Relationship between biomarkers of inflammation, oxidative stress and endothelial/microcirculatory function in successful aging versus healthy youth: a transversal study.

BACKGROUND: There is a functional decline of endothelial- dependent vasodilatation in the aging process. The aims of this study were to investigate if various microcirculatory parameters could correlate to anthropometrical variables, oxidative stress and inflammatory biomarkers in successful aging and compare the results to young healthy controls. METHODS: Healthy elderly women (HE, 74.0 ± 8.7 years, n = 11) and young controls (YC, 23.1 ± 3.6 years, n = 24) were evaluated through nailfold videocapillaroscopy (NVC), venous occlusion plethysmography (VOP) and laboratorial analysis. Functional capillary density (FCD) and diameters, maximum red blood cell velocity (RBCVmax) during the reactive hyperemia response/RBCVbaseline after 1 min arterial occlusion at the finger base, time to reach RBCVmax were determined by NVC, peak increment of forearm blood flow (FBF) during the reactive hyperemia response (%Hyper) and after 0.4 mg sublingual nitroglycerin (%Nitro) by VOP and lipidogram, fibrinogen, fasting and postload glucose, oxidized LDL-cholesterol (oxLDL), sICAM, sVCAM, sE-Selectin, interleukines 1 and 6 and TNF-α by laboratorial analysis. Correlations and linear multiple regression (LMR) between %Hyper, %Nitro, microcirculatory parameters, oxidative stress and inflammatory biomarkers were investigated. RESULTS: sVCAM, sE-Selectin and oxLDL were higher and RBCVmax/RBCVbaseline and %Hyper lower in HE, while %Nitro and FCD remained unchanged. Fibrinogen, LDL-cholesterol, oxLDL correlated negatively to %Hyper while sVCAM correlated negatively to %Hyper and RBCVmax/RBCVbaseline. Healthy aged women presented dilated capillaries with sustained perfusion and endothelial dysfunction with preserved vascular smooth muscle reactivity. Fibrinogen, LDL-cholesterol, oxidized-LDL and sVCAM correlated negatively to endothelial function but not to microcirculatory parameters. Oxidized-LDL and sVCAM could determine %Hyper through LMR. CONCLUSION: Oxidized-LDL and sVCAM might be used as endothelial dysfunction biomarkers for elderly with normal cardiovascular risk factors.

Long-term exposure to organochlorine pesticides and thyroid status in adults in a heavily contaminated area in Brazil.

Organochlorine (OC) pesticides are endocrine disruptors altering the thyroid hormonal system. The aim of this study is to investigate the relationship between exposure to OC pesticides and thyroid status in adults from a rural area in Rio de Janeiro, Brazil, heavily contaminated with OC pesticides. A cross-sectional study was carried out in 303 men and 305 women >14 years old. Concentrations of 19 OC pesticides and levels of free thyroxine (T4), total triiodothyronine (T3), thyroid-stimulating hormone (TSH), anti-thyroperoxidase (TPOAb) and anti-thyroglobulin (TgAg) antibodies were analyzed in serum samples. Associations between OC pesticides concentrations and values of biochemical thyroid parameters were determined using multivariate regression models stratified by gender. Prevalence of subclinical hyperthyroidism and the presence of TPOAb antibodies were higher than those described for euthyroid populations elsewhere. After adjusting for confounders, total T3 levels were associated with lower concentrations of endosulphan 2 in men and with higher alpha-chlordane, p,p'-dichlorodiphenyltrichloroethane (DDT), endosulphan 2, and methoxychlor in women. Levels of free T4 showed inverse association with beta-hexachlorocyclohexane (HCH) and p,p'-DDT in men, and were positively associated with hexachlorobenzene (HCB), heptachlor, o,p'-DDT, and p,p'-DDT in women. TSH levels were associated with higher beta-HCH in men. A positive association was observed between exposure methoxychlor in males and presence of TPOAb, but no association with TPOAb was found in women. These results suggest that OC pesticides can affect the thyroid system through gender-specific mechanisms that may differ among compounds. Further detailed investigations and health monitoring should be warranted for this population.

