral mastectomy. Preclinical work from our laboratory demonstrated that in BRCA1-deficient breast cells, oestrogen and its metabolites are capable of driving DNA damage and subsequent genomic instability, which are well-defined early events in BRCA1-related cancers. Based on this, we hypothesise that a chemopreventive approach which reduces circulating oestrogen levels may reduce DNA damage and genomic instability, thereby providing an alternative to risk-reducing surgery. METHODS AND ANALYSIS: 12 premenopausal women with pathogenic BRCA1 mutations and no previous risk-reducing surgery will be recruited from family history clinics. Participants will be allocated 1:1 to two arms. All will undergo baseline breast biopsies, blood and urine sampling, and quality of life questionnaires. Group A will receive goserelin 3.6 mg/28 days by subcutaneous injection, plus oral anastrozole 1 mg/day, for 12 weeks. Group B will receive oral tamoxifen 20 mg/day for 12 weeks. Following treatment, both groups will provide repeat biopsies, blood and urine samples, and questionnaires. Following a 1-month washout period, the groups will cross over, group A receiving tamoxifen and group B goserelin and anastrozole for a further 12 weeks. After treatment, biopsies, blood and urine samples, and questionnaires will be repeated. DNA damage will be assessed in core biopsies, while blood and urine samples will be used to measure oestrogen metabolite and DNA adduct levels. ETHICS AND DISSEMINATION: This study has ethical approval from the Office for Research Ethics Committees Northern Ireland (16/NI/0055) and the Medicines and Healthcare products Regulatory Agency (MHRA) (reference: 32485/0032/001-0001). The investigational medicinal products used in this trial are licensed and in common use, with well-documented safety information. Dissemination of results will be via high-impact journals and relevant national/international conferences. A copy of the results will be offered to the participants and be made available to patient support groups. TRIAL REGISTRATION NUMBER: EudraCT: 2016-001087-11; Pre-results.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Predisposição Genética para Doença/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Ubiquitina-Proteína Ligases/genética , Adulto , Anastrozol/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/prevenção & controle , Quimioprevenção/métodos , Estudos Cross-Over , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Gosserrelina/uso terapêutico , Heterozigoto , Humanos , Mutação , Irlanda do Norte , Seleção de Pacientes , Pré-Menopausa/fisiologia , Prognóstico , Medição de Risco , Taxa de Sobrevida , Tamoxifeno/uso terapêutico , Resultado do Tratamento
18.
Medicine (Baltimore) ; 97(50): e13718, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30558090

RESUMO

RATIONALE: Takotsubo syndrome (TTS) most commonly occurs in postmenopausal women who have been exposed to a triggering event such as acute physical or emotional distress. Sepsis-induced TTS in young premenopausal women were rarely reported. In particular, the relationship between sepsis-induced TTS and sepsis-induced cardiomyopathy (SIC) remains to be illuminated. PATIENT CONCERNS: Two young premenopausal women were admitted to the hospital with sepsis and myocardial involvement. DIAGNOSIS: Both patients fully met the Mayo Clinic criteria for TTS. INTERVENTIONS: Both patients received anti-infection and fluid infusion treatment. OUTCOMES: Both patients were discharged without complications and the follow-up ultrasonic echocardiography showed normal results. LESSONS: In this report, we describe 2 young premenopausal women with sepsis-induced TTS. There is an overlap between sepsis-induced TTS and SIC, and SIC could be a special type of TTS, which occurs under the stress of sepsis.


