Clinicians in the Veterans Health Administration initiate gender-affirming hormone therapy in concordance with clinical guideline recommendations.

Background: Gender-affirming hormone therapy (GAHT) is a common medical intervention sought by transgender and gender diverse (TGD) individuals. Initiating GAHT in accordance with clinical guideline recommendations ensures delivery of high-quality care. However, no prior studies have examined how current GAHT initiation compares to recommended GAHT initiation. Objective: This study assessed guideline concordance around feminizing and masculinizing GAHT initiation in the Veterans Health Administration (VHA). Methods: The sample included 4,676 veterans with a gender identity disorder diagnosis who initiated feminizing (n=3,547) and masculinizing (n=1,129) GAHT between 2007 and 2018 in VHA. Demographics and health conditions on veterans receiving feminizing and masculinizing GAHT were assessed. Proportion of guideline concordant veterans on six VHA guidelines on feminizing and masculinizing GAHT initiation were determined. Results: Compared to veterans receiving masculinizing GAHT, a higher proportion of veterans receiving feminizing GAHT were older (≥60 years: 23.7% vs. 6.3%), White non-Hispanic (83.5% vs. 57.6%), and had a higher number of comorbidities (≥7: 14.0% vs. 10.6%). A higher proportion of veterans receiving masculinizing GAHT were Black non-Hispanic (21.5% vs. 3.5%), had posttraumatic stress disorder (43.0% vs. 33.9%) and positive military sexual trauma (33.5% vs.16.8%; all p-values<0.001) than veterans receiving feminizing GAHT. Among veterans who started feminizing GAHT with estrogen, 97.0% were guideline concordant due to no documentation of contraindication, including venous thromboembolism, breast cancer, stroke, or myocardial infarction. Among veterans who started spironolactone as part of feminizing GAHT, 98.1% were guideline concordant as they had no documentation of contraindication, including hyperkalemia or acute renal failure. Among veterans starting masculinizing GAHT, 90.1% were guideline concordant due to no documentation of contraindications, such as breast or prostate cancer. Hematocrit had been measured in 91.8% of veterans before initiating masculinizing GAHT, with 96.5% not having an elevated hematocrit (>50%) prior to starting masculinizing GAHT. Among veterans initiating feminizing and masculinizing GAHT, 91.2% had documentation of a gender identity disorder diagnosis prior to GAHT initiation. Conclusion: We observed high concordance between current GAHT initiation practices in VHA and guidelines, particularly for feminizing GAHT. Findings suggest that VHA clinicians are initiating feminizing GAHT in concordance with clinical guidelines. Future work should assess guideline concordance on monitoring and management of GAHT in VHA.

Menopausal Hormone Therapy, an Ever-Present Topic: A Pilot Survey about Women's Experience and Medical Doctors' Approach.

Background and Objective: Menopause can be associated with many clinical manifestations: vasomotor symptoms, urogenital problems, and additional psychological disturbances, such as anxiety, mood changes, and sleep alterations. The prolonged lack of hormones also increases the risk of long-term consequences. Hormone Replacement Treatment (HRT) in menopause consists of the administration of estrogen, alone or associated to progesterone, to relieve these uncomfortable disturbances and to prevent the onset of other pathologic conditions. The aim of this study is to examine the prevalence of HRT use in a sample of menopausal women and their experience with menopause and HRT. This study also investigates the knowledge of general practitioners (GPs) and gynecologists about HRT and its prescription. Materials and Methods: We conducted a cross-sectional population survey on 126 women of 50-59 years in an industrial city in the North of Italy, Vercelli (Novara), in Eastern Piedmont. We also presented a questionnaire on the topic to 54 medical doctors (GPs and gynecologists) of the same area. Results: The prevalence of HRT use in our sample was 11.9%. In total, a good percentage of the users affirmed to be satisfied with HRT. Additionally, a minority of women reported being ideally against the use of replacement hormones, were advised against using HRT by doctors, and did not use it because of the fear of side effects. We found a positive association between patient education, health care attitude, and HRT usage. A significant number of women knew about HRT from the media, and most of them were not informed by a health professional. Despite this, the interviewed doctors considered their knowledge about HRT as 'good' and would recommend HRT: only 5.6% would not prescribe it. Conclusions: Our results highlight the need for information about HRT among patients and health professionals, along with the need for more effective communication, evaluation, and suggestion of treatment.

Hormone therapy in women with benign breast disease - What little is known and suggestions for clinical implementation.

