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Transgender individuals struggle with a misalignment between their biological and interpersonal self, in order to rectify this issue gender affirming health care is used to re-align the two aspects of themselves. The American Psychiatric Association defines transgender individuals as those who are assigned one gender identity at birth and identify as another later in life (Yarbrough 2023). There are various different gender orientations that a person canidentify with but most of the examples will focus on male-to-female (MTF) or female-to-male (FTM) transgender experiences. The current standard on gender affirming care focuses on various steps of diagnosis, traditional therapy, hormone therapy and surgical interventions (Yarbrough 2023). Transgender children suffer academically and socially due to having an internal struggle with their gender dysphoria, often affecting their everyday life (Boyle 2022). The argument against gender affirming care for minors focuses on the ability of minors to conceptualize the long-lasting effects the care will have on their body as well as the fear theindividual will change their mind over time. The argument for gender affirming care for minors views the issue as necessary medical care that treats a life-threatening issue. This paper will conduct a thorough review of current opinions on gender affirming care for minors, addressing gaps in understanding of what care is given and the effects the care has on the individual with a special note on beneficence, non-maleficence, and autonomy using a deontological ethical framework.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder responsible for over half of dementia cases, with two-thirds being women. Growing evidence from preclinical and clinical studies underscores the significance of sex-specific biological mechanisms in shaping AD risk. While older age is the greatest risk factor for AD, other distinct biological mechanisms increase the risk and progression of AD in women including sex hormones, brain structural differences, genetic background, immunomodulation and vascular disorders. Research indicates a correlation between declining estrogen levels during menopause and an increased risk of developing AD, highlighting a possible link with AD pathogenesis. The neuroprotective effects of estrogen vary with the age of treatment initiation, menopause stage, and type. This review assesses clinical and observational studies conducted in women, examining the influence of estrogen on cognitive function or addressing the ongoing question regarding the potential use of hormone replacement therapy (HRT) as a preventive or therapeutic option for AD. This review covers recent literature and discusses the working hypothesis, current use, controversies and challenges regarding HRT in preventing and treating age-related cognitive decline and AD. The available evidence indicates that estrogen plays a significant role in influencing dementia risk, with studies demonstrating both beneficial and detrimental effects of HRT. Recommendations regarding HRT usage should carefully consider the age when the hormonal supplementation is initiated, baseline characteristics such as genotype and cardiovascular health, and treatment duration until this approach can be more thoroughly investigated or progress in the development of alternative treatments can be made. [ABSTRACT FROM AUTHOR]

Background: There is a continued debate on whether menopausal hormone therapy (MHT) protects women against Alzheimer's disease (AD). It is also unclear whether phytoestrogen could be an alternative treatment for AD. Objective: To investigate whether mixed study findings may be due to differences in age at initiation of MHT and duration of prescription of different types of MHT using meta-analyses. Methods: After a systematic literature search, meta-analyses were carried out using Cochrane Revman 5.4.1.software including data from large nationwide studies of registered medically diagnosed AD and prescribed MHT. These analyses were stratified for duration and type of treatment, by age at start of prescription of therapy. Insufficient quality data were available for phytoestrogen treatment and AD meta-analyses. Results: A total of 912,157 women were included from five registries, of whom 278,495 had developed AD during follow-up. Meta-analyses suggested a small increased AD risk after 5–10 years prescription of combination MHT regardless of age, and over 10 years only in women younger than 60 years of age. No association was seen for estrogen alone for women younger than 60 years of age, but AD risk did increase for women over 60 years of age for up to 5 years of MHT prescriptions. Conclusions: Combination MHT should probably be prescribed for less than 5 years after menopause to reduce risk for AD, while estrogen alone should not be prescribed to women over 60. For phytoestrogen, small treatment trials suggested some benefit of tempeh (fermented soy), which should be investigated further. [ABSTRACT FROM AUTHOR]

Background Sex hormone changes during menopausal transition contribute to declining skin health. However, how menopause and its treatment by hormone replacement therapy (HRT) impact the skin barrier and immune system is unclear. Objectives To examine how menopause and HRT affect the skin barrier and immune cell composition in postmenopausal women following irritant challenge. Methods Two cohorts of postmenopausal women were recruited to the study. The first cohort consisted of 10 untreated women [HRT–; mean (SEM) age 56.5 (1.6) years (range 48–63)] and the second was composed of 8 women receiving HRT [HRT+; mean (SEM) age 54.0 (2.1) years (range 48–63)]. Skin irritation was induced by applying topical sodium lauryl sulfate (SLS) 1.25% to occluded buttock skin for 48 h. Clinical assessment was conducted after 24 h, followed by biopsy of both SLS-challenged and unchallenged skin for analysis of skin barrier proteins and immune cell distribution using immunofluorescence. Results Clinically, there were no significant differences in skin irritant responses between those taking or not taking HRT (including increased skin redness and blood flow). In response to SLS challenge a significant increase in transepidermal water loss (P < 0.05), filaggrin deposition and cytokeratin 10 (K10)+ cell layers (P < 0.01) was observed in individuals receiving HRT compared with the HRT– group. Following SLS challenge in individuals taking HRT, a significant (P < 0.01) reduction in CD207+ cells in the epidermis was observed, accompanied by an increase of CD207+ cells in the dermis, indicative of migrating Langerhans cells (LCs). Significantly fewer migrating LCs were found in those who were not receiving HRT (P < 0.01). Furthermore, the numbers of dermal dendritic cells (DCs), macrophages, and CD11c+CD206– and CD68+CD206– subsets were found to be significantly (P < 0.05) higher in those taking HRT following SLS challenge. Conclusions Individuals receiving HRT displayed enhanced skin barrier response to SLS challenge with thicker filaggrin and increased K10+ epidermal cell layers. Following challenge, HRT users exhibited elevated LC, inflammatory DC and macrophage counts in the dermis. These may render skin both more prone to inflammation and more capable of resolving it, while also promoting skin repair. [ABSTRACT FROM AUTHOR]

• Managing Vasomotor symptoms in 2024. Vasomotor symptoms (VMS) affect 70% of menopausal women and are considered as hallmark symptoms of the menopausal transition experienced by over three quarters of women and severely by 25% of women. Estrogen withdrawal alone is not fully responsible for the onset of the menopausal vasomotor symptoms and the mechanism of altered thermoregulation appears to be centrally mediated with alterations in hypothalamic neurotransmitters playing a key part. The loss of thermoregulatory control coexists with the altered Kisspeptin- Neurokinin B-Dynorphin-expressing (KNDy) neurons of the arcuate nucleus signaling triggered by menopause. Aim of the review was to explore evidence-based non-hormonal pharmacological interventions for treating vasomotor symptoms. Comprehensive overview of relevant literature. In the population where, hormonal options are contraindicated or not preferred by the patient, it is essential to explore evidence-based non-hormonal pharmacological interventions for treating vasomotor symptoms. The 2024 landscape of available treatments has expanded yet again, arming the providers with an even wider range of possibilities to help their patients. Fezolinetant, is the first NK3R antagonist developed for the purpose of treating hot flashes in menopausal women. NK3R antagonists provide a safe and effective treatment option for managing menopausal women with VMS. [ABSTRACT FROM AUTHOR]

Background: Burning mouth syndrome (BMS) is a chronic pain condition affecting the oral cavity. This condition mostly affects peri‐ or postmenopausal women; for this reason, sexual hormonal changes have been implicated in BMS pathogenesis. Methods: A systematic review was performed in MEDLINE/PubMed, Scopus, Web of Science, Cochrane Library and EMBASE without restriction for language or year. Eligibility criteria were controlled studies addressing the PICO question: (P) patients with BMS; (I) detection of the sex hormones; (C) patients without BMS; (O) changes on sexual hormones as a risk factor for BMS severity. Risk of bias was performed with Newcastle‐Ottawa Quality Assessment Scale. Results: Four studies were included. Salivary levels were evaluated in three studies and serum blood was used in one. Three studies analysed oestradiol and/or dehydroepiandrosterone (DHEA), two assessed progesterone and one evaluated follicle‐stimulating hormone (FSH). Oestradiol results were contradictory, with two studies reporting lower levels in BMS patients compared to controls and one finding the opposite. DHEA was statistically lower in the BMS group in one study. Progesterone showed opposite results in two studies, although none with statistical significance. FSH was statistically higher in the BMS group compared to controls. Correlation of hormones with quality of life was performed in three studies and there was no significant correlation with self‐perceived symptoms severity. Conclusion: Sexual hormones can be altered in BMS, especially oestradiol. Despite these changes, we did not find correlation between hormone fluctuation and BMS symptoms intensity affecting quality of life. These findings suggested the need for further investigation on hormonal alterations, which may be a promising target on BMS management. [ABSTRACT FROM AUTHOR]

Recombinant human growth hormone therapy, which was introduced in the 1980s, is now routine for children with advanced chronic kidney disease (CKD) who are exhibiting growth impairment. Growth hormone usage remains variable across different centers, with some showing low uptake. Much of the focus on growth hormone supplementation has been on increasing height because of social and psychological effects of short stature. There are, however, numerous other changes that occur in CKD that have not received as much attention but are biologically important for pediatric growth and development. This article reviews the current knowledge about the multisystem effects of growth hormone therapy in pediatric patients with CKD and highlights areas where additional clinical research is needed. We also included clinical data on children and adults who had received growth hormone for other indications apart from CKD. Ultimately, having robust clinical studies which examine these effects will allow children and their families to make more informed decisions about this therapy. [ABSTRACT FROM AUTHOR]

