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16 pages, 1701 KiB  
Article
Aromatase Inhibitor-Induced Carpal Tunnel Syndrome Immunohistochemical Analysis and Clinical Evaluation: An Observational, Cross-Sectional, Case–Control Study
by Iakov Molayem, Lucian Lior Marcovici, Roberto Gradini, Massimiliano Mancini, Silvia Taccogna and Alessia Pagnotta
J. Clin. Med. 2025, 14(15), 5513; https://doi.org/10.3390/jcm14155513 - 5 Aug 2025
Abstract
Background/Objectives: Breast cancer was the leading cause of malignant tumors among women in 2022. About two-thirds of breast cancer cases are hormone-receptor-positive. In these patients, aromatase inhibitors are a mainstay of treatment, but associated musculoskeletal symptoms can negatively affect patient compliance. Aromatase-inhibitor-induced [...] Read more.
Background/Objectives: Breast cancer was the leading cause of malignant tumors among women in 2022. About two-thirds of breast cancer cases are hormone-receptor-positive. In these patients, aromatase inhibitors are a mainstay of treatment, but associated musculoskeletal symptoms can negatively affect patient compliance. Aromatase-inhibitor-induced carpal tunnel syndrome represents one of the main causes of aromatase inhibitor discontinuation, with a non-compliance rate of up to 67%, potentially leading to increased cancer mortality. This study investigates estrogen receptor expression in aromatase-inhibitor-induced carpal tunnel syndrome tissues, in order to better define its etiopathogenesis and derive preventive or therapeutic measures that can improve aromatase inhibitor patient compliance. To our knowledge, there is no study on this subject in the literature. Methods: Between 2023 and 2024, we recruited 14 patients at the Jewish Hospital of Rome, including seven patients with aromatase-inhibitor-induced carpal tunnel syndrome (study group) and seven with postmenopausal idiopathic carpal tunnel syndrome (control group). Each patient was evaluated based on a clinical visit, a questionnaire, instrumental exams, and serum hormone dosages and were treated with open carpal tunnel release surgery, during which transverse carpal ligament and flexor tenosynovium samples were collected. For immunohistochemical experiments, sections were treated with anti-estrogen receptor α and anti-estrogen receptor β antibodies. Results: The immunohistochemical features in the study and control groups were similar, demonstrating that tissues affected by aromatase-inhibitor-induced carpal tunnel syndrome are targets of direct estrogen action and that estrogen deprivation is correlated with disease etiogenesis. Surgery was effective in patient treatment. Conclusions: Aromatase-inhibitor-induced carpal tunnel syndrome represents a newly defined form of the disease. This syndrome represents one of the main causes of aromatase inhibitor discontinuation, due to its negative impact on the patient’s quality of life. The identification by clinicians of aromatase inhibitor use as a possible risk factor for carpal tunnel syndrome development is of essential importance, as early diagnosis and prompt management can improve patient compliance and overall breast cancer treatment outcomes. Full article
(This article belongs to the Section General Surgery)
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14 pages, 529 KiB  
Article
Is the Addition of CO2 Laser to β3-Adrenoceptor Agonist Mirabegron Effective in the Management of Overactive Bladder? Results of a Randomized Controlled Trial
by Konstantinos Kypriotis, Anastasia Prodromidou, Stavros Athanasiou, Dimitrios Zacharakis, Nikolaos Kathopoulis, Athanasios Douligeris, Veatriki Athanasiou, Lina Michala and Themos Grigoriadis
Medicina 2025, 61(7), 1198; https://doi.org/10.3390/medicina61071198 - 30 Jun 2025
Viewed by 270
Abstract
Background and Objectives: This study aimed to assess whether the addition of fractional CO2 laser therapy to standard pharmacologic treatment with Mirabegron, a β3-adrenoceptor agonist, enhances the clinical outcomes in the management of overactive bladder syndrome (OAB) in postmenopausal women. Materials [...] Read more.
