Search Results (194)

Adjuvant endocrine therapy for early breast cancer significantly reduces recurrence but increases bone fragility. Given limited data on denosumab (60 mg every 6 months) in premenopausal patients receiving endocrine therapy for early breast cancer, we conducted a retrospective real-world study at the Gemelli Hospital (September 2018–January 2025). A descriptive analysis was performed. The primary endpoint was to assess efficacy, evaluated by changes in bone mineral density via dual-energy X-ray absorptiometry and by monitoring bone turnover markers, particularly serum C-terminal telopeptide of type I collagen. Safety was evaluated based on adverse endocrine therapy events (osteoporotic fractures) and adverse denosumab events (osteonecrosis of the jaw). Sixty-nine patients were eligible for the study. Endocrine therapy included ovarian function suppression with exemestane (89.8%) or tamoxifen (10.1%). Baseline spinal osteoporosis decreased from 20.3% to 5.8%, osteopenia from 39.1% to 34.8%, with normal T-scores rising from 17.4% to 34.8%. Femoral improvements were similar. Serum C-terminal telopeptide of type I collagen levels (evaluated in 35.8%) showed stable reduction in 97%. Denosumab adherence was 89.9%. One osteonecrosis of the jaw case occurred (1.4%); no fractures were reported. Denosumab demonstrated efficacy in improving bone density and reducing bone turnover, with excellent adherence and favorable safety. Longer follow-up is needed to assess post-discontinuation effects. Full article

Background/Objectives: Pelvic organ prolapse (POP) is a common condition that significantly impacts quality of life. Research has focused largely on older women, while experiences of younger women remain relatively underexplored despite challenges unique to this population. Informed by the biopsychosocial model of illness, this study aims to assess the symptom burden, treatment goals, and information needs of younger women complaining of prolapse by analyzing questionnaire responses from an existing electronic Personal Assessment Questionnaire—Pelvic Floor (ePAQ-PF) dataset. Methods: Mixed-methods content analysis was conducted using free-text data from an anonymized multi-site ePAQ-PF dataset of 5717 responses collected across eight UK NHS trusts (2018–2022). A quantitative, deductive approach was first used to identify younger women (≤50 years old) with self-reported prolapse. ePAQ-PF scores for younger women with prolapse were compared with those aged >50 years, using Mann–Whitney tests. Free-text response data were analyzed inductively to qualitatively explore younger women’s symptom burden, treatment goals, and information needs. Results: Of the 1473 women with prolapse identified, 399 were aged ≤50 years. ePAQ-PF scores of the younger cohort demonstrated significantly greater symptom severity and bother than those aged >50, particularly in bowel, prolapse, vaginal, body image, and sexual health domains (p < adjusted threshold). Qualitative analysis undertaken to understand women’s concerns and priorities produced five health-related themes (physical health; functionality; psychosocial and emotional wellbeing; reproductive and sexual health; and healthcare journeys) and a sixth intersecting theme representing information needs. Conclusions: The findings highlight the substantial symptom burden of younger women with prolapse, as well as treatment goals and information needs specific to this population. The development of age-specific resources is identified as a requirement to support this group. Full article

Background and Objectives: The objective of this review is to evaluate the current evidence regarding hormone treatments for both premenopausal and postmenopausal women with early-stage hormone receptor (HR) positive breast cancer. Materials and Methods: An in-depth exploration of the existing literature was conducted, with landmark clinical trials such as TEXT, SOFT, ATLAS, and aTTom serving as primary references. Results: Through an extensive review of the literature, our findings indicate that for premenopausal women with HR-positive, HER2-negative BC with a low risk of recurrence, standard 5-year monotherapy with tamoxifen represents the optimal therapeutic management, given its favorable clinical outcomes and lower associated toxicity. In contrast, for premenopausal women with an intermediate to high risk of recurrence with the same tumor characteristics, the most effective approach stated in the literature is a combination of ovarian suppression therapy (chemical/surgical) and an aromatase inhibitor/selective estrogen receptor modulator (tamoxifen), with a possible extension of the standard therapeutic period. In postmenopausal patients with HR-positive, HER2-negative breast cancer with a low recurrence risk, the first line of treatment is usually a standard 5-year period of treatment with aromatase inhibitors (AIs)(letrozole, anastrozole, or exemestane). On the other hand, in postmenopausal women with an intermediate to high risk, combination therapy might be needed, as well as an extension of the standard therapeutic time. Conclusions: Treatment consensus depends on pre- vs. postmenopausal status and recurrence risk. Full article