Obesity, metabolic syndrome, impaired fasting glucose, and microvascular dysfunction: a principal component analysis approach.

BACKGROUND: We aimed to evaluate the multivariate association between functional microvascular variables and clinical-laboratorial-anthropometrical measurements. METHODS: Data from 189 female subjects (34.0 ± 15.5 years, 30.5 ± 7.1 kg/m2), who were non-smokers, non-regular drug users, without a history of diabetes and/or hypertension, were analyzed by principal component analysis (PCA). PCA is a classical multivariate exploratory tool because it highlights common variation between variables allowing inferences about possible biological meaning of associations between them, without pre-establishing cause-effect relationships. In total, 15 variables were used for PCA: body mass index (BMI), waist circumference, systolic and diastolic blood pressure (BP), fasting plasma glucose, levels of total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG), insulin, C-reactive protein (CRP), and functional microvascular variables measured by nailfold videocapillaroscopy. Nailfold videocapillaroscopy was used for direct visualization of nutritive capillaries, assessing functional capillary density, red blood cell velocity (RBCV) at rest and peak after 1 min of arterial occlusion (RBCV(max)), and the time taken to reach RBCV(max) (TRBCV(max)). RESULTS: A total of 35% of subjects had metabolic syndrome, 77% were overweight/obese, and 9.5% had impaired fasting glucose. PCA was able to recognize that functional microvascular variables and clinical-laboratorial-anthropometrical measurements had a similar variation. The first five principal components explained most of the intrinsic variation of the data. For example, principal component 1 was associated with BMI, waist circumference, systolic BP, diastolic BP, insulin, TG, CRP, and TRBCV(max) varying in the same way. Principal component 1 also showed a strong association among HDL-c, RBCV, and RBCV(max), but in the opposite way. Principal component 3 was associated only with microvascular variables in the same way (functional capillary density, RBCV and RBCV(max)). Fasting plasma glucose appeared to be related to principal component 4 and did not show any association with microvascular reactivity. CONCLUSIONS: In non-diabetic female subjects, a multivariate scenario of associations between classic clinical variables strictly related to obesity and metabolic syndrome suggests a significant relationship between these diseases and microvascular reactivity.

Long term exposure to organochlorine pesticides and thyroid function in children from Cidade dos Meninos, Rio de Janeiro, Brazil.

A pesticide factory in Cidade dos Meninos village, Duque de Caxias County, Rio de Janeiro, Brazil, ended its activity in 1961, leading to widespread contamination of the environment by several organochlorine pesticides. The aim of this study was to investigate the effects of chronic exposure to organochlorine pesticides on thyroid hormone levels in children residing in Cidade dos Meninos. In a population-based survey carried out between 2003 and 2004, serum concentration of 19 pesticides and levels of free thyroxine (T4), total triiodothyronine (T3) and thyroid-stimulating hormone (TSH) were determined in 193 children younger than 15 years old. Multivariate linear regression was conducted to examine thyroid hormone levels according to quintiles of organochlorine exposure, controlling for age, gender and serum lipid content. Free T4 and TSH levels were within reference values (0.7-1.8 ng/dl and 0.35-5.5 mU/l), whereas total T3 was above the reference range (80-180 ng/dl) in 28% of children. More than 60% of the children had detectable levels of most organochlorine pesticides. With the exception of heptachlor and methoxychlor, total T3 levels showed a significant increasing linear trend regardless of pesticide type to which children were exposed. Free T4 levels were positively and significantly associated only with exposure to p,p'-DDD, endosulfan 1, and dieldrin. No significant trend was found for TSH. Data showed that exposure of children to organochlorine pesticides produced a significant increase in serum total T3 concentrations. The clinical implications of such a total T3 elevation and subsequent development are uncertain and warrant the need for health monitoring of these children.

