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• Aggressive angiomyxoma is a rare mesenchymal myxoid neoplasm in women at reproductive age. • The main treatment is surgery, but local recurrence rate is high. • Careful preoperative evaluation and long-term follow-up are important. Aggressive angiomyxoma is an uncommon mesenchymal neoplasm characterized by a high recurrence rate, usually observed in the lower genital tract of women during their reproductive age. Seventeen cases of aggressive angiomyxoma confirmed by pathology from January 2007 to December 2021 in Beijing Chao-yang Hospital were included. We collected clinical data and summarized the clinical and immunohistochemical features. All seventeen included patients were females, aged between 23 and 57 years (mean, 37.7 years; median, 42 years). Fourteen patients were newly diagnosed and three were recurrent. The tumors were located in vulva (58.8 %), vagina (23.5 %), buttock (11.8 %), and cervix (5.9 %). The tumors size were 2 to 15 cm in greatest dimension (mean 8 ± 4.4 cm, median 6 cm). Follow-up data was available for nine patients, which ranged from 25 to 124 months (mean, 82 months; median, 80 months). At the end of follow-up, no other recurrence or metastasis was reported. Immunohistochemical analysis showed immunoreactive for estrogen (10/11) and progesterone (8/11) receptor, desmin (6/8), smooth muscle actin (4/10), and vimentin (4/4), S-100 (1/8) and CD34 (1/7). The Ki67 level was less than 5 % in five cases. AAM is a hormone-sensitive, distinct rare mesenchymal neoplasm with high incidence of local recurrence. Surgery is the preferred treatment, with complete resection being an essential prerequisite for minimizing the risk of recurrence. [ABSTRACT FROM AUTHOR]

• The association between cognition and hormone therapy (HT) changed after 2002. • The Women's Health Initiative study altered the health profile of those using HT. • The association between HT and cognition is influenced by a selection effect. Mild cognitive impairment may be caused by pathophysiological changes occurring decades prior to symptom development. It has been hypothesised that oestrogen can prevent such changes. We aimed to investigate the association between postmenopausal hormone therapy and cognition in Danish female twins and to examine differences in this association before and after publication of the findings from the Women's Health Initiative study in 2002. This study includes cognitive assessment of 4510 twins aged 50+ years. Information on hormone therapy was obtained through Danish health registries. The association between current hormone therapy use and cognition was analysed in twins aged 50+ using both cross-sectional, intrapair and longitudinal analysis, adjusting for age, education, social class, and unobserved familial confounding. Cross-sectionally, systemic HT users aged 70+ had a significantly lower cognitive function than non-users, whereas systemic HT users aged 50–69 did not differ from non-users before 2002. Longitudinal data in younger twins aged 50–69 showed a significantly lower cognitive function in systemic HT users after 2002 compared to non-users. Systemic HT users aged 70+ showed that the lower cognitive function was most explicit before 2002, whereas after 2002 the cognitive function was closer to non-users. Twins aged 50–69 who changed from systemic HT to local HT after 2002, or dropped it altogether, performed cognitively better. Our findings cautiously indicate a change in the association between cognition and hormone therapy use after 2002, which suggests an alteration in the hormone therapy user profile in the wake of the 2002 WHI publication. [ABSTRACT FROM AUTHOR]

Over the last 70 years, oestrogen therapy for the management of menopausal symptoms has undergone a metamorphosis from perceived cardiovascular protection to perceived cardiovascular risk. The former perception is based on the convincing evidence from the Nurses' Health Study cohorts and the epidemiological data surrounding early menopause. The latter, and later, perception is based on the disquieting results from two randomised controlled studies, the Heart and Estrogen/Progestin Replacement Study (HERS) and the Women's Health Initiative study (WHI). The reality is probably more nuanced than the conclusions presented by any of these studies. When face to face with a patient, the clinician must negotiate the appropriate decision pathway around the interaction between cardiovascular risk, cardiovascular disease, menopause, and oestrogen +/− progestogen–containing hormone therapy. The metamorphosis from perceived cardiovascular protection to perceived cardiovascular risk, a perception largely led by the Women's Health Initiative study, has shifted the clinician's risk/benefit decision-making away from prescribing menopausal hormone therapy (MHT) for menopausal symptoms. A more nuanced view of the literature and the greater availability of different modes of delivery and formulations of MHT should give the clinician the knowledge and confidence to prescribe appropriate MHT for the greater benefit of midlife health and cardiovascular safety. Image by Bronwyn G. A. Stuckey. [ABSTRACT FROM AUTHOR]

Infantile epileptic spasms syndrome (IESS) with Down syndrome has good treatment response and good seizure outcomes with high-dose adrenocorticotrophic hormone (ACTH) therapy. We investigated the early treatment response of epileptic spasms (ES), long-term seizure outcome, and efficacy of very-low-dose ACTH therapy for IESS with Down syndrome. We retrospectively investigated patients with Down syndrome and IESS between April 1983 and January 2023. We defined response to treatment as clinical remission and electrographic resolution of hypsarrhythmia after treatment for more than one month and early treatment as any treatment for ES within three months of initiation of treatment. Long-term seizure outcomes were determined by the presence of any type of seizure within one year of the last visit. We investigated the dosage and efficacy of very-low-dose ACTH therapy. Thirty patients were enrolled with a median follow-up period of 7.7 years (range: 1.3 to 19.1). The response and relapse rates in the early treatment were 83.3% and 16.0%, respectively. The seizure-free rate of long-term seizure outcomes was 80.0%. Long-term seizure outcomes correlated with early treatment response to ES. The response rate of very-low-dose ACTH therapy was 59.3%. The efficacy of ACTH therapy tended to be dose-dependent (P = 0.055). Early treatment response to ES may be useful in predicting long-term seizure outcomes of IESS with Down syndrome. Very-low-dose ACTH therapy was the most effective treatment for ES and could exhibit dose-dependent efficacy. Depending on the IESS etiology, the ACTH dose could be reduced to minimize its side effects. [ABSTRACT FROM AUTHOR]

Sex hormones have biological effects on inflammation, and these might contribute to the sex-specific features of depression. C-reactive protein (CRP) is the most widely used inflammatory biomarker and consistent evidence shows a significant proportion (20–30 %) of patients with major depressive disorder (MDD) have CRP levels above 3 mg/L, a threshold indicating at least low-grade inflammation. Here, we investigate the interplay between sex hormones and CRP in the cross-sectional, observational Biomarkers in Depression Study. We measured serum high-sensitivity (hs-)CRP, in 64 healthy controls and 178 MDD patients, subdivided into those with hs-CRP below 3 mg/L (low-CRP; 53 males, 72 females) and with hs-CRP above 3 mg/L (high-CRP; 19 males, 34 females). We also measured interleukin-6, testosterone, 17-β-estradiol (E2), progesterone, sex-hormone binding globulin (SHBG), follicle-stimulating and luteinising hormones, and calculated testosterone-to-E2 ratio (T/E2), free androgen and estradiol indexes (FAI, FEI), and testosterone secretion index. In males, high-CRP patients had lower testosterone than controls (p = 0.001), and lower testosterone (p = 0.013), T/E2 (p < 0.001), and higher FEI (p = 0.015) than low-CRP patients. In females, high-CRP patients showed lower SHGB levels than controls (p = 0.033) and low-CRP patients (p = 0.034). The differences in testosterone, T/E2 ratio, and FEI levels in males survived the Benjamini-Hochberg FDR correction. In linear regression analyses, testosterone (β = −1.069 p = 0.033) predicted CRP concentrations (R2 = 0.252 p = 0.002) in male patients, and SHBG predicted CRP levels (β = −0.628 p = 0.009, R2 = 0.172 p = 0.003) in female patients. These findings may guide future research investigating interactions between gonadal and immune systems in depression, and the potential of hormonal therapies in MDD with inflammation. • Males with MDD show decreased levels of testosterone and TSI. • Females with MDD and healthy controls have similar sex hormone levels. • Males with MDD with high-CRP have decreased levels of testosterone. • Females with MDD and high-CRP have decreased levels of SHBG. • In MDD, CRP levels are predicted by testosterone in males and by SHBG in females. [ABSTRACT FROM AUTHOR]

Introduction: Recurrent postmenopausal bleeding (PMB) occurs in 6%–25% of postmenopausal women who have experienced a previous episode of PMB. The question of whether recurrent PMB leads to a higher risk of endometrial cancer (EC) in comparison to a single episode of PMB is, however, controversial. Furthermore, little is known about predictive factors for recurrent PMB. Material and Methods: A multicenter prospective cohort study was conducted over a 5‐year period in four hospitals in the Netherlands. Women with PMB undergoing endometrial sampling and aged 40 years and older were included. Occurrence of recurrent PMB was retrospectively determined. Primary outcomes included (1) the incidence of recurrent PMB and (2) differences in pathological findings between patients with a single episode vs recurrent PMB. Secondary outcomes included (1) the association between diagnosis of benign polyps at first PMB and pathological findings at recurrent PMB and (2) factors predictive for recurrent PMB. Results: A total of 437 women with PMB were included, of whom 360 were at risk of recurrent PMB. With a median follow‐up of 61 months (IQR (Interquartile range) 44–73), 26.4% experienced recurrent PMB. Patients with recurrent PMB were more often diagnosed with benign polyps (34.7% vs. 25.1%, p‐value 0.015) and less frequently with a malignancy (5.3% vs. 17.8%, p‐value 0.015), compared to patients with a single episode of PMB. Benign polyps at initial PMB were not associated with a (pre)malignancy at recurrence (OR 4.16, 95% CI 0.75–23.03). Predictive factors for recurrent PMB included use of hormone replacement therapy (HRT) (OR 3.32, 95% CI 1.64–6.72), and benign polyps at initial PMB (OR 1.80, 95% CI 1.07–3.04). Conclusions: Recurrent PMB is common in women with a previous episode of PMB. Compared to patients with a single episode of PMB, patients with recurrent PMB and benign histological outcomes at accurate workup during their first episode were less often diagnosed with malignancies and more frequently with benign polyps. Benign polyps at first PMB are predictive for recurrent PMB, but not for a higher risk of (pre)malignancy. [ABSTRACT FROM AUTHOR]

