Mechanisms and Interventions to Address Cardiovascular Risk of Gender-affirming Hormone Therapy in Trans Men

• Status: Not yet recruiting
• Trial end date: 2023-08-31
• Target enrollment: 0
• Participant gender: All

Summary

Gender-identity differences are becoming increasingly diagnosed in the US and treatment with gender-affirming hormone therapy (GAHT) is associated with improved mental health outcomes. However, GAHT has been associated with cardiovascular risk in adult transgender patients, although mechanisms and treatments have not been explored. Understanding the cardiovascular effects and exploring the potential of a lipid sensitive statin as a potential treatment is important to optimizing safe treatment strategies for transgender men in mitigating this modifiable risk factor, and designing and implementing effective interventions.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Yale University
• Treatments: Atorvastatin

Criteria

Inclusion Criteria:

• Two groups (n=10 each) of subjects will be recruited to complete this study: 1) trans men between 18 and 35 years; 2) cisgender women between 18 and 35 years (Controls). They will have a body mass index (BMI) 18-30 kg·m-2. Our subjects will be matched on BMI and IR, using hemoglobin A1c and Homeostatic Model Assessment of Insulin Resistance technique (HOMA-IR) in order to isolate testosterone effects from other co-morbidities that may impact BP, sympathetic activity or endothelial function. Subjects will have HbA1c of 4-5.9% and a HOMA-IR of 0.5-1.4 to be included in the study. 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 CV medications.

Exclusion Criteria:

• Subjects with the following histories or conditions will be excluded from the study:

Gynecologic: a. current or past estrogen-dependent neoplasia, b. unexplained vaginal bleeding, c. history of uterine fibroids, d. current pregnancy, e. known or suspected breast or uterine cancer, f. partial or complete hysterectomy.

Cardiac: a. myocardial infarction, ventricular tachycardia or fibrillation, b. angina, c. valvular disease (mitral insufficiency or stenosis, aortic insufficiency or stenosis), d. congestive heart failure, orthopnea, paroxysmal nocturnal dyspnea, e. current arrhythmias, f. prosthetic valves.

Pulmonary: a. current cigarette smokers, or pipe or cigar smokers, b. chronic obstructive pulmonary disease, c. adult asthma, d. dyspnea on exertion, e. current bronchitis, pneumonia, or tuberculosis, f. lung carcinoma, g. pulmonary embolus, h. deep vein thrombosis.

Vascular: a. claudications or history of peripheral vascular disease, b. abdominal or thoracic aortic aneurysm, or repair of same, c. cerebral aneurysm, vascular malformations, d. hypertension, systolic or diastolic, or strong family history of hypertension.

Gastrointestinal: a. GI malignancy, b. hepatitis or other liver disease, current, c. splenomegaly from any cause, d. Cholecystitis, e. current diverticulosis or diverticulitis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, f. previous gastrointestinal surgery.

Infectious Disease: any ongoing intercurrent infection. Hematologic/Oncologic: a. receiving chemotherapy or radiation therapy, b. any metastatic malignancy, c. anemia (hematocrit < 35), d. thrombocytopenia or thrombocytosis, e. neutropenia, f. hematologic malignancy, g. bleeding dyscrasia.

Neurologic: a. history of cerebral vascular accident with any neurologic sequels, b. uncontrolled seizures (e.g., more than 1 seizure/year), c. transient ischemic attacks, d. dementia, e. neurologic conditions producing dyscoordination, peripheral neuropathy, or myopathy.

Endocrine: a. diabetes mellitus, b. any untreated endocrinopathy. Renal: a. chronic renal diseases, b. any history of renal disease or impairment, c. current urinary tract infection.

Musculoskeletal: a. inflammatory arthritis history (e.g., rheumatoid, psoriatic, Reiters), b. any history of pathologic fractures, including vertebral compression fractures.

Pharmacologic: a. any illegal drug use, b. alcohol use greater than an average of 4 oz/day over 30 days, c. coumadin or heparin use.