A randomized clinical trial of transdermal (gel) versus oral estrogen for endometrial preparation in frozen embryo transfer cycle.

OBJECTIVE: The aim of this study was to compare endometrial thickness with the use of transdermal estrogen (gel) versus oral estrogen (pills) for endometrial preparation in the frozen embryo transfer cycle and serum estrogen concentrations during the preparation cycle, side effects, and chemical and clinical pregnancy rates. METHODS: This was a prospective, randomized controlled trial of women undergoing endometrial preparation for cryopreserved blastocyst transfer. A total of 88 women were randomized, of which 82 completed the study protocol. Of this group, 44 received 6 mg/day of estradiol valerate orally (pills group) and 38 received 4.5 mg/day of estradiol hemihydrate transdermally (gel group). Endometrial thickness was measured using transvaginal ultrasound between the 7 and 10th day of the cycle. Serum estradiol concentrations were measured on the day of initiating the cycle, on control transvaginal ultrasounds, and on the day of embryo transfer. Side effects were documented at each study visit. p<0.05 were adopted as statistically significant. The groups were compared using Student's t-test for continuous variables and chi-square or Fisher's exact test for categorical variables. RESULTS: There were no significant group differences (p>0.05) in endometrial thickness, biochemical and clinical pregnancy rates, miscarriage rate, blood estradiol concentrations, duration of estradiol administration, or cycle cancellation rates. CONCLUSION: Endometrial preparation with transdermal estrogen yielded similar reproductive outcomes to oral estrogen with fewer side effects.

Effect of hormone therapy on blood pressure and hypertension in postmenopausal women: a systematic review and meta-analysis.

IMPORTANCE: Menopausal hormone therapy (HT) includes a wide variety of hormonal compounds, and its effect on blood pressure is still uncertain. OBJECTIVE: The aim of this study was to assess evidence regarding the effect of HT on blood pressure in postmenopausal women and its association with arterial hypertension. EVIDENCE REVIEW: This systematic review and meta-analysis included randomized clinical trials and prospective observational studies. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and the incidence of hypertension were assessed. All stages were independently performed by two reviewers. For blood pressure outcome, standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated as effect measures. Heterogeneity was assessed using the I2 statistic. The results are presented based on the HT type. The incidence of hypertension was compared using descriptive analyses. FINDINGS: Eleven studies were included with 81,041 women evaluated, of which 29,812 used HT. The meta-analysis, conducted with 8 studies and 1,718 women, showed an increase in SBP with the use of oral conjugated equine estrogens plus progestogen (SMD = 0.60 mm Hg, 95% CI = 0.19 to 1.01). However, oral or transdermal use of estradiol plus progestogen (SMD = -2.00 mm Hg, 95% CI = -7.26 to 3.27), estradiol alone, and tibolone did not show any significant effect. No significant effect on DBP was observed for any formulation. Women who used oral estrogen plus progestogen had a higher risk of incident hypertension than those who never used it. CONCLUSIONS AND RELEVANCE: The effect of HT on blood pressure is influenced by the formulation used, especially the type of estrogen. The combined formulations of conjugated equine estrogens plus progestogen increased SBP and the risk of hypertension, which was not observed among estradiol plus progestogen, estradiol alone, and tibolone users.

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)

Uterotrophic and in vitro screening for (anti)estrogenic activity of dipyrone.

Dipyrone is a commonly used analgesic in many countries and there is limited data on its possible endocrine disrupting effects. We performed a screening for in vivo and in vitro anti(estrogenic) activity of dipyrone. For the in vivo uterotrophic assay, immature female rats (22-days-old) were treated daily by oral gavage for three days with different doses of dipyrone alone (50, 100, 200 mg/kg/day) and associated with three ethynylestradiol (EE) doses (1, 3 and 10 µg/kg/day), which were based on a dose-response curve experiment. The uterine weight was used as a biomarker for estrogenicity. In a parallel in vitro approach, we used a yeast-based transcriptional activation reporter gene assay (Yeast Estrogen Screening - YES) for assessment of estrogenic agonistic and antagonistic effects of dipyrone and its main metabolites 4-methylaminoantipyrine (MAA) and 4-aminoantipyrine (AA). In the uterotrophic assay, animals that received EE at 1, 3 and 10 µg/kg/day showed an increase in relative uterine weight compared with vehicle-only rats (canola oil). Dipyrone did not increase uterine weight at any dose tested (50, 100 and 200 mg/kg/day) in relation to vehicle control, indicating absence of estrogenic activity. Furthermore, co-administration of dipyrone (50 and 200 mg/kg/day) and EE (1, 3 or 10 µg/kg/day) was unable to block EE estrogenic action in comparison to the groups treated with EE alone, indicating absence of antiestrogenic activity. In the YES assay dipyrone and its metabolites did not demonstrate estrogen agonistic or antagonistic properties in the yeast cells. These results suggest that dipyrone and its metabolites do not produce (anti)estrogenic effects in vivo or in vitro.

