Estrogen Replacement Research Articles

A focus on progestogens in hormone replacement therapy

Key content Women receiving estrogen replacement require concomitant progestogen to prevent endometrial hyperplasia and carcinoma. A variety of progestogens are used in hormone replacement therapy (HRT), with different advantages and disadvantages and routes of administration. Progestogenic side effects may be mild but can be debilitating and lead to the discontinuation of HRT, so progestogens should be tailored to the individual woman. Combined HRT containing estrogen and progestogens may be associated with a small increase in the absolute risk of breast cancer, which is not seen in women taking estrogen alone. However, this risk is small, particularly when compared with other modifiable lifestyle risk factors. The addition of certain progestogens to estrogen in the long term may be associated with an increased risk of heart disease, breast cancer and dementia. Learning objectives To understand relative advantages and disadvantages of the different progestogens, regimens and routes of administration. To be aware of current evidence for types, dose and routes of administration of different progestogens. To be able to prescribe progestogens safely in terms of side effect and risk profiles that are individualised to the patient. Ethical issues Well‐informed counselling including absolute, individualised risks for women considering HRT with a progestogenic component is essential to allow patients to make well‐informed choices.

ICI 182,780 Attenuates Selective Upregulation of Uterine Artery Cystathionine β-Synthase Expression in Rat Pregnancy.

Endogenous hydrogen sulfide (H2S) produced by cystathionine β-synthase (CBS) and cystathionine-γ lyase (CSE) has emerged as a novel uterine vasodilator contributing to pregnancy-associated increases in uterine blood flow, which safeguard pregnancy health. Uterine artery (UA) H2S production is stimulated via exogenous estrogen replacement and is associated with elevated endogenous estrogens during pregnancy through the selective upregulation of CBS without altering CSE. However, how endogenous estrogens regulate uterine artery CBS expression in pregnancy is unknown. This study was conducted to test a hypothesis that endogenous estrogens selectively stimulate UA CBS expression via specific estrogen receptors (ER). Treatment with E2β (0.01 to 100 nM) stimulated CBS but not CSE mRNA in organ cultures of fresh UA rings from both NP and P (gestational day 20, GD20) rats, with greater responses to all doses of E2β tested in P vs. NP UA. ER antagonist ICI 182,780 (ICI, 1 µM) completely attenuated E2β-stimulated CBS mRNA in both NP and P rat UA. Subcutaneous injection with ICI 182,780 (0.3 mg/rat) of GD19 P rats for 24 h significantly inhibited UA CBS but not mRNA expression, consistent with reduced endothelial and smooth muscle cell CBS (but not CSE) protein. ICI did not alter mesenteric and renal artery CBS and CSE mRNA. In addition, ICI decreased endothelial nitric oxide synthase mRNA in UA but not in mesenteric or renal arteries. Thus, pregnancy-augmented UA CBS/H2S production is mediated by the actions of endogenous estrogens via specific ER in pregnant rats.

The Correlation Between Progesterone and Mammographic Density in Postmenopausal Women: A Systematic Review of the Literature and Meta-Analysis.

Higher mammographic breast density in premenopausal and postmenopausal women is related to a higher breast cancer risk. In this review, we analyze the correlation between estrogen, progesterone, and mammographic density in postmenopausal women and clarify whether these findings are consistent across different types of mammographic breast density. We extracted data concerning mammographic density increases in the populations treated with estrogen-only hormone replacement therapy and those treated with estrogen and progestin hormone replacement therapy. Postmenopausal women treated with estrogen and progesterone regimens had a statistically significant lesser mammographic density increase than estrogen-only hormone replacement therapy regimens.

Effect of Growth Hormone and Estrogen Replacement Therapy on Bone Mineral Density in Women with Turner Syndrome: A Meta-Analysis and Systematic Review.