Testosterone gender affirming hormone therapy (T-GAHT) is frequently used by transgender and gender-diverse individuals assigned female at birth to establish masculinizing characteristics. Although many seek parenthood, particularly as a gestational parent or through surrogacy, the current standard guidance of fertility counseling for individuals on testosterone (T) lacks clarity. At this time, individuals are typically recommended to undergo fertility preservation or stop treatment, associating T-therapy with a loss of fertility; however, there is an absence of consistent information regarding the true fertility potential for transgender and gender-diverse adults and adolescents. This review evaluates recent studies that utilize animal models of T-GAHT to relate to findings from clinical studies, with a more specific focus on fertility. Relevant literature based on murine models in post- and prepubertal populations has suggested reversibility of the impacts of T-GAHT, alone or following gonadotropin-releasing hormone agonist (GnRHa), on reproduction. These studies reported changes in clitoral area and ovarian morphology, including corpora lutea, follicle counts, and ovarian weights from T-treated mice. Future studies should aim to determine the impact of the duration of T-treatment and cessation on fertility outcomes, as well as establish animal models that are clinically representative of these outcomes with respect to gender diverse populations. [ABSTRACT FROM AUTHOR]

Context Transgender and gender diverse (TGD) individuals have greater access to genital surgery (GS) with improved insurance coverage and access to trained surgeons and interdisciplinary gender-affirming providers. Objective To determine perioperative medical and behavioral health outcomes in transfeminine (TF) individuals undergoing GS, with use of a specific gender-affirming hormone therapy (GAHT) algorithm based on individualized risk factor assessment. Methods In this retrospective observational cohort study, we collected preoperative and postoperative data from 183 TF individuals at a single tertiary referral center from 2017 to 2022, grouping patients by those who continued estradiol (Group 1) vs those who had temporarily discontinued estradiol for 2 to 6 weeks preoperatively (Group 2). Data included clinical and biochemical assessment, GAHT regimens, validated behavioral health measures, and postoperative complications. Main outcomes included venous thromboembolism (VTE) incidence, non-VTE postoperative complication incidence, and change in behavioral health assessments. Results The majority of individuals continued estradiol perioperatively (Group 1; 138 [75.4%]). Individuals who temporarily held estradiol preoperatively (Group 2; 45 [24.6%]) were statistically older (P <.01), had higher incidence of cardiometabolic comorbidities (P <.01), and higher Caprini scores (P <.01). Group 1 was statistically more likely to use oral estradiol (P <.01). One episode (0.05%) of VTE occurred (Group 1). There was no significant difference in postoperative complications or behavioral health measures between groups. Conclusion An individualized algorithm for preoperative hormone management for TF GS resulted in perioperative continuation of GAHT for the majority of individuals without significantly increasing the risk for postoperative surgical complications, while maintaining stable behavioral health measures perioperatively. [ABSTRACT FROM AUTHOR]

Background Endogenous sex steroids influence the pubertal growth spurt and adult height. However, the impact of puberty suppression and sex steroids on growth in transgender adolescents is sparsely studied. Aim We investigated pubertal growth, serum IGF-I and IGF binding protein-3 (IGFBP-3), and adult height of transgender adolescents receiving hormone therapy. Methods Observational study of a national cohort (2016-2023) comprising 219 transgender adolescents <18 years of age. Treatment consisted of gonadotropin-releasing hormone agonist combined with estradiol or testosterone (adjusted to serum concentrations between 0 and +2 SDs corresponding to the gender identity). Results Adult height was within ±2 SD for sex assigned at birth. Most trans girls reached adult height within references of girls. For trans girls (bone age ≤15 years before treatment), a growth spurt was observed during estradiol therapy. IGF-I and height SD score (SDS) declined during oral estradiol administration (−0.13 SDS per month, P =.059, and −0.02 SDS, P =.001, respectively). We observed significantly lower adult height compared to target height for trans girls (−2.7 cm, P =.01) and significant differences between height SDS before treatment and at adult height (−0.35 SDS, P <.001). Half of the trans boys remained short (<−2 SD) compared to references for boys, and most completed growth spurt before initiation of treatment. IGFBP-3 declined following testosterone treatment. There was a significant difference between height SDS before treatment and at adult height (−0.17 SDS, P <.001). Discussion and Conclusion The minor reduction in adult height of trans girls after hormone treatment may be beneficial to some, whereas trans boys did not experience height gain. [ABSTRACT FROM AUTHOR]

Context The plasma metabolome is a functional readout of metabolic activity and is associated with phenotypes exhibiting sexual dimorphism, such as cardiovascular disease. Sex hormones are thought to play a key role in driving sexual dimorphism. Objective Gender-affirming hormone therapy (GAHT) is a cornerstone of transgender care, but longitudinal changes in the plasma metabolome with feminizing GAHT have not been described. Methods Blood samples were collected at baseline and after 3 and 6 months of GAHT from transgender women (n = 53). Participants were randomized to different anti-androgens, cyproterone acetate or spironolactone. Nuclear magnetic resonance-based metabolomics was used to measure 249 metabolic biomarkers in plasma. Additionally, we used metabolic biomarker data from an unrelated cohort of children and their parents (n = 3748) to identify sex- and age-related metabolite patterns. Results We identified 43 metabolic biomarkers altered after 6 months in both anti-androgen groups, most belonging to the very low- or low-density lipoprotein subclasses, with all but 1 showing a decrease. We observed a cyproterone acetate-specific decrease in glutamine, glycine, and alanine levels. Notably, of the metabolic biomarkers exhibiting the most abundant "sex- and age-related" pattern (higher in assigned female children and lower in assigned female adults, relative to assigned males), 80% were significantly lowered after GAHT, reflecting a shift toward the adult female profile. Conclusion Our results suggest an anti-atherogenic signature in the plasma metabolome after the first 6 months of feminizing GAHT, with cyproterone acetate also reducing specific plasma amino acids. This study provides novel insight into the metabolic changes occurring across feminizing GAHT. [ABSTRACT FROM AUTHOR]

HIV prevalence among transgender women (TW) in Tijuana, Mexico is estimated at 22%. Pre-exposure prophylaxis (PrEP) reduces the risk of HIV acquisition by > 90%, though uptake in Tijuana has been low due to limited availability. The interplay between PrEP and gender stigmas may also serve as a barrier to PrEP uptake among TW in Tijuana. Experiences of gender- and PrEP- stigmas were assessed quantitatively (Quan) among 110 HIV-negative TW and qualitatively (Qual) among 17 TW through semi-structured interviews guide by the Health Stigma and Discrimination Framework. Qual findings were triangulated with Quant data to identify factors that may support gender affirmation and reduce PrEP stigma in an explanatory sequential Quan → Qual fashion. Most participants were < 40 years of age (80%), while approximately half had at least a high school education (48.2%) and were accessing gender-affirming hormone therapy (56.4%). Mean expectations of gender stigma were greatest for endorsing negative future expectations from others (M = 17.69; possible range 0–36). PrEP stigma was prominent among those who associated negative stereotypes with PrEP users, such as poor judgment (M = 45.91; possible range 14–70) and high personal risk attributes (M = 28.61; possible range 12–60). While PrEP knowledge was low among the qualitative sample, participants identified gender-, PrEP-, and intersectional- stigmas as potential barriers to PrEP uptake. Participants suggested that resilience strategies used to combat gender stigma could also mitigate PrEP stigma. Enhancing resilience skills at the intersection of gender and PrEP stigma may reduce these barriers, facilitating greater PrEP uptake as it becomes more available in Mexico. [ABSTRACT FROM AUTHOR]

Background: Women may lack awareness of the existence of Hormone Replacement Therapy (HRT), its benefits, and potential drawbacks. Furthermore, they may be uninformed about the treatability of menopausal symptoms. Consequently, there is a need to evaluate the knowledge, attitudes, and practices related to HRT among menopausal women within the Malaysian population. Presently, no studies have reported on the inside, attitudes, and practices regarding HRT among menopausal women in Kuala Lumpur. This study sought to determine the prevalence, knowledge, attitude, and practice (KAP) towards HRT and its association with socio-demographic characteristics of the study population. Method: A cross-sectional study was conducted among menopausal women (n = 404) living in Kuala Lumpur, Malaysia. Data was collected using convenient sampling. This research consists of 5 major parts which are (A) Socio-demographic characteristics of participants, (B) HRT knowledge among respondents, (C) Attitudes towards HRT, (D) Practice of HRT, and (E) Menopausal symptoms. All appropriate data from the project was analyzed using IBM SPSS Statistics Ver 26. Results: A total of 404 participants were recruited in this survey. Overall, participants had good knowledge (n = 254, 62.9%) and negative attitude (n = 213, 52.7%) towards HRT. The majority of them (83.4%) had never taken HRT. The common menopausal symptoms reported were hot flashes (35.4%), irritability/ mood swings (31.9%), and night sweats (29.2%). There was a significant association between knowledge of menopause and HRT and attitude towards HRT use. Participants (68.7%, n = 103) with poor knowledge of menopause and HRT showed a negative attitude towards HRT (p < 0.01). Conclusions: Overall, the prevalence of HRT use among the respondents is low. 83.4% of them have never taken HRT before. There was a positive correlation between knowledge and attitude towards HRT use. Healthcare systems should educate the public using various educational tools and social media. [ABSTRACT FROM AUTHOR]

