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.

Selective Glucocorticoid Replacement Following Unilateral Adrenalectomy for Hypercortisolism and Primary Aldosteronism.

CONTEXT: An institutional study previously demonstrated that cosyntropin stimulation testing on postoperative day 1 (POD1-CST) identified patients at risk for adrenal insufficiency (AI) following unilateral adrenalectomy (UA) for adrenal-dependent hypercortisolism (HC) and primary aldosteronism (PA), allowing for selective glucocorticoid replacement (GR). OBJECTIVE: This study re-evaluates the need for GR following UA for patients with HC and PA in a larger cohort. METHODS: A prospective database identified 108 patients who underwent UA for mild autonomous cortisol excess (MACE) (n = 47), overt hypercortisolism (OH) (n = 27), PA (n = 22), and concurrent PA/HC (n = 12) from September 2014 to October 2020; all underwent preoperative evaluation for HC. MACE was defined by the 1 mg dexamethasone suppression test (cortisol >1.8 µg/dL), with ≥5 defined as OH. GR was initiated for basal cortisol ≤5 or stimulated cortisol ≤14 (≤18 prior to April 2017) on POD1-CST. RESULTS: Fifty-one (47%) patients had an abnormal POD1-CST; 54 (50%) were discharged on GR (27 MACE, 20 OH, 1 PA, 6 PA/HC). Median duration of GR was OH: 6.0 months, MACE: 2.1 months, PA: 1 month, PA/HC: 0.8 months. Overall, 26% (n = 7) of patients with OH and 43% (n = 20) of patients with MACE did not require GR. Two (2%) patients with OH had normal POD1-CST but developed AI several weeks postoperatively requiring GR. None experienced life-threatening AI. CONCLUSION: POD1-CST identifies patients with HC at risk for AI after UA, allowing for selective GR. One-quarter of patients with OH and nearly half of patients with MACE can forgo GR after UA. Patients with PA do not require evaluation for AI if concurrent HC has been excluded preoperatively.

Association between serum uric acid and carotid atherosclerosis in elderly postmenopausal women: A hospital-based study.

BACKGROUND: Carotid atherosclerosis (CAS) is associated with increased cardiovascular risk and implicated in 20-30% of strokes. METHODS: 504 patients were included in this study. The detailed medical history and the results of physical examination, carotid ultrasound examination, and routine laboratory tests were collected. Logistic regression analyses were conducted to analyze the relationship between the SUA and the presence of carotid plaques. And the relationship between SUA and the progression of CAS was analyzed by multiple linear regression. The effect of hormone replacement therapy (HRT) on CAS has also be evaluated. RESULTS: 412 patients (81.7%) had carotid plaques of different sizes by carotid ultrasound examination. We found a positive association between the level of SUA and the probability of having carotid plaque by univariate logistic regression (OR: 2.01, 95% CI: 1.83-2.19, p = 0.003). At 2 years post-discharge, we found that 1 mg/dL increase in SUA levels was expected to 0.946% increase in plaque score and 0.026 cm increase in carotid intima-media thickness, separately. Moreover, patients treated by long-term HRT (≥5 years) had a lower level of SUA and blood lipid and the less change of plaque score and carotid intima-media thickness than patients without HRT. CONCLUSION: The presence and progression of CAS had significantly positive associations with the level of SUA. And the HRT may have the ability to prevent the presence and progression of CAS. However, the safety and long-term outcome of HRT on CAS should be evaluated in further studies.

Descrição de medicamentos prescritos para a terapia hormonal em serviços de saúde especializados para transexuais e travestis no Rio Grande do Sul, 2020 / Descripción de medicamentos recetados para terapia hormonal en servicios de salud especializados para transexuales y travestis en Rio Grande do Sul, Brasil, 2020 / Description of drugs prescribed for hormone therapy in specialized health services for transsexual and transvestite persons in Rio Grande do Sul, Brazil, 2020