Purpose: Individuals with gender dysphoria (GD) may request hormone therapy and various surgical operations to change their physical characteristics. The present study aimed to investigate the effects of two treatments, mastectomy and gender-affirming hormone therapy (GAHT), on adults with GD who were assigned female at birth (GD AFAB). Methods: In this cross-sectional study, we gathered data from a total of 269 individuals in three groups: (a) untreated group (n = 121), (b) GAHT group (n = 84) who had been receiving treatment for at least 6 months, and (c) GAHT-MAST group (n = 64) who had been using GAHT for at least 6 months and had undergone mastectomy at least 3 months prior. All participants were asked to complete the Symptom Checklist-90-Revised (SCL-90-R), the Body Uneasiness Test (BUT), and the World Health Organization's Quality of Life Questionnaire- Brief Form, Turkish Version (WHOQOL-BREF-Tr). Results: We found that individuals in the untreated group had higher psychopathological symptoms and body uneasiness scores, and lower quality of life scores compared to both GAHT and GAHT-MAST groups. There was no difference in psychopathology between the GAHT-MAST group and the GAHT group, but body uneasiness scores were lower, and quality of life scores were higher in the GAHT-MAST group. Conclusion: Our study suggests that individuals receiving GAHT improved mental health, body satisfaction, and overall quality of life. Combining mastectomy with GAHT may further enhance these benefits. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Hot flashes are a common side effect of endocrine therapy (ET) that contribute to poor quality of life and decreased treatment adherence.Patients with breast cancer wo were receiving ET and experiencing hot flashes were enrolled through three parallel, randomized trials conducted in the United States, China, and South Korea. Participants were randomized to either immediate acupuncture (IA) or delayed acupuncture control (DAC). IA participants received 20 acupuncture sessions over 10 weeks, whereas DAC participants received usual care, then crossed over to acupuncture with a reduced intensity. The primary end point was a change in score on the endocrine symptom subscale of the Functional Assessment of Cancer Therapy (FACT)‐Endocrine Symptoms between baseline and week 10. Secondary end points included the hot flash score and the FACT‐Breast score. A planned pooled analysis of individual patient data was performed using longitudinal mixed models.In total, 158 women with stage 0–III breast cancer were randomized (United States, n = 78; China, n = 40; South Korea, n = 40). At week 10, IA participants reported statistically significant improvements in the endocrine symptom subscale score (mean change ± standard error: 5.1 ± 0.9 vs. 0.2 ± 1.0; p = .0003), the hot flash score (−5.3 ± 0.9 vs. −1.4 ± 0.9; p < .003), and the FACT‐Breast total score (8.0 ± 1.6 vs. −0.01 ± 1.6; p = .0005) compared with DAC participants. The effect of the acupuncture intervention differed by site (p = .005).Acupuncture led to statistically and clinically meaningful improvements in hot flashes, endocrine symptoms, and breast cancer‐specific quality of life in women undergoing ET for breast cancer in the United States, China, and South Korea. [ABSTRACT FROM AUTHOR]

Hormone receptor-positive (HR+) breast cancer (BC) is the most common type of breast cancer among women worldwide, accounting for 70–80% of all invasive cases. Patients with HR+ BC are commonly treated with endocrine therapy, but intrinsic or acquired resistance is a frequent problem, making HR+ BC a focal point of intense research. Despite this, the malignancy still lacks adequate in vitro and in vivo models for the study of its initiation and progression as well as response and resistance to endocrine therapy. No mouse models that fully mimic the human disease are available, however rat mammary tumor models pose a promising alternative to overcome this limitation. Compared to mice, rats are more similar to humans in terms of mammary gland architecture, ductal origin of neoplastic lesions and hormone dependency status. Moreover, rats can develop spontaneous or induced mammary tumors that resemble human HR+ BC. To date, six different types of rat models of HR+ BC have been established. These include the spontaneous, carcinogen-induced, transplantation, hormone-induced, radiation-induced and genetically engineered rat mammary tumor models. Each model has distinct advantages, disadvantages and utility for studying HR+ BC. This review provides a comprehensive overview of all published models to date. [ABSTRACT FROM AUTHOR]

Background: Hormone therapy (HT) use among menopausal women declined after negative information from the 2002 Women's Health Initiative (WHI) HT study. The 2017 post-intervention follow-up WHI study revealed that HT did not increase long-term mortality. However, studies on the effects of the updated WHI findings are lacking. Thus, we assessed the impact of the 2017 WHI findings on HT use in Taiwan. Methods: We identified 1,869,050 women aged 50–60 years, between June and December 2017, from health insurance claims data to compare HT use in the 3 months preceding and following September 2017. To address the limitations associated with interval-censored data, we employed an emulated repeated cross-sectional design. Using logistic regression analysis, we evaluated the impact of the 2017 WHI study on menopausal symptom-related outpatient visits and HT use. In a scenario analysis, we examined the impact of the 2002 trial on HT use to validate our study design. Results: Study participants' baseline characteristics before and after the 2017 WHI study were not significantly different. Logistic regressions demonstrated that the 2017 study had no significant effect on outpatient visits for menopause-related symptoms or HT use among women with outpatient visits. The scenario analysis confirmed the negative impact of the 2002 WHI trial on HT use. Conclusions: The 2017 WHI study did not demonstrate any impact on either menopause-related outpatient visits or HT use among middle-aged women in Taiwan. Our emulated cross-sectional study design may be employed in similar population-based policy intervention studies using interval-censored data. [ABSTRACT FROM AUTHOR]

Background: Significant scientific research has been conducted concerning menopausal syndrome(MPS), yet few bibliometric analyses have been performed. Our aim was to recognise the 100 most highly cited published articles on MPS and to analytically evaluate their key features. Methods: To identify the 100 most frequently cited articles, a search was conducted on Web of Science using the term 'menopausal syndrome'. Articles that matched the predetermined criteria were scrutinised to obtain the following data: citation ranking, year of publication, publishing journal, journal impact factor, country of origin, academic institution, authors, study type, and keywords. Results: The publication period is from January 1, 2000, to August 31, 2022. The maximum number of citations was 406 and in 2012. The median citations per year was 39.70. Most of the articles focused on treatment and complications. These articles were published in 36 different journals, with the Journal of MENOPAUSE having published the greatest number (14%). Forty-eight articles (48%) were from the United States, with the University of Pittsburgh being the leading institute (9%). Joann E. Manson was the most frequent first author (n = 6). Observational studies were the most frequently conducted research type (n = 53), followed by experimental studies (n = 33). Keyword analysis identified classic research topics, including genitourinary syndrome of menopause, bone mineral density (BMD), and anti-mullerian hormone (AMH) loci. Conclusion: Using bibliometrics, we conducted an analysis to identify the inadequacies, traditional focal points, and potential prospects in the study of MPS across current scientific areas. Treatment and complications are at the core of MPS research, whereas prediction and biomarkers have less literature of high quality. There is a necessity for innovative analytical metrics to measure the real effect of these papers with a high level of citation on clinical application. [ABSTRACT FROM AUTHOR]

