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Search Results (243)

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Keywords = hormone replacement treatment

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20 pages, 1388 KiB  
Article
Beyond Bone Mineral Density: Real-World Fracture Risk Profiles and Therapeutic Gaps in Postmenopausal Osteoporosis
by Anamaria Ardelean, Delia Mirela Tit, Roxana Furau, Oana Todut, Gabriela S. Bungau, Roxana Maria Sânziana Pavel, Bogdan Uivaraseanu, Diana Alina Bei and Cristian Furau
Diagnostics 2025, 15(15), 1972; https://doi.org/10.3390/diagnostics15151972 - 6 Aug 2025
Abstract
Background/Objectives: Osteoporosis remains a leading cause of morbidity in postmenopausal women, yet many high-risk individuals remain undiagnosed or untreated. This study aimed to assess the prevalence of osteoporosis and osteopenia, treatment patterns, and skeletal fragility indicators in a large cohort of postmenopausal [...] Read more.
Background/Objectives: Osteoporosis remains a leading cause of morbidity in postmenopausal women, yet many high-risk individuals remain undiagnosed or untreated. This study aimed to assess the prevalence of osteoporosis and osteopenia, treatment patterns, and skeletal fragility indicators in a large cohort of postmenopausal women undergoing DXA screening. Methods: We analyzed data from 1669 postmenopausal women aged 40–89 years who underwent DXA evaluation. BMD status was categorized as normal, osteopenia, or osteoporosis. Treatment status was classified based on active antiosteoporotic therapy, calcium/vitamin D supplementation, hormonal therapy (historical use), or no treatment. Logistic regression models were used to explore independent predictors of osteoporosis and treatment uptake. Results: A total of 45.0% of women had osteoporosis and 43.5% had osteopenia. Despite this, 58.5% of the population, over half of women with osteoporosis, were not receiving any active pharmacologic treatment. Bisphosphonates were the most prescribed therapy (17.9%), followed by calcium/vitamin D supplements (20.6%). A prior history of fragility fractures and radiological bone lesions were significantly associated with lower BMD (p < 0.05). Historical hormone replacement therapy (HRT) use was not associated with current BMD (p = 0.699), but women with HRT use reported significantly fewer fractures (p < 0.001). In multivariate analysis, later menopause age and low BMD status predicted higher odds of receiving active treatment. Conclusions: Our findings highlight a substantial care gap in osteoporosis management, with treatment primarily initiated reactively in more severe cases. Improved screening and earlier intervention strategies are urgently needed to prevent fractures and reduce the long-term burden of osteoporosis. Full article
(This article belongs to the Special Issue Diagnosis and Management of Osteoporosis)
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21 pages, 13450 KiB  
Article
Distinctive Characteristics of Rare Sellar Lesions Mimicking Pituitary Adenomas: A Collection of Unusual Neoplasms
by Andrej Pala, Nadja Grübel, Andreas Knoll, Gregor Durner, Gwendolin Etzrodt-Walter, Johannes Roßkopf, Peter Jankovic, Anja Osterloh, Marc Scheithauer, Christian Rainer Wirtz and Michal Hlaváč
Cancers 2025, 17(15), 2568; https://doi.org/10.3390/cancers17152568 - 4 Aug 2025
Viewed by 14
Abstract
Background/Objectives: Pituitary tumors account for over 90% of all sellar region masses. However, a spectrum of rare neoplastic, inflammatory, infectious, and vascular lesions—benign and malignant—can arise in the intra- and parasellar compartments and clinically and radiologically mimic PitNETs. We report a cohort [...] Read more.
