Estrogen Replacement Treatment Research Articles

Primary ovarian insufficiency- An overview: Part 2 diagnosis and management

Loss of normal ovarian function before the age of 40 characterizes primary ovarian insufficiency (POI), sometimes called premature ovarian failure or early menopause. Many women all around the globe deal with this serious reproductive health issue. The purpose of this study is to provide a broad perspective on how to identify and treat primary ovarian insufficiency. Clinical symptoms, hormone profiles, and ovarian imaging all play a role in making a diagnosis of POI. Genetic predisposition, autoimmune disease, and medical intervention are all possible origins. Counseling and treatment techniques for afflicted women can only be used when a timely and correct diagnosis has been made. Hormone replacement treatment (HRT) for symptom alleviation, avoidance of long-term consequences including osteoporosis and cardiovascular disease, and preservation of fertility are all part of the management of postmenopausal irritability (POI). To reduce the severity of menopausal symptoms and safeguard bone health, oestrogen replacement treatment is needed. HRT selection should be patient-specific, taking into account factors like as age, co-morbidities, and individual preferences. If a young woman is diagnosed with POI and she wants to have children in the future, she and her doctor should talk about fertility preservation strategies such oocyte or ovarian tissue cryopreservation. The latest treatments and possible revolutionary methods to POI management are also discussed in this overview. Stem cell therapy, ovarian tissue transplantation, and hormone manipulation are all examples of such unproven methods. While these treatments are still in their infancy, they show promise for the future of POI management. In conclusion, this review article gives a comprehensive, up-to-date explanation of how primary ovarian insufficiency is diagnosed and treated. Early detection, proper counselling, and individualised treatment plans are emphasised for afflicted females. The reproductive and overall health results of these people may be improved with a deeper knowledge of the processes producing POI and the development of more effective medicines.

Growth in girls with Turner syndrome.

Turner syndrome (TS) is a chromosomal disorder affecting females characterized by short stature and gonadal dysgenesis. Untreated girls with TS reportedly are approximately 20-cm shorter than normal girls within their respective populations. The growth patterns of girls with TS also differ from those of the general population. They are born a little smaller than the normal population possibly due to a mild developmental delay in the uterus. After birth, their growth velocity declines sharply until 2 years of age, then continues to decline gradually until the pubertal age of normal children and then drops drastically around the pubertal period of normal children because of the lack of a pubertal spurt. After puberty, their growth velocity increases a little because of the lack of epiphyseal closure. A secular trend in height growth has been observed in girls with TS so growth in excess of the secular trend should be used wherever available in evaluating the growth in these girls. Growth hormone (GH) has been used to accelerate growth and is known to increase adult height. Estrogen replacement treatment is also necessary for most girls with TS because of hypergonadotropic hypogonadism. Therefore, both GH therapy and estrogen replacement treatment are essential in girls with TS. An optimal treatment should be determined considering both GH treatment and age-appropriate induction of puberty. In this review, we discuss the growth in girls with TS, including overall growth, pubertal growth, the secular trend, growth-promoting treatment, and sex hormone replacement treatment.

Aortic size predicts aortic dissection in Turner syndrome - A 25-year prospective cohort study

BackgroundWomen with Turner syndrome (TS) have an increased risk of aortic dissection. The current recommended cutoff to prevent aortic dissection in TS is an aortic size index (ASI) of ≥2.5 cm/m2. This study estimated which aortic size had the best predictive value for the risk of aortic dissection, and whether adjusting for body size improved risk prediction. MethodsA prospective, observational study in Sweden, of women with TS, n = 400, all evaluated with echocardiography of the aorta and data on medical history for up to 25 years. Receiver operating characteristic (ROC) curves, sensitivity and specificity were calculated for the absolute ascending aortic diameter (AAD), ascending ASI and TS specific z-score. ResultsThere were 12 patients (3%) with aortic dissection. ROC curves demonstrated that absolute AAD and TS specific z-score were superior to ascending ASI in predicting aortic dissection. The best cutoff for absolute AAD was 3.3 cm and 2.12 for the TS specific z-score, respectively, with a sensitivity of 92% for both. The ascending ASI cutoff of 2.5 cm/m2 had a sensitivity of 17% only. Subgroup analyses in women with an aortic diameter ≥ 3.3 cm could not demonstrate any association between karyotype, aortic coarctation, bicuspid aortic valve, BMI, antihypertensive medication, previous growth hormone therapy or ongoing estrogen replacement treatment and aortic dissection. All models failed to predict a dissection in a pregnant woman. ConclusionsIn Turner syndrome, absolute AAD and TS-specific z-score were more reliable predictors for aortic dissection than ASI. Care should be taken before and during pregnancy.