Conservation breeding programs (CBPs) are often the lifeline between extinction and survival for many imperilled amphibian species. With the goal of recovering wild populations, CBP success is reliant on their ability to successfully manage ex situ populations over time, breed viable offspring, and maintain genetic diversity and adaptive potential. Reproductive technologies have emerged as an important tool in the conservation toolkit to allow managers to improve reproductive output and genetic management, and their use in amphibian conservation is expanding. To date, studies investigating the efficacy of hormone therapies in amphibians typically only report spawning and fertility rates and do not monitor offspring to later stages of development. For the first time, here we assess the effect of hormone therapies on captive breeding outcomes beyond oviposition, to the point of metamorphosis, in the critically endangered Baw Baw frog, Philoria frosti. To determine the effect of hormone therapy on spawning success and offspring viability, male-female pairs were administered either 0 µg/g gonadotropin-releasing hormone agonist (GnRHa), 0.5 µg/g GnRHa, or 0.5 µg/g GnRHa + 10 µg/g metoclopramide (MET) (n = 12 pairs/treatment), and the number of pairs ovipositing, time to oviposition, clutch size, metamorph mass, and the proportion and number (mean and total) of offspring to metamorphosis were quantified. Overall, the percentage of pairs that oviposited was high across all treatment groups (92-100%). The percentage of fertile clutches was highest in the GnRHa group (92%) and lowest in the GnRHa + MET group (82%), though differences were not statistically significant. Both hormone treatment groups took significantly less time to oviposit than the control pairs. Notably, the proportion of eggs developing to metamorphosis was significantly higher in the GnRHa group, resulting in 74% (total eggs=539) metamorphosing compared to approximately 50% in the control and GnRHa +MET treatments (total eggs= 273 and 264, respectively). Interestingly, weight at metamorphosis was statistically similar across all groups, and results are consistent with previous studies in this species that show a narrow range in size at metamorphosis. The continued application of GnRHa is recommended to improve conservation outcomes for the critically endangered Baw Baw frog. The outcomes of this research advance our understanding of the impact of hormone therapies on reproductive outcomes and will inform amphibian conservation breeding programs globally. [ABSTRACT FROM AUTHOR]

Background: Transgender patients often cannot access a provider who is knowledgeable about providing gender-affirming hormone therapy (GAHT). This study evaluated primary care provider (PCP) comfort and experience with, opinions about, and knowledge of prescribing GAHT to adults. Methods: An anonymous Qualtrics survey was distributed to PCPs in San Diego County. Fisher's exact test assessed any association between age, years in practice, or practice setting and 1) comfort in prescribing GAHT and 2) favorable statements about learning about, providing, and benefitting from training in GAHT. T-tests determined relationship between age, years in practice, or practice type setting with number of correctly answered multiple choice knowledge-based questions out of 4. Results: Out of 220 responses, median age was 41, 60% had practiced for ≤ 10 years, and 19% had practiced in an academic setting. Forty-two percent did not receive any education about transgender healthcare during medical training. The most commonly reported barrier to providing GAHT was lack of training (74%). PCPs age ≤ 41 (67% vs 49%, p = 0.009), PCPs practicing for ≤ 10 years (65% vs 51%, p = 0.037), and PCPs in non-academic settings (64% vs. 41%, p = 0.013) were more likely to report being comfortable with prescribing GAHT. PCPs age ≤ 41 (89% vs 62%, p < 0.001) and PCPs practicing for ≤ 10 years (86% vs 66%, p < 0.001) were more likely to show interest in learning about GAHT. PCPs age ≤ 41 (74% vs 46%, p < 0.001) and PCPs practicing for ≤ 10 years (70% vs 50%, p = 0.003) were more likely to show interest in prescribing GAHT. Knowledge scores were higher for PCPs age ≥42 (mean 1.7 vs 1.4, p = 0.033) and PCPs working in academic centers (mean 2.0 vs 1.4, p = 0.002). Conclusion: Younger (age ≤ 41) and early career (practicing for ≤ 10 years) PCPs reported being more comfortable with prescribing GAHT and had more favorable opinions in learning about, providing, and benefitting from training in GAHT. They are interested in providing GAHT; however, few prescribe GAHT with most reporting lack of training as a major barrier. This was evident with overall low knowledge scores regardless of age, experience, or clinical setting and underscores the need for increased educational efforts in transgender care throughout medical training. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions Gender‐affirming hormone therapy (GAHT) includes estrogen preparations and androgen inhibitors for transgender women, and testosterone preparations for transgender men. The aim of the study was to investigate possible effects of GAHT on lower urinary tract symptoms (LUTS) and sexual function among transgender individuals.Fifty‐one transgender men and 47 transgender women were prospectively recruited. Four validated female questionnaires (Bristol Female Lower Urinary Tract Symptoms [BFLUTS] questionnaire, the Medical, Epidemiologic, and Social aspects of Aging [MESA] questionnaire, Urgency, the Severity and Impact Questionnaire [USIQ], and the Female Sexual Function Index [FSFI]) and two validated male questionnaires (International Prostate Symptom Score [IPSS], and the International Index of Erectile Function [IIEF]) were used to assess LUTS and sexual function among transgender men and women, respectively, before and during GAHT. Follow‐up was performed over a period of 3–12 months.Thirty‐four transgender men (mean age 24.4 ± 7.6 years) and 31 transgender women (mean age 29 ± 8.7 years) completed all questionnaires, before and during GAHT. Testosterone treatment was associated with a statistically significant improvement in sexual desire among transgender men, as reflected in the FSFI questionnaire (4.5 ± 1.2 vs. 3.6 ± 1.3, P = 0.002). None of the three LUTS questionnaires showed statistically significant changes during the treatment with testosterone preparations. Estrogen treatment was associated with a statistically significant decrease in erectile function among transgender women, as reflected by the IIEF questionnaire (9.0 ± 7.2 vs. 14.1 ± 11.1, P = 0.012). No significant changes were found in LUTS during the treatment with estrogen preparations, except for a slight worsening of nocturia (2.1 ± 1.8 vs. 1.1 ± 1.4, P = 0.009).GAHT was not found to be associated with significant LUTS in both transgender men and women. Nevertheless, some effects on sexual function were observed, mainly a decrease in erectile function among transgender women and an increase in sexual desire among transgender men. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionsThis study aimed to evaluate physician–patient alignment on menopausal symptom burden and impact for women experiencing natural vasomotor symptoms (nVMS) or VMS induced by endocrine therapy for breast cancer (iVMS).For this real-world, cross-sectional survey, physicians from the USA and five European countries provided data for consulting patients experiencing nVMS/iVMS; patients optionally self-reported their experiences. Alignment between physician and patient responses was assessed using weighted Cohen’s κ analysis.Physicians and patients completed 1029 pairs of surveys (846 nVMS; 183 iVMS). In 28.1% of cases for nVMS and 29.6% for iVMS, patients reported more severe vasomotor symptoms (VMS) than physicians; alignment of responses was slight (nVMS, κ = 0.1364, p ≤ 0.0001; iVMS, κ = 0.1014, p = 0.039). For the non-VMS symptoms surveyed, 18.5–34.9% of patients with nVMS and iVMS reported symptoms without a corresponding physician report; sleep disturbances, cognitive difficulties and mood changes were among the symptoms most under-reported by physicians. Alignment regarding the impact of nVMS and iVMS on sleep, mood and overall quality of life was moderate.Only slight to moderate physician–patient alignment was found across all areas surveyed. These findings suggest that physicians often underestimate the severity of VMS and the presence of other menopausal symptoms, highlighting a need to improve physician–patient communication. [ABSTRACT FROM AUTHOR]

Distant recurrence in women with oestrogen receptor-positive early breast cancer persists at a constant rate for more than 20 years after diagnosis, with little equivalent data for oestrogen receptor-negative breast cancer. Using the database of the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) we investigated rates of distant breast-cancer recurrence in oestrogen receptor-positive and oestrogen receptor-negative tumours and trends in outcomes over time. In this pooled analysis of randomised controlled trial data, patients in the EBCTCG database of more than 650 000 women in trials of treatment for early-stage breast cancer were screened for eligibility. Women were eligible if they were enrolled between 1990 and 2009 and newly diagnosed with oestrogen receptor-positive breast cancer and scheduled for at least 5 years of endocrine therapy, or oestrogen receptor-negative disease, and if they were younger than 75 years at diagnosis, had a tumour diameter of 50 mm or less, and fewer than ten positive axillary lymph nodes, and no evidence of distant metastases at entry. Trial of neoadjuvant therapy, or those in which adjuvant therapy was unclear, and women with oestrogen receptor-negative, progesterone receptor-positive disease, or those for whom outcome or baseline data were missing were excluded. The primary outcome was time to first distant recurrence as defined by each trial, ignoring any locoregional recurrence or contralateral breast cancer. 10-year risks of distant recurrence by period of diagnosis were compared using Cox regression adjusted for patient and tumour characteristics, trial, and assigned treatment. Of the 652 258 women with early breast cancer in the EBCTCG database on Jan 17, 2023, patient-level data were available from 151 randomised trials that included 155 746 women. Rates of distant tumour recurrence improved similarly in women with oestrogen receptor-positive and oestrogen receptor-negative tumours. 80·5% of the improvement for oestrogen receptor-positive disease and 89·8% of the improvement for eostrogen receptor-negative disease was explained by changes in patient and tumour characteristics and improved treatments, but remained significant (p<0·0001). More recently diagnosed patients were more likely to have node-negative disease. 10-year distant recurrence risks during 1990–99 versus 2000–09 were as follows: for node-negative disease, 10·1% versus 7·3% for oestrogen receptor-positive disease and 18·3% versus 11·9% for oestrogen receptor-negative disease; for disease with one to three positive nodes, 19·9% versus 14·7% for oestrogen receptor-positive disease and 31·9% versus 22·1% for oestrogen receptor-negative disease; and for disease with four to nine positive nodes, 39·6% versus 28·5% for oestrogen receptor-positive disease and 47·8% versus 36·5% for oestrogen receptor-negative disease. After adjustment for therapy, rates were reduced by 25% (oestrogen receptor-positive disease) and 19% (oestrogen receptor-negative disease) after 2000 versus the 1990s, with similar improvements observed in oestrogen receptor-positive disease beyond 5 years. Most of the improvement in trial outcomes is explained by a greater proportion of women with lower-risk disease entering trials and improved adjuvant treatment. After adjustment, women diagnosed since 2000 have about a fifth lower rate of distant recurrence than the 1990s. Long-term risks of distant recurrence for oestrogen receptor-positive disease remain, but are about a tenth lower now than in our previous report. Cancer Research UK, UK Medical Research Council. [ABSTRACT FROM AUTHOR]

