The Effect of Sex Steroid Replacement Therapy in the Hypogonadism and Transgender Active-Duty Population

NCT06247267 | Recruiting FDA Drug

• 1 other identifier: Transgender Study
• Study Type: observational
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

It has been known that both estrogen and testosterone are the major sex steroids regulating bone metabolism and other physiological changes in both male and female, respectively. In postmenopausal women, osteoporosis is a major concern secondary to the lack of estrogen. These patients also experience a number of physiological changes that affect their life permanently to include hot flashes, irritability, difficulty concentrating, depression and mental confusion. In hypogonadal men, testosterone deficiency could lead to higher prevalence of depression, osteoporosis, fracture and frailty. Given the new military policy starting to support treatment for gender identity dysphoria military personnel, the number of transgender patients in our Endocrinology clinic has been slowly increasing over the past several months. These patients will require either testosterone replacement therapy or estrogen therapy to achieve their desired sexual characteristics. However, as mentioned above, the lack of estrogen or testosterone in female and male, respectively, could cause several issue in their body composition, cognitive function and quality of life. We designed this prospective case-control study to include patients with hypogonadism and the transgendered populations to learn about the long-term effects of these hormonal replacement therapies on bone density, fractures, memory/cognitive function and quality of life. This is a repetitive measures study taken at baseline, 6-months, and 12-months for three groups consisting of at least 75 subjects. The study will involve 3 arms, i.e. Group 1 primary/secondary untreated hypogonadism, Group 2 male-to female (MTF), and Group 3 female-to-male (FTM) participants that are planning to start hormone replacement therapy as per standard clinical guidelines.

Conditions

Hypogonadism; Gender Identity Dysphoria

Keywords

Transgender; Gender dysphoria; Hypogonadism

Outcome Measures

Primary Outcomes (2)

• Effects of sex steroid hormone replacement therapy on body composition

  Subjects will undergo Dual energy X-ray Absorptiometry conducted by the research coordinator assessing bone density, body composition, and risk of fractures.

  12 months

• Effects of sex steroid hormone replacement therapy in treating hypogonadism and in transgender patients using Dual energy X-ray Absorptiometry assessing body composition and Bone Mineral Density

  We designed this prospective case-control study to include patients with hypogonadism and the transgendered populations to learn about the long-term effects of these hormonal replacement therapies on bone density, fractures, memory/cognitive function and quality of life. This is a repetitive measures study taken at baseline, 6-months, and 12-months for three groups consisting of at least 75 subjects. The study will involve 3 arms, i.e. Group 1 primary/secondary untreated hypogonadism, Group 2 male-to female (MTF), and Group 3 female-to-male (FTM) participants that are planning to start hormone replacement therapy as per standard clinical guidelines.

  12 months

Secondary Outcomes (1)

• Examination and comparison of the general health questionnaire among the three study groups

  12 months

Other Outcomes (2)

• Examination and comparison of the Beck Depression Inventory (a 21-item self-reporting questionnaire for evaluating the severity of depression in normal and psychiatric populations) among the three study groups

  12 months

• Examination and comparison of the Wechsler Memory Scale (a comprehensive tool for assessing verbal, visual, working, and recognition memory)

  12 months

Study Arms (3)

Primary/Secondary Untreated Hypogonadism

Subjects in group 1 will take clinically indicated testosterone replacement therapy (Fortesta-injection, gel and transdermal) for 12 months with titration for a serum total T level between 300-600 ng/dL.

Drug: Fortesta

Male-to-Female (MTF)

Subjects in group 2 will take clinically indicated estrogen therapy (Estradiol-orally and transdermal and/or spironolactone-orally) for 12 months for hormonal transition period.

Drug: Estradiol

Female-to-Male (FTM)

Subjects in group 3 will take clinically indicated testoserone replacement therapy (Fortesta-injection, gel and transdermal) for 12 months for hormonal transition period.

Drug: Fortesta

Interventions

Fortesta DRUG

Primary/secondary untreated hypogonadism patients receive Fortesta injection, gel and transdermal treatment for 12 months with titration for a serum total T level between 300-600ng/dL.

Primary/Secondary Untreated Hypogonadism

Estradiol DRUG

Male-to-female (MTF) receive Estradiol orally and transdermal and/or spironolactone-orally) treatment for 12 months for hormonal transition period.

Male-to-Female (MTF)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Gender Eligibility Details: Patients (male and female health care beneficiaries of the military system) between the ages of 18 to 65 who have been diagnosed with primary hypogonadism and/or under the care for gender identity dysphoria and have been on a stable dose of sex hormonal therapy
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study findings will be generalized to patients ages of 18 to 65 who are planning to be placed on sex steroid hormone either for hypogonadism or transgender treatment as per clinical guidelines.

You may qualify if:

• Male and female DoD health care beneficiaries
• Ages 18-65
• Diagnosed with primary hypogonadism or transgender treatment for at least 6 months
• Under care for gender identity dysphoria
• On stable dose of sex steroid hormonal therapy for at least 6 months prior to enrolling
• Must be living in the Washington, D.C. area for at least 12 months following enrollment

You may not qualify if:

• Pregnancy, plan for pregnancy in the next 12 months
• Cardiac disease, especially coronary artery disease
• Malabsorption disorder
• Gastrointestinal surgeries
• Significant renal or liver dysfunction
• Seizure disorders
• recent orders to move out of the geographic area
• Age less than 18 years old or older than 65 years old
• Scheduled for deployment

Sponsors & Collaborators

• Walter Reed National Military Medical Center: lead

Study Sites (1)

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889-5600, United States

RECRUITING

MeSH Terms

Conditions

Hypogonadism; Gender Dysphoria

Interventions

Testosterone Propionate; Estradiol

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases; Sexual Dysfunctions, Psychological; Mental Disorders

Intervention Hierarchy (Ancestors)

Testosterone; Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrenes; Estranes; Estradiol Congeners

Study Officials

• Thanh D Hoang, MD

  Walter Reed National Military Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

CAPT Than D Hoang, D.O., MC, USN

CONTACT

301-295-5165; thanh.d.hoang.mil@health.mil

Iris E Morris, BA

CONTACT

301-319-4599; iris.e.morris3.civ@health.mil

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 26, 2023
• First Posted: February 7, 2024
• Study Start: March 9, 2021
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: July 29, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)