Osteoporosis is a serious implication of Turner syndrome (TS). Common methods for the treatment of TS are growth hormone (GHT) and estrogen replacement therapy (ERT). We examined the relationship between the treatment of TS and bone mineral density (BMD) of the lumbar spine. The purpose of our study was to show the currency of BMD states among patients with TS for treatment with GHT and ERT. We searched databases for studies published from inception to April 2023. The articles were related to TS, osteoporosis, ERT, GHT, BMD and treatment patients with TS. We applied the selection criteria: lumbar spine values at L1-L4; dual-energy X-ray absorptiometry (DXA); treatment which was applied: one group of articles: ERT and two group of articles: GHT; results performed as means ± SD. In total, 79 articles were analyzed, of which 20 studies were included and 5 were considered for meta-analysis. The total number of women in the articles selected was 71. Based on the results of the meta-analysis, the effect of ERT on BMD demonstrated a significant increase in BMD (the standardized mean difference in the random model was 0.593 g/cm2, 95% CI: 0.0705 to 1.116; p = 0.026), which showed that treatment with estrogen particularly increases bone mass during treatment, which contributes to reducing the risk of fractures. The effect of GHT on BMD demonstrated a non-significant decrease in BMD in patients with TS. The results for growth hormone show that this therapy does not improve bone density. However, our review emphasizes the beneficial effect of supplementing growth hormone (GH) on the clinical presentation of TS.

P04.03.B VENOUS THROMBOEMBOLISM AND OTHER VASCULAR COMPLICATIONS IN PAEDIATRIC PATIENTS FOLLOWING CRANIOPHARYNGIOMA SURGERY: A SINGLE-CENTER, RETROSPECTIVE STUDY

Abstract BACKGROUND Craniopharyngioma (CP), although slow growing and histologically benign, carries considerable morbidity, particularly in the postoperative period: hypothalamus-pituitary dysfunction and electrolyte disorders represent common complications. Moreover, in these patients, the increased risk of deep venous thrombosis (DVT) and the possible development of fusiform intracranial aneurysms are well known. However, data are still poor, especially in the pediatric population. The aim of our study was to describe the occurrence and timing of DVT and other vascular alterations in neurosurgical operated CP patients and to evaluate the role of predisposing factors in the development of post-surgical and late vascular events. MATERIAL AND METHODS This was a single-center, retrospective study. We investigated 19 patients (11 males, 8 females, mean age 10.47±4.29) diagnosed with CP, who had been subjected to neurosurgery between December 2016 and August 2022 in Meyer Children’s Hospital IRCCS in Florence. Demographic and clinical characteristics and surgical data were recorded for each participant. RESULTS Five patients (26.3%, 3 females, 2 males, median age 15 years) presented vascular events, all during sodium imbalance. Calcium at lower limits was detected in four of them. Three DVT (two with associated pulmonary embolism, including one female patient’s death) developed after surgery, more frequently at 7-10 days (two patients were central catheter carriers, one obese patient showed hypercholesterolemia and hypertriglyceridemia). In a patient in hyponatraemic state a vascular parietal alteration compatible with pseudoaneurysm was described soon after neurosurgery, requiring vascular stenting and prolonged intensive care. Superficial vein thrombophlebitis was a late complication in an overweight female patient on estrogenic replacement therapy. CONCLUSION Patients with CP undergoing neurosurgical brain tumor resection are at a higher risk of developing DVT and vascular alterations, thus careful follow-up should be done in these patients. In our study, we found that the phase of transition from central diabetes insipidus (CDI) to syndrome of inappropriate antidiuretic hormone secretion (SIADH) is probably a significative time for developing this complication; so, we recommend careful monitoring of symptoms suggestive of vascular events in CP operated patients. However, we suggest the execution of a deep vein ultrasound examination in the post-neurosurgical two-four weeks for an early diagnosis of this problem for reducing the risk of severe complications.

