Hormone Replacement Research Articles

Sheehan’s syndrome presenting with panhypopituitarism and central diabetes insipidus: a case report

BackgroundSheehan’s syndrome is a rare condition, which is classically characterized by anterior pituitary hypofunction following postpartum shock or hemorrhage. While diabetes insipidus (DI) is not commonly associated with Sheehan’s syndrome, we present a rare case of a multiparous female developing rapid-onset panhypopituitarism and DI following severe postpartum hemorrhage.Case presentationA previously healthy 39-year-old woman, gravida 5, para 4, presented with hypovolemic shock after vaginal delivery, attributed to severe postpartum hemorrhage, necessitating emergent hysterectomy. Although her shock episodes resolved during hospitalization, she developed intermittent fever, later diagnosed as adrenal insufficiency. Administration of hydrocortisone effectively resolved the fever. However, she subsequently developed diabetes insipidus. Diagnosis of Sheehan’s syndrome with central diabetes insipidus was confirmed through functional hormonal tests and MRI findings. Treatment consisted of hormone replacement therapy, with persistent panhypopituitarism noted during a ten-year follow-up period.ConclusionsSheehan’s syndrome is a rare complication of postpartum hemorrhage. Central diabetes insipidus should be suspected, although not commonly, while the patient presented polyuria and polydipsia. Besides, the potential necessity for long-term hormonal replacement therapy should be considered.

A qualitative exploration of experiences of gender identity and gender questioning among adults with Klinefelter syndrome/XXY.

People with Klinefelter syndrome (KS/XXY) may be at higher risk of gender dysphoria than the general population and gender diversity needs greater recognition and consideration in services for people affected. This study aimed to give systematic insights into experiences of gender diversity among people with KS/XXY, which could inform more person-centered care for people with KS/XXY and contribute to practical guidance for healthcare professionals. We conducted individual, semi-structured interviews with 11 adults with diagnosed KS/XXY. The verbatim interview transcripts were analyzed using experiential reflexive thematic analysis, which identified four themes: (1) Experience of gender, which described participants' experiences of exploring and negotiating their gender identity; (2) Navigating expectations, which described how participants' gender uncertainty was associated with confusion, isolation, and shame, and how fears about other people's reactions caused participants to keep their gender identity secret; (3) Testosterone assumptions, which described how participants needed more discussion and counseling before testosterone replacement therapy (TRT), and how some benefited from treatment with alternative hormones to testosterone; and (4) A different approach, which described participants' experiences of care at gender identity clinics. The findings give new insights into the gender identity journeys of people with KS/XXY, from early attempts to understand and make sense of gender, through dealing with social pressures, the development of gender identities more congruent with feelings, and experiences with hormone replacement therapy. The practice implications include that there should be improved consideration of gender identity in care for KS/XXY, better psychological support for those affected by gender diversity, and more consideration given to alternatives to testosterone-based therapies. Future research could explore the experiences of gender identity among different groups of people with KS/XXY, the development of gender identity over time, the effects of TRT on gender identity, and healthcare providers' knowledge and attitudes about gender identity and KS/XXY.

Use of an estradiol transdermal spray in women with menopausal symptoms: a non-interventional study

Objective This study aimed to investigate the effectiveness, tolerability and application of estradiol metered-dose transdermal spray (EMDTS) in postmenopausal women during real-world use. Methods This was a prospective, non-interventional, multicenter, observational phase IV cohort study. The Menopause Rating Scale II (MRS II) was used to assess symptoms and clinical response. Safety was assessed by the occurrence of adverse events and adverse drug reactions (ADRs). Results A total of 451 postmenopausal women were enrolled at 52 gynecological practices across Germany; 383 patients were evaluated for effectiveness and 430 patients for safety. Mean age was 54.3 ± 7.4 years. In total, 228 patients (59.5%) received EMDTS monotherapy and 155 patients (40.5%) received EMDTS plus progestogens. Significant improvements (p < 0.0001) from baseline in symptom severity were recorded for all 11 items of the MRS II at 3, 6 and 12 months of treatment. At 12 months, 81.4% of patients reported improvement in hot flushes/sweating. At final visit, 73% of patients and 77% of physicians were ‘satisfied/very pleased’ with EMDTS. Most common ADRs were headache (n = 6), nausea (n = 4), dizziness (n = 4) and pruritus (n = 3). Conclusions EMDTS is an effective, well tolerated and easily applied hormone replacement therapy for women experiencing postmenopausal symptoms.