Objetivo: Descrever os medicamentos prescritos para o tratamento hormonal do processo transexualizador em estabelecimentos de saúde de atendimento especializado para pessoas transexuais e travestis no Rio Grande do Sul, Brasil. Métodos: Estudo descritivo, com coleta de dados nesses estabelecimentos, no período maio-setembro/2020, utilizando-se instrumento elaborado pelos(as) pesquisadores(as). Obtiveram-se dados sobre o perfil de usuários(as) e características do cuidado farmacológico de tratamento hormonal. Resultados: A pesquisa contemplou todos os sete serviços do estado. Para mulheres transexuais e travestis, medicamentos antiandrogênicos e espironolactona foram prescritos em todos os serviços. Apenas um estabelecimento não prescreveu ciproterona. Todos os estabelecimentos de saúde realizaram prescrição de medicamentos a base de estrógenos, com diferenças na via de administração; para homens transexuais, todos prescreveram andrógenos por via intramuscular. Conclusão: A pesquisa aponta os medicamentos prescritos e sua diversidade, ratificando a necessidade da produção de informação para implementação das políticas de equidade no Sistema Único de Saúde.

Objetivo: Describir los medicamentos prescritos para el tratamiento hormonal en establecimientos de salud que brindan atención especializada a transexuales y travestis en Rio Grande do Sul, Brasil. Métodos: Estudio descriptivo, con recolección de datos en los establecimientos, entre mayo y septiembre de 2020, utilizando el instrumento desarrollado por los investigadores. Se obtuvieron datos sobre el perfil de usuarios (as) y características del cuidado farmacológico de tratamiento hormonal. Resultados: La encuesta abarcó los siete servicios estatales. Para las mujeres transgénero y travestis se prescribieron antiandrógenos y espironolactona en todos los servicios. Sólo un establecimiento no prescribió ciproterona. Todos los establecimientos de salud prescribieron medicamentos a base de estrógenos con diferencias en la vía de administración. Para los hombres transgénero, todos los andrógenos se recetan por vía intramuscular. Conclusión: La investigación destaca la diversidad de medicamentos prescritos, ratificando la necesidad de producir información para la implementación de políticas de equidad en el Sistema de Salud Brasileño.

Objective: To describe the drugs prescribed for hormone treatment as part of the transsexualization process in health facilities providing specialized care for transsexual and transvestite persons in the state of Rio Grande do Sul, Brazil. Methods: This was a descriptive study based on data collected in health facilities between May and September 2020 using the instrument developed by the researchers. Results: The survey covered all seven services in the state. Antiandrogen drugs and spironolactone were prescribed for transsexuals and transvestites women in all services. Only one service did not prescribe cyproterone. All health facilities prescribed estrogen-based drugs, although with differences in the route of administration. In the case of transsexuals men, all services prescribed androgens to be administered via the intramuscular route. Conclusion: The study indicates which drugs are prescribed and their diversity, ratifying the need to produce information for the implementation of equity policies in the Brazilian National Health System.

Thyroxine Supplementation in Pregnant Women After Thyroidectomy for Thyroid Cancer and Neonatal Birth Weight.

Patients are often supplemented with a sufficient dose of thyroxine after thyroidectomy for thyroid cancer. However, the influence of thyroxine supplementation on fetal growth in pregnant women after thyroidectomy for thyroid cancer remains unclear. The aim of this study was to investigate the effect of thyroxine supplementation on neonatal birth weight. This cohort study included 49,896 pregnant women (278 patients with a history of thyroidectomy for thyroid cancer and 39,363 control cases after exclusion). Thyroid parameters were examined in pregnant women and their newborns. The associations between maternal thyroid function and neonatal birth weight and small for gestational age were studied using regression analyses. In the levothyroxine supplementation group, free thyroxine (FT4) levels were significantly higher in both early pregnancy (P < 0.001) and late pregnancy (P < 0.001) groups than in the control group. Furthermore, levels of neonatal thyroid stimulating hormone (P = 0.032) and birth weight (P = 0.043) were significantly lower than those in the control group. We also observed a significant inverse association between maternal FT4 levels in early pregnancy and neonatal birth weight (P=0.028), especially in male newborns (P=0.036). In summary, after thyroidectomy for thyroid cancer, a sufficient dose of thyroxine supplementation in early pregnancy is significantly associated with reduced birth weight and may need to be monitored.

Uterine adhesion: Is luteal phase prior to follicular phase in uterine adhesiolysis?