Background: Endocrine resistance driven by sustained activation of androgen receptor (AR) signaling pathway in advanced prostate cancer (PCa) is fatal. Characterization of mechanisms underlying aberrant AR pathway activation to search for potential therapeutic strategy is particularly important. Rac GTPase-activating protein 1 (RACGAP1) is one of the specific GTPase-activating proteins. As a novel tumor proto-oncogene, overexpression of RACGAP1 was related to the occurrence of various tumors. Methods: Bioinformatics methods were used to analyze the relationship of expression level between RACGAP1 and AR as well as AR pathway activation. qRT-PCR and western blotting assays were performed to assess the expression of AR/AR-V7 and RACGAP1 in PCa cells. Immunoprecipitation and immunofluorescence experiments were conducted to detect the interaction and co-localization between RACGAP1 and AR/AR-V7. Gain- and loss-of-function analyses were conducted to investigate the biological roles of RACGAP1 in PCa cells, using MTS and colony formation assays. In vivo experiments were conducted to evaluate the effect of RACGAP1 inhibition on the tumor growth. Results: RACGAP1 was a gene activated by AR, which was markedly upregulated in PCa patients with CRPC and enzalutamide resistance. AR transcriptionally activated RACGAP1 expression by binding to its promoter region. Reciprocally, nuclear RACGAP1 bound to the N-terminal domain (NTD) of both AR and AR-V7, blocking their interaction with the E3 ubiquitin ligase MDM2. Consequently, this prevented the degradation of AR/AR-V7 in a ubiquitin-proteasome-dependent pathway. Notably, the positive feedback loop between RACGAP1 and AR/AR-V7 contributed to endocrine therapy resistance of CRPC. Combination of enzalutamide and in vivo cholesterol-conjugated RIG-I siRNA drugs targeting RACGAP1 induced potent inhibition of xenograft tumor growth of PCa. Conclusion: In summary, our results reveal that reciprocal regulation between RACGAP1 and AR/AR-V7 contributes to the endocrine resistance in PCa. These findings highlight the therapeutic potential of combined RACGAP1 inhibition and enzalutamide in treatment of advanced PCa. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionThis study aimed to investigate the association of hormone replacement therapy (HRT) use, type, duration and age of commencement with myocardial infarction (MI) and stroke in postmenopausal Korean women.This nested case–control study used data from the National Health Insurance Service database to analyze 2017 data from women aged ≥50 years and diagnosed with natural menopause between 2004 and 2007. Among 356,160 eligible women, 36,446 used HRT for ≥1 year and 319,714 did not (controls). These two groups were matched 1:1 for statistical analysis. Type and duration were categorized into three categories.Women who started estrogen–progestogen therapy (EPT) or estrogen therapy (ET) in their 50s, or EPT or tibolone in their ≥60s exhibited a lower stroke risk than controls. MI risk was lower among women who used tibolone – regardless of duration – or EPT or ET for 1–3 years than among controls. Stroke risk was lower with tibolone use for ≥5 years or with EPT or ET use for 1–3 years or ≥5 years than non-users.Our study may support the beneficial effect of HRT by showing that Korean postmenopausal women who used HRT at a relatively younger and healthier age had a relative benefit for MI and stroke. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions The effect of hormone replacement therapy (HRT) on colorectal cancer (CRC) mortality and all‐cause mortality remains unclear. We conducted a systematic review and dose–response meta‐analysis to determine the effects of HRT on CRC mortality and all‐cause mortality.We searched the electronic databases of PubMed, Embase, and The Cochrane Library for all relevant studies published until January 2024 to investigate the effects of HRT exposure on survival rates for patients with CRC. Two reviewers independently extracted individual study data and evaluated the risk of bias between the studies using the Newcastle‒Ottawa Scale. We performed a two‐stage random‐effects dose–response meta‐analysis to examine a possible nonlinear relationship between the year of HRT use and CRC mortality.Ten cohort studies with 480,628 individuals were included. HRT was inversely associated with the risk of CRC mortality (hazard ratios (HR) = 0.77, 95% CI (0.68, 0.87), I2 = 69.5%, p < 0.05). The pooled results of seven cohort studies revealed a significant association between HRT and the risk of all‐cause mortality (HR = 0.71, 95% CI (0.54, 0.92), I2 = 89.6%, p < 0.05). A linear dose–response analysis (p for nonlinearity = 0.34) showed a 3% decrease in the risk of CRC for each additional year of HRT use; this decrease was significant (HR = 0.97, 95% CI (0.94, 0.99), p < 0.05). An additional linear (p for nonlinearity = 0.88) dose–response analysis showed a nonsignificant decrease in the risk of all‐cause mortality for each additional year of HRT use.This study suggests that the use of HRT is inversely associated with all‐cause and colorectal cancer mortality, thus causing a significant decrease in mortality rates over time. More studies are warranted to confirm this association. [ABSTRACT FROM AUTHOR]

Background: Hormone therapy, which is widely prescribed for prostate cancer, might induce cognitive impairment and affect the autonomy of elderly patients. However, previous studies provided conflicting results. The aim of this systematic review and meta‐analysis was to synthesize the longitudinal impact of hormone therapy on objective (cognitive tests) and subjective (questionnaires) cognition. Methods: A search was performed of the PubMed, Web of Science, and PsycINFO databases. Studies that longitudinally assessed cognition in patients undergoing androgen‐deprivation therapy and new‐generation hormone therapy were considered. To perform a meta‐analysis, available scores were aggregated and classified into six objective domains and one subjective domain. Weighted mean effect sizes were computed using a random effect model. Results: Twenty studies were included in the systematic review (1440 patients), and 15 could be included in the meta‐analysis (1093 patients). In the systematic review, 20%–50% of patients had objective cognitive impairment before treatment initiation. The meta‐analysis revealed a decline in subjective cognition (g = −0.44; p =.03) with androgen‐deprivation therapy and new‐generation hormone therapy. All other effect sizes were small (from g = −0.02 to g = 0.18), and none of them indicated a significant decline in objective cognition. Significant heterogeneity was observed in all domains of objective cognition. Conclusions: This synthesis presents the first meta‐analytic evidence of the negative impact of androgen‐deprivation therapy and new‐generation hormone therapy on subjective cognition. In contrast, there was no conclusive evidence of a decline in objective cognition. The high heterogeneity underscores the need for homogeneous cognitive research on prostate cancer. Plain Language Summary: There is no consensus on the cognitive impairment induced by hormone therapy for prostate cancer, despite the implications for patients' care and daily life.This synthesis of published studies demonstrated an increase in perceived cognitive difficulties but did not prove a decline in cognitive performance during treatment. This systematic review and meta‐analysis demonstrates that hormone therapy for prostate cancer has an impact on perceived cognitive impairment. Few studies have assessed the impact of new‐generation hormone therapy on objective cognition, and there was no conclusive evidence of objective decline, regardless of the treatment generation. [ABSTRACT FROM AUTHOR]

Background: We aimed to compare the prognostic values of 'localized treatment to the primary lesion (LT) plus hormone therapy (HT)' versus 'HT alone' in metastatic hormone-sensitive prostate cancer (mHSPC). Methods: We conducted a systematic search through the databases of PubMed®, Web of Science®, and Cochrane library® in April 2023 based on the PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) statement. A pooled meta-analysis was performed to assess the prognostic differences between LT + HT and HT alone according to randomized and non-randomized controlled studies (RCTs and NRCTs, respectively). Results: The search identified three RCTs and eight NRCTs. In RCTs, LT did not show prognostic benefits regarding biochemical-failure free rate nor overall survival (OS), although in patients with low tumor burdens, the LT + HT group showed better OS (HR: 0.68, 95% CI: 0.54–0.86). In the NRCTs, the LT+HT group showed superior progression-free survival (hazard ratio (HR): 0.42, 95% confidence interval (CI): 0.21–0.87), cancer-specific survival (HR: 0.39, 95% CI: 0.20–0.76), and OS (HR: 0.63, 95% CI: 0.57–0.69) to the HT alone group. In addition, better OS was observed in the LT +HT group regardless of the type of treatment modality for LT; radical prostatectomy (HR: 0.52, 95% CI: 0.39–0.69), radiotherapy (HR: 0.63, 95% CI: 0.56–0.71) in NRCTs. Conclusions: LT to the primary lesion in metastatic hormone-sensitive prostate cancer may provide prognostic benefits and especially in patients with low tumor burden. [ABSTRACT FROM AUTHOR]

Background: Depression is a prevalent mental health problem in postmenopausal women. Given its significant impact on the quality of life and overall well-being of postmenopausal women, there is need for a comprehensive review and meta-analysis of the existing research globally. This systematic review and meta-analysis evaluated the global prevalence of depression and potential associated factors in postmenopausal women. Methods: The Cochrane Library, PubMed, EMBASE, Web of Science, MEDLINE, and PsycINFO databases were systematically searched from inception to March 22, 2023. The meta-analysis used the random-effects model to calculate the prevalence of depression rates and associated factors. In addition, subgroup analysis and sensitivity analysis were performed. Publication bias was assessed using funnel plots, Egger's test, and nonparametric trim-and-fill tests. Results: The meta-analysis included 50 studies that involved 385,092 postmenopausal women. The prevalence of depression in postmenopausal women was 28.00% (95% CI, 25.80–30.10). Among the factors relevant to depression among postmenopausal women, marital status (OR: 2.03, 95%CI: 1.33–3.11), history of mental illness (OR: 2.31, 95%CI: 1.50–3.57), chronic disease (OR: 3.13, 95%CI: 2.20–4.44), menstrual cycle (OR: 1.42, 95%CI: 1.17–1.72), abortion numbers (OR: 1.59, 95%CI: 1.40–1.80), menopausal symptoms (OR: 2.10, 95%CI: 1.52–2.90), and hormone replacement therapy (OR: 1.76, 95%CI: 1.31–2.35) were risk factors, while physical activity (OR: 0.56, 95%CI: 0.53–0.59), number of breastfed infants (OR: 0.43, 95%CI: 0.19–0.97), menopause age (OR: 0.44, 95%CI: 0.37–0.51) were preventive factors. Conclusions: This study demonstrated that the prevalence of postmenopausal depression is high, and some risk factors and protective factors associated with it have been identified. It is necessary to improve screening and management and optimize prevention and intervention strategies to reduce the harmful effects of postmenopausal depression. [ABSTRACT FROM AUTHOR]

Background: Teratomas are germ cell tumors composed of somatic tissues from up to three germ layers. Primary retroperitoneal teratomas usually develop during childhood and are uncommon in adults and in the retroperitoneal space. While there are only a few cases of retroperitoneal thyroid tissue, we report a unique case of a retroperitoneal papillary thyroid carcinoma. Case presentation: A 41-year-old woman presented in our institution due to intermitted unspecific abdominal pain. Magnetic resonance imaging detected a multi-cystic solid retroperitoneal mass ventral to the psoas muscle and the left iliac artery. After surgical removal of the retroperitoneal mass, histology sections of the specimen indicated evidence of papillary thyroid carcinoma cells. A staging computed tomography scan of the body showed no further manifestations. To reduce the risk of recurrence, total thyroidectomy was performed followed by radioiodine therapy with lifelong hormone substitution. Conclusions: Primary retroperitoneal teratoma with evidence of papillary thyroid carcinoma is a rare condition. Preoperative diagnosis is difficult due to its non-specific clinical manifestation and lack of specific radiologic findings. Histopathology analysis is necessary for diagnosis. Although surgery is considered the first line treatment, there is still discussion about the extent of resection and the need for total thyroidectomy with adjuvant radioiodine therapy. [ABSTRACT FROM AUTHOR]