Use of cooled buffalo semen as a strategy to increase conception rates in fixed-time artificial insemination programs during unfavorable reproductive periods / [Uso de sêmen resfriado de búfalo como estratégia para aumentar as taxas de concepção em programas de inseminação artificial em tempo fixo, durante períodos reprodutivos desfavoráveis]

The objective of this study was to compare the reproductive efficiency of dairy buffaloes undergoing fixed-time artificial insemination (FTAI) protocols based on progesterone/estrogen (P4/E2) and eCG during unfavorable breeding season using cooled (CS) and frozen semen (FS). A total of 446 buffaloes (> 40 days postpartum) were randomly distributed into four blocks (years): B1-2014 (n = 143), B2-2015 (n = 34), B3-2016 (n = 90), and B4-2017 (n = 179). Each block was subdivided into two (AI with CS and FS using the same ejaculate of each bull). Thus, the block subdivision was as follows: B1 (CS = 71 and FS = 72); B2 (CS = 18 and FS = 16); B3 (CS = 47 and FS = 43); and B4 (CS = 90 and FS = 89). The ejaculates of eight Murrah bulls collected using an artificial vagina were divided into two aliquots: one aliquot was diluted in Botu-Bov® commercial extender and cooled (BB-CS), and the other was diluted in the same extender and frozen (BB-FS). BB-CS aliquots were cooled at 5 °C/24 h using a refrigerator. BB-FS group aliquots were also cooled, and after equilibrating at 5 °C for 4 h, were placed in a 21-L Styrofoam box, 5 cm above the surface of liquid nitrogen. In the afternoon (A) on D0 (2:00 p.m.) the animals received EB 2.0 mg IM (Estrogin®) and an ear implant (CRESTAR® 3.0 mg P4). At D9 (A), the implant was removed, and the animals received eCG 400 IU IM (Folligon® 5000) + Cloprostenol PGF2α 0.530 mg IM (Sincrocio®). At D10 (A), the animals received EB 1.0 mg IM (Estrogin®), and at D12 (8:00 a.m.), AI was performed. At D42, pregnancy was diagnosed via ultrasonography. Total CRs were 48.2% CS and 34.6% FS for years 2014 to 2017, with a significant difference of 13.7% (P<0.05). In conclusion, cooled semen resulted in higher CR than frozen semen in dairy buffaloes under the P4/E2 and eCG FTAI during the unfavorable reproductive season.(AU)

O objetivo deste estudo foi comparar a eficiência reprodutiva de búfalas leiteiras submetidas a protocolos de inseminação artificial em tempo fixo (IATF) à base de progesterona/estrogênio (P4/E2) e eCG, durante a estação reprodutiva desfavorável, usando-se sêmen resfriado (SR) e congelado (SC) Um total de 446 búfalas (> 40 dias após o parto) foi distribuído aleatoriamente em quatro blocos (anos): B1-2014 (n = 143), B2-2015 (n = 34), B3-2016 (n = 90) e B4-2017 (n = 179). Cada bloco foi subdividido em dois (IA com SR e SC utilizando-se a mesma ejaculação de cada touro). Assim, a subdivisão do bloco foi a seguinte: B1 (SR = 71 e SC = 72); B2 (SR = 18 e SC = 16); B3 (SR = 47 e SC = 43); e B4 (SR = 90 e SC = 89). Os ejaculados de oito touros Murrah coletados com vagina artificial foram divididos em duas alíquotas: uma alíquota diluída em diluente comercial Botu-Bov® e resfriada (BB-SR), e a outra diluída no mesmo diluente e congelada (BB-SC). As alíquotas de BB-SR foram resfriados a 5°C/24h usando-se um refrigerador. As alíquotas do grupo BB-SC também foram resfriadas e, após equilíbrio a 5°C por 4h, foram colocadas em uma caixa de isopor de 21L, 5 cm acima da superfície do nitrogênio líquido. À tarde (A), no D0 (14h), os animais receberam BE 2,0 mg IM (Estrogin®) e um implante auricular (Crestar® 3,0 mg P4). No D9 (A), o implante foi retirado e os animais receberam eCG 400 UI IM (Folligon® 5000) + cloprostenol PGF2α 0,530 mg IM (Sincrocio®). No D10 (A), os animais receberam BE 1,0mg IM (Estrogin®), e, no D12 (8h da manhã), foram realizadas as IAs. No D42, a gestação foi diagnosticada por ultrassonografia. As taxas de concepção (TC) totais foram 48,2% SR e 34,6% SC para os anos de 2014 a 2017, com uma diferença significativa de 13,7% (P<0,05). Em conclusão, o sêmen resfriado resultou em maior TC do que o sêmen congelado em bubalinos leiteiros sob P4/E2 e eCG FTAI durante a estação reprodutiva desfavorável.(AU)

