Clinical trial NCT04036500
Conditions: Transgender Persons
Sponsor: Medical College of Wisconsin
Start date: 2019-09-23; Completion date: 2020-07-13
Enrollment: 11 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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. 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.

Arms: arm 1: 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.
Interventions: intervention 1: Estradiol
Intervention descriptions: intervention 1: Patients will be given estradiol: 1 mg oral and 1 mg sublingual.

Protocol documents:
ICF_001.pdf: 
 
 
 
Sublingual Estradiol Versus Oral Estradiol in Transgender Women 
 
Informed Consent Form V2.0, Approved 08Jun2020 
 
NCT04036500 


Medical College of Wisconsin & Froedtert Hospital 
Informed Consent for Research 
Clinical Interventions template - Version: March 30, 2018 
 
IRB Protocol Number: PRO 00035015 
IRB Approval Period: 6/8/2020 – 6/7/2021 
Page 1 of 13 
Version: 2 
 
 
EFFECTIVE 
 
6/8/2020 
 
MCW/FH IRB
 
 
Medical College of Wisconsin and Froedtert Hospital 
INTRODUCTION TO THE INFORMED CONSENT 
 
Name of Subject: ____________________________ 
 
Sublingual Estradiol Versus Oral Estradiol in Transgender Women 
 
Jenna Sarvaideo, DO, Assistant Professor of Medicine 
Department of Medicine 
jsarvaideo@mcw.edu 
(845) 548-4536 
Medical College of Wisconsin 
8701 Watertown Plank Road 
Milwaukee WI 53226 
 
 
You are invited to take part in this research. You can decide whether to take part in this project 
or not. You are free to say yes or no. If there is anything that you do not understand, please ask 
questions. 
 
 
Definitions 
 
Estradiol – Estradiol is a form of estrogen, a sex hormone that helps regulate many 
processes in the body. In estrogen therapy for transgender individuals, it is used for 
its feminizing effects in male-to-female (MTF) patients. 
Sublingual Administration – A way to take a drug that involves holding a tablet 
under the tongue and letting it dissolve.  
Oral Administration – A way of taking a drug that involves swallowing a tablet whole 
Metabolism – Drug metabolism describes how a body interacts with a drug. Many 
parts of the body, such as the liver, are involved in metabolizing drugs. This may 
include anything from changing the structure of the drug to make it more active, to 
breaking down the drug so it can be removed from the body. 
Percutaneous Intravenous Catheter – This refers to an “IV” that is inserted into a 
vein, usually in the arm, that will allow us to draw blood samples. 


Medical College of Wisconsin & Froedtert Hospital 
Informed Consent for Research 
Clinical Interventions template - Version: March 30, 2018 
 
IRB Protocol Number: PRO 00035015 
IRB Approval Period: 6/8/2020 – 6/7/2021 
Page 2 of 13 
Version: 2 
 
 
EFFECTIVE 
 
6/8/2020 
 
MCW/FH IRB
 
Purpose 
This project is being done to learn more about 
sublingual estradiol compared to oral 
estradiol. Understanding the differences in 
absorption and metabolism based on these 
routes of administration will help us to design 
future studies on the safety and efficacy of 
both methods for transgender individuals.  
Length 
 You will be in this research project for two 
full days, which will be about one week 
apart  
 Each of the two days requires about an 8-
hour time commitment 
 
Risks 
This is a brief list of the most commonly seen 
side effects. The full consent form after this 
introduction contains a more complete list of 
potential research risks. 
 
