RESUMO
PURPOSE: While it is common for menstrual cycles to cease within the initial 6 months of treatment, there are instances where some transgender men may not experience this cessation. We analyzed transgender men undergoing gender-affirming hormone therapy (GAHT) with testosterone who experienced breakthrough bleeding in order to identify the factors associated with this condition. METHODS: In this case-control study, 24 transgender men in the case group and 48 in the control group were assessed for clinical, sociodemographic, hormonal, and body composition variables using dual-energy X-ray absorptiometry. All participants had been on GATH for at least 6 months. RESULTS: A few transgender men experienced persistent breakthrough bleeding, which was associated with decreased testosterone levels and free androgen index (FAI) compared with controls (p = 0.002 and p = 0.008, respectively). Among individuals with breakthrough bleeding, 50% had testosterone levels below the lowest tertile calculated for the sample, compared with 18.8% on controls (p = 0.007). After therapy adjustment, testosterone levels increased compared with the values obtained in the initial bleeding episode (p = 0.031). Eight transgender men required the addition of an oral progestogen to achieve amenorrhea, and these individuals had higher BMI than those in whom the adjustment of the parenteral testosterone dose was adequate (p = 0.026). A univariate prevalence ratio analysis revealed a negative association of persistent bleeding with testosterone levels (p = 0.028) and FAI levels (p = 0.019). CONCLUSION: Higher BMI and lower levels of testosterone and FAI were the main factors associated with breakthrough bleeding in transgender men.
Assuntos
Terapia de Reposição Hormonal , Testosterona , Pessoas Transgênero , Humanos , Masculino , Feminino , Adulto , Testosterona/efeitos adversos , Testosterona/administração & dosagem , Testosterona/sangue , Estudos de Casos e Controles , Terapia de Reposição Hormonal/métodos , Terapia de Reposição Hormonal/efeitos adversos , Hemorragia Uterina/induzido quimicamente , Hemorragia Uterina/epidemiologia , Procedimentos de Readequação Sexual/efeitos adversos , Procedimentos de Readequação Sexual/métodos , Transexualidade/tratamento farmacológico , Transexualidade/sangue , Adulto Jovem , Androgênios/efeitos adversos , Androgênios/administração & dosagem , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Menopause has been associated with an increased risk of cardiovascular disease. It has been shown that isoflavones protect vascular endothelial cells against induced oxidative stress injury. Therefore, the present study aimed to investigate the association between the dietary intake of isoflavones and the presence of subclinical cardiovascular disease (CVD) in postmenopausal women. METHODS: Ninety-six postmenopausal women [mean (SD) age 55.2 (4.9) years, body mass index (BMI) 27.2 (4.6) kg m-2 ] completed the study protocol. Habitual physical activity was assessed using a digital pedometer, resting metabolic rate was measured by indirect calorimetry and dietary intake was assessed via a validated food frequency questionnaire. Subclinical CVD was defined as carotid artery intima-media thickness (C-IMT) >0.9 mm and/or the presence of one or more atherosclerotic plaques in any of the studied segments. RESULTS: Mean (SD) C-IMT was 0.74 (0.2) mm, 25% of participants were found to have atherosclerotic plaques and the prevalence of subclinical CVD was 35%. Participants with subclinical CVD were more likely to consume less selenium, magnesium, folate and isoflavones, even after adjusting for total energy intake. A multivariate-adjusted regression model showed that a BMI >27 kg m-2 was associated with 90% higher risk of having ≥1 plaque and/or C-IMT >0.9 mm (P = 0.017). Higher oestradiol levels (P = 0.004) and isoflavone intake (P = 0.021) were independently associated with a lower risk of having subclinical CVD. CONCLUSIONS: In the present study, we observed that a higher isoflavone dietary intake was associated with a lower risk of subclinical CVD in postmenopausal women, independent of BMI and endogenous oestradiol levels.