Estrogen replacement therapy: effects of starting age on final height of girls with chronic kidney disease and short stature

Estrogen replacement therapy: effects of starting age on final height of girls with chronic kidney disease and short stature

Supraphysiologic doses of 17β-estradiol aggravate depression-like behaviors in ovariectomized mice possibly via regulating microglial responses and brain glycerophospholipid metabolism

Background17β-Estradiol (E2) is generally considered neuroprotective in humans. However, the current clinical use of estrogen replacement therapy (ERT) is based on the physiological dose of E2 to treat menopausal syndrome and has limited therapeutic efficacy. The efficacy and potential toxicity of superphysiological doses of ERT for menopausal neurodegeneration are unknown.MethodsIn this study, we investigated the effect of E2 with a supraphysiologic dose (0.5 mg/kg, sE2) on the treatment of menopausal mouse models established by ovariectomy. We performed the open field, Y-maze spontaneous alternation, forced swim tests, and sucrose preference test to investigate behavioral alterations. Subsequently, the status of microglia and neurons was detected by immunohistochemistry, HE staining, and Nissl staining, respectively. Real-time PCR was used to detect neuroinflammatory cytokines in the hippocampus and cerebral cortex. Using mass spectrometry proteomics platform and LC–MS/ MS-based metabolomics platform, proteins and metabolites in brain tissues were extracted and analyzed. BV2 and HT22 cell lines and primary neurons and microglia were used to explore the underlying molecular mechanisms in vitro.ResultssE2 aggravated depression-like behavior in ovariectomized mice, caused microglia response, and increased proinflammatory cytokines in the cerebral cortex and hippocampus, as well as neuronal damage and glycerophospholipid metabolism imbalance. Subsequently, we demonstrated that sE2 induced the pro-inflammatory phenotype of microglia through ERα/NF-κB signaling pathway and downregulated the expression of cannabinoid receptor 1 in neuronal cells, which were important in the pathogenesis of depression.ConclusionThese data suggest that sE2 may be nonhelpful or even detrimental to menopause-related depression, at least partly, by regulating microglial responses and glycerophospholipid metabolism.

Peri-menopausal symptoms and its management by Yoga Therapy

With increased life expectancy today, women spend one-third of their life after menopause. Thus, more attention is needed towards peri-menopausal symptoms estrogen replacement therapy is the most effective treatment, however it has its own limitations. The present need is to explore new options for the management of perimenopausal symptoms. Yogic life style is a way of living which aims to improve the body, day and mind to Pranayama and Dhyana. Yoga been utilized as a therapeutic tools to achieve positive tools to achieve positive health and control and cure disease. The exact same as to how Yoga helps in various disease states is not known. There could be neurohormonal pathways with selective effect in each pathological situation. There have been multiple studies that have combined the many aspects of Yoga into a general Yoga session in order to investigate its effect on perimenopausal symptoms. Integrated approach of Yoga therapy can improve hot flushes and night sweats. There is increasing evidence suggesting that even the short-term practice of Yoga can decrease both psychological and physiological risk factors for cardiovascular disease studies conclude that our age old therapy, Yoga is fairly effective in managing perimenopausal symptoms.

Protective effect of phytoestrogens on nonalcoholic fatty liver disease in postmenopausal women.

Non-alcoholic fatty liver disease (NAFLD) is a progressive metabolic disease characterized by hepatic steatosis, inflammation, and fibrosis that seriously endangers global public health. Epidemiological studies have shown that the incidence of non-alcoholic fatty liver disease in postmenopausal women has significantly increased. Studies have shown that estrogen deficiency is the main reason for this situation, and supplementing estrogen has become a new direction for preventing the occurrence of postmenopausal fatty liver. However, although classical estrogen replacement therapy can reduce the incidence of postmenopausal NAFLD, it has the risk of increasing stroke and cardiovascular diseases, so it is not suitable for the treatment of postmenopausal NAFLD. More and more recent studies have provided evidence that phytoestrogens are a promising method for the treatment of postmenopausal NAFLD. However, the mechanism of phytoestrogens in preventing and treating postmenopausal NAFLD is still unclear. This paper summarizes the clinical and basic research evidence of phytoestrogens and reviews the potential therapeutic effects of phytoestrogens in postmenopausal NAFLD from six angles: enhancing lipid metabolism in liver and adipose tissue, enhancing glucose metabolism, reducing oxidative stress, reducing the inflammatory response, regulating intestinal flora, and blocking liver fibrosis (Graphical Abstract).

