Summary

To prepare its 2017 guideline on hormone treatment for trans people, the Endocrine Society (a body of hormone doctors) paid Mayo Clinic reviewers to gather all studies on cross-sex hormones and heart health. They found 29 studies. Almost all simply observed patients, and many had no comparison group. Testosterone in trans men worsened cholesterol, raising 'bad' cholesterol and blood fats and lowering 'good' cholesterol. Estrogen in trans women raised blood fats. Heart attacks, strokes, blood clots and deaths were too rarely reported to measure risk, though they were more common in trans women. The reviewers judged the evidence low quality. The review mainly shows how little was known about heart safety when the guideline was written. Larger studies published since (for example Getahun 2018 and Nota 2019) are not included.

Key findings

• The review was paid for by the Endocrine Society to support its 2017 guideline on treating gender dysphoria (distress about one's sex) with hormones.
• It included 29 studies covering 3,231 trans women and 1,500 trans men; only 1 randomly assigned treatment, 17 just compared people before and after, and only 4 had a comparison group.
• In trans men, after 2 or more years, testosterone was linked to higher blood fats (triglycerides, up 21.4 mg/dL), higher 'bad' cholesterol (up 17.8 mg/dL) and lower 'good' cholesterol (down by up to 8.5 mg/dL).
• In trans women, blood fats were higher after 2 or more years (up 31.9 mg/dL), with no clear change in cholesterol.
• Among trans women, studies reported 56 blood clots in 1,767 people, 14 heart attacks in 1,073, 8 strokes in 859 and 139 deaths in 1,486, including 23 heart-related deaths and 26 suicides.
• Among trans men, studies reported only 1 blood clot in 771, 1 heart attack in 478, no strokes in 340 and 13 deaths in 651.
• The reviewers rated the overall evidence as low quality, likely affected by selective reporting, with little data on the health events that matter most to patients.

Abstract

BACKGROUND: Transgender individuals receive cross-sex hormonal therapy to induce desired secondary sexual characteristics despite limited data regarding its effects on cardiovascular health. METHODS: A comprehensive search of several databases up to 7 April 2015 was conducted for studies evaluating the effect of sex steroid use on lipids, myocardial infarction, stroke, venous thromboembolism (VTE), and mortality in transgender individuals. Pairs of reviewers selected and appraised the studies. A random-effects model was used to pool weighted mean differences and 95% confidence intervals (CIs). RESULTS: We found 29 eligible studies with moderate risk of bias. In female-to-male (FTM) individuals, sex steroid therapy was associated with statistically significant increases in serum triglyceride (TG) levels at 3 to 6 months and at ≥24 months (21.4 mg/dL; 95% CI: 0.14 to 42.6) and in low-density lipoprotein cholesterol (LDL-C) levels at 12 months and ≥24 months (17.8 mg/dL; 95% CI: 3.5 to 32.1). High-density lipoprotein cholesterol (HDL-C) levels decreased significantly across all follow-up periods (highest at ≥24 months, -8.5 mg/dL; 95% CI: -13.0 to -3.9). In male-to-female (MTF) individuals, serum TG levels were significantly higher at ≥24 months (31.9 mg/dL; 95% CI: 3.9 to 59.9) without any changes in other parameters. Few myocardial infarction, stroke, VTE, and death events were reported (more frequently in MTF individuals). CONCLUSIONS: Low-quality evidence suggests that sex steroid therapy may increase LDL-C and TG levels and decrease HDL-C level in FTM individuals, whereas oral estrogens may increase TG levels in MTF individuals. Data about important patient outcomes remain sparse.

Conclusion

Low-quality evidence suggests that sex steroid therapy may increase LDL-C and TG levels and decrease HDL-C level in FTM individuals, whereas oral estrogens may increase TG levels in MTF individuals. Data about important patient outcomes remain sparse.