Objective: While infertility affects about 15% of women during their reproductive years, its long-term impact on stroke mortality after this period remains unclear. This study aims to investigate the association between infertility and stroke mortality in women using data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. Methods: We analyzed data from 75,778 female participants aged 55-74 years with a median follow-up of 16.84 years. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for stroke mortality, adjusting for potential confounders. Results: Among participants, 14.53% reported infertility. During follow-up, 1,159 women died from stroke. Compared to women without infertility, those with infertility had a higher risk of stroke mortality (HR 1.21, 95% CI 1.04-1.41, p = 0.016). This association remained statistically significant after adjusting for age, race, education level, marital status, smoking status, body mass index, history of hypertension, history of heart attack, history of diabetes mellitus, birth control pill use, hormone replacement therapy, endometriosis, first menstrual period and pregnancy history (HR 1.20, 95% CI 1.02-1.42, p = 0.029). Sensitivity and subgroup analyses yielded consistent results. Conclusion: The findings of this study indicate that infertility is associated with an increased risk of stroke mortality in women. Further research is needed to confirm these findings and elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Growth hormone (GH) deficiency (GHD) in children and adolescents can vary in severity and origin, with GH replacement therapy proving effective in achieving genetic target height. Optimal outcomes are seen in those treated early and with higher doses. As patients approach adult height, priorities shift towards optimizing metabolic effects, maintaining body composition, and enhancing bone mass and muscle strength. Transitioning from pediatric to adult care presents challenges, including accurately identifying candidates for continued GH therapy, reevaluating persistent GHD, and preventing treatment discontinuation. Assessing readiness for transition and self-management skills is crucial. This Policy and Practice Review provides a comprehensive overview of current policies, regulations, and guidelines pertinent to managing GHD transition in Belgium. We integrate perspectives from national academic and nonacademic clinical stakeholders in pediatric and adult endocrine care to provide an updated policy framework. This framework underscores the importance of sustained GH therapy during transition, particularly for individuals with persistent GHD, with the goal of optimizing practices and improving outcomes during this critical period. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to assess the efficacy and safety of combining goserelin with anastrozole in neoadjuvant endocrine therapy (NET) for patients diagnosed with premenopausal breast cancer. Methods: A retrospective analysis was conducted on the clinicopathological data of 34 patients diagnosed with premenopausal breast cancer who underwent NET in the Department of Breast Surgery at Baotou Cancer Hospital between March 2016 and December 2019. Additionally, the feasibility of using goserelin combined with anastrozole for premenopausal endocrine therapy was assessed. Results: The duration of NET ranged from 6 to 72 months, with a mean of 22.5 months and a median of 18 months. In patients with progressive disease, endocrine therapy was assessed over a period of 6 to 18 months, with a mean of 13.1 months and a median of 13 months. Among the 28 patients assessed, 12 (42.86%) were found to have stable disease, subsequently receiving chemotherapy. Of these, seven patients demonstrated good compliance, and 5 achieved a pathological complete response. Including the 2 patients who responded favorably to NET alone, a total of 7 patients attained a pathological complete response. Additionally, 16 patients achieved complete cell cycle arrest following treatment. A significant correlation was observed between the clinical efficacy assessment and the pathological assessment of NET (P < 0.05). Conclusion: Although NET was safe for patients diagnosed with premenopausal breast cancer, it should not be considered in isolation from chemotherapy. Transitioning to chemotherapy in a timely manner can significantly enhance treatment outcomes. The duration of NET should be guided by clinical assessment rather than being constrained by a predetermined time frame. [ABSTRACT FROM AUTHOR]

Hormone receptor-positive breast cancer (BC) is the most prevalent subtype of BC and is generally correlated with a favorable prognosis. This study aimed to determine the incidence and survival trends among women diagnosed with hormone receptor-positive BC between 1990 and 2019. Female patients with hormone receptor-positive BC for calendar years 1990–2019 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database and categorized into six diagnostic groups according to the year of diagnosis. Age-adjusted incidence rates (IRs) were calculated using joinpoint regression. We used the Kaplan–Meier method and multivariate Cox regression analyses to determine the association between diagnostic groups, and overall survival (OS) and BC-specific survival (BCSS). The final analysis included 370,729 women, among whom 37,943 (10.2%), 49,266 (13.3%), 55,652 (15.0%), 64,451 (17.4%), 77,127 (20.8%), and 86,290 (23.3%) were diagnosed between 1990 and 1994, 1995–1999, 2000–2004, 2005–2009, 2010–2014, and 2015–2019, respectively. Within the overall cohort, IRs gradually increased from 70 per 100,000 in 1990 to 113 per 100,000 in 2019 (average annual percent change, 1.59%; 95% CI, 1.18–1.99). Multivariate Cox regression analysis revealed that the survival outcomes gradually improved over nearly three decades among hormone receptor-positive BC patients, with a 0.8% and 1.3% decrease in risk for all-cause and BC-specific mortality each year, respectively. Compared to 1990–1994, hormone receptor-positive BC patients diagnosed in 2015–2019 had a 22% lower risk of all-cause death (hazard ratio [HR], 0.78; 95% CI, 0.76–0.81) and a 27% lower risk of BC-specific death (HR, 0.73; 95% CI, 0.70–0.76). The development of treatment strategies within the past three decades, especially endocrine therapy, may contribute to the continuous improvement of clinical outcomes in patients with hormone receptor-positive BC. [ABSTRACT FROM AUTHOR]

Estrogen receptor alpha (ERα) plays a critical role in breast cancer (BC) progression, with endocrine therapy being a key treatment for ERα + BC. However, resistance often arises due to somatic mutations in the ERα ligand-binding domain (LBD). Lasofoxifene, a third-generation selective estrogen receptor modulator, has shown promise against Y537S and D538G mutations. However, the emergence of a novel F404 mutation in patients with pre-existing LBD mutations raises concerns about its impact on lasofoxifene efficacy. This study investigates the impact of the dual Y537S and F404V mutations on lasofoxifene's efficacy. Using molecular dynamics simulations and molecular mechanics/Poisson-Boltzmann surface area (MM-PBSA) free energy calculations, we found that the dual mutation reduces lasofoxifene binding affinity and binding free energy, disrupts crucial protein-ligand interactions, and induces significant conformational changes in the ligand-binding pocket. These alterations are likely due to the loss of the pi-pi stacking interaction in the F404V mutation. These findings suggest a potential reduction in lasofoxifene efficacy due to the dual mutation. Further experimental validation is required to confirm these results and fully understand the impact of dual mutations on lasofoxifene's effectiveness in ERα + metastatic BC. [ABSTRACT FROM AUTHOR]

Background: Monocytes comprise subsets of classical, intermediate and non-classical monocytes with distinct anti- or pro-tumor effects in breast cancer (BC). They are modulated by estrogen, and can contribute to BC control by endocrine therapy in preclinical models. Methods: To elucidate whether changes in monocyte subsets are associated with treatment and response, we investigated peripheral blood samples of 73 postmenopausal women with estrogen receptor (ER) positive BC, who received aromatase inhibitor therapy with or without the mucin-1 vaccine tecemotide in the ABCSG34 trial. Blood was retrieved at baseline, midterm and end of therapy, and was analyzed for the distribution and ER expression of monocyte subsets by flow cytometry. Results: When 40 healthy, age-matched women were compared with BC patients before treatment start, ER levels of monocytes did not differ, yet patients presented with a higher frequency of classical and fewer non-classical monocytes. Endocrine therapy triggered a significant increase in ER levels in all monocyte subsets, without affecting subset distribution. Vaccination had no overall impact on subset frequency and ER expression. Yet, a shift from intermediate to classical monocytes during therapy correlated with changes in plasma cytokines and chemokines and was significantly associated with low residual cancer burden in vaccinated patients. Without tecemotide, baseline ER levels in classical monocytes were significantly higher in women with good response to endocrine therapy. Conclusions: This study identified classical monocytes to be associated with ER positive BC and with patient response to neoadjuvant endocrine treatment and cancer vaccination. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionThis study aimed to describe the vaginal microbiome of women with premature ovarian insufficiency (POI) receiving systemic hormone therapy (HT).Forty women with POI receiving systemic HT for at least 6 months, who were sexually active, were included in the descriptive cross-sectional study. Vaginal secretion was collected for DNA extraction followed by pyrosequencing of the 16S rRNA. The samples were pooled into phylogenetic groups (Ravel groups I–V).Women had mean age of 37.13 (± 7.27) years and POI diagnosis at age 27.90 (± 8.68) years, and a mean HT duration of 8.20 (± 8.73) years. It was observed that 33.4% of the women presented group I flora, with a predominance of Lactobacillus crispatus; 9% group II flora, with a predominance of Lactobacillus gasseri; 33.4% group III flora, with a predominance of Lactobacillus iners; 15.2% group IV flora, with a predominance of anaerobic bacteria; and 9% group V flora, with a predominance of Lactobacillus jensenii.Women with POI receiving HT presented a vaginal microbiome with a predominance of lactobacilli in the composition of the vaginal flora, specifically L. crispatus and L. iners when evaluated by molecular biology through pyrosequencing of 16S rRNA. [ABSTRACT FROM AUTHOR]