Microcirculatory function in postmenopausal women: role of aging, hormonal exposure and metabolic syndrome.

Menopausal hormone therapy (HT) has shown conflicting cardiovascular endpoints, depending on the women studied. The endothelium is the main site for sex steroids cardiovascular action. To assess the influence of age, previous hormonal exposure and of metabolic syndrome (MS) on microcirculatory function, we studied 68 normotensive non-diabetic postmenopausal women, 34-70 years old, by dynamic nailfold videocapillaroscopy evaluating red blood cell velocity (RBCV) at baseline and during the reactive hyperemia response after 1 min ischemia (RBCV(max)) and time taken to reach it (TRBCV(max)). There was an inverse correlation between RBCV and RBCV(max), versus age (p=0.02 for both) and time since menopause (TSM, p=0.01 and p=0.03, respectively). Women who used oral contraceptives in the past showed higher RBCV (1.51+/-0.10 vs. 1.43+/-0.09 mm/s, p=0.01) and RBCV(max) (1.70+/-0.11 vs. 1.63+/-0.07 mm/s, p=0.03) compared to never user ones. A longer time after menopause without HT was associated to lower RBCV(max) (p=0.05). Women with MS had longer TRBCV(max) (9.85+/-1.77 vs. 8.47+/-1.71 s, p=0.02), as well as those with higher hematocrit, hemoglobin and leukocyte counts (p=0.03, p=0.01 and p=0.03, respectively) and lower HDL (p=0.03). In conclusion, in postmenopausal women of low cardiovascular risk, advanced age, longer TSM, longer time after menopause without HT and MS were associated to microcirculatory function impairment, whereas past use of oral contraceptives seemed to have a protective effect.

Sexual Function Under Adequate Estrogen Therapy in Women After Oophorectomy Versus Natural Menopause.

Background: There is scarce evidence regarding endogenous postmenopausal ovarian testosterone (T) production and estrogen replacement roles in different sexual domains. This study aimed to determine whether lower endogenous T in oophorectomized women that were estradiol (E2)-treated influenced global or specific domains of sexual function. Depressive and cognitive symptoms were evaluated to exclude potential confounders. Materials and Methods: Eighty-one recently postmenopausal women treated with transdermal E2, 36 with bilateral oophorectomy (O), and 45 controls (C) were investigated through hormonal profile, Female Sexual Function Index, Mini Mental, and Beck Depression Inventory. Results: T levels, as expected, were lower in O than in C (p = 0.001); nonetheless, O presented a lower risk of sexual dysfunction (55.6% vs. 85.7%, p = 0.037), due to less pain (p = 0.005), increased lubrication (p = 0.012), and satisfaction (p = 0.042). O, however, required 50% higher E2 gel doses to control vasomotor symptoms (VMS) than did C. In O, all T measurements were positively, although weakly, correlated with desire (r = 0.374-0.381, p = 0.016-0.024). E2 levels were positively correlated with arousal in all women (r = 0.338, p = 0.038) and in O (r = 0.521, p = 0.032). Depression and cognition scores did not differ between the groups. Conclusions: Despite lower T levels, O women receiving E2 therapy had better global sexual function. Earlier onset and longer E2 treatment could have prevented vulvovaginal atrophy in O. Oophorectomized patients may require higher doses of E2 replacement. E2 levels, achieved by appropriate hormone therapy for VMS control, and very low T levels correlated with distinct sexual domains and may act in complementary areas of sexuality in postmenopausal women.

Testosterone therapy for women with low sexual desire: a position statement from the Brazilian Society of Endocrinology and Metabolism.

