Assistência ginecológica aos transgênero / Gynecological care for transgenders

Transgênero (trans) é um termo que alberga toda a diversidade de gênero. A incongruência de gênero faz parte desse espectro e refere-se à pessoa cuja identidade de gênero é oposta ao sexo que lhe foi atribuído no nascimento. A terapia hormonal de afirmação de gênero, bem como a cirurgia de afirmação de gênero, é necessária para adequar o corpo ao gênero ao qual a pessoa se identifica. Os homens trans necessitam da terapia com testosterona, que visa reduzir as concentrações de estradiol e incrementar a testosterona circulante para níveis fisiológicos masculinos, resultando em masculinização. A mulher trans receberá o estradiol, associado ou não a um antiandrogênico, visando reduzir a testosterona e incrementar o estrogênio para níveis femininos, resultando em feminização. A cirurgia de afirmação de gênero é, frequentemente, requerida para completar as modificações fenotípicas para o homem e a mulher trans. O ginecologista e obstetra tem um papel crucial no provimento de cuidados a essa população. O presente artigo visa sistematizar algumas ações que o ginecologista e obstetra pode oferecer e que têm potencial para melhorar a qualidade de vida dos homens e mulheres trans. (AU)

Transgenero (trans) is an umbrella term that encompasses all gender diversity. Gender Incongruity is part of this spectrum and refers to the person whose gender identity is opposed to the sex assigned to them at birth. Gender-affirming hormone therapy as well as gender-affirming surgery are necessary to adapt the body to the gender to which the person identifies. Trans men require testosterone therapy to reduce estradiol concentrations and increase circulating testosterone to male physiological levels resulting in masculinization. Trans women will receive estradiol associated or not with an antiandrogenic to reduce testosterone and increase estrogen to female levels resulting in feminization. gender-affirming surgery is often required to complete phenotypic modifications for trans men and women. The gynecologist and obstetrician plays a crucial role in to provide care to this population. This article aims to systematize some actions that the gynecologist and obstetrician can offer to improve the quality of life of trans men and women. (AU)

Protective Effect and Mechanism of Kuntai Capsule on Angiotensin II -Induced Hypertension in Ovariectomized Rats / 中国结合医学杂志

OBJECTIVE@#To explore the protective effect and mechanism of Kuntai (KT) Capsule on angiotensin II (Ang II)-induced hypertension in ovariectomized (OVX) rats.@*METHODS@#Fifty-four rats were randomly divided into 6 groups according to a random number table, 9 in each group: control, OVX sham+Ang II, OVX, OVX+Ang II, OVX+Ang II +E2, and OVX+Ang II +KT. OVX rats model was constructed by retroperitoneal bilateral ovariectomy. After 4 weeks of pretreatment with KT Capsule [0.8 g/(kg·d) and 17- β -estradiol (E2, 1.2 mg/(kg·d)] respectively, Ang II was injected into a micro-osmotic pump with a syringe to establish a hypertensive rat model. Blood pressure of rat tail artery was measured in a wake state of rats using a non-invasive sphygmomanometer. Blood pressure changes were compared between the intervention groups (OVX+Ang II +KT, OVX+Ang II +E2) and the negative control group (OVX+Ang II). Serum malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were detected respectively. The expressions of oxidative stress-related protein superoxide dismutase2 (SOD2) and anti-thioredoxin (TRX), autophagy marker protein [beclin1, light chain (LC) 3 II/I ratio and autophagy canonical pathway protein phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR)] were evaluated by Western blotting.@*RESULTS@#Compared with the OVX+Ang II group, the systolic blood pressure of OVX+Ang II +KT group was significantly lowered (P<0.05) but not the diastolic blood pressure. Besides, SOD2 and TRX protein levels in mycardial tissues were significantly reduced in the OVX+Ang II +KT group compared with the OVX+Ang II group (P<0.05). Oxidative stress serum markers MDA and SOD were down- and up-regulated in the OVX+Ang II +KT group, respectively (P<0.05). Compared with OVX+Ang II group, the levels of cardiac proteins beclin-1 and LC3II/LC3 I in OVX+Ang II +KT group were also up-regulated (P<0.05), and the expression levels of p-PI3K, p-AKT and mTOR protein were down-regulated (P<0.05).@*CONCLUSION@#KT could protect blood pressure of Ang II-induced OVX rats by inhibiting oxidative stress and up-regulating protective autophagy.

Serum estradiol levels decrease after oophorectomy in transmasculine individuals on testosterone therapy / 亚洲男科学杂志(英文版)

Transmasculine individuals, considering whether to undergo total hysterectomy with bilateral salpingectomy, have the option to have a concomitant oophorectomy. While studies have evaluated hormone changes following testosterone therapy initiation, most of those patients have not undergone oophorectomy. Data are currently limited to support health outcomes regarding the decision to retain or remove the ovaries. We performed a retrospective chart review of transmasculine patients maintained on high-dose testosterone therapy at a single endocrine clinic in Vancouver, British Columbia, Canada. Twelve transmasculine individuals who underwent bilateral oophorectomy and had presurgical and postsurgical serum data were included. We identified 12 transmasculine subjects as controls, who were on testosterone therapy and did not undergo oophorectomy, but additionally matched to the first group by age, testosterone dosing regimen, and body mass index. There was a statistically significant decrease in the estradiol levels of case subjects postoophorectomy, when compared to presurgical estradiol levels (P = 0.02). There was no significant difference between baseline estradiol levels between control and case subjects; however, the difference in estradiol levels at follow-up measurements was significant (P = 0.03). Total testosterone levels did not differ between control and case subjects at baseline and follow-up (both P > 0.05). Our results demonstrate that oophorectomy further attenuates estradiol levels below what is achieved by high-dose exogenous testosterone alone. Correlated clinical outcomes, such as impacts on bone health, were not available. The clinical implications of oophorectomy versus ovarian retention on endocrinological and overall health outcomes are currently limited.