N-myc Downstream-Regulated Gene 2 (Ndrg2): A Critical Mediator of Estrogen-Induced Neuroprotection Against Cerebral Ischemic Injury.

Growing evidence indicates that estrogen plays a pivotal role in neuroprotection against cerebral ischemia, but the molecular mechanism of this protection is still elusive. N-myc downstream-regulated gene 2 (Ndrg2), an estrogen-targeted gene, has been shown to exert neuroprotective effects against cerebral ischemia in male mice. However, the role of Ndrg2 in the neuroprotective effect of estrogen remains unknown. In this study, we first detected NDRG2 expression levels in the cortex and striatum in both female and male mice with western blot analyses. We then detected cerebral ischemic injury by constructing middle cerebral artery occlusion and reperfusion (MCAO-R) models in Ndrg2 knockout or conditional knockdown female mice. We further implemented estrogen, ERα, or ERβ agonist replacement in the ovariectomized (OVX) Ndrg2 knockout or conditional knockdown female mice, then tested for NDRG2 expression, glial fibrillary acidic protein (GFAP) expression, and extent of cerebral ischemic injury. We found that NDRG2 expression was significantly higher in female than in male mice in both the cortex and striatum. Ndrg2 knockouts and conditional knockdowns showed significantly aggravated cerebral ischemic injury in female mice. Estrogen and ERβ replacement treatment (DPN) led to NDRG2 upregulation in both the cortex and striatum of OVX mice. Estrogen and DPN also led to GFAP upregulation in OVX mice. However, the effect of estrogen and DPN in activating astrocytes was lost in Ndrg2 knockout OVX mice and primary cultured astrocytes, but partially retained in conditional knockdown OVX mice. Most importantly, we found that the neuroprotective effects of E2 and DPN against cerebral ischemic injury were lost in Ndrg2 knockout OVX mice but partially retained in conditional knockdown OVX mice. These findings demonstrate that estrogen alleviated cerebral ischemic injury via ERβ upregulation of Ndrg2, which could activate astrocytes, indicating that Ndrg2 is a critical mediator of E2-induced neuroprotection against cerebral ischemic injury.

Distal Radius Fraktürü Ve Şiddetli Osteoporoz Saptanan Primer Amenoresi Olan Bir Turner Sendromu Olgusu

Turner Syndrome (TS) is partial or total monosomy X with a prevalence of 2500/1 and characterized by premature ovarian failure, short stature, and multiple skeletal anomalies and is also called congenital ovarian dysplasia. Delayed puberty and estrogen deficiency are some of the determining factors for Osteoporosis formation in TS. Bone mineral density is among the best parameters to evaluate the bone mineral condition. Most female TS patients need estrogen replacement treatment to stimulate and continue feminization and to prevent osteoporosis. Forty-two years-old patient with TS was admitted to our clinic for rehabilitation following a right distal radius fracture occurring when she was trying to get up from the floor trying to get support from her right hand. The patient with primary amenorrhea wasn't admitted to the hospital before except her admittance for amenorrhea when she was 20 years old and was diagnosed with Turner syndrome. In her bone mineral density (DXA) measurement, L2-L4 vertebra BMD T-score was -4.0 (0.719 g/cm), Z score was -3.8, total femur T-score was 1.7 (0.788 g/cm) and femur neck T score was -1.7 (0.799). No pathological vertebral fractures were detected. The patient was given oral risedronate sodium 35 mg and calcium 1200 mg vitD 3 880 IU/day treatment for osteoporosis and followed-up. Our aim in this case presentation was to present the fact that severe osteoporosis and fracture may occur unless early hormone replacement treatment is started in a primary amenorrheic patient with Turner Syndrome.