Background and Objectives: This study aimed to assess whether the addition of fractional CO2 laser therapy to standard pharmacologic treatment with Mirabegron, a β3-adrenoceptor agonist, enhances the clinical outcomes in the management of overactive bladder syndrome (OAB) in postmenopausal women. Materials and Methods: Τhis was a prospective, randomized, double-blind, sham-controlled trial including 50 postmenopausal women with moderate-to-severe OAB symptoms. Participants were randomized (1:1) to receive mirabegron 50 mg daily in combination with either active fractional CO2 laser therapy (Group A) or sham laser treatment (Group B). Both groups underwent three monthly sessions of vaginal laser treatment and were followed for a total of four months. Clinical assessments were performed at baseline and monthly visits (T0–T3), using validated instruments including the Overactive Bladder Questionnaire (OAB-q), King’s Health Questionnaire (KHQ), Urinary Distress Inventory (UDI-6), Pelvic Floor Impact Questionnaire (PFIQ-7), Patient Global Impression of Improvement (PGI-I), and 3-day voiding diaries. The trial was registered at ClinicalTrials.gov (Identifier: NCT03846895). Results: Significant symptom improvement was observed within both groups over time, with reductions in urinary frequency, urgency, nocturia, and incontinence episodes, as well as improvements in quality-of-life scores. However, intergroup comparisons revealed no statistically significant differences in any primary or secondary outcomes. Both treatment modalities demonstrated similar effectiveness across all measured parameters. Conclusions: In this randomized controlled trial, the adjunctive use of fractional CO2 laser therapy did not offer additional clinical benefit beyond mirabegron monotherapy in the short-term management of OAB. These findings underscore the need for further investigation into tailored therapeutic strategies, particularly in populations with overlapping genitourinary syndrome of menopause or more refractory OAB symptoms. Full article
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14 pages, 1290 KiB  
Article
Sexual Quality of Life in Postmenopausal Women: A Comparative Randomized Controlled Trial of Intravaginal PRP Therapy Versus Local Hormonal Treatments
by Geanina Sacarin, Ahmed Abu-Awwad, Nitu Razvan, Marius Craina, Bogdan Hogea, Bogdan Sorop, Simona-Alina Abu-Awwad, Mircea Diaconu, Nicolae Ciprian Pilut and Madalina-Ianca Suba
Medicina 2025, 61(7), 1140; https://doi.org/10.3390/medicina61071140 - 25 Jun 2025
Viewed by 528
Abstract
Background and Objectives: Genitourinary syndrome of menopause (GSM) is a prevalent and distressing condition in postmenopausal women, often leading to sexual dysfunction characterized by vaginal dryness, pain, and reduced libido. While local estrogen therapy remains the standard treatment, due to safety concerns [...] Read more.
Background and Objectives: Genitourinary syndrome of menopause (GSM) is a prevalent and distressing condition in postmenopausal women, often leading to sexual dysfunction characterized by vaginal dryness, pain, and reduced libido. While local estrogen therapy remains the standard treatment, due to safety concerns and contraindications, there is growing interest in the exploration of alternative interventions. This study aimed to compare the effectiveness and safety of intravaginal platelet-rich plasma (PRP) therapy versus local hormonal treatment in improving sexual function and vaginal health in postmenopausal women. Materials and Methods: A prospective, controlled clinical trial was conducted between January 2023 and December 2024 across three private gynecology clinics in Timișoara, Romania. Ninety postmenopausal women aged between 50 and 65 years with FSFI scores ≤ 23 were randomized into two groups: one receiving three monthly sessions of autologous PRP and the other undergoing 12 weeks of vaginal estriol therapy. Outcomes were assessed using validated tools—the Female Sexual Function Index (FSFI), the Vaginal Health Index (VHI), the Patient Global Impression of Improvement (PGI-I), and patient satisfaction scores—at baseline, week 6, and week 12. Results: Both of the treatment groups demonstrated significant improvements in FSFI and VHI scores at 12 weeks, with the PRP group showing a slightly higher, though not statistically significant, mean increase in the total FSFI (+10.1 vs. +9.3 points). Clinical gains were also observed in lubrication, elasticity, and dyspareunia. Patient satisfaction was high in both groups (93.3% PRP vs. 88.9% hormonal), and there were no reports of serious adverse events during the study period. The PRP group exhibited fewer side effects, without systemic symptoms, supporting its favorable safety profile. Conclusions: PRP therapy is a well-tolerated, hormone-free treatment that offers clinically meaningful improvements in sexual function and vaginal health, comparable to estrogen therapy. It may be particularly beneficial for women with contraindications to hormones or in advanced postmenopause. Further long-term studies are needed to confirm these findings and optimize treatment protocols. Full article
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12 pages, 253 KiB  
Article
FFA Patient Profile Analysis Based on the Authors’ Observations and a Review of the Literature—An Original Survey
by Michał Owczarek, Magdalena Jałowska, Agnieszka Mariowska, Wiktoria Grochowska, Joanna Szyszkowska, Daria Metelkina and Maciej Marek Spałek
J. Clin. Med. 2025, 14(12), 4346; https://doi.org/10.3390/jcm14124346 - 18 Jun 2025
Viewed by 557
Abstract
Background/Objectives: Frontal fibrosing alopecia (FFA) is a scarring alopecia with an unclear aetiology, primarily affecting postmenopausal women. This study aims to identify potential risk factors contributing to FFA development and progression, as well as provide a clinical profile to aid in the [...] Read more.
