Efficacy and safety of Zi Gui Nv Zhen® capsules used in TCM for fertility preservation in patients with diminished ovarian reserve.

OBJECTIVE: To evaluate for the first time whether Zi Gui Nv Zhen® capsules (ZGNZC), until now used in traditional Chinese medicine (TCM) for menopausal complaints, can increase the fertility of Chinese women with diminished ovarian reserve (DOR). METHODS: Prospective, randomized, open-labeled 3-monthly study; 109 DOR patients (aged 20-40 years) receiving either ZGNZC (experimental group, n = 75) or not (control group, n = 34). Main outcomes: markers for ovarian function, thickness/type of the endometrium during ovulation, and pregnancy rate. Between-group analysis (A) comparing experimental vs. control group and within-group analysis (B) comparing data at baseline and after study in each of both groups. RESULTS: (A) Between-group-analysis: patients with ZGNZC had a higher endometrium thickness (0.75 vs. 0.62; p<.05) and higher anti-Müllerian hormone (AMH, 0.50 vs. 0.40; p<.05) than control group. Pregnancy rates were higher in the experimental than the control group (26.7% vs. 14.7%; n.s.). (B) Within-group-analysis: ZGNZC decreased levels of follicle-stimulating hormone (FSH, 11.42 vs. 8.69), increased estradiol-levels (E2, 56.09 vs. 73.36), and type A endometrium rates (5.3% vs. 39.7%) (all p< .05) and increased antral follicle count (AFC, 2 vs. 3). All hepato-renal biomarkers remained within the norm. The tolerability was good. There were no adverse events. CONCLUSIONS: In women with DOR who wish to conceive, three months' application of ZGNZC can improve ovarian function and oocyte quality by adjusting the neuroendocrine system, can improve endometrial properties and proliferation, necessary for a healthy pregnancy, and increased the clinical pregnancy rate in our prospective randomized observational study.

Effect of oral phytoestrogens on endometrial thickness and breast density of perimenopausal and postmenopausal women: A systematic review and meta-analysis.

BACKGROUND: Phytoestrogens constitute an alternative, non-pharmacologic approach for the management of menopausal symptoms. However, few studies have focused on their safety, specifically in relation to endometrial thickness and breast density. AIM: To systematically search for and quantitatively synthesize the evidence regarding the effect of phytoestrogens on endometrial thickness and breast density in perimenopausal and postmenopausal women. METHODS: Randomized controlled trials (RCTs) examining the effect of phytoestrogens compared with placebo or menopausal hormone therapy (MHT) on endometrial thickness and/or breast density in perimenopausal or postmenopausal women were searched for in the MEDLINE, CENTRAL and Scopus databases as well as "gray literature" sources until October 31, 2018. Main outcomes were the change from baseline in endometrial thickness and breast density. Statistical analysis was performed with RevMan 5.3, using R language and Open Meta-Analyst software. RESULTS: The meta-analysis for endometrial thickness included 30 RCTs (with a total of 3497 women), and that for breast density four RCTs (with a total of 674 women). Phytoestrogens did not affect endometrial thickness compared with placebo [weighted mean difference (WMD) -0.04 mm, 95% confidence interval (CI) -0.18 to 0.11, I2 66%] or MHT (WMD -1.40 mm, 95% CI -2.98 to 0.18, I2 84%). In addition, phytoestrogens did not affect breast density compared with placebo [standardized mean difference (SMD) -0.76, 95% CI -1.54 to 0.2, I2 95%). CONCLUSION: Phytoestrogens have no effect on endometrial thickness or breast density, when administered at various doses and for various durations, in perimenopausal and postmenopausal women. However, the high heterogeneity of the studies makes it necessary to conduct RCTs with less risk of systematic error.

Do extracts of oral soybean augment the trophic effect of estrogen on the rat uterus?

OBJECTIVE: To evaluate whether soybean extracts and estrogens present additive effects on adult rat uterus. METHODS: Fifty ovariectomized rats were randomly divided into five equal groups of ten animals: Control, treated with vehicle; SE46 and SE120, treated with 46 and 120 mg/kg soybean concentrated extract (SE), respectively; EE, treated with conjugated equine estrogens (CE) 50 µg/kg; SE120 + EE, treated with 50 µg/kg (CE) plus 120 mg/kg SE. The substances were administered daily by gavage for 21 consecutive days. Thereafter the animals were weighed and killed by decapitation; trunk blood was collected for hormone determinations. Uteri were removed immediately and fixed in 10% formaldehyde, followed by dehydration, embedding in paraffin and 6-m sections staining with hematoxylin and eosin for histomorphometric analyses of myometrium and endometrium. After ANOVA analysis of the data, the study was complemented with the Tukey-Kramer test for multiple comparisons. RESULTS: The concentrated extract of soybean at high concentration (SE 120 kg/mg) and estrogens proved to have a trophic effect on the uterus (endometrium and myometrium) of castrated rats. In groups SE120, EE and SE120 + EE, all morphometric parameters examined (number of glands, eosinophils, blood vessels and the glandular area) were increased. No significant addictive effects of soybean extract plus estrogens were detected in the SE120 + EE group. CONCLUSIONS: Our results indicate that soy extract has a trophic effect on rat uterine structures. Treatment of ovariectomized rats with a concentrated soy extract in combination with conjugated estrogens had no addictive effect on the uterine response.

