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AIM: Cardiovascular (CV) risk assessment in transgender individuals remains poorly understood. Emerging data suggest a potential increase in CV risk associated with gender-affirming hormone therapy(GAHT). Conventional tools such as coronary artery calcium(CAC) scoring may underestimate risk in this young population. Advanced imaging techniques (coronary computed tomography angiography CCTA and 3-dimensional supra-aortic trunk ultrasonography SATUS) may provide more accurate evaluation, but their relevance in transgender cohorts has not yet been established. We aimed to assess early CV risk modification of GAHT using several innovative imaging techniques. METHODS: We conducted a prospective, single-center study at Bordeaux University Hospital, enrolling transgender individuals initiating or continuing GAHT. Participants undergone clinical and biological assessment and CV imaging(CAC, CCTA, SATUS) at baseline and after 18months. RESULTS: Thirty-four participants (17transmen (TM), 17transwomen (TW) were included. At baseline, TM were younger than TW (22.7±5.3 vs 29.7±9.7years,p=0.008), had higher HDLc (1.36 vs 1.18mmol/L,p=0.01), and higher smoking prevalence (70.6% vs 11.8%, p=0.001). Both groups had a CAC score and carotid plaque volume of zero. During follow-up, TW showed a modest increase in carotid plaque volume and CAC scores, whereas TM showed no change. Progression of coronary plaque volume was observed in 70% of TW compared with 22% of TM, indicating a clear, although non-significant, trend toward greater atherosclerotic development in TW. CONCLUSION: This pilot study suggests a more pronounced progression of atherosclerosis in TW undergoing GAHT, detectable particularly through CCTA. These findings support refined CV monitoring and highlight the need for larger, long-term studies to guide preventive strategies in transgender populations.

Our study examines how advanced imaging tools can better detect early cardiovascular risk in transgender individuals on gender-affirming hormone therapy, highlighting a tendency toward greater atherosclerosis progression in transgender women. Traditional tools like coronary calcium scoring may underestimate risk in this generally young transgender population, making more sensitive and innovative imaging techniques such as coronary CT angiography and 3D vascular ultrasound particularly valuable.Improving cardiovascular monitoring in transgender people could help develop more effective prevention strategies and enhance long-term heart health.

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Non-adherence to endocrine therapy was associated with insufficient knowledge and poor beliefs towards treatment. A culturally-appropriate education tool may be needed to improve patient care. This study aimed to evaluate a newly developed education tool, with two phases of evaluation involving experts and potential users consisting of breast cancer patients on endocrine therapy. Expert evaluation involved assessment by a multi-disciplinary panel (n = 10) using three tools to assess different aspects of quality: Ensuring Quality Information for Patients (EQIP); Patient Education Materials Assessment Tool (PEMAT), which consists of Understandability and Actionability scales; and Suitability Assessment of Materials (SAM). The mean scores for EQIP (90.3%), PEMAT (Understandability: 98.2%; Actionability: 96.3%) and SAM (93.4%) revealed that the education tool exhibited good quality. User-based evaluation utilised pre- and post-questionnaires to evaluate user satisfaction via Consumer Information Rating Form (CIRF) and to evaluate the effects of the education tool on knowledge as well as beliefs, assessed using Beliefs about Medicines Questionnaire (BMQ). Patients were recruited from a university hospital and a national cancer institute. Results from CIRF indicated that the participants (n = 62) were satisfied with the comprehensibility, utility and design quality of the education tool. There was a significant improvement for knowledge (1.89 vs. 3.39, p < 0.01) and BMQ-General scores: General-Harm (2.24 vs. 1.91, p < 0.01) and General-Overuse (2.81 vs. 2.44, p < 0.01) after patients were introduced to the education tool. The findings indicated that the education tool may help to improve education for breast cancer patients on endocrine therapy.