Ovarian dynamics of buffalo (Bubalus bubalis) synchronized with different hormonal protocols.

The study evaluates the effect of three hormonal protocols on ovarian dynamics and progesterone (P4) secretion of buffalo (Bubalus bubalis). Twenty-nine pluriparous Murrah buffaloes were used. The protocols were as follows: OVSYNCH (n = 10): 100 µg of gonadorelin (day 0), 500 µg of cloprostenol (day 7), and 100 µg of gonadorelin (day 9). CIDR+EB (intravaginal device (CIDR®) + estradiol benzoate; n = 10): CIDR plus 2 mg of EB (day 0), withdrew of CIDR, 500 µg of cloprostenol (day 7) and 1 mg of EB (day 8). CIDR+eCG (n = 9): CIDR plus 2 mg of EB (day 0), withdrew of CIDR, 500 µg of cloprostenol and 400 IU of eCG (day 7). Follicles were counted with an ultrasound and measured at 0, 24, and 54 h. The maximum follicle diameter and ovulation were evaluated at 70, 80, and 94 h after CIDR withdrew. Estrous was detected per 1 h three times daily. Blood samples were collected on days 0, 7, 10, 15, and 22 to determine P4 concentration. In CIDR+EB protocol, 50% of buffaloes presented estrous, at 69.6 h. All buffaloes ovulated. CIDR+eCG group had the shortest (69 h) ovulation time. No treatment differences for follicular population, maximum follicle diameter, and P4 concentration on days 7 and 10 (P > 0.05) were found. The P4 concentration in OVSYNCH and CIDR+eCG protocols were > 1 ng/ml, on days 15 and 22 (P < 0.05). There was no difference in ovarian activity; however, the P4 secretion was normal in the OVSYNCH and CIDR+eCG protocols compared to the CIDR+EB protocol.

Are oral oestrogens effective in preventing urinary tract infection in postmenopausal woman. / Son efectivos los estrógenos orales en la prevención de infección del tracto urinario en mujeres posmenopáusicas.

INTRODUCCIÓN: La infección del tracto urinario es una patología frecuente, con un alto riesgo de recurrencia, por lo que representa un importan-te motivo de consulta. Dentro de la población más afectada se encuentran las mujeres postmenopáusicas debido a la caída de los niveles de estrógenos, tanto locales como sistémicos, perdiéndose la barrera protectora de la vía urinaria contra agentes patógenos. Entre las variadas medidas que potencialmente disminuirían el riesgo de infección urinaria se ha planteado el uso de estrógenos, sin embargo, no está claro si realmente son efectivos. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud a nivel mundial, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis, preparamos tablas de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos seis revisiones sistemáticas que en conjunto incluyen siete estudios primarios, de los cuales, cuatro son ensayos aleatorizados. Concluimos que no está claro si los estrógenos orales disminuyen el riesgo de desarrollar infección del tracto urinario sintomática, porque la certeza de la evidencia es muy baja.

Heart fat and carotid artery atherosclerosis progression in recently menopausal women: impact of menopausal hormone therapy: The KEEPS trial.