Benign breast disease encompasses a spectrum of lesions within the breast. While some lesions pose no increase in risk, others may elevate the likelihood of developing breast cancer by four- to five-fold. This necessitates a personalized approach to screening and lifestyle optimization for women. The menopausal transition is a critical time for the development of benign breast lesions. Increased detection can be attributed to the heightened precision and utilization of screening mammography, with or without the use of supplemental imaging. While it is widely acknowledged that combined hormone therapy involving estrogen and progesterone may elevate the risk of breast cancer, data from the Women's Health Initiative (WHI) indicates that estrogen-alone therapies may actually reduce the overall risk of cancer. Despite this general understanding, there is a notable gap in information regarding the impact of hormone therapy on the risk profile of women with specific benign breast lesions. This review comprehensively examines various benign breast lesions, delving into their pathophysiology and management. The goal is to enhance our understanding of when and how to judiciously prescribe hormone therapy, particularly in the context of specific benign breast conditions. By bridging this knowledge gap, the review provides valuable insights into optimizing healthcare strategies for women with benign breast disease, and offers a foundation for more informed decision-making regarding hormone therapy.

Testosterone therapy over 60 months improves aging male symptoms scores in all men with adult-onset testosterone deficiency.

OBJECTIVE: We evaluated change (Δ) in AMSS in men with adult-onset testosterone deficiency (TD) on/not on testosterone undecanoate (TU) by analysing a registry of men with adult-onset TD. METHODS: Analyses were performed using non-parametric statistics to determine ΔAMSS at 6-12 monthly intervals in men on/not on TU and movement in AMSS. Factors predicting ΔAMSS were established via linear/multiple regression. RESULTS: TU was significantly associated with lower AMSS values compared with that at baseline/prior assessment during the initial 42 months treatment; 259 of the 260 men showed improvement. In the 361 men not on TU, AMSS values increased during 60 months of follow-up compared with that at baseline/prior assessment; improvement after 60 months was evident in 1 man, whilst AMSS remained the same or worsened in 213 and 147 men, respectively. In men on TU, baseline AMSS was inversely associated with ΔAMSS (R2 = 0.97), with no other factors reaching significance. Baseline AMSS, age, serum total testosterone (TT), waist circumference (WC), and diastolic blood pressure (BP) were associated with ΔAMSS in men not on TU. DISCUSSION: We show that TU was associated with lower AMSS in men with adult-onset TD whilst non-treatment led to increased values. Baseline AMSS values inversely predicted ΔAMSS in both groups.

Alteraciones cognitivas asociadas al tratamiento de hormonoterapia en pacientes con cáncer de mama: una revisión sistemática / Cognitive alterations associated with hormone therapy in patients with breast cancer: A systematic review

Objetivo: determinar las alteraciones cognitivas asociadas al tratamiento de hormonoterapia en pacientes con cáncer de mama. Método: el presente trabajo consiste en una revisión sistemática de estudios experimentales internacionales sobre los efectos de la hormonoterapia en las funciones cognitivas en mujeres con cáncer de mama, siguiendo la declaración PRISMA. Para su selección se han seguido unos criterios metodológicos estrictos, incluyendo únicamente estudios longitudinales con evaluaciones de línea base y/o grupo control. Resultados: a pesar de las discrepancias descritas, los resultados muestran deterioro significativo en memoria verbal, funciones ejecutivas, aprendizaje verbal y velocidad de procesamiento. Conclusiones: de cara a futuras investigaciones se recomienda utilizar unos criterios metodológicos más estrictos y realizar seguimientos a largo plazo, teniendo en cuenta que la media de administración de estos tratamientos oscila entre 5 y 10 años.(AU)

Objective: to determine the cognitive alterations associated with hormone therapy in breast cancer patients. Methods: the present work consists of a systematic review of international experimental studies on the effects of hormone therapy on cognitive functions in women with breast cancer, following the PRISMA statement. Strict methodological criteria were followed for its selection, including only longitudinal studies with baseline and/or control group evaluations. Results: despite the discrepancies described, the results show significant impairment in verbal memory, executive functions, verbal learning, and processing speed. Conclusions: for future research it is recommended to use stricter methodological criteria and to carry out long-term follow-ups, considering that the average time of administration of these treatments’ ranges between 5 and 10 year.(AU)

Preservación de la fertilidad en personas transgénero del espectro masculino. Revisión narrativa de la literatura / Fertility preservation in transmasculine people: Narrative review