Background/Objectives: Pituitary tumors account for over 90% of all sellar region masses. However, a spectrum of rare neoplastic, inflammatory, infectious, and vascular lesions—benign and malignant—can arise in the intra- and parasellar compartments and clinically and radiologically mimic PitNETs. We report a cohort of 47 such rare and cystic midline intracranial lesions, emphasizing their distinctive morphological, clinical, and imaging features and the personalized treatment strategies applied. Methods: In this retrospective single-center study, we reviewed all patients treated for suspected PitNETs via transsphenoidal approach between 2015 and 2024. Of 529 surgical cases, we excluded confirmed PitNETs, meningiomas, and classical intradural craniopharyngiomas. Collected data encompassed patient demographics, tumor characteristics, presenting symptoms, extent of resection or medical therapy, endocrine outcomes, and follow-up information. Results: Among all 529 patients who underwent surgical treatment for sellar lesions from 2015 to 2024, 47 cases (8.9%) were identified as rare or cystic masses. Forty-six underwent transsphenoidal resection; one patient with hypophysitis received corticosteroid therapy alone. Presenting symptoms included headache (n = 16), dizziness (n = 5), oculomotor disturbances (n = 2), and visual impairment (n = 17). Endocrine dysfunction was found in 30 patients, 27 of whom required hydrocortisone replacement. Histopathological diagnoses were led by colloid cysts (n = 14) and Rathke’s cleft cysts (n = 11). The remaining 22 cases comprised plasmacytoma, germinoma, lymphoma, pituicytoma, inverted papilloma, metastatic carcinoma, chordoma, nasopharyngeal carcinoma, chloroma, and other rare entities. Preoperative imaging diagnosis proved incorrect in 38% (18/47) of cases, with several lesions initially misidentified as PitNETs. Conclusions: Nearly 9% of presumed PitNETs were rare, often benign or inflammatory lesions requiring distinct management. Most could be safely resected and demonstrated excellent long-term outcomes. Yet, despite advanced imaging techniques, accurate preoperative differentiation remains challenging, with over one-third misdiagnosed. Clinical red flags—such as early hormone deficits, rapid progression or atypical imaging findings—should prompt early interdisciplinary evaluation and, when indicated, image-guided biopsy to avoid unnecessary surgery and ensure tailored therapy. Full article
(This article belongs to the Special Issue Pituitary Tumors: Clinical and Surgical Challenges)
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38 pages, 1678 KiB  
Review
Rethinking Osteoporosis Drugs: Can We Simultaneously Address Sarcopenia?
by Zoran Gavrilov and Jasna Lojk
Int. J. Mol. Sci. 2025, 26(14), 6924; https://doi.org/10.3390/ijms26146924 - 18 Jul 2025
Viewed by 514
Abstract
Osteoporosis and sarcopenia are two aspects of the geriatric syndrome that frequently occur together and affect one another in a condition referred to as osteosarcopenia. Preventive and treatment options for osteosarcopenia exist but are mainly focused on the treatment of osteoporosis, as there [...] Read more.
Osteoporosis and sarcopenia are two aspects of the geriatric syndrome that frequently occur together and affect one another in a condition referred to as osteosarcopenia. Preventive and treatment options for osteosarcopenia exist but are mainly focused on the treatment of osteoporosis, as there is still no FDA-approved treatment for sarcopenia. Drugs for osteoporosis include antiresorptive and anabolic drugs and hormonal replacement therapies and are prescribed based on age, BMD and other patient characteristics, which, however, do not include the possible co-existence of sarcopenia. As several studies and clinical trials have shown that the pharmacological treatment of osteoporosis can also affect muscle tissue, in either a positive or negative manner, sarcopenia should be another factor affecting the choice of treatment, especially when facing equal treatment options for osteoporosis. The aim of this review was to summarize our current knowledge on the effects of FDA-approved drugs for the treatment of osteoporosis on muscle quality, mass and function. A better understanding of the effects that certain drugs have on muscle tissue might in the future help us to simultaneously at least partially also address the wasting of muscle tissue and avoid further pharmacologically induced decline. Full article
(This article belongs to the Section Molecular Pharmacology)
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24 pages, 657 KiB  
Article
Sexual Functioning and Depressive Symptoms in Levothyroxine-Treated Women with Postpartum Thyroiditis and Different Vitamin D Status
by Karolina Kowalcze, Joanna Kula-Gradzik, Anna Błaszczyk and Robert Krysiak
Nutrients 2025, 17(13), 2091; https://doi.org/10.3390/nu17132091 - 24 Jun 2025
Viewed by 487
Abstract
Background/Objectives: Hypothyroidism and thyroid autoimmunity have a negative effect on women’s sexual health, which is only partially reversed by thyroid hormone substitution. Sexual functioning in thyroid disorders after delivery has been poorly researched. The aim of our study was to compare the [...] Read more.