ABSTRACT: To compare the patients' outcomes of Asherman syndrome who underwent uterine adhesiolysis in luteal phase or follicular phase.A retrospective cohort study.A tertiary hospital in China.Four hundred sixty-four women suffered intrauterine adhesion who underwent monopolar adhesiolysis from March 2014 to March 2017 were analyzed. One hundred seventy-eight patients underwent operations in follicular phase (OFP) and 286 underwent operations in luteal phase (OLP).Hormone therapy was accompanied with an intrauterine device and a second-look hysteroscopy was performed postoperatively.Endometrial thickness in women was analyzed by a transvaginal 3-dimensional ultrasound examination. Re-adhesion was confirmed by a second-look hysteroscopy 3 months after hysteroscopic adhesiolysis. Pregnancy rate was acquired by questionnaires 3 months after a second-look hysteroscopy.OLP has advantages with thicker luteal endometrium (P = .001), higher pregnancy rates (P < .001), and lower re-adhesion rates (P = 0015) compared to these values of OFP.For Asherman syndrome, our study showed that OLP is more feasible than OFP in intrauterine adhesiolysis.

Menopausal hormone therapy for women living with HIV.

People living with HIV are ageing, and a growing number of women living with HIV are entering menopause. Women living with HIV commonly have bothersome vasomotor symptoms and onset of menopause at earlier ages; both factors go on to affect quality of life and systemic health. Vasomotor symptoms and early menopause are both indications for menopausal hormone therapy; however, current evidence suggests that this therapy is seldom offered to women living with HIV. Additionally, women living with HIV have several risks to bone health and are likely to benefit from the bone-strengthening effects of menopausal hormone therapy. We present an assessment of the benefits and risks of menopausal hormone therapy in the context of HIV care and propose a practical approach to its prescription. If considered in the appropriate clinical context with discussion of risks and benefits, menopausal hormone therapy might provide substantial benefits to symptomatic menopausal women living with HIV and improve health-related quality of life.

Weight gain and obesity rates in transgender and gender-diverse adults before and during hormone therapy.

BACKGROUND: Obesity rates and weight changes in adults on gender-affirming hormone therapy are lacking or limited by small sample sizes, duration, and location. SUBJECTS/METHODS: This longitudinal study followed the body mass index and body weights of 470 transgender and gender-diverse adult patients (247 transfeminine and 223 transmasculine; mean age, 27.8 years) seen at a Federally Qualified Health Center and an academic endocrinology practice, both in Washington DC USA. Body weight and body mass index were recorded at baseline and at multiple follow-up clinical visits up to 57 months after the initiation of gender-affirming hormone therapy. The outcomes of this study were the changes to body weight and obesity rates following hormone therapy. RESULTS: Within 2-4 months of starting gender-affirming hormone therapy, the mean body weight increased in the transmasculine group by 2.35 (1.15-3.55) kg and further increased beyond 34 months. Among the transfeminine group, the mean body weight was stable for the first 21 months of hormone therapy and then began to steadily increase, particularly in those under 30 years old. The prevalence of obesity at baseline was 25% in the transfeminine group and 39% in the transmasculine group. Following the initiation of hormone therapy, rates of obesity ranged from 42 to 52% among the transmasculine group and 21 to 30% among transfeminine group. Following 11-21 months of hormone therapy, weight gain ≥5 kg was seen among 21% of transfeminine individuals and 30% of transmasculine individuals. CONCLUSIONS: As compared with transfeminine individuals, transmasculine individuals have greater rates of obesity and weight gain before and during hormone therapy. Body weight and body mass index should be routinely monitored before and after the initiation of gender-affirming hormone therapy. Multidisciplinary weight-reduction interventions should be promoted where appropriate.

Thyroid Hormone Therapy and Incident Stroke.