OBJECTIVE: Heart fat deposition has been linked to atherosclerosis, and both accelerate after menopause. Hormone therapy (HT) may differentially slow heart fat deposition and progression of atherosclerosis, depending on the specific HT agent or its route of administration. Our objective was to evaluate the effects of different HT agents, oral and transdermal, on associations between heart fat accumulation and atherosclerosis progression, measured by carotid intima-media thickness (CIMT), in recently menopausal women from the Kronos Early Estrogen Prevention Study (KEEPS) trial. METHODS: KEEPS was a randomized, placebo-controlled trial of the effects of 0.45 mg/d oral conjugated equine estrogens (o-CEE) or 50 mcg/d transdermal 17ß-estradiol (t-E2), compared with placebo, on 48 months progression of CIMT. Epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT) volumes were quantified by computed tomography. RESULTS: In all, 467 women (mean age [SD] 52.7 [2.5]; 78.2% White; 30% on o-CEE, 30.8% t-E2, 39.2% placebo) with heart fat volumes and CIMT at baseline and 48 months were included. EAT and PAT changes were not associated with CIMT progression; however, the assigned treatment significantly modified the association between PAT (but not EAT) change and CIMT progression. In the o-CEE group, adjusted CIMT progression was 12.66 µm (95% confidence interval [CI] 1.80, 23.52) lower than in t-E2 group (P = 0.02), and 10.09 µm (95% CI 0.79, 19.39) lower than in placebo group (P = 0.03), as per 1-SD increase in PAT. CONCLUSION: Compared with t-E2, o-CEE appears to slow down the adverse effect of increasing PAT on progression of atherosclerosis. Whether this beneficial association is specific to CEE or to the oral route of CEE administration is unclear and should be assessed further.

A cumulative index of exposure to endogenous estrogens and breast cancer by molecular subtypes in northern Mexican women.

PURPOSE: To evaluate breast cancer (BC) molecular subtypes association with reproductive characteristics and an index of cumulative exposure to endogenous estrogens (EEI) in Mexican women. METHODS: We performed a study of incident cases and population controls in northern Mexico. We included BC cases with tumor molecular classification in their medical records (n = 509), and classified them as HR+/HER2- (ER+ and/or PR+ and HER2-) (n = 289), HER2+ (HR+ or HR-) (n = 117) or triple negative (TN) (n = 103). We matched controls (n = 1030) by age and place of residence with index cases. Women were interviewed about their reproductive history, from which the EEI was developed. We used logistic regression models to estimate BC molecular subtypes associations with reproductive characteristics and EEI. RESULTS: The EEI was higher in all subtypes compared to controls (Median HR+/HER2- 27.25, HER2+ 26.8, TN 24.2 vs. controls 22.8 years, p < 0.05), and was associated with HR+/HER2- (ORT3 vs. T1 = 2.58, 95% CI 1.77-3.55, p-trend < 0.001) and HER2+ (ORT3 vs. T1 = 4.17, 95% CI 2.15-8.08, p-trend < 0.001) BC. Additionally, HR+/HER2- tumors were positively associated with age at first pregnancy and age at menopause, and negatively with age at menarche, parity and breastfeeding. The HER2+ subtype was associated in the same direction as HR+/HER2- tumors with all the reproductive characteristics except for age at menarche. TN tumors were negatively associated with parity and breastfeeding. CONCLUSION: Endogenous estrogens exposure throughout Mexican women reproductive life may contribute to the development of all but TN BC, however, these findings should be confirmed in other Hispanic populations.

CCR3 antagonist impairs estradiol-induced eosinophil migration to the uterus in ovariectomized mice

Eosinophils are abundant in the reproductive tract, contributing to the remodeling and successful implantation of the embryo. However, the mechanisms by which eosinophils migrate into the uterus and their relationship to edema are still not entirely clear, since there are a variety of chemotactic factors that can cause migration of these cells. Therefore, to evaluate the role of CCR3 in eosinophil migration, ovariectomized C57BL/6 mice were treated with CCR3 antagonist SB 328437 and 17β-estradiol. The hypothesis that the CCR3 receptor plays an important role in eosinophil migration to the mouse uterus was confirmed, because we observed reduction in eosinophil peroxidase activity in these antagonist-treated uteruses. The antagonist also influenced uterine hypertrophy, inhibiting edema formation. Finally, histological analysis of the orcein-stained uteruses showed that the antagonist reduced eosinophil migration together with edema. These data showed that the CCR3 receptor is an important target for studies that seek to clarify the functions of these cells in uterine physiology.

Leptin actions through the nitrergic system to modulate the hypothalamic expression of the kiss1 mRNA in the female rat.