Background/Objectives: Hypothyroidism and thyroid autoimmunity have a negative effect on women’s sexual health, which is only partially reversed by thyroid hormone substitution. Sexual functioning in thyroid disorders after delivery has been poorly researched. The aim of our study was to compare the effect of levothyroxine on sexual response and depressive symptoms in women with postpartum thyroiditis (PPT) and different vitamin D status. Methods: The study population consisted of three matched groups of women with the hypothyroid phase of PPT: two groups with subclinical and one with overt thyroid hypofunction. Each group included similar numbers of women with normal and low vitamin D status. For the following six months, one group of women with subclinical hypothyroidism and all women with overt thyroid hypofunction received levothyroxine. At the beginning and at the end of the study, all participants completed questionnaires evaluating female sexual function (FSFI) and depressive symptoms (BMI-II). The remaining outcomes of interest included thyroid antibody titers, and the serum levels of 25-hydroxyvitamin D, TSH, free thyroid hormones, sex hormones, and prolactin. Results: Before levothyroxine substitution, women with overt and subclinical disease differed in the total FSFI score, all domain scores, and the overall BDI-II score. Within each study group, domain scores for desire were greater in women with vitamin D sufficiency than in those with vitamin D deficiency/insufficiency. Testosterone and estradiol levels were lower in women with overt than in women with subclinical hypothyroidism, while the opposite relationship was found for prolactin. Levothyroxine treatment improved all domains of female sexual function and reduced the total BDI-II score in both patients with overt and subclinical hypothyroidism and normal vitamin D status. In women with vitamin D deficiency/insufficiency, the impact of this agent was limited to arousal, lubrication, and sexual satisfaction. Levothyroxine replacement reduced thyroid antibody titers only in women with normal vitamin D status. The impact on testosterone was limited to women with normal vitamin D status, and was more pronounced in women with overt than subclinical disease. The effect on estradiol and prolactin, observed only in overt disease, was unrelated to vitamin D status. The increase in sexual functioning correlated with the following: 25-hydroxyvitamin D levels (in vitamin D-deficient/insufficient women); the impact on thyroid peroxidase antibodies, free triiodothyronine and testosterone (for desire and arousal); and the changes in the overall BDI-II score. Five years later, the quality of life was better in vitamin D-sufficient women receiving levothyroxine in the postpartum period. Conclusions: Low vitamin D status attenuates the impact of levothyroxine on female sexual function and depressive symptoms in women with the hypothyroid phase of PPT. Full article
(This article belongs to the Special Issue Vitamins and Human Health: 3rd Edition)
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19 pages, 1701 KiB  
Article
A Preclinical Investigation of Estrogenic Bone Protection in a Hypertensive Rat Model Under Gender-Affirming Hormone Therapy
by Lucas Streckwall, Germán A. Colareda, Daiana Escudero, Romina G. Diaz and Juan M. Fernández
Biology 2025, 14(6), 650; https://doi.org/10.3390/biology14060650 - 3 Jun 2025
Viewed by 550
Abstract
The goal of gender-affirming hormone therapy (GAHT) is to align an individual’s physical characteristics with their gender identity by suppressing endogenous sex hormones and replacing them with those consistent with their gender. Transgender women undergoing GAHT are at higher risk of cardiovascular complications, [...] Read more.
The goal of gender-affirming hormone therapy (GAHT) is to align an individual’s physical characteristics with their gender identity by suppressing endogenous sex hormones and replacing them with those consistent with their gender. Transgender women undergoing GAHT are at higher risk of cardiovascular complications, and since clinical evidence suggests that hypertension is associated with increased bone loss, we investigated the effects of estrogen treatment on bone health in a hypertensive transgender animal model. Male spontaneously hypertensive rats were orchiectomized (Orch), and half of them received estrogen treatment (Orch + Es), while a third group remained intact as controls. Bone marrow progenitor cells (BMPCs) were isolated to assess osteogenic potential, and femurs were collected for histological and mechanical analysis. BMPCs from Orch + Es rats exhibited enhanced osteogenic potential compared to those from Orch rats. Histological analysis revealed a higher number of osteocytes and fewer adipocytes in the Orch + Es group. Mechanical testing showed reduced bone strength in Orch rats, which was partially preserved in Orch + Es animals. In conclusion, estrogen administration mitigated the deleterious effects of testosterone depletion on BMPCs and provided protective effects on bone structure and strength in this preclinical model of GAHT in hypertensive rats. Full article
(This article belongs to the Special Issue Osteoblast Differentiation in Health and Disease)
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12 pages, 890 KiB  
Article
Evaluation of Epigenetic Age Acceleration in Growth Hormone (GH)-Deficient Children After 6 Months of Recombinant Human GH Replacement Therapy: Anti-Ageing GH vs. Pro-Ageing Insulin-like Growth Factor 1 (IGF-1)?