CONTEXT: Stroke is a leading cause of death and disability and there is a need to identify modifiable risk factors. OBJECTIVE: We aimed to determine the relationship between thyroid hormone treatment intensity and incidence of atrial fibrillation and stroke. METHODS: We conducted a retrospective cohort study using data from the Veterans Health Administration between 2004 and 2017, with a median follow-up of 59 months. The study population comprised 733 208 thyroid hormone users aged ≥18 years with at least 2 thyroid stimulating hormone (TSH) measurements between thyroid hormone initiation and incident event (atrial fibrillation or stroke) or study conclusion (406 030 thyroid hormone users with at least 2 free thyroxine [T4] measurements). RESULTS: Overall, 71 333/643 687 (11.08%) participants developed incident atrial fibrillation and 41 931/663 809 (6.32%) stroke. In multivariable analyses controlling for pertinent factors such as age, sex, and prior history of atrial fibrillation, higher incidence of stroke was associated with low TSH or high free T4 levels (ie, exogenous hyperthyroidism; eg, TSH <0.1 mIU/L; OR 1.33; 95% CI, 1.24-1.43; free T4>1.9 ng/dL, OR 1.17, 95% CI 1.06-1.30) and high TSH or low free T4 levels (ie, exogenous hypothyroidism; eg, TSH >5.5 mIU/L; OR 1.29; 95% CI, 1.26-1.33; free T4 <0.7 ng/dL; OR 1.29; 95% CI, 1.22-1.35) compared with euthyroidism (TSH >0.5-5.5 mIU/L and free T4 0.7-1.9 ng/dL). Risk of developing atrial fibrillation and stroke was cumulative over time for both patients with exogenous hyperthyroidism and hypothyroidism. CONCLUSION: Both exogenous hyper- and hypothyroidism were associated with increased risk of stroke, highlighting the importance of patient medication safety.

Reproductive functions and fertility preservation in transgender women: a French case series.

RESEARCH QUESTION: The reproductive potential of transgender people may be impaired by gender-affirming hormone treatment (GAHT) and is obviously suppressed by gender-affirming surgery involving bilateral orchiectomy. The evolution of medical support for transgender people has made fertility preservation strategies possible. Fertility preservation in transgender women mainly relies on sperm cryopreservation. There are few studies on this subject, and the sample sizes are small, and so it difficult to know whether fertility preservation procedures are feasible and effective in trans women. DESIGN: This retrospective study reports the management of fertility preservation in transgender women referred to the study centre for sperm cryopreservation, and the semen parameters of trans women were compared with those of sperm donors. RESULTS: Ninety-six per cent of transgender women who had not started treatment benefitted from sperm cryopreservation, compared with 80% of those who attempted a therapeutic window and 50% of those receiving hormonal treatment at the time of sperm collection. No major impairment of semen parameters was observed in transgender women who had not started GAHT compared with sperm donors. However, even though the frequency of oligozoospermia was no different, two transgender women presented azoospermia. Some transgender women who had started GAHT could benefit from sperm freezing. None of them were treated with gonadotrophin-releasing hormone (GnRH) analogues. CONCLUSIONS: Parenthood strategies for transgender people have long been ignored, but this is an important issue to consider, especially because medical treatments and surgeries may be undertaken in adolescents or very young adults. Fertility preservation should ideally be offered prior to initiation of GAHT.

Reproductive risk factors of pterygium in postmenopausal women: a nationwide study in the Republic of Korea.

This study is to elucidate the associations between female reproductive factors and pterygium. A total of 1,339,969 postmenopausal women in a retrospective cohort of Korean National Health Insurance Service data on ages 40 and above in 2009 was included. Cox proportional hazards regression was conducted to assess the hazard ratio (HR) for pterygium according to reproductive factors. Late menarche, early menopause, short reproductive period, increasing parity (≥ 2 children), breastfeeding (≥ 6 months), and no use of hormone replacement therapy (HRT) or oral contraceptive (OC) were significantly associated with risk of pterygium. In multivariate analysis, the HR for pterygium was 1.764 (95% confidence interval [CI], 1.529-2.035) for menarche age ≥ 17 years (reference: menarche age < 12 years). The HR of menopause age ≥ 55 years was 0.782 (95% CI, 0.724-0.845) (reference: menopause age < 40 years). The HR of parity ≥ 2 was 1.261 (95% CI, 1.148-1.385) (reference: nulliparity). The HR of breastfeeding ≥ 1 year was 1.663 (95% CI, 1.564-1.768) (reference: no breastfeeding). The HRs of HRT and OC use for any length of time were lower than those for the non-user groups (reference). Reproductive factors that increase estrogen exposure have protective effects against pterygium in females.