Estradiol risks: 
There are few risks associated with taking 
estradiol in such a short-term dosing schedule 
(two days, one week apart). However, the 
risks of systemic estradiol include: 
 
Swelling 
 
Hypertension 
 
Blood clots  
 
Headache  
 
Mood changes  
 
Skin rash  
 
Weight gain  
 
GI disturbance 
 
Blood Draw risks:  
Risks or discomforts from having your blood 
drawn include: 
 
Bruising or hematoma 
 
Infection from blood draw 
 
Pain from percutaneous intravenous 
catheter 
Procedures 
If you choose to participate, you will be asked 
to spend approximately 8 hours in the Adult 
Translational Research Unit on two different 
days, about one week apart. You will be 
assigned to a suite where you can do 
activities such as eat, watch TV, or read 
during the course of the 8 hours. During that 
time, we will be drawing blood at various 
points to study blood estrogen levels over 
time. 
 
List of visits: 
 
Screening and Information Visit  
- Total Number: 1 
- Total Time: 30 min 
 
Oral Estradiol Visit 
- Total Number: 1 
- Total Time: 8-9 hours 
 
Sublingual Estradiol Visit 
- Total Number: 1 
- Total Time: 8-9 hours 
 
Procedures that will occur at various 
visits: 
Invasive Procedures 
- You will have 7 blood draws taken at 
hours 0,1,2,3,4,6,8 on each of the 
two days. 
 
Non-invasive Procedures 
- Vitals will be taken at the beginning 
of each visit (blood pressure, pulse, 
respiration rate, height, weight) 
- You will be provided estradiol 1 mg 
ORALLY after time 0 blood draw on 
day 1. 


Medical College of Wisconsin & Froedtert Hospital 
Informed Consent for Research 
Clinical Interventions template - Version: March 30, 2018 
 
IRB Protocol Number: PRO 00035015 
IRB Approval Period: 6/8/2020 – 6/7/2021 
Page 3 of 13 
Version: 2 
 
 
EFFECTIVE 
 
6/8/2020 
 
MCW/FH IRB
 
My Other Options 
You do not have to join this project. Your other 
options may include: 
 Joining a different project 
 Routine care for this condition 
 Getting no treatment for this condition 
Benefits 
We don’t know if this project will help you. Your 
condition may get better but it could stay the 
same or even get worse. 
- You will be provided estradiol 1 mg 
SUBLINGUALLY after time 0 blood 
draw on day 2. 
 
If you have more questions about this project at any time, you can call Jenna Sarvaideo at 
(845) 548-4536 
 
If you have questions about your rights as a participant, want to report any problems or 
complaints, or offer input, you can call the MCW/Froedtert Hospital Research Subject 
Advocate at 414-955-8844. 


Medical College of Wisconsin & Froedtert Hospital 
Informed Consent for Research 
Clinical Interventions template - Version: March 30, 2018 
 
IRB Protocol Number: PRO 00035015 
IRB Approval Period: 6/8/2020 – 6/7/2021 
Page 4 of 13 
Version: 2 
 
 
EFFECTIVE 
 
6/8/2020 
 
MCW/FH IRB
CONSENT TO PARTICIPATE IN RESEARCH 
A1. INTRODUCTION – WHY ARE WE ASKING YOU TO PARTICIPATE? 
You are being invited to participate in this research because you are a transgender male-to-
female individual who is naïve to hormone therapy. You meet the requirements of being an 
English speaker, 18 years of age or older, without a severe needle phobia or history of 
orchiectomy. You also do not have a history of breast cancers, active or recent clotting disease 
or liver disease. 
 
A total of about 10 people are expected to participate in this research the Medical College of 
Wisconsin/Froedtert Hospital. 
 
The Director of the project is Jenna Sarvaideo, DO, in the Division of Endocrinology and 
Molecular Medicine at the Medical College of Wisconsin. A research team works with Dr. 
Sarvaideo. You can ask who these people are.  
 
The Endocrine Society and the Medical College of Wisconsin are funding this study. There are 
no financial conflicts or conflicts of interest in this study. 
 
 
A2. DO I HAVE TO PARTICIPATE? 
You can decide whether to take part in this research or not. You are free to say yes or no. If you 
say no, your regular medical care will not change. Even if you join this project, you do not have 
to stay in it. You may stop at any time.  
 