Weight Management and Metabolism in Postmenopausal Women: A Review

Post-menopause is a critical period in a woman's life marked by significant hormonal changes that affect metabolism and weight management. This review paper examines the physiological changes impacting weight and metabolism in postmenopausal women, the associated health risks, and effective strategies for managing weight during this stage of life. Google Scholar, PubMed, Medline and Cochrane electronic databases related to weight management in postmenopausal women were searched. Adopting a holistic approach that includes lifestyle modifications; dietary adjustments like a phytoestrogen-rich diet, physical activity, behavioural changes, and potentially hormone replacement therapy can help manage weight effectively.

Levothyroxine synthesis impurities are neither mutagenic nor genotoxic: Insilico, Ames test and micronucleus test studies

In vitro and in silico tests were used to assess the possible genotoxicity and mutagenicity of five impurities that may be present in levothyroxine, a drug used for thyroid hormone replacement therapy. Neither ToxTree nor VEGA (Virtual Models for evaluating the properties of chemicals within a global architecture) identified cause for concern for any of the impurities. Ames test results (doses up to 1 mg per plate), with or without metabolic activation, were negative. The micronucleus test with TK6 (human lymphoblastoid) cells, at doses up to 500 µg/mL, with or without metabolic activation, also gave negative results.

Risk factors for breast cancer subtypes by race and ethnicity: A scoping review.

Breast cancer is comprised of distinct molecular subtypes. Studies have reported differences in risk factor associations with breast cancer subtypes, especially by tumor estrogen receptor (ER) status, but their consistency across racial and ethnic populations has not been comprehensively evaluated. We conducted a qualitative, scoping literature review using the Preferred Reporting Items for Systematic Reviews and Meta-analysis, extension for Scoping Reviews to investigate consistencies in associations between 18 breast cancer risk factors (reproductive, anthropometric, lifestyle, and medical history) and risk of ER-defined subtypes in women who self-identify as Asian, Black or African American, Hispanic or Latina, or White. We reviewed publications between January 1, 1990 and July 1, 2022. Etiologic heterogeneity evidence (convincing, suggestive, none, or inconclusive) was determined by expert consensus. Publications per risk factor ranged from 14 (benign breast disease history) to 66 (parity). Publications were most abundant for White women, followed by Asian, Black or African American, and Hispanic or Latina women. Etiologic heterogeneity evidence was strongest for parity, followed by age at first birth, post-menopausal BMI, oral contraceptive use, and estrogen-only and combined menopausal hormone therapy. Evidence was limited for other risk factors. Findings were consistent across racial and ethnic groups, although the strength of evidence varied. The literature supports etiologic heterogeneity by ER for some established risk factors that are consistent across race and ethnicity groups. However, in non-White populations evidence is limited. Larger, more comparable data in diverse populations is needed to better characterize breast cancer etiologic heterogeneity.

Assessment of endometrial and subendometrial three-dimensional power Doppler angiography evaluated by the VOCAL method in frozen-thawed embryo transfer cycles on hormone replacement therapy