Advantages and limitations of estrogen replacement therapy on hypogonadal survivors of childhood cancer.

Hypogonadism is a significant late complication in childhood cancer survivors (CCS). The aim of this study was to elucidate the advantages and limitations of estrogen replacement therapy (ERT) for CCS with hypogonadism. Seventeen CCS were divided into two groups: gonadal hypogonadism (GH) group (n = 8) and central hypogonadism (CH) group (n = 9). Pearson correlation coefficients were used to investigate the impact of cancer management on final height, bone density, and uterine development. Seven of GH group had hematologic malignancies, and all of them underwent total body irradiation before bone marrow transplantation. The GH group showed significant positive correlations between the onset age of disease treatment and final height (p < 0.05, R = 0.712) and uterine size following ERT (p < 0.05, R = 0.775). All CCS in the CH group had brain tumors, and seven of them received chemotherapy. There were trends towards positive and negative correlations between the onset age of disease treatment and final height (p = 0.09, R = 0.598) or uterine size (p = 0.07, R = -0.669), respectively. A negative correlation trend was observed between the age at ERT initiation and final height (p = 0.07, R =-0.769) or bone density (p = 0.18, R = -0.626) in six CH patients who received growth hormone therapy. Five CCS in both groups experienced osteoporosis, despite receiving ERT. Individualized management strategies beyond ERT are essential to reduce long-term complications in CCS with hypogonadism, considering the type and timing of cancer treatment.

Factors of reduced bone mineral density in children with Turner syndrome

Decreased bone mineral mass is one of the significant somatic problems for adolescents with Turner syndrome. The results of our own study, which estimates the state of bone mineral density in children with Turner syndrome depending on age, karyotype variant, spontaneous or stimulated onset of sexual development are present in the publication. A high frequency of bone mineral density deficiency in patients with Turner syndrome was established, regardless of the presence of puberty. Changes in bone density in girls with spontaneous puberty are less common. The difference in bone mineral density between patients with Turner syndrome and the control group from the age of 11 years was shown. Positive effect of replacement estrogen therapy on bone tissue condition in Turner syndrome is shown.

Growth hormone therapy is associated with improved uterine dimensions in girls with Turner syndrome prior to oestrogen replacement.

Adult women with Turner syndrome (TS) have high rates of miscarriage, presumably due to the abnormal size and shape of the uterus. There is a paucity of data regarding the determinants of uterine volume (UtVol) in young girls with TS before the initiation of oestrogen replacement therapy (ERT). We performed a cross-sectional study on premenarchal girls with TS, aged 5-15 years, pubertal stage B1-B3, not having received ERT (n = 73) and 50 age-matched healthy controls. Anthropometric parameters and a history of growth hormone (GH) therapy (≥1 year) were noted. Uterine length (UtL), UtVol, and mean-ovarian-volume (MOV) standard-deviation scores (SDS) were determined from transabdominal ultrasonography data. Girls with TS had lower median UtVol-SDS (-1.07 vs. 0.86; p < .001), UtL-SDS (-3.72 vs. -0.41; p < .001) and MOV-SDS (-5.53 vs. 1.96; p < .001) compared to age-matched controls. Among TS girls, recipients of GH (n = 38) had higher UtVol-SDS (-0.63 vs. -1.39; p = .0001), UtL-SDS (-1.73 vs. -6.49; p < .0001) but similar MOV-SDS compared to nonrecipients (n = 35). Those with normal uterine volume for age (NUVA, n = 29) had earlier initiation (7.8 vs. 9.3 years; p = .03) and a longer duration of GH (3.71 vs. 2.14 years; p = .002) than those with low UtVol for age (n = 44). UtVol-SDS correlated with duration of GH (ρ = 0.411, p = .01) and negatively with age at GH initiation (ρ = -0.479, p = .003). In a model adjusted for pubertal status, karyotype and height-SDS, GH use could independently predict having NUVA (odds ratio: 5.09, confidence interval: 1.63-15.94, p = .005). GH therapy has a stimulatory effect on uterine dimensions in pre-and peripubertal girls with TS. Earlier initiation and longer duration of GH is important in TS girls before ERT.