by Antonello E. Rigamonti, Valentina Bollati, Chiara Favero, Benedetta Albetti, Adele Bondesan, Nicoletta Marazzi, Silvano G. Cella and Alessandro Sartorio
J. Clin. Med. 2025, 14(11), 3840; https://doi.org/10.3390/jcm14113840 - 29 May 2025
Viewed by 486
Abstract
Background: One of the most debated topics in experimental and clinical endocrinology is the impact of hypo- and hyper-somatotropism on the extension/shortening of the lifespan, the results of experimental, clinical, and epidemiological studies being extremely conflicting. Biological age, a surrogate of lifespan, can [...] Read more.
Background: One of the most debated topics in experimental and clinical endocrinology is the impact of hypo- and hyper-somatotropism on the extension/shortening of the lifespan, the results of experimental, clinical, and epidemiological studies being extremely conflicting. Biological age, a surrogate of lifespan, can be measured through different methods, including the age-related epigenetic modifications of DNA. Objective: The present study aimed to evaluate the biological (epigenetic) age and age acceleration in a group of growth hormone (GH)-deficient (GHD) children (F/M = 5/5; age: 11.0 ± 2.7 years), treated with recombinant human GH (rhGH) for 6 months at a daily dose of 0.025–0.035 mg/kg. Results: Treatment with rhGH significantly increased height velocity and circulating insulin-like growth factor 1 (IGF-1) levels. Biological and chronological ages were significantly correlated at baseline and after 6 months of rhGH replacement therapy. Treatment with rhGH reduced age acceleration, an effect that became significant only after adjustment for IGF-1. In a linear regression model for longitudinal data, after adjustment for rhGH treatment, age acceleration was significantly associated with IGF-1 levels, an effect missing when considering the interaction rhGH treatment × age acceleration at 6 months of rhGH treatment. Conclusions: (rh)GH, when administered to GHD children, exerts anti-ageing effects, which become evident after removal of the presumably pro-ageing effects of IGF-1. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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37 pages, 1073 KiB  
Review
Cognitive Function in Peri- and Postmenopausal Women: Implications for Considering Iron Supplementation
by Mun Sun Choi, Emily R. Seiger and Laura E. Murray-Kolb
Nutrients 2025, 17(11), 1762; https://doi.org/10.3390/nu17111762 - 23 May 2025
Viewed by 1046
Abstract
Menopause is associated with significant hormonal and reproductive changes in women. Evidence documents interindividual differences in the signs and symptoms associated with menopause, including cognitive decline. Hypothesized reasons for the cognitive decline include changes in hormone levels, especially estrogen, but study findings have [...] Read more.
Menopause is associated with significant hormonal and reproductive changes in women. Evidence documents interindividual differences in the signs and symptoms associated with menopause, including cognitive decline. Hypothesized reasons for the cognitive decline include changes in hormone levels, especially estrogen, but study findings have been inconsistent. Hormone replacement therapies (HRTs) are often recommended to alleviate menopause-related symptoms in both peri- and postmenopausal women. However, the North American Menopause Society does not recommend the use of HRT for the management of cognitive complaints in perimenopausal women due to lack of evidence. Additionally, there are many women for which the use of HRT is contraindicated. As such, it would be helpful to have an alternative method for alleviating symptoms, including declines in cognition, during the menopause transition. Iron supplementation may be a promising candidate as it has been associated with improved cognitive performance in premenopausal women with iron deficiency and iron deficiency anemia. Because many women will experience heavy blood losses during perimenopause, they are at risk of becoming iron deficient and/or anemic. The use of iron supplementation in women with iron deficiency may serve to not only improve iron status but also to alleviate many of the signs and symptoms associated with perimenopause (lethargy, depressed affect, etc.), including cognitive decline. However, evidence to inform treatment protocols is lacking. Well-designed studies of iron supplementation in perimenopausal women are needed in order to understand the potential of such supplementation to alleviate the cognitive decline associated with perimenopause. Full article
(This article belongs to the Special Issue Iron and Brain and Cognitive Function Across the Lifespan)
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32 pages, 2325 KiB  
Review
Comprehensive Evaluation and Future Perspectives of Non-Surgical Contraceptive Methods in Female Cats and Dogs
by Sheila I. Peña-Corona, Melissa Aurea Vaquera-Guerrero, José Cerbón-Gutiérrez, Juan I. Chávez-Corona, Adrián E. Iglesias-Reyes, Alonso Sierra-Reséndiz, Juan José Pérez-Rivero, Socorro Retana-Márquez, Pablo Adrián Vizcaino-Dorado, David Quintanar-Guerrero, Gerardo Leyva-Gómez and Dinorah Vargas-Estrada
Animals 2025, 15(10), 1501; https://doi.org/10.3390/ani15101501 - 21 May 2025
Viewed by 1169
Abstract
The issue of stray cats and dogs is a global concern with considerable implications for animal welfare and public health. This review aims to provide an updated and comprehensive analysis of non-surgical contraceptive methods tested in studies controlled in vivo in feline and [...] Read more.