Background/Objectives: Frontal fibrosing alopecia (FFA) is a scarring alopecia with an unclear aetiology, primarily affecting postmenopausal women. This study aims to identify potential risk factors contributing to FFA development and progression, as well as provide a clinical profile to aid in the differential diagnosis. Methods: The study included 19 women diagnosed with FFA. The participants completed a 20-question survey based on a literature review of potential risk factors. Statistical analyses were performed to investigate the associations between patient characteristics and FFA. Results: All patients were female and their mean age was 60.58 years (SD = 12.81). In 63.1% of the cases, FFA onset occurred postmenopause, with a mean latency of 8.17 years. In the majority of cases, the diagnostic delay exceeded five years. The average menarche age was 13.68 years (SD = 2.06), whereas late menarche (≥15 years) was found in two subjects. A history of reproductive organ or breast malignancy was reported by 42.1% of the patients, which frequently required surgery. Most subjects did not receive hormone replacement therapy, or hormonal contraception. The most prevalent comorbidity was hypothyroidism (89.47%). Although smoking was rare among the subjects, hair colouring was quite common, yet no participant underwent scalp aesthetic procedures. In 47.4% of cases, scalp itching or pain was present. Sunscreens were frequently used, mostly on a daily or seasonal basis. Conclusions: FFA predominantly affects women in their early 60s, often following the menopause. In our study, a tendency toward an early menopause and an above-average menarche age of the subjects was observed. In the analysed group, only reproductive and breast cancers were reported, which requires further investigation. Frequent β-blocker use, second only to levothyroxine, may suggest that they play a role in FFA pathogenesis. Itching and pain of the scalp may contribute to the correct diagnosis, although these symptoms are not universal. Moreover, sunscreens were indicated as a potential trigger, yet avoiding them should not be routinely recommended due to the risk of carcinogenesis. The variability in the diagnostic delay emphasises the need for increasing clinician awareness and conducting further research. Full article
(This article belongs to the Section Dermatology)
12 pages, 488 KiB  
Article
Association Between Endogenous Equol Production and the Onset of Overactive Bladder in Postmenopausal Women
by Hiroyuki Honda, Tomohiro Matsuo, Hidenori Ito, Shota Kakita, Shintaro Mori, Kyohei Araki, Kensuke Mitsunari, Kojiro Ohba, Yasushi Mochizuki and Ryoichi Imamura
J. Clin. Med. 2025, 14(12), 4183; https://doi.org/10.3390/jcm14124183 - 12 Jun 2025
Viewed by 700
Abstract
Objectives: Equol, a gut-derived metabolite of soy isoflavones with estrogenic activity, may influence bladder aging. However, the association between overactive bladder (OAB), which is closely linked to bladder aging, and the estrogenic effects of equol remains unknown. Therefore, this study investigated the [...] Read more.