Associations of sex hormone levels with body mass index (BMI) in men: a cross-sectional study using quantile regression analysis / 亚洲男科学杂志(英文版)

Body mass index (BMI) has been increasing globally in recent decades. Previous studies reported that BMI was associated with sex hormone levels, but the results were generated via linear regression or logistic regression, which would lose part of information. Quantile regression analysis can maximize the use of variable information. Our study compared the associations among different regression models. The participants were recruited from the Center of Reproductive Medicine, The First Hospital of Jilin University (Changchun, China) between June 2018 and June 2019. We used linear, logistic, and quantile regression models to calculate the associations between sex hormone levels and BMI. In total, 448 men were included in this study. The average BMI was 25.7 (standard deviation [s.d.]: 3.7) kg m-2; 29.7% (n = 133) of the participants were normal weight, 45.3% (n = 203) of the participants were overweight, and 23.4% (n = 105) of the participants were obese. The levels of testosterone and estradiol significantly differed among BMI groups (all P < 0.05). In linear regression and logistic regression, BMI was associated with testosterone and estradiol levels (both P < 0.05). In quantile regression, BMI was negatively associated with testosterone levels in all quantiles after adjustment for age (all P < 0.05). BMI was positively associated with estradiol levels in most quantiles (≤80th) after adjustment for age (all P < 0.05). Our study suggested that BMI was one of the influencing factors of testosterone and estradiol. Of note, the quantile regression showed that BMI was associated with estradiol only up to the 80th percentile of estradiol.

Acupuncture combined with auricular point sticking for girls aged 3-8 years with incomplete precocious puberty: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the efficacy and safety of acupuncture combined with auricular point sticking for girls aged 3-8 years with incomplete precocious puberty (IPP).@*METHODS@#Sixty girls with IPP were randomly divided into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 2 cases were eliminated). The girls in the control group were treated with healthy diet and proper exercise for 12 weeks. On the basis of the treatment in the control group, the girls in the observation group were treated with acupuncture combined with auricular point sticking. The acupuncture was applied at Sanyinjiao (SP 6), Guanyuan (CV 4), Guilai (ST 29), etc., the needles were retained for 20 min, acupuncture was given twice a week (once every 3 days). The auricular point sticking was applied at Luanchao (TF2), Neishengzhiqi (TF2), Neifenmi (CO18), Yuanzhong (AT2,3,4i), etc., twice a week. The treatment was given for 12 weeks. Before treatment, after treatment and in follow-up after 12 weeks of treatment completion, the Tanner stage of breast, serum contents of sex hormone (luteinizing hormone [LH], follicle-stimulating hormone [FSH], estradiol [E2]) were observed. The ovarian volume, the number of follicles with diameter>4 mm, and the uterine volume were measured by abdominal color Doppler ultrasound. In addition, the safety of the observation group was evaluated.@*RESULTS@#Compared with before treatment, the Tanner stage of breast in the observation group was improved after treatment and in follow-up (P<0.05); after treatment and in follow-up, the Tanner stage of breast in the observation group was better than that in the control group (P<0.05). Compared with before treatment, the serum levels of LH and E2 in the observation group were increased (P<0.05), and the volume of bilateral ovaries was larger (P<0.05) in follow-up. Compared with before treatment, the serum contents of LH, FSH and E2 in the control group were increased (P<0.05), the volume of bilateral ovaries was larger (P<0.05), and the number of follicles was increased (P<0.05) after treatment and in follow-up. The serum levels of LH, FSH and E2 in the observation group were lower than those in the control group (P<0.05), the volume of bilateral ovaries was smaller than that in the control group (P<0.05), and the number of follicles was lower than that in the control group (P<0.05). Compared with before treatment, the uterine volume in the two groups was larger in follow-up (P<0.05). There was no statistically significant difference between the two groups after treatment and in follow-up (P>0.05). During the treatment, 3 cases in the observation group had slight abdominal pain and subcutaneous blood stasis, without serious adverse reactions.@*CONCLUSION@#Acupuncture combined with auricular point sticking could improve the Tanner stage of breast, reduce the level of sex hormone, slow down the development and maturation of ovary and follicle, and control the degree and speed of sexual development in girls aged 3-8 years with IPP.

Estudo do composto STX140, um análogo do estradiol, em linhagens de melanoma humano / STX140 compound study in human melanoma