Despite limited research on refractory and/or endocrine therapy failure in elderly metastatic breast cancer (MBC) patients, a prior study showed that low-dose oral cyclophosphamide (CY) can improve the overall survival rate of MBC patients, possibly through the immunoregulation of regulatory T cells (Tregs). We preliminarily investigated the combination of endocrine therapy (ET) with oral low-dose CY as salvage therapy in elderly patients via peripheral blood regulatory T-cell analyses. In addition, we evaluated the associations of tumor tertiary lymphoid structures (TLSs) with therapeutic outcomes. HR+/HER2− advanced breast cancer patients who received low-dose CY combined with ET or ET only from April 2015 to August 2021 were enrolled in this retrospective study. The primary outcome was the clinical control rate (CCR), and the secondary outcome was progression-free survival (PFS). Circulating T lymphocyte subpopulations represented by Tregs were monitored during treatment by flow cytometry methods. TLSs wereconfirmed by hematoxylin–eosin staining of pretreatment specimens, and CD3, CD4, and Foxp3 were detected using Opal multicolor immunofluorescence. A total of 85 patients who received CY + ET and 50 patients who received ET only were enrolled, the percentage of patients who received CCR was 73% (62/85) vs. 70% (45/50), and the objective response rate (ORR) was 28% (24/85) vs. 24% (12/50). No deaths occurred during the study period. The mean PFS time was 13 vs. 11 months (P = 0.03). In the CY + ET group, decreases in CD4+/CD25+/Foxp3+ T cells (P < 0.001) were favorable for both clinical control and prolonged PFS (P < 0.001). Compared with patients without TLSs, those with TLSs were more likely to have better clinical control and PFS (mean time = 6 months), and a greater number of Treg cells during TLS pretreatment correlated with longer PFS (P = 0.043). Oral low-dose CY combined with standard ET exerts immunological effects by decreasing Treg levels to achieve improved clinical responses. Moreover, patients with TLSs might benefit more from such therapy than those without TLSs, and a high Treg cell count in TLSs before treatment predicts better therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Prostate cancer (PC) is a major global health concern affecting male individuals. Among its variants, androgen-independent prostate cancer exhibits slow progression and lacks effective treatment targets, rendering it insensitive to hormone therapy. Recent reports have highlighted the significance of Mortalin, an important oncogene, in tumor migration and invasion through various signaling pathways. Experimental evidence from in-vivo and in-vitro studies indicate upregulated expression of Mortalin in prostate cancer tissues. Moreover, it has been shown to regulate the epithelial-mesenchymal transition (EMT) process via the Wnt/β-catenin signaling pathway, thereby promoting prostate cancer proliferation and metastasis. These findings suggest that Mortalin may serve as a promising novel immunotherapeutic target for prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Sex hormones and sex chromosomes play a vital role in cardiovascular disease. Testosterone plays a crucial role in men's health. Lower testosterone level is associated with cardiovascular and cardiometabolic diseases, including inflammation, atherosclerosis, and type 2 diabetes. Testosterone replacement is beneficial or neutral to men's cardiovascular health. Testosterone deficiency is associated with cardiovascular events. Testosterone supplementation to hypogonadal men improves libido, increases muscle strength, and enhances mood. We hypothesized that sex chromosomes (XX and XY) interaction with testosterone plays a role in arterial stiffening. Methods: We used four core genotype male mice to understand the inherent contribution of sex hormones and sex chromosome complement in arterial stiffening. Age-matched mice were either gonadal intact or castrated at eight weeks plus an additional eight weeks to clear endogenous sex hormones. This was followed by assessing blood pressure, pulse wave velocity, echocardiography, and ex vivo passive vascular mechanics. Results: Arterial stiffening but not blood pressure was more significant in castrated than testes-intact mice independent of sex chromosome complement. Castrated mice showed a leftward shift in stress–strain curves and carotid wall thinning. Sex chromosome complement (XX) in the absence of testosterone increased collagen deposition in the aorta and Kdm6a gene expression. Conclusion: Testosterone deprivation increases arterial stiffening and vascular wall remodeling. Castration increases Col1α1 in male mice with XX sex chromosome complement. Our study shows decreased aortic contractile genes in castrated mice with XX than XY sex chromosomes. Plain Language Summary: Cardiovascular disease is the leading cause of death worldwide. Cardiovascular disease presents differently in men and women. While men develop plaque buildup in large arteries, women develop buildup in the microvessels in the heart. Arterial stiffening, which is the hardening of arteries, increases with age in both men and women. Aging, coupled with the decline in sex hormones, exacerbates cardiovascular disease in women compared to men. Men with XY sex chromosomes have higher circulating testosterone, while women with XX sex chromosomes have increased circulating estradiol. The potential benefits of sex hormone replacement therapy are shown in men and women. Indeed, testosterone replacement deficiency is associated with adverse cardiovascular outcomes in men. Whether adverse events are dependent or independent of sex hormones' interaction with sex chromosomes is unknown. This study used the four core genotype mice comprising males with either XX or XY sex chromosome complement. We show castration increases arterial stiffening and collagen deposition on the arterial wall. We also identified the escapee and smooth muscle contractile genes that may play a role in arterial stiffening. Our data suggests that testosterone deprivation mediates arterial stiffening and remodeling. Highlights: Castration increases pulse wave velocity independent of blood pressure in male FCG mice. Castration-mediated carotid artery leftward shift in stress–strain. Arterial remodeling, including collagen deposition and decrease in contractile genes, was more significant in mice with XX sex chromosome complement. [ABSTRACT FROM AUTHOR]

Background: Thyroid hormones were reported to exert neuroprotective effects after ischemic stroke by reducing the burden of brain injury and promoting post-ischemic brain remodeling. Objective: We aimed to analyze the value of thyroid hormone replacement therapy (THRT) due to pre-existing hypothyroidism on the clinical course and outcome of aneurysmal subarachnoid hemorrhage (SAH). Methods: SAH individuals treated between January 2003 and June 2016 were included. Data on baseline characteristics of patients and SAH, adverse events and functional outcome of SAH were recorded. Study endpoints were cerebral infarction, in-hospital mortality and unfavorable outcome at 6 months. Associations were adjusted for outcome-relevant confounders. Results: 109 (11%) of 995 individuals had THRT before SAH. Risk of intracranial pressure- or vasospasm-related cerebrovascular events was inversely associated with presence of THRT (p = 0.047). In multivariate analysis, THRT was independently associated with lower risk of cerebral infarction (adjusted odds ratio [aOR] = 0.64, 95% confidence interval [CI] = 0.41–0.99, p = 0.045) and unfavorable outcome (aOR = 0.50, 95% CI = 0.28–0.89, p = 0.018), but not with in-hospital mortality (aOR = 0.69, 95% CI = 0.38–1.26, p = 0.227). Conclusion: SAH patients with THRT show lower burden of ischemia-relevant cerebrovascular events and more favorable outcome. Further experimental and clinical studies are required to confirm our results and elaborate the mechanistic background of the effect of THRT on course and outcome of SAH. [ABSTRACT FROM AUTHOR]

A growing number of people identify as transgender and gender non-binary in the USA and worldwide. Concomitantly, an increasing number of patients are receiving gender-affirming hormone therapy (GAHT) to achieve gender congruence. GAHT has far-ranging effects on clinical and subclinical markers of cardiovascular risk. Transgender patients also appear to be at higher risk for cardiovascular diseases compared to their cisgender peers and the impact of gender-affirming therapy on cardiovascular health is unclear. Studies on the effect of GAHT on cardiovascular outcomes are confounded by differences in GAHT regimens and methodological challenges in a diverse and historically hard-to-reach population. Current cardiovascular guidelines do not incorporate gender identity and hormone status into risk stratification and clinical decision-making. In this review, we provide an overview on the cardiometabolic impact and clinical considerations of GAHT for cardiovascular risk in transgender patients. [ABSTRACT FROM AUTHOR]

Gender Affirming Hormone Therapy (GAHT) is a key therapeutic approach which aims to help trans and gender diverse (or simply "trans") individuals' transition from their sex-presumed-at-birth to their experienced gender identity. Previous reviews have focused on synthesizing quantitative experiences; however, a qualitative lens is important to understand the personal journey of GAHT. This review provides a qualitative meta-synthesis of the experiences of trans people around the world who have undergone GAHT to elicit contextualized understanding of the changes experienced. Systematic searches of eight databases identified an initial 2670 papers, refined to a final 28 papers. Overall, findings suggested that the GAHT journey is unique and elicited a myriad of changes which, whilst challenging at times, were life-changing and brought about positive psychological, physical, and social changes. Other themes explored GAHT not being treated as a fix-all for associated mental health issues, the rules that govern appraisal of physical changes, how privilege and social identity evolve, and the power of affirmation. This work offers important recommendations to improve the care offered to trans people undergoing GAHT. Namely, person-centered support is essential, and peer-navigation may be a useful future direction to explore. [ABSTRACT FROM AUTHOR]

