The fracture healing is impaired in osteoporosis. Piper sarmentosum is a plant, which contains potent antioxidant, naringenin that may enhance fracture healing. The present histological study aimed to determine the effects of water extract of Piper sarmentosum on the late phase of fracture healing in estrogen-deficient rats. Twenty four female Sprague-Dawley rats (200-250 gm) were obtained. Six rats underwent sham operation and the rest were ovariectomized. Six weeks post-ovariectomy all the rats were fractured at the mid-diaphysis of the right femur and a K-wire was inserted for internal fixation. The sham group was given vehicle (normal saline) and the ovariectomized group was randomly subdivided into three groups: (i) ovariectomized-control group supplemented with vehicle; (ii) ovariectomized+estrogen replacement therapy group treated with estrogen (100 µg/kg/day) and (iii) ovariectomized+Piper sarmentosum group treated with Piper sarmentosum water extract (125 mg/kg). Following six weeks of treatment, the rats were sacrificed and the right femora were harvested for histological assessment of fracture callus. The ovariectomized-control group showed a significant delay in fracture healing compared to the sham, ovariectomized-estrogen replacement therapy and ovariectomized-Piper sarmentosum groups. The median callus score for the ovariectomized-Piper sarmentosum group was 4.50 (range, 4-5), which was significantly higher than the median callus score 3.50 (range, 3-4) for the ovariectomized-control group (P=0.019). However, there was no significant (P>0.05) difference in the callus score among the sham, ovariectomized-estrogen replacement therapy and ovariectomized-Piper sarmentosum groups groups. Treatment with water extract of Piper sarmentosum proved beneficial in the fracture healing in estrogen-deficient rats.

Menopause and diabetes are associated with significant increase in the expression of inflammatory markers in respiratory system. In the present study, we investigated the simultaneous effect of swimming exercise and treatment with genistein on the lungs of ovariectomized diabetic rats. In this experiment, sixty female Wistar rats were randomly divided into six groups. Healthy control: (sham), ovariectomized female rats: (OVX) (rats that underwent bilateral ovariectomy), ovariectomized diabetic group: (OVX.Dia) (ovariectomized rats that were fed with high-fat diet), ovariectomized diabetic group treated with swimming: (OVX.Dia. Exe) (8 weeks of swimming training), ovariectomized diabetic group treated with genistein: (OVX.Dia. Gen) (8 weeks genistein administration, 1 mg/kg /day, s.c.), ovariectomized diabetic group treated with genistein and swimming exercise: (OVX.Dia. Gen.Exe). To induce diabetes, the diabetic groups received a high-fat diet for four weeks. The studied groups did swimming exercise or received genistein for eight weeks. At the end of the experiment, the lung tissue was removed under anesthesia and the amount of IL1β factor in the lung tissue was analyzed by western blot technique. The amount of IL1β factor in ovariectomized and ovariectomized diabetic rat was significantly increased compared to the control group. Genistein treatment and swimming exercise in ovariectomized diabetic rats decreased the amount of IL1β factor in the studied groups compared to the ovariectomized diabetic group. Swimming training and genistein treatment ameliorated expression levels of inflammatory biomarkers (IL1β) in the lung of ovariectomized diabetic rats.

Background and Menopause is a physiological process and diabetes is a metabolic disease that occurs more frequently in older women. The present study investigated the effects of diabetes on some biochemical parameters and histopathological changes in ovariectomized rats.
Thirty two adult female rats were divided into four groups of 8 and studied for 55 weeks. The animals were assigned into a control group, an ovariectomized group (55 weeks), a third group in which diabetes was induced in the last 5 weeks of the study in rats with intact ovary. The next group included ovariectomized rats (for 55 weeks) in which diabetes was induced in the last 5 weeks of the study. Pathological alterations of liver, kidney, pancreas, lung and some serum biochemical parameters were determined in each group at the end of the study.
Diabetic and diabetic ovariectomized rats showed increase in serum levels of blood glucose, AST, ALT, GGT, ALP, calcium, urea, TG and HDL compared with the control group (P Our findings suggest that long term reduction of estrogen in ovariectomized diabetic rats can reduce the serum levels of glucose, AST, ALT, GGT, urea, VLDL and triglycerides compared with non ovariectomized diabetic rats.