Assuntos
Cardiomiopatias/complicações , Sepse/etiologia , Cardiomiopatia de Takotsubo/complicações , Administração Intravenosa , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/microbiologia , Cardiomiopatias/patologia , Ecocardiografia/métodos , Eletrocardiografia , Feminino , Humanos , Pessoa de Meia-Idade , Pré-Menopausa/fisiologia , Sepse/tratamento farmacológico , Cardiomiopatia de Takotsubo/diagnóstico por imagem , Cardiomiopatia de Takotsubo/microbiologia , Cardiomiopatia de Takotsubo/patologia , Resultado do Tratamento
19.
J Electrocardiol ; 51(6): 1085-1089, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30497735

RESUMO

Both obesity and menopause are significant cardiovascular risk factors. In postmenopausal women the protective effect of estrogens is reduced and menopause is frequently associated with occurrence of other significant cardiovascular factors including obesity. This study was focused on evaluating the effect of obesity on the QRS complex in pre- and postmenopausal women. We present results of analysis of 199 electrocardiograms of pre- and postmenopausal women analyzed in relation to the body mass index within normal limits (BMI 20 to 24.9 kg/m2) and obesity (BMI > 30 kg/m2), respectively. Obesity in premenopausal women and menopause significantly affected both the electrical axis (EA) and maximum QRS spatial vector magnitude (QRSmax). The highest QRSmax and electrical axis values were observed in premenopausal lean women, and they were significantly higher as than in the premenopausal obese women, postmenopausal lean and obese women (QRSmax: 1.66 ±â€¯0.4 mV, 1.17 ±â€¯0.35 mV, 1.4 ±â€¯0.46 mV, and 1.35 ±â€¯0.39 mV, resp.). (EA: 56.4 ±â€¯18.0°, 38.22 ±â€¯18.38°, 45.82 ±â€¯18.63°, and 36.75 ±â€¯17.51°). The differences between obese premenopausal women, lean and obese postmenopausal women were not statistically significant. These differences were reflected in 12-lead ECG amplitude. The presence of additional cardiovascular risk factors did not affect the ECG parameters. Obesity significantly affected QRS complex in premenopausal women. This effect was comparable with the effect of menopause. Because all QRS complex changes were within normal limits, these results suggest that ECG evaluation in women should go beyond traditional diagnostic categories and consider the relationship between ECG changes and two cardiovascular risk factors - obesity and menopause.


Assuntos
Eletrocardiografia , Obesidade/fisiopatologia , Pós-Menopausa/fisiologia , Pré-Menopausa/fisiologia , Adulto , Idoso , Índice de Massa Corporal , Doenças Cardiovasculares , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco
20.
Cien Saude Colet ; 23(11): 3577-3586, 2018 Nov.
Artigo em Português | MEDLINE | ID: mdl-30427431

RESUMO

To verify the association between obesity and demographic, clinical and lifestyle variables in climacteric women, a cross-sectional study was conducted in outpatient clinics, with 469 women aged 40 to 65 years in the city of São Paulo, Brazil. The dependent variables were: obesity according to body mass index (BMI) and obesity according to percentage of body fat (% BF). The main explanatory variable was: climacteric phase (pre or postmenopausal); and control variables were: age; years of formal study; parity; menopausal hormone therapy (MHT) use; physical activity practice and smoking habit. Multiple regression analysis was performed using the Stata 9.2 software. According to the BMI, obesity was positively associated with parity (RR = 1.62, 95% CI = 1.11-2.37) and, negatively, with years of formal study (RP = 0.71, CI 95% = 0.55-0.91) and with physical activity practice (PR = 0.45, 95% CI = 0.33-0.61). According to the % BF, obesity was positively associated with parity (PR = 1.60, 95% CI = 1.03-2.49) and negatively with physical activity practice (PR = 0.43; 95% CI = 0.29-0.63). While being active physically was protective, multiparity was a risk factor for developing obesity for women in this study.


Assuntos
Tecido Adiposo , Estilo de Vida , Menopausa/fisiologia , Obesidade/epidemiologia , Adulto , Idoso , Índice de Massa Corporal , Brasil/epidemiologia , Estudos Transversais , Exercício , Feminino , Humanos , Pessoa de Meia-Idade , Paridade , Pós-Menopausa/fisiologia , Gravidez , Pré-Menopausa/fisiologia , Fatores de Risco , Fumar/epidemiologia
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