To study whether midluteal serum estradiol (E2) levels are associated with the live birth rate in hormone replacement therapy frozen embryo transfer (HRT-FET) cycles in patients with optimal midluteal serum progesterone (P4) levels. Observational prospective cohort study. Public fertility clinic. A total of 412 women had an HRT-FET cycle single blastocyst transfer from January 2020 to November 2022. The HRT-FET cycle priming regimen included oral E2 (6mg/24 h) administered in the evening, followed by vaginal P4 (400mg/12 h). Serum E2 and P4 levels were measured using a standardized method, 2–4 hours after the latest P4 administration and 9–14 hours after E4 administration on the day of blastocyst transfer, day 6 of P4 administration. Patients with serum P4 levels (<11 ng/mL [35 nmol/L]) on the day of transfer received additional rectal P4 (400mg/12 h). No additional E2 dose was administered. The primary outcome was the live birth rate (LBR) in relation to E2 levels at blastocyst transfer day. The optimal serum E2 levels correlating with ongoing pregnancy were ≥292 pg/mL and <409 pg/mL (≥1,070 pmol/L and <1,500 pmol/L). The LBR was 59% (60/102) when E2 levels were within this range, whereas a significantly lower LBR of 39% (101/260) was seen in patients when E2 levels were <292 pg/mL (<1,070 pmol/L) and of 28% (14/50) when E2 levels were ≥409 pg/mL (≥1,500 pg/mL). In a logistic regression analysis, adjusting for serum P4 level ≥11 ng/mL or <11 ng/mL (≥35 nmol or <35 nmol/L) on the day of transfer, body mass index, age at oocyte retrieval, day 5 or 6 vitrified blastocysts, and blastocyst score, the adjusted risk difference of live birth was −0.21 (−0.32; −0.10) when the E2 level was <292 pg/mL (<1,070 pmol/L) and −0.31 (−0.45; −0.18) when the E2 level was ≥409 pg/mL (≥1,500 pmol/L) compared with E2 levels ≥292 pg/mL and <409 pg/mL (≥1,070 and <1,500 pmol/L). Importantly, only 25% of patents had optimal levels. The study shows a significant association between serum E2 levels and reproductive outcomes in an HRT-FET cohort in which optimal serum P4 levels were secured. Midluteal serum E2 levels are associated with the LBR in HRT-FET cycles, and E2 levels should neither be too high nor too low. EudraCT No.: 2019-001539-29. [ABSTRACT FROM AUTHOR]

Due to increasing life expectancy, women spend a significant part of their lives in menopause. Women with a history of endometriosis are more likely to become menopausal at an early age due to bilateral oophorectomy or repeated ovarian surgery. In addition, some medical therapies used for endometriosis, such as gonadotropin releasing hormone agonists or progestins reduce bone mineral density. Furthermore, women with endometriosis have a higher background risk of cardiovascular disorders and hypercholesterolemia. Hence, it is important to recommend the use of hormone replacement therapy (HRT) to these women when they become menopausal, at least until the age of natural menopause. Although based on limited data, there is a possibility of reactivation of symptoms of endometriosis or its lesions, and a theoretical possibility of malignant transformation, although this remains unproven. Therefore, women should be advised in the light of this information before starting HRT after the age of natural menopause and are asked to seek help if they experience symptoms that may indicate these changes. Estrogen only HRT should be avoided and combined HRT preparations should be recommended, even after a hysterectomy. [ABSTRACT FROM AUTHOR]

In this narrative review, we attempt to provide an overview of the evidence regarding the role of estrogen (receptors) in cutaneous melanoma (CM). We reviewed 68 studies and 4 systematic reviews and meta-analyses published from 2002 up to and including 2022. The prevailing presence of estrogen receptor β (ERβ) instead of estrogen receptor α (ERα) in CM is notable, with ERβ potentially playing a protective role and being less frequently detected in progressive cases. While men with CM generally experience a less favorable prognosis, this distinction may become negligible with advancing age. The role of oral contraceptives (OC) and hormone replacement therapy (HRT) in CM remains controversial. However, recent studies tend to associate the use of these exogenous hormones with a heightened risk of CM, mostly only when using estrogen therapy and not in combination with progesterone. On the contrary, the majority of studies find no substantial influence of in vitro fertilization (IVF) treatment on CM risk. Reproductive factors, including younger age at first childbirth, higher parity, and shorter reproductive life, show conflicting evidence, with some studies suggesting a lower CM risk. We suggest an important role for estrogens in CM. More research is needed, but the integration of estrogens and targeting the estrogen receptors in melanoma therapy holds promise for future developments in the field. [ABSTRACT FROM AUTHOR]

There is evidence suggesting that endocrine interventions such as hormone replacement therapy and hormonal contraception can increase breast cancer (BC) risk. Sexual steroid hormones like estrogens have long been known for their adverse effects on BC development and progression via binding to estrogen receptor (ER) α. Thus, in recent years, endocrine interventions that include estrogens have been discussed more and more critically, and their impact on different BC subgroups has increasingly gained interest. Carriers of pathogenic variants in BRCA1/2 genes are known to have a high risk of developing BC and ovarian cancer. However, there remain open questions to what extent endocrine interventions targeting ERα or the progesterone receptor further increase cancer risk in this subgroup. This review article aims to provide an overview and update on the effects of endocrine interventions on breast cancer risk in the general population in comparison to BRCA1/2 mutation carriers. Finally, future directions of research are addressed, to further improve the understanding of the effects of endocrine interventions on high-risk pathogenic variant carriers. [ABSTRACT FROM AUTHOR]

Hormone receptor-positive and HER2-negative breast cancer (HR+/HER2-BC) is the most common type with a favorable prognosis under endocrine therapy. However, it still demonstrates unpredictable progression and recurrences influenced by high tumoral diversity and microenvironmental status. To address these heterogeneous molecular characteristics of HR+/HER2-BC, we aimed to simultaneously characterize its transcriptomic landscape and genetic architecture at the same resolution. Using advanced single-cell RNA and DNA sequencing techniques together, we defined four distinct tumor subtypes. Notably, the migratory tumor subtype was closely linked to genomic alterations of EGFR, related to the tumor-promoting behavior of IL6-positive inflammatory tumor-associated fibroblast, and contributing to poor prognosis. Our study comprehensively utilizes integrated analysis to uncover the complex dynamics of this breast cancer subtype, highlighting the pivotal role of the migratory tumor subtype in influencing surrounding cells. This sheds light on potential therapeutic targets by offering enhanced insights for HR+/HER2-BC treatment. [ABSTRACT FROM AUTHOR]

In the majority of children with growth hormone (GH) deficiency (GHD), normal GH secretion may occur before the attainment of final height. The aim of the study was to assess the incidence of persistent and transient GHD and the effectiveness of recombined human GH (rhGH) therapy in children with isolated, idiopathic GHD with respect to the moment of therapy withdrawal and according to different diagnostic criteria of GHD. The analysis included 260 patients (173 boys, 87 girls) with isolated, idiopathic GHD who had completed rhGH therapy and who had been reassessed for GH and IGF-1 secretion. The incidence of transient GHD with respect to different pre- and post-treatment criteria was compared together with the assessment of GH therapy effectiveness. The incidence of transient GHD, even with respect to pediatric criteria, was very high. Normal GH secretion occurred before the attainment of near-final height. Application of more restricted criteria decreased the number of children diagnosed with GHD but not the incidence of transient GHD among them. Poor response to GH therapy was observed mainly in the patients with normal IGF-1 before treatment, suggesting that their diagnosis of GHD may have been a false positive. Further efforts should be made to avoid the overdiagnosis GHD and the overtreatment of patients. [ABSTRACT FROM AUTHOR]

The article offers information on the potential link between progestins and the development of central nervous system meningiomas. Topics include the controversial role of various progestins in meningioma growth, the specific high-dose progestins implicated in this relationship, and the findings of a case-control study conducted using data from the French national health system.

Background Many studies have examined patient-related factors affecting adjuvant hormone therapy adherence in patients with breast cancer. Our study aimed to examine associations of family-related factors with adjuvant hormone therapy discontinuation and breast cancer–specific mortality. Methods By cross-linking 7 Swedish health registers, we performed a cohort study that included all patients with breast cancer who initiated adjuvant hormone therapy during 2006-2019 in Sweden (N = 10 701). A group-based multitrajectory model was used to identify familial adversity groups based on 3 dimensions: material deprivation, negative family dynamics, and loss or threat of loss. Cox proportional hazard models were used to investigate associations of familial adversity with hormone therapy discontinuation and breast cancer–specific mortality. Results We identified 5 distinctive familial adversity groups among the cohort participants. Compared with women who had low familial adversity, higher risks to discontinue adjuvant hormone therapy were observed among women with material deprivation (hazard ratio [HR] = 1.31, 95% confidence interval [CI] = 1.20 to 1.43), negative family dynamics (HR = 1.16, 95% CI = 1.06 to 1.28), loss or threat of loss (HR = 1.15, 95% CI = 1.00 to 1.32), or high familial adversity (HR = 1.53, 95% CI = 1.40 to 1.68). Furthermore, women with material deprivation (HR = 1.37, 95% CI = 1.05 to 1.79), negative family dynamics (HR = 1.41, 95% CI = 1.01 to 1.97), or high adversity (HR = 1.67, 95% CI = 1.26 to 2.23) were at higher risk of dying from breast cancer. Conclusion Familial adversity is associated with a higher risk of adjuvant hormone therapy discontinuation and breast cancer–specific mortality. Family-related factors identified in our study may help identify high-risk patients for interventions to prevent treatment discontinuation and subsequently improve breast cancer outcomes. [ABSTRACT FROM AUTHOR]

