An Early Phase 1 interventional study of Estradiol in Transgender Persons, sponsored by Medical College of Wisconsin. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-04-11.
Sponsored by Medical College of Wisconsin · Early Phase 1, Interventional, and Treatment
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.
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.
Medical College of Wisconsin is the lead sponsor of 540 studies on the registry; 120 are open to participants now.
Of its 71 completed or terminated interventional studies of FDA-regulated products, 56 (79%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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.
Drug: Estradiol
Patients will be given estradiol: 1 mg oral and 1 mg sublingual.
Maximum Serum Concentration of Estradiol
Time frame: 8 hours
Area Under the Serum Concentration Versus Time Curve
Mean for Area Under the Curve(AUC) for sublingual estradiol.
Time frame: 8 hours
Oral Clearance of Estradiol
Time frame: 8 hours
Ratio of Estrone to Estradiol
Descriptive statistics, such as mean for ratio of estrone to estradiol
Time frame: 8 hours
Subjects were recruited by flyers in clinic waiting room and in clinic physician referrals. Subjects were initially screened over the phone with the screening criteria (n=17). There were 11 eligible subjects. One subject signed a consent form, but was withdrawn prior to initiation of the study.
| Milestone | Estradiol 1 mg Oral First, Then Estradiol 1 mg Sublingual |
|---|---|
| Started | 11 |
| Completed | 10 |
| Not completed | 1 |
| pg/mL | Estradiol 1 mg Oral First, Then Estradiol 1 mg Sublingual |
|---|---|
| Max sublingual serum estradiol | 144 ± 90 |
| Max oral serum estradiol | 35 ± 8 |
Mean for Area Under the Curve(AUC) for sublingual estradiol.
| mg*h/L | Estradiol 1 mg Oral First, Then Estradiol 1 mg Sublingual |
|---|---|
| Area Under the Serum Concentration Versus Time Curve | 74.0883 ± 17.18 |
| mL/hour | Estradiol 1 mg Oral First, Then Estradiol 1 mg Sublingual |
|---|---|
| Oral Clearance of Estradiol | NA ± NA |
Descriptive statistics, such as mean for ratio of estrone to estradiol
| Ratio | Estradiol Oral |
|---|---|
| estradiol to estrone ratio, sublingual | 1.1 ± 1 |
| estradiol to estrone ratio, oral | 0.7 ± 0.4 |
Collected over Adverse event data was collected for an 9 day period (time in which participants were in the study). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Oral Estradiol | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) |
| Sublingual Estradiol | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) |
| Age, Categorical(Participants) | Estradiol Oral |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 10 |
| >=65 years | 0 |
| Sex/Gender, Customized(Participants) | Estradiol Oral |
|---|---|
| Transgender Woman | 10 |
| Ethnicity (NIH/OMB)(Participants) | Estradiol Oral |
|---|---|
| Hispanic or Latino | 1 |
| Not Hispanic or Latino | 9 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Estradiol Oral |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 1 |
| White | 9 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — All individual participant data that underlie results in a publication.
Supporting information: Study protocol, Sap, Icf, Csr
This study is completed, as verified in Apr 2025. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Medical College of Wisconsin