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BACKGROUND: Salvage radiotherapy (RT) is a standard treatment for non-metastatic prostate cancer recurrence after radical prostatectomy (RP), yet the efficacy of concurrent hormone therapy remains debated. This systematic review and meta-analysis evaluates the impact of adding hormone therapy to adjuvant or salvage RT on key survival outcomes. METHODS: We searched PubMed, Scopus, Web of Science, and clinical trial registries for randomized phase 2 or 3 trials comparing RT alone versus RT with hormone therapy (anti-androgens or androgen deprivation therapy) in patients undergoing RP. A random-effects meta-analysis with the inverse variance method was performed for overall survival (OS), metastasis-free survival (MFS), and progression-free survival (PFS) after extracting the corresponding hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Four trials with generally low risk of bias were identified. Pooled HRs were 0.85 (95% CI: 0.72-0.99) for OS, 0.82 (95% CI: 0.70-0.96) for MFS, and 0.58 (95% CI: 0.51-0.66) for PFS, favoring hormone therapy. Following a sensitivity analysis that excluded the results of one of the four trials, the significance for OS was no longer observed. CONCLUSION: Hormone therapy with post-RP RT significantly improves OS, MFS, and PFS in prostate cancer patients. Although the benefit in OS appears less robust, these findings support the significant role of hormone therapy in delaying disease progression. PROSPERO Registration Number: CRD42024597336.

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BACKGROUND: Craniofacial fibrous dysplasia (CFD) is a non-malignant disease characterized by fibro-osseous lesions in the affected bones. Management is multidisciplinary, with surgery often serving as the mainstay of treatment and stratified according to four anatomical zones. This study aimed to evaluate the long-term outcomes and assess potential modifications to the algorithm. METHODS: This retrospective study included patients diagnosed with CFD or McCune-Albright syndrome (MAS) who received surgical intervention between 1972 and 2000, with a follow-up period exceeding 20 years. Demographic characteristics, surgical procedures, and follow-up computed tomographic scans and photographs were included in the analysis. RESULTS: Of 93 surgically treated patients with CFD/MAS, 13 were available for ≥20-year follow-up, with complete data and CT imaging (mean 30 ± 6 years, range 20-40 years). Ten patients underwent radical resection and immediate bone graft reconstruction, and two of them experienced recurrence. Three patients underwent therapeutic optic nerve decompression, and two patients experienced post-surgical vision improvement. One patient underwent surgery for hearing loss in the external auditory canal and experienced improved hearing post-surgery. One patient diagnosed with MAS experienced significant relief from craniofacial pain after receiving adjuvant hormone therapy. CONCLUSIONS: Surgical strategies tailored to the four anatomical zones of CFD yield satisfactory outcomes. For Zone 1 lesions, based on our experience, radical resection followed by immediate bone graft reconstruction is a viable option. In Zone 3, therapeutic rather than prophylactic optic nerve decompression is suggested. Orthognathic surgery is also a viable option for such patients, improving occlusion and facial appearance.

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Estetrol is a natural estrogen with a favorable safety profile, showing minimal effects on liver proteins, blood clotting, and breast tissue, which may reduce the risks of blood clots and cardiovascular disease. This review presents the profile of estetrol in support of the rationale of two pivotal phase 3 clinical trials, E4COMFORT I and E4COMFORT II, as well as the design of those. E4COMFORT I and II are aimed at assessing the efficacy and safety of estetrol in the treatment of moderate to severe vasomotor symptoms in postmenopausal women. The E4COMFORT I and II trials were divided into an efficacy part (arms 1-3) and a safety part (arm 4). Efficacy was evaluated through a randomized, double-blind, placebo-controlled study examining two doses of estetrol (15 mg and 20 mg) in postmenopausal participants, both hysterectomized and non-hysterectomized, who experienced 7 or more moderate to severe vasomotor symptoms per day (or 50 or more per week). To comply with Food and Drug Administration and European Medicines Agency guidelines for long-term safety assessments in both groups, these trials evaluated the overall and endometrial safety of unopposed estetrol and of estetrol combined with natural progesterone. The total enrolment across the E4COMFORT I and II trials was 2576 participants. The results of these trials are expected to give a thorough understanding of estetrol 's potential as a new, distinctive treatment option for women with postmenopausal symptoms. CLINICALTRIALS REGISTRATION: NCT04209543 and NCT04090957.