Objectives: Equol, a gut-derived metabolite of soy isoflavones with estrogenic activity, may influence bladder aging. However, the association between overactive bladder (OAB), which is closely linked to bladder aging, and the estrogenic effects of equol remains unknown. Therefore, this study investigated the association between endogenous equol production and onset and severity of OAB in postmenopausal women. Methods: The study included 128 postmenopausal women, newly diagnosed with OAB, who were categorized into equol- and non-equol-producing groups based on urinary equol levels as measured by enzyme-linked immunosorbent assay. Patient clinical characteristics, OAB Symptom Score (OABSS), and urodynamic parameters were assessed. Propensity score matching was performed to minimize confounding factors related to the timing of lower urinary tract symptom (LUTS) onset. Results: Equol producers exhibited a significantly later onset of LUTS than non-producers (68.7 ± 10.9 vs. 62.7 ± 10.7 years, p = 0.002). Equol producers were more prevalent in the late-onset group (58.6% vs. 31.0%, p = 0.002), which had significantly higher urinary equol concentrations than the early-onset group (p = 0.014). No significant differences were observed in total OABSS or subscale scores between the groups, suggesting that equol did not affect symptom severity. Propensity score-matched analysis (n = 104) confirmed that equol non-production was an independent risk factor for early-onset LUTS (OR, 1.930; 95% CI, 1.248–4.049; p = 0.014). Conclusions: Endogenous equol production was significantly associated with the delayed onset of OAB in postmenopausal women. Thus, equol may serve as a protective factor and non-invasive biomarker to guide individualized prevention and early intervention strategies in urological care for women. Full article
(This article belongs to the Topic Gynecological Endocrinology Updates)
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12 pages, 505 KiB  
Article
Assessment of Possibility of Using Ultrasound Imaging in Treatment of Stress Urinary Incontinence in Women—Preliminary Study
by Gabriela Kołodyńska, Maciej Zalewski, Aleksandra Piątek, Anna Mucha, Krystyna Rożek-Piechura and Waldemar Andrzejewski
Bioengineering 2025, 12(6), 633; https://doi.org/10.3390/bioengineering12060633 - 10 Jun 2025
Viewed by 446
Abstract
The number of people suffering from urinary incontinence increases every year. Along this trend, the knowledge of society increases regarding the various methods available for treating this ailment. Both patients and researchers are constantly looking for new treatments for urinary incontinence. One of [...] Read more.
The number of people suffering from urinary incontinence increases every year. Along this trend, the knowledge of society increases regarding the various methods available for treating this ailment. Both patients and researchers are constantly looking for new treatments for urinary incontinence. One of the new solutions is sonofeedback of the pelvic floor muscles, which may help to strengthen them and thus reduce the problem. The aim of this study was to evaluate the effectiveness of sonofeedback and transvaginal electrostimulation in increasing the bioelectrical activity of pelvic floor muscles in postmenopausal women with stress urinary incontinence. Sixty women with stress urinary incontinence were enrolled in the study. The patients were divided into two groups: A, where sonofeedback was used, and B, where electrostimulation of the pelvic floor muscles was performed with biofeedback training. In patients, the resting bioelectrical activity of the pelvic floor muscles was assessed using an electromyograph. The assessment of the resting bioelectrical activity of the pelvic floor muscles was performed before the therapy, after the 5th training, and after the therapy. It was observed that after the end of the therapy, the average bioelectrical potential increased by 1.1 µV compared with the baseline in group A. It can be suggested that the sonofeedback method is comparatively effective in reducing symptoms that are associated with urinary incontinence as an electrostimulation method with biofeedback training. Full article
(This article belongs to the Section Biosignal Processing)
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17 pages, 2825 KiB  
Article
A Novel Direct Butyrate Generator Reduces Belly Pain in a Randomized, Double-Blind, Placebo-Controlled Clinical Study
by Edward Dosz, Devin Conley and Michael Lelah
Nutraceuticals 2025, 5(2), 14; https://doi.org/10.3390/nutraceuticals5020014 - 6 Jun 2025
Viewed by 1562
Abstract
This study aimed to evaluate the effects of ButyraGen®, a direct butyrate generator, on digestive health in a real-world setting. A 6-week, randomized, double-blind, placebo-controlled, virtual clinical study was conducted starting with 596 participants. Participants were randomly assigned to either the [...] Read more.
This study aimed to evaluate the effects of ButyraGen®, a direct butyrate generator, on digestive health in a real-world setting. A 6-week, randomized, double-blind, placebo-controlled, virtual clinical study was conducted starting with 596 participants. Participants were randomly assigned to either the 200 mg ButyraGen® active or placebo group. Questionnaires were administered electronically to assess gastrointestinal health outcomes. Statistically significant improvements were observed in belly pain for the active ButyraGen® group compared with the placebo group, particularly in women, and particularly in post-menopausal women. The active group showed a higher likelihood of achieving clinically significant improvements in digestive health measures. ButyraGen® supplementation demonstrated statistically significant benefits in rapidly improving gastrointestinal health and quality of life, especially in women and those with upper and lower GI symptoms. Full article
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17 pages, 956 KiB  
Review
Gender-Specific Differences in Diastolic Dysfunction and HFpEF: Pathophysiology, Diagnosis, and Therapeutic Strategies
by Francesca Coppi, Gianluca Pagnoni, Francesca Grossule, Ashraf Nassar, Arianna Maini, Giuseppe Masaracchia, Francesco Sbarra, Elisa Battigaglia, Enrico Maggio, Daniela Aschieri, Federica Moscucci, Marcello Pinti, Anna Vittoria Mattioli, Francesco Fedele and Susanna Sciomer
J. Cardiovasc. Dev. Dis. 2025, 12(6), 213; https://doi.org/10.3390/jcdd12060213 - 5 Jun 2025
Viewed by 787
Abstract
: Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of heart failure cases and is primarily characterized by impaired diastolic function, leading to increased ventricular filling pressures and symptoms like dyspnea and reduced exercise tolerance. Significant gender-specific differences are observed, [...] Read more.
: Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of heart failure cases and is primarily characterized by impaired diastolic function, leading to increased ventricular filling pressures and symptoms like dyspnea and reduced exercise tolerance. Significant gender-specific differences are observed, with women, particularly post-menopausal, experiencing higher prevalence and distinct clinical profiles compared to men. Diastolic dysfunction in HFpEF involves altered cellular mechanisms such as reduced SERCA2a expression, impacting calcium handling and myocardial relaxation. Diagnostic strategies mainly employ echocardiography, including Doppler imaging, tissue Doppler imaging, and strain imaging, to assess ventricular relaxation and stiffness. However, early identification remains challenging, necessitating advanced tools like cardiac magnetic resonance and exercise stress testing for accurate diagnosis, especially in women who often present with subtle symptoms. Treatment options for HFpEF have traditionally been limited, but recent trials, notably EMPEROR-PRESERVED and DELIVER, demonstrated significant cardiovascular benefits using sodium–glucose cotransporter-2 (SGLT2) inhibitors. Additionally, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown promising results, particularly in obese patients. Despite these advances, gender differences in therapeutic response necessitate further research for personalized management strategies. Understanding sex-specific pathophysiological mechanisms and optimizing diagnostic criteria remain essential to improving prognosis and quality of life in HFpEF patients. Full article
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14 pages, 470 KiB  
Article
Sexual Dysfunction in the Life Cycle of Women: Implications for Psychological Health
by Samet Kırat
Healthcare 2025, 13(11), 1268; https://doi.org/10.3390/healthcare13111268 - 27 May 2025
Viewed by 790
Abstract
Objective: Sexual dysfunction (SD) is a prevalent but frequently overlooked condition that adversely affects women’s quality of life and psychological well-being. This study aimed to examine the relationship between SD and depression, anxiety, and stress levels during premenopausal, pregnancy, and postmenopausal. Methods: This [...] Read more.
Objective: Sexual dysfunction (SD) is a prevalent but frequently overlooked condition that adversely affects women’s quality of life and psychological well-being. This study aimed to examine the relationship between SD and depression, anxiety, and stress levels during premenopausal, pregnancy, and postmenopausal. Methods: This prospective, cross-sectional study included 300 women aged 18–70 who presented with SD symptoms to a tertiary care gynecology outpatient clinic. Participants were categorized into premenopausal, pregnant, and postmenopausal groups. Sexual function was assessed using the Female Sexual Function Index (FSFI), and psychological status was evaluated with the Depression Anxiety and Stress Scale (DASS-21). Univariate and multivariate logistic regression analyses were conducted to identify risk factors associated with SD. Results: The results showed that SD prevalence varied across life stages, with the highest rate (96%) observed in postmenopausal women. Significant decreases were found in all FSFI subscales, particularly lubrication and orgasm, during the postmenopausal period (p < 0.001). Although DASS-21 total scores did not differ significantly between groups (p = 0.227), severe stress was more prevalent in premenopausal women (p = 0.018). Univariate logistic regression revealed that older age, higher parity, and menopause increased SD risk (p < 0.001), while employment (p = 0.006), higher education (p = 0.012), and pregnancy (p < 0.001) were protective factors. Multivariate analysis identified parity as the only independent variable significantly increasing SD risk (p = 0.011). Weak but significant negative correlations were found between FSFI total score and DASS-21 total (r = −0.137, p = 0.018), anxiety (r = −0.135, p = 0.019), and depression (r = −0.176, p = 0.002) scores. Conclusion: These findings highlight the importance of individualized assessment and treatment approaches for women’s sexual health across different life stages, considering the influence of various biological, psychological, and social factors. Full article
(This article belongs to the Special Issue Gender, Sexuality and Mental Health)
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62 pages, 4346 KiB  
Review
Hormone Replacement Therapy and Cardiovascular Health in Postmenopausal Women
by Wenhan Xia and Raouf A. Khalil
Int. J. Mol. Sci. 2025, 26(11), 5078; https://doi.org/10.3390/ijms26115078 - 24 May 2025
Viewed by 2063
Abstract
Sex-related differences are found not only in the reproductive system but also across various biological systems, such as the cardiovascular system. Compared with premenopausal women, cardiovascular disease (CVD) tends to occur more frequently in adult men and postmenopausal women (Post-MW). Also, during the [...] Read more.