Assuntos
Doenças Cardiovasculares/epidemiologia , Dieta , Isoflavonas/administração & dosagem , Pós-Menopausa , Índice de Massa Corporal , Doenças Cardiovasculares/patologia , Espessura Intima-Media Carotídea , Estudos Transversais , Estradiol/sangue , Exercício Físico , Feminino , Humanos , Pessoa de Meia-Idade , Sobrepeso/epidemiologia , Placa Aterosclerótica/patologia , Fatores de RiscoRESUMO
PURPOSE: This study aimed to investigate the association between the Mediterranean diet (MD), body composition, and bone mineral density (BMD) in postmenopausal women. METHODS: In this cross-sectional study, 105 apparently healthy postmenopausal women aged between 45 and 65 years were included. BMD, percentage body fat, and appendicular lean mass index (ALMI, appendicular lean mass/height squared) were assessed by dual-energy X-ray absorptiometry. Dietary intake was assessed by a validated food frequency questionnaire. Assessment of MD adherence was based on intake of cereals, vegetables, fruits, meats, dairy products, fish, red wine, and olive oil, and expressed as the Mediterranean diet score (MDS). RESULTS: Women with higher adherence to the MD had higher ALMI (6.6 ± 0.8 kg/m2 vs. 6.3 ± 0.7 kg/m2; p = 0.039) and lumbar spine BMD (1.076 ± 0.149 vs. 0.997 ± 0.143 g/cm2; p = 0.007) compared to those with lower MDS. Linear regression analysis adjusted for previous hormone therapy, previous smoking behavior, and habitual physical activity showed an independent positive contribution of MDS to lumbar spine BMD (mean difference 0.088 g/cm2, 95% confidence interval 0.028-0.147; p = 0.004) and ALMI (mean difference 0.296 kg/m2, 95% confidence interval 0.020-0.591; p = 0.049). CONCLUSION: Bone mineral density at the lumbar spine and ALMI were positively associated with the MDS in a sample of postmenopausal women from a non-Mediterranean region.
Assuntos
Densidade Óssea/fisiologia , Dieta Mediterrânea/estatística & dados numéricos , Músculo Esquelético/fisiologia , Pós-Menopausa/fisiologia , Idoso , Composição Corporal , Índice de Massa Corporal , Estudos Transversais , Registros de Dieta , Feminino , Humanos , Vértebras Lombares , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Testosterone is the main hormonal agent used for cross-sex hormone therapy in female-to-male transgender persons. Our aim was to systematically review the literature concerning the effects of testosterone on body mass index (BMI), blood pressure, hematocrit, hemoglobin, lipid profile, and liver enzymes in transgender men. PUBMED and EMBASE were searched for studies published until March 2017. Studies were included if they reported interventions with any dose of testosterone and comparison of variables before and during treatment. Of 455 potentially eligible articles, 13 were reviewed. Study duration ranged from 6 to 60 months, sample size ranged from 12 to 97 patients, and the most common treatment was parenteral testosterone undecanoate 1000 mg/12 weeks. Slight but significant increases in BMI were reported (from 1.3 to 11.4%). Three out of seven studies assessing the impact of different testosterone formulations on blood pressure detected modest increases or clinically irrelevant changes in this variable. In another study, however, two patients developed hypertension, which was resolved after cessation of testosterone therapy. Decreases in HDL-cholesterol and increases in LDL-cholesterol were consistently observed. Eight studies observed a relationship between testosterone and increased hemoglobin (range: 4.9-12.5%) and hematocrit (range: 4.4-17.6%), but discontinuation of androgen therapy was not necessary. In one study, two patients developed erythrocytosis (hematocrit >52%) after 9 and 12 months of treatment. One study analyzing testosterone formulations observed smaller increases in hemoglobin and hematocrit with testosterone gel. Six studies assessing liver function showed slight or no changes. Overall, the quality of evidence was low, given the lack of randomized clinical/controlled trials and the small sample sizes. In conclusion, exogenous testosterone administration to transgender men was associated with modest increases in BMI, hemoglobin/hematocrit, and LDL-cholesterol, and with decreases in HDL-cholesterol. Long-term studies are needed to assess the long-term risks of testosterone therapy, particularly as they relate to cardiometabolic risks such as diabetes, dyslipidemia and the metabolic syndrome.