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

January 30, 2024 updated by: Thanh Hoang, Walter Reed National Military Medical Center

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Estimated)

75

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

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.

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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
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.
Drug: Fortesta
Female-to-male (FTM) receive Fortesta injection, gel and transdermal treatment for 12 months for hormonal transition period.
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
Male-to-female (MTF) receive Estradiol orally and transdermal and/or spironolactone-orally) treatment for 12 months for hormonal transition period.
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
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.
Drug: Fortesta
Female-to-male (FTM) receive Fortesta injection, gel and transdermal treatment for 12 months for hormonal transition period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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
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.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Examination and comparison of the general health questionnaire among the three study groups
Time Frame: 12 months
Subjects will undergo a quality of life general health assessment conducted by study investigators
12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 12 months
Subjects will undergo the Beck Depression Inventory conducted by study investigators. Scores of 0-9: indicates minimal depression 10-18: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression. Higher total scores indicate more severe depressive symptoms. Some items on the BDI have more than one statement marked with the same score.
12 months
Examination and comparison of the Wechsler Memory Scale (a comprehensive tool for assessing verbal, visual, working, and recognition memory)
Time Frame: 12 months
Subjects will undergo the Wechsler memory scale conducted by study investigators. The Wechsler Memory Scale is an individually administered battery designed to assess various memory and working memory abilities of individuals (e.g. auditory memory, visual memory, visual working memory, immediate memory, delayed memory.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Walter Reed National Military Medical Center

Investigators

  • Principal Investigator: Thanh D Hoang, MD, Walter Reed National Military Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2019

Primary Completion (Estimated)

January 1, 2025

Study Completion (Estimated)

January 1, 2025

Study Registration Dates

First Submitted

April 26, 2023

First Submitted That Met QC Criteria

January 30, 2024

First Posted (Estimated)

February 7, 2024

Study Record Updates

Last Update Posted (Estimated)

February 7, 2024

Last Update Submitted That Met QC Criteria

January 30, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Transgender Study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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