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

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

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

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

Mammography and breast ultrasound analysis in male and female transgender persons using long-term gender affirming hormone therapy: a cross-sectional study in Brazil.

AIM: There is not much information about breast health in transgender (transexual) persons given the historical stigma that this population suffers. This research aimed to describe breast imaging patterns in transgender (trans) women and men that had been using gender affirmation hormone treatment for at least 3 years. MATERIAL AND METHODS: In this observational, cross-sectional study, 67 transgender individuals (34 trans women and 33 trans men) had mammography and breast ultrasound performed. We also classified the findings by the American College of Radiology - Breast Imaging Reporting and Data System (ACR BI-RADS®). RESULTS: We found that there was a higher frequency of dense breasts in trans women (75.8%) and in trans men (66,6%) than expected for cisgender (cis) women. CONCLUSIONS: This study highlights the importance of a deeper understanding of the image patterns of transgender breasts because of hormonal effects that the gender transition entails so we can offer better health care and preventive services in the transgender (transexual) population.

Serum concentrations of progesterone and prolactin as predictors of success in in vitro fertilization: A retrospective cohort study.

OBJECTIVE: The aim of this study is to determine whether the serum concentrations of progesterone and/or prolactin after fresh embryo transfer are associated with pregnancy rates in in vitro fertilization treatment. METHODS: This retrospective cohort study evaluated in vitro fertilization treatments with fresh embryo transfer, which were performed between 2013 and 2019 in a private clinic in Curitiba, Brazil. The serum concentrations of progesterone and prolactin were evaluated by chemiluminescence nine days after oocyte retrieval. The type of progesterone supplementation and pituitary blockage during the cycle of oocyte stimulation were evaluated. RESULTS: 330 fertilization cycles were performed in the 293 studied patients. The mean age of patients was 35.5±4.1years. The most seen isolated infertility factor was endometriosis (24.2% of the cases), while progesterone supplementation was performed intramuscularly in 73.9% of the cases. The progesterone values above 32.1ng/ml at day 9 (D9) were associated with better pregnancy rates. In cycles using antagonist and intramuscular luteal phase supplementation, higher pregnancy rates with progesterone values above 37.83ng/ml were observed. Moreover, prolactin showed no significant association with any of the studied variables. CONCLUSIONS: The serum progesterone concentrations above 32.1ng/ml at D9 that were taken one week before pregnancy testing were associated with successful in vitro fertilization treatment. Furthermore, prolactin showed no significant association with any of the studied variables.

Assessment of Nerve Fiber Density and Expression of Hormonal Receptors Within Rectosigmoid Endometriosis Nodules.

STUDY OBJECTIVE: To assess nerve fiber density and expression of hormone receptors in bowel endometriosis. DESIGN: Cross-sectional study. SETTING: Private hospital. PATIENTS: Women with endometriosis undergoing laparoscopic segmental bowel resection (n = 54). INTERVENTIONS: Tissue samples were obtained from patients with surgically treated rectosigmoid endometriosis. MEASUREMENTS AND MAIN RESULTS: The rectosigmoid specimen containing the endometriosis nodule was manually sectioned and divided into 3 areas: core of the nodule, margin of the nodule, and healthy bowel tissue. The intensity of expression of estrogen and progesterone receptors was evaluated by immunohistochemistry and measured according to the Allred score. Nerve fibers were stained by immunohistochemistry using Protein Gene Product 9.5, and the density of nerve fillets was counted and expressed in number/mm². All glandular and stromal cells stained for estrogen; however, glandular cells stained more strongly than stromal cells (61.1% vs 35.2%; p = .01). Most of glandular and stromal cells stained strongly for progesterone receptors (90.7% vs 98.1%; p = .2). The density of nerve fibers was very high in the margin of the nodule (172.22±45.66/mm²), moderate in healthy bowel tissue (111.48±48.57/mm²), and very low in the core of the nodule (7.31±4.9/mm²); p = .01. CONCLUSION: Both glandular and stromal cells within the rectosigmoid endometriosis nodule express estrogen and progesterone receptors. Higher intensity of expression of estrogen receptors occurs in glandular cells. The density of nerve fibers is extremely high at the nodule margin and very low in the center of the nodule.

Evaluation of the Seroprevalence of Infectious Diseases in 2,445 in vitro Fertilization Cycles.

