Transgender PersonsEarly Phase 1NCT04036500
Transgender Estradiol
A Early Phase 1 study testing Estradiol in people with Transgender Persons, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
Blogs, word-of-mouth, and small studies from the 1990s in the premature ovarian insufficiency and menopause populations have suggested sublingual or transdermal estradiol may be safer and/or more effective than an oral formulation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Transgender Persons
- What is being tested?
- Estradiol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Sep 2019to 13 Jul 2020
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Transgender male-to-female
- Naive to hormone therapy
- English speaker
- 18 years of age or older
Who cannot join
- History of hormone replacement therapy
- Orchiectomy
- Needle phobia
- Serious bleeding condition
- Active deep vein thrombosis, pulmonary embolism or history of these conditions
- Active or recent (e.g., within the past year) arterial thromboembolic disease (e.g., stroke, myocardial infarction)
Show all 11Show fewer
- Liver dysfunction or disease
- History of breast cancer
- Known sensitivity or allergy to any components of the medications used
- Taking potent CYP3A4 inhibitors or inducers, as determined by team pharmacist
- Taking a medication that may cause additional physical or mental harm if stopped
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Sublingual Estradiol Versus Oral Estradiol in Transgender Women
Blogs, word-of-mouth, and small studies from the 1990s in the premature ovarian insufficiency and menopause populations have suggested sublingual or transdermal estradiol may be safer and/or more effective than an oral formulation. Sublingual administration entails holding the estrogen tablet under the tongue and allowing it to dissolve, where its absorption is enhanced by the rich vascularization under the tongue. According to Price et al., sublingual administration results in rapid absorption with significantly higher estradiol levels than does comparable oral dosing. This is likely because sublingual administration will bypass metabolism by the intestines and liver. The transdermal route, which also bypasses first-pass metabolism, is not associated with an increased venous thromboembolic risk nor a significant increase in plasma triglycerides or HDL-cholesterol levels. As such, transdermal estrogen is often preferred over oral formulations, although it is relatively expensive and not accessible to many transgender women. Conversely, sublingual administration of estrogen tablets is widely available and could be a cost-effective alternative to transdermal estrogen. However, there are no well-conducted studies that have evaluated the safety and efficacy of sublingual estrogen therapy in the transgender population. This pilot study will elucidate how estrogen levels in the blood change following sublingual versus oral administration of estradiol in transgender women. This data may be used later to design larger studies on safety and efficacy.
Additionally, analyzing a dosage method that patients themselves have tried independently and found effective is also important. This approach incorporates intelligence from the transgender community into our research, creating new knowledge that is supported by data but is founded in existing community insights. Thus, the outcomes of this research have the potential to integrate patient input while also aiding in the development of safety recommendations, with the goal of better caring for our transgender patients.
Primary aim. To establish the pharmacokinetics of sublingual estradiol versus oral estradiol in transgender women.
Read the detailed description
Patient will plan on being in the Adult Translational Research Unit (A-TRU) for 8 hours. They will be assigned to a suite. They will get 7 blood draws at hours 0,1,2,3,4,6,8 and vitals at the beginning of the visit. Vitals will include height, weight, blood pressure, respiration rate, and pulse. Subject is able to eat while in the A-TRU. Day 1 patient will take estradiol 1 mg ORALLY after time 0 blood draw. The medication will be given by registered nurse. A wash-out period of at least one week will allow for complete clearance of the exogenous oral estradiol before testing the pharmacokinetics of sublingual estradiol on the same ten patients in the same manner. Subject cannot take any hormone replacement therapy between their research appointments. On day 2, subject will take estradiol 1 mg SUBLINGUALLY after time 0 blood draw, supervised by a research team member to ensure proper dissolution. Blood will be drawn at hours 0,1,2,3,4,6,8 as on day 1.
- Conditions
- Transgender Persons
- Being tested
- Estradiol
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EstradiolDrug
Patients will be given estradiol: 1 mg oral and 1 mg sublingual.
| Study group | Role | What they receive |
|---|---|---|
| Estradiol 1 mg oral first, then Estradiol 1 mg sublingual | Experimental | Subjects will take estradiol 1 mg orally after time 0 blood draw. They will get 7 blood draws at hours 0,1,2,3,4,6,8. A wash-out period of at least one week will allow for complete clearance of the exogenous oral estradiol before testing the pharmacokinetics of sublingual estradiol on the same ten patients in the same manner. On day 2 of study, subject will take estradiol 1 mg sublingually after time 0 blood draw, supervised by a research team member to ensure proper dissolution. Blood will be drawn at hours 0,1,2,3,4,6,8 as on day 1 of study. Receives: Drug: Estradiol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Serum Concentration of Estradiol
Measured: 8 hours
Area Under the Serum Concentration Versus Time Curve
Mean for Area Under the Curve(AUC) for sublingual estradiol.
Measured: 8 hours
Oral Clearance of Estradiol
Measured: 8 hours
Secondary outcomes (1)
Ratio of Estrone to Estradiol
Descriptive statistics, such as mean for ratio of estrone to estradiol
Measured: 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2019
- Study start23 Sep 2019
- Primary completion13 Jul 2020
- Study completion13 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Transgender PersonsStudies 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
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jenna Sarvaideo, Medical College of Wisconsin
- Investigators
- Jenna L Investigator, DO, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04036500
- Sponsor's protocol ID
- PRO00035015
- Status last verified
- Apr 2025
- First submitted
- 25 Jul 2019
- Last updated
- 11 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data that underlie results in a publication.