BACKGROUND: The effectiveness of in vitro fertilization cycles / frozen-thawed embryo transfer cycles depends on a number of factors, the endometrial one being of great importance. Adequate endometrial and subendometrial blood supply is considered necessary for successful implantation. Currently, the possibilities of non-invasive assessment of the implantation properties of the endometrium are limited to the use of ultrasound. AIM: The aim of this study was to assess the performance of endometrial and subendometrial three-dimensional power Doppler angiography combined with the Virtual Organ Computer-aided Analysis (VOCAL) method in frozen-thawed embryo transfer cycles on hormone replacement therapy and compare the obtained data among the women examined. MATERIALS AND METHODS: This prospective study included 20 women. Doppler measurements were carried out three times — on the day of progesterone initiation, the day before embryo transfer and on the day of embryo transfer. The VOCAL software assessed the endometrial and subendometrial volume and blood flow indices such as vascularization index, flow index, and vascularization flow index. Patients were divided into two study groups depending on the onset of clinical pregnancy. RESULTS: On the day of progesterone initiation among patients who got pregnant, we observed higher vascularization (3.52 ± 1.99 vs. 1.05 ± 1.36; p = 0.03) and vascularization flow (1.54 ± 0.98 vs. 0.63 ± 0.55; p = 0.03) indices compared to women with a negative result. Moreover, endometrial vascularization index on the day of progesterone initiation was positively correlated with the estrogen dose among both pregnant (r = 0.61; p = 0.04) and non-pregnant (r = 0.9; p = 0.0008) women. No differences in subendometrial blood flow indices depending on the onset of pregnancy were obtained, just as endometrial blood flow indices the day before embryo transfer and on the day of embryo transfer were comparable between women in the both study groups. CONCLUSIONS: Three-dimensional power Doppler angiography evaluated by the Virtual Organ Computer-aided Analysis (VOCAL) method is a promising tool for non-invasive assessment of endometrial receptivity in frozen-thawed embryo transfer programs. However, further studies are required on a larger patient sample to form conclusions that are more accurate.

Peripheral arterial disease in women.

Peripheral arterial disease (PAD) represents one of the most frequent manifestations of atherosclerosis in men and women. In both sexes, PAD is related to classical risk factors of atherosclerosis, which are similarly distributed, but some additional factors determine differences between men and women. More frequent asymptomatic disease in women than in men and less frequent screening in women may result in a false underestimation of the prevalence of PAD in women. All these factors may cause delayed diagnosis and treatment of PAD in women. Estrogen hormones have vasoprotective properties that lower the prevalence of atherosclerosis in women of younger age. However, estrogen probably does not have a protective role against the development of cardiovascular disease in women of an older age. Hormone replacement therapy (HRT) of less than one year does not appear to reduce the odds of developing PAD in postmenopausal women. It may even increase the risk of morbidity from vascular interventions. However, some studies indicated that HRT for more than one year significantly decreases the risk of PAD if administered early after the last menstruation. Also, treatment of PAD in women differs to some extent from men.

Outcomes of thyroidectomy in symptomatic, euthyroid Hashimoto's patients: a case control study.

Hashimoto's thyroiditis (HT) is managed with thyroid hormone replacement to maintain a euthyroid state. A subset of patients have refractory symptoms, which improve with thyroidectomy (TT). There remains a reluctance to proceed with surgery due to perceptions of complications, and limited data availability regarding improvements in quality of life (QoL). This retrospective case control study aims to analyse the outcomes and QoL scores for symptomatic euthyroid HT patients who underwent TT. Thirty euthyroid patients who underwent TT for the management of HT between 2017 and 2022 were identified. An age-matched control group of patients who underwent TT for symptomatic multinodular goitre (MNG) were randomly selected. Demographics, biochemistry, histology, outcomes, and pre- and post-operative SF-36 and ThyPRO-39 scores were compared between groups. There were no surgical complications in the HT group, whilst two MNG patients had complications. There was a similar rate of parathyroid auto-transplantation in both groups, more glands were transplanted in the HT group. There was a significant difference in pre- and post-operative QoL scores for both groups. Comparison revealed a significant improvement in hyperthyroid symptoms, social life and daily life scores in the HT group. There was a significant difference in pre- and post-operative anti-TPO, anti-TG and TSH levels in the HT group. Patients with symptomatic Hashimoto's thyroiditis, despite being euthyroid, may benefit from total thyroidectomy however this remains under-utilized. This study demonstrated that thyroidectomy was associated with an improvement in validated post-operative quality of life scores and was not associated with increased complication rates for appropriately selected patients.

The intersection between menopause and depression: overview of research using animal models.