Hormone therapy, especially androgen deprivation therapy (ADT), is effective against prostate cancer (PC), whereas long-term ADT is a risk for metabolic/cardiovascular disorders including diabetes (DM), hypertension (HT) and dyslipidemia (DL), and might result in progression to castration-resistant prostate cancer (CRPC). We thus conducted a multicenter retrospective cohort study to ask whether CRPC progression would be associated positively with HT, DM or DL and negatively with statins prescribed for treatment of DL. In this study, 1,112 nonmetastatic PC patients undergoing ADT were enrolled. Univariate statistical analyses clearly showed significant association of HT or DM developing after ADT onset, though not preexisting HT or DM, with early CRPC progression. On the other hand, preexisting DL or statin use, but not newly developed DL or started statin prescriptions following ADT, was negatively associated with CRPC progression. Multivariate analysis revealed significant independent association of the newly developed DM or HT, or preexisting statin use with CRPC progression [adjusted hazard ratios (95% confidence intervals): 3.85 (1.65–8.98), p = 0.002; 2.75 (1.36–5.59), p = 0.005; 0.25 (0.09–0.72), p = 0.010, respectively]. Together, ADT-related development of HT or DM and preexisting statin use are considered to have positive and negative impact on CRPC progression, respectively. [ABSTRACT FROM AUTHOR]

Background: Bidirectional crosstalk between HER2 and estrogen receptor (ER) pathways may influence outcomes and the efficacy of endocrine therapy (ET). Low HER2 expression levels (HER2-low) have emerged as a predictive biomarker in patients with breast cancer (BC). Methods: PALLAS is an open, international, phase 3 study evaluating the addition of palbociclib for 2 years to adjuvant ET in patients with stage II-III ER-positive/HER2-negative BC. To assess the impact of HER2 expression on patient outcomes in the phase III PALLAS trial, we analyzed (1) the association between rate of HER2-low with demographic and clinicopathological parameters, (2) the prognostic value of HER2-low status on invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS) and (3) HER2 expression's value as a predictive biomarker of response to palbociclib. HER2-low was defined as HER2 immunohistochemistry (IHC) 1 + or IHC 2 + with negative in situ hybridization (ISH). All pathologic evaluation was performed locally. Prognostic and predictive power of HER2 were assessed with Cox models. Results: From the original PALLAS intention-to-treat population (N = 5753), 5304 patients (92.2%) were included in this analysis. Among these, 2254 patients (42.5%) were classified as having HER2 IHC 0 (HER2-0), and 3050 (57.5%) as having HER2-low disease (1838 with IHC 1 + and 1212 with IHC 2 +). Median follow-up was 59.8 months. HER2-low prevalence varied significantly across 21 participating countries (range 16.7% to 75.6%; p < 0.001) and was more frequent in patients enrolled in North America (63.1%) than in Europe (53.4%) or other regions (53.4%) (p < 0.001). HER2 status was not significantly associated with iDFS in a multivariable Cox model (hazard ratio 0.93, 95% confidence interval 0.81 – 1.06). No significant interaction was observed between treatment arm and HER2 status for iDFS (p = 0.43). Similar results were obtained for DRFS and OS. Conclusions: In this large, prospective, global patient cohort, no differences were observed in clinical parameters, prognosis, or differential benefit from palbociclib between HER2-0 and HER2-low tumors. Significant geographic variability was observed in the prevalence of HER2-low status, suggesting a high degree of variation in pathologic assessment of HER2 expression without impact on outcomes. [ABSTRACT FROM AUTHOR]

Background: There is growing interest in investigating genetic explanations for transgender identity. In the spirit of a Community-Engaged Research Framework, which highlights the importance of involving community members who would be impacted by research throughout the entire research process, it is important for researchers to understand transgender and gender expansive individuals' views and concerns regarding the potential harms and benefits of transgender identity genetic research (TIGR). Aim: To evaluate the thoughts, opinions, and beliefs in the transgender and gender diverse communities toward TIGR Methods: We conducted an online survey study, asking 409 transgender and gender diverse individuals about their views regarding potential benefits and risks of TIGR. Results: Participants demonstrated a mixture of positive and negative opinions on the search for a genetic contribution to gender identity. Overall, there was a slight trend toward more positive views, with 71% agreeing or strongly agreeing that TIGR made them feel hopeful. Discussion: Given the varied and nuanced views held within the transgender and gender diverse communities toward transgender genetic research, we hope that this study can be one of many evaluating this topic, and that our findings, and those of future studies, can serve as a foundation for conducting transgender genetic research in a way that is in alignment with the ethos and priorities of the transgender and gender diverse communities. [ABSTRACT FROM AUTHOR]

Background: For many trans folks, gender-affirming hormone therapy (GAHT) is a desired affirming procedure that has been linked with positive health outcomes, however literature has had little focus on the journeys of trans people as they access GAHT. Aim: To understand trans people's journey of accessing GAHT to delineate supports necessary to better engage trans individuals into gender-affirming care. Method: This study conducted semi-structured interviews with a sample of 15 Australian trans adults who participated in a larger study investigating the effects of a cyproterone acetate titration protocol. Findings: A four-factor thematic structure was created from the data. Theme one describes early cognizance of being trans and the pivotal moments in their trans realization. The second theme explores the rapid engagement with community to begin accessing information and affirming healthcare, including GAHT. The third theme explores barriers to engaging in GAHT and theme four reflects on advice participants have for other trans people who are considering GAHT. Conclusion: Findings from this study emphasize the importance of providing support to young trans people to help reconcile their gender identity and assist them to engage into care as early as possible. It also highlights the key role that community plays in providing links to affirming information and providers of GAHT – but also emphasizes the importance of considering how to engage with community who may be missed. The experience of accessing GAHT is personal and contextual, but signaling of affirming safe spaces and access to salient information may be key strategies to better support trans people choosing to access GAHT. [ABSTRACT FROM AUTHOR]

Background: Transgender and non-binary individuals face unique challenges when it comes to fertility preservation (FP). Objective: Despite the growing prevalence of gender dysphoria (GD) and gender transitioning, there is a lack of clear guidelines and consensus on the management of these patients in the FP setting. Clinicians and institutions providing FP services should ensure that they are aware of the needs and circumstances of this underrepresented group of patients and offer them accurate and evidence-based information when counseling and tailoring their FP treatment. Materials and methods: For this scoping review, three major search engines were used. Including Embase, Epistemonikos, Google Scholar, MEDLINE and PubMed. Sources of grey literature were also explored (ResearchGate and Web of Science). The combination of only two keywords [transgender] AND [fertility preservation] was used up to May 2023. Results: The available evidence on clinical management and FP outcomes in transgender patients is limited and mainly originates from case reports or small case series. The main limitation of current FP services for transgender and non-binary individuals is the lack of scientific evidence regarding their care. Discussion: Overall, FP in transgender patients requires individualized and realistic plans, and psychological counseling should be offered. This review aims to provide the latest evidence coming from original studies to facilitate proper counseling and fertility management for these individuals. Conclusions: Inclusive health systems that provide comprehensive reproductive health care to transgender individuals can help them make informed decisions about FP and improve their quality of life. Future research is needed to establish more robust evidence-based guidelines for the management of transgender and non-binary individuals in the FP setting. [ABSTRACT FROM AUTHOR]

Background: Transgender individuals frequently undergo gender-affirming hormone therapy (GAHT) during their gender transition which plays a vital role in gender identity affirmation. Cholelithiasis, a common condition affecting 10-15% of the US population, has been linked to estrogen therapy in cisgender women. Despite the fact that hormonal profiles achieved after GAHT are not always identical to cisgender individuals, the effects of GAHT on gallbladder disease (GBD) risk have not been evaluated in transgender populations. This research aims to address this gap utilizing a large nationwide database. Methods: The study analyzed medical records data from the TrinetX database from 52,847 trans men and 38,114 trans women. Four cohorts were created: trans women and men either receiving either hormone therapy or no intervention. Descriptive statistics were calculated before matching to estimate disease burden. The groups were then propensity score matched on known risk factors (age, race, BMI, etc.) and rates of GBD were compared. Results: Before matching, trans women on hormone therapy (TWHT) had a significantly higher 10-year GBD probability than those naïve to therapy (TWNI) (4.69% vs 1.88%). For trans men, there was no significant difference in 10-year rates between those on therapy (TMHT) and those not (TMNI) (3.15% vs 3.87%). Cholecystectomy rates were significantly higher for TWHT than TWNI (1.10% vs. 0.57%), but similar between TMHT and TMNI (0.95% vs. 1.10%). After accounting for risk factors, TWHT had increased GBD risk (HR 1.832), while TMHT showed no significant change. Discussion: This study suggests a link between estrogen GAHT and increased GBD risk in transgender women. Notably, testosterone GAHT did not offer protection against GBD in transgender men, contrary to expectations. This study is, to our knowledge, the first to describe the burden of GBD in the transgender population and to investigate the effects of GAHT on GBD risk. [ABSTRACT FROM AUTHOR]

Background: Gender affirmation through hormone replacement therapies and surgery can significantly improve the health and wellbeing of some transgender, nonbinary, and gender diverse people. Despite the well-documented benefits of gender affirming care, barriers persist for many trans and gender diverse people, particularly those in rural areas. Aims: This exploratory study aimed to identify the barriers trans and gender diverse people faced when seeking to medically affirm their gender in the rural state of Tasmania, Australia. Methods: This article draws on qualitative data from a mixed-methods online survey of 84 trans and gender diverse Tasmanians aged 18-70. Results: Participants identified financial and geographical barriers, discrimination, and medical gatekeeping as the three key factors that prevented or delayed their gender affirmation. Conclusion: Costly services that require multiple referrals to access limit trans and gender diverse patients' options, impacting their mental health and wellbeing. Gender affirmation on the basis of informed consent would reduce unnecessary medical gatekeeping and improve trans and gender diverse health and wellbeing. [ABSTRACT FROM AUTHOR]