Characterization of Benign Breast Diseases and Association With Age, Hormonal Factors, and Family History of Breast Cancer Among Women in Sweden.

Importance: Benign breast diseases (BBDs) are common and associated with breast cancer risk, yet the etiology and risk of BBDs have not been extensively studied. Objective: To investigate the risk of BBDs by age, hormonal factors, and family history of breast cancer. Design, Setting, and Participants: This retrospective cohort study assessed 70 877 women from the population-based Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA) who attended mammographic screening or underwent clinical mammography from January 1, 2011, to March 31, 2013, at 4 Swedish hospitals. Participants took part in a comprehensive questionnaire on recruitment. All participants had complete follow-up through high-quality Swedish national registers until December 31, 2015. Pathology medical records on breast biopsies were obtained for the participants, and BBD subtypes were classified according to the latest European guidelines. Analyses were conducted from January 1 to July 31, 2020. Exposures: Hormonal risk factors and family history of breast cancer. Main Outcomes and Measures: For each BBD subtype, incidence rates (events per 100 000 person-years) and multivariable Cox proportional hazards ratios (HRs) with time-varying covariates were estimated between the ages of 25 and 69 years. Results: A total of 61 617 women within the mammographic screening age of 40 to 69 years (median age, 53 years) at recruitment with available questionnaire data were included in the study. Incidence rates and risk estimates varied by age and BBD subtype. At premenopausal ages, nulliparity (compared with parity ≥3) was associated with reduced risk of epithelial proliferation without atypia (EP; HR, 0.62; 95% CI, 0.46-0.85) but increased risk of cysts (HR, 1.38; 95% CI, 1.03-1.85). Current and long (≥8 years) oral contraceptive use was associated with reduced premenopausal risk of fibroadenoma (HR, 0.65; 95% CI, 0.47-0.90), whereas hormone replacement therapy was associated with increased postmenopausal risks of epithelial proliferation with atypia (EPA; HR, 1.81; 95% CI, 1.07-3.07), fibrocystic changes (HR, 1.60; 95% CI, 1.03-2.48), and cysts (HR, 1.98; 95% CI, 1.40-2.81). Furthermore, predominantly at premenopausal ages, obesity was associated with reduced risk of several BBDs (eg, EPA: HR, 0.31; 95% CI, 0.17-0.56), whereas family history of breast cancer was associated with increased risk (eg, EPA: HR, 2.11; 95% CI, 1.48-3.00). Conclusions and Relevance: These results suggest that the risk of BBDs varies by subtype, hormonal factors, and family history of breast cancer and is influenced by age. Better understanding of BBDs is important to improve the understanding of benign and malignant breast diseases.

Comparison of Dosing Schemes for Thyroid Hormone Replacement Therapy After Thyroidectomy.