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IMPORTANCE AND OBJECTIVES: Many breast cancer survivors struggle with menopausal symptoms due to oncological treatment-induced hormone deficiency, or because they experience menopause some years after completing treatment, but have limited menopause treatment options. Estrogen replacement therapy is the most effective treatment for menopausal symptoms, but is not recommended after breast cancer because it can increase the risk of relapse. Our objectives were to review the evidence and develop a consensus statement to define the role of menopausal hormone therapy after breast cancer, and to highlight evidence gaps to inform future research. METHODS: A 25-member multidisciplinary panel developed the consensus statements using a modified Delphi methodology. The panel consisted of 18 senior doctors who voted (5 GP menopause specialists, 5 gynecologists, 4 medical oncologists, 3 breast surgical oncologists, and 1 breast radiologist), and 7 members who did not vote (4 patient representatives, 1 medical oncologist, 1 urologist and 1 administrator). Consensus was defined as ≥70% agreement with low-to-moderate variation in extent of agreement (mean absolute deviation from median of ≤0.75). We reviewed current evidence relating to use of vaginal and systemic menopausal hormone therapy ("MHT", also known as "hormone therapy," "HT" or "hormone replacement therapy," "HRT") after breast cancer diagnosis, and adjuvant endocrine (anti-estrogen) therapy, and developed a narrative synthesis. Finally, four additional breast cancer specialists peer-reviewed the manuscript. DISCUSSION AND CONCLUSIONS: The panel agreed that some women may choose to take MHT, (off-label use) and accept an increased risk of relapse in exchange for relief from menopausal symptoms and an improved quality of life, and that preferences may vary according to individual circumstances and the absolute risk of relapse. All respondents agreed or strongly agreed with statements supporting shared decision making and individualized menopause care (MADM 0.29).In our review of the literature, we found mainly moderate quality evidence concerning use of vaginal and systemic estrogen after breast cancer, and high quality evidence concerning the benefits of anti-estrogen therapy for estrogen receptor positive breast cancer. Based on the available data, we recommend that shared decisions are based on (1) an individual's menopausal symptoms and impact on quality of life, (2) the potential increase in an individual's risk of relapse by use of menopausal hormone therapy, and (3) patient preferences, views and treatment goals. Clinicians and patients can use our findings to make informed menopause treatment choices after breast cancer. We strongly recommend registering all patients considering MHT after breast cancer in a clinical study (eg, MENopausal hormone therapy and Outcomes After Breast Cancer, the MENO-ABC trial).

