Mortality trends over five decades in adult transgender people receiving hormone treatment: a report from the Amsterdam cohort of gender dysphoria.

BACKGROUND: Increased mortality in transgender people has been described in earlier studies. Whether this increased mortality is still present over the past decades is unknown. Therefore, we aimed to investigate trends in mortality over five decades in a large cohort of adult transgender people in addition to cause-specific mortality. METHODS: We did a retrospective cohort study of adult transgender people who visited the gender identity clinic of Amsterdam University Medical Centre in the Netherlands. Data of transgender people who received hormone treatment between 1972 and 2018 were linked to Statistics Netherlands. People were excluded if they used alternating testosterone and oestradiol treatment, if they started treatment younger than age 17 years, or if they had ever used puberty-blockers before gender-affirming hormone treatment. Standardised mortality ratios (SMRs) were calculated using general population mortality rates stratified by age, calendar period, and sex. Cause-specific mortality was also calculated. FINDINGS: Between 1972 and 2018, 8831 people visited the gender identity clinic. 4263 were excluded from the study for a variety of reasons, and 2927 transgender women and 1641 transgender men were included in the study, with a total follow-up time of 40 232 person-years for transgender women and 17 285 person-years for transgender men. During follow-up, 317 (10·8%) transgender women died, which was higher than expected compared with general population men (SMR 1·8, 95% CI 1·6-2·0) and general population women (SMR 2·8, 2·5-3·1). Cause-specific mortality in transgender women was high for cardiovascular disease, lung cancer, HIV-related disease, and suicide. In transgender men, 44 people (2·7%) died, which was higher than expected compared with general population women (SMR 1·8, 95% CI 1·3-2·4) but not general population men (SMR 1·2, 95% CI 0·9-1·6). Cause-specific death in transgender men was high for non-natural causes of death. No decreasing trend in mortality risk was observed over the five decades studied. INTERPRETATION: This observational study showed an increased mortality risk in transgender people using hormone treatment, regardless of treatment type. This increased mortality risk did not decrease over time. The cause-specific mortality risk because of lung cancer, cardiovascular disease, HIV-related disease, and suicide gives no indication to a specific effect of hormone treatment, but indicates that monitoring, optimising, and, if necessary, treating medical morbidities and lifestyle factors remain important in transgender health care. FUNDING: None.

Kidney hemodynamic function in men and postmenopausal women with type 2 diabetes and preserved kidney function.

The progression of kidney disease may differ between sexes in type 2 diabetes (T2D), with previous studies reporting a slower decline in women. Glomerular hyperfiltration is a key factor driving the kidney function decline. The current study aimed to investigate the differences in kidney hemodynamic function between men and women with T2D. A cross-sectional analysis of pooled data from three studies compared kidney hemodynamic function between men and postmenopausal women with T2D without overt nephropathy. The outcome measures were glomerular filtration rate (GFR; inulin clearance), effective renal plasma flow (ERPF; p-aminohippurate clearance), filtration fraction (GFR/ERPF), and renal vascular resistance (RVR; mean arterial pressure/renal blood flow). Glomerular hydraulic pressure (PGLO) as well as afferent and efferent vascular resistance were estimated by Gomez formulae. Sex differences were assessed with linear regression models adjusted for systolic blood pressure, glucose, use of renin-angiotensin system blockers, and body mass index. In total, 101 men [age: 63 (58-68) yr, body mass index: 31.5 ± 3.9 kg/m2, GFR: 111 ± 18 mL/min, HbA1c: 7.4 ± 0.7%] and 27 women [age: 66 (62-69) yr, body mass index: 30.9 ± 4.5 kg/m2, GFR: 97 ± 11 mL/min, HbA1c: 7.1 ± 0.5%] were included. GFR was higher in men versus women [11.0 mL/min (95% confidence interval: 3.6, 18.4)]. Although statistically nonsignificant, PGLO trended higher in men [1.9 mmHg (95% confidence interval: -0.1, 4.0)], whereas RVR [-0.012 mmHg/L/min (95% confidence interval: -0.022, -0.002)] and afferent vascular resistance were lower [-361 dyn/s/cm5 (95% confidence interval: -801, 78)]. In conclusion, in adults without overt nephropathy, GFR was higher in men compared with women. PGLO also trended to be higher in men. Both findings are possibly related to afferent vasodilation and suggest greater prevalence of hyperfiltration. This could contribute to accelerated GFR loss over time in men with T2D.NEW & NOTEWORTHY In adults with type 2 diabetes, men had higher markers of hyperfiltration, which could potentially explain the accelerated progression of diabetic kidney disease in men compared with women.

The effect of transgender hormonal treatment on high density lipoprotein cholesterol efflux capacity.