Uterine fibroids (leiomyomas) are benign tumors whose growth is influenced by estrogen and progesterone. This study aimed to compare the profiles of differentially expressed long non-coding RNAs (lncRNAs) in fibroids from postmenopausal and premenopausal women to identify hormone-responsive lncRNAs. RNA sequencing was performed on six pairs of fibroid (Fib) and adjacent myometrium (Myo) tissues from postmenopausal women. Out of 7876 normalized lncRNAs, 3684 were differentially expressed (≥1.5-fold), with 1702 upregulated and 1982 downregulated in Fib. Comparative analysis with a previously published premenopausal dataset identified 741 lncRNAs that were altered based on their menopausal status, including 62 lncRNAs that were uniquely dysregulated in postmenopausal samples. Overall, 9 lncRNAs were selected for validation by PCR in an expanded cohort of 31 postmenopausal and 84 premenopausal paired samples. Several lncRNAs, including LINC02433, LINC01449, SNHG12, H19, and HOTTIP, were upregulated in premenopausal Fib but not in postmenopausal ones, while ZEB2-AS1 displayed the opposite pattern. CASC15 and MIAT were elevated in Fib from both groups, although the increase was less pronounced in the postmenopausal group. LINC01117 was significantly downregulated in postmenopausal Fib, with no change observed in premenopausal samples. Additionally, analysis based on MED12 mutation status revealed that lncRNAs such as LINC01449, CASC15, and MIAT showed limited or reduced differential expression (mutation-positive vs. mutation-negative) in postmenopausal patients compared to the premenopausal group. These findings indicate that lncRNA expression in fibroids is modulated by menopausal status, likely reflecting hormonal influence. Hormone-responsive lncRNAs may play key roles in fibroid pathogenesis and represent potential targets for therapeutic intervention. Full article

Background/Objectives: HER2-positive breast cancer is an aggressive subtype with an established responsiveness to HER2-targeted therapies like ado-trastuzumab emtansine (T-DM1). However, inter-patient variability in treatment response and toxicity remains a challenge. Hormonal status, particularly menopausal state, may influence breast cancer behavior, therapeutic tolerance, and outcomes, yet data on its effect in patients treated with T-DM1 are scarce. This study aimed to evaluate whether menopausal status independently affects treatment response, side effects, and survival outcomes in HER2-positive breast cancer patients receiving T-DM1, accounting for the confounding role of age. Methods: This retrospective cohort study included 98 female patients with HER2-positive breast cancer treated with T-DM1: 53 premenopausal and 45 postmenopausal. The clinical characteristics, metastatic patterns, treatment history, T-DM1 outcomes, and toxicities were recorded. The statistical analysis included chi-square, t-tests, Mann–Whitney U tests, and Spearman’s correlations. Partial correlation analyses were conducted to isolate the effect of menopausal status by controlling for age. Results: The postmenopausal patients showed higher rates of lung metastasis (42.2% vs. 20.8%) and mortality (60.0% vs. 39.6%) than premenopausal patients. However, no significant differences were found in the T-DM1 response or toxicity profiles. After adjusting for age, menopausal status had no independent association with the treatment outcomes or side effects. Age was the dominant factor influencing performance status, metastatic burden, and mortality risk. Conclusions: Menopausal status affects disease presentation but not T-DM1 efficacy or toxicity when age is accounted for. Treatment decisions should consider age and clinical profile rather than menopausal classification alone when managing HER2-positive breast cancer with T-DM1. Full article