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STUDY QUESTION: How does gender-affirming hormone therapy (GAHT) regimen impact testicular spermatogenesis in transgender and gender diverse (TGD) individuals? SUMMARY ANSWER: Cyproterone acetate (CPA) and progesterone significantly impair spermatogenesis, whereas spironolactone does not, compared to no use of anti-androgen. WHAT IS KNOWN ALREADY: GAHT is known to suppress spermatogenesis in TGD individuals assigned male at birth, but the extent of impairment varies across hormone regimens. Prior studies suggest that anti-androgens and progestogens may exert distinct effects on testicular function, but direct comparisons between regimens are limited. STUDY DESIGN, SIZE, DURATION: This was a retrospective single-center cohort study including 287 TGD patients who underwent gender-affirming orchiectomy between November 2017 and January 2024. A total of 573 testis specimens were histologically reviewed. PARTICIPANTS/MATERIALS, SETTING, METHODS: All included patients had received GAHT prior to surgery, with exposure categorized based on the type and duration of hormone therapy. The primary exposure variables were estrogen use (N = 287, 100%), anti-androgen type (CPA: N = 127, 44.3%; spironolactone: N = 110, 38.3%), and progesterone use (N = 73, 25.4%). Testicular histology was evaluated to determine spermatogenesis stage, and multivariable regression was performed to identify independent predictors of impaired sperm maturation. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 287 patients were included in the study period, and 573 testis specimens were reviewed. Mean age at surgery was 33.9 years (SD = 11.7, range = 18.4-80.6), and duration of GAHT was 3.8 years (SD = 3.0, range = 1-28). Older age was associated with impairment in spermatogenesis, with a mean age of 41.4 (SD = 12.8, range = 23.0-66.5) for end-stage testis failure and a mean age of 33.4 (SD = 11.2, range = 20.2-80.6) for complete maturation (P = 0.002). Hormone therapy duration did not show a significant difference between groups (P = 0.22). GAHT included estrogen (n = 287, 100%), progesterone (n = 73, 25.4%), and an anti-androgen (n = 259, 90.2%). CPA (n = 127, 44.3%) and spironolactone (N = 110, 38.3%) were the most common anti-androgens used. Spermatogenesis was most significantly impaired with the use of CPA, with only 8.7% of patients having active spermatogenesis versus 53.3% of patients taking spironolactone (P < 0.001). Progesterone use had an independent negative effect on spermatogenesis (P = 0.005). LIMITATIONS, REASONS FOR CAUTION: The retrospective design and absence of a control group of untreated individuals limit direct causal inferences. Variability in GAHT duration, adherence, and regimen composition may introduce confounding effects due to self-reporting. Additionally, histological assessment alone does not confirm functional fertility potential, and future studies should explore this aspect. WIDER IMPLICATIONS OF THE FINDINGS: These findings provide clinically relevant insights for fertility counseling in TGD individuals, emphasizing that CPA and progesterone significantly impair spermatogenesis, whereas spironolactone may allow for greater preservation of sperm maturation. This has implications for fertility preservation discussions prior to GAHT initiation and may inform individualized hormone regimen selection based on reproductive goals. STUDY FUNDING/COMPETING INTEREST(S): This research received no specific grant or funding. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: n/a.

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OBJECTIVE: Compare the risk of developing Vestibular schwannoma in patients prescribed Hormone Therapy (HT). METHODS: We performed a systematic review in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA), the search was conducted in English, and we included all the studies that met the following criteria: (a) Participants who presented with VS; (b) Patients prescribed Hormone Replacement Therapy (HRT); (c) Prospective, retrospective or case-control study. RESULTS: Of the 146 articles, four met the inclusion criteria and were included in the systematic review and meta-analysis. Two studies documented an increased relative risk of Vestibular schwannoma in patients that had ever used hormone replacement therapy, another study found an incidence rate 2.2 times higher than the expected incidence rate and the other study indicated a 10% increased odds of the Vestibular Schwannoma in patients who have ever used hormone replacement therapy. CONCLUSION: The use of hormone replacement therapy was associated with an increased relative risk of Vestibular Schwannoma but also demonstrated a lack of a definitive association. LEVEL OF EVIDENCE: Level 1.

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Obesity is highly prevalent among women during the menopausal transition, yet current guidelines still offer limited direction on how to address it in this context. In this Letter, we emphasize the need to incorporate obesity assessment and treatment into menopause care. Obesity worsens vasomotor and genitourinary symptoms and alters the risk profile of menopausal hormone therapy, particularly increasing thromboembolic risk with oral formulations. A more integrated approach-combining hormone therapy with obesity management strategies-could improve metabolic outcomes, relieve symptoms, and lower long-term cardiovascular and oncologic risks. Future guidelines should explicitly address this overlap to support more individualized care for women in midlife.