BACKGROUND AND AIMS: A decrease in high-density lipoprotein (HDL)-cholesterol concentrations during transgender hormone therapy has been shown. However, the ability of HDL to remove cholesterol from arterial wall macrophages, termed cholesterol efflux capacity (CEC), has proven to be a better predictor of cardiovascular disease (CVD) largely independently of HDL-concentrations. In addition, the serum capacity to load macrophages with cholesterol (cholesterol loading capacity, CLC) represents an index of pro-atherogenic potential. As transgender individuals are exposed to lifelong exogenous hormone therapy (HT), it becomes of interest to study whether HDL-CEC and serum CLC are affected by HT. HDL-CEC and serum CLC have been evaluated in 15 trans men treated with testosterone and in 15 trans women treated with estradiol and cyproterone acetate at baseline and after 12 months of HT. METHODS: Total HDL-CEC from macrophages and its major contributors, the ATP-binding cassette transporters (ABC) A1 and ABCG1 HDL-CEC and HDL-CEC by aqueous diffusion were determined by a radioisotopic assay. CLC was evaluated in human THP-1 macrophages. RESULTS: In trans women, total HDL-CEC decreased by 10.8% (95%CI: -14.3;-7.3; p < 0.001), ABCA1 HDL-CEC by 23.8% (-34.7; -12.9; p < 0.001) and aqueous diffusion HDL-CEC by 4.8% (-8.4;-1.1; p < 0.01). In trans men, only aqueous diffusion HDL-CEC decreased significantly, -9.8% (-15.7;-3.9; p < 0.01). ABCG1 HDL-CEC did not change in either group. Serum CLC and HDL subclass distribution were not modified by HT in both groups. CONCLUSIONS: Total HDL-CEC decreased during HT in trans women, with a specific reduction in ABCA1 CEC. This finding might contribute to a higher CVD risk.

Variation in sensitivity and rate of change in body composition: steps toward individualizing transgender care.

OBJECTIVE: Transgender individuals sometimes report a lack of physical change during hormone treatment, such as alterations in muscle tone or fat distribution. Identifying characteristics of this subgroup could be a step toward individualizing hormone therapy in transgender individuals. Therefore, we study the variation of changes in body composition and characteristics associated with a lack of change. DESIGN AND METHODS: Body composition measures were recorded in 323 transmen and 288 transwomen at every visit from the start of hormone therapy to a maximum of 24 months follow-up. Absence of change was defined as transmen with a decrease in lean body mass or transwomen with a decrease in fat percentage. RESULTS: A lack of change at 24 months was observed in 19 of 94 (20.2%) transmen and in 9 of 96 (9.4%) transwomen. The risk of not achieving change in body composition was related to lower testosterone levels and less suppression of LH in transmen (OR: 0.67, 95% CI: 0.48-0.94 per SD increase in testosterone and OR: 1.36, 95% CI: 1.01-1.83 per SD increase in LH). CONCLUSIONS: There is a large variation in body composition changes during hormone therapy, with a substantial proportion of individuals with no measurable effects. In transmen, serum testosterone and LH were associated with a lack of change, but serum hormone levels were not associated with body composition changes in transwomen. The results provide a rationale for individualizing hormone therapy in transmen, by considering individual effects rather than solely relying on a standardized dosage of hormone therapy.

Cardiometabolic Effects of Testosterone in Transmen and Estrogen Plus Cyproterone Acetate in Transwomen.

CONTEXT: The impact of gender-affirming hormone therapy (HT) on cardiometabolic parameters is largely unknown. OBJECTIVE: The effects of 1 year of treatment with oral or transdermal administration of estrogen (plus cyproterone) and transdermal or IM application of testosterone on serum lipid levels and blood pressure (BP) were assessed in transgender persons. DESIGN AND METHODS: In this prospective, observational substudy of the European Network for the Investigation of Gender Incongruence, measurements were performed before and after 12 months of HT in 242 transwomen and 188 transmen from 2010 to 2017. RESULTS: Mean values are reported. In transmen, HT increased diastolic BP (2.5%; 95% CI, 0.6 to 4.4) and levels of total cholesterol (TC; 4.1%; 95% CI, 1.5 to 6.6), low-density lipoprotein-cholesterol (LDL-C; 13.0%; 95% CI, 9.2 to 16.8), and triglycerides (36.9%; 95% CI, 29.8 to 44.1); high-density lipoprotein-cholesterol levels decreased (HDL-C; 10.8%; 95% CI, -14.0 to -7.6). In transwomen, HT slightly decreased BP (systolic BP, -2.6%, 95% CI, -4.2 to -1.0; diastolic BP, -2.2%, 95% CI, -4.0 to -0.4) and decreased levels of TC (-9.7%; 95% CI, -11.3 to -8.1), LDL-C (-6.0%; 95% CI, -8.6 to 3.6), HDL-C (-9.3%; 95% CI, -11.4 to -7.3), and triglycerides (-10.2%; 95% CI, -14.5 to -5.9). CONCLUSION: Unfavorable changes in lipid profile were observed in transmen; a favorable effect was noted in transwomen. HT effects on BP were negligible. Long-term studies are warranted to assess whether and to what extent HT in trans individuals results in a differential effect on cardiovascular disease outcomes.