Purpose: Worldwide, trans people are known to take hormones without prescription or take higher or lower doses than prescribed. The study's goal was examination of the social context behind provision and receiving of gender-affirming hormonal therapy (GAHT) in Russia, as well as collection of opinions on the organization of healthcare. Methods: Semi-structured interviews with 20 trans individuals and 6 endocrinologists. Results: Trans respondents started GAHT between 2004 and 2022. Over that period, the number of trans-competent endocrinologists increased and it became easier to receive the diagnosis F64.0 "transsexualism" (ICD-10), which qualifies one to obtain GAHT. However, the majority still took hormones without supervision. The reasons for self-medication included: the lack of the diagnosis, high cost of appointments and tests, age under 18, and self-perceived understanding of principles of GAHT. Most endocrinologists learnt about GAHT after being approached by a trans patient. They received information from advanced training courses and academic literature. The specialists had diverse opinions on the ideal policy of providing GAHT to trans people, but all claimed that in Russian political realities they found the diagnosis "transsexualism" a necessary prerequisite for initiating GAHT to safeguard both doctors and patients. Conclusions: The lack of strict law enforcement in the pharmacological sphere in Russia enabled many trans people to initiate GAHT without supervision. Trans-competent endocrinologists were available for those who needed them. Under current political circumstances it is unlikely that the informed consent model (prescription without a psychiatric diagnosis) can be implemented in Russia. [ABSTRACT FROM AUTHOR]

Introduction: Prescribing testosterone for gender affirming hormone therapy (GAHT) has been increasing in Australia with much of this practice done by general practitioners (GPs) and there are current AusPATH guidelines on how this can be done appropriately. There has been limited data collected from GPs about how well these patients are monitored and the adverse effects (AEs) that are experienced by this population of patients. Objectives: The primary objective of this study was to collect data about monitoring and adverse effects of GAHT provided in GP settings. Methods: The PUSH! Audit was a cross-sectional study that collected data from 9 GP Clinics across 5 Australian cities who provided GAHT with testosterone. Data was also collected about cisgender men who were prescribed testosterone for testosterone deficiency (TD) as a comparison group (n = 209). Results: The patients in the GAHT group (n = 277) tended to be younger (29.8 vs 54.9), with significant prevalence of smoking (21.8%) and anxiety/depression (37.2%) although this was not significantly higher that the comparison group. Most of the GAHT group had a testosterone level recorded in their file (90.6%) and the most common route of administration of testosterone was by intra-muscular injection (89.9%). The testosterone levels were mainly in the target range for males (75.7%) with only a small percentage registering levels above the target range (5.6%). Of the measured AEs, whilst there were significant prevalence of liver abnormalities and hypercholesterolemia, this was not significantly different to the TD group. The hypertension prevalence was lower in the GAHT group. Of the reported AEs, acne (10.1%) and balding (4.7%) were the only two AEs that were significantly reported. Conclusion: This study shows that GAHT with testosterone can be provided effectively in general practice with high levels of success and very low levels of AEs. [ABSTRACT FROM AUTHOR]

Progestin-associated meningioma is a rare complication of cyproterone acetate (CPA), an anti-androgen commonly prescribed in feminizing hormone therapy regimens for transgender and gender-diverse individuals. A dose-response association has been observed, particularly with longer-term exposure to doses ≥ 50 mg daily; however, the dose below which CPA use is safe remains unclear. We herein report the cases of 2 transgender women using CPA who developed meningioma. Novel aspects of our cases include: (i) the presence of symptomatic giant meningiomas (> 5 cm), including multiple meningiomas in one patient, requiring urgent surgical intervention; (ii) meningioma development with both high-dose, long duration and low-dose, shorter duration CPA; and (iii) the presence of a PIK3CA missense variant in one patient, which may play a role in the pathogenesis of progestin-associated meningioma. Our cases highlight the real-world risk of this likely underreported adverse effect and underscore the importance of clinician vigilance for neurological sequelae. We suggest using the lowest dose of CPA that maintains adequate androgen suppression, with consideration of alternative anti-androgens where appropriate. [ABSTRACT FROM AUTHOR]

Objective: We sought to review the biology and clinical benefits of genistein, a plant-derived isoflavone with emphasis on perimenopausal and postmenopausal women. The focus is on assessing its impact on skin health and aesthetics as well as bone density and cardiovascular and metabolic functions. Methods: This narrative review used PubMed to collect studies relating to the biology and clinical effects of genistein on postmenopausal signs and symptoms, including bone density loss, metabolic issues and symptoms, and skin aging. Articles were selected based on relevance to the scope of genistein's influence on estrogen receptors and their downstream effects. This review included in vitro, in vivo, animal, and human studies. Results: According to the current literature, genistein demonstrates efficacy in mitigating menopausal signs and symptoms such as hot flashes, bone density loss and rate of osteoporosis, and skin aging. It shows a protective effect against cardiovascular diseases by improving lipid profiles, weight changes, and reducing low-density lipoprotein cholesterol. It also displays benefits in increasing bone mineral density but has not displayed the side effects commonly associated with estrogen replacement. Regarding skin health, genistein appears to enhance photoprotection, wound healing, elasticity, and hydration, inhibits skin cancer, and reduces wrinkles. Conclusion: Genistein acts as a selective estrogen receptor modulator (SERM) with benefits across a spectrum of menopausal signs and symptoms, presenting a viable alternative to estrogen replacement in perimenopausal and postmenopausal women. Its utility extends to improving cardiovascular health, bone density, and skin quality, making it a comprehensive treatment option for peri and postmenopausal women. [ABSTRACT FROM AUTHOR]

Monitoring of hormone replacement therapy represents a major challenge in the management of congenital adrenal hyperplasia (CAH). In the absence of clear guidance and standardised monitoring strategies, there is no consensus among clinicians regarding the relevance of various biochemical markers used in practice, leading to wide variability in their application and interpretation. In this review, we summarise the published evidence on biochemical monitoring of CAH. We discuss temporal variations of the most commonly measured biomarkers throughout the day, the interrelationship between different biomarkers, as well as their relationship with different glucocorticoid and mineralocorticoid treatment regimens and clinical outcomes. Our review highlights significant heterogeneity across studies in both aims and methodology. However, we identified key messages for the management of patients with CAH. The approach to hormone replacement therapy should be individualised, based on the individual hormonal profile throughout the day in relation to medication. There are limitations to using 17‐hydroxyprogesterone, androstenedione and testosterone, and the role of additional biomarkers such 11‐oxygenated androgens which are more disease specific should be further established. Noninvasive monitoring via salivary and urinary steroid measurements is becoming increasingly available and should be considered, especially in the management of children with CAH. Additionally, this review indicates the need for large scale longitudinal studies analysing the interrelation between different monitoring strategies used in clinical practice and health outcomes in children and adults with CAH. [ABSTRACT FROM AUTHOR]

The association between current use of oral contraceptives (OCs) among women younger than 50 years (n  = 306 541), and hormone therapy (HT) among women aged 50 years or older (n  = 323 203), and coronavirus 2019 (COVID-19) infection and hospitalization was evaluated in this population-based cohort. Current OC/HT use was recorded monthly using prescription dispensing data. COVID-19 infections were identified from March 2020 through February 2021. COVID-19 infections and hospitalizations were identified through diagnosis codes and laboratory tests. We used weighted generalized estimating equations models to estimate multivariable adjusted odds ratios (aORs) for COVID-19 infection associated with time-varying OC/HT use. Among women with COVID-19, logistic regression models were used to evaluate OC/HT use and COVID-19 hospitalization. Over 12 months, 11 727 (3.8%) women younger than 50 years and 8661 (2.7%) women aged 50 years or older experienced COVID-19 infections. There was no evidence of an association between OC use and infection (aOR = 1.05; 95% CI, 0.97-1.12). There was a modest association between HT use and infection (aOR = 1.19; 95% CI, 1.03-1.38). Women using OCs had a 39% lower risk of hospitalization (aOR = 0.61; 95% CI, 0.38-1.00), but there was no association of HT use with hospitalization (aOR = 0.89; 95% CI, 0.51-1.53). These findings do not suggest a meaningfully greater risk of COVID-19 infection associated with OC or HT use. OC use may be associated with lower COVID-19 hospitalization risk. [ABSTRACT FROM AUTHOR]

Introduction: Acne remains one of the most common inflammatory dermatoses seen worldwide. There are significant challenges when managing acne relating to a variety of factors, including (1) lack of consensus on the use of the numerous available grading systems and outcome measures, (2) appreciation of the numerous areas that relate to severity, (3) the chronic nature of acne which requires a longitudinal approach to management (including both facial and truncal disease), and (4) the need to target acne early to avoid physical and psychosocial scarring. Consideration of these aspects when managing acne should result in improved outcomes. Acne guidelines review the available evidence based on robust clinical trials and are usually supplemented with some expert opinion when evidence is not available. Methods: In this paper, the UK Acne Working Group reflects on the latest National Institute for Health and Care Excellence (NICE) acne guidelines with a goal of providing additional practical insights. Conclusion: The group have identified areas where new evidence has now become available since the formulation of the NICE acne guidelines. This publication considers newly approved acne medications in the UK, guidance on assessing acne severity, approaches to managing truncal acne, acne sequelae, and adult female acne with hormonal therapies. Plain Language Summary: The National Institute for Health and Care Excellence (NICE) produced acne guidelines in June 2021 for clinicians and patients. New evidence and information on practical aspects of acne management have emerged since this time. A panel of clinicians with expertise in acne discuss herein some areas of interest that may support acne management, some of which could be considered in a second iteration of NICE acne guidelines. These areas include how to assess acne, the medical approach to truncal acne, how clinicians may manage the long-lasting acne sequelae of scarring and darkly pigmented spots, and the use of medical hormonal therapies for women (such as birth control pills) to manage acne that may have a causative contribution of hormone imbalances. [ABSTRACT FROM AUTHOR]