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BACKGROUND: While most women experience significant perimenopausal symptoms, only a percentage utilize hormone-replacement therapy (HRT). Despite the publicized risks, HRT provides benefits beyond perimenopausal symptom improvement, including decreased risk of cardiovascular disease, stroke, osteoporosis, and affective disorders, and quality of life. METHODS: Subjects were recruited randomly in four clinics. The survey data is uploaded to a survey platform. Data were analyzed to identify reasons for HRT refusal, and to see what associations exist between menopause severity and use of HRT. RESULTS: 71 subjects in total completed the survey. 25 (35%) have never used HRT, and 46 (65%) have used it before. 17 (24%) individuals stated that concerns regarding cancer were central to decision-making on whether they opted to utilize HRT. Possible cancer risk was the most common concern (34, 48%) among the entire study population. The difference between the two groups was not significant regarding specific concerns and reasons as to why they did or did not receive this treatment for menopause. For the Menopause Rating Scale (MRS), the non-HRT group (Group 1) mean was 7.79, and the HRT group (Group 2) mean was 15.07. This difference was significant (two-tailed p = 0.0009).  Conclusions: Findings from this study show there is still a large proportion of women concerned about risks of HRT especially regarding cancer. Future studies aimed at addressing significance in HRT's effect on osteoporosis, cardiovascular disease, and more that impact the morbidity and mortality of menopausal women could be vital to finding a unified stance on this topic.

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BACKGROUND: Women with a pathogenic variant in BRCA1 or BRCA2 are at high risk of developing ovarian cancer and often recommended to undergo bilateral salpingo-oophorectomy at an early age resulting in surgical menopause. Menopausal hormone therapy (MHT) is an effective way to mitigate the adverse outcomes of early menopause; however, the safety of MHT on breast cancer risk in this population has not been established. METHODS: We conducted a prospective matched analysis of MHT use following menopause and breast cancer risk in BRCA carriers. Women who initiated MHT were matched one-to-one with women who had not initiated MHT by gene, year of birth, and age at menopause, resulting in 676 matched pairs. MHT use collected by questionnaire included formulation and mode of administration. RESULTS: After a mean of 5.6 years there were 87 incident breast cancer cases in the 676 exposed women (12·9%) and 128 cases in the 676 unexposed women (18·9%) (P = 0·002). Compared to their unexposed matched controls, women who used estrogen alone (E) experienced a significantly decreased risk of breast cancer (HR = 0·37; 95%: CI 0·24-0·57). There was no protective or adverse effect associated with the use of E plus progestogen (E + P) (HR = 0·94; 95%CI 0·54-1·63). CONCLUSIONS: Our findings suggest there is no significant increase in the risk of breast cancer in BRCA carriers with the use of MHT and that E alone might be protective.

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PURPOSE: Androgen deprivation therapy (ADT) for prostate cancer typically reduces prostate volume. This study investigated how the timing of ADT relative to low-dose-rate (LDR) brachytherapy influences the resulting dosimetric outcomes. METHODS: Using deformable image registration and principal component analysis on pre- and post-ADT magnetic resonance images of 34 patients, we developed a statistical model of ADT-induced prostate deformation. We applied this model to 30 low-dose-rate (LDR) brachytherapy plans (prescription dose: 145 Gy) to simulate seed displacement and dose distribution changes from prostate shrinkage. Prostate deformation over time post-ADT was categorized into early, linear, and late response phases. Dosimetric outcomes were analyzed across scenarios with varying prostate volume reduction magnitudes and different intervals between ADT initiation and brachytherapy. RESULTS: When ADT was initiated concurrently with brachytherapy, the model predicted substantial dose escalation if prostate shrinkage occurred early (prostate D90 ∼206 Gy; urethral V200 ∼47.7%) compared to late shrinkage response (D90 ∼183 Gy; V200 ∼7.1%). In contrast, separating the treatments in time greatly mitigated this effect. For example, assuming early response, performing brachytherapy 3 months before ADT yielded a prostate D90 of ∼183.0 Gy (urethral V200 ∼7.7%), while delaying brachytherapy to 3 months after ADT yielded a D90 of ∼177.8 Gy (V200 ∼1.2%). CONCLUSIONS: Dosimetric analysis showed that greater prostate volume reduction, early ADT response, and concurrent ADT all corresponded to substantially increased doses to the prostate and urethra. Clinically, these findings underscore the importance of carefully planning the timing of ADT relative to brachytherapy to optimize target coverage and minimize unintended dose escalation to normal tissues.