The effects of metformin and letrozole on endometrium and ovary in a rat model.

OBJECTIVE: The effects of metformin and letrozole on endometrium and ovarian reserve were studied in a rat model. METHODS: Forty female Wistar albino mature rats at 8 weeks, weighing 180-260 g, were used for the study. These rats were randomly divided into four groups. Control group, eight rats, was given no medication by oral gavage. The rats in low-dose metformin group, 10 rats, were given 100 mg/kg/day of oral metformin. The rats in high-dose metformin group, 10 rats, were given 200 mg/kg/day of oral metformin. The rats in letrozole, 10 rats, were given 0.1 mg/kg/day of oral letrozole. RESULTS: There was statistically significant difference in the endometrial thickness between the treatment groups and control group. The primordial follicle count was comparable in all treatment groups compared with control. Finally, there was no significant difference in total follicle count between the treatment groups and control. CONCLUSIONS: This study showed that both metformin and letrozole had similar effects on endometrium and ovary in the rat model. Additionally, metformin had a little effect on endometrium than letrozole. Although metformin and letrozole might have tendency to enhance the total follicle count in the rat model, they had comparable effects on ovarian follicles and did not change the ovarian reserve compared with control.

Consumption of a flaxseed-rich food is not more effective than a placebo in alleviating the climacteric symptoms of postmenopausal women.

Our objective in this work was to test the effects of daily intake of bread produced with partially defatted ground flaxseed on the climacteric symptoms and endometrial thickness of postmenopausal women. A double-blind, placebo-controlled, randomized clinical trial was performed with 38 women who had been postmenopausal for 1-10 y and consumed 2 slices of bread containing 25 g of flaxseed (46 mg lignans) or wheat bran (<1 mg lignans; control) every day for 12 consecutive weeks. The outcome variables were the daily number of hot flashes, the Kupperman Menopausal Index (KMI), and endometrial thickness. The plasma lipid profile (total cholesterol and HDL, LDL, and VLDL cholesterol fractions and triglycerides) and the hormones estradiol, follicle-stimulating hormone, thyroid-stimulating hormone, and free thyroxine also were measured. Food intake was evaluated by means of 2 24-h recalls, before and after the treatment. Twenty patients in the study group and 18 in the control group completed the study. The general characteristics did not differ between the 2 groups at the start of the study. Both had significant, but similar, reductions in hot flashes and KMI after 3 mo of treatment. Moreover, endometrial thickness was not affected in either group. Our findings clearly show that although flaxseed is safe, its consumption at this level (46 mg lignans/d) is no more effective than placebo for reducing hot flashes and KMI.

O tratamento com isoflavonas mimetiza a ação do estradiol no acúmulo de gordura em ratas ovariectomizadas / Treatment with isoflavones replaces estradiol effect on the tissue fat accumulation from ovariectomized rats

OBJETIVO: As isoflavonas (ISO) presentes na soja são consideradas fitoestrógenos. A administração de fitoestrógenos tem efeito benéfico nos distúrbios da pós-menopausa que são caracterizados pela suspensão da função ovariana com declínio da secreção de estrogênio e conseqüentes desajustes histomorfológicos e metabólicos. O objetivo do presente estudo foi investigar o efeito da suplementação com ISO sobre a espessura do endométrio uterino, o acúmulo de gordura tecidual, o colesterol HDL e a glicose plasmática de ratas ovariectomizadas (OVX). MÉTODOS: Ratas Wistar com 60 dias de vida sofreram cirurgia bilateral para retirada dos ovários. Após o período de 8 dias de recuperação foram divididas em três grupos: falso operada (GC), OVX não-tratadas com ISO (GI) e as OVX suplementadas com ISO (GII). Foram retirados e pesados o útero, as gorduras uterinas e retroperitoneais. Também foram coletadas amostras de sangue para dosagem da concentração de HDL e glicose. RESULTADOS: A OVX promoveu atrofia do endométrio, diminuição do peso do útero e diminuição do HDL. O tratamento com ISO promoveu diminuição dos estoques de gorduras uterina e retroperitoneal, aumento de HDL e redução da glicemia, porém não teve efeito uterotrófico. CONCLUSÕES: Os dados do presente estudo mostram que o tratamento com ISO promove redução da adiposidade, o que pode estar relacionado à redução da lipogênese e ao aumento da lipólise.