The issue of stray cats and dogs is a global concern with considerable implications for animal welfare and public health. This review aims to provide an updated and comprehensive analysis of non-surgical contraceptive methods tested in studies controlled in vivo in feline and canine females. Immunocontraception via vaccination against gonadotropin-releasing hormone (GnRH), the luteinizing hormone receptor, zona pellucida proteins, and sperm, or use of viral-vectored delivery, is yet developing. Hormonal treatment (progestins, androgens, or GnRH) analogs act directly to block the reproductive axis. However, it produced essential side effects. Analogs of kisspeptin, non-steroid anti-inflammatory drugs such as firocoxib, and delivery of cytotoxins to the pituitary have shown non-conclusive results. Additional methods have also been tested, such as intraovarian injection of necrosing compounds or intravaginal and intrauterine devices. At present, neither of these methods offers permanent sterility that can replace surgical sterilization techniques. To our knowledge, none are currently authorized by the Food and Drug Administration (FDA) or the European Medicines Agency (EMA) for contraceptive methods or sterilization of cats or dogs. Therefore, it is necessary to continue the development of a compound that warrants the sterility of cats and dogs. Full article
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15 pages, 1447 KiB  
Article
Effects of Hormone Replacement Treatment with Estrogen and Progestins on the Vascular Renin–Angiotensin System of Ovariectomized Rats
by Laís Almeida Menezes, Patrick Wander Endlich, Deiviany Santana Santos Lima, A. Augusto Peluso, Simone Alves de Almeida, Mariana Veronez Borgo, Robson Augusto Souza Santos and Glaucia Rodrigues de Abreu
Int. J. Mol. Sci. 2025, 26(10), 4930; https://doi.org/10.3390/ijms26104930 - 21 May 2025
Viewed by 565
Abstract
The renin–angiotensin system (RAS) is the main endocrine and tissular component responsible for controlling cardiovascular homeostasis, which can be modulated by estrogen levels. This study investigated the effects of hormone treatments with estrogen and progestins on angiotensin-(1-7)-mediated [Ang-(1-7)] vasodilation in ovariectomized rats and [...] Read more.
The renin–angiotensin system (RAS) is the main endocrine and tissular component responsible for controlling cardiovascular homeostasis, which can be modulated by estrogen levels. This study investigated the effects of hormone treatments with estrogen and progestins on angiotensin-(1-7)-mediated [Ang-(1-7)] vasodilation in ovariectomized rats and the possible mechanisms involving the RAS. Female Wistar rats were divided into the following groups: sham (SHAM), ovariectomized (OVX), OVX and treated with 17β-estradiol (E2) (OE2), OVX and treated with E2 and drospirenone (OE2 + DRSP), and OVX and treated with medroxyprogesterone (MPA). Hormonal treatment was delivered via gavage for 28 days. Vascular responses to Ang-(1-7) were assessed in isolated aortic rings, and a Western blot of the thoracic aorta was used to determine the protein levels of angiotensin II (Ang II) type-1 receptor (AT1R), Ang II type-2 receptor (AT2R), Ang-(1-7) receptor (Mas), angiotensin-converting enzyme 2 (ACE2), and endothelial nitric oxide synthase (eNOS). The results showed impaired vascular reactivity caused by ovariectomy. Ang-(1-7) induced vasodilation in the OE2, OE2 + DRSP, and MPA-treated groups, while the administration of the AT2R antagonist (PD123319) or the selective Mas antagonist (A779) increased the extent of vasorelaxation induced by Ang-(1-7) in the OVX + MPA group. There were no differences in the aortic levels of AT1R or ACE2 between the groups, but the MPA group showed significantly increased levels of AT2R and eNOS. We concluded that ovariectomy induced vascular dysfunction linked to RAS regulation, and both estrogen (E2) and progestins differentially restored these parameters. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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22 pages, 2887 KiB  