Menopause is associated with a redistribution of adipose tissue towards central adiposity, known to cause insulin resistance. Exercise training and crocin improve blood glucose and insulin resistance, and prevent obesity and type 2 diabetes.  The purpose of this study was to investigate the effect of aerobic training and crocin consumption on visceral fat cell size and insulin resistance in ovariectomized rats fed with high-fat diet. 72 female rats were divided into two groups: ovariectomized (56) and non-ovariectomized (16). Then the rats of these two groups were divided into groups fed with high-fat diet (40% fat) and normal diet. The ovariectomized rats + high-fat diet were divided into 6 groups as follows: 1- control 2- moderate intensity aerobic training 3-  high intensity aerobic training 4- crocin 5- moderate intensity aerobic training + crocin and 6- high intensity aerobic training + crocin. The target groups performed high-intensity aerobic exercise (80-85% VO2max) and moderate aerobic exercise (60-70% VO2max) and received crocin at the rate of 60 mg/kg for 8 weeks. Relative weight of perirenal visceral fat, size of cells and serum levels of glucose, insulin and insulin resistance index (HOMA) were measured. The findings were analyzed by two-way analysis of variance. Moderate intensity training with crocin consumption caused a significant decrease in the relative weight of perirenal fat (p=0.0001). Also, the relative weight of perirenal fat was significantly lower in the high intensity training + crocin group than in the high-fat diet+ ovariectomized group (p≤0.001). The fat cell size in the two training groups (moderate and intense) was significantly lower than the high-fat diet + ovariectomized group (p=0.001), and the difference between the crocin group and the high-fat diet + ovariectomized group was also significant (p=0.03). Fat cell size in exercise groups (moderate and intense) + crocin was also significantly lower than the high-fat diet + ovariectomized group (p≤0.05). High intensity training caused a significant decrease in insulin resistance (p=0.028) and glucose concentration (p=0.041) compared to the ovariectomized + high-fat diet group. Consumption of crocin decreased insulin resistance (p=0.013) and decreased insulin concentration (p=0.008). Also, moderate intensity exercise + crocin caused a significant decrease in glucose (p=0.022), insulin (p=0.011) and insulin resistance (p=0.005) compared to the ovariectomized group + high-fat diet. Consumption of crocin and aerobic training separately and in combination with can reduce visceral fat tissue weight and fat cell size and improve insulin resistance in ovariectomized rats fed with high-fat diet. High-intensity aerobic training seems to be more effective in improving insulin resistance and reducing fat cell size than moderate-intensity training. No additive effects in combination of crocin with exercise training were observed in improvement of insulin resistance or fat cell size.

Ovariectomy is a standard experimental model of menopause in rodent to investigate postmenopausal women . The aim of this study was to evaluate effects acute and chronic estrogen deficiency on lipid profile and glucose serum in ovariectomized (OVX) rats.
In this experimental study, Twenty-four adult female Wistar rats were divided into three groups of eight rats. The first group: sham-control, Second group: ovariectomized rats (for five weeks), Third group: ovariectomized rats (for fifty five weeks). Blood samples were taken from the right cardiac ventricle in each group at the end of the study. Fasting blood glucose and Lipid profile biomarkers such as total cholesterol, triglyceride, HDL cholesterol and LDL cholesterol were determined using enzymatic procedure. VLDL and Atheroginc index were calculated according to computational procedures.
The results indicated that short time ovariectomy cause increase glucose, triglyceride, high density lipoprotein, low density lipoprotein ,TG/ HDL ratio and Atherogenic index than the long term ovariectomized rats .
These results suggested that long term estrogen deficiency after ovariectomy, improving lipid profile and blood glucose levels compared to the short time estrogen deficiency during ovariectomized rats.

Estrogen replacement therapy remains current as a therapeutic approach to treat menopausal symptoms and may significantly affect hormone-producing cells in the female pituitaries. The aim of this study was to examine the histological parameters of pituitary mammotrophs and prolactin secretion after chronic estradiol treatment in ovariectomized adult female rats, reflecting premature menopause.
In this experimental study, adult female Wistar rats were divided into non-ovariectomized (C), ovariectomized (OVX) and estradiol-treated ovariectomized (OVX) groups. Estradiol dipropionate [0.625 mg/kg body mass per day] was administered for four weeks, while the C and OVX groups received vehicle alone. Mammotrophs were identified by the peroxidase-antiperoxidase (PAP) immunohistochemical procedure, while prolactin concentrations were measured by the non-isotopic two-step assay (Delfia) method. Comparison of the differences between groups was performed using one-way analysis of variance (ANOVA) and Tukay (honest significant difference) HSD test.
Ovariectomy caused significant (P Estradiol supplementation in ovariectomized females is followed by stimulatory histological and secretory changes of the mammotrophs. These results could serve as indicators of possible prolactinome development upon estradiol application in premature menopausal subjects.

Estrogen deficiency is associated with unfavorable changes in body composition and abdominal fat deposition. The consequences of these changes lead to metabolic abnormalities and differential fat distribution. Seventy female Wistar rats (weight: 170.73±15.82gr mean±SD) were divided into 7 groups:Intact(one group),sham (two groups), ovariectomized (two groups), ovariectomized, receiving estradiol valerate(one group) and ovariectomized, receiving sesame oil (one group).The intact rats were anesthetized and visceral fat was then taken from the abdominal cavity and weighed immediately. Two weeks after operation, one group of ovariectomized rats and one group of sham rats were sacrified and visceral fat was measured. The estradiol receiving ovariectomized group and vehicle group were given equal volumes of 17β-estradiol(30μg/kg, sc, 5 d/wk) and sesame oil for 8 weeks, respectively. After 8 weeks, all animals were sacrificied and intra- abdominal fat depots were dissected and weighed. Data were analyzed with one-way ANOVA and post-hoc and using paired t test. The differences were considered significant at P<0.05. After two weeks of surgery, the ovariectomized rats showed insignificant increase in body weight and visceral fat weight, whereas, after eight weeks, body weight increased significantly in ovariectomized rats (P<0.05). Estradiol replacement decreased body weight and visceral fat weight, however this decrease was only significant in body weight(P<0.05). The results indicate that estrogen deficiency following ovariectomy leads to increase in both body weight and visceral fat, showing that replacement of this hormone could decrease body weight without affecting visceral fat.