O câncer de pele pode ser classificado como não melanoma e melanoma. O melanoma apresenta baixa incidência entre os cânceres de pele, porém é a forma mais letal e é considerado um dos tipos mais resistentes ao tratamento. Devido à infiltração de células malignas nos tecidos, vasos linfáticos e vasos sanguíneos, o melanoma invade e se espalha rapidamente. Suas metástases são frequentemente localizadas em linfonodos, cérebro, fígado e outros órgãos. Melanomas metastáticos abrigam múltiplas mutações gênicas e muitos tumores apresentam resistência aos tratamentos, como por exemplo com inibidores BRAF, devido à mutações e ativação de vias paralelas. Ou seja, existe uma necessidade clara da busca de novas opções de tratamento. Em trabalho realizado por nosso grupo, Massaro et al mostraram que o derivado de estradiol 2- Metoxiestradiol induz apoptose em células de melanoma e senescência. Neste sentido, o composto STX140, (um análogo do estradiol com biodisponibilidade superior), que já se mostrou eficaz no combate ao câncer de mama em diversos estudos in vitro e in vivo, será então avaliado para sua ação no melanoma de forma inédita. Este trabalho teve como principal objetivo explorar a ação antitumoral em células de melanoma do composto STX140, especialmente a indução de senescência. Utilizando a cultura de células de melanoma foram realizados os ensaios de: viabilidade celular - IC50, formação de colônias, análise do ciclo celular e caracterização de morte celular por citometria de fluxo, ensaio In vitro scratch, coloração para ß-galactosidase, PCR quantitativo e ELISA. Os resultados mostraram que o composto STX140: diminui a viabilidade celular, inibe a proliferação, formação de colônias e migração em linhagens de melanoma (não resistentes e resistentes ao vemurafenibe, inibidor de BRAF). Além do mais, o composto atuou diminuindo a secreção da interleucina pró-tumoral IL-8 em células resistentes. O STX140 induziu senescência nas células de melanoma que foram positivas para ß-galactosidase, também havendo aumento da expressão de genes chave de vias de senescência (CDKN1A e GADD45A) nas células de melanoma resistentes tratadas com o composto. Em conclusão, o STX140 mostrou ter um potencial antitumoral contra o melanoma, diminuindo sua viabilidade celular, inibindo sua proliferação e migração, induzindo senescência, diminuindo a secreção de interleucina pró- tumoral, com efeito mais acentuado nas linhagens de melanoma resistente

Skin cancer can be classified as non-melanoma and melanoma. Melanoma has a low incidence among skin cancers, but it is the most lethal form and is considered one of the most resistant to treatment. Due to the infiltration of malignant cells into tissues, lymphatic vessels and blood vessels, melanoma invades and spreads rapidly. Its metastases are often located in lymph nodes, brain, liver and other organs. Metastatic melanomas presents multiple gene mutations and many tumors are resistant to treatments, such as with BRAF inhibitors, due to mutations and activation of parallel pathways. In other words, there is a clear need to search for new treatment options. In work carried out by our group, Massaro et al showed that the estradiol derivative 2- Methoxyestradiol induces apoptosis in melanoma cells and senescence. In this sense, the compound STX140, (an estradiol analogue with superior bioavailability), which has already been shown to be effective against breast cancer in vitro and in vivo studies will be then evaluated for its action on melanoma. The main objective of this work is to explore the antitumor action of the compound STX140 in melanoma cells, especially the induction of senescence. Using the melanoma cell culture the following assays were performed: cell viability - IC50, clonogenic, cell cycle analysis and cell death characterization by flow cytometry, wound assay, staining for ß-galactosidase, quantitative PCR and ELISA. Preliminary data from this work showed that the compound STX140: decreases cell viability, inhibits proliferation, colony formation and migration in melanoma cell lines (non-resistant and resistant to vemurafenib, BRAF inhibitor). It also decreased the secretion of pro-tumor interleukin IL-8 in resistant cells. STX140 induced senescence in melanoma cells, that were positive for ß-galactosidase, and there was also increased expression of key genes of senescence pathways (CDKN1A and GADD45A) in resistant melanoma cells treated with the compound. In conclusion, STX140 has been shown to have antitumor potential against melanoma, decreasing its cell viability, inhibiting its proliferation and migration, inducing senescence, decreasing pro-tumor interleukin secretion, with a more pronounced effect on resistant melanoma cell lines

Estradiol inhibits differentiation of mouse macrophage into a pro-inflammatory phenotype by upregulating the IRE1α-XBP1 signaling axis / 南方医科大学学报

OBJECTIVE@#To explore the mechanism by which estradiol modulates the immunophenotype of macrophages through the endoplasmic reticulum stress pathway.@*METHODS@#Peritoneal macrophages isolated from C57 mice were cultured in the presence of 60 ng/mL interferon-γ (IFN-γ) followed by treatment with estradiol (1.0 nmol/L) alone, estradiol with estrogen receptor antagonist (Acolbifene, 4 nmol/L), estradiol with IRE1α inhibitor (4 μ 8 C), or estradiol with IRE1α agonist. After the treatments, the expression levels of MHC-Ⅱ, iNOS and endoplasmic reticulum stress marker proteins IRE1α, eIF2α and ATF6 in the macrophages were detected with Western blotting, and the mRNA levels of TGF-β, IL-6, IL-10 and TNF-α were detected with RT-PCR.@*RESULTS@#Estrogen treatment of the macrophages significantly decreased the expressions of M1-related proteins MHC-Ⅱ (P=0.021) and iNOS (P < 0.001) and the mRNA expressions of TNF-α (P=0.003) and IL-6 (P=0.004), increased the mRNA expression of TGF-β (P=0.002) and IL-10 (P=0.008), and up-regulated the protein expressions of IRE1α (P < 0.001) and its downstream transcription factor XBP-1 (P < 0.001). Addition of the estrogen inhibitor obviously blocked the effect of estrogen. Compared with estrogen treatment alone, combined treatment of the macrophages with estrogen and the IRE1α inhibitor 4 μ 8 C significantly up-regulated the protein expressions of MHC-Ⅱ (P=0.002) and iNOS (P=0.003) and the mRNA expressions of TNF-α (P=0.003) and IL-6 (P=0.024), and obviously down-regulated the mRNA expression of TGF-β (P < 0.001) and IL-10 (P < 0.001); these changes were not observed in cells treated with estrogen and the IRE1α agonist.@*CONCLUSION@#Estrogen can inhibit the differentiation of murine macrophages into a pro-inflammatory phenotype by up-regulating the IRE1α-XBP-1 signaling axis, thereby producing an inhibitory effect on inflammatory response.