Background Inequities in guideline-concordant treatment receipt contribute to worse survival in Black patients with breast cancer. Inequity-reduction interventions (eg, navigation, bias training, tracking dashboards) can close such treatment gaps. We simulated the population-level impact of statewide implementation of inequity-reduction interventions on racial breast cancer inequities in North Carolina. Methods Using registry-linked multipayer claims data, we calculated inequities between Black and White patients receiving endocrine therapy (n = 12 033) and chemotherapy (n = 1819). We then built cohort-stratified (endocrine therapy and chemotherapy) and race-stratified Markov models to simulate the potential increase in the proportion of patients receiving endocrine therapy or chemotherapy and subsequent improvements in breast cancer outcomes if inequity-reducing intervention were implemented statewide. We report uncertainty bounds representing 95% of simulation results. Results In total, 75.6% and 72.1% of Black patients received endocrine therapy and chemotherapy, respectively, over the 2006-2015 and 2004-2015 periods (vs 79.3% and 78.9% of White patients, respectively). Inequity-reduction interventions could increase endocrine therapy and chemotherapy receipt among Black patients to 89.9% (85.3%, 94.6%) and 85.7% (80.7%, 90.9%). Such interventions could also decrease 5-year and 10-year breast cancer mortality gaps from 3.4 to 3.2 (3.0, 3.3) and from 6.7 to 6.1 (5.9, 6.4) percentage points in the endocrine therapy cohorts and from 8.6 to 8.1 (7.7, 8.4) and from 8.2 to 7.8 (7.3, 8.1) percentage points in the chemotherapy cohorts. Conclusions Inequity-focused interventions could improve cancer outcomes for Black patients, but they would not fully close the racial breast cancer mortality gap. Addressing other inequities along the cancer continuum (eg, screening, pre- and postdiagnosis risk factors) is required to achieve full equity in breast cancer outcomes. [ABSTRACT FROM AUTHOR]

Aim: To investigate effects of hormone replacement therapy in postmenopausal women on factors associated with metabolic flexibility related to whole‐body parameters including fat oxidation, resting energy expenditure, body composition and plasma concentrations of fatty acids, glucose, insulin, cortisol, and lipids, and for the mitochondrial level, including mitochondrial content, respiratory capacity, efficiency, and hydrogen peroxide emission. Methods: 22 postmenopausal women were included. 11 were undergoing estradiol and progestin treatment (HT), and 11 were matched non‐treated controls (CONT). Peak oxygen consumption, maximal fat oxidation, glycated hemoglobin, body composition, and resting energy expenditure were measured. Blood samples were collected at rest and during 45 min of ergometer exercise (65% VO2peak). Muscle biopsies were obtained at rest and immediately post‐exercise. Mitochondrial respiratory capacity, efficiency, and hydrogen peroxide emission in permeabilized fibers and isolated mitochondria were measured, and citrate synthase (CS) and 3‐hydroxyacyl‐CoA dehydrogenase (HAD) activity were assessed. Results: HT showed higher absolute mitochondrial respiratory capacity and post‐exercise hydrogen peroxide emission in permeabilized fibers and higher CS and HAD activities. All respiration normalized to CS activity showed no significant group differences in permeabilized fibers or isolated mitochondria. There were no differences in resting energy expenditure, maximal, and resting fat oxidation or plasma markers. HT had significantly lower visceral and total fat mass compared to CONT. Conclusion: Use of hormone therapy is associated with higher mitochondrial content and respiratory capacity and a lower visceral and total fat mass. Resting energy expenditure and fat oxidation did not differ between HT and CONT. [ABSTRACT FROM AUTHOR]

Hypothyroidism is a chronic condition combated by a daily oral supplementation of levothyroxine. In addition to the need for frequent dosing, oral administration may result in variable absorption of the drug leading to a failure in achieving normal thyroid function. Therefore, the development of a long-acting injectable system capable of delivering the drug is necessary. This work was aimed at developing sustained release microparticles loaded with levothyroxine. The microparticles were produced through the emulsification-solvent evaporation method using 2 grades of biocompatible and biodegradable polyesters: poly(ᴅ,ʟ-lactide-co-glycolide) (PLGA) and poly(ᴅ,ʟ-lactide) (PLA). Both polymers produced microparticles with very similar sizes (1.9 µm) and zeta potential values (around -22.0 mV). However, PLA microparticles had a significantly higher drug loading (6.1% vs. 4.4%, respectively) and encapsulation efficiency (36.8%, vs. 26.1%, respectively) when compared to PLGA counterparts. While both types of microparticles displayed a biphasic release pattern in vitro , a slower rate of release was observed with PLA microparticles. Moreover, a similar biphasic release pattern was found in vivo , with an initial phase of rapid release followed by a slower phase in the subsequent 10 days. These results indicate the possibility of developing levothyroxine loaded polyester microparticles as a potential long-acting thyroid hormone replacement therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Hormone replacement therapy (HRT) is considered the gold standard for management of vasomotor and vaginal symptoms of menopause. Vasomotor symptoms of menopause may include hot flashes and diaphoresis that vary in intensity and duration. Other symptoms of menopause can include vaginal atrophy and dryness, leading to dyspareunia and increased risk of infection. These symptoms can be impactful on a woman's life and HRT has data to support its efficacy, however, HRT carries significant risks that are generally well known, including risk of stroke, cardiovascular disease, breast cancer, and venous thromboembolism. These risks were most well characterized by several landmark trials published in the early 2000s. There are several nuances to prescribing HRT that can make doing so complex. These include consideration of cyclic vs continuous administration and of tapering therapy. Additionally, estrogen is available in a variety of dosage forms including injections and transdermal formulations. However, for women with an intact uterus, estrogen will need to be combined with progestin or bazedoxifene (a selective estrogen receptor modulator – SERM), both once daily oral formulations, in order to minimize malignancy risk. Though product preference and considerations of dosing may vary depending on practitioner preference, this brief report aims to clarify some nuances to prescribing or recommending HRT. [ABSTRACT FROM AUTHOR]

Purpose: Standard-of-care for HER2-positive metastatic breast cancer (HER2 + mBC) patients consists of trastuzumab ± pertuzumab with chemotherapy in first-line (1L), and ado-trastuzumab emtansine (T-DM1) or the more recently approved trastuzumab deruxtecan (T-DXd) in second-line (2L). Contemporary data on treatment sequencing and real-world effectiveness is limited. This study aims to report 2L treatments and outcomes among HER2 + mBC patients in the United States (US). Methods: HER2 + mBC patients initiating 2L treatment (index date) between January 2014 and February 2021 were identified from the Syapse Learning Health Network (LHN) database. Summary statistics for patient characteristics, treatment received, reasons for 2L discontinuation and time to 2L-clinical outcomes are reported. Results: Of the 312 patients initiating 2L treatment, had a median age of 59 years (interquartile range [IQR], 50–66) at the start of 2L. The majority were white (69%) and had de novo mBC (62%). Top three 2L regimens included T-DM1 ± endocrine therapy (29%), trastuzumab/pertuzumab/taxane (10%) and T-DM1/trastuzumab (8%). Around 88% discontinued 2L and 63% received subsequent treatment. Median time-to-next-treatment was 10.6 months (95% CI, 8.8–13.3) and real-world progression-free-survival was 7.9 months (95% CI, 7.0–9.9). Among 274 patients who discontinued 2L, 47% discontinued due to progression and 17% because of intolerance/toxicity, respectively. Conclusion: This real-world US study showed that approximately two-thirds of 2L patients received subsequent therapy and disease progression was the most common reason for 2L discontinuation highlighting the need for timely 2L treatment with the most efficacious drug to allow patients to achieve longer treatment duration and delayed progression. [ABSTRACT FROM AUTHOR]

Purposes: To investigate the effect and safety of ovarian tissue cryopreservation (OTC) for fertility preservation in female patients with hematological diseases. Methods: We designed a retrospective study. The clinical data of patients with hematological diseases undergoing OTC admitted to Peking University People's Hospital from April 2017 to January 2023 were analyzed and summarized. Results: A total of 24 patients were included in the study, including 19 patients with malignant hematological diseases and 5 patients with non-malignant hematological diseases. The former included 14 patients with acute leukemia, 1 patient with chronic leukemia, and 4 patients with myelodysplastic syndrome, while the latter 5 patients were aplastic anemia (AA). 16 patients had received chemotherapy before OTC. The average age of 24 patients was 22.80 ± 6.81 years. The average anti-Mullerian hormone (AMH) was 1.97 ± 2.12 ng/mL, and the average follicle-stimulating hormone (FSH) was 7.01 ± 4.24 IU/L in examination before OTC. FSH was greater than 10.0 IU/L in 4 cases. The pre-OTC laboratory tests showed that the average white blood cell (WBC) count was (3.33 ± 1.35) × 109/L, the average hemoglobin was 91.42 ± 22.84 g/L, and the average platelet was (147.38 ± 114.46) × 109/L. After injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF), blood transfusion, and iron supplementation in pre-OTC treatment, the average WBC count was (4.91 ± 3.07) × 109/L, the average hemoglobin was 98.67 ± 15.43 g/L, and the average platelet was (156.38 ± 103.22) × 109/L. Of the 24 patients, 22 underwent laparoscopic bilateral partial oophorectomy and oophoroplasty, and 2 underwent laparoscopic unilateral oophorectomy. The average duration of OTC was 59.54 ± 17.58 min, and the average blood loss was 32.1 ± 41.6 mL. The maximum blood loss was 200 mL. There was no significant difference in WBC count and hemoglobin concentration after OTC compared to pre-OTC period. Only the platelet count after OTC surgery was significantly different from that before surgery ([134.54 ± 80.84 vs. 156.38 ± 103.22] × 109/L, p < 0.05). None of the 24 patients had serious complications after OTC. 2 patients had mild infection symptoms, but both recovered well. 23 patients underwent hematopoietic stem cell transplantation (HSCT) after OTC. The median and interquartile range from OTC to the pretreatment of HSCT was 33 (57) days, and the median and interquartile range from OTC to HSCT was 41 (57) days. Seven of them began pretreatment of HSCT within 20 days and began HSCT within 30 days after OTC. All patients were followed up. Of the 23 patients who underwent HSCT after surgery, 22 presented with amenorrhea and 1 with scanty menstrual episodes. Seven patients underwent hormone replacement therapy (HRT) after HSCT. A patient with AA underwent ovarian tissue transplantation (OTT) 3 years after HSCT and resumed regular menstruation 6 months after OTT. Conclusions: Ovarian tissue cryopreservation has a promising future in fertility protection in patients with hematological diseases. However, patients with hematological malignancies often have received gonadotoxic therapy before OTC, which may be accompanied by myelosuppression while patients with non-malignant hematological diseases often present with severe hemocytopenia. So perioperative complete blood count of patients should be paid attention to. There was no significant difference in the WBC count and hemoglobin concentration in patients with hematological diseases before and after OTC surgery, and the platelet count decreased slightly within the normal range. Infection is the most common post-OTC complication, and HSCT pretreatment can be accepted as early as the 10th day after OTC. OTC has no adverse effects on patients with hematological diseases and does not delay HSCT treatment. For young patients with hematological diseases, OTC is an effective method of fertility preservation. [ABSTRACT FROM AUTHOR]