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BACKGROUND: Effective long-term care for breast cancer survivors requires collaboration among providers. Traditional Chinese medicine (TCM) physicians complement symptom management and quality of life. However, how collaboration between TCM physicians and Western medical oncologists/surgeons influences treatment adherence and outcomes remains unclear. Exploring this relationship may optimize interdisciplinary care. OBJECTIVE: To explore the role of hormone therapy (HT) adherence in the relationship between physician partnership and survival outcomes in breast cancer survivors. We specifically assessed whether stronger connectedness between medical oncologists/surgeons and TCM physicians improves recurrence and mortality rates through improved HT adherence. METHODS: We conducted a retrospective, population-based study using Taiwan's National Health Insurance Research Database. We identified adult women with newly diagnosed breast cancer who underwent mastectomy from 2007 to 2016 and received at least 12 months of adjuvant HT. We constructed a physician-level care network for each patient where a tie between physicians was weighted by the number of patients sharing. Tie strength represented the connection between medical oncologists/surgeons and TCM physicians during the year before initial adjuvant HT. The primary endpoints were recurrence and mortality. RESULTS: Among 50,671 patients (median age 52 years), only 40.6% maintained HT adherence. Patients whose oncologists/surgeons and TCM physicians had stronger connectedness showed significantly lower recurrence and mortality risks, with adjusted hazard ratios of 0.97 (95% confidence interval [CI] 0.92-1.03), 0.90 (95% CI 0.85-0.96), and 0.91 (95% CI 0.84-0.98) for low, medium, and high connectedness, respectively, compared to patients without TCM care. The effect of physician partnerships on progression-free survival was partially mediated by adherence to long-term adjuvant HT (12.2%). CONCLUSIONS: Enhanced connectedness between oncologists/surgeons and TCM physicians was associated with increased HT adherence and improved progression-free survival in breast cancer survivors. Our findings suggested that fostering interdisciplinary physician collaboration could benefit long-term outcomes for breast cancer patients via HT adherence.

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Background/Objectives: Therapeutic resistance remains a major obstacle in breast cancer management, particularly among estrogen receptor-positive (ERα+) tumors that initially respond to endocrine therapy such as tamoxifen. Type XI collagen (COL11A1), a minor fibrillar collagen secreted by cancer-associated fibroblasts, has recently emerged as a stromal biomarker linked to tumor progression, immune modulation, and poor prognosis in several solid malignancies. Methods: We conducted a narrative review of the literature indexed in PubMed, Scopus, and Web of Science between 2011 and 2025, including original research, reviews, and clinical studies addressing COL11A1 expression and function in breast cancer. Mechanistic studies in other cancer types (ovarian, pancreatic, lung) were also evaluated when relevant to breast cancer biology. Results: Across multiple cancer types, COL11A1 overexpression correlates with stromal remodeling, epithelial-mesenchymal transition, and resistance to both hormone therapy and chemotherapy. In breast cancer, emerging data suggest a potential prognostic role and possible involvement in shaping the immune microenvironment. Nevertheless, most evidence derives from retrospective or preclinical studies, and clinical validation remains limited. Conclusions: COL11A1 represents a promising, though still exploratory, biomarker of therapeutic resistance and immune modulation in breast cancer. Future prospective and subtype-specific studies are needed to clarify its diagnostic and therapeutic value and to determine whether its inclusion in immunohistochemical panels could enhance patient stratification and guide personalized treatment.