Article
Therapeutic Advantages of Isoflavone Glycoside and Aglycone Forms of Sophoricoside in the Amelioration of Postmenopausal Symptoms: Bone Health, Metabolic Regulation, and Systemic Inflammation
by Jeong-Won Ahn, Hyun-Soo Kim, Kongara Damodar, Hee-Hyun Shin, Kyung-Mi Kim, Jung-Youl Park, Yeong-Min Yoo, Jae-Chul Jung and Seong-Soo Joo
Molecules 2025, 30(10), 2218; https://doi.org/10.3390/molecules30102218 - 20 May 2025
Viewed by 596
Abstract
This study investigates the therapeutic potential of sophoricoside and its aglycone metabolite, genistein, derived from Styphnolobium japonicum L. fruit, as natural alternatives to hormone replacement therapy for postmenopausal symptom management. Using Lactobacillus plantarum to model intestinal biotransformation, we compared glycoside-rich (Rex) and aglycone-rich [...] Read more.
This study investigates the therapeutic potential of sophoricoside and its aglycone metabolite, genistein, derived from Styphnolobium japonicum L. fruit, as natural alternatives to hormone replacement therapy for postmenopausal symptom management. Using Lactobacillus plantarum to model intestinal biotransformation, we compared glycoside-rich (Rex) and aglycone-rich (Rex-AG) extracts in ovariectomized rats. Both treatments significantly reduced weight gain and alleviated vaginal dryness, with Rex demonstrating superior thermoregulatory stabilization. Histological and molecular analyses revealed preserved trabecular bone integrity through the downregulation of RANKL and upregulation of TGF-β. Both extracts exhibited potent anti-inflammatory effects in adipose tissue, suppressing IL-6 and TNF-α, while regulating adipogenesis markers (FABP4, KLF, leptin, PPARγ) more effectively than 17β-estradiol. Serum genistein concentrations confirmed its efficient biotransformation and systemic bioavailability. Importantly, the treatments showed favorable safety profiles with no adverse effects on organ weight. These findings establish S. japonicum L. fruit-derived phytoestrogens as promising candidates for the comprehensive management of postmenopausal symptoms, offering an efficacious and safer alternative to conventional hormone therapy. Full article
(This article belongs to the Section Natural Products Chemistry)
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30 pages, 5825 KiB  
Article
Estradiol Reverses Ovariectomy-Induced Disruption of Hypothalamic Gene Expression and Behavior via Modulation of Gonadotropin Releasing Hormone and Calcium Signaling Pathways
by Asim Muhammad, Mubashir Muhammad, Xiaohuan Chao, Chunlei Zhang, Jiahao Chen, Huan Yang, Shuhan Liu, Yuan Ding, Ziming Wang, Hongwei Bi, Wen Guo, Junhong Fan and Bo Zhou
Animals 2025, 15(10), 1467; https://doi.org/10.3390/ani15101467 - 19 May 2025
Cited by 1 | Viewed by 535
Abstract
Estrogen plays a crucial role in regulating reproductive and neuroendocrine functions, yet the molecular mechanisms underlying its effects on the hypothalamus remain incompletely understood. This study investigates the transcriptional and behavioral changes induced by ovariectomy (OVX) and estradiol (E2) supplementation in female C57BL/6J [...] Read more.