Background: The diagnostic accuracy of the exercise treadmill test (ETT) remains suboptimal in premenopausal women. Menstrual cycle phases display hormonal variations and biological effects in premenopausal women. The early and late follicular phases of the menstrual cycle demonstrate nearly four-fold differences in estrogen levels. Methods: This study assessed the variability in ETT results between the early and late follicular phases in premenopausal women. This study included premenopausal females with regular menstrual cycles and chest pain. As per the study protocol, patients underwent two separate ETTs at the early and late follicular phases of the menstrual cycle. Hormones and high-sensitivity cardiac troponin T (hs-cTnT) were measured. The primary endpoint was the ST segment/heart rate (HR) index. The secondary endpoints were maximum ST/HR slope, ST segment depression, HR and blood pressure (BP) response, exercise capacity, and hs-cTnT change after ETT. Results: False-positive ETT results were common in premenopausal women. The early follicular phase displayed significantly higher hs-cTnT and BP responses to ETT compared to the late follicular phase. This study reports that ETT results are similar between the early and late follicular phases of the menstrual cycle in premenopausal women. Biological variability is observed in the BP and hs-cTnT response to ETT between the two phases. Conclusions: The menstrual cycle phase (early versus late follicular phase) did not affect the ETT results. The consideration of estrogen and hormonal status when evaluating the diagnostic test results can improve our understanding of cardiovascular disease in women. Full article

To elucidate the changes in gas exchange across the life course, we estimated the age trajectories of O₂ saturation, CO₂ (as either end-tidal or serum bicarbonate), resting heart rate, and resting respiratory rate from age 2 yr onward in female and male patients separately. We utilized two sources’ data: electronic health records (EHR) representing ambulatory visits of approximately 53,000 individuals and sleep clinic polysomnogram (PSG) records representing an additional ~21,000. We used linear regression to estimate age-group-specific mean response levels for women and men. We compared estimated female–male differences between pre- and post-pubertal children and between pre- and post-menopausal periods among adults. Women between 15 and 45 years had higher O₂ saturation and lower serum bicarbonate levels or end-tidal CO₂ levels than men of similar ages. For O₂ saturation and for both measures of CO₂, the female–male difference was larger on average among adults at pre-menopausal ages than those at post-menopausal ages. Women had higher O₂ saturation throughout their lives than men; however, the difference disappeared in the elderly. Women between menarche and menopause had significantly lower end-tidal CO₂ and serum bicarbonate than men of similar ages. After menopause, however, women appeared to have higher mean levels of both end-tidal CO₂ and serum bicarbonate than men. Full article

HSD3B1 encodes an enzyme that catalyzes the conversion of adrenal precursors into potent sex steroids. A common germline variant (c.1100C) enhances this effect and is linked to breast cancer (BC) progression. As the HSD3B1 genotypes contribute to differences in local and adrenal steroid production, their transcriptional and phenotypic effects on cancers influenced by hormonal signaling such as BC and endometrial cancer (EC)—particularly in relation to menopausal status—remain unclear. We analyzed BC and EC sequenced from patients that received diagnostic tests in oncology clinics, and we determined the germline HSD3B1 c.1100 genotype (AA, AC, CC) from tumor DNA sequencing by using variant allele frequency, with inferred menopausal status assumed by age at molecular profiling. Whole-transcriptome RNA sequencing and gene set enrichment analysis showed that adrenal-permissive homozygous (CC) tumors in premenopausal ER + BC were enriched for hormone-related pathways, including Estrogen Response Early (NES ≈ +1.8). In premenopausal triple-negative BC, adrenal-restrictive homozygous (AA) tumors exhibited the elevated expression of immune and epithelial genes and the increased prevalence of MED12 alterations (AA 0.25% vs. CC 8%, p < 0.01). In endometrioid EC, CC tumors demonstrated the suppression of immune and proliferative pathways. Postmenopausal cases had higher progesterone receptor IHC positivity (AA 75% vs. CC 83%, p < 0.05) and numerically more frequent ESR1 copy number gains (AA 2.0% vs. CC 4.0%). Results highlight context-specific associations between germline HSD3B1 genotypes and tumor biology in BC and EC. Full article

Cystic mucinous neoplasms (MCNs) of the pancreas are rare cystic tumors, accounting for approximately 2–5% of all pancreatic neoplasms. They predominantly occur in premenopausal women and are typically located in the body or tail of the pancreas. Due to their potential for malignant transformation, especially in cases associated with invasive carcinoma such as pancreatic ductal adenocarcinoma, early detection, complete surgical resection, and rigorous postoperative surveillance are essential. The occurrence of MCNs in male patients is exceedingly rare, comprising only about 2% of reported cases, and often resulting in preoperative diagnostic challenges. Molecular analyses have identified a strong association between KRAS mutations and disease progression in MCNs, underscoring their potential role as prognostic markers despite limited diagnostic utility. In this report, we present two additional cases of MCNs in male patients, highlighting their histopathological features and the ancillary investigations undertaken to support diagnosis. Full article