OBJECTIVE: To evaluate the seroprevalence of positive markers for syphilis, human immunodeficiency virus (HIV) I and II, human T cell lymphotropic virus (HTLV) I and II, and hepatitis B and C among women undergoing in vitro fertilization (IVF). METHODS: We conducted a retrospective analysis among patients who underwent IVF, between January 2013 and February 2016, and who had complete screening records. RESULTS: We analyzed 1,008 patients who underwent IVF, amounting to 2,445 cycles. Two patients (0.2%) tested positive for HIV I and II and none for HTLV I and II. Three patients (0.3%) had positive screening for syphilis, and two (0.2%) had positive hepatitis C antibody test (anti-HCV). A positive hepatitis B virus surface antigen (HbsAg) test was observed in 4 patients (0.4%), while 47 (4.7%) patients were positive for IgG antibody to hepatitis B core antigen (anti-HbC IgG), and only 1 (0.1%) was positive for IgM antibody to hepatitis B core antigen (anti-HbC IgM). The anti-HbS test was negative in 659 patients (65.3%). Only 34.7% of the patients had immunity against the Hepatitis B virus. Patients with an anti-HbS negative result were older than those with a hepatitis B test (anti-HbS) positive result (36.3 versus 34.9; p < 0.001). CONCLUSION: The present study showed lower infection rates than the Brazilian ones for the diseases studied in patients undergoing IVF. Only a few patients were immunized against hepatitis B.

OBJETIVO: Avaliar a soroprevalência de marcadores positivos para sífilis, vírus da imunodeficiência humana (HIV) I e II, vírus linfotrópicos de células T humanas (HTLV) I e II e hepatite B e C em mulheres submetidas a fertilização in vitro (FIV). MéTODOS: Realizamos uma análise retrospectiva entre as pacientes submetidas a FIV, entre janeiro de 2013 e fevereiro de 2016, e que possuíam prontuários completos. RESULTADOS: Foram analisadas 1.008 pacientes submetidas a FIV, totalizando 2,445 ciclos. Duas pacientes (0,2%) apresentaram resultado positivo para HIV I e II, e nenhuma para HTLV I e II. Três pacientes (0,3%) apresentaram triagem positiva para sífilis, e duas (0,2%) apresentaram teste de pesquisa de anticorpos anti-HCV (anti-HCV) positivo. Um teste de antígeno de superfície do vírus da hepatite B (HbsAg) positivo foi observado em 4 pacientes (0,4%), enquanto 47 (4,7%) pacientes foram positivas para anticorpos IgG contra o antígeno de superfície da hepatite B (IgG anti-HbC), e apenas 1 (0,1%) foi positiva para anticorpos IgM contra o antígeno central da hepatite B (IgM anti-HbC). O teste de anticorpos contra hepatite B (anti-HbS) foi negativo em 659 pacientes (65,3%). Apenas 34,7% das pacientes tinham imunidade contra o vírus da hepatite B. Pacientes com resultado negativo anti-HbS eram mais velhas do que aquelas com resultado positivo anti-HbS (36,3 versus 34,9; p < 0,001). CONCLUSãO: Este estudo mostrou taxas de infecção inferiores às taxas brasileiras para as doenças estudadas em pacientes submetidas à FIV. Apenas alguns pacientes foram imunizados contra a hepatite B.

Hysteroscopic and aspiration biopsies in the histologic evaluation of the endometrium, a comparative study.

This study aimed to compare the quality of histological endometrial samples collected through Pipelle aspiration and hysteroscopic biopsies to assess the agreement between these 2 biopsies in the histological diagnosis of malignancy and to compare the costs of both biopsies.This was a cross-sectional study. Forty-five women were biopsied, first using Pipelle and immediately after using hysteroscopy. The material collected was sent for analysis, and hysteroscopy was considered the gold standard. The results were divided into the following 3 categories: normal (atrophic, proliferative, and secretory endometrium); polyps; and malignancies. We report the agreement between Pipelle and hysteroscopy in the diagnosis of malignancy and compare their costs.The study showed that while analyzing endometrial malignancies, Pipelle sampling had 100% sensitivity and specificity. In the detection of polyps, Pipelle sampling showed 26.1% sensitivity, 88.9% specificity, 75% positive predictive value, 48.5% negative predictive value, and 53.7% accuracy. Agreement with hysteroscopy in the diagnosis of malignancy was 100%. The Pipelle device costs 27 times less than hysteroscopic biopsy for health insurance companies. This cost is 13.7 times lower in the Brazilian Unified Health System.Endometrial biopsies using the Pipelle have a high accuracy for endometrial cancer and a low accuracy for polyps. We detected 100% agreement between the reports of Pipelle and hysteroscopy with regard to malignancy. Pipelle is the most cost-effective method of endometrial biopsy.

An individualized approach to the management of vaginal atrophy in Latin America.