Abstract P3119: Identifying The Windows Of Cardiac Risk And Opportunity In Menopause

Post-acute myocardial infarction (AMI) mortality has significant sex differences with a bias towards higher rates in women. While treatment inequities and access to care profoundly impact outcomes, biological factors also contribute to survival discrepancies. One complicating factor that drives worse outcomes in women is menopause. Understanding the biological basis for AMI mortality risk and the exacerbating role of menopause has been hampered by the lack of an animal model that recapitulates the dynamic changes associated with the perimenopausal transition. We used a mouse model of menopause in which ovarian failure is gradually induced following treatment with 4-vinylcyclohexene diepoxide (VCD, 160 mg/kg, 15d), allowing for examination of cardiac alterations established during perimenopause. Echocardiography revealed no contractile changes during perimenopause, but cardiac myofilament activation was significantly affected. Calcium re-uptake by SERCA was impaired by the end of perimenopause. Changes in calcium handling were associated with alterations in calcium handling protein expression and phosphorylation. Activation of RISK and SAFE signaling molecules that protect against ischemia-reperfusion (IR) injury was altered throughout perimenopause, and the RISK-SAFE response to IR differed at points during perimenopause. The myocardial response to cardioprotective estrogen receptor activation also varied throughout perimenopause. Together these data reveal significant, nonlinear alterations in myocardial physiology and endogenous protective signing pathways during perimenopause. Disruptions in endogenous protection and calcium handling are established prior to menopause, providing possible mechanisms for worse post-menopausal AMI outcomes. The altered response to estrogen receptor activation preceding menopause may explain the inconsistent effectiveness of post-menopausal estrogen replacement therapy.

Modern approach to the management of genitourinary syndrome in women with gynecological malignancies.

The term genitourinary syndrome of menopause was first used in 2014 by the North American Menopause Society and the International Society for the Study of Women's Sexual Health to describe conditions previously known as atrophic vaginitis, urogenital atrophy, or vulvovaginal atrophy. It is a complex, chronic, progressive condition characterized by a wide range of signs and symptoms affecting sexual function and the tissues of the urinary and genital tracts. The main cause of genitourinary syndrome of menopause is estrogen deficiency caused by ovarian removal or dysfunction. The most bothersome symptoms are vaginal dryness, decreased vaginal lubrication, and pain during penetration and intercourse. They all have a negative impact on the quality of life. The main goal of treatment is to relieve the symptoms. Treatment modalities are pharmacological or non-pharmacological. The first-line treatment for mild to moderate symptoms is the use of personal lubricants and moisturizers, but the gold standard is estrogen replacement therapy. Hormone therapy may not be an option for women with hormone-dependent cancer.

Primary Amenorrhea in Adolescents: Approach to Diagnosis and Management

Primary amenorrhea (PA) describes the complete absence of menses by the age of 15 years. It is a devastating diagnosis that can affect the adolescent’s view of her femininity, sexuality, fertility and self-image. A normal menstrual cycle can occur only in the presence of: a properly functioning hypothalamus–pituitary axis, well-developed and active ovaries, outflow tract without abnormalities. Any dysfunction in any of these players can result in amenorrhea. PA evaluation includes the patient’s medical history, physical examination, pelvic ultrasonography and initial hormone evaluation, limited to the serum-follicle-stimulating hormone (FSH) and luteinizing hormone, testosterone and prolactin. A karyotype should be obtained in all adolescents with high FSH serum levels. The main causes of PA, whether or not accompanied by secondary sexual characteristics, include endocrine defects of the hypothalamus–pituitary–ovarian axis, genetic defects of the ovary, metabolic diseases, autoimmune diseases, infections, iatrogenic causes (radiotherapy, chemotherapy), environmental factors and Müllerian tract defects. PA management depends on the underlying causes. Estrogen replacement therapy at puberty has mainly been based on personal experience. PA can be due to endocrine, genetic, metabolic, anatomical and environmental disorders that may have severe implications on reproductive health later in life. In some complex cases, a multidisciplinary team best manages the adolescent, including a pediatrician endocrinologist, gynecologist, geneticist, surgeon, radiologist, and psychologist.