Breast cancer is the leading cause of death among women, and its treatment often involves chemotherapy and hormone therapy, which can compromise bone mineral density (BMD). Tamoxifen, a selective estrogen receptor modulator, has different effects depending on the patient’s hormonal status. On the one hand, in postmenopausal women, it has a protective effect on BMD; on the other hand, in premenopausal women, it can accelerate bone loss, increasing the risk of osteoporosis and fractures. The reduction in estrogen levels during treatment is a key factor in this bone loss. This review underscores the importance of early risk assessment and regular monitoring of bone mineral density, along with the adoption of individualized pharmacological and non-pharmacological strategies, such as calcium and vitamin D supplementation and physical exercise, to preserve bone health in premenopausal women with breast cancer undergoing endocrine therapy. Full article

Sex differences in metabolic disorders and susceptibility to chronic diseases induced by a high-fat diet (HFD) exhibit significant dimorphic characteristics. A long-standing male-centric bias in medical research and healthcare, predominantly focused on male physiological traits, has hindered the precise treatment of metabolic diseases in female patients. A comprehensive understanding of sex differences in metabolic health and their underlying mechanisms is crucial for advancing personalized health promotion and precision medicine. This review systematically elucidates sex-specific manifestations in high-fat diet-associated metabolic disorders: males predominantly develop visceral adiposity, insulin resistance, and dyslipidemia, accompanied by a significantly elevated risk of cardiovascular and metabolic syndromes. Premenopausal females maintain metabolic homeostasis through the estrogen-mediated optimization of glucose and lipid metabolism and oxidative stress buffering mechanisms, whereas postmenopausal-phase females experience dramatic metabolic vulnerability due to z loss of protective barriers. Furthermore, we emphasize multidimensional mechanistic interpretations of metabolic sexual dimorphism from perspectives including sex chromosome complement, sex hormone signaling pathways, epigenetic regulation, gut microbiota composition, and neuroendocrine dimorphism. This work provides critical theoretical foundations for rectifying unisex research paradigms and optimizing sex-specific early warning systems and precision therapeutic strategies for metabolic disorders. Full article

Background: Adult granulosa cell tumours (AGCT) of the ovary account for 2–5% of ovarian tumours, with 30% occurring in women of childbearing age. Despite a good prognosis, up to 25% recur. There is a paucity of high-quality evidence to guide management. Objective: To describe management of AGCT across multiple gynaecological cancer centres. Methods: Retrospective analysis of electronic patient records from six gynaecological cancer centres in Southwest England between 2000 and 2021 (n = 119). Results: We included 107 patients with a median follow-up of 60 months (0–261 months). Most (97/107; 90.7%) were diagnosed with stage I disease (31.8% stage Ic). Primary management was staging surgery in 33/107 (30.8%), hysterectomy and bilateral salpingo-oophorectomy (BSO) (28/107; 26.2%), or conservation of an ovary (17/107; 15.9%). Three had a subsequent pregnancy. A quarter (27/107; 25.2%) were diagnosed with recurrent disease. Fifteen patients (15/107; 14%) had multiple recurrences. Recurrence was more likely if cyst rupture was reported at surgery (38.7%) compared with no rupture (14.3%; p < 0.001). The recurrence rate was higher with ovarian conservation (6/17; 35.3%) compared with BSO (21/90; 23.3%; p < 0.01), and all recurrences involved the residual ovary. Of the 11 deaths, 6 (54.5%) were attributed to progressive disease. Conclusions: Although survival with early-stage disease is good, ovarian cystectomy or unilateral ovarian conservation was associated with increased risk of recurrence. There is no conclusive evidence to support a contralateral oophorectomy in pre-menopausal women, but completion surgery should at least be considered, either immediately or after childbearing/assisted reproductive treatment. Full article