The ovariectomized animals are good models to evaluate the effect of different steroid hormone treatments on implantation events and the pattern of integrin expression. Therefore, this study was performed to compare the expression of integrins and osteopontin (OPN) in correlation with pinopode development in ovariectomized mice endometrium which was subjected to steroid hormones. Ovariectomized mice were subjected to estrogen, progesterone and estrogen-progesterone hormones. Their uterine horns were evaluated for integrin expression by immunohistochemistry and real-time RT-PCR and for pinopodedevelopment by transmission and scanning electron microscopic studies. No immunostaining for integrin and OPN molecules were detected in the endometrium of non-ovariectomized mice except inmetestrus phase. The α4 and β1 integrin genes were expressed in all phases of estrous cycle. In ovariectomized mice, no reaction was detected in the endometrium of control, sham and estrogen-treatedgroups, but in both progesterone-treated groups, all examined genes were expressed. There was not anycorrelation between pinopodes and integrin expression in ovariectomized mice. The progesterone is more effective on endometrial integrin expression than estrogen and differences in the expression pattern of integrins reflect their important and different roles in embryo implantation. The pinopodes may have minoreffect in mice implantation or have some delay in their expressions in ovariectomized mice which were subjected to exogenous hormones.

Several experimental and clinical studies support beneficial effects of Trigonella foenum-graecum (fenugreek) in the management of metabolic diseases and inflammatory disorders. The purpose of this study was to examine the effect of T. foenum-graecum seed extract in reducing the metabolic and inflammatory alternations associated with menopause. In this experimental study, 49 rats were divided into seven groups: (I) sham-control, (II) ovariectomized-control,(III and IV) ovariectomized treated with 50 and 150 mg/kg of T. foenum-graecum seed ethanolic extract, (V and VI) ovariectomized treated with 50 and 150 mg/kg of T. foenum-graecum hexanic extract, (VII) ovariectomized-positive control treated with 10 µg/kg of estradiol. The extracts were injected intraperitoneally one day after ovariectomy and the treatments were lasted for 42 days. Fasting blood glucose and body weight gain increased significantly in the ovariectomized-control group compared with that in the sham animals (P < 0.05). Administration of estradiol and T. foenum-graecum (50 and 150 mg/dL of hexanic extract and 150 mg/kg of ethanolic extract) significantly diminished the increase in glucose and body weight (P < 0.05). The serum level of interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the ovariectomized control group was significantly higher than those in the sham animals (P < 0.05). Both hexanic and ethanolic extracts as well as estradiol were able to decrease level of these cytokines in the serum of ovariectomized rats (P < 0.05). The results of the present study show that administration of T. foenum-graecum corrects metabolic and inflammatory alterations associated with ovariectomy and has a potential for the management of menopause.

Calcium phosphates, particularly hydroxyapatite, are the main inorganic compounds of vertebrate bone.In this study, nanohydroxyapatite was prepared using kombucha Symbiotic Culture of Bacteria and Yeast (SCOBY), and its effect was investigated on osteoporosis in ovariectomized rats.  Kombucha-nanohydroxyapatite was synthesized by adding phosphoric acid to the kambucha scoby. Characterization of the nanoparticle was performed through X-ray diffraction, X-ray fluorescence, and transmission electron microscopy techniques. Female rats were divided into 5 groups: control, ovariectomized groups, and three ovariectomized groups treated with concentrations of 25, 50, and 100 mg/kg of nanoparticles. At the end of the treatment period, the levels of calcium, phosphorus, parathyroid hormone, and activity of alkaline phosphatase were measured in the blood samples. Calcium and phosphorus levels were also measured in bone and liver. The bone was evaluated histopathologically. The synthesis of nanohydroxyapatite with particle size of 30 nm was confirmed through the use of X-ray diffraction (XRD) and TEM techniques. A significant increase in calcium and phosphorus levels in the femur bone was observed in the ovariectomized group, which received the highest nanoparticle concentration compared to the ovariectomized group. Parathyroid hormone and alkaline phosphatase activity inhibition were increased in ovariectomized rats following treatment with the highest nanoparticle concentration. In the mentioned group, bone trabeculae proliferation and increased lacuna-containing osteocytes were also observed. This study suggested that the highest concentration of kombucha-nanohydroxyapatite could be partially absorbed into bone tissues and recover the bone-destructive changes caused by ovariectomy, although additional experiments are needed for confirmation.