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Metaboloma/efeitos dos fármacos , Testosterona/farmacologia , Pessoas Transgênero , Testes de Química Clínica , Hematócrito , Testes Hematológicos , Humanos , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/enzimologia , MasculinoRESUMO
PURPOSE: To examine the effect of habitual physical activity (PA) on the metabolic and hormonal profiles of women with polycystic ovary syndrome. MATERIALS AND METHODS: Anthropometric, metabolic and hormonal assessment and determination of habitual PA levels with a digital pedometer were evaluated in 84 women with PCOS and 67 age- and body mass index (BMI)-matched controls. PA status was defined according to number of steps (≥7500 steps, active, or <7500 steps, sedentary). RESULTS: BMI was lower in active women from both groups. Active PCOS women presented lower waist circumference (WC) and lipid accumulation product (LAP) values versus sedentary PCOS women. In the control group, active women also had lower WC, lower values for fasting and 120-min insulin, and lower LAP than sedentary controls. In the PCOS group, androgen levels were lower in active versus sedentary women (p = 0.001). In the control group, free androgen index (FAI) was also lower in active versus sedentary women (p = 0.018). Homeostasis model assessment of insulin resistance and 2000 daily step increments were independent predictors of FAI. Each 2000 daily step increment was associated with a decrease of 1.07 in FAI. CONCLUSIONS: Habitual PA was associated with a better anthropometric and androgenic profile in PCOS.
Assuntos
Androgênios/metabolismo , Exercício Físico/fisiologia , Resistência à Insulina , Insulina/metabolismo , Síndrome do Ovário Policístico/metabolismo , Adulto , Antropometria , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Síndrome do Ovário Policístico/patologia , Testosterona , Circunferência da CinturaRESUMO
Androgens may directly modulate early ovarian follicular development in preantral stages and androgen excess before puberty may disrupt this physiological process. Therefore, the aim of this study was to investigate the dynamics of follicular morphology and circulating androgen and estradiol levels in prepubertal Wistar rats acutely exposed to androgens. Prepubertal female Wistar rats were distributed into three groups: control, equine chorionic gonadotropin (eCG) intervention and eCG plus dehydroepiandrosterone (DHEA) intervention (eCG+DHEA). Serum DHEA, testosterone and estradiol levels were determined, and ovarian morphology and morphometry were assessed. The eCG+DHEA group presented increased serum estradiol and testosterone levels as compared with the control group (P<0.01), and higher serum DHEA concentration v. the eCG-only and control groups (P<0.01). In addition, the eCG+DHEA group had a higher number of, and larger-sized, primary and secondary follicles as compared with the control group (P<0.05). The eCG group presented intermediate values for number and size of primary and secondary follicles, without significant differences as compared with the other two groups. The number of antral follicles was higher in the eCG+DHEA and eCG groups v. controls (P<0.05). The number of primordial, atretic and cystic follicles were similar in all groups. In conclusion, the present experimental model using an acute eCG+DHEA intervention was useful to investigate events involved in initial follicular development under hyperandrogenic conditions, and could provide a reliable tool to study defective follicular development with possible deleterious reproductive consequences later in life.