A research project is different from routine medical care in three ways: 1) there are extra risks 
that we will tell you about in this form; 2) you may have some extra medical tests and visits; 3) 
the research procedures, tests and visits follow a set plan that must be kept. 
 
A3. WHY IS THIS PROJECT BEING DONE? 
In this study, we want to find out more about the pharmacokinetics (way a drug is processed by 
the body) of oral and sublingual estradiol in transgender women. This pilot study will investigate 
the estrogen levels in the blood for both routes of administration, which will help us determine 
whether different doses may be necessary for the two methods in transgender women. We are 
looking specifically at these two ways of giving estradiol because it has been suggested that 
sublingual estradiol may be safer and/or more effective than oral administration.   
 
The data from this pilot study may be used later to design larger studies on safety and efficacy, 
since there are no well-conducted studies that have evaluated how effective or safe sublingual 
estrogen therapy is in the transgender population. Estradiol has been approved by the FDA for 
use in biologic females, but its use in transgender women is considered “off-label.” We hope to 
obtain data that will increase our understanding of its use in transgender women as well. 
 
This study will likely not help you directly. We hope the information from this study will help us 
develop a better understanding of the pharmacokinetics of sublingual estradiol in transgender 


Medical College of Wisconsin & Froedtert Hospital 
Informed Consent for Research 
Clinical Interventions template - Version: March 30, 2018 
 
IRB Protocol Number: PRO 00035015 
IRB Approval Period: 6/8/2020 – 6/7/2021 
Page 5 of 13 
Version: 2 
 
 
EFFECTIVE 
 
6/8/2020 
 
MCW/FH IRB
women. This will allow us to continue studying this potentially safer, more effective option for 
hormone replacement therapy. 
 
 
 
B1. WHAT WILL HAPPEN IF I PARTICIPATE? 
Screening procedures:  
If you decide to join, some screening questions will be asked first to see whether you are 
eligible. A study team member will meet with you in person or over the phone to discuss the 
requirements. To participate in this study, you must: 
- 
Be 18 years or older 
- 
Be a male-to-female transgender individual 
- 
Be an English-speaker 
- 
NOT have had an orchiectomy (surgical removal of one or both testicles) 
- 
NOT have a phobia of needles 
- 
NOT have a serious bleeding disorder 
- 
NOT have a history of breast cancer  
- 
NOT have a known sensitivity or allergy to any components of the medications used 
- 
NOT have active deep vein thrombosis, pulmonary embolism or history of these 
conditions 
- 
NOT have active or recent (e.g., within the past year) arterial thromboembolic disease 
(e.g., stroke, myocardial infarction) 
- 
NOT have liver dysfunction or disease 
- 
Stop taking potent CYP3A4 inhibitors or inducers, as determined by team pharmacist 
- 
NOT be taking a medication that may cause additional physical or mental harm if 
stopped  
 
During this screening visit, you are welcome to ask questions about the study and voice any 
potential concerns. We will also ask you questions about any medications or supplements you 
are taking. If you are taking certain medications that may interact with estrogen, we will ask you 
to go through a washout period for the drug(s).  
Washout: This study may involve a washout period; the length of time will depend on which 
medicine you are taking, since some medicines leave the body faster than others.  A washout 
period is the time that you go without medicine in order to get all of the medicine out of your 
body. This is done to make sure your old medicine does not interact with the drugs (estrogen) in 
the study. The time without medicine may make your condition or symptoms that are treated by 
your medicine worse for a period of time. 
If the screening information shows that you meet the requirements, then you will be able to start. 
The research team will schedule your participation visits based on your availability and the 
availability of the Adult Translational Research Unit. If the screening information shows that you 
cannot be in the research, the research doctor will discuss other options with you and/or refer 
you back to your regular doctor.  
 
Research groups 
Every participant in this study will receive the same drug, in the same dose and route of 
administration. There will be no placebo group, no randomization, and no blinding.  
 
