HypogonadismNCT06247267
The Effect of Sex Steroid Replacement Therapy in the Hypogonadism and Transgender Active-Duty Population
An observational study of Hypogonadism and Gender Identity Dysphoria, run by Walter Reed National Military Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypogonadism, Gender Identity Dysphoria
- What is being tested?
- Fortesta and Estradiol
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Mar 2021to Aug 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- recent orders to move out of the geographic area
- Age less than 18 years old or older than 65 years old
- Scheduled for deployment
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600
Thanh D Hoang, MD, 301-295-6220, thanh.d.hoang.mil@health.mil
Iris E Robbins, BA, 301-319-4599, iris.e.robbins1.civ@health.mil
About this study
Official title: The Effect on Sex Steroid Replacement Therapy in the Hypogonadism and Transgender Active-Duty Population on Bone Density, Fractures, Memory/Cognitive Function and Qualities of Life
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.
Read the detailed description
The Endocrine Society defines male hypogonadism as a clinical syndrome that results from failure of the testis to produce physiological levels of testosterone (androgen deficiency) and the normal number of spermatozoa caused by disruption of one or more levels of the hypothalamic-pituitary-gonadal (HPG) axis. It is characterized by low serum testosterone/ high LH/high FSH concentrations (primary hypogonadism) or low testosterone/low LH/low FSH (secondary hypogonadism). The main constellation of signs and symptoms may include erectile dysfunction , decreased libido and volume of ejaculation, decreased lean body mass with increased body fat, loss of body and facial hair, weakness, fatigue, anemia and decreased bone density. There is only little data from large cross-sectional studies that address the impact of hypogonadism on morbidity. However, some small studies have concluded that testosterone deficiency could lead to a higher prevalence of depression, osteoporosis, fracture and frailty . Hypogonadism defined as serum total testosterone level <300 ng/dl has been shown to be related to decreased bone mineral density (BMD). Further review of the literature found various epidemiological studies in men that showed the associations between testosterone and estradiol levels and BMD. They found that estrogen has a major role in regulating bone resorption but both estrogen and testosterone play a role in maintaining bone formation. A recent published trial in 2017 also showed that testosterone replacement therapy in older men was associated with significant greater improvements in stair-climbing power, muscle mass and power. Similar studies found that deficiency of testosterone would lead to decrease in lean mass, muscle size and strength. Given that these two sex steroid hormones, testosterone and estrogen, play an important role in men and women, respectively, we also study their long-term effects in the transgender population once they were started on the opposite gender hormone and lack of their own endogenous production.
- Conditions
- Hypogonadism, Gender Identity Dysphoria
- Being tested
- Fortesta, Estradiol
- Keywords
- Transgender, Gender dysphoria, Hypogonadism
- Medical subject headings
- Hypogonadism, Gender Dysphoria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FortestaDrug
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.
EstradiolDrug
Male-to-female (MTF) receive Estradiol orally and transdermal and/or spironolactone-orally) treatment for 12 months for hormonal transition period.
