Mechanisms of Blood Pressure Dysfunction in Transmen Receiving Testosterone

NCT04524325 | Withdrawn

• 1 other identifier: 2000027735
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Transgender Men; Blood Pressure; Hyperandrogenism

Keywords

transgender; baroreflex; testosterone

Outcome Measures

Primary Outcomes (7)

• Muscle Sympathetic Nerve Activity (MSNA)

  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.

  3 hours

• Systolic Blood Pressure (SBP)

  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.

  3 hours

• Diastolic Blood Pressure (DBP)

  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.

  3 hours

• Mean Arterial Pressure (MAP)

  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.

  3 hours

• Sympathetic Baroreflex (BR) Gain

  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.

  3 hours

• Frequency in the Neural Cardiovascular Control

  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.

  0.5 hours

• Electrocardiogram (ECG)

  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.

  3 hours

Secondary Outcomes (2)

• Brachial Artery Mean Blood Flow Velocity

  3 hours

• Cardiovagal Baroreflex (BR) Gain

  3 hours

Study Arms (2)

Trans men

ACTIVE COMPARATOR

transgender men taking physiologic doses of testosterone for gender affirming hormone therapy

Other: Trans men

control

NO INTERVENTION

cisgender women not receiving testosterone and with normal sex hormone levels

Interventions

Trans men OTHER

We are studying the effects of testosterone taken by trans men on mechanisms of blood pressure control and comparing those results to cisgender women that have normal (ie lower) testosterone levels.

Trans men

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Transgender men will be recruited for participating in the experimental group; cisgender women will be recruited for participation in the control group.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead
• The John B. Pierce Laboratory: collaborator

MeSH Terms

Conditions

Hyperandrogenism

Condition Hierarchy (Ancestors)

46, XX Disorders of Sex Development; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Adrenogenital Syndrome; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Gonadal Disorders; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: There is 1 group of trans men (n=20) and 1 group of cisgender women (n=20). Study procedures, protocols, and measurements will be the same for both groups and performed and/or taken in a similar time period.

Study Record Dates

• First Submitted: August 17, 2020
• First Posted: August 24, 2020
• Study Start: January 1, 2023
• Primary Completion: July 1, 2023
• Study Completion: June 30, 2024
• Last Updated: November 3, 2022

Record last verified: 2022-10