BACKGROUND: Current thyroid hormone replacement therapy (THRT) is built on weight-based standard calculation of dose. A novel Poisson regression model, which accounts for seven clinical variables, was recently proposed to improve accuracy of THRT. We aimed to compare the accuracy of estimated THRT dose to reach euthyroid and the difference in predicted dose between the Poisson (scheme A) and the weight-based standard (scheme B) in patients following total thyroidectomy for benign disease. METHODS: We retrospectively reviewed medical record of patients who underwent total or completion thyroidectomy for benign disease at a single institution between 2011 and 2019. The THRT dose was calculated using both schemes. We compared the difference between calculated THRT and prediction rates for optimal THRT dosing needed to achieve a euthyroid state between dosing schemes. Patients were evaluated for achieving euthyroid state, defined as TSH 0.45-4.5 mIU/L. We also compared dosing error rates (> 25 mcg over- and underdosing) between schemes. Prediction rates were compared by BMI tertiles to account for the effect of BMI extremes in achieving euthyroid state. The difference in predicted dose between schemes was calculated in both the total sample size and patients that met euthyroid. A measure of agreement, Kappa, was used to estimate agreement between dosing schemes. RESULTS: A total of 406 patients underwent total thyroidectomy for benign disease, with 184 having sufficient follow up data confirming euthyroid state. Of the 184 patients, 85.9% (n = 158) were women, 81% (n = 149) were Hispanic, and 56.5% (n = 104) were obese with a median BMI of 30.8 kg/m2. Scheme A resulted in a higher, but not statistically significant, accuracy rate (A: 60.3%, n = 111 versus B: 53.8%, n = 99; P = 0.21). Overdosing errors were lower with Scheme A (A:17.9% versus B: 32.1%; P = 0.0025) and less extreme > 25 µg (A: 17.9% versus B: 26.1%; P = 0.08). A trend in improved accuracy in patients with a BMI > 35 kg/m2 was noted (A: 46.9% versus B: 34.4%; P = 0.20). Scheme A also resulted in less overdosing errors in obese patients compared to Scheme B (A: 19.2% versus 45.2%; P = 0.0006). The average difference in predicted dose between schemes was an entire dose difference, mean of 16.0 µg and 15.8 µg for the total and euthyroid samples respectively. Furthermore, for the majority of patients the predicted dose did not match between the two dosing schemes for total and euthyroid samples, 76% (n = 311) and 76% (n = 141) respectively. In patients that achieved euthyroid, agreement between dosing schemes was low to moderate (Kappa = 0.360). CONCLUSIONS: Lower rates of overdosing were found for scheme A, particularly with obese patients. No statistically significant differences in predicted THRT dose was observed between schemes. The difference in predicted dose between schemes was on average 15 ug, correlating with an entire dose. The consideration of clinical variables other than weight (scheme A) when determining optimal THRT dosing may be of importance to prevent overdoses, with particular clinical relevance in patients with higher BMIs.

Association between menopausal hormone therapy, mammographic density and breast cancer risk: results from the E3N cohort study.

BACKGROUND: Menopausal hormone therapy (MHT) is a risk factor for breast cancer (BC). Evidence suggests that its effect on BC risk could be partly mediated by mammographic density. The aim of this study was to investigate the relationship between MHT, mammographic density and BC risk using data from a prospective study. METHODS: We used data from a case-control study nested within the French cohort E3N including 453 cases and 453 matched controls. Measures of mammographic density, history of MHT use during follow-up and information on potential confounders were available for all women. The association between MHT and mammographic density was evaluated by linear regression models. We applied mediation modelling techniques to estimate, under the hypothesis of a causal model, the proportion of the effect of MHT on BC risk mediated by percent mammographic density (PMD) for BC overall and by hormone receptor status. RESULTS: Among MHT users, 4.2% used exclusively oestrogen alone compared with 68.3% who used exclusively oestrogens plus progestogens. Mammographic density was higher in current users (for a 60-year-old woman, mean PMD 33%; 95% CI 31 to 35%) than in past (29%; 27 to 31%) and never users (24%; 22 to 26%). No statistically significant association was observed between duration of MHT and mammographic density. In past MHT users, mammographic density was negatively associated with time since last use; values similar to those of never users were observed in women who had stopped MHT at least 8 years earlier. The odds ratio of BC for current versus never MHT users, adjusted for age, year of birth, menopausal status at baseline and BMI, was 1.67 (95% CI, 1.04 to 2.68). The proportion of effect mediated by PMD was 34% for any BC and became 48% when the correlation between BMI and PMD was accounted for. These effects were limited to hormone receptor-positive BC. CONCLUSIONS: Our results suggest that, under a causal model, nearly half of the effect of MHT on hormone receptor-positive BC risk is mediated by mammographic density, which appears to be modified by MHT for up to 8 years after MHT termination.

Hormonal and Metabolic Changes of Aging and the Influence of Lifestyle Modifications.

Increased life expectancy combined with the aging baby boomer generation has resulted in an unprecedented global expansion of the elderly population. The growing population of older adults and increased rate of age-related chronic illness has caused a substantial socioeconomic burden. The gradual and progressive age-related decline in hormone production and action has a detrimental impact on human health by increasing risk for chronic disease and reducing life span. This article reviews the age-related decline in hormone production, as well as age-related biochemical and body composition changes that reduce the bioavailability and actions of some hormones. The impact of hormonal changes on various chronic conditions including frailty, diabetes, cardiovascular disease, and dementia are also discussed. Hormone replacement therapy has been attempted in many clinical trials to reverse and/or prevent the hormonal decline in aging to combat the progression of age-related diseases. Unfortunately, hormone replacement therapy is not a panacea, as it often results in various adverse events that outweigh its potential health benefits. Therefore, except in some specific individual cases, hormone replacement is not recommended. Rather, positive lifestyle modifications such as regular aerobic and resistance exercise programs and/or healthy calorically restricted diet can favorably affect endocrine and metabolic functions and act as countermeasures to various age-related diseases. We provide a critical review of the available data and offer recommendations that hopefully will form the groundwork for physicians/scientists to develop and optimize new endocrine-targeted therapies and lifestyle modifications that can better address age-related decline in heath.

