Background: Male-to-female transsexual women or transwomen who undergo cross-sex hormone treatments experience increased health-related risks (e.g., increased rates of cardiovascular disease and premature death). Yet, the exact mechanism by which altering biochemistry leads to metabolic impairment remains unclear. While much attention has been paid to cross-sex hormone therapy, little is known about the metabolic risk associated with orchiectomy. Methods: To address the above limitation, we prospectively enrolled 12 transwomen: 4 who had undergone bi-lateral orchiectomy and 8 who had not. Both groups were using cross-sex hormones. Glucose tolerance was assessed using a standard 75g oral glucose tolerance test. Hepatic steatosis was assessed by 1H magnetic resonance spectroscopy. The amount of subcutaneous and visceral abdominal fat was determined from a single abdominal axial image at the level between the vertebral L2 and L3 bodies. Baseline venous fasting blood sampling was performed for measurement of hemoglobin A1c, glucose, insulin, sex hormones, and sex hormone binding globulin. Results: The major novel findings were: (1) orchiectomy and cross-sex hormone therapy is associated with less hepatic steatosis and insulin resistance; (2) orchiectomy may be metabolically protective, and (3) circulating concentrations of sex hormones may be a major determinant of metabolic health in transwomen. Conclusions: To our knowledge, this is the first study to suggest an independent and protective role of orchiectomy on the metabolic health of transwomen.

Background

The aim of the current study was to examine whether the use of highly active antiretroviral therapy (HAART) in patients with HIV is associated with changes in pericardial fat and myocardial lipid content measured by cardiovascular magnetic resonance (CMR).

Methods

In this prospective case-control study, we compared 27 HIV seropositive (+) male subjects receiving HAART to 22 control male subjects without HIV matched for age, ethnicity and body mass index. All participants underwent CMR imaging for determination of pericardial fat [as volume at the level of the origin of the left main coronary artery (LM) and at the right ventricular free wall] and magnetic resonance spectroscopy (MRS) for evaluation of intramyocardial lipid content (% of fat to water in a single voxel at the interventricular septum). All measurements were made by two experienced readers blinded to the clinical history of the study participants. Two-sample t-test, Spearman's correlation coefficient or Pearson's correlation coefficient and multivariable logistic regression were used for statistical analysis.

Results

Pericardial fat volume at the level of LM origin was higher in HIV (+) subjects (33.4 cm(3) vs. 27.4 cm(3), p = 0.03). On multivariable analysis adjusted for age, Framingham risk score (FRS) and waist/hip ratio, pericardial fat remained significantly associated to HIV-status (OR 1.09, p = 0.047). For both HIV (+) and HIV (-) subjects, pericardial fat volume showed strong correlation with intramyocardial lipid content (r = 0.58, p < 0.0001) and FRS (r = 0.53, p = 0.0002). Among HIV (+) subjects, pericardial fat was significantly higher in patients with lipo-accumulation (37 cm(3) vs. 27.1 cm(3), p = 0.03) and showed significant correlation with duration of both HIV infection (r = 0.5, p = 0.01) and HAART (r = 0.46, p = 0.02).

Conclusions

Pericardial fat content is increased in HIV (+) subjects on chronic HAART (>5 years), who demonstrate HAART-related lipo-accumulation and prolonged HIV duration of infection. Further investigation is warranted to determine whether increased pericardial fat is associated with higher cardiovascular risk leading to premature cardiovascular events in this patient population.

Background

People with human immunodeficiency virus (PWH) face increased risks for heart failure and adverse heart failure outcomes. Myocardial steatosis predisposes to diastolic dysfunction, a heart failure precursor. We aimed to characterize myocardial steatosis and associated potential risk factors among a subset of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) participants.

Methods

Eighty-two PWH without known heart failure successfully underwent cardiovascular magnetic resonance spectroscopy, yielding data on intramyocardial triglyceride (IMTG) content (a continuous marker for myocardial steatosis extent). Logistic regression models were applied to investigate associations between select clinical characteristics and odds of increased or markedly increased IMTG content.

Results

Median (Q1, Q3) IMTG content was 0.59% (0.28%, 1.15%). IMTG content was increased (> 0.5%) among 52% and markedly increased (> 1.5%) among 22% of participants. Parameters associated with increased IMTG content included age (P = .013), body mass index (BMI) ≥ 25 kg/m2 (P = .055), history of intravenous drug use (IVDU) (P = .033), and nadir CD4 count < 350 cells/mm³ (P = .055). Age and BMI ≥ 25 kg/m2 were additionally associated with increased odds of markedly increased IMTG content (P = .049 and P = .046, respectively).

Conclusions

A substantial proportion of antiretroviral therapy-treated PWH exhibited myocardial steatosis. Age, BMI ≥ 25 kg/m2, low nadir CD4 count, and history of IVDU emerged as possible risk factors for myocardial steatosis in this group.

Clinical trials registration

NCT02344290; NCT03238755.