Sex hormone replacement therapy for individuals with Turner syndrome.

Turner syndrome is a relatively common genetic condition resulting from absence of all or part of the second sex chromosome. Individuals with Turner syndrome commonly exhibit cardiovascular, endocrine, renal, reproductive, and/or psychosocial abnormalities, among other conditions. Most girls with Turner syndrome have hypergonadotropic hypogonadism and therefore need sex steroid hormonal replacement therapy. The optimal estrogen replacement treatment regimen to induce pubertal development is still being determined. The goals of the estrogen replacement are to mimic the normal physical and social development for timing and progression of puberty. Treatment should begin at 11-12 years of age, with dose increases every 6 months over a 2-3 year period. Initiation with low doses of estrogen is crucial to preserve growth potential. On the other hand, delaying estrogen replacement may be deleterious to bone and uterine health.

Physiological and functional changes in the stratum corneum restored by oestrogen in an ovariectomized mice model of climacterium.

Significant decreases in hormonal levels at menopause induce physiological and functional discomfort in the skin. Representative changes at menopause are based on so-called dry skin. However, there is no evidence to explain the mechanism, even though hydration of the stratum corneum (SC) in women at menopause is comparable with that at premenopause but is enhanced by hormone replacement therapy. This study objective was to evaluate structural and functional changes in the SC in ovariectomized mice model of menopause. Hydration of the SC, recovery of the permeability barrier function, integrity and cohesion of the SC, and irritant dermatitis were analysed in mice that underwent ovariectomy with or without replacement of 17ß-estradiol. In ovariectomized mice, hydration of the SC was reduced, recovery of permeability barrier function after acute disruption was impaired, and integrity of the SC was weakened and was associated with increased cohesion and increased levels of irritant dermatitis. Oestrogen replacement treatment restored all changes. Immunohistochemistry revealed reduced levels of expression of desmoglein-1 and differentiation markers of epidermis in ovariectomized mice compared with control mice and mice with oestrogen replacement treatment. These changes might be directly associated with weakened integrity and impaired permeability barrier function of the SC in ovariectomized mice. This study results reveal that so-called dry skin at menopause is caused by not only lower hydration of the SC but also complicated structural and functional changes in the SC and skin.

The effect of atorvastatin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (HMG-CoA), on the prevention of osteoporosis in ovariectomized rabbits.

Osteoporosis is a most frequent systemic skeletal disease characterized as low bone mineral density and microarchitectural deterioration of bone tissue, resulting in increased bone fragility and fracture risk. Although several drugs such as bisphosphonates, estrogen replacement treatment, and selective estrogen receptor modulators have been used to treat osteoporosis, all these are not the ideal drugs because of insufficient curative ability and adverse side effects. Recently, atorvastatin has ordinarily been prescribed as an anti-hyperlipidemia drug, not as an anti-osteoporosis drug. However, its clinical outcome and potential treatment mechanism are still unclear. In this study, the bilateral ovariectomy of rabbits was duplicated to develop osteoporosis animal model. The effect of atorvastatin on in vivo was determined, and the functional mechanism was studied in vitro after the curative effect was explored. Atorvastatin was observed to significantly increase the mechanical parameters such as maximum load, stiffness, and energy-absorbing capacity, and it improved the microarchitecture. The anti-osteoporosis activity of atorvastatin may be the result of the promotion of differentiation of osteoblasts by inducing synthesis of vascular endothelial growth factor, bone morphogenetic protein 2 (BMP2), core-binding factor alpha 1 (CBFα1), and inhibition of osteoclast formation through the osteoprotegerin (OPG)-receptor activator for the nuclear factor κB ligand (RANKL) system. Our study observations give reliable experimental evidence for clinical application of atorvastatin to treat the disorder of osteoporosis.

Bone mineralization disorders as a complication of anorexia nervosa - etiology, prevalence, course and treatment.