Sex-related differences are found not only in the reproductive system but also across various biological systems, such as the cardiovascular system. Compared with premenopausal women, cardiovascular disease (CVD) tends to occur more frequently in adult men and postmenopausal women (Post-MW). Also, during the reproductive years, sex hormones synthesized and released into the blood stream affect vascular function in a sex-dependent fashion. Estrogen (E2) interacts with estrogen receptors (ERs) in endothelial cells, vascular smooth muscle, and the extracellular matrix, causing both genomic and non-genomic effects, including vasodilation, decreased blood pressure, and cardiovascular protection. These observations have suggested beneficial effects of female sex hormones on cardiovascular function. In addition, the clear advantages of E2 supplementation in alleviating vasomotor symptoms during menopause have led to clinical investigations of the effects of menopausal hormone therapy (MHT) in CVD. However, the findings from these clinical trials have been variable and often contradictory. The lack of benefits of MHT in CVD has been related to the MHT preparation (type, dose, and route), vascular ERs (number, variants, distribution, and sensitivity), menopausal stage (MHT timing, initiation, and duration), hormonal environment (progesterone, testosterone (T), gonadotropins, and sex hormone binding globulin), and preexisting cardiovascular health and other disorders. The vascular effects of sex hormones have also prompted further examination of the use of anabolic drugs among athletes and the long-term effects of E2 and T supplements on cardiovascular health in cis- and transgender individuals seeking gender-affirming therapy. Further analysis of the effects of sex hormones and their receptors on vascular function should enhance our understanding of the sex differences and menopause-related changes in vascular signaling and provide better guidance for the management of CVD in a gender-specific fashion and in Post-MW. Full article
(This article belongs to the Special Issue Hormone Replacement Therapy)
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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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15 pages, 2135 KiB  
Review
Cardiovascular Disease Risk in Women with Menopause
by María Fasero and Pluvio J. Coronado
J. Clin. Med. 2025, 14(11), 3663; https://doi.org/10.3390/jcm14113663 - 23 May 2025
Cited by 1 | Viewed by 2128
Abstract
Background and objective: Menopause is a significant physiological milestone in a woman’s life, coinciding with increased cardiovascular disease (CVD) risk due to various health-related changes. This narrative review focuses on cardiovascular health-related alterations during menopause and their implications on vascular function. Methods [...] Read more.
Background and objective: Menopause is a significant physiological milestone in a woman’s life, coinciding with increased cardiovascular disease (CVD) risk due to various health-related changes. This narrative review focuses on cardiovascular health-related alterations during menopause and their implications on vascular function. Methods: An electronic database search was performed, drawing from sources such as PubMed and Google Scholar. Publications were included if they addressed CVD risk in peri- and postmenopausal women, and examined the impact of hormonal changes, traditional risk factors (e.g., hypertension, hyperlipidemia, diabetes), or lifestyle factors (e.g., diet, physical activity) on CVD. Results: Estrogen deficiency is pivotal, leading to adverse effects such as endothelial dysfunction, increased arterial stiffness, and lipid profile deterioration. Characteristics of menopause, including the age at onset, type or stage of menopause, and severity of symptoms, further modulate CVD risk. Additionally, the impact of traditional risk factors is amplified during this period. Strategies for the prevention of CVD in menopausal women are critically assessed, with a focus on lifestyle modifications, dietary interventions, and physical activity. Conclusions: This narrative review describes the potential benefits and risks of hormone therapy, alongside lipid-lowering therapies. Emphasis is placed on individualized risk assessment and management, highlighting the need for regular cardiovascular screenings and proactive management of risk factors. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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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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13 pages, 578 KiB  
Review
Oral Manifestations in Menopause—A Scoping Review
by Anca Labunet, Adriana Objelean, Andreea Kui, Laura Rusu, Alexandra Vigu and Sorina Sava
Medicina 2025, 61(5), 837; https://doi.org/10.3390/medicina61050837 - 1 May 2025
Viewed by 888
Abstract
Background and Objectives: Menopause is a natural physiological process involving hormone production changes, affecting many functions and systems. This scoping review offers a contemporary outlook on oral issues related to menopause, such as saliva production, periodontal and alveolar bone issues, and changes [...] Read more.