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sublingual Estradiol Versus Oral Estradiol in Transgender Women
- ClinicalTrials.gov ID
- NCT04036500
- Acronym / sponsor ID
- PRO00035015
- Conditions
- Transgender Persons
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- 23 Sep 2019 (actual)
- Primary completion
- 13 Jul 2020 (actual)
- Study completion
- 13 Jul 2020 (actual)
- First posted
- 29 Jul 2019 (actual)
- Results
- Posted 1 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Blogs, word-of-mouth, and small studies from the 1990s in the premature ovarian insufficiency and menopause populations have suggested sublingual or transdermal estradiol may be safer and/or more effective than an oral formulation. Sublingual administration entails holding the estrogen tablet under the tongue and allowing it to dissolve, where its absorption is enhanced by the rich vascularization under the tongue. According to Price et al., sublingual administration results in rapid absorption with significantly higher estradiol levels than does comparable oral dosing. This is likely because sublingual administration will bypass metabolism by the intestines and liver. The transdermal route, which also bypasses first-pass metabolism, is not associated with an increased venous thromboembolic risk nor a significant increase in plasma triglycerides or HDL-cholesterol levels. As such, transdermal estrogen is often preferred over oral formulations, although it is relatively expensive and not accessible to many transgender women. Conversely, sublingual administration of estrogen tablets is widely available and could be a cost-effective alternative to transdermal estrogen. However, there are no well-conducted studies that have evaluated the safety and efficacy of sublingual estrogen therapy in the transgender population. This pilot study will elucidate how estrogen levels in the blood change following sublingual versus oral administration of estradiol in transgender women. This data may be used later to design larger studies on safety and efficacy.
Additionally, analyzing a dosage method that patients themselves have tried independently and found effective is also important. This approach incorporates intelligence from the transgender community into our research, creating new knowledge that is supported by data but is founded in existing community insights. Thus, the outcomes of this research have the potential to integrate patient input while also aiding in the development of safety recommendations, with the goal of better caring for our transgender patients.
Primary aim. To establish the pharmacokinetics of sublingual estradiol versus oral estradiol in transgender women.
Detailed description
Patient will plan on being in the Adult Translational Research Unit (A-TRU) for 8 hours. They will be assigned to a suite. They will get 7 blood draws at hours 0,1,2,3,4,6,8 and vitals at the beginning of the visit. Vitals will include height, weight, blood pressure, respiration rate, and pulse. Subject is able to eat while in the A-TRU. Day 1 patient will take estradiol 1 mg ORALLY after time 0 blood draw. The medication will be given by registered nurse. A wash-out period of at least one week will allow for complete clearance of the exogenous oral estradiol before testing the pharmacokinetics of sublingual estradiol on the same ten patients in the same manner. Subject cannot take any hormone replacement therapy between their research appointments. On day 2, subject will take estradiol 1 mg SUBLINGUALLY after time 0 blood draw, supervised by a research team member to ensure proper dissolution. Blood will be drawn at hours 0,1,2,3,4,6,8 as on day 1.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Estradiol 1 mg oral first, then Estradiol 1 mg sublingual | Experimental | Drug: EstradiolSubjects will take estradiol 1 mg orally after time 0 blood draw. They will get 7 blood draws at hours 0,1,2,3,4,6,8. A wash-out period of at least one week will allow for complete clearance of the exogenous oral estradiol before testing the pharmacokinetics of sublingual estradiol on the same ten patients in the same manner. On day 2 of study, subject will take estradiol 1 mg sublingually after time 0 blood draw, supervised by a research team member to ensure proper dissolution. Blood will be drawn at hours 0,1,2,3,4,6,8 as on day 1 of study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Transgender male-to-female
- Naive to hormone therapy
- English speaker
- 18 years of age or older
Key exclusion criteria (11 listed)
- History of hormone replacement therapy
- Orchiectomy
- Needle phobia
- Serious bleeding condition
- Active deep vein thrombosis, pulmonary embolism or history of these conditions
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 |
|---|---|---|
| EstradiolPatients will be given estradiol: 1 mg oral and 1 mg sublingual. | Drug | Estradiol 1 mg oral first, then Estradiol 1 mg sublingual |
Primary outcome
Maximum Serum Concentration of Estradiol
Time frame: 8 hours
Area Under the Serum Concentration Versus Time Curve
Time frame: 8 hours
Mean for Area Under the Curve(AUC) for sublingual estradiol.
Oral Clearance of Estradiol
Time frame: 8 hours
1 secondary outcome
Ratio of Estrone to Estradiol
Time frame: 8 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. All individual participant data that underlie results in a publication.
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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. This study is not recruiting at the moment.
Jenna L Investigator, DO principal investigator
Medical College of Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Estradiol in people with Transgender Persons, run by Medical College of Wisconsin 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 4 inclusion and 11 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: finished, as of the sponsor's last update on 11 Apr 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Serum Concentration of Estradiol (time frame: 8 hours). The study lists 3 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 11 Apr 2025.