Gonadotrophin-releasing hormone (GnRH) is the main controller of the reproductive axis and stimulates the synthesis and secretion of gonadotrophins. Estrogen is the main peripheral factor controlling GnRH secretion, and this action is mainly mediated by the transsynaptic pathway through nitric oxide, kisspeptin, leptin, among other factors. Kisspeptin is the most potent factor known to induce GnRH release. Nitric oxide and leptin also promote GnRH release; however, neurons expressing GnRH do not express the leptin receptor (OB-R). Leptin seems to modulate the expression of genes and proteins involved in the kisspeptin system. However, few kisspeptin-synthesizing cells in the arcuate nucleus (ARC) and few cells, if any, in the preoptic area (POA) express OB-R; this indicates an indirect mechanism of leptin action on kisspeptin. Nitric oxide is an important intermediate in the actions of leptin in the central nervous system. Thus, this work aimed to verify the numbers of nNOS cells were activated by leptin in different hypothalamic areas; the modulatory effects of the nitrergic system on the kisspeptin system; and the indirect regulatory effect of leptin on the kisspeptin system via nitric oxide. Ovariectomized rats were treated with estrogen or a vehicle and received an intracerebroventricular (i.c.v.) injection of a nitric oxide donor, leptin or neuronal nitric oxide synthase (nNOS) enzyme inhibitor. Thirty minutes after the injection, the animals were decapitated. Leptin acts directly on nitrergic neurons in different hypothalamic regions, and the effects on the ventral premammillary nucleus (PMV) and ventral dorsomedial hypothalamus (vDMH) are enhanced. The use of a nitric oxide donor or the administration of leptin stimulates the expression of the kisspeptin mRNA in the ARC of animals with or without estrogenic action; however, these changes are not observed in the POA. In addition, the action of leptin on the expression of the kisspeptin mRNA in the ARC is blocked by a nitric oxide synthesis inhibitor. We concluded that the effects of leptin on the central nervous system are at least partially mediated by the nitrergic system. Also, nitric oxide acts on the kisspeptin system by modulating the expression of the kisspeptin mRNA, and leptin at least partially modulates the kisspeptin system through the nitrergic system, particularly in the ARC.

CCR3 antagonist impairs estradiol-induced eosinophil migration to the uterus in ovariectomized mice.

Eosinophils are abundant in the reproductive tract, contributing to the remodeling and successful implantation of the embryo. However, the mechanisms by which eosinophils migrate into the uterus and their relationship to edema are still not entirely clear, since there are a variety of chemotactic factors that can cause migration of these cells. Therefore, to evaluate the role of CCR3 in eosinophil migration, ovariectomized C57BL/6 mice were treated with CCR3 antagonist SB 328437 and 17ß-estradiol. The hypothesis that the CCR3 receptor plays an important role in eosinophil migration to the mouse uterus was confirmed, because we observed reduction in eosinophil peroxidase activity in these antagonist-treated uteruses. The antagonist also influenced uterine hypertrophy, inhibiting edema formation. Finally, histological analysis of the orcein-stained uteruses showed that the antagonist reduced eosinophil migration together with edema. These data showed that the CCR3 receptor is an important target for studies that seek to clarify the functions of these cells in uterine physiology.

Son efectivos los estrógenos orales en la prevención de infección del tracto urinario en mujeres posmenopáusicas / Are oral oestrogens effective in preventing urinary tract infection in postmenopausal woman

INTRODUCCIÓN: La infección del tracto urinario es una patología frecuente, con un alto riesgo de recurrencia, por lo que representa un importan-te motivo de consulta. Dentro de la población más afectada se encuentran las mujeres postmenopáusicas debido a la caída de los niveles de estrógenos, tanto locales como sistémicos, perdiéndose la barrera protectora de la vía urinaria contra agentes patógenos. Entre las variadas medidas que potencialmente disminuirían el riesgo de infección urinaria se ha planteado el uso de estrógenos, sin embargo, no está claro si realmente son efectivos. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud a nivel mundial, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis, preparamos tablas de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos seis revisiones sistemáticas que en conjunto incluyen siete estudios primarios, de los cuales, cuatro son ensayos aleatorizados. Concluimos que no está claro si los estrógenos orales disminuyen el riesgo de desarrollar infección del tracto urinario sintomática, porque la certeza de la evidencia es muy baja.