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Background: High-risk prostate cancer is often treated with combined androgen deprivation therapy (ADT) and radiotherapy (RT). Blood biomarkers may enable treatments to be tailored to individual patients. Metabolomics, the study of small-molecule alterations in blood, is promising, and lipids are emerging as potential markers of poor prognosis. This study aims to investigate metabolic changes during prostate cancer treatment and their correlation to disease outcome. Methods: This study included 136 blood plasma samples from 35 patients with high-risk prostate cancer treated with RT and ADT, recruited from the Uppsala/Umeå Comprehensive Cancer Consortium (U-CAN) project. Blood samples were collected before, during, and after treatment and analyzed at Metabolon Inc. (Durham, NC, USA). To study differences in metabolic levels during treatment, three different sampling time points were considered: before ADT, in-between ADT and RT, and after RT. Both multivariate (orthogonal projections to latent structures, OPLS) and univariate analyses were performed, where statistical significance in combination with a large fold change was considered indicative of a substantial change. Results: Significant changes in metabolite levels were observed. Many of the significant metabolites for the whole course of treatment were also significant during ADT but not during RT, indicating that changes during ADT dominated the overall treatment. Changes were found to be especially common in steroids and fatty acids. Multivariate analysis revealed significant differences in metabolites between relapsing and non-relapsing patients. Among the significant metabolites were cholesterol and epiandrosterone. Conclusions: Metabolomics can identify biomarkers for prostate cancer treatment response and relapse. Further studies are needed to identify patterns and individual metabolites to personalize treatment strategies for prostate cancer.

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Introduction: Gender-affirming hormone therapy (GAHT) is associated with improvements in gender congruence and changes in psychosocial functioning, yet its effects on social health are not yet known. Social health, i.e., someone having adequate quantity and quality of relationships to meet their needs for meaningful connection, is a key determinant of quality of life. Understanding potential changes in social health during GAHT is therefore essential to information provision for trans and gender diverse (TGD) people. The study, AFFIRM Relationships, aims to prospectively examine how GAHT affects social health and to isolate the biological effects of hormonal intervention relative to other gender-affirming treatments (i.e., mastectomy and voice training). Methods: We will conduct a multi-arm prospective longitudinal cohort study of TGD people who start GAHT, gender-affirming voice training, or gender-affirming mastectomy, prospectively following participants from before starting treatment to 3, 6, 12, and 24 months after starting treatment. We will examine changes in social health, including potential changes in social networks. We aim to disentangle the ways in which social health changes after GAHT by examining changes in psychosocial functioning and the potential roles of social stigma and gender congruence. Furthermore, we will compare the effects of GAHT, which induces a systemic biological change, to the effects of voice training and mastectomy, which are non-systemic interventions, to better understand the unique biological effects of GAHT. Ethics and dissemination: Ethical approval for this study was granted by the Medical Ethical Committee of Amsterdam UMC (study no. 2024.0927). Results from this study will be disseminated via academic peer-reviewed publications, adapted into guidelines for clinical care, and we will co-design dissemination strategies for the TGD community together with a group of lived experienced experts (LEEs). Registration: N/A.

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PURPOSE: This narrative review aims to highlight key learning points from the Women's Health Initiative (WHI) studies, providing a nuanced appraisal of menopausal hormone therapy (MHT) risks and benefits in postmenopausal women. METHODS: A structured PubMed search was conducted using MeSH terms and keywords for MHT, bone health, cardiovascular and metabolic disease, cancer (breast, endometrial, ovarian, colorectal), and cognitive outcomes. The search included clinical trials, observational studies, and systematic reviews published in the English language. RESULTS: WHI data reveal that both combined conjugated equine estrogen-medroxyprogesterone acetate (CEE-MPA) and CEE-only therapy significantly reduce hip, vertebral, and total fracture risk, with further skeletal protection from calcium and vitamin D co-administration. Cardiovascular outcomes are strongly influenced by timing: initiation before age 60 or within 10 years of menopause may confer benefit, while delayed initiation (≥65 years) increases risks of coronary events and stroke, supporting the "window of opportunity" hypothesis. CEE-MPA therapy increases invasive breast cancer incidence (especially in prior users), while estrogen-only therapy is associated with a marginal non-significant reduction in breast cancer risk. Both regimens lowered colorectal cancer incidence during active treatment. Early MHT initiation has no effect on cognitive function, whereas late initiation increases dementia risk. CONCLUSIONS: WHI findings underscore the importance of individualized, time-sensitive MHT use, with benefits and risks shaped by formulation, timing, and patient characteristics. These insights continue to inform evolving clinical practice.