Background: Transgender men use exogenous androgen for male pattern virilization. Hysterectomy and bilateral salpingo-oophorectomy (HBSO) is performed to stop the endogenous estrogen secretion. Cardiovascular disease (CVD) risk has been shown to increase with long-term use of androgens and the removal of estrogen. We aimed to investigate the CVD risk in these individuals by measuring internal and common carotid artery intima–media thicknesses (CIMT). Methods: In this cohort study, data were collected from transgender men who had undergone HBSO and used androgens for at least two years (median treatment duration was 5 years in our research). Cisgender women in the same age range were selected as the control group. Demographics, vital signs, and hematological values of transgender patients and cisgender women subjects in the control group were noted. CVD markers were compared with sonographically measured CIMT values. Results: The mean age and body mass index (BMI) of the study group were 32.6 and 25.3, respectively. Weight, systolic–diastolic blood pressure, hemoglobin, hematocrit, low-density lipoprotein (LDL), serum triglyceride (TG), HbA1c levels, internal CIMT, and common CIMT values of the study group were higher, while the high-density lipoprotein (HDL) level was significantly lower compared the control group (p1 = 0.025, p2 = 0.010, p3 = 0.002, p4 = 0.001, p5 = 0.001, p6 = 0.012, p7 = 0.008, p8 = 0.007, p9 = 0.013, and p10 = 0.001). There was also an increase in the body weight, BMI, LDL, and TG levels of the study group after the testosterone treatment (p1 = 0.025, p2 = 0.019, p3 = 0.001, p4 = 0.001, and p5 = 0.001). Conclusions: We demonstrated that the use of testosterone therapy in transgender men is associated with higher CIMT values. While further investigation is needed to assess morbidity and mortality rates, we recommend that regular clinical and radiological examinations be performed in these individuals to accurately evaluate the risk of CVD. [ABSTRACT FROM AUTHOR]

Background/Objectives: There is evidence of overtreatment in patients with subclinical hypothyroidism (SCH). We aimed to identify the proportion of patients treated for SCH and the determinants of thyroid hormone therapy initiation. Methods: We included a random sample of adult Veterans diagnosed with SCH from 1 January 2016 to 31 December 2018 and conducted univariate and multivariable logistic regression to identify factors associated with levothyroxine initiation. Results: Out of 229 Veterans with SCH [90.0% male, 87.2% White, 99.1% non-Hispanic, median age (interquartile range; IQR) 68 (17) years], 27.5% were treated with levothyroxine. The treated group had a higher proportion of White patients (95.2% vs. 84.2%, p = 0.039), a higher thyrotropin level [median (IQR), 6.98 (2.06) mIU/L vs. 6.14 (1.10) mIU/L, p = 0.0002], a higher proportion of patients with thyrotropin level ≥ 10 mIU/L (11.1% vs. 3.0%, p = 0.021), a lower frequency of confirmatory thyroid testing before initiating levothyroxine (49.2% vs. 97.0%, p < 0.0001), and a similar frequency of thyroid autoimmunity testing (3.2% vs. 0.6%, p = 0.18) compared to the untreated group. In a multivariable logistic regression analysis, White race (OR = 4.50, 95% CI 1.19 to 17.08, p = 0.026) and index thyrotropin level [OR = 1.71, 95% CI 1.24 to 2.35, p = 0.001; for every SD increase (1.6 mIU/L)] were associated with higher odds of treatment. Conclusions: Three in 10 Veterans with SCH received levothyroxine, often based on a single abnormal thyroid test without autoimmunity assessment. White race and higher thyrotropin level were linked to increased odds of starting treatment, indicating potential disparities and the influence of SCH severity on decision-making. [ABSTRACT FROM AUTHOR]

Fifty-two years have passed since President Nixon launched the "War on Cancer". Despite unparalleled efforts and funds allocated worldwide, the outlined goals were not achieved because cancer treatment approaches such as chemotherapy, radiation therapy, hormonal and targeted therapies have not fully met the expectations. Based on the recent literature, a new direction in cancer therapy can be proposed which targets connections between cancer cells and their microenvironment by chemical means. Cancer–stromal synapses such as immunological synapses between cancer and immune cells provide an attractive target for this approach. Such synapses form ligand–receptor clusters on the interface of the interacting cells. They share a common property of involving intercellular clusters of spatially proximate and cooperatively acting proteins. Synapses provide the space for the focused intercellular signaling molecules exchange. Thus, the disassembly of cancer–stromal synapses may potentially cause the collapse of various tumors. Additionally, the clustered arrangement of synapse components offers opportunities to enhance treatment safety and precision by using targeted crosslinking chemical agents which may inactivate cancer synapses even in reduced concentrations. Furthermore, attaching a cleavable cell-permeable toxic agent(s) to a crosslinker may further enhance the anti-cancer effect of such therapeutics. The highlighted approach promises to be universal, relatively simple and cost-efficient. We also hope that, unlike chemotherapeutic and immune drugs that interact with a single target, by using supramolecular large clusters that include many different components as a target, the emergence of a resistance characteristic of chemo- and immunotherapy is extremely unlikely. [ABSTRACT FROM AUTHOR]

Simple Summary: Improved outcomes have been reported with adjuvant treatment combining cyclin-dependent kinase 4/6 inhibitors with endocrine therapy, in high-risk patients with ER-positive and HER2-negative breast cancer, regardless of age. In this real-world data analysis, MonarchE and NataLEE high-risk patients accounted for 9.5% and 33% of patients undergoing upfront surgery, respectively. Significantly higher eligibility rates were observed in patients who underwent a mastectomy, >70 years and ≤40 years for adjuvant abemaciclib and ribociclib, and in patients >80 years for ribociclib. A higher discontinuation rate for abemaciclib was reported in patients ≥65 years and it can be assumed that discontinuation rates may increase with more older patients. If the results of the NataLEE trial translate into clinical practice, the number of patients potentially eligible for adjuvant CDK4/6 inhibitors may increase, especially in the elderly population. Background: Despite early diagnosis, approximately 20% of patients with ER-positive and HER2-negative breast cancer (BC) will experience disease recurrence. Improved survival has been reported with adjuvant treatment combining cyclin-dependent kinase 4/6 inhibitors with endocrine therapy, in high-risk patients with ER-positive and HER2-negative BC, regardless of age. Older patients have higher rates of ER-positive/HER2-negative BC than younger patients. Methods: In this real-world data analysis, MonarchE and NataLEE high-risk patients accounted for 9.5% and 33% of patients undergoing upfront surgery, respectively. Significantly higher eligibility rates were observed in patients who underwent a mastectomy, >70 years and ≤40 years for adjuvant abemaciclib and ribociclib, and in patients >80 years for ribociclib. Results: Eligibility rates in patients ≤40 years and >80 years who underwent mastectomy were 27.8% and 24.7% for abemaciclib, respectively, and 56.6% and 65.2% for ribociclib, respectively. A higher discontinuation rate for abemaciclib was reported in patients aged ≥65 years and it can be assumed that discontinuation rates may increase in even older patients. Conclusions: If the results of the NataLEE trial translate into clinical practice, the number of patients potentially eligible for adjuvant CDK4/6 inhibitors may increase, especially in the elderly population. [ABSTRACT FROM AUTHOR]

Simple Summary: Menopause remains a complex challenge after breast cancer. Menopausal symptoms, whether iatrogenic or premature due to cancer treatment, significantly affect health and quality of life. Menopausal hormone therapy is currently deemed unsafe in hormone-sensitive breast cancer. Unfortunately, the alternative non-hormonal therapies are not as effective in controlling menopausal symptoms. The aim of our narrative review was to determine the risk of recurrence of breast cancer in breast cancer survivors taking menopausal hormone therapy. Data on this topic are of low quality and outdated. This review highlights the need for future research to help navigate this difficult path. Menopausal symptoms negatively impact quality of life in breast cancer survivors. The paucity of data on the impact of Menopausal Hormone Therapy (MHT) on oncological outcomes in these patients limits informed clinical discussion. Defining the risk of cancer recurrence with MHT is central to the appraisal of risk/benefit, particularly with low-risk disease (based on genomic profile). The aim of this review is to summarize the current data evaluating MHT in breast cancer patients. A systematic review of the literature was performed to evaluate the impact of MHT on oncological outcomes in breast cancer survivors. Three major databases (PubMed, EMBASE and Medline) were searched. The review included all prospective studies published in English. Four randomized control trials and four non-randomized prospective studies were identified. An increase in breast cancer recurrence with MHT was observed in the early randomized trials whilst no increased risk of recurrence was reported in the observational studies. There remains a need to quantify MHT-related recurrence risk in patients with molecularly favorable disease. [ABSTRACT FROM AUTHOR]