Analysis of Estrogen Effects on Eruption of Rat Molars / Análisis de los Efectos del Estrógeno en la Erupción de Molares de Rata

ABSTRACT: Tooth eruption requires resorption of the alveolar bone interposed between the tooth germ and the oral mucosa (coronal bone). The cells responsible for bone resorption are the osteoclasts and their activity can be reduced or inactivated by estrogen hormone. We aimed to investigate the effects of estrogen on the process of tooth eruption in rats. Thirty-three Wistar rats, aged two-to-17-days, were divided into control, sham and estrogen-treated groups. After daily injections with estrogen, the animals were euthanized and the jaws removed and processed for histological analysis. We performed clinical examination, morphological analysis, quantification of the number of osteoclasts on the surface of the coronal bone and immunohistochemical analysis of estrogen receptor type alpha (ERα). Estrogen therapy was effective, which could be confirmed by the higher estrogen plasma levels on treated animals. However, it had no effect on tooth development or tooth eruption. Progressive bone resorption was observed and the number of osteoclasts on coronal bone was not affected on hormoneinjected animals, allowing tooth to erupt at the same time observed in untreated animals. Immunohistochemistry for ERα confirmed the presence of this type of receptor in osteoclasts, osteoblasts and osteocytes. Taken together, our results showed that estrogen stimulation was not sufficient to decrease the number of osteoclasts on the coronal bone, supporting the idea that, although estrogen may have a protective activity on bone resorption, this may not apply to the alveolar bone that is meant to be resorbed during eruptive process.

RESUMEN: La erupción dental requiere la resorción del hueso alveolar interpuesto entre el germen dental y la mucosa oral (hueso coronal). Las células responsables de la resorción ósea son los osteoclastos y su actividad puede reducirse o inactivarse por la hormona del estrógeno. Objetivos: apuntamos a investigar los efectos del estrógeno en el proceso de la erupción dental en ratas. Treinta y tres ratas Wistar, de dos a 17 días de edad, se dividieron en grupos de control, Sham y se trataron con estrógenos. Los animales fueron eutanizados después del tratamento con estrógeno y se procesaron las mandíbulas para el análisis histológico. Se realizó el examen clínico, el análisis morfológico, la cuantificación del número de osteoclastos en la superficie del hueso coronal y el análisis inmunohistoquímico del tipo de receptor de estrógeno alfa (ERα). La terapia de estrógeno fue eficaz, lo que podría ser confirmado por los niveles plasmáticos más altos de estrógeno en los animales tratados. Sin embargo, no se observó ningún efecto sobre el desarrollo de los dientes o la erupción dental. Se observó una resorción ósea progresiva y el número de osteoclastos en el hueso coronal no se vio afectado en los animales inyectados con hormonas, permitiendo que el diente erupcionó durante el mismo período de tiempo observado en animales no tratados. La inmunohistoquímica para el ERα confirmó la presencia de este tipo de receptor en los osteoclastos, osteoblastos y osteocitos. Nuestros resultados mostraron que la estimulación del estrógeno no fue suficiente para reducir el número de osteoclastos en el hueso coronal confirmando que, si bien el estrógeno puede tener una actividad protectora en la resorción ósea, esto puede no se aplica al hueso alveolar que está destinado a ser rerecurrido durante el proceso eruptivo.

Early onset of action with a 17ß-estradiol, softgel, vaginal insert for treating vulvar and vaginal atrophy and moderate to severe dyspareunia.

OBJECTIVE: The softgel 17ß-estradiol (E2) vaginal inserts (4 and 10 µg; Imvexxy; TherapeuticsMD, Boca Raton, FL) are FDA approved for treating moderate to severe dyspareunia associated with postmenopausal vulvar and vaginal atrophy (VVA). The objective here was to determine responder rates at week 2 and whether week-2 findings predicted week-12 responders in the REJOICE trial. METHODS: Postmenopausal women received E2 vaginal inserts 4, 10, or 25 µg, or placebo for 12 weeks. Proportion of responders (having ≥2 of the following: vaginal superficial cells >5%, vaginal pH <5.0, or dyspareunia improvement of ≥1 category) were calculated. Odds ratios (ORs) for positive response at week 12 given a positive response at week 2 were determined in the efficacy evaluable (EE) population. RESULTS: The responder rate (in EE population [n = 695]) was 74% to 82% with E2 inserts versus 24% with placebo at week 2, and 72% to 80% versus 33% at week 12. Positive treatment responses were 9- to 14-fold higher with vaginal E2 than with placebo at week 2, and 5- to 8-fold higher at week 12. Response at week 2 predicted response at week 12 in the total population (OR 13.1; 95% CI, 8.8-19.7) and with active treatment only (OR 7.9; 95% CI, 4.7-13.2). CONCLUSIONS: A high percentage of postmenopausal women with moderate to severe dyspareunia responded with the E2 softgel vaginal insert at week 2, and a positive response at week 2 predicted a positive response at week 12.