OBJECTIVE: Isoflavones (ISO) present in soybean are named phytoestrogens because they show estrogen effect. The use of isoflavones has beneficial effect in disturbance of post-menopause, which is characterized by ovarian function suppression. Decreasing of estrogen secretion and consequent morphologic and metabolic disarrangements are observed in female hormonal decline. The aim of present work was to investigate the effect of ISO on the fat accretion of uterin endometric tissue, and HDL and glucose blood concentration from ovariectomized rats (OVX). METHODS: Female Wistar rats with 60 days-old were submitted a surgery to remove bilaterally the ovarium. After 8-day recovery period the animals were distributed into three groups: sham operate (GC); OVX ISO untreated (GI) and OVX supplemented with ISO (G II). Total uterus mass, uterus fat and retroperitoneal fat pad, were removed, washed and weighted. Samples of uterus were histological processed to measure endometrium thickness. Blood samples were also collected to analyze the concentration of HDL and glucose. The OVX caused endometric atrophy, decrease of uterus weight and HDL reduction. The treatment with ISO provoked decrease of uterin and retroperitoneal fat pad. HDL increase and glycemia reduction were also observed. However, there was no uterotrophic effect. CONCLUSIONS: ISO treatment causes decrease in tissue fat accretion from ovariectomized rats.

[Treatment with isoflavones replaces estradiol effect on the tissue fat accumulation from ovariectomized rats]. / O tratamento com isoflavonas mimetiza a ação do estradiol no acúmulo de gordura em ratas ovariectomizadas.

OBJECTIVE: Isoflavones (ISO) present in soybean are named phytoestrogens because they show estrogen effect. The use of isoflavones has beneficial effect in disturbance of post-menopause, which is characterized by ovarian function suppression. Decreasing of estrogen secretion and consequent morphologic and metabolic disarrangements are observed in female hormonal decline. The aim of present work was to investigate the effect of ISO on the fat accretion of uterine endometric tissue, and HDL and glucose blood concentration from ovariectomized rats (OVX). METHODS: Female Wistar rats with 60 days-old were submitted a surgery to remove bilaterally the ovarium. After 8-day recovery period the animals were distributed into three groups: sham operate (GC); OVX ISO untreated (GI) and OVX supplemented with ISO (G II). Total uterus mass, uterus fat and retroperitoneal fat pad, were removed, washed and weighted. Samples of uterus were histological processed to measure endometrium thickness. Blood samples were also collected to analyze the concentration of HDL and glucose. The OVX caused endometric atrophy, decrease of uterus weight and HDL reduction. The treatment with ISO provoked decrease of uterine and retroperitoneal fat pad. HDL increase and glycemia reduction were also observed. However, there was no uterotrophic effect. CONCLUSIONS: ISO treatment causes decrease in tissue fat accretion from ovariectomized rats.

Hallazgos histeroscópicos en la hemorragia uterina anormal con biopsia a ciegas previa negativa / Hysteroscopic findings in abnormal uterine bleeding with a previous negative blind biopsy

Estudiamos una muestra de 408 pacientes, en un estudio retrospectivo, tratando de evaluar la fiabilidad del estudio biópsico a ciegas para el diagnóstico de la patología endometrial. Se realiza histeroscopia diagnóstica en aquellas pacientes que presentan algún tipo de hemorragia uterina anormal (HUA). Premenopáusicas (267); posmenopáusicas (141); cíclicas (305); acíclicas (103), y que previamente han sido estudiadas con una biopsia endometrial con resultado negativo (legrado en posmenopáusicas y en hemorragias cíclicas y biopsia endometrial [Z-sampler] en premenopáusicas). Realizamos estudio estadístico con pruebas de la X2 mediante análisis informático SPSS. La biopsia endometrial presenta un alto índice de falsos negativos; no diagnosticando, en este estudio, hasta un 37,2 por ciento de patología orgánica en premenopáusicas y un 43,8 por ciento en posmenopáusicas, fundamentalmente a expensas de pólipos y miomas e incluso adenocarcinomas de endometrio (1,4 por ciento). Los hallazgos histeroscópicos no fueron condicionados por el tipo de hemorragia ni por la condición premenopáusica o posmenopáusica. La histeroscopia debe ser considerada el método diagnóstico de elección en el estudio de la hemorragia uterina anormal, y debe combinarse siempre con el diagnóstico anatomopatológico (AU)

Correlación entre el diagnóstico ultrasonográfico e histológico en patología endometrial / Correlation between of the ultrasonography and histology diagnostic in endometrium pathology