Primary Ovarian Insufficiency in Women With Addison's Disease.

CONTEXT: Primary ovarian insufficiency (POI) is defined by menopause before 40 years of age. POI prevalence is higher among women with autoimmune Addison's disease (AAD) than in the general population, but their clinical characteristics are insufficiently studied. OBJECTIVE: To assess the prevalence of POI in a large cohort of women with AAD and describe clinical, immunological, and genetic characteristics. METHODS: An observational population-based cohort study of the Norwegian National Addison Registry. The Norwegian Prescription Database was used to assess prescription of menopausal hormone replacement therapy (HRT). A total of 461 women with AAD were studied. The primary outcome measure was prevalence of POI. Secondary outcomes were clinical characteristics, autoantibodies, and genome-wide single nucleotide polymorphism variation. RESULTS: The prevalence of POI was 10.2% (47/461) and one-third developed POI before 30 years of age. POI preceded or coincided with AAD diagnosis in more than half of the women. The prevalence of concomitant autoimmune diseases was 72%, and AAD women with POI had more autoantibodies than AAD women without (≥2 autoantibodies in 78% vs 25%). Autoantibodies against side-chain cleavage enzyme (SCC) had the highest accuracy with a negative predictive value for POI of 96%. HRT use was high compared to the age adjusted normal population (11.3 % vs 0.7%). CONCLUSION: One in 10 women with AAD have POI. Autoantibodies against SCC are the most specific marker for autoimmune POI. We recommend testing women with AAD <40 years with menstrual disturbances or fertility concerns for autoantibodies against SCC.

Comparison of vaginal progesterone gel combined with oral dydrogesterone versus intramuscular progesterone for luteal support in hormone replacement therapy-frozen embryo transfer cycle.

BACKGROUND: It remains under subject of debate regarding the optimal route of luteal support for hormone replacement therapy- frozen embryo transfer (HRT-FET) cycles. We compared efficacy of vaginal progesterone gel combined with oral dydrogesterone and intramuscular progesterone for HRT-FET lutein support. METHODS: This is a retrospective observational study. After matching for propensity score of getting vaginal + oral treatment, a total of 208 FET cycles in the vaginal progesterone combined with oral dydrogesterone and 624 cycles in the intramuscular progesterone group were enrolled. Pregnancy outcomes and neonatal outcomes including chemical pregnancy rate, clinical pregnancy rate, implantation rate, spontaneous abortion rate, live birth rate, gestational weeks, pre-term delivery, birth weight, and congenital anomalies rate were compared. RESULTS: No significant differences were observed in patient characteristics such as age, duration of infertility, type of infertility, or hormone level after matching. Chemical pregnancy rate (68.3 % versus 70.5 %), clinical pregnancy rate (64.9 % versus 64.4 %), implantation rate (52.3 % versus 50.2 %), spontaneous abortion rate (21.5 % versus 18.4 %), and live birth rate (49.0 % versus 51.3 %) were similar in both group without statistically significant difference. No significant differences in neonatal outcomes were observed between the two groups. CONCLUSION: We observed similar pregnancy outcomes in both vaginal progesterone gel combined with oral dydrogesterone and intramuscular progesterone protocol. Vaginal progesterone gel combined with oral dydrogesterone can be substituted for intramuscular progesterone given that vaginal plus oral use has good safety and is more convenient and may be associated with less side effect caused by intramuscular injection.

Use of thyroid hormones in hypothyroid and euthyroid patients: A 2020 THESIS questionnaire survey of members of the Danish Endocrine Society.