The article presents a study on trends in estrogen therapy (ET) use from a sample of ambulatory care visits to evaluate co-prescription of ET and sedating potentially inappropriate medications (PIMS) and assess whether ET was a marker for polypharmacy in women aged 65 and older. Topics include demographic and clinical characteristics of 2006-2016 ambulatory visits, prevalence of estrogen prescribing in ambulatory visits, and association between ET and polypharmacy.

After rigorous adjustment, radical prostatectomy was associated with a lower risk of prostate cancer–specific and overall mortality, especially in patients with higher-risk disease, in comparison to other treatments according to data from a large, prospective, multicenter, community-based cohort of men with localized prostate cancer. The optimal treatment of localized prostate cancer (PCa) remains controversial. To compare long-term survival among men who underwent radical prostatectomy (RP), brachytherapy (BT), external beam radiation therapy (EBRT), primary androgen deprivation therapy (PADT), or monitoring (active surveillance [AS]/watchful waiting [WW]) for PCa. This is a cohort study with long-term follow-up from the multicenter, prospective, largely community-based Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. Men with biopsy-proven, clinical T1–3aN0M0, localized PCa were consecutively accrued within 6 mo of diagnosis and had clinical risk data and at least 12 mo of follow-up after diagnosis available. PCa risk was assessed, and multivariable analyses were performed to compare PCa-specific mortality (PCSM) and all-cause mortality by primary treatment, with extensive adjustment for age and case mix using the Cancer of the Prostate Risk Assessment (CAPRA) score and a well-validated nomogram. Among 11 864 men, 6227 (53%) underwent RP, 1645 (14%) received BT, 1462 (12%) received EBRT, 1510 (13%) received PADT, and 1020 (9%) were managed with AS/WW. At a median of 9.4 yr (interquartile range 5.8–13.7) after treatment, 764 men had died from PCa. After adjusting for CAPRA score, the hazard ratios for PCSM with RP as the reference were 1.57 (95% confidence interval [CI] 1.24–1.98; p < 0.001) for BT, 1.55 (95% CI 1.26–1.91; p < 0.001) for EBRT, 2.36 (95% CI 1.94–2.87; p < 0.001) for PADT, and 1.76 (95% CI 1.30–2.40; p < 0.001) for AS/WW. In models for long-term outcomes, PCSM differences were negligible for low-risk disease and increased progressively with risk. Limitations include the evolution of diagnostic and therapeutic strategies for PCa over time. In this nonrandomized study, the possibility of residual confounding remains salient. In a large, prospective cohort of men with localized PCa, after adjustment for age and comorbidity, PCSM was lower after local therapy for those with higher-risk disease, and in particular after RP. Confirmation of these results via long-term follow-up of ongoing trials is awaited. We evaluated different treatment options for localized prostate cancer in a large group of patients who were treated mostly in nonacademic medical centers. Results from nonrandomized trials should be interpret with caution, but even after careful risk adjustment, survival rates for men with higher-risk cancer appeared to be highest for patients whose first treatment was surgery rather than radiotherapy, hormones, or monitoring. [ABSTRACT FROM AUTHOR]

The study reported in this paper explores the experiences of 95 people with intersex variations constituting an international English-speaking sample who completed a mixed methods survey comprises questions designed by the authors to explore 1) genital variations and medical interventions (and pressures to undertake them), 2) experiences with sex education, and 3) experience of physical intimacy, including use of safer sex devices and sexually transmitted infections. Surgeries on minors were common and typically not consensual, often resulting in the need for revisions. Pressures for surgeries most commonly were made by doctors. Experiences of sex education often failed to be inclusive of intersex bodies, with information about menstruation and hygiene rarely provided, and many participants having to learn on their own. Participants had a diversity of experiences of physical intimacy beyond penetration. For those who had experienced penetration, vaginal intercourse was enjoyable for some, but many found it painful. Conversely, anal intercourse was enjoyed by many and rarely found to be painful. The paper concludes by highlighting the importance of an intersex-specific approach to sexual health for this population. [ABSTRACT FROM AUTHOR]

The article discusses the concept of chemoprotection of the ovary during chemotherapy as a potential strategy for fertility preservation. It highlights the challenges and limitations of current approaches to fertility preservation, such as cryopreservation, and explores the potential benefits of chemoprotection as a complementary strategy. The study by Wu et al. is referenced, which investigates the use of CHEK1/2 inhibitors to protect the ovary during chemotherapy. The article emphasizes the need for further research and validation of chemoprotective agents, as well as the importance of integrating fertility preservation considerations into oncological trials and drug development. [Extracted from the article]

Recommendations from the Children's Oncology Group Long-Term Follow-Up (COG-LTFU) Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer emphasize the importance of reproductive health care, yet little is known regarding adherence to these recommendations and non-fertility-related sexual and reproductive health (SRH) outcomes. Follow-up of outcomes on the basis of the COG-LTFU guidelines was assessed in female patients who underwent fertility preservation consultation before gonadotoxic therapy between 2016 and 2022 at a single institution and were at least 6 months from treatment completion. We included 140 patients, with a mean time of 2.7 years from treatment completion. Eighty-six patients were 12 years old or older, of whom sexual activity was recorded in 59 (68.7%), and 12 of 31 (38.7%) sexually active patients underwent sexual function assessment. The 57 (66.3%) patients at high risk of premature ovarian insufficiency (POI) at diagnosis were more likely than minimal-risk counterparts (29, 33.7%) to have abnormal uterine bleeding (42.1% vs 17.2%, P =.03), to be diagnosed with POI (29.8% vs 0%, P =.01), and to have sexual activity recorded (77.2% vs 51.7%, P =.03). Of 17 patients with POI, 82.4% were on hormone replacement therapy, and 58.8% had undergone bone mineral density testing. This study adds to the limited literature regarding non-fertility-related SRH outcomes after gonadotoxic therapy and illustrates opportunities to improve adherence to the COG-LTFU guidelines. Increased attention to SRH guidelines may increase detection and treatment of SRH conditions, improving the health and quality of life of female cancer survivors. [ABSTRACT FROM AUTHOR]

Purpose: To identify associations between systemic drugs and the incidence of diabetic macular oedema (DME). Of interest was to find beneficial and/or deleterious associations of used drugs. Methods: A historic cohort design based on administrative data. Study population consisted of 150 353 individuals with diabetes. Endpoint event was the development of DME (ICD‐10 H36.01), censoring events were death or study end December 2017. The follow‐up started between 1997 and 2010. The systemic medication consisted of 95 substances. We constructed a nested case–control study design comparing 2630 cases with DME to 13 144 age‐ and sex‐matched controls without DME. Results are reported as odds ratios (ORs) with 95% confidence intervals (CIs) based on conditional logistic regression models. Results: Incidence rate for DME was 1.80 per 1000 person‐years (95% CI 1.73–1.87). In all, we observed a lower incidence rate of DME in females (IRR 0.57; 95% CI 0.52–0.62) compared to males. Exposure to hormone replacement therapy estradiol (OR 0.42; 0.25–0.68), temazepam (0.23; 0.08–0.62) and allopurinol (0.61; 0.43–0.86) were associated with lower risk of DME, while use of insulin or insulin analogue (3.30; 2.99–3.64), sulfonylureas (1.21; 1.05–1.40), diuretic furosemide (1.90; 1.61–2.24), calcium channel blocker amlodipine (1.53; 1.34–1.75), ACE inhibitors ramipril (1.66; 1.46–1.89) and enalapril (1.38; 1.16–1.64) were associated with an increased risk of DME. Conclusions: Large‐scale studies examining the incidence of DME are lacking. Our findings suggest that associations of systemic medications with the incidence of DME may shed light on the pathogenesis of complex DME, encouraging further studies. [ABSTRACT FROM AUTHOR]