OBJECTIVE: To summarize current evidence regarding testosterone treatment for women with low sexual desire. MATERIALS AND METHODS: The Female Endocrinology and Andrology Department of the Brazilian Society of Endocrinology and Metabolism invited nine experts to review the physiology of testosterone secretion and the use, misuse, and side effects of exogenous testosterone therapy in women, based on the available literature and guidelines and statements from international societies. RESULTS: Low sexual desire is a common complaint in clinical practice, especially in postmenopausal women, and may negatively interfere with quality of life. Testosterone seems to exert a positive effect on sexual desire in women with sexual dysfunction, despite a small magnitude of effect, a lack of long-term safety data, and insufficient evidence to make a broad recommendation for testosterone therapy. Furthermore, there are currently no testosterone formulations approved for women by the relevant regulatory agencies in the United States, Brazil, and most other countries, and testosterone formulations approved for men are not recommended for use by women. CONCLUSION: Therefore, testosterone therapy might be considered if other strategies fail, but the risks and benefits must be discussed with the patient before prescription. Arch Endocrinol Metab. 2019;63(3):190-8.

Use of vascular Doppler ultrasound to detect acute estradiol vascular effect in postmenopausal women.

OBJECTIVES: To report on a simple practical test for assessing acute estradiol vascular effects on healthy and unhealthy postmenopausal women. INTRODUCTION: Estradiol acts in the endothelium to promote vasodilatation through genomic and non-genomic mechanisms, but its vascular action may be impaired in diabetes mellitus, hypertension, smoking and obesity. METHODS: Nineteen postmenopausal women (nine healthy and 10 with two or more of the above factors) of similar age and time since menopause were examined with vascular Doppler ultrasound. Resistance indexes and systolic and diastolic flow velocities were determined for the brachial and internal carotid arteries at baseline and 20 minutes after administration of a nasal estradiol formulation, available on the market, which reaches 1,200-1,500 pg/ml in the serum in 10-30 minutes. Estradiol blood levels were measured at 30 minutes. RESULTS: The carotid resistance index increased 14.2% (vasoconstriction) in the unhealthy group after estradiol, from a mean +/- S.E. of 0.56 +/- 0.016 at baseline to 0.64 +/- 0.05 (p=0.033), and remained unchanged in healthy women. Brachial diastolic flow velocity increased 19.7% (vasodilatation) in healthy women, from 16.2 +/- 1.93 to 19.4 +/- 0.64 cm/s (p=0.046), and did not change in the unhealthy subjects. Estradiol levels were similar in both groups. DISCUSSION: Healthy postmenopausal women showed brachial vasodilatation while unhealthy postmenopausal women displayed vasoconstriction at the carotid artery. Vascular responses to estradiol were divergent between the groups. CONCLUSIONS: The acute estradiol test, coupled with Doppler ultrasound, seemed to be able to differentiate women with normal and abnormal endothelial function in a simple, non-invasive manner.

Occupational exposure to pesticides, reproductive hormone levels and sperm quality in young Brazilian men.

The association of occupational exposure to current-use pesticides with reproductive hormones, semen quality, and genital measures was investigated among young men in the South of Brazil. A cross-sectional study was conducted in 99 rural and 36 urban men aged 18-23 years. Information on pesticide use was obtained through questionnaire. Serum and semen samples were analyzed for sex hormones and sperm parameters, respectively, and measurement of anogenital distance (AGD) and testis volume (TV) were performed. Associations were explored using multivariate linear regression. Rural men had poorer sperm morphology, higher sperm count, and lower LH levels relative to urban subjects. Lifetime use of pesticides, especially herbicides and fungicides, was associated with poorer morphology and reduced LH and prolactin, with evidence of a linear pattern. Maternal farming during pregnancy was associated with larger AGD and TV. Chronic occupational exposure to modern pesticides may affect reproductive outcomes in young men.

[Effects of transdermic estrogen therapy, isolated or in association with micronized progesterone, on clotting factors in overweight or normal postmenopausal women]. / Efeitos da terapia estrogênica transdérmica isolada ou associada à progesterona micronizada nos fatores de coagulação em mulheres menopausadas com e sem sobrepeso.