En el Servicio de Medicina General del Hospital Municipal Dr. Francisco Antonio Rísquez de Caracas, se realizó un estudio de diseño transversal, prospectivo, con la finalidad de determinar la correlación existente entre el Ultrasonido Ginecológico y la Biopsia de Endometrio como método de diagnóstico en Patología Endometrial. Fueron evaluadas 100 pacientes intervenidas quirúrgicamente entre los años 1993 y 1995, obteniéndose los siguientes resultados: Sensilidad (S): 69,8 por ciento; Específicidad (E): 78,3 por ciento; Valor Predictivo (VPP): 84,6 por ciento; Valor Predictivo Negativo (VPN): 60,4 por ciento; Tasa de Falsos Negativos (TFN): 19 por ciento; Efectividad (Ef): 73 por ciento y Error Diagnóstico (E-Dx): 27 por ciento. Se concluye, que el ultrasonido es un método sensible, específico, de alta eficacia y valor predictivo positivo, así como de bajo costo, inocuo, no invasivo y rápido, en el diagnóstico de la Patología Endometrial

Danazol concentrations in ovary, uterus, and serum and their effect on the hypothalamic-pituitary-ovarian axis during vaginal administration of a danazol suppository.

OBJECTIVE: To determine danazol concentrations in the ovary, uterus, and serum during daily vaginal administration of a danazol suppository and to examine its effect on the hypothalamic-pituitary-ovarian axis. DESIGN: Sampling of tissues after vaginal or oral administration of danazol and sampling of blood during control and danazol-administration menstrual cycles. SETTING: Outpatient volunteers and inpatients at a public hospital. PARTICIPANTS: Thirty patients who were to undergo hysterectomy and oophorectomy because of uterine leiomyoma and eight regularly menstruating volunteers. INTERVENTIONS: Danazol was administered as a vaginal suppository (100 mg) or orally (400 mg). MAIN OUTCOME MEASURE: Danazol concentrations in the ovary, uterus, and serum, and serum E2 and P levels. RESULTS: Danazol concentrations in the ovary and uterus after daily vaginal administration of a suppository containing 100 mg danazol were comparable to those after daily oral administration of 400 mg danazol, but the serum danazol concentration was much lower. Menstrual cycle patterns of serum E2 and P levels were normal during daily vaginal administration of a danazol suppository. CONCLUSION: Daily administration of a suppository containing 100 mg danazol produces high ovarian and uterine concentrations but low serum concentrations, and no effect was detected on the hypothalamic-pituitary-ovarian axis.

Development and structure of the extra-embryonic membranes of the ferret. A light microscopic and ultrastructural study.

Light and electron microscopic observations on the development and structure of the extra-embryonic membranes of the ferret are described. By day 16 of pregnancy trophoblastic villi consisting of a cytotrophoblastic core with a peripherally located phagocytic syncytiotrophoblast have penetrated deeply into the endometrium. During its invasion the syncytiotrophoblast removes endometrial glandular cells and some of the adjacent stromal tissue. The maternal blood vessels remain intact and eventually become surrounded by the syncytiotrophoblast. A marked hypertrophy of the maternal capillary endothelium then begine. By day 28 the maternal capillary endothelial cells attain their maximum height. The cytoplasm of these cells contains numerous cisternae of rough endoplasmic reticulum and a well-developed Golgi apparatus, features which are typical of protein-secreting cells. The maternal blood vessels are separated from the syncytiotrophoblast by a thick layer of amorphous material which stains positively with PAS. Alcian blue staining in the presence of critical concentrations of magnesium chloride indicates the presence of both sulphated and carboxylated acid mucopolysaccharides. It may be that the amorphous material contributes significantly to the nutritional requirements of the developing fetus. Invaginations of the syncytiotrophoblast plasma membrane facing this amorphous layer are often seen. Coated vesicles and substances in contact with the outer surface of the membrane are therefore likely to be endocytozed. The acid phosphatase in the syncytiotrophoblast is consistent with the presence of lysosomes and catabolic function. Regions of paraplacental cellular trophoblast which lie in close association with the endometrium, but do not penetrate it, appear to specialize in endocytosis. The haemophagus organ, which is located at the antimesometrial pole, is the site of rupture of maternal blood vessels, and the extravasated blood lies in close association with the chorio-allantoic membrane. The maternal blood cells ingested by the trophoblast in this area are presumably an important source of iron for the embryo. The cellular trophoblast in the paraplacental regions is well equipped with hydrolytic enzymes, as shown by histochemical tests for acid phosphatase. It seems likely that these regions are concerned with embryotrophic endocytotic nutrition supplementing endothelio-chorial nutrition.