Purpose: To assess the efficacy of neoadjuvant endocrine therapy in female HR‐positive/HER2‐negative breast cancer patients. Data and Methods: We identified female patients aged ≥18 years with cT1‐4N0‐XM0, HR(+), and HER2(−) breast cancer from the National Cancer Database. The patients who underwent surgery first were categorized as "surgery‐first," while those who received NET before surgery were classified as "NET." Propensity score‐matching, Cox proportional‐hazard model, variance inflation factors, and interaction analysis were employed to estimate the correlation between NET and survival outcomes. Results: Among 432,387 cases, 2914 NET patients and 2914 surgery‐first patients were matched. Compared with the surgery‐first group, the NET group received less adjuvant chemotherapy (p < 0.001). Furthermore, the NET group exhibited higher survival probabilities compared with the surgery‐first group (3 years: 91.4% vs. 82.1%; 5 years: 82.1% vs. 66.8%). Multivariate Cox analysis indicated that NET was associated with improved OS (surgery‐first vs. NET: HR 2.17, 95% CI: 1.93–2.44). Age over 55 years old, having public insurance, higher CDCC score, higher NSBR grade, ER(+)PR(−), and advanced clinical stage were related to worse OS (all p < 0.05). There was an interaction between age, race, income, and home and treatment regimen (all p < 0.05). Conclusion: NET may be a more effective treatment procedure than surgery‐first in female HR‐positive/HER2‐negative, non‐metastatic breast cancer patients. Future clinical studies with more detailed data will provide higher‐level evidence‐based data. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explores cryopreservation thyroid autotransplantation as an alternative to hormonal replacement therapy for patients who underwent thyroidectomy during childhood or adulthood. The research evaluates the impact of modern cryopreservation techniques on follicular cell integrity through a feasibility study and literature review. Results indicate preserved tissue architecture and cell viability. Animal and human studies demonstrate successful transplantation outcomes. However, long-term follow-up data are lacking. The findings suggest promising viability of cryopreserved thyroid tissue, yet further research is needed to assess hormone secretion and ensure sustained functionality. This alternative therapy could offer tailored hormone production, aligning with physiological needs. Background and aims: This paper aims to study an alternative solution to hormonal replacement therapy in specific groups of patients who underwent thyroidectomy during childhood or adulthood. After cryopreservation, thyroid autotransplantation could be an alternative solution which would allow us to use the ability of the thyroid tissue of producing hormones according to the physiological needs of the body. Materials and methods: A feasibility study about the effects of the most modern cryopreservation techniques on the structural and functional integrity of the follicular cells of the thyroid tissue has been carried out. Patients who could benefit from the treatment have been found for both autotransplant techniques. Additionally, a literature review has been conducted. Results: The histological analysis has shown that cryopreservation does not alter the original architecture, and the culture examination that cell viability is successfully preserved. Moreover, both thyroid autotransplantation studies on animals and those on humans that were found in the literature have shown good results regarding the viability and functionality of the transplant. Conclusions: The viability of cryopreserved thyroid tissue found in this study is encouraging. Further studies to evaluate the levels of FT3, FT4 and thyroglobulin in thyroid tissue after cryopreservation are needed to verify that the secretory properties of the thyrocytes have been maintained intact. Furthermore, autotransplanted cases found in the literature do not have a long-term follow-up. [ABSTRACT FROM AUTHOR]

Simple Summary: Oestrogen and progesterone are two sex hormones that are important in the development of cancer of the inner lining of the uterus and endometrial cancer (EC). Oestrogen binds to the oestrogen receptor (ER) and progesterone to the progesterone receptor (PR). The presence of these receptors is important because the response to hormonal therapy is higher when the receptors are present. However, as EC grows and spreads throughout the body, ER and PR may be lost. In this study, we found that tumours that have spread to other organs throughout the blood and tumours that have spread in the abdomen have a relatively high presence of ER/PR, while tumours located in the lymph nodes have a lower presence of PR. ER/PR-IHC were not lower in tumours that had previously been treated with radiotherapy. This might influence the application of hormonal therapy in the future. Background: Response to hormonal therapy in advanced and recurrent endometrial cancer (EC) can be predicted by oestrogen and progesterone receptor immunohistochemical (ER/PR-IHC) expression, with response rates of 60% in PR-IHC > 50% cases. ER/PR-IHC can vary by tumour location and is frequently lost with tumour progression. Therefore, we explored the relationship between ER/PR-IHC expression and tumour location in EC. Methods: Pre-treatment tumour biopsies from 6 different sites of 80 cases treated with hormonal therapy were analysed for ER/PR-IHC expression and classified into categories 0–10%, 10–50%, and >50%. The ER pathway activity score (ERPAS) was determined based on mRNA levels of ER-related target genes, reflecting the actual activity of the ER receptor. Results: There was a trend towards lower PR-IHC (33% had PR > 50%) and ERPAS (27% had ERPAS > 15) in lymphogenic metastases compared to other locations (p = 0.074). Hematogenous and intra-abdominal metastases appeared to have high ER/PR-IHC and ERPAS (85% and 89% ER-IHC > 50%; 64% and 78% PR-IHC > 50%; 60% and 71% ERPAS > 15, not significant). Tumour grade and previous radiotherapy did not affect ER/PR-IHC or ERPAS. Conclusions: A trend towards lower PR-IHC and ERPAS was observed in lymphogenic sites. Verification in larger cohorts is needed to confirm these findings, which may have implications for the use of hormonal therapy in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer is a complex disease with multiple risk factors, distinct histological subtypes, and a variety of available therapeutic options. The disease's pathogenesis involves several molecular mechanisms, such as genetic mutations, defects in the DNA mismatch repair (MMR) pathway, hormonal signaling pathway imbalances, epigenetic changes, and disturbances in angiogenesis. On the other hand, molecular biomarkers seem to have an essential role in the diagnosis, prognosis, prediction of therapeutic response, and monitoring of disease progression in endometrial cancer. This review highlights the most significant dysregulated molecular mechanisms and reveals the relationship between specific biomarkers and targeted therapy approaches in the fight against endometrial cancer. Endometrial cancer is one the most prevalent gynecological cancers and, unfortunately, has a poor prognosis due to low response rates to traditional treatments. However, the progress in molecular biology and understanding the genetic mechanisms involved in tumor processes offers valuable information that has led to the current classification that describes four molecular subtypes of endometrial cancer. This review focuses on the molecular mechanisms involved in the pathogenesis of endometrial cancers, such as genetic mutations, defects in the DNA mismatch repair pathway, epigenetic changes, or dysregulation in angiogenic or hormonal signaling pathways. The preclinical genomic and molecular investigations presented allowed for the identification of some molecules that could be used as biomarkers to diagnose, predict, and monitor the progression of endometrial cancer. Besides the therapies known in clinical practice, targeted therapy is described as a new cancer treatment that involves identifying specific molecular targets in tumor cells. By selectively inhibiting these targets, key signaling pathways involved in cancer progression can be disrupted while normal cells are protected. The connection between molecular biomarkers and targeted therapy is vital in the fight against cancer. Ongoing research and clinical trials are exploring the use of standard therapy agents in combination with other treatment strategies like immunotherapy and anti-angiogenesis therapy to improve outcomes and personalize treatment for patients with endometrial cancer. This approach has the potential to transform the management of cancer patients. In conclusion, enhancing molecular tools is essential for stratifying the risk and guiding surgery, adjuvant therapy, and cancer treatment for women with endometrial cancer. In addition, the information from this review may have an essential value in the personalized therapy approach for endometrial cancer to improve the patient's life. [ABSTRACT FROM AUTHOR]

A network of healthcare professionals specializing in transgender care was established in Croatia in 2011, and legal advancements were subsequently made in 2014. Both achievements made gender transition more transparent and thus more attainable in Croatia. This observational study was conducted to assess the number of transgender individuals initiating gender-affirming hormone treatment (GAHT) in Croatia and describes trends in age and sex assigned at birth. Between 2011 and 2022, a total of 111 transgender individuals initiated GAHT. Within the cohort, 52 were assigned male at birth (AMAB) and 59 were assigned female at birth (AFAB). The overall annual incidence rate of transgender individuals initiating GAHT was 0.52 per 100,000 age-adjusted individuals. There was a statistically significant increase (p < 0.01) in transgender individuals commencing GAHT before the COVID-19 pandemic. Furthermore, a rising trend toward masculinizing rather than feminizing treatment was identified (p < 0.05), particularly among younger transgender individuals. The COVID-19 pandemic disrupted these trends in 2020, except for the trend of initiating therapy at a younger age (p < 0.01). The annual incidence and age distribution trends of transgender individuals initiating GAHT in Croatia closely mirrored those in other European countries, with a higher prevalence of individuals assigned female at birth. The study underscores a significant rise in the number of individuals initiating gender-affirming hormone treatment, emphasizing the need for proper legal regulation and healthcare system response. [ABSTRACT FROM AUTHOR]

The article provides an overview of the development and use of the PFA-100 analyzer for platelet function testing. It explains that prior to the introduction of the PFA-100 in 1997, platelet function testing relied on less accurate methods. The PFA-100 was found to be a better predictor of certain conditions and demonstrated good agreement with platelet aggregation results. The article also discusses the challenges faced in implementing the PFA-100 in clinical practice. Additionally, it mentions studies that have used the PFA-100 to assess platelet function in various settings, including the effects of chocolate milk consumption and stroma-free hemoglobin oxygen carrier. Overall, the PFA-100 is described as a rapid and sensitive test that provides valuable insights into platelet function. [Extracted from the article]