Menopausal women may experience symptoms of depression, sometimes even progressing clinical depression requiring treatment to improve quality of life. While varying levels of estrogen in perimenopause may contribute to an increased biological vulnerability to mood disturbances, the effectiveness of estrogen replacement therapy (ERT) in the relief of depressive symptoms remains controversial. Menopausal depression has a complex, multifactorial etiology, that has limited the identification of optimal treatment strategies for the management of this psychiatric complaint. Nevertheless, clinical evidence increasingly supports the notion that estrogen exerts neuroprotective effects on brain structures related to mood regulation. Indeed, research using preclinical animal models continues to improve our understanding of menopause and the effectiveness of ERT and other substances at treating depression-like behaviors. However, questions regarding the efficacy of ERT in perimenopause have been raised. These questions may be answered by further investigation using specific animal models of reduced ovarian function. This review compares and discusses the advantages and pitfalls of different models emulating the menopausal stages and their relationship with the onset of depressive-like signs, as well as the efficacy and mechanisms of conventional and novel ERTs in treating depressive-like behavior. Ovariectomized young rats, middle-to-old aged intact rats, and females treated with reprotoxics have all been used as models of menopause, with stages ranging from surgical menopause to perimenopause. Additionally, this manuscript discusses the impact of organistic and therapeutic variables that may improve or reduce the antidepressant response of females to ERT. Findings from these models have revealed the complexity of the dynamic changes occurring in brain function during menopausal transition, reinforcing the idea that the best approach is timely intervention considering the opportunity window, in addition to the careful selection of treatment according to the presence or absence of reproductive tissue. Additionally, data from animal models has yielded evidence to support new promising estrogens that could be considered as ERTs with antidepressant properties and actions in endocrine situations in which traditional ERTs are not effective.

Heterotopic ovarian transplantation instead hormonal replacement therapy after radical hysterectomy for cervical cancer: case report and review of literature.

Only a few case reports have described heterotopic ovarian tissue transplantation (OTT) with the only objective of restoring ovarian function. Case report and review of the literature forreporting cases of heterotopic OTT with the only aim of restoring ovarian endocrine function. In a cancer survivor woman with a history of hysterectomy and bilateral oophorectomy for cervical cancer and because she poorly tolerated hormone replacement therapy (HRT), we performed a heterotopic OTT in a pelvic subcutaneous "pocket" after an OT cryostorage of 17years. A cyclic ovarian endocrine function started 3months after OTT with an immediate patient self-described improvement of her quality of life. A second OTT was performed 19months after, due to hot flushes recurrence and FSH increase. Despite a cyclic endocrine function, progesterone levels have always been low, resulting in a relative hyperoestrogenism state. In the future, the indications of heterotopic OTT could be spread in alternative to HRT. However, our data suggest that the heterotopic graft environment is less favorable to corpus luteum development, and further studies are needed to assay the best site of heterotopic graft, the optimal number of ovarian cortexfragmentsto graft, and the potential risk of relapse in case of malignant residual disease.

Pharmacotherapeutic Considerations on Telomere Biology: The Positive Effect of Pharmacologically Active Substances on Telomere Length.

Telomeres are part of chromatin structures containing repeated DNA sequences, which function as protective caps at the ends of chromosomes and prevent DNA degradation and recombination, thus ensuring the integrity of the genome. While telomere length (TL) can be genetically inherited, TL shortening has been associated with ageing and multiple xenobiotics and bioactive substances. TL has been characterised as a reliable biomarker for the predisposition to developing chronic pathologies and their progression. This narrative review aims to provide arguments in favour of including TL measurements in a complex prognostic and diagnostic panel of chronic pathologies and the importance of assessing the effect of different pharmacologically active molecules on the biology of telomeres. Medicines used in the management of cardiovascular diseases, diabetes, schizophrenia, hormone replacement therapy at menopause, danazol, melatonin, and probiotics have been studied for their positive protective effects against TL shortening. All these classes of drugs are analysed in the present review, with a particular focus on the molecular mechanisms involved.