To evaluate HRT action over hemostasis we treated 45 postmenopausal women, divided in: Group 1 (N= 22, hysterectomized) and Group 2 (N= 23, with uterus), at the average age of 51.6 years and average BMI of 27.1 kg/m(2), with no significant difference in the base-line, with 17beta-oestradiol, 50 mcg/day, transdermic and continuous (group 1) associated to micronized progesterone 200 mg 12 days per month (group 2). The average of 2 samples of TAP, PTT, fibrinogen and platelet number was measured monthly during 3 months. For the total sample, there was a PTT shortening along treatment, from the second evaluation on (p= 0.006). Fibrinogen in Group 2 was significantly higher than in Group 1, from the second evaluation on (p= 0.0005). Patients with BMI > 25 presented a greater TAP shortening (p= 0.040) and a smaller fibrinogen drop (p= 0.033) than patients with BMI < 25. Prothrombotic effects predominated, especially in overweight women and in those who used progesterone.

Hot flashes: emerging cardiovascular risk factors in recent and late postmenopause and their association with higher blood pressure.

OBJECTIVE: The aim of the study was to compare the endothelial function of symptomatic (self-reported hot flashes >3 on a scale of 0-10) versus asymptomatic (≤3) women in different postmenopause stages, and to examine if the association between hot flashes and endothelial function was independent of classical cardiovascular risk factors observed during the analysis. METHODS: Noninvasive venous occlusion plethysmography within two groups: recent (recent postmenopause [RPM], <10 y, n = 63) and late (late postmenopause [LPM], ≥10 y, n = 67) postmenopause. RESULTS: Symptomatic women showed lower forearm blood flow and lower percentage increment of it during the reactive hyperemia response; higher systolic (P < 0.0001 in RPM and P = 0.0008 in LPM) and diastolic (P = 0.0005 in RPM and P = 0.0219 in LPM) blood pressure; highest score for perimenopausal hot flashes (P = 0.0007 in RPM and P < 0.0001 in LPM), longer duration of prior oral contraceptive use (P = 0.009 in RPM and P = 0.0253 in LPM), and higher current sleep disorders (P < 0.0001 in RPM and P = 0.0281 in LPM) compared with asymptomatic ones. In the LPM group, symptomatic women also had higher prevalence of previous hypertension diagnosis (P = 0.0092). During multivariate analysis, blood flow during the reactive hyperemia response was associated with hot flashes after adjusting for age, body mass index, and systolic blood pressure (odds ratio 0.55 [0.36-0.84] in RPM and odds ratio 0.7 [0.5-0.97] in LPM). CONCLUSIONS: In both phases, recent and late post menopause, hot flashes were associated with endothelial dysfunction and higher systolic and diastolic blood pressure, but the relationship between hot flashes and endothelial dysfunction was independent of blood pressure.

Low testosterone levels are associated with endothelial dysfunction in oophorectomized early postmenopausal women.

BACKGROUND: The actual consequences of low testosterone levels in women remain uncertain. OBJECTIVE: To assess endogenous testosterone influence on body composition, vascular and metabolic function in recent postmenopausal women. DESIGN: We studied 81 postmenopausal women under transdermal estradiol (E2) replacement therapy, 36 with bilateral oophorectomy (group O), and 45 controls (group C) through venous occlusion plethysmography, bioimpedance, DEXA, biochemical, hormonal, and inflammatory profile. RESULTS: Total testosterone level (TT) in group O was 11.0 (4.0-17.75) vs 23.0 (10.0-42.5) ng/dl in group C (P=0.001). Forearm blood flow, in ml/min/100  ml tissue, was lower in group O compared to group C at baseline (1.57 (1.05-2.47) vs 2.19 (1.59-2.66) P=0.036), following reactive hyperemia response (endothelium-dependent flow mediated dilatation, 3.44 (2.38-4.35) vs 4.3 (3.09-5.52), P=0.031) and following nitroglycerin (endothelium-independent dilation, 1.39 (0.99-1.7) vs 1.76 (1.15-2.0), P=0.025), with a positive correlation between TT and all parameters except for the reactive hyperemia response (r=0.233-0.312, P=0.036-0.004). The sVCAM1 levels were negatively correlated with TT (r=-0.320, P=0.005). E2 and other hormone levels, biochemical parameters and body composition did not differ between groups. Multiple linear regressions showed that the levels of TT, compared with other confounding variables, may explain the variation observed on endothelial parameters, with low explanatory power. CONCLUSION: The absence of ovarian testosterone production in recent postmenopausal oophorectomized women was associated with deleterious effects on endothelial function.