Cross-sectional analysis of gonadal hormone expression and relevant factors in female centenarians in Hainan, China / 中南大学学报(医学版)

OBJECTIVES@#Gonadal hormone is essential for the health of postmenopausal women, however, few studies have focused on the epidemiological distribution of gonadal hormones in postmenopausal women in very late postmenopausal women. This study aims to investigate and analyze the differences of serum gonadal hormone content and its influential factors among female centenarians in Hainan, China.@*METHODS@#The questionnaire and physical examination data of 741 female centenarians and 401 elderly females in Hainan Province were collected, and venous blood samples were taken to detect the indexes of lipid metabolism, bone metabolism, and gonadal hormone. The differences of gonadal hormones and relavant factors in female centenarians were analyzed and compared.@*RESULTS@#The serum levels of estradiol and progesterone of female centenarians were significantly higher than those of the elderly females (both P<0.001). The serum levels of estradiol and testosterone of ethnic minority centenarians were higher than those in Han nationality (P<0.001), and the serum estradiol and testosterone concentrations were relatively higher when the daily activities were more than 10 min (both P<0.05). Serum estradiol concentration was negatively correlated with apolipoprotein A-I, high density lipoprotein, triglyceride and bone formation markers such as calcium, inorganic phosphorus and vitamin D3, and was positively correlated with the special sequence of β-collagen (markers of bone resorption) (all P<0.01).@*CONCLUSIONS@#For the extremely late postmenopausal women (such as centenarians), there may be characteristic expressions of gonadal hormones, especially estradiol. There is an unprotective correlation of serum estradiol with lipid metabolism index and bone metabolism index in female centenarians, so it is necessary to evaluate the estrogen content and the use of estrogen therapy in postmenopausal women.

Hippocampus is involved in 17β-estradiol exacerbating experimental occlusal inter- ference-induced chronic masseter hyperalgesia in ovariectomized rats / 北京大学学报(医学版)

OBJECTIVE@#To investigate the influence of chronic masseter hyperalgesia induced by 17β-estradiol (E2) and experimental occlusal interference (EOI) on underlying mechanism in hippocampus of ovariectomized (OVX) rats.@*METHODS@#In the study, 32 OVX rats were randomly divided into 4 groups (8 rats/group): The control group was OVX group, and 0 μg/d E2 (vehicle) injection was started 7 d after OVX without EOI; in the experimental group (1) OVX + E2 group, 80 μg/d E2 injection was started 7 d after OVX without EOI; in the experimental group (2) OVX + EOI group, vehicle injection was started 7 d after OVX and EOI was applied 17 d after OVX; in the experimental group (3) OVX + E2 + EOI group, 80 μg/d E2 injection was started 7 d after OVX and EOI was applied 17 d after OVX. Bilateral masseter muscle mechanical withdrawal thresholds were measured before OVX, 7 days after OVX (before E2 injection), 17 days after OVX (10 days after E2 injection and before EOI) and 24 days after OVX (7 days after EOI). Immunofluorescence staining was used to reveal phospho-extracellular signal regulated kinase 1/2 (p-ERK1/2)-positive neurons in CA3 of hippocampus. The protein expression of p-ERK1/2 in hippocampus was detected using Western Blot.@*RESULTS@#Compared with the control group [left side: (135.3±8.5) g, right side: (135.4±10.8) g], bilateral masseter muscle mechanical withdrawal thresholds of OVX+E2 group [left side: (113.3±5.6) g, right side: (112.5 ± 5.6) g] and OVX+EOI group [left side: (93.3±5.4) g, right side: 90.8±5.5) g] were decreased (P < 0.01). Bilateral masseter muscle mechanical withdrawal thresholds were significantly lower in OVX+E2+EOI group [left side: (81.2±6.2) g, right side: 79.8±7.7) g] than in the control, OVX+E2 and OVX+EOI groups (P < 0.05). The proportion of p-ERK1/2 positive neurons in the CA3 region of the hippocampus was increased in the control, OVX+E2, OVX+EOI and OVX+E2+EOI groups in turn, and the difference between the groups was statistically significant (P < 0.05). p-ERK1/2 protein expression was increased in the control, OVX+E2 and OVX+EOI groups in turn, but the difference was not statistically significant (P>0.05). p-ERK1/2 expression was significantly higher in OVX+E2+EOI group than in the other three groups (P < 0.05).@*CONCLUSION@#High concentration of E2 could exacerbated EOI-induced chronic masseter hyperalgesia in ovariectomized rats, and its central mechanism may be related to the upregulation of the phosphorylation of ERK1/2 in hippocampus.

Evaluation of Hormonal Influence in Patients with Fractures Attributed to Osteoporosis / Avaliação da influência hormonal em pacientes com fraturas atribuídas a osteoporose

Abstract Objective The present study aims to evaluate the influence of hormonal levels of vitamin D, calcitonin, testosterone, estradiol, and parathyroid in patients with fractures attributed to osteoporosis when compared with young patients with fractures resulting from high-impact accidents. Methods Blood samples were collected from 30 elderly patients with osteoporosisattributed fractures (T-score ≤-2.5) (osteoporotic group), and from 30 young patients with fractures resulting from high-impact accidents (control group). Measurement of 1,25-hydroxyvitamin D (Kit Diasorin, Saluggia, Italy), calcitonin (Kit Siemens, Tarrytown, NY, USA), testosterone, estradiol, and parathyroid hormone (Kit Beckman Couter, Indianapolis, IN, United States) was performed using a chemiluminescence technique. Data were inserted into a Microsoft Excel (Microsoft Corp., Armonk, WA, USA) spreadsheet and analyzed using Statview statistical software. Results showing non-normal distribution were analyzed with nonparametric methods. The Mann-Whitney test was applied for group comparison, and a Spearman test correlated hormonal levels. Statistical significance was set at p < 0.05. All analyzes compared gender and subjects with and without osteoporosis. Results Women with osteoporosis had significantly lower levels of estradiol and vitamin D (p = 0.047 and p = 0.0275, respectively). Men with osteoporosis presented significantly higher levels of parathyroid hormone (p = 0.0065). There was no significant difference in testosterone and calcitonin levels. Conclusion Osteoporosis patients presented gender-related hormonal differences. Women had significantly lower levels of estradiol and vitamin D, whereas men had significantly higher parathyroid hormone levels, apparently impacting the disease.