La terapia hormonal de afirmación de género con testosterona (GAHT, por sus siglas en inglés) permite, a las personas transgénero del espectro masculino, modificar las características sexuales secundarias del sexo asignado al nacer, aliviando así los síntomas de la disforia de género durante el proceso denominado transición. Sin embargo, se debe tener presente que se desconoce, en la actualidad, el efecto de la GAHT sobre la fertilidad a largo plazo, y el potencial efecto gonadotóxico de la misma. La demanda de un correcto asesoramiento reproductivo y la opción de realizar técnicas de preservación de la fertilidad (PF) han aumentado de forma exponencial en los últimos años, comportando cambios profundos en el manejo clínico de estas personas. En este artículo se realiza una revisión bibliográfica sobre el efecto de la GAHT a nivel reproductivo y en la fertilidad, junto con las técnicas de PF disponibles en este colectivo, principalmente la vitrificación de ovocitos. Además, realizamos un análisis de los resultados reproductivos publicados hasta la fecha tras el uso de técnicas de preservación, y exponemos los últimos avances de laboratorio en relación con la criopreservación de tejido ovárico y la maduración in vitro de ovocitos, junto con las opciones de futuro en población transgénero del espectro masculino.(AU)

Gender affirming hormone therapy (GAHT) in transmasculine people (individuals who identify as men or on the masculine spectrum and were assigned female sex at birth) makes it possible to modify the secondary sexual characteristics of the sex assigned at birth, thus alleviating the symptoms of gender dysphoria, during the process called transition. However, it is necessary to highlight that the effect of GAHT on long-term fertility and its potential gonadotoxic effects are currently unknown. Knowledge of the effects of testosterone on fertility and reproduction has increased recently, whilst the request for comprehensive reproductive counselling and the option of performing fertility preservation (FP) techniques have increased exponentially in recent years, leading to profound changes in the clinical management of this population. In this review, we analyzed all the information published regarding the effect of GAHT on reproduction and the FP techniques available in this group, mainly oocyte vitrification. In addition, we carry out an exhaustive analysis of the reproductive results published to date after the use of preservation techniques and present the latest laboratory advances concerning ovarian tissue cryopreservation and in vitro oocyte maturation, together with future options in the transmasculine people.(AU)

Challenges in Diagnosis and Treatment of Male Hypogonadism.

Hypogonadism is a condition characterized by diminished or absent production of sex hormones by the testicles in men and the ovaries in women. Hypogonadism is classified into primary and secondary hypogonadism. Each type of hypogonadism can be caused by congenital and acquired factors. There are many factors that contribute to the occurrence of hypogonadism, including genetic and developmental disorders, infection, kidney disease, liver disease, autoimmune disorders, chemotherapy, radiation, surgery, and trauma. This represents the considerable challenge in diagnosing hypogonadism.The goals of treatment include restore sexual functionality and well-being, initiating and sustaining virilization, osteoporosis prevention, normalize growth hormone levels in elderly men if possible, and restoring fertility in instances of hypogonadotropic hypogonadism. The main approach to treating hypogonadism is hormone replacement therapy. Male with prostate cancer, breast cancer, and untreated prolactinoma are contraindicated for hormone replacement therapy. When selecting a type of testosterone therapy for male with hypogonadism, several factors need to be considered, such as the diversity of treatment response and the  type of testosterone formulation. The duration of therapy depends on individual response, therapeutic goals, signs and symptoms, and hormonal levels. The response to testosterone therapy is evaluated based on symptoms and signs as well as improvements in hormone profiles in the blood. Endocrine Society Clinical Practice Guideline recommend therapeutic goals based on the alleviation of symptoms and signs, as well as reaching testosterone levels between 400 - 700 ng/dL (one week after administering testosterone enanthate or cypionate) and maintaining baseline hematocrit.Hormone therapy is the primary modality in the management of hypogonadism. The variety of signs and symptoms makes early diagnosis of this condition challenging. Moreover, administering hypogonadism therapy involves numerous considerations influenced by various patient factors and the potential for adverse effects. This poses a challenge for physicians to provide targeted hypogonadism therapy with minimal complications.

Menopausal symptoms and the awareness of menopausal-related information in low-income mid-aged women from Guayaquil, Ecuador.