Background and Objectives: Menopause is a natural physiological process involving hormone production changes, affecting many functions and systems. This scoping review offers a contemporary outlook on oral issues related to menopause, such as saliva production, periodontal and alveolar bone issues, and changes in the microbiome, and it also investigates the effects of hormonal therapy. Materials and Methods: A literature search from 2019 to 2024 was conducted according to PRISMA-ScR guidelines. Articles investigating the oral effects of menopause were included. Results: A total of 30 studies were covered; 8 focused on salivary alterations, 5 on periodontal issues, 7 on bone, 3 on the microbiome, and 7 on multiple oral problems, showing that xerostomia and altered taste are the most common oral manifestations, followed by indirect causal effects on periodontitis. Many of these alterations can be contained through regular consultations and adequate hygiene. Some alveolar bone changes may occur after menopause and are associated with osteoporosis. Conclusions: Postmenopausal women experience notable reductions in salivary flow, pH levels, and taste sensitivity, which are associated with hormonal fluctuations as well as factors such as age, medication use, and treatments for climacteric symptoms. This population is at increased risk for periodontitis, tooth loss, altered taste, lichen planus, candidiasis, and decreased bone mineral density, which also affect the peri-implant area. Osteoporosis and hormonal changes can play a significant role in causing these increased risks. Maintaining proper oral hygiene and consistently monitoring bone health are essential. While changes in the oral microbiome are more heavily influenced by reductions in salivary flow than by menopause itself, hormone therapy may help improve periodontal health by reducing harmful bacteria and fostering a more balanced microbial environment. The intricate impact of hormones on oral health highlights the necessity for further research. Full article
(This article belongs to the Section Dentistry and Oral Health)
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18 pages, 5370 KiB  
Article
Labisia pumila var. alata Extract Induces Apoptosis Cell Death by Inhibiting the Activity of Oestrogen Receptors in MCF-7 Breast Cancer Cells
by Muhammad Faiz Zulkifli, Zolkapli Eshak, Mohd Helmy Mokhtar and Wan Iryani Wan Ismail
Int. J. Mol. Sci. 2025, 26(8), 3748; https://doi.org/10.3390/ijms26083748 - 16 Apr 2025
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Abstract
Labisia pumila var. alata (LP) is an herbaceous shrub commonly used by women to promote health and vitality, alleviate postmenopausal symptoms, and enhance libido. Research indicates that LP possesses significant oestrogenic and antiproliferative properties towards breast cancer; however, the specific mechanisms involved remain [...] Read more.
Labisia pumila var. alata (LP) is an herbaceous shrub commonly used by women to promote health and vitality, alleviate postmenopausal symptoms, and enhance libido. Research indicates that LP possesses significant oestrogenic and antiproliferative properties towards breast cancer; however, the specific mechanisms involved remain unclear. We investigate the oestrogenic effects of LP in inducing apoptosis in human breast adenocarcinoma (MCF-7) cells and the mechanisms underlying this process. Docking analysis reveals that the phytoestrogens in LP can bind to oestrogen receptors (ER), specifically ERα and ERβ. MTT assays demonstrate that LP has a dose- and time-dependent antiproliferative effect on MCF-7 cells. Furthermore, the antiproliferative activity of LP on MCF-7 cells is inhibited by Fulvestrant, indicating that its effects are mediated through oestrogen receptors. Flow cytometry analysis shows that the antiproliferative effect of LP results from the induction of apoptosis in MCF-7 cells. The activation of caspase 3, along with caspase 8 and caspase 9, suggests that LP triggers apoptosis through both intrinsic and extrinsic pathways. The findings regarding the aqueous extract of LP and its impact on the proliferative activity of MCF-7 cells may have significant therapeutic and preventive implications for future drug development, particularly in the context of breast cancer. Full article
(This article belongs to the Special Issue Medicinal Plants and Bioactive Compounds in Health and Disease)
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