Resumo Objetivo Avaliar a influência dos níveis hormonais de vitamina D, calcitonina, testosterona, estradiol e paratormônio em pacientes com fratura atribuída a osteoporose, quando comparados com pacientes jovens que tiveram fraturas decorrentes de acidente de alto impacto. Métodos Foram coletadas amostras de sangue de 30 pacientes idosos com fratura atribuída a osteoporose (T-score ≤-2,5) (grupo com osteoporose) e 30 amostras de sangue de pacientes jovens que sofreram fraturas decorrentes de acidentes de alto impacto (grupo controle). Foram realizadas dosagem de 1,25-hidroxivitamina D (Kit Diasorin, Saluggia, Italy), calcitonina (Kit Siemens, Tarrytown, NY, USA), testosterona, estradiol e paratormônio (Kit Beckman Couter, Indianapolis, IN, United States) pela técnica de quimiluminescência. Os dados foram inseridos em uma planilha de dados no programa Microsoft Excel (Microsoft Corp., Redmond, WA, EUA) e analisados pelo programa de estatística Statview. Os resultados que apresentaram distribuição não normal foram analisados com métodos não paramétricos. Para análise de variáveis comparando-se os dois grupos, aplicou-se o teste Mann-Whitney. Foi utilizado o teste de correlação de Spearman para a correlacionar os níveis hormonais. Um valor-p >0.05 foi considerado significante. Todas as análises foram feitas comparando gênero e grupos de pacientes come sem osteoporose. Resultados Mulheres com osteoporose apresentam níveis significativamente menores de estradiol e vitamina D (p = 0.047 e p = 0.0275), respectivamente. Homens com osteoporose demonstraram níveis significativamente maiores de paratormônio (p = 0.0065). Não houve diferença significativa nos níveis de testosterona e calcitonina. Conclusão Existem diferenças hormonais entre os gêneros na osteoporose. Em mulheres, níveis significativamente menores de estradiol e vitamina D e, nos homens, níveis significativamente maiores de paratormônio, parecem influenciar na doença.

Terapia hormonal de la menopausia en el año 2021 / Hormone therapy for menopause in 2021

Describe los planteamientos sobre el beneficio de la terapia de reemplazo hormonal en las mujeres en la menopausia y el riesgo de contraer cáncer de mama con el uso prolongado del mismo.

El climaterio como etapa fisiológica crucial en la prevención de la enfermedad cardiovascular / The climacteric as a crucial physiological stage in the prevention of cardiovascular disease

El climaterio es una etapa fisiológica que permite al médico reconocer tempranamente los riesgos de patologías y la gran oportunidad de revertirlas. Este trabajo examinará la evidencia actual de la terapia hormonal en la prevención primaria de la enfermedad cardiovascular en mujeres, así como la importancia que igualmente tienen la indemnidad de los ovarios, el peso normal, el uso correcto de antibióticos, la preservación de la microbiota intestinal, las dietas antioxidantes, los estilos de vida saludables y el obligatorio abandono del hábito de fumar.

Plasma metabolite changes in anestrous dairy cows with negative energy balance identified using 1H NMR technology / [Alterações do metabólito plasmático em vacas leiteiras com balanço energético negativo identificado usando a tecnologia 1H NMR]

The objective of the present study was to investigate the different plasma metabolites between anestrus and estrus postpartum dairy cows and to provide a theoretical basis for prevention of anestrus in dairy farm cows. In the experiment, one hundred and sixty-seven Holstein dairy cows were selected with similar age and parity. According to the concentration of ß-hydroxybutyric acid, non-esterified fatty acids and glucose in plasma during 14 to 21 days in milk, all dairy cows were determined as having a status of energy balance. According to the results of clinical symptom, rectal and B ultrasound examination at 60 to 90 days postpartum, these cows were divided into twenty estrus and twenty-four anestrus group, other dairy cows were removed. 1H nuclear magnetic resonance technology was utilized to detect the plasma metabolites changes and screen different plasma metabolites between anestrus and estrus cows. Ten different metabolites including alanine, glutamic acid, asparagine, creatine, choline, phosphocholine, glycerophosphocholine, low-density lipoprotein, and very-low-density lipoprotein were significantly decreased in anestrous cows compared with estrous cows. Metabolic pathway analyses indicated that differential metabolites were primarily involved in amino acid and glycerophospholipid metabolism. These metabolites and their enrichment pathways indicate that reduced steroid hormone synthesis precursors result in lower levels of estradiol and progesterone and cause anestrus in negative energy balance. These data provide a better understanding of the changes that may affect estrus of postpartum dairy cows at NEB status and lay the ground for further research.(AU)