The impact of physical activity and exercise interventions on symptoms for women experiencing menopause: overview of reviews

BackgroundWomen experiencing problematic menopausal symptoms report lower health-related quality of life and greater healthcare use than women without symptoms. Not all women want to or are able to take hormone replacement therapy. Strengthening the evidence for menopause symptom-management options, including physical activity, improves agency for women.AimThis overview assesses effectiveness of physical activity and exercise interventions targeting women experiencing menopause symptoms.MethodsMedline, Embase, CINAHL, Scopus, The Cochrane Database of Systematic Reviews and Social Science Citation Index were searched (June 2023) for systematic reviews of physical activity and exercise interventions targeting women experiencing menopause. Reviews were assessed using AMSTAR-2 and a best-evidence approach to synthesis without meta-analysis (SWIM) was adopted. The protocol was registered on PROSPERO (CRD42022298908).ResultsSeventeen reviews included 80 unique relevant primary studies with 8983 participants. There is evidence showing improvement of physical, urogenital, and total symptoms following yoga interventions. Evidence for vasomotor and psychological symptoms was inconclusive. Findings for aerobic exercise were inconclusive although there were some examples of beneficial effects on total and vasomotor symptoms. Evidence was very limited for other types of physical activity and impact on physical, sexual and urogenital symptoms.ConclusionThere is some evidence that yoga, and to lesser extent, aerobic exercise may be beneficial for some menopause symptoms, but there is insufficient evidence to recommend a particular form of exercise. Current reviews categorise women on menopause status; broadening this to include ethnicity, income status, employment and other factors will allow better understanding of context for successful interventions.

Breast Cancer is Increased in Women with Primary Ovarian Insufficiency.

DNA damage/repair gene variants are associated with both primary ovarian insufficiency (POI) and cancer risk. We hypothesized that a subset of women with POI and family members would have increased risk for cancer. Case-control population-based study using records from 1995-2022. Two major Utah academic healthcare systems serving 85% of the state. Women with POI (n=613) were identified using ICD codes and reviewed for accuracy. Relatives were linked using the Utah Population Database. Cancer diagnoses were identified using the Utah Cancer Registry. The relative risk of cancer in women with POI and relatives was estimated by comparison to population rates. Whole genome sequencing was performed on a subset of women. Breast cancer was increased in women with POI (OR [95%CI] 2.20 [1.30, 3.47]; p=0.0023) and there was a nominally significant increase in ovarian cancer. Probands with POI were 36.5±4.3 years and 59.5±12.7 years when diagnosed with POI and cancer, respectively. Causal and candidate gene variants for cancer and POI were identified.Among second-degree relatives of these women, there was an increased risk of breast (1.28 [1.08, 1.52]; p=0.0078) and colon cancer (1.50 [1.14, 1.94]; p=0.0036). Prostate cancer was increased in first- (1.64 [1.18, 2.23]; p=0.0026), second- (1.54 [1.32, 1.79]; p<0.001), and third-degree relatives (1.33 [1.20, 1.48]; p<0.001). Data suggest common genetic risk for POI and reproductive cancers. Tools are needed to predict cancer risk in women with POI and potentially to counsel about risks of hormone replacement therapy.

Improvement of early miscarriage rates in women with adenomyosis via oxytocin receptor antagonist during frozen embryo transfer-a propensity score-matched study

BackgroundDysfunctional uterine peristalsis seems to play a pivotal role in hindering embryo implantation among women diagnosed with adenomyosis. This research aims to investigate whether administering an oxytocin receptor antagonist during a frozen embryo transfer (FET) cycle using a hormone replacement therapy (HRT) protocol can enhance in vitro fertilization (IVF) outcomes for infertile women affected by adenomyosis.MethodsBetween January 2018 and June 2022, our reproductive center conducted IVF-FET HRT cycles for infertile women diagnosed with adenomyosis. Propensity score matching was employed to select matched subjects between the two groups in a 1:1 ratio. Following this, 168 women received an oxytocin receptor antagonist during FET, constituting the study group, while the matched 168 women underwent FET without this antagonist, forming the control group. We conducted comparative analyses of baseline and cycle characteristics between the two groups, along with additional subgroup analyses.ResultsThe study group exhibited notably lower rates of early miscarriage compared to the control group, although there were no significant differences in clinical pregnancy rates, ongoing pregnancy rates, and live birth rates between the two groups. Multivariate analysis revealed a negative correlation between the use of oxytocin receptor antagonists and early miscarriage rates in women with adenomyosis. Subgroup analyses, categorized by age, infertility types, and embryo transfer day, showed a substantial decrease in early miscarriage rates within specific subgroups: women aged ≥ 37 years, those with secondary infertility, and individuals undergoing day 3 embryo transfers in the study group compared to the control group. Furthermore, subgroup analysis based on adenomyosis types indicated significantly higher clinical pregnancy rates, ongoing pregnancy rates and live birth rates in the study group compared to the control group among women with diffuse adenomyosis.ConclusionsAdministering an oxytocin receptor antagonist during FET may reduce the early miscarriage rates in women with adenomyosis.

