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

• このレビューは、ホルモンによる性別違和（自分の性別に対する苦痛）の治療に関する、内分泌学会の2017年のガイドラインを支えるために、同学会が費用を出しました。
• トランス女性3,231人とトランス男性1,500人を対象とした29件の研究が含まれていました。治療を無作為に割り当てたのは1件だけで、17件は前後を比較しただけで、比較群があったのは4件だけでした。
• トランス男性では、2年以上後に、テストステロンは、より高い血中脂肪（トリグリセリド、21.4 mg/dL上昇）、より高い「悪玉」コレステロール（17.8 mg/dL上昇）、より低い「善玉」コレステロール（最大8.5 mg/dL低下）と関連していました。
• トランス女性では、2年以上後に血中脂肪が高く（31.9 mg/dL上昇）、コレステロールには明確な変化はありませんでした。
• トランス女性について、研究は、1,767人中56件の血栓、1,073人中14件の心臓発作、859人中8件の脳卒中、1,486人中139件の死亡（心臓関連の死亡23件と自殺26件を含む）を報告しました。
• トランス男性について、研究は、771人中1件の血栓、478人中1件の心臓発作、340人中0件の脳卒中、651人中13件の死亡のみを報告しました。
• レビュー担当者は、全体のエビデンスを低品質で、選択的な報告の影響を受けている可能性が高く、患者にとって最も重要な健康上の事象に関するデータがほとんどないと評価しました。

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.