Background Relatively little is known about the differences in prognostic factors for early vs late recurrence among women with early stage estrogen receptor–positive breast cancer. Methods We analyzed factors related to early (<5 years) vs late (≥5 years) recurrence in 2992 women with stage I-IIB estrogen receptor–positive breast cancer in the Pathways Study, a prospective cohort of women with breast cancer enrolled between 2006 and 2013, with ascertainment of recurrence and death through December 2021. Results After a median follow-up of 13.3 years, 341 (13.8%) women had recurrences, including 181 (53.7%) with late recurrence. Higher stage and grade were associated with recurrence regardless of timing, whereas progesterone receptor negativity was associated with early but not late recurrence. Receipt of endocrine therapy was associated with reduced risk of overall recurrence, but the length of endocrine therapy was not statistically significant in multivariable models. Minoritized racial and ethnic groups, including Asian, Black, and Hispanic women, had higher risk of early but not late recurrence compared to non-Hispanic White women. The trend of higher risk of early recurrence among these groups remained after adjustment for clinical, demographic, and socioeconomic factors but was statistically significant only in Asian women. Conclusions Our study revealed potentially important distinctions for early vs late recurrence, including the associations with progesterone receptor negativity and self-identified race and ethnicity. Possible higher risk of early recurrence among Asian, Black, and Hispanic women provides novel evidence for the existence of disparities in cancer outcomes, even within the breast cancer subtype indicative of generally good prognosis. [ABSTRACT FROM AUTHOR]

Background Despite the wide use of a 3-month gonadotropin-releasing hormone (GnRH) agonist for ovarian function suppression in premenopausal breast cancer patients, it remains unclear whether it is as effective and safe as a 1-month GnRH agonist regimen when combined with selective estrogen receptor modulators or aromatase inhibitors, especially in younger patients. Methods This retrospective cohort study included 1109 premenopausal hormone receptor–positive breast cancer patients treated with GnRH agonist plus selective estrogen receptor modulator or aromatase inhibitor. The estradiol (E2) inhibition rate within 1-24 months after treatment with 1-month or 3-month GnRH agonist in cohorts and different subgroups was analyzed. Results Following 1:1 propensity score matching, 950 patients with a mean age of 39 years and a median follow-up of 46 months were included. Both the 1-month and 3-month groups achieved more than 90% E2 inhibition within 24 months (94.53% vs 92.84%, with a 95% confidence interval for the difference ranging from −4.78% to 1.41%), confirming the noninferiority of 3-month GnRH agonist. Both 1-month and 3-month GnRH agonist rapidly and consistently reduced E2 levels. Of the patients, 60 (6.3%) experienced incomplete ovarian function suppression, with similar rates in the 1-month and 3-month groups (5.5% vs 7.2%). Incomplete ovarian function suppression mainly occurred within the first 12 months, with age younger than 40 years and no prior chemotherapy being the risk factors. Similar disease-free survival and overall survival were found in the 1-month and 3-month groups and in patients with complete and incomplete ovarian function suppression (P  >  .05). Conclusions The ovarian function suppression with 3-month GnRH agonist was not inferior to that with 1-month GnRH agonist, regardless of age or combination with a selective estrogen receptor modulator or an aromatase inhibitor. [ABSTRACT FROM AUTHOR]

Menopause is characterized by many physiologic changes due to decreasing hormone levels. Genitourinary syndrome of menopause causes vulvovaginal symptoms, urinary symptoms, and sexual symptoms. This systematic review evaluated the effectiveness and harms of vaginal estrogen, nonestrogen hormone therapies, and vaginal moisturizers with regard to patient-reported outcomes. Background: Postmenopausal women commonly experience vulvovaginal, urinary, and sexual symptoms associated with genitourinary syndrome of menopause (GSM). Purpose: To evaluate effectiveness and harms of vaginal estrogen, nonestrogen hormone therapies, and vaginal moisturizers for treatment of GSM symptoms. Data Sources: Medline, Embase, and CINAHL through 11 December 2023. Study Selection: Randomized controlled trials (RCTs) of at least 8 weeks' duration enrolling postmenopausal women with at least 1 GSM symptom and reporting effectiveness or harms of hormonal interventions or vaginal moisturizers. Data Extraction: Risk of bias and data extraction were performed by one reviewer and verified by a second reviewer. Certainty of evidence (COE) was assessed by one reviewer and verified by consensus. Data Synthesis: From 11 993 citations, 46 RCTs evaluating vaginal estrogen (k = 22), nonestrogen hormones (k = 16), vaginal moisturizers (k = 4), or multiple interventions (k = 4) were identified. Variation in populations, interventions, comparators, and outcomes precluded meta-analysis. Compared with placebo or no treatment, vaginal estrogen may improve vulvovaginal dryness, dyspareunia, most bothersome symptom, and treatment satisfaction. Compared with placebo, vaginal dehydroepiandrosterone (DHEA) may improve dryness, dyspareunia, and distress, bother, or interference from genitourinary symptoms; oral ospemifene may improve dryness, dyspareunia, and treatment satisfaction; and vaginal moisturizers may improve dryness (all low COE). Vaginal testosterone, systemic DHEA, vaginal oxytocin, and oral raloxifene or bazedoxifene may provide no benefit (low COE) or had uncertain effects (very low COE). Although studies did not report frequent serious harms, reporting was limited by short-duration studies that were insufficiently powered to evaluate infrequent serious harms. Limitations: Most studies were 12 weeks or less in duration and used heterogeneous GSM diagnostic criteria and outcome measures. Few studies enrolled women with a history of cancer. Conclusion: Vaginal estrogen, vaginal DHEA, oral ospemifene, and vaginal moisturizers may improve some GSM symptoms in the short term. Few long-term data exist on efficacy, comparative effectiveness, tolerability, and safety of GSM treatments. Primary Funding Source: Agency for Healthcare Research and Quality and Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42023400684) [ABSTRACT FROM AUTHOR]

Hypoparathyroidism is a disease characterized by inadequate or absent parathyroid hormone (PTH) levels. It manifests with hypocalcemia, hyperphosphatemia, and elevated urinary fractional excretion of calcium. The conventional therapy with calcium supplementation and active vitamin D analogs is limited by the pill burden, unstable calcium concentrations, and significant renal and bone complications. Hence, the development of replacement therapies utilizing PTH or PTH-related receptor modulators has emerged as a promising therapeutic avenue. rhPTH (1-84) (NATPARA®) is a once-daily injection of full-length recombinant human parathyroid hormone that was initially approved by the U.S. Food and Drug Administration(FDA) in 2015 for hypoparathyroidism. However, it was recalled from the U.S. market in 2019, and its production will cease globally by the end of 2024. TransCon™ PTH, known as palopegteriparatide, utilizes an innovative technology to provide a sustained release of PTH (1-34) prodrug. It has received approval from the European Medicines Agency and is currently undergoing FDA review. Eneboparatide is a PTH receptor 1 agonist, designed to stimulate a specific receptor configuration. Encaleret is a negative allosteric modulator of the calcium-sensing receptor and rescues the secretion of naive PTH inAutosomal Dominant Hypocalcemia type 1. MBX 2109 is an investigational once-weekly PTH prodrug that addresses thefrequent administration challenge. EB612, the tablet form of PTH(1-34), is the first oral hormone replacement treatment for hypoparathyroidism. Recent developments in the management of chronic hypoparathyroidism hold promise as a therapeutic approach to restore physiological function, manage symptoms, and prevent associated complications. [ABSTRACT FROM AUTHOR]

To discuss the increasing visibility of non-binary individuals and inclusive policies and practices in assisted reproductive technologies (ART). Comparison between traditional ART approach designed for binary genders and propose approach in non-binary individuals. Traditional ART services, designed for binary genders, must adapt to address the unique fertility needs of non-binary patients. This includes using gender-neutral language, providing comprehensive fertility assessments, and offering hormone therapy and fertility preservation options. Children of non-binary parents benefit from open communication about gender diversity, enhancing psychological well-being. Positive societal attitudes and inclusive environments in schools are crucial for preventing discrimination and promoting mental health. A systemic approach is required to make ART inclusive. This involves training staff, adjusting facilities, updating documentation, and advocating for supportive legislation. Addressing the reproductive needs of non-binary individuals ensures equitable access to care and supports their family-building goals. Ensuring the well-being of children in non-binary families requires psychological support, inclusive healthcare, legal recognition, social support, and comprehensive education. [ABSTRACT FROM AUTHOR]

Background: Although sex hormones are recognized to induce immune variations, the effect of hormonal therapy use on immunity is only poorly understood. Here, we quantified how hormonal therapy use affects HIV‐1 immune markers in cis women (CW) and trans women and non‐binary people (TNBP) with HIV. Methods: We considered CD4, CD8 and lymphocyte measurements from cis men (CM), CW and TNBP in the Swiss HIV Cohort Study. We modelled HIV‐1 markers using linear mixed‐effects models with an interaction between 'gender' (CW, TNBP) and 'hormonal therapy use' (yes/no). Models were adjusted on age, ethnicity, education level, time since start of antiretroviral therapy and use of intravenous drugs. We assessed the inflammatory effect of hormonal therapy use in 31 TNBP using serum proteomics measurements of 92 inflammation markers. Results: We included 54 083 measurements from 3092 CW and 83 TNBP, and 147 230 measurements from 8611 CM. Hormonal therapy use increased CD4 count and CD4:CD8 ratio in TNBP more than in CW (pinteraction = 0.02 and 0.007, respectively). TNBP with hormonal therapy use had significantly higher CD4 counts [median = 772 cells/μL, interquartile range (IQR): 520–1006] than without (617 cells/μL, 426–892). This was similar to the effect of CW versus CM on CD4 T cells. Hormonal therapy use did not affect serum protein concentrations in TNBP. Conclusion: This study highlights the potential role of hormonal therapy use in modulating the immune system among other biological and social factors, especially in TNBP with HIV. [ABSTRACT FROM AUTHOR]