[Hormonal therapy of menopause: 2004 position of the Department of Female Endocrinology and Andrology of the Brazilian Society of Endocrinology and Metabolism]. / Terapia hormonal da menopausa: posicionamento do Departamento de Endocrinologia Feminina e Andrologia da SBEM em 2004.

After randomized clinical trials produced impact and questions at the medical community on menopause hormonal therapy (MHT), the Department of Female Endocrinology and Andrology of the Brazilian Society of Endocrinology convened a group of specialists to produce an informative, critical and position paper, offering guidelines for those who practice or are called to express their opinion on menopause therapy. MHT is indicated for relief of vasomotor symptoms, maintenance of vaginal tropism, bone mass and collagen preservation, sexual and general well-being. Studies on primary cardiovascular prevention are not conclusive, and thus insufficient to indicate or not MHT for this purpose. Schemes and forms of association should de individualized. Whenever possible, one should use 17-beta estradiol, associated to natural progesterone or its derivatives in women with an intact uterus, at the lowest effective doses. Duration of therapy depends on its aims, and should be periodically re-evaluated through an individual indication/contra-indication balance. Orientation toward a healthier lifestyle, with smoking cessation, adequate calcium intake and a low fat diet, together with regular physical activity is fundamental during menopause.

Female infertility of endocrine origin.

Infertility is defined as the failure to conceive, with no contraception, after one year of regular intercourse in women<35 years and after 6 months in women>35 years. A review on causes, management and treatment of endocrine causes of was performed. Epidemiological data suggest that around 10% to 15% of couples are infertile. Anovulatory problems are responsible from 25% to 50% of causes of . Advanced age, obesity, and drugs, have a negative effect on fertility. Different hypothalamic, pituitary, thyroid, adrenal, and ovarian disorders may affect fertility as well. Infertility is a growing phenomenon in developed societies. We here provide information about how to identify endocrine patients with ovulatory dysfunction. Women must be advised about limiting factors to be avoided, in order to protect their fertility.

Association between serum levels of organochlorine pesticides and sex hormones in adults living in a heavily contaminated area in Brazil.

BACKGROUND: Several studies have investigated the effects of organochlorine (OC) pesticides on adverse reproductive outcomes. However, few previous studies explored their effects on sex hormones. OBJECTIVE: To examine the association between serum concentrations of OC pesticides and levels of sex hormones in adult population in a rural area in Brazil heavily contaminated with these pesticides. METHODS: A cross-sectional study with 304 men and 300 women was undertaken. Wet weight serum concentrations of 19 OC pesticides (dichloro-diphenyl-trichloroethane [DDT] and hexachlorocyclohexane [HCH], among others) were determined in all participants. Testosterone levels were obtained for men and estradiol, progesterone, prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) for women. Associations between OC pesticides and sex hormones were evaluated using linear regression models. RESULTS: Prevalence of women with non-physiological hyperprolactinemia was 4%. After adjusting for serum lipids and confounders, heptachlor and o,p'-DDT concentrations in men were associated with lower testosterone levels, while peri- and postmenopausal women (N=77) showed inverse associations between LH and hexachlorobenzene (HCB), p,p'-DDT, p,p'-DDD (dichloro-diphenyl-dichloroethane), endosulfan 1 and 2, aldrin and mirex, as well as between FSH and p,p'-DDD, endosulfan 1 and aldrin. Premenopausal women (N=210) did not show statistically significant associations between OC pesticides and sex hormones. CONCLUSIONS: Inverse associations between OC pesticide concentrations and testosterone in men and LH and FSH in peri-/postmenopausal women, together with the high proportion of women with elevated prolactin, suggest that these OC compounds may have triggered anti-androgenic effects in men and estrogenic effects in women in this population.