O objetivo do presente estudo foi investigar os diferentes metabolitos do plasma entre o cio e o cio pós-parto de vacas leiteiras e fornecer uma base teórica para a prevenção do cio de vacas em fazendas de leite. No experimento, foram selecionadas 127 vacas leiteiras Holstein com idade e paridade similares. De acordo com a concentração de ß- ácido hidroxibutírico, ácidos graxos não esterificados e glicose no plasma entre 14 e 21 dias no leite, todas as vacas leiteiras foram determinadas em estado de equilíbrio energético. De acordo com os resultados dos sintomas clínicos, do exame de ultra-som retal e B aos 60 a 90 dias pós-parto, estas vacas foram divididas em vinte cios e vinte e quatro grupos de cio, outras vacas leiteiras foram removidas. A tecnologia de ressonância magnética nuclear 1H foi utilizada para detectar as alterações dos metabólitos plasmáticos e para triar diferentes metabólitos plasmáticos entre as vacas do cio e do cio. Dez diferentes metabólitos incluindo alanina, ácido glutâmico, asparagina, creatina, colina, fosfocholina, glicerofosfocolina, lipoproteína de baixa densidade e lipoproteína de muito baixa densidade foram significativamente diminuídos nas vacas antróficas em comparação com as vacas estro. As análises da via metabólica indicaram que os metabólitos diferenciais estavam principalmente envolvidos no metabolismo de aminoácidos e glicerofosfolipídios. Estes metabólitos e suas vias de enriquecimento indicam que a redução dos precursores da síntese de hormônios esteróides resulta em níveis mais baixos de estradiol e progesterona e causa anestros no balanço energético negativo. Estes dados fornecem uma melhor compreensão das mudanças que podem afetar o cio das vacas leiteiras pós-parto no estado de NEB e preparam o terreno para mais pesquisas.(AU)

Intravaginal progesterone device (1. 9g) and estradiol benzoate for follicular control in the mare during spring and summer / [Implante intravaginal de progesterona (1, 9g) e benzoato de estradiol no controle folicular de éguas durante a primavera e o verão]

The objective of this study was to evaluate follicular growth and ovulatory rates in mares treated with an intravaginal progesterone device (P4) during the 10-day period, associated with the use of estradiol benzoate (EB). The results were compared during the transition period (ET) in the spring and the breeding season in the summer (ER). The variables were submitted to ANOVA (Tukey's test), considering P<0.05. No ovulation occurred during the permanence of the P4 implant in both experimental periods. The ovulatory rate in the ER was 100% (n = 8) and in the ET 62.5% (n = 5; P = 0.0547). Significant differences were observed (<0.001), in both periods, comparing follicular growth rates during the permanence of P4 device (ER: 1.33 ± 0.89mm/d; ET: 1.00 ± 0.81mm/d) to the period without P4 (ER: 3.63 ± 1.33 mm/d; ET: 3.31 ± 1.66 mm/d). The present study demonstrated applicability and efficiency of a hormonal protocol using P4 intravaginal device and EB for follicular control in mares, both during ET and ER.

O objetivo deste trabalho foi avaliar a taxa de crescimento folicular e a taxa ovulatória em éguas tratadas com dispositivo intravaginal de progesterona (P4) durante o período de 10 dias, associado à utilização de benzoato de estradiol (BE). Os resultados foram comparados durante o período de transição (ET) da primavera com a época de reprodução no verão (ER). As variáveis foram submetidas à ANOVA (teste de Tukey), considerando-se P<0,05. Nenhuma ovulação ocorreu durante a permanência do dispositivo de P4 em ambos os períodos experimentais. A taxa ovulatória na ER foi de 100% (n = 8) e na ET, de 62,5% (n=5; P=0,0547). Diferença significativas (<0,001) foram observadas, em ambos os períodos experimentais, comparando as taxas de crescimento folicular durante a permanência da P4 (ER: 1,33 ± 0,89mm/d; ET: 1,00 ± 0,81mm/d) com o período sem P4 (ER: 3,63 ± 1,33mm/d; ET: 3,31 ± 1,66mm/d). O presente estudo demonstrou aplicabilidade e eficiência do protocolo hormonal utilizando dispositivo intravaginal de P4 e BE para controle folicular de éguas, tanto na ET quanto na ER.

Insuficiencia ovárica primaria en adolescentes: revisión de la literatura a propósito de un caso clínico / Primary ovarian insufficiency in adolescents: review of the literature regarding a clinical case

El objetivo de este manuscrito es realizar una revisión y actualización de la literatura de la insuficiencia ovárica primaria (IOP) en población adolescente, a partir del diagnóstico, manejo y seguimiento de un caso clínico. La insuficiencia ovárica primaria se define como la menopausia en una mujer antes de los 40 años, acompañada de amenorrea, hipogonadismo hipergonadotrópico e infertilidad. Su prevalencia varía entre 1 a 2%, y en mujeres menores de 20 años su prevalencia es un caso de cada 10,000. Aunque se sabe que muchas afecciones pueden llevar a una IOP, la más común es la causa idiopática. La presentación clínica es diversa, y varios trastornos diferentes pueden también, llevar a esta condición. CASO CLÍNICO: Se presenta el caso de una adolescente de 17 años, previamente sana, con historia de amenorrea secundaria, no embarazada, con examen físico general y ginecológico normal. Se solicita estudio analítico complementario resultando con niveles de hormona folículo estimulante (FHS), estradiol (E2) y hormona antimülleriana (AMH) compatibles con una insuficiencia ovárica como la observada en la posmenopausia. Se inicia terapia hormonal (TH) clásica con estradiol y progesterona, siendo posteriormente reemplazada por anticoncepción hormonal combinada (AHC) oral, coincidente con el inicio de vida sexual, con respuesta favorable y sangrados regulares. La IOP tiene graves consecuencias para la salud incluyendo trastornos psicológicos como angustia, síntomas depresivos o depresión, infertilidad, osteoporosis, trastornos autoinmunes, cardiopatía isquémica, y un mayor riesgo de mortalidad. La enfermedad de Hashimoto es el trastorno autoinmune más frecuente asociado a la IOP. Su tratamiento y diagnóstico deben establecerse de forma precoz para evitar consecuencias a largo plazo. La terapia con estrógenos es la base del tratamiento para eliminar los síntomas de la deficiencia de estrógenos, además de evitar las consecuencias futuras del hipogonadismo no tratado. También el manejo debe incluir los siguientes dominios: fertilidad y anticoncepción, salud ósea, problemas cardiovasculares, función psicosexual, psicológica y neurológica, informando a los familiares y a la paciente sobre la dimensión real de la IOP y la necesidad de tratamiento multidisciplinario en muchos casos. CONCLUSIÓN: El caso presentado, pese a ser infrecuente, permite abordar de manera sistematizada el diagnostico de IOP y evaluar alternativas de manejo plausibles para evitar graves consecuencias en la salud, así como conocer respuesta clínica y de satisfacción de la adolescente.