OBJECTIVE: To assess menopausal symptoms and determine awareness of menopausal related information in mid-aged women. METHODS: This was a cross-sectional study in which 140 women aged 40 to 60 years from Guayaquil, Ecuador were surveyed with the short 10-item Cervantes Scale (CS-10) and a questionnaire containing personal data and questions assessing awareness of menopause related information. RESULTS: The mean age of the sample was 48.0 ± 5.6 years. More than half of surveyed women had low education and non-urban residency, none were on menopausal hormone therapy, 33.6% had hypertension, 35% were postmenopausal, 78.6% had an increased body mass index (overweight/obese) and 92.9% had abdominal obesity (waist > 88 cm). The average CS-10 score was 15.3 ± 9.0 with a median of 14.0. The three most frequent menopausal symptoms were muscle-joint pain (75.0%), changes in skin texture (74.3%) and vaginal dryness (71.4%). Regarding awareness of information related to the menopause, it was found that 98.6% of women had no idea about what the menopause is and the average age of its onset. Interestingly, although 61.4% knew that during the menopause there is weight gain, 57.9% were sedentary. Married, postmenopausal, older and less educated women presented higher mean total CS-10 scores. Contrarily, those with less awareness of menopause related information present lower scores. CONCLUSION: In this low-income mid-aged female sample there was a high rate of non-awareness regarding information related to the menopause, including an unhealthy cardiometabolic profile. There is a need for educational programs aimed to increase awareness in this high-risk population in relation to the surveyed aspects in order to improve their health status and prevent chronic conditions.

Long-acting growth hormone in the treatment of growth hormone deficiency in children: a systematic literature review and network meta-analysis.

The purpose of this study is to compare the relative efficacy and safety of long-acting growth hormone (LAGH) as a growth hormone replacement therapy in prepubertal children with growth hormone deficiency (GHD). We searched the PubMed, Embase, CNKI, and Wanfang databases from inception to July 2023 and identified eleven relevant studies. PEG-LAGH showed better effect on height velocity (mean difference [MD]: - 0.031, 95% credibility interval [CrI]: - 0.278, 0.215) than somatrogon (MD: 0.105, 95% CrI: - 0.419, 0.636), somapacitan (MD: 0.802, 95% CrI: - 0.451, 2.068) and lonapegsomatropin (MD: 1.335, 95% CrI: - 0.3, 2.989) when compared with daily growth hormone (DGH). Furthermore, in terms of height standard deviation score, PEG-LAGH demonstrated better improvement (MD: - 0.15, 95% CrI: - 1.1, 0.66) than somatrogon (MD: - 0.055, 95% CrI: - 1.3, 0.51) and somapacitan (MD: 0.22, 95% CrI: - 0.91, 1.3). PEG-LAGH (risk ratio [RR]: 1.00, 95% CrI: 0.82, 1.2) reduced the risk of adverse events compared with other LAGH (somatrogon, RR: 1.1, 95% CrI: 0.98, 1.2; somapacitan, RR: 1.1, 95% CrI: 0.96, 1.4; lonapegsomatropin, RR, 1.1, 95% CrI: 0.91, 1.3) and was comparable with DGH. This is the first study to indirectly compare the LAGH thorough a network meta-analysis and provide evidence of the optimal efficacy of various LAGH specifically PEG-LAGH and acceptable safety profile in prepubertal children with GHD.

Recommendations for managing patients with hypothyroidism.

ABSTRACT: The American Thyroid Association recommends levothyroxine monotherapy for treating hypothyroidism, a condition that affects 4.6% of the US population. However, up to 15% of these patients experience residual symptoms despite normalized thyroid-stimulating hormone levels, and may benefit from an endocrinology referral. Additional high-quality studies are needed to further evaluate patient preferences, as well as to investigate long-term outcomes of combination therapy and continue exploring therapeutic options for hypothyroidism management among specific patient subgroups.

Increased rate of pancreatitis in gender diverse and transgender patients on hormone therapy: a case series study.

BACKGROUND: There is limited data on the incidence of gastrointestinal-specific pathology in gender non-conforming (GNC) populations. METHODS: Retrospective analysis of pancreatitis incidence rates in transgender and GNC persons exposed and not exposed to gender-affirming hormone therapy (GAHT). RESULTS: 7 of the 1333 patients on hormone therapy had an incidence of pancreatitis. 0 of the 615 patients with no history of GAHT use developed pancreatitis. Representing a 6.96 (95% CI 2.76 to 848.78) for the development of pancreatitis in patients with exposure to GAHT therapy. CONCLUSION: Clinicians working with GNC individuals should be aware of this possible association.