Estrogen plays a crucial role in regulating reproductive and neuroendocrine functions, yet the molecular mechanisms underlying its effects on the hypothalamus remain incompletely understood. This study investigates the transcriptional and behavioral changes induced by ovariectomy (OVX) and estradiol (E2) supplementation in female C57BL/6J mice. RNA sequencing was performed to identify differentially expressed genes (DEGs) across control (CK), E2, OVX, and OVX+E2 groups, followed by functional enrichment and pathway analyses. Behavioral assessments, including open field, Y-maze, and elevated plus maze tests, were conducted to evaluate anxiety-like and cognitive behaviors. Results revealed significant alterations in GnRH signaling, neurotransmission, and inflammatory pathways, with key genes such as Elk1, Prkcb, and Camk2a differentially expressed in response to estrogen modulation. OVX-induced neuroendocrine disruptions were partially reversed by E2 treatment, as evidenced by transcriptomic and behavioral outcomes. Pearson correlation analysis further linked gene expression patterns with phenotypic traits, providing insights into estrogen’s regulatory mechanisms in the hypothalamus. These findings enhance our understanding of estrogen-mediated neuroendocrine regulation and may have implications for hormone replacement therapies in postmenopausal disorders. Full article
(This article belongs to the Special Issue Behavioral and Cognitive Genomics in Animals)
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8 pages, 394 KiB  
Article
Benchmark for Setting ACTH Cell Dosage in Clinical Regenerative Medicine for Post-Operative Hypopituitarism
by Tatsuma Kondo, Hidetaka Suga, Kazuhito Takeuchi, Yutaro Fuse, Yoshiki Sato, Toshiaki Hirose, Harada Hideyuki, Yuichi Nagata and Ryuta Saito
Diseases 2025, 13(4), 112; https://doi.org/10.3390/diseases13040112 - 10 Apr 2025
Viewed by 564
Abstract
Background/Objectives: Our objective is to develop hormone-producing pituitary cells that can function in the same manner as the human body and provide more effective treatments than current hormone replacement therapy. We have already established a technique for generating hypothalamic–pituitary organoids using feeder-free human [...] Read more.
Background/Objectives: Our objective is to develop hormone-producing pituitary cells that can function in the same manner as the human body and provide more effective treatments than current hormone replacement therapy. We have already established a technique for generating hypothalamic–pituitary organoids using feeder-free human pluripotent stem cells (hPSCs) and demonstrated their effectiveness in vivo through transplantation into hypopituitary mouse models. To prospectively determine the upper limit of transplanting adenohypophyseal cells into humans, we investigated the human maximum secretion capacity of adrenocorticotropic hormone (ACTH) and growth hormone (GH). Methods: We analyzed data from 28 patients with pituitary adenomas, among whom 16 evinced no abnormality of ACTH secretion and 12 showed no GH secretion on corticotropin-releasing hormone (CRH) and growth hormone-releasing hormone-2 (GHRP-2) stimulation testing. Results: The average ACTH peak value after CRH stimulation tests was 97.2 pg/mL, and the average GH peak value after GHRP-2 stimulation tests was 25.1 ng/mL. Conclusions: These data will likely serve as benchmarks of ACTH and GH secretion when transplanting cultured cells into humans. Full article
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17 pages, 2384 KiB  
Article
The Contractile Function of Ventricular Cardiomyocytes Is More Sensitive to Acute 17β-Estradiol Treatment Compared to Atrial Cardiomyocytes
by Tatiana A. Myachina, Xenia A. Butova, Raisa A. Simonova, Denis A. Volzhaninov, Anastasia M. Kochurova, Galina V. Kopylova, Daniil V. Shchepkin and Anastasia D. Khokhlova
Cells 2025, 14(8), 561; https://doi.org/10.3390/cells14080561 - 8 Apr 2025
Viewed by 623
Abstract
17β-estradiol (E2) is the most active metabolite of estrogen with a wide range of physiological action on cardiac muscle. Previous studies have reported E2 effects predominantly for the ventricles, while the E2 impact on the atria has been less examined. In this study, [...] Read more.