Is prostaglandin F2α administration at the beginning of a progesterone and estradiol-based treatment for FTAI an effective strategy in Bos taurus heifers?

The objective was to evaluate effects of prostaglandin (PG) F2α administration at the beginning of a progesterone and estradiol-based treatment period on ovarian response and pregnancy rate (P/AI) in Bos taurus beef heifers. Heifers were treated with 500 µg of cloprostenol administered: a) in two half-doses (250 µg) at the time of progesterone device insertion and removal (two-PG), or b) in a single dose at the time of device removal (one-PG). In the two-PG group, administration of PG at device insertion resulted in lesser serum progesterone concentrations during the 7-d treatment period (P < 0.05). Additionally, diameter of the follicle from which ovulation occurred was greater, and ovulation occurred earlier in the two-PG compared with one-PG group (P < 0.05). Fixed-time artificial insemination (FTAI) was performed in 3479 heifers with two times for FTAI (48 compared with 54 h from device removal). There was no effect on P/AI percentage for the PG treatment or the time of FTAI. The FTAI at 54 h resulted in a greater P/AI percentage in the one-PG than two-PG group (70.5%, 253/359 and 63.5%, 254/400, respectively; P < 0.05). There were no differences between PG treatments when FTAI was performed at 48 h after device removal. In conclusion, the administration of PG at the time of intravaginal progesterone device insertion results in lesser progesterone concentrations, and an increased size of the follicle from which ovulation occurs, and the time of ovulation is earlier after device removal. The pregnancy rate was not affected by the PG administration at the time of device insertion.

Fractional CO2 laser versus promestriene and lubricant in genitourinary syndrome of menopause: a randomized clinical trial.

OBJECTIVE: The aim of this study was to compare the effects of fractional CO2 laser therapy, promestriene, and vaginal lubricants on genitourinary syndrome treatment and sexual function in postmenopausal women. METHODS: We performed a randomized clinical trial including 72 postmenopausal women over the age of 50 years. The women were randomized into three intervention groups to receive one of the following treatments: three sessions of intravaginal fractional CO2 laser therapy; 10 mg of intravaginal promestriene cream 3 times a week; and vaginal lubricant application alone. Vaginal maturation, Vaginal Health Index (VHI) score, and Female Sexual Function Index (FSFI) were evaluated at baseline and after 14 weeks of therapy. RESULTS: We observed an improvement in the vaginal elasticity, volume, moisture, and pH in the CO2 laser and promestriene groups. The VHI score at 14 weeks was higher in the CO2 laser group (mean score 18.68) than in the promestriene (15.11) and lubricant (10.44) groups (P < 0.001). Regarding vaginal maturation, basal cells were reduced and superficial cells were increased after treatment. This improvement was more significant in the CO2 laser group (P <0.001). The FSFI score only showed improvement in the desire and lubrication domains in the CO2 laser group. There were no differences in total FSFI score among the three treatment groups. There were no adverse effects associated with any of the treatments. CONCLUSIONS: The use of fractional CO2 laser therapy to treat genitourinary syndrome resulted in better short-term effects than those of promestriene or lubricant with respect to improving the vaginal health in postmenopausal women.

Women's Health Initiative clinical trials: potential interactive effect of calcium and vitamin D supplementation with hormonal therapy on cardiovascular disease.