The objective of this manuscript is to review and update the literature on primary ovarian insufficiency (POI) in an adolescent population, based on the diagnosis, management and follow-up of a clinical case. Primary ovarian insufficiency is defined as menopause in a woman before the age of 40, accompanied by amenorrhea, hypergonadotropic hypogonadism, and infertility. Its prevalence varies between 1 to 2%, and in women under 20 years of age its prevalence is one case in every 10,000. Although it is known that many conditions can lead to POI, the most common is the idiopathic cause. The clinical presentation is diverse, and several different disorders can also lead to this condition. CLINICAL CASE: The case of a 17-year-old adolescent, previously healthy, with a history of secondary amenorrhea, not pregnant, with a normal general physical and gynecological examination is presented. A complementary analytical study is requested, resulting in levels of follicle stimulating hormone (FHS), estradiol (E2) and anti-müllerian hormone (AMH) compatible with ovarian insufficiency such as that observed in postmenopause. Classic hormonal therapy (HT) with estradiol and progesterone was started, later being replaced by combined hormonal contraception (CHC), coinciding with the beginning of sexual life, with a favorable response and regular bleeding. POI has serious health consequences including psychological disorders such as distress, depressive symptoms or depression, infertility, osteoporosis, autoimmune disorders, ischemic heart disease, and an increased risk of mortality. Hashimoto's disease is the most common autoimmune disorder associated with POI. Its treatment and diagnosis must be established early to avoid long-term consequences. Estrogen therapy is the mainstay of treatment to eliminate the symptoms of estrogen deficiency, in addition to avoiding the future consequences of untreated hypogonadism. Management should also include the following domains: fertility and contraception, bone health, cardiovascular problems, psychosexual, psychological and neurological function, informing family members and the patient about the real dimension of POI and the need for multidisciplinary treatment in many cases. CONCLUSION: The case, although infrequent, allows a systematic approach to the diagnosis of POI and evaluate plausible management alternatives to avoid serious health consequences, as well as to know the clinical response and satisfaction of the adolescent.

Falsely elevated serum estradiol due to heterophile antibody interference: a case report

SUMMARY Falsely elevated estradiol is rare, may result from heterophile antibody interference, and can result in unnecessary investigation and intervention. We present the case of a 56-year-old female with falsely elevated estradiol levels inconsistent with her overall clinical picture, which ultimately led to an unnecessary surgical procedure. With the use of alternative analytical platforms and a heterophile antibody blocking agent, we determined the false elevation was due to heterophile antibody interference. Clinicians must suspect and investigate for laboratory error when the clinical picture contradicts laboratory results.

Use of estradiol cypionate to induce ovulation in buffalo raised in floodplain areas of Itacoatiara, Amazonas / [Uso do cipionato de estradiol na indução da ovulação de búfalas criadas em várzea da região de Itacoatiara, Amazonas]

This study aimed to determine the efficiency of estradiol cypionate (EC) as an ovulation inducer in a Timed Artificial Insemination protocol. 69 buffalo cows received an intravaginal progesterone device and 2mg of estradiol benzoate (EB) at D0. On D9, the intravaginal device was removed and 0.53mg of prostaglandin (PGF2α) and 400UI of equine chorionic gonadotrophin (eCG) were applied. The cows were distributed into two groups: the first group received 1mg of EC (ECG) in D9, and the second group received 1mg of EB (EBG) in D10. Inseminations occurred on D11. Ovarian activity and pregnancy diagnosis were analyzed by ultrasonography. There was no difference (P>0.05) in follicular diameter (9.6 ± 0.89mm vs. 10.7 ± 1.12mm; P=0.06), in ovulation rate (90.9% vs. 90.9%; P=1) and pregnancy rate (58.8% vs. 62.9%; P=0.79), however, buffalo cows from the ECG treatment have less time between P4 removal and ovulation when compared to EBG buffalos (37.4h vs. 52.8h; P=0.001), respectively. Thus, it was concluded that the implantation of TAI in the floodplain of Amazonas is feasible and the use of EC results in successful rates, similar to EB.(AU)