17β-estradiol (E2) is the most active metabolite of estrogen with a wide range of physiological action on cardiac muscle. Previous studies have reported E2 effects predominantly for the ventricles, while the E2 impact on the atria has been less examined. In this study, we focused on the direct E2 effects on atrial and ventricular contractility at the cellular and molecular levels. Single atrial and ventricular cardiomyocytes (CM) from adult (24 weeks-old) female Wistar rats were incubated with 10 nM E2 for 15 min. Sarcomere length and cytosolic [Ca2+]i transients were measured in mechanically non-loaded CM, and the tension–length relationship was studied in CM mechanically loaded by carbon fibers. The actin–myosin interaction and sarcomeric protein phosphorylation were analyzed using an in vitro motility assay and gel electrophoresis with Pro-Q Diamond phosphoprotein stain. E2 had chamber-specific effects on the contractile function of CM with a pronounced influence on ventricular CM. The characteristics of [Ca2+]i transients did not change in both atrial and ventricular CM. However, in ventricular CM, E2 reduced the amplitude and maximum velocity of sarcomere shortening and decreased the slope of the passive tension–length relationship that was associated with increased TnI and cMyBP-C phosphorylation. E2 treatment accelerated the cross-bridge cycle of both atrial and ventricular myosin that was associated with increased phosphorylation of the myosin essential light chain. This study shows that E2 impairs the mechanical function of the ventricular myocardium while atrial contractility remains mostly preserved. Hormonal replacement therapy (HRT) with estrogen is by far the most effective therapy for treating climacteric symptoms experienced during menopause. Here we found a chamber specificity of myocardial contractile function to E2 that should be taken into account for the potential side effects of HRT. Full article
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8 pages, 247 KiB  
Communication
Endocrinology of Primary Ovarian Insufficiency: Diagnostic and Therapeutic Clues
by Jan Tesarik
Endocrines 2025, 6(2), 18; https://doi.org/10.3390/endocrines6020018 - 8 Apr 2025
Viewed by 1301
Abstract
Background: This paper briefly reviews the most important endocrine features of primary ovarian insufficiency (POI) and shows their relevance for the diagnosis and treatment of this condition. Introduction: Endocrine disturbances in POI cause problems for both the fertility and general health status of [...] Read more.
Background: This paper briefly reviews the most important endocrine features of primary ovarian insufficiency (POI) and shows their relevance for the diagnosis and treatment of this condition. Introduction: Endocrine disturbances in POI cause problems for both the fertility and general health status of the affected women. Both subfertility and infertility result from the depletion of growing ovarian follicles which, in its turn, is the causative factor of hypoestrogenism; this is responsible for most of the general health problems affecting women. Method: Search of literature. Results and conclusion: A combination of high-serum follicle-stimulating hormone (FSH) and low 17β-estradiol (E2) concentrations is a key feature characterizing POI and is the decisive element for POI diagnosis. However, an in-depth search for possible genetic and non-genetic causes is important for adequate counseling regarding prevention and early intervention. The treatment of general health problems, based on correcting hypoestrogenism through hormone replacement therapy (HRT), is relatively easy. On the other hand, resolving infertility is a much more difficult task, and oocyte donation is the only really efficient instrument. Fertility preservation is a suitable alternative in patients with early POI diagnosis, in whom some viable follicles are still present in the ovaries. In patients who refuse oocyte donation, intraovarian injection of autologous platelet-rich plasma and in vitro activation of dormant follicles may be considered. Other innovative treatments, such as stem cell therapies or nuclear transfer, are currently under investigation. Full article
(This article belongs to the Section Female Reproductive System and Pregnancy Endocrinology)
68 pages, 19995 KiB  
Review
Sexual Dimorphism in Cardiometabolic Diseases: From Development to Senescence and Therapeutic Approaches
by Thea Chevalley, Marion Dübi, Laurent Fumeaux, Maria Serena Merli, Alexandre Sarre, Natacha Schaer, Umberto Simeoni and Catherine Yzydorczyk
Cells 2025, 14(6), 467; https://doi.org/10.3390/cells14060467 - 20 Mar 2025
Viewed by 1450
Abstract
The global incidence and prevalence of cardiometabolic disorders have risen significantly in recent years. Although lifestyle choices in adulthood play a crucial role in the development of these conditions, it is well established that events occurring early in life can have an important [...] Read more.
The global incidence and prevalence of cardiometabolic disorders have risen significantly in recent years. Although lifestyle choices in adulthood play a crucial role in the development of these conditions, it is well established that events occurring early in life can have an important effect. Recent research on cardiometabolic diseases has highlighted the influence of sexual dimorphism on risk factors, underlying mechanisms, and response to therapies. In this narrative review, we summarize the current understanding of sexual dimorphism in cardiovascular and metabolic diseases in the general population and within the framework of the Developmental Origins of Health and Disease (DOHaD) concept. We explore key risk factors and mechanisms, including the influence of genetic and epigenetic factors, placental and embryonic development, maternal nutrition, sex hormones, energy metabolism, microbiota, oxidative stress, cell death, inflammation, endothelial dysfunction, circadian rhythm, and lifestyle factors. Finally, we discuss some of the main therapeutic approaches, responses to which may be influenced by sexual dimorphism, such as antihypertensive and cardiovascular treatments, oxidative stress management, nutrition, cell therapies, and hormone replacement therapy. Full article
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