Anorexia nervosa (AN) most often has its onset in adolescence, which is a crucial period to achieve peak bone mass. The hormonal abnormalities (hypoestrogenism, hypercortisolism, decreased secretion of dehydroepiandrosterone, testosterone, insulin-like growth factor) and malnutrition are associated with profound bone mineralization disorders. Densitomertic bone mineral density (BMD) values for osteopenia and osteoporosis were found respectively in 35-98% and 13-50% of women with AN. Prospective studies indicate a further decline in BMD at the beginning of treatment and a crucial importance of weight gain and return of spontaneous menses for its growth. Due to frequent chronic and relapsing course of AN densitometric assessment of BMD is recommended in all patients with AN and amenorrhea lasting around twelve months. In order to establish standards for the treatment of osteoporosis in AN, studies on pharmacological treatment are conducted. There are promising results indicating the improvement in BMD after treatment with physiologic oestrogen replacement treatment and sequential administration of medroxyprogesterone in teenage girls and bisphosphonates in adult women. Supplementation of vitamin D and adequate consumption of calcium from diet are recommended. Further studies on the effectiveness of long-term treatment of osteoporosis with regard to the possibility of increase in BMD and reducing the risk of osteoporotic fractures are needed.

Effect of Estrogen Replacement Treatment on VEGF in Serum and Retina in Rats

Vascular endothelial growth factor (VEGF) is a molecule implicated in the pathogenesis of several eye diseases. In this experimental study, we planned to evaluate the effects of surgical menopause and hormone replacement therapy on VEGF levels. Thus, we studied the effects of treatments involving estrogen, estrogen and progesterone (E/P) in combination, and genistein, which is a selective estrogen modulator, on serum VEGF levels and the expression of VEGF in the retinas of rats with surgical menopause. The rats were randomly divided into five groups. Bilateral ovariectomy (OVX) was performed in all groups except for the sham-operated group. estrogen, E/P, genistein or water (sham and control groups) treatments were given for 8 weeks through the orogastric catheter. Serum VEGF level and immunohistochemical staining of VEGF in retinal tissue were analyzed in each group. Serum VEGF levels were significantly higher in the OVX + estrogen and OVX + genistein groups than in the control and sham groups. It was also higher in the OVX + E/P group than in the sham and control groups; however, in this case, the difference was not statistically significant. The OVX + estrogen, OVX + E/P, and OVX + genistein groups exhibited increased VEGF staining in comparison with the control and sham groups. However, the difference was not statistically significant. The current study demonstrated that estrogen replacement treatment (ERT) leads to an increase in serum VEGF levels and progesterone plays a protective role in this increase. The ERT used in this study had no effect on VEGF expression in the retina.

1H-NMR and HPLC–MS/MS-based global/targeted metabolomic evaluation of Hypericum perforatum L. intervention for menopause

Hypericum perforatum L., which includes a wide range of bioactive substances and is sold as a functional food formulation, has been used as an alternative to estrogen replacement treatment to relieve menopausal syndromes. However, methods to track HPL mechanisms and link them to metabolism disorder regulation during menopause periods have been lacking. To investigate HPL function in endocrine-related metabolic recognition, we applied both global and targeted metabolomic methods on ovariectomised rat serum and urine metabolites for treatment-specific metabolic profiling and to explore biomarkers and deduce their mechanisms via1H-NMR and HPLC–MS/MS techniques. Results from the comparison of metabolite levels of rats that underwent an ovariectomy (OVX) before and after the administration of different doses of HPL showed that HPL can reverse the disordered changes induced in multiple biomarkers by menopausal syndromes. Through screening, identification, and quantification of the differential regulatory metabolites, 23 metabolites involved in 4 major metabolic pathways, including the arginine, taurine, pyruvate and tryptophan metabolic pathways, were highlighted as important for explaining the mechanisms of HPL. These pathways may be applicable for explanations of other menopausal syndrome symptoms, such as depression and hot flashes, and the effects of other herbs rich in flavonoids with menopause remission potential.