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ABSTRACT: Gender minority (GM) persons have been reported to experience chronic pain at higher rates than the general population, yet comprehensive pain phenotyping in this group remains underexplored. The goal of this cross-sectional study was to characterize chronic pain and pain-related factors in GM persons and examine associations of these characteristics with gender identity and gender-affirming hormone therapy (GHT). One hundred three GM adults completed validated questionnaires assessing pain characteristics and severity, sleep, fatigue, stress, trauma, and the chronic overlapping pain condition (COPC) screener. Participants included those who identify as transgender men (TGM), transgender women (TGW), and gender-expansive persons (all assigned female sex at birth). Overall, 50.5% of the entire cohort reported the presence of chronic pain. Transgender men and gender-expansive persons reported greater pain severity, pain interference, fibromyalgianess, stress, and sleep disturbances compared with TGW. Widespread pain was common (36%-45.8% across groups), and 15.5% of the entire cohort met criteria for fibromyalgia. Transgender men and gender-expansive individuals also had increased numbers of COPCs than TGW. Stress, but not GHT type or gender identity, was significantly associated with chronic pain in multivariable models. Chronic pain and nociplastic symptoms are highly prevalent among GM persons, particularly among TGM and gender-expansive persons, and stress appears to be a key contributor to the pain phenotype. These findings underscore the need for longitudinal research into the biopsychosocial drivers of chronic pain in the GM population and the effects of GHT on pain in GM persons.

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Following a rigorous systematic review of the literature, the International Menopause Society (IMS) has produced detailed new recommendations and key messages on women's midlife health, menopause and menopause hormone therapy (MHT) to help guide healthcare professionals to optimize their management of women at this critical stage of life. The term MHT has been used to cover therapies including estrogens, progestogens and combined regimens. This guidance provides a summary of the recommendations and key messages generated from the systematic review process. The longer version, including the detailed text, key meta-analyses, references, figures and supplementary materials, will be published simultaneously online and can be accessed via the IMS website (https://www.imsociety.org/statements/ims-recommendations/). The quality of evidence and the strength of recommendations used in this guideline are based on the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) and the Appraisal of Guidelines for Research & Evaluation II (AGREE II) approaches. The new recommendations now include levels of evidence, grades of recommendations, good practice points and key messages.The recommendations were developed by a body of 38 authors and 26 support team members derived from the IMS and other organizations. Global stakeholder surveys, targeted at both healthcare providers and consumers, were initially conducted to identify the key questions. A Publication Steering Committee (PSC) provided oversight of the process through regular meetings and ensured consistency of methodology. By the end of the process, 30 completed sections were submitted by the authors to individual lead reviewers selected from the PSC to provide peer review and finally endorsed by the PSC, IMS board and stakeholders. Overall, 341 recommendations (285 supported by research data and 56 good practice points) and 38 key messages have been formulated. These span a diverse range of health topics, including lifestyle, midlife body changes, vasomotor symptoms, genitourinary syndrome of menopause, osteoporosis, cardiometabolic health, dementia, premature ovarian insufficiency and various malignancies. A new section addresses the often-overlooked topic of sarcopenia which requires urgent attention. Current controversial topics, such as the influence of the media, the role of the pharmaceutical industry and publication ethics, are also explored.The overall aim of these recommendations and guidelines is to provide the blueprint for the management of women's midlife health and menopause, given the latest available evidence. In preparing these international recommendations, experts have endeavored to consider geographical variations in medical care, prevalence of diseases/conditions, symptom severity, availability and licensing of MHT and alternatives, and country-specific attitudes of the public, medical community and health authorities toward menopause management.