Different endometrial preparation protocols on first frozen-thawed embryo transfer outcomes after hysteroscopic polypectomy: A retrospective cohort study.

To evaluate the optimal endometrial preparation protocol for frozen-thawed embryo transfer (FET) following hysteroscopic polypectomy. This was a retrospective clinical cohort study involving 464 patients who underwent their first FET after polyp resection between January 2021 and July 2023. The cohorts were categorized into three groups: the natural cycle (NC) group (n = 139), the ovarian induction (OI) group (n = 117), and the hormone replacement therapy (HRT) group (n = 208). In the initial unadjusted analysis, both NC and OI cycles exhibited similar pregnancy rates but were associated with significantly higher implantation rate (56.5%, 57.1% vs 42.0%, P < 0.001), clinical pregnancy rate (73.4%, 74.4% vs 57.2%, P = 0.001), and ongoing pregnancy rate (OPR; 67.6%, 63.2% vs 51.0%, P = 0.005) compared to the HRT group. Additionally, the three groups demonstrated comparable abortion rate (7.8%, 14.9% vs 10.9%, P = 0.299). After adjusting for potential confounders in the multiple logistic regression model, the HRT protocol resulted in a 54% significantly lower OPR compared to the NC protocol (adjusted odds ratio [aOR] = 0.46, 95% confidence interval [CI]: 0.28-0.77; P = 0.003). Meanwhile, the OPR difference between the OI protocol and the NC protocol remained insignificant (OI vs NC: aOR = 0.62, 95% CI: 0.35-1.12; P = 0.112). The ovulatory-FET scheme (NC and OI) following hysteroscopic polyp resection displayed promising clinical outcomes compared with HRT-FET scheme. The regimen without exogenous estrogen administration should be prioritized for endometrial preparation protocol after polypectomy.

The Effects of Flaxseed Consumption on Glycemic Control in Native American Postmenopausal Women with Hyperglycemia and Hyperlipidemia.

Glucose control in postmenopausal women is influenced by many factors, such as hormones, lifestyle variables, and genetics. Limited data exist on the effect of whole flaxseed on glucose status in postmenopausal Native American women. The aim of this study was to investigate the glucose management effect of a flaxseed dietary intervention on postmenopausal Native American women. In this study, 55 Native American postmenopausal women (aged 47-63 years) with borderline hyperglycemia (>100 and <126 mg/dL) and mild to moderate hypercholestorolemia (≥200 to ≤380 mmol/L), who were not on hormone replacement therapy, were enrolled. Participants were randomly assigned to one of the three dietary regimens (control, flaxseed, and flaxseed + fiber) for three months, receiving interventions in the form of bread, muffins, and flaxseed powder. Despite daily consumption of flaxseed across diverse food formats, no significant changes in glucose (p = 0.3, p = 0.2), insulin levels (p = 0.59, p = 0.9), or HOMA-IR (p = 0.84, p = 0.66) were observed compared to their respective baseline values within the flaxseed and flaxseed + fiber groups, respectively. Conversely, the control group showed a significant rise in final glucose values from baseline (p = 0.01). However, the incorporation of ground flaxseed into low-glycemic foods holds potential for beneficial effects through maintaining glucose status among postmenopausal Native American women. This research provides critical insights into the effects of flaxseed, emphasizing the need for continued exploration to understand its role in supporting glucose management among postmenopausal Native American women. Further exploration is required to investigate the potential long-term impact and the use of flaxseed in managing glucose levels in this demographic.

