Effects of Cross-sex Hormone Treatment on Cardiac Function, Myocardial and Hepatic Fat Content, Its (Anti)-Atherogenic Implications and Effects on the Insulin System: a Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Hepatic lipid content
研究概览
简要总结
Background: Sex hormones are believed to play an important role in the development and progression of cardiovascular disease. However, the gender gap in onset and mortality is not yet completely understood. Transsexuals undergoing hormone therapy are a promising collective for analyzing the effects of sex hormones on atherosclerosis and other cardiovascular disease. Objectives of the study: To identify gender-specific cardiovascular changes attributed to high-dose hormone therapy in male-to-female (MtF) and female-to-male(FtM) transgender using sonography and magnet resonance spectroscopy. Study design: Longitudinal cohort study. Transsexuals will undergo two 3 Tesla MRI scan sessions: 1. baseline (before hormone treatment) and 2. after 6 months of treatment. An oral glucose tolerance test (OGTT) will be performed at baseline and 6 months after treatment onset. An overall study duration of 12 months is proposed.
Materials and Methods: MRI measurements will be performed on a 3 Tesla scanner. Study population: 10 FtM, 10 male-to-female MtF transsexuals (aged 18-50), free of hormone-medication at baseline. Relevance and implications of the study: Changes in atherosclerotic risk due to hormone therapy have been studied to no definite results and so far, little is known about the effects of hormone therapy on hepatic and myocardial fatty tissue. Hence this study will provide important new data on the broad clinical aspects of sex hormones as hormone replacement therapy in particularly opposite-sex hormone therapy.
详细描述
Background Atherosclerosis has been shown to differ in men and women regarding disease risk, onset time and overall mortality. This gender gap is mostly attributed to sex hormones. Pre-menopausal women have less atherosclerosis risk than men of the same age; on the other hand, however, overall mortality due to cardiovascular disease is higher in women. Nonalcoholic fatty liver which is associated with liver cirrhosis and higher atherosclerotic risk due to impaired liver function is more common in men and postmenopausal women as well. Therefore, a protective effect of estrogen has been proposed. Excessive androgens on the contrary have been associated with atherogenic effects. Thus, men with high exogenous testosterone supply show higher atherosclerosis risk as do women suffering from polycystic ovary syndrome and hence hyperandrogenemia while men with an androgen deficit have an increased risk of atherosclerosis as well. Nonetheless, these findings could not be backed up by clinical intervention studies yet and further research on this gender gap is necessary. Transsexuals are usually treated with high-dose opposite-sex hormone therapy at least for one year before they undergo operations. Therefore, they are an auspicious collective to study hormone-dependent changes in atherosclerosis risk and lipid profile. Even though it has been shown that lipoproteins change during hormone therapy, leading to an increase in triglycerides and cholesterol, significant effects on atherosclerotic risk have not yet been detected. However, there is hardly any data yet available on the effect of hormone therapy on cardiovascular risk factors and morbidities as nonalcoholic fatty liver, increased fatty tissue in the myocardial cells. Effects on heart function may exist as well since elevated lipids can induce cardiac steatosis and hence diminish the diastolic heart function.
Furthermore, hormone therapy has been associated with elevated blood pressure. However, while the increased cholesterol and triglycerides may boost the risk, estrogen is believed to be a protective factor. Therefore, the effects of hormone therapy on cardiovascular disease are hard to estimate and will be further analyzed in this study. Objectives of the study
- To examine the influence of high-dose, long-term opposite-sex steroid hormone treatment on hepatic and cardiac fatty tissue and heart function in female to-male (FtM) and male-to-female (MtF) transsexuals using 3 Tesla MRS.
- To examine the influence of high-dose, long-term opposite-sex steroid hormone treatment on systolic and diastolic heart function in female to-male (FtM) and male-to-female (MtF) transsexuals using 3 Tesla MRS.
- To examine the influence of high-dose, long-term opposite-sex steroid hormone treatment on carotid-media-thickness in female to-male (FtM) and male-to-female (MtF) transsexuals using sonography.
- To examine the influence of high-dose, long-term opposite-sex steroid hormone treatment on diabetes risk and insulin sensitivity & secretion in female to-male (FtM) and male-to-female (MtF) transsexuals via the oral glucose tolerance test (OGTT) and blood sampling.
Study Design This pilot study is designed as a longitudinal mono-center study. 40 transsexual subjects (20 FtM, 20 MtF) will undergo two 3 -Tesla 1H magnet resonance spectroscopy as well as 2 sonography measurements. The first scans (baseline) will be performed before treatment, the second scans after 6 months of high-dose, long-term cross-sex hormone treatment.
Subject Section Transsexuals urging gender reassignment in a clinical setting will be enrolled in this study. 20 female-to-male (FtM) and 20 male-to-female (MtF) transsexuals will be recruited. There will be no transsexual placebo group implemented in the study because of ethical reasons. The hormone therapy they will receive is purely clinical indicated and is prescribed by a doctor not included in the study. This study does not influence either the choice nor the beginning or end of the cross-sex hormone therapy
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •DSM-IV diagnosis of Gender Identity Disorder
- •age over 18 years
排除标准
- •age under 18 years severe neurological or internal diseases
- •steroid hormone treatment within 2 months prior to inclusion (including birth control pill, phytohormones)
- •treatment with psychotropic agents such as SSRIs
- •any implant or stainless-steel graft
- •abnormal values in routine laboratory screening or general physical examination
- •current substance abuse (determined using drug screening at the screening visit)
- •pregnancy (determined at screening visit and first MRI scan)
- •failure to comply with the study protocol or to follow the instructions of the investigating
研究组 & 干预措施
Transgender women
Transgender individuals assigned male at birth undergoing estrogen and antiandrogen hormone therapy
干预措施: gender affirming hormone therapy (Drug)
Transgender men
Transgender individuals assigned female at birth undergoing testosterone hormone therapy
干预措施: gender affirming hormone therapy (Drug)
结局指标
主要结局
Hepatic lipid content
时间窗: 6 months
changes in the hepatic lipid content (in percent) due to long-term gender-affirming hormone therapy therapy measured by MRT
Pancreatic lipid content
时间窗: 6 months
changes in pancreatic lipid content (in percent) due to long-term gender-affirming hormone therapy therapy measured by MRT
Myocardial lipid content
时间窗: 6 months
changes in myocardial lipid content (in percent) due to long-term gender-affirming hormone therapy therapy measured by MRT
Cardiac function
时间窗: 6 months
the effect of the hormone therapy on heart function (systolic and diastolic)
changes in insulin secretion via OGTT
时间窗: 6 months
changes in insulin secretion via OGTT
Changes in insulin sensitivity via OGTT
时间窗: 6 months
changes in insulin sensitivity via OGTT
次要结局
未报告次要终点
研究者
Alexandra Kautzky-Willer
Principal Investigator
Medical University of Vienna