Endothelial function and insulin resistance in early postmenopausal women with cardiovascular risk factors: importance of ESR1 and NOS3 polymorphisms.

Cardiovascular benefits from estradiol activation of nitric oxide endothelial production may depend on vascular wall and on estrogen receptor alpha (ESR1) and nitric oxide synthase (NOS3) polymorphisms. We have evaluated the microcirculation in vivo through nailfold videocapillaroscopy, before and after acute nasal estradiol administration at baseline and after increased sheer stress (postocclusive reactive hyperemia response) in 100 postmenopausal women, being 70 controls (healthy) and 30 simultaneously hypertensive and diabetic (HD), correlating their responses to PvuII and XbaI ESR1 polymorphisms and to VNTR, T-786C and G894T NOS3 variants. In HD women, C variant allele of ESR1 Pvull was associated to higher vasodilatation after estradiol (1.72 vs 1.64 mm/s, p = 0.01 compared to TT homozygotes) while G894T and T-786C NOS3 polymorphisms were connected to lower increment after shear stress (15% among wild type and 10% among variant alleles, p = 0.02 and 0.04). The G variant allele of ESR1 XbaI polymorphism was associated to higher HOMA-IR (3.54 vs. 1.64, p = 0.01) in HD and higher glucose levels in healthy women (91.8 vs. 87.1 mg/dl, p = 0.01), in which increased waist and HOMA-IR were also related to the G allele in NOS3 G894T (waist 93.5 vs 88.2 cm, p = 0.02; HOMA-IR 2.89 vs 1.48, p = 0.05). ESR1 Pvull, NOS3 G894T and T-786C polymorphism analysis may be considered in HD postmenopausal women for endothelial response prediction following estrogen therapy but were not discriminatory for endothelial response in healthy women. ESR1 XbaI and G894T NOS3 polymorphisms may be useful in accessing insulin resistance and type 2 diabetes risks in all women, even before menopause and occurrence of metabolic disease.

Testosterone therapy for women with low sexual desire: a position statement from the Brazilian Society of Endocrinology and Metabolism

ABSTRACT Objective To summarize current evidence regarding testosterone treatment for women with low sexual desire. Materials and methods The Female Endocrinology and Andrology Department of the Brazilian Society of Endocrinology and Metabolism invited nine experts to review the physiology of testosterone secretion and the use, misuse, and side effects of exogenous testosterone therapy in women, based on the available literature and guidelines and statements from international societies. Results Low sexual desire is a common complaint in clinical practice, especially in postmenopausal women, and may negatively interfere with quality of life. Testosterone seems to exert a positive effect on sexual desire in women with sexual dysfunction, despite a small magnitude of effect, a lack of long-term safety data, and insufficient evidence to make a broad recommendation for testosterone therapy. Furthermore, there are currently no testosterone formulations approved for women by the relevant regulatory agencies in the United States, Brazil, and most other countries, and testosterone formulations approved for men are not recommended for use by women. Conclusion Therefore, testosterone therapy might be considered if other strategies fail, but the risks and benefits must be discussed with the patient before prescription. Arch Endocrinol Metab. 2019;63(3):190-8

Early postmenopausal women with cardiovascular risk factors improve microvascular dysfunction after acute estradiol administration.