Assuntos
Androgênios/farmacologia , Folículo Ovariano/crescimento & desenvolvimento , Maturidade Sexual/efeitos dos fármacos , Animais , Feminino , Folículo Ovariano/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
AIMS: The aim of this study was to assess the effects of orlistat on weight loss-related clinical variables in overweight/obese women with polycystic ovary syndrome (PCOS) and to compare treatment with orlistat vs. metformin in this group. METHODS: We conducted a systematic review and meta-analysis of the evidence about the use of orlistat in women with PCOS. We searched the literature published until May 2015 in MEDLINE, Cochrane Central Register of Controlled Trials and LILACS. RESULTS: Of 3951 studies identified, nine were included in the systematic review (three prospective, non-randomised studies and six randomised control trials). Eight studies used the Rotterdam criteria and 1 used NIH criteria to diagnose PCOS. Data suggest that orlistat promotes a significant reduction in BMI/weight in overweight/obese PCOS women. Eight studies evaluated orlistat impact on testosterone. Seven reported an improvement in testosterone levels. Eight studies evaluated impact on insulin resistance, and five reported improvement. Finally, five studies evaluated impact on lipid profile, and four reported improvement. Three randomised control trials were included in the fixed effects model meta-analysis for a total of 121 women with PCOS. Orlistat and metformin had similar positive effects on BMI (-0.65%, 95% CI: -2.03 to 0.73), HOMA (-3.60%, 95% CI: -16.99 to 9.78), testosterone (-2.08%, 95% CI: -13.08 to 8.93) and insulin (-5.51%, 95% CI: -22.27 to 11.26). CONCLUSION(S): The present results suggest that orlistat leads to significant reduction in BMI/body weight in PCOS. In addition, the available evidence indicates that orlistat and metformin have similar effects in reducing BMI, HOMA, testosterone and insulin in overweight/obese PCOS women. This study was registered in PROSPERO under number CRD42014012877.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Lactonas/uso terapêutico , Metformina/uso terapêutico , Obesidade Mórbida/tratamento farmacológico , Síndrome do Ovário Policístico , Fármacos Antiobesidade/administração & dosagem , Feminino , Humanos , Lactonas/administração & dosagem , Metformina/administração & dosagem , Obesidade Mórbida/complicações , OrlistateRESUMO
BACKGROUND: Adolescence is a time characterised by changes in reproductive hormones and menstrual patterns, which makes it difficult to diagnose polycystic ovary syndrome (PCOS) in this population. The diagnosis of PCOS has a great physical and psychosocial impact on the young person. Despite the importance of a diagnosis of PCOS at adolescence, data available are limited. AIMS: This review focuses on analysing markers of PCOS diagnosis and possible treatments in adolescence. RESULTS: Although, during adolescence, diagnosis criteria of PCOS overlap with physiological changes including clinical manifestations of hyperandrogenism (acne and hirsutism), oligo/amenorrhoea, anovulation and ovarian microcysts, there is agreement that irregular menses and hyperandrogenaemia should be used to diagnose PCOS in this population. Moreover, considering that PCOS phenotype could change through the reproductive age and that adolescents display heterogeneous ovarian morphology, it has been proposed that diagnosis of PCOS should be confirmed after the age of 18. The first-line treatment for menstrual irregularity and hirsutism are oral contraceptive pills (OCPs) and for obesity and metabolic abnormalities are lifestyle changes. Insulin-sensitizer drugs, such as metformin, may be added to the treatment in the presence of metabolic alterations. Antiandrogen drugs may also be associated for treating moderate to severe hirsutism. During adolescence, physiological changes overlap with signs and symptoms of PCOS; thus the diagnosis criteria should be carefully considered. Regarding the treatment of adolescents with PCOS, non-pharmacological interventions include lifestyle changes. Pharmacological treatments comprise OCPs, antiandrogens and metformin, used isolated or combined. CONCLUSIONS: During adolescence, physiological changes overlap with signs and symptoms of PCOS; thus the diagnosis criteria should be carefully considered. Regarding the treatment of adolescents with PCOS, non-pharmacological interventions include lifestyle changes. Pharmacological treatments comprise OCPs, antiandrogens and metformin, used isolated or combined.