OBJECTIVE: In the absence of guidelines specific for Latin America, a region where the impact of menopause is becoming increasingly important, an evidence-based specialist opinion on management of vaginal atrophy will help improve outcomes. METHODS: An advisory board meeting was convened in São Paulo, Brazil, to discuss practical recommendations for managing vaginal atrophy in women in Latin America. Before the meeting, physicians considered various aspects of the condition, summarizing information accordingly. This information was discussed during the meeting. The expert consensus is now summarized. RESULTS: In Latin America, given the relatively early age of menopause, it will be beneficial to raise awareness of vaginal atrophy among women before they enter menopause, considering cultural attitudes and involving partners as appropriate. Women should be advised about lifestyle modifications, including attention to genital hygiene, clothing, and sexual activity, and encouraged to seek help as soon as they experience vaginal discomfort. Although treatment can be started at any time, prompt treatment is preferable. A range of treatments is available. By addressing the underlying pathology, local estrogen therapy can provide effective symptom relief, with choice of preparation guided by patient preference. An individualized treatment approach should be considered, giving attention to patients' specific situations. CONCLUSIONS: It is critical that women are empowered to understand vaginal atrophy. Educating women and healthcare providers to engage in open dialogue will facilitate appreciation of the benefits and means of maintaining urogenital health, helping to improve outcomes in middle age and beyond. Women should receive this education before menopause.

The prevalence and clinical associations of hypovitaminosis D in pregnant women from Brazil.

OBJECTIVE: To study the prevalence and the clinical and demographic associations of hypovitaminosis D in pregnant women from southern Brazil. METHODS: In this cross-sectional study, pregnant women attending prenatal care at two university clinics in Curitiba, Brazil, were investigated for clinical and demographic data and for serum levels of vitamin D, calcium, and parathyroid hormone. Data were collected during summer (January 26 to March 4, 2016) or winter (July 28 to August 31, 2016). RESULTS: The study included 520 women, with 264 studied in winter and 256 in summer. The median vitamin D level was 53.41 nmol/L; 227 (43.7%) women had vitamin D deficiency (<49.92 nmol/L), 193 (37.1%) had vitamin D insufficiency, and 100 (19.2%) had a normal level (≥74.88 nmol/L). The vitamin D serum level was linked to the season (P<0.001) and the body mass index (P=0.026). Women with HIV infections had a lower prevalence and women with pre-eclampsia had a higher prevalence of hypovitaminosis D (P<0.001 and P=0.025, respectively). The association between pre-eclampsia and low vitamin D status was independent of body mass index, tobacco exposure, maternal age, and pregnancy duration (P=0.043; odds ratio 1.014-2.795). CONCLUSION: The rate of hypovitaminosis D in pregnant women from southern Brazil was high. Hypovitaminosis D was more common in winter and was associated with pre-eclampsia.

Tissue selective estrogen complexes (TSECs) differentially modulate markers of proliferation and differentiation in endometrial cells.

Selective estrogen receptor modulators (SERMs) have tissue-specific estrogen receptor (ER) modulating properties. Combining an SERM with one or more estrogens to form a tissue selective estrogen complex (TSEC) can provide an improved blend of tissue-specific ER agonist and antagonist effects. While both estrogens and SERMs affect the uterine endometrium, not all TSECs reverse the endometrial effects of estrogens preventing endometrial proliferation and hyperplasia. Their action in uterine cells is not completely understood. HOXA 10, leukemia inhibitory factor (LIF), progesterone receptor (PR), and EMX2 are genes known to regulate endometrial proliferation and differentiation. The expression of these genes was used to assess endometrial effects of SERMs and TSECs. We evaluated the effects of raloxifene (RAL), tamoxifen (TAM), lasofoxifene (LAS), bazedoxifene acetate (BZA), and progesterone (P) alone and in combination with estradiol (E2) in Ishikawa cells. Increased HOXA10, LIF, PR, and EMX2 messenger RNA (mRNA) expression was noted in E2-treated cells compared with vehicle-treated controls. All TSECs maintained E2-induced PR expression and all except TAM prevented estrogen-induced LIF expression. The TSEC containing BZA uniquely decreased HOXA10 expression and increased EMX2 expression. The TSECs alter endometrial cell proliferation by selective modulation of estrogen responsive genes, maintaining the antiproliferative effects mediated by PR and inhibiting LIF. The differential effect of TSECs on endometrial gene expression suggests a mechanism by which they manifest differential effects on endometrial safety against the risk of estrogen-induced endometrial hyperplasia.

Osteoporosis after transplantation.

Transplantation is an established therapy for end-stage diseases of kidney, lung, liver, and heart among others. Osteoporosis and fragility fractures are serious complications of organ transplantation, particularly in the first post-transplant year. Many factors contribute to the pathogenesis of osteoporosis following organ transplantation. This review addresses the mechanisms of bone loss that occurs both in the early and late post-transplant periods, including the contribution of the immunosuppressive agents as well as the specific features to bone loss after kidney, lung, liver, cardiac, and bone marrow transplantation. Prevention and treatment for osteoporosis in the transplant recipient are also discussed.

Treatment with bazedoxifene, a selective estrogen receptor modulator, causes regression of endometriosis in a mouse model.