Influence of melatonin on plasma glucose-regulated protein 78 levels in ovariectomized female rats

In rats with surgically induced primary ovarian failure, melatonin may influence intra-retroperitoneal fat and a number of metabolic factors, which are risk factors for a number of disorders, including endometrial cancer (EC). The aim of this study is to investigate the influence of melatonin treatment in female rats with surgically induced menopause on the plasma glucose-regulated protein ​​78 (GRP78) levels as a risk factor of EC. In the current study 40 mice were included. At 14 days post-ovariectomy the animals were exposed to estrogen replacement treatment and combined treatment of estrogen and melatonin. The treatment duration, with products and doses recommended for veterinary use, was 12 consecutive weeks. The plasma estrogen and GRP78 level was measured. Groups which received estrogen associated with melatonin had a lower level of GRP78 compared to the control group. This study supports the idea that melatonin influences plasma estrogen level, which is directly, correlated with plasma GRP78 level, suggesting the implication of GRP78 in the pathogenesis of EC.

Estrogen via estrogen receptor beta partially inhibits mandibular condylar cartilage growth

Temporomandibular joint (TMJ) diseases predominantly afflict women, suggesting a role for female hormones in the disease process. However, little is known about the role of estrogen receptor (ER) signaling in regulating mandibular condylar cartilage growth. Therefore, the goal of this study was to examine the effects of altered estrogen levels on the mandibular condylar cartilage in wild type (WT) and ER beta Knockout (KO) mice. 21-day-old female WT (n=37) and ER beta KO mice (n=36) were either sham operated or ovariectomized, and treated with either placebo or estradiol. The mandibular condylar cartilage was evaluated by histomorphometry, proliferation was analyzed by double ethynyl-2'-deoxyuridine/bromodeoxyuridine (EdU/BrdU) labeling, and assays on gene and protein expression of chondrocyte maturation markers were performed. In WT mice, ovariectomy caused a significant increase in mandibular condylar cartilage cell numbers, a significant increase in Sox9 expression and a significant increase in proliferation compared with sham operated WT mice. In contrast, ovariectomy did not cause any of these effects in the ER beta KO mice. Estrogen replacement treatment in ovariectomized WT mice caused a significant decrease in ER alpha expression and a significant increase in Sost expression compared with ovariectomized mice treated with placebo. Estrogen replacement treatment in ovariectomized ER beta KO mice caused a significant increase in Col2 expression, no change in ER alpha expression, and a significant increase in Sost expression. Estrogen via ER beta inhibits proliferation and ER alpha expression while estrogen independent of ER beta induces Col2 and Sost expression.

The Role of Estrogen on Rat Parotid Gland after Menopause

Objective: To determine the histopathological changes of estrogen deficiency and estrogen replacement treatment in parotid gland of ovariectomized rats. Method: Female albino rats were divided into 3 groups: sham, ovariectomized, and ovariectomized with estrogen replacement. Histopathological evaluation of rat parotid glands were done by using the diameter of acinus and striated duct (SD), height of SD, and interacinar connective tissue thickness. Apoptosis in parotid gland were examined by TUNEL staining. Results: Except interacinar connective tissue thickness, there were no significant differences between the sham-operated control and ovariectomized group in terms of the diameter of acinus and striated duct (SD) and height of SD. Estrogen replacement resulted in significant increase in the height of SD and interacinar connective tissue thickness. Apoptotic index was higher in both ovariectomized and estrogen replacement group compared to sham-operated control. Conclusion: Although estrogen replacement did not reduce apoptotic index in parotid gland of overiectomized rat, it may have some positive influence on saliva secretion by increasing interaciner connective tissue thickness.

Placental Extract Improves Hippocampal Neuronal Loss and Fear Memory Impairment Resulting From Chronic Restraint Stress in Ovariectomized Mice

We have recently found that combination of ovariectomy (OVX) and chronic restraint stress causes cognitive dysfunction and reduces hippocampal CA3 neurons in female rats and mice and that estrogen replacement and chronic treatment with Ginkgo biloba extract EGb 761 suppress the OVX/stress-induced behavioral and morphological changes. In this study, we examined the effect of placental extract on the memory impairment and neuromorphological change in OVX/stress-subjected mice. Female Slc:ICR strain mice were randomly divided into four groups: vehicle-treated OVX, porcine placental extract (120 and 2160 mg/kg)-treated OVX, and sham-operated control groups. Two weeks after surgical operation, OVX mice underwent restraint stress for 21 days (6 h/day), and all animals were then subjected to a contextual fear conditioning test followed by morphological examination by Nissl staining. Placental extract was orally administered once daily until the behavioral analysis was carried out. Chronic treatment with both doses of placental extract improved the OVX/stress-induced fear memory impairment and Nissl-positive cell loss of the hippocampal CA3 region, although it did not affect the loss of bone mineral density and increase in body weight after OVX. These results have important implications for the neuroprotective and cognition-enhancing effects of placental extract in postmenopausal women.