Effervescent Tablets Formulation of Jicama (Pachyrhizus erosus) Extract with Various Concentrations of Binders and Sweeteners

Osteoporosis is a major public health problem. Exogenous estrogen or Hormone Replacement Therapy (HRT) is the potential therapy for osteoporosis. Still, the patient rarely chooses this treatment because of the risk of breast and endometrial cancer. Phytoestrogens or estrogen-like compounds, particularly isoflavones, are a potentially safe alternative to HRT. Jicama (Pachyrhizus erosus) is a plant that contains many phytoestrogens. This research aimed to determine the physicochemical characteristics of jicama extract in effervescent tablets with various concentrations of binder and sweetener. The manufacturing of jicama effervescent tablets used raw materials extracted from 96% p.a. ethanol by maceration. The extract is then formulated with various binder concentrations (PVP 40 and gelatin) and sweeteners (lactose and Mannitol) using the wet granulation method. Based on the test results on the physicochemical properties of tablets, all the formula meets the requirement of a good tablet, and the preferred formula is Formula 4 with 0.75% of PVP40 and 47,75% Mannitol. Ethanol extract of jicama can be formulated into effervescent tablets and has the potential to be developed as a treatment for osteoporosis.&#x0D; Keywords: Xicama Extract, Fitoestrogen, Estrogen-like therapy, Osteoporosis, Effervescent tablet

Low-Dose Estrogens as Neuroendocrine Modulators in Functional Hypothalamic Amenorrhea (FHA): The Putative Triggering of the Positive Feedback Mechanism(s).

Functional hypothalamic amenorrhea (FHA) is a non-organic reversible chronic endocrine disorder characterized by an impaired pulsatile secretion of the gonadotropin-releasing hormone (GnRH) from the hypothalamus. This impaired secretion, triggered by psychosocial and metabolic stressors, leads to an abnormal pituitary production of gonadotropins. As LH and FSH release is defective, the ovarian function is steadily reduced, inducing a systemic hypoestrogenic condition characterized by amenorrhea, vaginal atrophy, mood changes and increased risk of osteoporosis and cardiovascular disease. Diagnosis of FHA is made excluding other possible causes for secondary amenorrhea, and it is based upon the findings of low serum gonadotropins and estradiol (E2) with evidence of precipitating factors (excessive exercise, low weight, stress). Treatments of women with FHA include weight gain through an appropriate diet and physical activity reduction, psychological support, and integrative approach up to estrogen replacement therapy. If no spontaneous ovarian function is restored, assisted reproductive technologies may be used when pregnancy is desired. Because subjects with FHA are hypoestrogenic, the use of low-dose estrogens has been proposed as a putative treatment to positively modulate the spontaneous restart of gonadotropin secretion, counteracting the blockade of the reproductive axis triggered by stress acting through the neuroendocrine pathways at the basis of positive feedback of estrogens. The mechanism through which low-dose estrogens acts is still unknown, but kisspeptin-secreting neurons may be involved.

Managing Early Onset Osteoporosis: The Impact of Premature Ovarian Insufficiency on Bone Health.