FortestaDrug
Female-to-male (FTM) receive Fortesta injection, gel and transdermal treatment for 12 months for hormonal transition period.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Fortesta |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 12 months
Secondary outcomes (1)
Examination and comparison of the general health questionnaire among the three study groups
Subjects will undergo a quality of life general health assessment conducted by study investigators
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2024
- Study start9 Mar 2021
- Primary completionAug 2025 (estimated)
- Study completionAug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypogonadismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Walter Reed National Military Medical Center
- Sponsor type
- US federal agency
- Responsible party
- Principal investigator, Thanh Hoang, Walter Reed National Military Medical Center
- Investigators
- Thanh D Hoang, MD, Principal investigator, Walter Reed National Military Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06247267
- Sponsor's protocol ID
- Transgender Study
- Status last verified
- Jul 2025
- First submitted
- 26 Apr 2023
- Last updated
- 29 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect on Sex Steroid Replacement Therapy in the Hypogonadism and Transgender Active-Duty Population on Bone Density, Fractures, Memory/Cognitive Function and Qualities of Life
- ClinicalTrials.gov ID
- NCT06247267
- Acronym / sponsor ID
- Transgender Study
- Conditions
- Hypogonadism, Gender Identity Dysphoria
- Keywords
- Transgender, Gender dysphoria, Hypogonadism
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Walter Reed National Military Medical CenterUS federal agency
- Study start
- 9 Mar 2021 (actual)
- Primary completion
- Aug 2025 (estimated)
- Study completion
- Aug 2025 (estimated)
- First posted
- 7 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The Endocrine Society defines male hypogonadism as a clinical syndrome that results from failure of the testis to produce physiological levels of testosterone (androgen deficiency) and the normal number of spermatozoa caused by disruption of one or more levels of the hypothalamic-pituitary-gonadal (HPG) axis. It is characterized by low serum testosterone/ high LH/high FSH concentrations (primary hypogonadism) or low testosterone/low LH/low FSH (secondary hypogonadism). The main constellation of signs and symptoms may include erectile dysfunction , decreased libido and volume of ejaculation, decreased lean body mass with increased body fat, loss of body and facial hair, weakness, fatigue, anemia and decreased bone density. There is only little data from large cross-sectional studies that address the impact of hypogonadism on morbidity. However, some small studies have concluded that testosterone deficiency could lead to a higher prevalence of depression, osteoporosis, fracture and frailty . Hypogonadism defined as serum total testosterone level <300 ng/dl has been shown to be related to decreased bone mineral density (BMD). Further review of the literature found various epidemiological studies in men that showed the associations between testosterone and estradiol levels and BMD. They found that estrogen has a major role in regulating bone resorption but both estrogen and testosterone play a role in maintaining bone formation. A recent published trial in 2017 also showed that testosterone replacement therapy in older men was associated with significant greater improvements in stair-climbing power, muscle mass and power. Similar studies found that deficiency of testosterone would lead to decrease in lean mass, muscle size and strength. Given that these two sex steroid hormones, testosterone and estrogen, play an important role in men and women, respectively, we also study their long-term effects in the transgender population once they were started on the opposite gender hormone and lack of their own endogenous production.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Primary/Secondary Untreated Hypogonadism | – | Drug: FortestaSubjects 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. |
| Male-to-Female (MTF) | – | Drug: EstradiolSubjects in group 2 will take clinically indicated estrogen therapy (Estradiol-orally and transdermal and/or spironolactone-orally) for 12 months for hormonal transition period. |
| Female-to-Male (FTM) | – | Drug: FortestaSubjects in group 3 will take clinically indicated testoserone replacement therapy (Fortesta-injection, gel and transdermal) for 12 months for hormonal transition period. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- Pregnancy, plan for pregnancy in the next 12 months
- Cardiac disease, especially coronary artery disease
- Malabsorption disorder
- Gastrointestinal surgeries
- Significant renal or liver dysfunction
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FortestaPrimary/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. | Drug | Primary/Secondary Untreated Hypogonadism |
| EstradiolMale-to-female (MTF) receive Estradiol orally and transdermal and/or spironolactone-orally) treatment for 12 months for hormonal transition period. | Drug | Male-to-Female (MTF) |
| FortestaFemale-to-male (FTM) receive Fortesta injection, gel and transdermal treatment for 12 months for hormonal transition period. | Drug | Female-to-Male (FTM) |
Primary outcome
Effects of sex steroid hormone replacement therapy on body composition
Time frame: 12 months
Subjects will undergo Dual energy X-ray Absorptiometry conducted by the research coordinator assessing bone density, body composition, and risk of fractures.
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
Time frame: 12 months
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.
1 secondary outcome
Examination and comparison of the general health questionnaire among the three study groups
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Thanh D Hoang, MD principal investigator
Walter Reed National Military Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hypogonadism and Gender Identity Dysphoria, run by Walter Reed National Military Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact CAPT Than D Hoang, D.O., MC, USN (301-295-5165, thanh.d.hoang.mil@health.mil), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effects of sex steroid hormone replacement therapy on body composition (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2025.