PURPOSE: The standard treatment of hypothyroidism is levothyroxine (LT4), which is available as tablets or soft-gel capsules in Denmark. This study aimed to investigate Danish endocrinologists' use of thyroid hormones in hypothyroid and euthyroid patients. METHODS: An e-mail with an invitation to participate in an online survey investigating practices about substitution with thyroid hormones was sent to all members of the Danish Endocrine Society (DES). RESULTS: Out of 488 eligible DES members, a total of 152 (31.2%) respondents were included in the analysis. The majority (94.1%) of responding DES members use LT4 as the treatment of choice. Other treatment options for hypothyroidism are also used, as 58.6% prescribe combination therapy with liothyronine (LT3) + LT4 in their clinical practice. LT4 + LT3 combination is preferred in patients with persistent symptoms of hypothyroidism despite biochemical euthyroidism on LT4 treatment. Over half of the respondents answered that thyroid hormone therapy is never indicated for euthyroid patients, but 42.1% will consider it for euthyroid infertile women with high antibody levels. In various conditions that could interfere with the absorption of LT4, most responding Danish endocrinologists prefer tablets and do not expect a significant difference when switching from one type of tablet formulation to another. CONCLUSION: The treatment of choice for hypothyroidism is LT4. Combination therapy with LT4 + LT3 is considered for patients with persistent symptoms. Even in the presence of conditions affecting bioavailability, responding Danish endocrinologists prefer LT4 tablets rather than newer LT4 formulations, such as soft-gel capsules.

A Danish nationwide study of risk factors associated with Type I and Type II endometrial cancer.

OBJECTIVE: To examine risk factors for Type I and Type II endometrial cancer (EC) and to directly compare the influence of risk factors for Type II with Type I tumors. Furthermore, to examine whether risk factors for high-grade Type I and Type II tumors differed from low-grade Type I tumors. METHODS: Women with EC diagnosed during 2000-2016 were identified in the Danish Cancer Registry. A case-control analysis was conducted with 1:15 random population controls matched on age and gender. Using conditional logistic regression, odds ratios and 95% confidence intervals on risk factors for Type I and II tumors were estimated. In case-case analyses, risk factors were evaluated in a direct comparison of cases grouped by tumor type and grade. RESULTS: We identified 6958 women with Type I EC and 1206 women with Type II EC. In the case-control analysis, nulliparity and diabetes were associated with increased risk of both tumor types, whereas hormone replacement therapy only increased the risk of Type I EC. When directly comparing Type I and II tumors, the influence of BMI ≥ 30, current smoking, and parity ≥ 3 was strongest for Type I EC. The associations for the majority of risk factors were similar for Type II and high-grade Type I tumors compared with low-grade Type II tumors. CONCLUSIONS: Risk factors for Type I and II tumors were overlapping suggesting that Type II tumors may be less estrogen-independent than previously anticipated. High-grade Type I tumors seemed to resemble Type II tumors more than low-grade Type I tumors.

Self-selection for mammography screening according to use of hormone replacement therapy: A systematic literature review.

Mammography screening participation may be influenced by the awareness of an increase in breast cancer risk due to hormone replacement therapy (HRT), which received particular attention upon publication of the Women's Health Initiative (WHI) trial results in 2002. Our aim was to synthesize evidence on a potential self-selection for mammography screening according to HRT use. We systematically searched the literature (MEDLINE, EMBASE, CINAHL) for studies reporting on the association between HRT use and mammography screening participation. Data were extracted independently by two reviewers. Overall, 2018 studies were identified. Of these, 32 studies from nine countries, predominantly from North America (50%) and Europe (28%), were included. In studies from all countries and 94% of all studies, higher mammography screening uptake among HRT users compared to non-users was reported. In all 21 studies reporting an odds ratio, the association was positive, and in about 70% of these studies, this association was ≥2. This also held true for studies exclusively using data collected before publication of the WHI findings in 2002 (63% of all studies). The association was not restricted to certain types of screening (organized vs. opportunistic) or certain types of HRT (combined vs. estrogen-only). We found a consistent and relevant association between mammography screening uptake and HRT use. This is of considerable relevance for the design and interpretation of studies investigating risk factors or evaluating preventive measures for breast cancer.