Endometriosis is a common estrogen-dependent disorder. Medical treatments currently consist of progestins or GnRH agonists; however, neither is fully effective and both entail significant side effects. Selective estrogen receptor (ER) modulators (SERM) have tissue-selective actions, acting as an ER agonist in some tissues and ER antagonist in others. The SERM bazedoxifene (BZA) effectively antagonizes estrogen-induced uterine endometrial stimulation without countering estrogenic effects in bone or central nervous system. These properties make it an attractive candidate for use in the treatment of endometriosis. Experimental endometriosis was created in reproductive-age CD-1 mice. After 8 wk, 10 animals received i.p. injections of BZA (3 mg/kg·d) for 8 wk, whereas 10 received vehicle control. Mice were killed, and implant size was assessed. The mean size of the implants after treatment was 60 mm(2) in the control group and 21 mm(2) in the BZA treatment group (P = 0.03). Quantitative PCR and immunohistochemical analysis were used to determine the effect on endometrial gene expression. PCNA, ERα, and LIF mRNA and protein expression were significantly decreased in endometrium of the treated group. Caspase 3 mRNA expression was increased. Expression of PR and Hoxa10 were not significantly altered by treatment. There was no evidence of ovarian enlargement or cyst formation. Decreased PCNA and ER expression demonstrated that the regression of endometriosis likely involved decreased estrogen-mediated cell proliferation. BZA may be an effective novel agent for the treatment of endometriosis due to greater endometrial-specific estrogen antagonism compared with other SERM.

Skeletal microstructural abnormalities in postmenopausal women with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is associated with osteoporosis and fragility fractures. The objectives of this study were to assess static and dynamic indices of cancellous and cortical bone structure in postmenopausal women with COPD. Twenty women with COPD who had not received chronic oral glucocorticoids underwent bone biopsies after double tetracycline labeling. Biopsies were analyzed by histomorphometry and µCT and compared with age-matched controls. Distribution of the patients according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) was: Type I (15%), Type II (40%), Type III (30%), and Type IV (15%). Mean (±SD) cancellous bone volume (15.20 ± 5.91 versus 21.34 ± 5.53%, p = .01), trabecular number (1.31 ± 0.26 versus 1.77 ± 0.51/mm, p = .003), and trabecular thickness (141 ± 23 versus 174 ± 36 µm, p = .006) were lower in patients than in controls. Connectivity density was lower in COPD (5.56 ± 2.78 versus 7.94 ± 3.08/mm, p = .04), and correlated negatively with smoking (r = -0.67; p = .0005). Trabecular separation (785 ± 183 versus 614 ± 36 µm, p = .01) and cortical porosity (4.11 ± 1.02 versus 2.32 ± 0.94 voids/mm(2); p < .0001) were higher in COPD while cortical width (458 ± 214 versus 762 ± 240 µm; p < .0001) was lower. Dynamic parameters showed significantly lower mineral apposition rate in COPD (0.56 ± 0.16 versus 0.66 ± 0.12 µm/day; p = .01). Patients with more severe disease, GOLD III and IV, presented lower bone formation rate than GOLD I and II (0.028 ± 0.009 versus 0.016+ 0.011 µm(3)/µm(2)/day; p = 04). This is the first evaluation of bone microstructure and remodeling in COPD. The skeletal abnormalities seen in cancellous and cortical bone provide an explanation for the high prevalence of vertebral fractures in this disease.

[Serum androgen concentrations and bone mineral density in postmenopausal ovariectomized and non-ovariectomized women]. / Androgênios séricos e densidade mineral óssea em mulheres ooforectomizadas e não ooforectomizadas na pós-menopausa.

OBJECTIVE: Compare levels of androgens and bone mineral density (BMD) of ovariectomized (OVX) and non-ovariectomized (NOVX) postmenopausal women. Forty women, 20 OVX and 20 NOVX, (53.9 +/- 4 years) were selected. METHODS: Total testosterone (TT), free testosterone (FT), androstenedione (AN), dehidroepiandrostenedione (DHEA) and its sulfate (DHEA-S) were measured. BMD was measured in 14 OVX and 16 NOVX. RESULTS: No differences between groups with regard to age, body mass index (BMI) and time since menopause were found. Mean levels of TT and FT were two-fold higher in NOVX group (60.91 versus 30.17 ng/dL, p = 0.0001; 1.00 versus 0.48 pg/mL, p = 0.003). BMD was not different between groups. Inverse correlations were found between BMI and TT (r = -0.3; p = 0.05); time since menopause and AN (r = -0.35; p = 0.02) and time since menopause and DHEA (r = -0.3; p = 0.01). CONCLUSION: Bilateral ovariectomy leads to a more severe androgen deficiency than natural menopause in postmenopausal women and did not compromise bone mass.