O objetivo deste trabalho foi determinar a eficiência do cipionato de estradiol (CE) como indutor de ovulação em um protocolo de inseminação artificial de tempo fixo. Para isso, 69 búfalas receberam no D0 um dispositivo intravaginal de progesterona e 2mg de benzoato de estradiol (BE). No D9, o dispositivo intravaginal foi removido e foram aplicados 0,53mg de prostaglandina (PGF2α) e 400UI de gonadotrofina coriônica equina (eCG), para, então, os animais serem divididos em dois grupos: um deles (GCE) recebeu 1mg de CE no D9, e o outro (GBE) recebeu 1mg de BE 24h após. As inseminações ocorreram no D11. A atividade ovariana e o diagnóstico de prenhez foram avaliados por ultrassonografia. Não houve diferença (P>0,05) no diâmetro folicular (9,6 ± 0,89mm vs. 10,7 ± 1,12mm; P=0,06), na taxa de ovulação (90,9% vs. 90,9%; P=1) e na taxa de prenhez (58,8% vs. 62,9%; P=0,79), no entanto búfalas do tratamento GCE apresentaram menor tempo entre a remoção da P4 e a ovulação, quando comparadas com as búfalas do GBE (37,4h vs. 52,8h; P=0,001), respectivamente. A implantação da IATF nas várzeas do Amazonas é viável e a utilização do CE resulta em taxas de sucesso similares ao BE.(AU)

Use of protein kinase C and phospholipase A2 inhibitors in bovine endometrial cells treated with estradiol and calcium ionophore / Uso de inibidores de proteína quinase C e fosfolipase A2 em células endometriais bovinas tratadas com estradiol e ionóforo de cálcio

The release of endometrial prostaglandin-F2α (PGF2α) in bovine females can be induced in vivo by estradiol (E2). However, its role in this mechanism has not been clarified. We hypothesized that E2 stimulates the activity and abundance of protein kinase C (PKC) and phospholipase A2 (PLA2). Our objective in this study was to analyze the effects of PKC and PLA2 inhibitors on PGF2α synthesis induced by E2 and calcium ionophore (CI) in bovine endometrial cells (BEND cells; Experiment 1). Additionally, we evaluated the abundance of PKC and PLA2 in endometrial explants of cows treated or not with E2 17 days after estrus (D17, D0 = estrus; Experiment 2). In Experiment 1, BEND cells were submitted to a PKC inhibitor (10 µM of C25H24N4O2; bisindolylmaleimide I, or BIS I), a PLA2 inhibitor (20 µM of arachydoniltrifluoromethane or AACOCF3), or none. The BEND cells were subsequently treated with E2 and CI, and PGF2α concentrations were measured in the culture medium through radioimmunoassay. For DIF-12 (PGF2α concentration 12 h after treatment subtracted from PGF2α concentration at hour 0), no PKC inhibitor effect was observed (P= 0.2709). However, DIF-12 was lower (P < 0.05) for groups treated with the PLA2 inhibitor and PLA2 inhibitor + CI + E2 groups than the control and CI + E2 groups. Thus, AACOCF3 was an efficient PLA2 inhibitor in the BEND cells culture system, and E2 did not stimulate the synthesis of PKC and PLA2. In Experiment 2, cyclic Nellore heifers received none (n = 5) or 3 mg (n = 6) of 17ß-E2 on D17 and were slaughtered 2 h after administration. The abundance of PKC and PLA2 in the endometrial tissue was evaluated using Western blotting analysis. No E2 effect was observed on PKC (P = 0.08) and PLA2 (P = 0.56). We concluded that E2 did not stimulate the activity and abundance of PKC and PLA2.(AU)

A liberação endometrial de prostaglandina-F2α (PGF2α) em fêmeas bovinas pode ser induzida in vivo pelo estradiol (E2). Entretanto o seu mecanismo de ação ainda não foi bem esclarecido. Nossa hipótese é que o E2 estimula a atividade e a abundância da proteína quinase C (PKC) e da fosfolipase A2 (PLA2). Nosso objetivo com este estudo foi analizar os efeitos de inibidores de PKC e PLA2 na síntese de PGF2α induzida por E2 e ionóforo de cálcio (CI) em células endometriais bovinas (células BEND; Experimento 1). Adicionalmente, nós avaliamos a abundância de PKC e PLA2 em explantes endometriais de vacas tratadas com ou sem E2 17 dias após o estro (D17, D0 = estro; Experimento 2). No Experimento 1, células BEND foram submetidas ao inibidor de PKC (10 µM de C25H24N4O2; bisindolylmaleimide I, ou BIS I), e ao inibidor de PLA2 (20 µM de arachydoniltrifluoromethane ou AACOCF3) ou a nenhum inibidor. As células BEND foram subsequentemente tratadas com E2 e CI e concentrações de PGF2α foram mensuradas no meio de cultura por radioimunoenssaio. Para DIF-12 (concentração de PGF2α 12 horas depois do tratamento, subtraída da concentração de PGF2α na hora 0), não foi observado efeito do inibidor de PKC (P = 0.2709). Entretanto DIF-12 foi menor (P < 0.05) nos grupos tratados com inibidor de PLA2 e inibidor de PLA2 + CI + E2 quando comparados com o grupo controle e o grupo CI + E2. O AACOCF3 foi um eficiente inibidor de PLA2 em sistema de cultura de células BEND e o E2 não estimulou a síntese de PKC e PLA2. No Experimento 2, novilhas Nelore cíclicas receberam 3 mg de 17ß-E2 (n = 6) ou nenhum tratamento (n = 5) no D17 e foram abatidas duas horas depois da administração dos tratamentos. A quantidade de PKC and PLA2 no tecido endometrial foi avaliada pela técnica de Western Blotting. Não foi observado efeito do E2 sobre a PKC (P= 0.08) e nem sobre a PLA2 (P= 0.56). Conclui-se que o E2 não estimulou a atividade e abundância de PKC e PLA2.(AU)