OBJECTIVE: This study aimed to compare endothelial microcirculatory function in hypertensive and diabetic (HD) and healthy postmenopausal women before and after nasal application of 17ß-estradiol. METHODS: Seventy-one women aged 42 to 59 years within 10 years of menopause, divided into HD (n = 31) and similar-age healthy (n = 40) women were evaluated noninvasively through nailfold videocapillaroscopy before and 1 hour after estradiol, measuring basal (RBCV) and maximum (RBCVmax) red blood cell velocity after 1 minute of arterial occlusion, representing baseline and endothelial-mediated vasodilation, and time to reach RBCVmax (TRBCVmax), representing microvascular compliance/stiffness. RESULTS: Hot flashes did not differ from or affect microvascular results. Before estradiol, HD showed lower RBCV (1.495 ± 0.20 vs 1.52 ± 0.10 mm/s, P = 0.019), borderline lower RBCVmax (1.655 ± 0.09 vs 1.706 ± 0.10 mm/s, P = 0.054), and shorter TRBCVmax (7.94 ± 1.44 vs 8.8 ± 2.03 s, P = 0.011) compared with healthy women. After estradiol, RBCV and RBCVmax increased, and TRBCVmax decreased in both groups (P = 0.0001 for all). HD women showed a higher RBCV increment (14.6% ± 2% vs 11.1 ± 1.4%, P = 0.021) associated with a smaller TRBCVmax reduction (23.6% ± 2% vs 31% ± 2%, P = 0.045). Changes in RBCVmax did not differ between HD (11.6% ± 1%) and healthy (8.3% ± 1.3%, P = 0.1) women. RBCV, RBCVmax, and TRBCVmax absolute values after estradiol were similar between groups. Past oral contraceptive exposure (P = 0.035) and cigarette smoking (P = 0.047) influenced healthy women's microvascular responses to estradiol, whereas triglyceride levels impaired HD vasodilation (P = 0.028). CONCLUSIONS: Before estradiol, HD presented impaired microvascular dilation and compliance compared with control women of similar age. After estradiol, HD recovered microvascular endothelial-mediated dilation, reaching similar absolute values, but the smaller reduction in TRBCVmax suggests irreversible microvascular stiffness.

Endothelial-mediated microcirculatory responses to an acute estradiol test are influenced by time since menopause, cumulative hormone exposure, and vasomotor symptoms.

OBJECTIVE: The aim of this study was to determine which factors could influence microcirculatory responses to an acute estradiol test during postmenopause. METHODS: Dynamic nailfold videocapillaroscopy was performed in 68 healthy 34- to 70-year-old postmenopausal women before and 1 hour after administration of 300 mug nasal estradiol. Red blood cell velocity (RBCV; mm/s) at rest and after the release of 60-second arterial occlusion (RBCVmax; mm/s) and time to reach it (TRBCVmax; s) were correlated to clinical and laboratory data. RESULTS: After estradiol administration, RBCV and RBCVmax increased by 13.4% and 9.4%, respectively, and TRBCVmax decreased by 29.1% (P = 0.0001 for all). These changes were not associated to the women's age but rather to time since menopause (P = 0.04; r = 0.245) and previous duration of hormone therapy (P = 0.03; r = 0.324). Past users of oral contraceptives presented higher velocities but smaller increases compared with never users (12.4% vs 17.7%, P = 0.022, for RBCV and 8.4% vs 13.7%, P = 0.028, for RBCVmax), and triglyceride levels were negatively associated to velocity increases (P = 0.05 and r = -0.243 for RBCV and P = 0.03 and r = -0.261 for RBCVmax) after estradiol administration. Previous smokers showed a smaller reduction in TRBCVmax, associated directly to total estimated number of smoked cigarettes (P = 0.03; r = -0.468). The reduction in TRBCVmax was also inversely related to the intensity of current vasomotor symptoms (P = 0.04; r = -0.252). CONCLUSIONS: Changes in RBCVs and TRBCVmax after estradiol administration indicate an increase in endothelial-dependent vasodilatation and vascular elasticity, respectively. Moreover, maintenance of endothelial responsiveness depends on cumulative exposure to sex steroids, duration of hormone deprivation, and triglyceride levels. Past smoking and current vasomotor symptoms could be associated to microvascular wall stiffness/elasticity.