OBJECTIVE: Data in humans and nonhuman primates have suggested a possible synergistic effect of vitamin D and calcium (CaD) and estrogen on the cardiovascular disease (CVD) risk factors. Using randomized trial data we explored whether the effect of menopausal hormone therapy (HT) on CVD events is modified by CaD supplementation. METHODS: A prospective, randomized, double-blind, placebo-controlled trial was implemented among postmenopausal women in the Women's Health Initiative. A total of 27,347 women were randomized to the HT trials (0.625 mg/d of conjugated equine estrogens [CEE] alone for women without a uterus vs placebo; or 0.625 mg of CEE in addition to 2.5 mg of medroxyprogesterone acetate daily [CEE + MPA] for women with a uterus vs placebo). After 1 year, 16,089 women in the HT trial were randomized to the CaD trial and received either 1,000 mg of elemental calcium carbonate and 400 IU of vitamin D3 daily or placebo. The mean (SD) duration of follow-up after CaD randomization was 6.2 (1.3) years for the CEE trial and 4.6 (1.1) years for the CEE + MPA trial. CVD and venous thromboembolism events evaluated in this subgroup analysis included coronary heart disease, stroke, pulmonary embolism, all-cause mortality, plus select secondary endpoints (total myocardial infarction, coronary revascularization, deep venous thrombosis, cardiovascular death, and all CVD events). Time-to-event methods were used and models were fit with a Cox proportional hazards regression model. RESULTS: In the CEE trial, CaD significantly modified the effect of CEE on stroke (P interaction = 0.04). In the CaD-placebo group, CEE's effect on stroke was harmful (hazard ratio [95% confidence interval] = 2.19[1.34-3.58]); however, it was neutral in the CaD-supplement group (hazard ratio [95% confidence interval] = 1.07[0.66-1.73]). We did not observe significant CEE-CaD interactions for coronary heart disease, total CVD events, or any of the remaining endpoints. In the CEE + MPA trial, there was no evidence that the effect of CEE + MPA on any of CVD endpoints was modified by CaD supplementation. CONCLUSIONS: CaD did not consistently modify the effect of CEE therapy or CEE + MPA therapy on CVD events. However, the increased risk of stroke due to CEE therapy appears to be mitigated by CaD supplementation. In contrast, CaD supplementation did not influence the risk of stroke due to CEE + MPA.

Timed artificial insemination plus heat I: effect of estrus expression scores on pregnancy of cows subjected to progesterone-estradiol-based protocols.

Expression of estrus near timed artificial insemination (TAI) is associated with greater fertility, and estrus detection could improve TAI fertility or direct TAI management, although accurate estrus detection can be difficult and time-consuming using traditional methods. The aim of this study is to evaluate influence of estrus on pregnancy (artificial insemination pregnancy rates (P/AI)) and to validate an alternative method to classify estrus/heat expression using tail chalking (HEATSC) in postpartum Bos indicus cows subjected to TAI in progesterone-estrogen-based protocols. In experiment 1 (Exp. 1), cows (5491) were subjected to visual observation of estrus after progesterone device removal, before TAI, and P/AI was evaluated according to estrus and body condition score (BCS). Cows received a progesterone device and 2 mg estradiol benzoate (EB). After 8 days, the device was removed and 150 µg of d-cloprostenol and 300 IU equine chorionic gonadotrophin was given. Later, animals in Exp. 1 received 1 mg EB and TAI 44 to 48 h. In the Exp. 2 - 3830 cows using similar protocol, received different ovulation inducers: 1 mg EB (n=1624) or 1 mg estradiol cypionate (EC; n=2206) on day 8 (D8). Cows were then marked with chalk, and HEATSC evaluated at TAI on D10 (HEATSC1 - no chalk removal=no estrus expression; HEATSC2 - partial chalk removal=low estrus expression; HEATSC3 - near complete/complete chalk removal=high estrus expression). In Exp. 1, cows showing estrus presented greater P/AI (48.4% v. 40.2%, P<0.05). In Exp. 2, P/AI (HEATSC1 - 40.0%; HEATSC2 - 49.7%; HEATSC3 - 60.9%; P<0.001), and larger follicle timed artificial insemination (LFTAI) (<0.001) varied according to HEATSC. There was no difference in P/AI (P=0.41) or LFTAI (P=0.33) according to ovulation inducer. Cows with greater BCS showed greater P/AI in both experiments (P<0.05). Estrus presence and greater HEATSC improved P/AI, and EC v. EB used promoted differential estrus manifestation (cows showing HEATSC2 and HEATSC3: 79.5% with EB v. 69.98% with EC use, P<0.001), however, with similar P/AI. The use of HEATSC in B. indicus cows subjected to TAI is useful to identify cows with greater estrus expression and consequently improved pregnancy rates in TAI, allowing the cows with low HEATSC to be targeted for additional treatments aimed at improving P/AI.