Effect of ovariectomy and high-fat diet on the expression of estrogen receptors and adipose tissue metabolism in wistar rats

This study addresses the increasing prevalence of obesity, especially among postmenopausal. Estrogen plays a crucial role in regulating adipose tissue in women, with its absence after menopause associated with metabolic complications. The study aimed to determine the lipolytic activity in different adipose tissue depots of ovariectomized rats submitted to a high-fat diet. Also, to analyze the expression of estrogen receptors in adipose tissues and perform histological and morphometric analyzes of these deposits. Female rats were ovariectomized (O) or sham operated (S). The animals were divided into groups: ovariectomized with high-fat diet (OF), sham-operated with high-fat diet (SF), ovariectomized with control diet (OC) or sham-operated with control diet as the control group (SC). After 24 weeks of consuming the diets, rats were killed and adipose tissue deposits were removed. Polymerase chain reaction was performed to analyze the expression of estrogen receptors in adipose tissues, lipolysis assay and histological analysis. Both the high-fat diet and ovariectomy increased body weight and adiposity. There was hypertrophy of adipocytes. Estrogen replacement therapy modulate lipolytic activity in different adipose depots, with different responses in relation to estrogen receptors. Estrogen receptor expression varied between fat depots. Mesenteric adipose tissue showed greater sensitivity to estrogen compared with others. Estrogen increased lipolytic activity in some fat depots, reducing in others. Expression of ERs depends of hormonal status and adipose tissue location, which may explain distinct actions of estrogen on the metabolism of adipose tissue and on the production of adipokines by them.

In vitro effects and mechanisms of Humulus lupulus extract on bone marrow progenitor cells and endothelial cells

Osteoporosis is the most common metabolic bone disorder and is associated with a high incidence of fractures. Angiogenesis and adequate blood flow are important during bone repair and maintenance. Estrogens play a key role in bone formation, in the prevention of bone resorption and vasculature maintenance. Hormone replacement therapy (HRT) has been used with great benefits for bone fracture prevention but has been linked to the development of serious important side effects, including cancer and stroke. Phytoestrogens are an attractive alternative to HRT because their chemical structure is similar to estradiol but, they could behave as selective modulators: acting as antagonists of estrogen receptors in the breast and endometrium and as agonists in the vascular endothelium and bone. Hops contain a wide variety of phytoestrogens that have individually been shown to possess estrogenic activity by either blocking or mimicking. In this study we have to evaluate the in vitro effects and mechanisms of action of hops extracts on the osteogenic and adipogenic capacity of bone marrow progenitor cells (BMPCs), and the angiogenic potential of EA.hy926 endothelial cells. We show that hops extracts increase the proliferative capacity of BMPCs and promote their osteogenic differentiation while decreasing their pro-osteoclastogenic capacity; and that these effects are mediated by the MAPK pathway. Additionally, hops extracts prevent the adipogenic differentiation of BMPCs and promote endothelial cell activity, by mechanisms also partially mediated by MAPK.

Silkworm (Bombyx mori L.) Has Beneficial Effects on Menopausal Symptoms by Enhancing Estrogen Receptor Signaling in Ovariectomized Mice.

Existing hormone replacement therapy for menopause has drawbacks, necessitating new treatment agents. Silkworms have demonstrated estrogenic properties, offering promising alternatives. We assessed the therapeutic effects of freeze-dried silkworm powder (SWP) on menopausal symptoms using an ovariectomized (OVX) mouse model. The experimental design comprised a sham surgery group (Sham), an OVX control group, a low-dose SWP group post-OVX (80 mg/kg, OVX-SWP-L), a high-dose SWP group post-OVX (160 mg/kg, OVX-SWP-H), and an estradiol treatment group post-OVX (OVX-E2). Treatments were administered orally thrice weekly over eight weeks; body weight was monitored weekly. The SWP-treated groups (SWP-L and SWP-H) exhibited less weight gain and increased uterine thickness than the OVX control. Molecular analyses demonstrated that SWP significantly enhanced the phosphorylation of estrogen receptor alpha (ERα), ERK, and AKT. Furthermore, biochemical assays revealed reduced serum neutral lipids across all SWP treatment groups. Notably, HDL-cholesterol levels were significantly increased in the SWP-L group compared to the OVX group. Serum estradiol concentrations were elevated in all the SWP groups, with significant increases in the high-dose group. These findings indicate that SWP may promote the activation of estrogen receptor signaling and improve symptoms associated with estrogen deficiency during menopause.