Mechanisms of Blood Pressure Dysfunction in Transmen Receiving Testosterone
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 主要终点
- Muscle Sympathetic Nerve Activity (MSNA)
研究概览
简要总结
The purpose of this research is to explore the effects of chronic androgen exposure on sympathetic nervous system activity (SNSA) and baroreflex control of blood pressure responses in transgender men (trans men) taking gender affirming hormone therapy (HT). Blood pressure, baroreflex gain, and frequency of sympathetic responses to changes in blood pressure will be assessed in trans men and a control group of cisgender women. To fully understand HT effects on blood pressure regulation in trans men, it is crucial to understand how both SNSA, and the pattern of SNSA, can be influenced by high levels of androgen exposure in the female cardiovascular system, as well as how the two regulatory components may interact.
详细描述
The purpose of this research is to study how testosterone affects blood pressure control in trans men. High testosterone levels are detrimental to the female cardiovascular system in that higher levels are associated with increased blood pressure. Humans control blood pressure in the autonomic nervous system via the baroreflex mechanism. The arterial baroreflex is a key autonomic homeostatic mechanism involved in maintaining arterial blood pressure, and gain of the baroreflex is used as a measure of the sensitivity of sympathetic responses that act to restore acute blood pressure fluctuations. This autonomic regulation of blood pressure is also characterized by rhythmic activity (changes in cardiac frequency), which can be observed by recording sympathetic nerve traffic. When the female cardiovascular system is exposed to elevated androgens, baroreflex gain is impaired, and blood control is less efficient during an orthostatic challenge. However, to best understand the effect of a given stimulus on autonomic function, changes in frequency of the SNSA response must also be quantified in addition to the gain. Sympathetic control of arterial blood pressure is most effective in a narrow frequency range, and if this frequency range for responsiveness should narrow further, control of arterial blood pressure becomes less efficient and presents as dysfunction. The central hypothesis for this research is that dysregulation of blood pressure in trans men taking testosterone for gender affirming HT is a function of both reduced baroreflex gain and narrowed frequency-dependent relationship between arterial pressure and peripheral sympathetic vascular responsiveness. Specifically, these studies test the hypothesis that androgen supplementation with HT is associated with 1) lower baroreflex gain during a lower body negative pressure (LBNP) challenge, and 2) a narrowed response frequency range that precedes impaired sympathetic vascular response dynamics in trans men compared to control cisgender women.
Study procedures include an oral glucose tolerance test (OGTT), microneurography of the median nerve in the forearm to assess SNSA, and 2 LBNP challenges designed to examine baroreflex gain during static LBNP and then the frequency of SNSA during oscillating LBNP (OLBNP). Participants complete 3 visits for this study. Visit 1 is for informed consent procedures; Visit 2 is a pre-screening visit to complete the OGTT; Visit 3 is for experimental testing to assess gain and the frequency range. Blood pressure, heart rate and muscle SNSA (MSNA) are measured during LBNP and OLBNP. MSNA is recorded using 2 microelectrodes inserted through the skin of the forearm to record activity (firing) of the median nerve. Blood samples are taken via IV placement to measure insulin and glucose during the OGTT for Visit 2, and then sex hormones and catecholamines during Visit 3. Results from the group of young trans men will be compared to a control group of cisgender women matched for age and body mass index.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Both groups (trans men and cisgender women) must be healthy and non-smoking. Control participants must be cisgender women with regular menses every 26-34 days. Trans men participants must be currently receiving testosterone for gender affirming hormone therapy where physiologic doses of exogenous Dihydrotestosterone have been administered (via injection or transdermal application) for at least 3 months as prescribed by their local endocrine provider as part of their clinically indicated hormone therapy. Doses can vary depending on the size and goals of each patient, but blood testosterone will be between 400-1000 ng/dl.
排除标准
- •Subjects who smoke, have diabetes, or BP>140/90 will be excluded.
- •Subjects will not be taking medications during the study, including any insulin-sensitizing or cardiovascular medications.
- •Subjects are excluded if they have lost > 5 kg of weight within the past 6 months or perform high-intensity exercise > 3 times/week.
结局指标
主要结局
Muscle Sympathetic Nerve Activity (MSNA)
时间窗: 3 hours
MSNA is recorded continuously at rest and during O/LBNP protocols with a tungsten microelectrode (0.2 diameters insulated shaft tapered to an uninsulated tip of \~1-5 μm) inserted percutaneously into the median nerve. Multiunit, postganglionic MSNA is distinguished from other sources of nerve activity by the presence of spontaneous pulse synchronous bursts, increased activity when the subject holds their breath or clenches their first (stretches forearm muscles around median nerve), or if activity does not change when the skin is stimulated by light brushing or stroking (indicates lack of skin nerve activity). Bursts of MSNA at rest and during LBNP are quantified as total activity (AU/min), burst frequency (bursts/min) and burst incidence (bursts/100 heartbeats). The MSNA burst incidence is expressed in bursts/100 heartbeats to normalize for differences in heart rate among subjects.
Sympathetic Baroreflex (BR) Gain
时间窗: 3 hours
Sympathetic BR gain is used as an index of sympathetic (neural) control of blood pressure, where gain is determined by the slope of the linear relationship between MSNA (burst/100 heartbeats) and DBP (mm Hg) at rest and during LBNP. The relationship produces a negative slope in that for a given subject, when DBP falls below the normal level sustained at rest, sympathetic activity increases to restore DBP back to that normal level. Thus, more MSNA bursts are observed at lower levels of DBP and vice versa. A steeper (more negative) slope suggests greater sensitivity of the baroreceptors to changes in blood pressure, and thereby more effective sympathetic control of blood pressure. A flatter slope suggests impaired BR sensitivity and blood pressure dysfunction, which is expected for the trans men group compared to cisgender women controls.
Systolic Blood Pressure (SBP)
时间窗: 3 hours
SBP is measured continuously with a Finometer beat-to-beat blood pressure measurement system at rest and during O/LBNP protocols. Units are mm Hg.
Mean Arterial Pressure (MAP)
时间窗: 3 hours
MAP at rest and during O/LBNP protocols is calculated as 1/3(SBP-DBP)+DBP using the beat-to-beat SBP and DBP measurements taken with the Finometer system. Units are mm Hg.
Diastolic Blood Pressure (DBP)
时间窗: 3 hours
DBP is measured continuously with a Finometer beat-to-beat blood pressure measurement system at rest and during O/LBNP protocols. Units are mm Hg.
Frequency in the Neural Cardiovascular Control
时间窗: 0.5 hours
The frequency of SBP, DBP and heart rate during OLBNP is analyzed in Matlab in a linear time-invariant system (LTI) framework. Heart rate and BP measures taken during OLBNP are low-pass filtered (0.05 Hz estimated example) and corrected for end-effects using a Hamming window. The derived impulse responses (IRs) are 1/3rd octave smoothed before calculating the frequency power spectra (0.001-0.05 Hz estimated example). The power of DBP and SBP at the OLBNP frequency are anticipated to be independently inversely related to the efficiency of BP control. Further, the difference in heart rate and SBP, and in heart rate and DBP, power at those frequencies reflects the degree of autonomic function, analogous to baroreflex gain.
Electrocardiogram (ECG)
时间窗: 3 hours
A 3-lead ECG is continuously recorded at rest and during the O/LBNP protocols. The R-wave of the QRS complex of the ECG recording will be used for measures of pulse interval by determining the amount of time in seconds between the R-waves of 2 consecutive QRS complexes.
次要结局
- Cardiovagal Baroreflex (BR) Gain(3 hours)
- Brachial Artery Mean Blood Flow Velocity(3 hours)