Assuntos
Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/terapia , Adolescente , Antagonistas de Androgênios/uso terapêutico , Anticoncepcionais Orais/uso terapêutico , Feminino , Hirsutismo/diagnóstico , Hormônios/uso terapêutico , Humanos , Hiperandrogenismo/diagnóstico , Estilo de Vida , Metformina/uso terapêutico , Obesidade/terapiaRESUMO
OBJECTIVE: To assess the effects of oral low-dose and non-oral hormone therapy (HT) on ultra-sensitive C-reactive protein (CRP), atrial natriuretic peptide (ANP), and cardiovascular risk factors in postmenopause. METHODS: In this randomized, cross-over study, 44 recently postmenopausal women, with no clinical evidence of cardiovascular disease, received oral low-dose HT (estradiol 1 mg + drospirenone 2 mg/day) for 3 months. Forty-two patients received non-oral, conventional HT (1.5 mg/day percutaneous 17ß-estradiol gel or equivalent for nasal route) for 3 months followed by 200 mg/day micronized progesterone by the vaginal route (14 days during each menstrual period). After 3 months, patients were crossed over without washout. Post-HT vs. pre-HT measures were determined: lipids, glucose, body mass index, waist circumference, fibrinogen, CRP-stratified levels, and ANP levels. The study was registered at clinical trials.gov (NCT01432028). RESULTS: The mean age was 51 ± 3 years and the mean time since the menopause was 22 ± 10 months. CRP-stratified high levels decreased in a higher number of non-oral HT patients, who moved to intermediate and low levels (p = 0.02). No effect of HT was observed on ANP levels (baseline 67.4 (18.4-104.5), low-dose oral 43.5 (14.4-95.9), non-oral 39.8 (15.5-67.5) pg/ml). Markers of endothelial function did not worsen with either low-dose oral or non-oral HT: von Willebrand factor (baseline 118 ± 37%, low-dose oral 119 ± 38%, non-oral 108 ± 3%, p < 0.01), fibrinogen (baseline 356 ± 58 mg/dl; low-dose oral 343 ± 77 mg/dl; non-oral 326 ± 71 mg/dl, p < 0.01). CONCLUSIONS: Low-dose oral and non-oral HT for 6 months had neutral or beneficial effects in recently postmenopausal women with no clinical evidence of cardiovascular disease.
Assuntos
Androstenos/administração & dosagem , Fator Natriurético Atrial/efeitos dos fármacos , Proteína C-Reativa/efeitos dos fármacos , Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios/métodos , Pós-Menopausa/efeitos dos fármacos , Administração Cutânea , Administração Intranasal , Administração Oral , Fator Natriurético Atrial/metabolismo , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares , Estudos Cross-Over , Combinação de Medicamentos , Feminino , Géis , Humanos , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Serotonin (5-HT) has been shown to participate in prolactin secretion through a complex process resulting in both positive and negative effects. Estrogen has also been recognized as being involved in this serotonergic effect on prolactin release. Therefore, the aim of the present study was to assess whether estradiol modulates serotonergic involvement in prolactin secretion though 5-HT1A and/or 5-HT2A/2C receptors. Ovariectomized female Wistar rats, treated for 2 weeks with estrogen to induce a hyperprolactinemic status (hyperestrogenic rats) or with sunflower oil vehicle (hypoestrogenic rats), were injected daily with normal saline solution or 6-chloro-2-(1-piperazinyl)pyrazine (MK-212), an 5-HT2A/2C receptor agonist, for 4 days. Other groups of ovariectomized animals received 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) or pindolol, an agonist and antagonist of the 5-HT1A receptor respectively, on the last day of treatment with estrogen or vehicle. Prolactin levels were compared among groups in each experiment under the distinct drug treatments. MK-212 was found to increase prolactin concentrations both in hyper- and hypoestrogenic females compared to controls (p<0.05). In contrast, prolactin levels remained similar to those of controls both in hyperestrogenic animals treated with 8-OH-DPAT and pindolol and in hypoestrogenic rats administered the same treatments. In conclusion, our findings indicate the involvement of 5-HT2A/2C receptors on prolactin release through serotonergic pathways in female animals, especially in hyperestrogenic states.