Effects of combined estrogen and progesterone replacement treatment on detrusor contractility and histology in oophorectomized rats

The aim of this study was to investigate the effects of estrogen plus progesterone treatment administered after surgical menopause on morphological and muscarinic receptor sensitivity in detrusor muscle bands of rats. A total of 40 female Albino-Wistar rats were assigned into two groups to undergo surgical menopause with sham operation (n = 10) and bilateral oophorectomy (n = 30). Thirty oophorectomized rats were assigned into three groups for different treatments administered for 8 weeks beginning from the 7th postoperative day. At the end of the 8th postoperative week, laparotomy was performed in all of them and the urinary bladders were excised and investigated with light microscope. All statistical analysis and graphs were performed using GraphPad Prism version 4. P < 0.05 was considered to be statistically significant. It was determined that average bodyweights were increased to some extent in oophorectomized and sham groups after treatment and while it was more marked in the group receiving estrogen therapy, bodyweights were decreased in the group receiving estrogen plus progesterone therapy. However, this was not statistically significant. No statistically significant difference was determined between the sham, placebo and 17-β estradiol treatment groups regarding contractile response of urinary bladder tapes to carbachol (P > 0.05). Contractile responses of urinary bladder tapes of the estrogen plus progesterone treatment group were found to be statistically lower than the placebo group (P < 0.05). Our in vitro findings demonstrate that treatment with estrogen plus progesterone decreases muscarinic activity in oophorectomized rats, whereas estrogen-only treatment does not. Our study establishes the basis for further studies to answer whether combination of estrogen and progesterone treatment can restore detrusor overactivity associated with sex hormone defects seen at menopause.

Effects of treadmill exercise training on liver fat accumulation and estrogen receptor alpha expression in intact and ovariectomized rats with or without estrogen replacement treatment

To explore the mechanism(s) of exercise training on ovariectomized (OVX)-induced liver lipid disorder, we observed effects of treadmill training on liver fat accumulation and ER alpha expression in intact and ovariectomized rats. Sixty female rats were randomly assigned to six groups: Sham sedentary (S-S), Sham exercised (S-EX), ovariectomized sedentary (O-S), ovariectomized exercised (O-EX), ovariectomized injected subcutaneously with 17beta-estradiol (E(2)) (O-E(2)), and ovariectomized treated with E(2) and exercise (O-E(2)-EX). Twelve weeks after intervention, OVX resulted in significantly higher body weight gain, intra-abdominal fat mass, serum levels of total cholesterol (TC), and liver triacylglycerol (TAG) concentrations and ER alpha expression than S-S group, while the relative uterus and liver mass, serum levels of E(2), TAG, and the ratio of high density lipoprotein (HDL) to TC were markedly lower in O-S group. All of these changes were decreased in O-S rats after treatment with E(2) alone with the exception of serum TC and HDL-C levels and liver ER alpha expression. Exercise alone significantly reversed the effect of OVX on serum E(2), the ratio of HDL-C to TC and the liver and intra-abdominal fat accumulation in OVX rats. The addition of E(2) to exercise induced the same uterus and lipid profile as E(2) alone. Moreover, an additive effect of exercise and E(2) was observed on liver ER alpha expression in Sham or OVX rats. In conclusion, treadmill training alone could prevent liver fat accumulation in OVX rats and the regulation of exercise on liver ER alpha expression in both OVX and Sham rats needs the presence of physical estrogen levels.