Breast cancer (BC) is the most prevalent malignancy among women worldwide, with a rising incidence in young, premenopausal patients. For those diagnosed with hormone receptor-positive (HR+) BC, tamoxifen is a cornerstone of adjuvant endocrine therapy, significantly reducing recurrence risk and improving long-term survival. However, its prolonged use poses challenges for women desiring pregnancy, prompting interest in temporary treatment interruption as a strategy to achieve reproductive goals while maintaining oncological safety. This systematic review evaluates the impact of tamoxifen on fertility, the feasibility of treatment interruption, and associated reproductive and oncological outcomes. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive search across major databases, identifying three relevant studies, including one randomized controlled trial (RCT) and two observational cohort studies. The findings suggest that temporary tamoxifen interruption allows for successful pregnancies without significantly increasing short-term recurrence rates. Notably, the POSITIVE trial demonstrated a pregnancy achievement rate of 74% and a live birth rate of 63.8%, with comparable three-year disease-free survival between patients who interrupted tamoxifen and those who continued therapy. However, concerns remain regarding tamoxifen’s teratogenic risks, emphasizing the need for strict contraceptive measures and preconception counseling. Despite emerging evidence supporting this approach, long-term safety data are limited. Further research is warranted to refine clinical recommendations and optimize reproductive counseling for young BC survivors. Full article

Endometriosis is common and poses significant morbidity of lasting impact to young, pre-menopausal women, while ovarian cancer is a lethal gynecologic condition. Both conditions need better treatment. The human omentum is an apron of adipose tissue in the abdominopelvic cavity, the same space in which endometriosis and ovarian cancer manifest. We aim to determine molecular cues emitted by the omentum that aid the trans-coelomic spread of endometriosis and ovarian cancer in the abdomen–pelvic/peritoneal space. Endometriosis and ovarian cancer patients were prospectively recruited. Primary cell cultures of surgically-resected omentum, endometriosis and ovarian cancer were generated, and conditioned media (CM) from the omentum was derived. They were used for in vitro assays to evaluate the effect of the omentum on cell migration, angiogenesis and proliferation in endometriosis and ovarian cancer. Omental CM promoted cell migration in primary cultures of endometriosis and ovarian cancer. Omental CM contained high levels of HGF, SDF-1a, MCP-1, VEGF-A, IL-6 and IL-8. The observed cell migration was blocked by c-MET inhibition, suggesting that HGF/c-MET signaling mediates cell migration in endometriosis and ovarian cancer. Furthermore, PTTG1 was consistently upregulated in the migrated cells in both endometriosis and ovarian cancer. The omentum provides a favorable environment for trans-coelomic spread of endometriosis and ovarian cancer. HGF, c-MET and PTTG1 are potential therapeutic targets for inhibiting the abdomen–pelvic/peritoneal spread of endometriosis and ovarian cancer. Full article

Background/Objectives: CDK4/6 inhibitors have changed the landscape of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (BC) management. It is essential to identify predictive and prognostic factors for the efficacy of CDK4/6 inhibitors. We aimed to investigate the differences in characteristics and outcomes of patients receiving first-line CDK4/6 inhibitors according to PgR status. Methods: This multicenter retrospective study included 351 patients treated with first-line CDK 4/6 inhibitors for HR-positive/HER2-negative metastatic BC. Patients were categorized based on their PgR expression levels, including the PgR-low (<20%) and PgR-high (≥20%) groups, and baseline characteristics, treatment responses, and survival outcomes were analyzed. Results: The median age was 57 years (range: 26–85). A total of 99 patients were premenopausal, and 252 patients were postmenopausal. There were 115 (32.8%) patients in the PgR-low group, while 236 (67.2%) were in the PgR-high group. The majority of patients (56.7%) presented with de novo metastatic disease. Visceral metastases presented in 44.2% of patients. Low PgR expression was significantly associated with lower estrogen receptor levels (p = 0.031), elevated Ki-67 levels (p = 0.002), a higher incidence of visceral metastases (p = 0.035), and recurrent disease (p = 0.019). In the multivariate analysis, low PgR expression was a significant independent predictor of worse progression-free survival (PFS) and overall survival (OS). Conclusions: We demonstrated that low PgR expression is independently and significantly correlated with shorter PFS and OS. These findings support low PgR expression as a valuable prognostic biomarker in metastatic BC patients treated with first-line CDK4/6 inhibitors. Full article