Premature ovarian insufficiency is a reproductive endocrine disorder characterized by the cessation of ovarian function before the age of 40 years. Although the etiopathology of POI remains largely unknown, certain causative factors have been identified. Individuals affected by POI are at an increased risk of experiencing bone mineral density (BMD) loss. Hormonal replacement therapy (HRT) is recommended for patients with POI to mitigate the risk of decreased BMD, starting from the time of diagnosis until reaching the average age of natural menopause. Various studies have compared the dose-effect relationship of estradiol supplementation, as well as different HRT formulations on BMD. The impact of oral contraception on reduced BMD or the potential benefits of adding testosterone to estrogen replacement therapy are still subjects of ongoing discussion. This review provides an overview of the latest advancements in the diagnosis, evaluation, and treatment of POI as it relates to BMD loss.

The Effects of Purple Sweet Potato (Ipomoea Batatas L.) Ethanol Extract on Bladder Urothelial Layer and Smooth Muscle Thicknesses in Menopausal Female Wistar Rats

Highlights: Purple sweet potatoes cultivated in Bali, Indonesia, were found to be rich in phytoestrogen due to the high levels of anthocyanin-type flavonoids. The phytoestrogen in purple sweet potato ethanol extract demonstrated estrogenic activity and the potential to substitute hormone replacement therapy (HRT) as the treatment of lower urinary tract symptoms. Abstract Postmenopausal women experience estrogen hormone deficiency, which can cause thinning of the smooth muscle and urothelial layer of the bladder, leading to lower urinary tract symptoms (LUTS). Hormone replacement therapy (HRT) has been the primary choice for addressing these problems. However, long-term prescription of HRT can result in several adverse effects, including a higher risk of breast cancer and cardiovascular diseases. Phytoestrogen, an estrogen-like compound derived from plants such as purple sweet potatoes (Ipomoea batatas L.), contains anthocyanin that could serve as a better alternative to estrogen replacement therapy. This study aimed to demonstrate the effects of phytoestrogens in purple sweet potatoes on the histomorphology of the bladder in menopausal female Wistar rats (Rattus norvegicus). This experimental study used a posttest-only control group design. A total of 36 Wistar rats undergoing ovariectomy were randomly assigned into two groups, with 18 samples in each group. The experimental group received the purple sweet potato ethanol extract orally, while the control group received a placebo. The structures of the smooth muscle and urothelial layer of the bladder were observed using a microscope. Data were analyzed using an independent t-test to compare bladder smooth muscle and urothelial layer thickness between groups, with a significance of p&lt;0.05. A normality test was performed to determine the normal distribution of the data. Normally distributed data were assessed to find the mean and standard deviation (SD). Significant differences were found in the mean thickness of the smooth muscle and urothelial layer between both groups (p=0.00), with both being thicker in the experimental group. In conclusion, phytoestrogens in purple sweet potatoes can influence the histomorphology of the bladder. Ovariectomized female Wistar rats that received purple sweet potato ethanol extract exhibited thicker smooth muscle and urothelial layer of the bladder.

Estrogen-regulated miRs in bone enhance osteoblast differentiation and matrix mineralization

Estrogen signaling is critical for the development and maintenance of healthy bone, and age-related decline in estrogen levels contributes to the development of post-menopausal osteoporosis. Most bones consist of a dense cortical shell and an internalmesh-like network of trabecular bone that respond differently to internal and external cues such as hormonal signaling. To date, no study has assessed the transcriptomic differences that occur specifically in cortical and trabecular bone compartments in response to hormonal changes. To investigate this, we employed a mouse model of post-menopausal osteoporosis (ovariectomy, OVX) and estrogen replacement therapy (ERT). mRNA and miR sequencing revealed distinct transcriptomic profiles between cortical and trabecular bone in the setting of OVX and ERT. Seven miRs were identified as likely contributors to the observed estrogen-mediated mRNA expression changes. Of these, four miRs were prioritized for further study and decreased predicted target gene expression in bone cells, enhanced the expression of osteoblast differentiation markers, and altered the mineralization capacity of primary osteoblasts. As such, candidate miRs and miR mimics may have therapeutic relevance for bone loss resulting from estrogen depletion without the unwanted side effects of hormone replacement therapy and therefore represent novel therapeutic approaches to combat diseases of bone loss.