Estrogen Replacement Reverses Olanzapine-Induced Weight Gain and Hepatic Insulin Resistance in Ovariectomized Diabetic Rats

Objectives: We investigated whether estrogen replacement modulated energy and glucose metabolic changes induced by olanzapine (OZP) and risperidone (RPD) in 90% pancreatectomized diabetic rats, some of whom had also been ovariectomized (OVX) and some of whom had not (sham). Methods: OVX diabetic rats were subcutaneously injected with estrogen replacement (17β-estradiol, 30 µg/kg/day) or a vehicle. Each group was divided into 3 subgroups, and each subgroup was orally either given a placebo, RPD (0.5 mg/kg body weight/day) or OZP (2 mg/kg body weight/day) for 8 weeks. Sham rats were also divided into 3 subgroups and given drugs in the same manner as the OVX rats were. All rats were fed high-fat diets. Results: OZP increased body weight and epididymal fat pads more than the control (vehicle) in sham and OVX rats. Increased body weight in OZP-treated sham and OVX rats was due to the increment in food intake, which was associated with potentiating the phosphorylation of hypothalamic adenosine-monophosphate-activated protein kinase. At euglycemic hyperinsulinemic clamping, OZP decreased glucose infusion rates and increased hepatic glucose output in OVX diabetic rats. In sham rats, OZP increased hepatic glucose output but not as much as in OVX rats. Hepatic insulin signaling and glucose sensing were attenuated in OZP-treated OVX rats, and the attenuation increased hepatic phosphoenolpyruvate carboxykinase expression to induce gluconeogenesis. These negative and harmful effects noted among OZP-treated OVX rats were reversed by estrogen replacement treatment. However, RPD did not alter body weight and peripheral insulin sensitivity in sham and OVX rats. Conclusions: OZP treatment should be avoided when treating diabetic and schizophrenic women, especially those in their postmenopausal period.

Tall Stature without Growth Hormone: Four Male Patients with Aromatase Deficiency

From preliminary observations, GH-IGF-I seems to be compromised in men with aromatase deficiency. The GH deficiency (GHD) coexists paradoxically with tall stature, raising the question whether or not a true GHD is part of this rare syndrome. To evaluate the GH secretion in aromatase-deficient men, their GH response to the GHRH plus arginine (GHRH-ARG) test was compared with that of normal subjects. The effect of estrogen replacement treatment on the GH-IGF-I axis in aromatase-deficient men was evaluated before and during therapy. A case-control study was conducted. Four adult men with aromatase deficiency were compared with 12 normal subjects. We measured the GH response to GHRH-ARG in aromatase-deficient men (at baseline and during estrogen treatment) and in normal subjects. Basal serum IGF-I was measured in both patients and controls. The response of GH to GHRH-ARG was severely impaired in men with aromatase deficiency and resulted in significantly lower (P < 0.001) levels than in normal subjects. Although normal, serum IGF-I levels were also significantly lower (P < 0.001) than in normal subjects. Both GH peak and IGF-I concentrations were not modified by estrogen therapy in men with aromatase deficiency. In aromatase-deficient men, GH response to potent provocative stimuli is impaired and is not restored by exogenous estrogens. Furthermore, a tall stature may be reached, notwithstanding the coexistence of GHD, if a prolonged time for growth is available due to a delay in bone maturation, and other growth factors different from GH (mainly insulin) promote growth.

Osteocalcin immunolabeling during the alveolar healing process in ovariectomized rats treated with estrogen or raloxifene

The influence of an estrogen-deficient state was evaluated in this study and also its treatments with estrogen (E 2) or with raloxifene (RLX) on the expression of osteocalcin during the periods of the chronology of the alveolar bone healing process (7, 14, 21, 28 and 42 post-extraction days) by means of immunohistochemistry reactions and histomorphometric analysis. Rats (200–220 g) with oestrus cycles normal were either OVX or sham-operated and divided into four groups: sham, OVX control (OVX/O), estrogen (OVX/E 2; 17 β-estradiol, 400 μg/mo) and raloxifene (OVX/RLX; 1 mg/kg bw/d) groups. Histomorphometric analysis showed the sham group presented the highest mean value of bone formation post-extraction. The reaction of immunohistochemistry for osteocalcin presented stronger expression of osteocalcin with predominance at 14 and 21 days on sham group. The OVX/RLX group presented better results than OVX/E 2, considering the expression of osteocalcin in osteoblastic lineage cells, but still inferior than the sham group. It was concluded that ovariectomy decreases the mineralization process and the osteocalcin expression during the chronology of the alveolar healing process that is not totally recovered with estrogen replacement or raloxifene treatment.