Laboratory Changes During Gender-Affirming Hormone Therapy in Transgender Adolescents.

OBJECTIVES: Guidelines for monitoring of medications frequently used in the gender-affirming care of transgender and gender-diverse (TGD) adolescents are based on studies in adults or other medical conditions. In this study, we aimed to investigate commonly screened laboratory measurements in TGD adolescents receiving gender-affirming hormone therapy (GAHT). METHODS: TGD adolescents were recruited from 4 study sites in the United States before beginning GAHT. Hemoglobin, hematocrit, hemoglobin A1c, alanine transaminase, aspartate aminotransferase, prolactin, and potassium were abstracted from the medical record at baseline and at 6, 12, and 24 months after starting GAHT. RESULTS: Two-hundred and ninety-three participants (68% designated female at birth) with no previous history of gonadotropin-releasing hormone analog use were included in the analysis. Hemoglobin and hematocrit decreased in adolescents prescribed estradiol (-1.4 mg/dL and -3.6%, respectively) and increased in adolescents prescribed testosterone (+1.0 mg/dL and +3.9%) by 6 months after GAHT initiation. Thirteen (6.5%) participants prescribed testosterone had hematocrit > 50% during GAHT. There were no differences in hemoglobin A1c, alanine transaminase, or aspartate aminotransferase. There was a small increase in prolactin after 6 months of estradiol therapy in transfeminine adolescents. Hyperkalemia in transfeminine adolescents taking spironolactone was infrequent and transient if present. CONCLUSIONS: Abnormal laboratory results are rare in TGD adolescents prescribed GAHT and, if present, occur within 6 months of GAHT initiation. Future guidelines may not require routine screening of these laboratory parameters beyond 6 months of GAHT in otherwise healthy TGD adolescents.

Hormone replacement therapy in women with iatrogenic premature ovarian insufficiency after radiotherapy for cervical cancer: A retrospective cohort and survey study.

OBJECTIVES: This study assessed the uptake of hormone replacement therapy (HRT) in cervical cancer patients with iatrogenic menopause. Survival in relation to HRT use was assessed via a retrospective chart study, and the severity of menopausal symptoms, motivations and barriers to starting HRT were examined via questionnaires. STUDY DESIGN: In total, 293 women under the age of 51 and treated with radiotherapy for cervical cancer between 2010 and 2020 were identified. Medical records were searched for information on HRT use. If still living, women were sent digital questionnaires addressing menopausal symptoms, quality of life (QoL) and potential barriers and motivations concerning HRT use. Univariable data were analysed using Mann-Whitney U, chi-square, and Fisher's exact test, while logistical regression was used to analyse relationships between certain variables and use of HRT and survival. RESULTS: Overall HRT uptake was 78.1 %, which was related to age and Charlson Comorbidity Index, but independent of the duration of radiotherapy or FIGO stage. Overall survival was higher for HRT users (χ2(1) = 4.3, p = 0.038). Questionnaires were sent to 193 patients and 100 completed it (response rate 51.8 %). Main reasons for HRT use were relief of hot flushes and improvement in QoL. For women below age 51, QoL was indeed higher for current HRT users than for non-HRT users (EQ-index 0.8 vs. 0.7, p = 0.008). CONCLUSIONS: HRT prescription rate was inversely correlated with age. Survival was not negatively affected by HRT use. It is important to stress the benefits of HRT and address women's fears regarding its use.

Metabolism of progestogens used for contraception and menopausal hormone therapy.

A variety of progestogens are widely used by women for contraception and menopausal hormone therapy. The progestogens undergo extensive metabolism by oral and parenteral routes of administration to form many metabolites. Although a small number of metabolites have been shown to be biologically active, most have not been tested for biologic activity. The present review shows that we know most about progesterone metabolism, followed by the metabolism of levonorgestrel and norethindrone. Very few studies have been carried out on metabolism of most of the progestogens. The clinical significance of this deficiency is that those progestogen metabolites that bind to the progesterone receptors may also bind to other steroid receptors and be responsible for some of the well-documented side effects of administered progestogens. We also discuss how obesity and genetic polymorphisms alter progestogen metabolism, and how development of oral progestogen formulations that are targeted to the colon, where the concentration of steroid-metabolizing enzymes is much lower than in the proximal gut, may have a beneficial effect on progestogen metabolism.

Gender-affirming hormone therapy and cardiovascular health in transgender adults.

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.