 


Medical College of Wisconsin & Froedtert Hospital 
Informed Consent for Research 
Clinical Interventions template - Version: March 30, 2018 
 
IRB Protocol Number: PRO 00035015 
IRB Approval Period: 6/8/2020 – 6/7/2021 
Page 6 of 13 
Version: 2 
 
 
EFFECTIVE 
 
6/8/2020 
 
MCW/FH IRB
 
 
Summary of Procedures 
 
DAY 1: After determining that you are eligible and scheduling your Day 1 visit and Day 2 visit, 
you will report to the Adult Translational Research Unit (A-TRU) at 7:30 AM on the pre-
scheduled date. The research team and assigned nurse will check you in and escort you to the 
assigned suite within the unit.  
1. Study team or PI will read and discuss this consent form with you. During the 
consenting, you are able to ask questions, voice concerns, and ask for more time to 
process/think about the information. You will have a minimum of 10 minutes—or 
longer if needed—before deciding to sign. 
2. If you consent to participation, the A-TRU nurse will take your vitals. This includes 
collecting your height and weight, taking your pulse and respiration rate, and 
measuring your blood pressure. 
3. The nurse will then draw the first of seven blood draws (time 0 hr).  
4. You will be provided estradiol 1 mg to take ORALLY (swallow whole). 
5. One hour after swallowing the estradiol, the nurse will return to draw your blood 
again (time 1 hr). This will be repeated at time 2,3,4,6, and 8 hr after taking the 
estradiol. You are required to stay within the A-TRU during this 8-hour period. 
a. During your time in the private A-TRU suite, you are free to eat food, which 
can be ordered from the staff present. A bed and TV are provided in the suite. 
b. One of the research team members will be present during the day for you to 
ask questions.  
6. A research team member will meet with you at time 8 hr to discuss the visit and 
ensure your Day 2 visit is scheduled for one week later.  
7. We ask that you refrain from smoking on the morning of your Day 2 visit, this may 
interfere with your tissues ability to absorb the sublingual estradiol. 
 
DAY 2: You will report to the A-TRU at 7:30 AM on the pre-scheduled date. The research team 
and assigned nurse will check you in and escort you to the assigned suite within the unit.  
1. The A-TRU nurse will take your vitals. 
2. The nurse will draw the first of seven blood draws (time 0 hr). 
3. You will be provided estradiol 1 mg to take SUBLINGUALLY. 
a. A research team member will be present to describe the precise way of 
taking the tablet. 
b. You will be instructed to hold the tablet under your tongue until it is entirely 
dissolved. DO NOT swallow the tablet. 
4. One hour after taking the sublingual estradiol, the nurse will return to draw your 
blood (time 1 hr). This will be repeated at time 2,3,4,6, and 8 hr after taking the 
estradiol. You are required to stay within the A-TRU during this 8-hour period. 
a. During your time in the private A-TRU suite, you are free to eat food, which 
can be ordered from the staff present. A bed and TV are provided in the suite. 
b. One of the research team members will be present during the day for you to 
ask questions.  
5. A research team member will meet with you at time 8 hr to discuss the visit. You will 
be provided a brief survey to complete. 
6. You will be given your $100 VISA gift card at the end of your Day 2 participation. 
 


Medical College of Wisconsin & Froedtert Hospital 
Informed Consent for Research 
Clinical Interventions template - Version: March 30, 2018 
 
IRB Protocol Number: PRO 00035015 
IRB Approval Period: 6/8/2020 – 6/7/2021 
Page 7 of 13 
Version: 2 
 
 
EFFECTIVE 
 
6/8/2020 
 
MCW/FH IRB
The blood draw samples will be sent to Wisconsin Diagnostic Laboratories and provided to 
ARUP for analysis. ARUP stands for Associated Regional and University Pathologists. ARUP is 
a national reference laboratory based in Salt Lake City, UT that provides laboratory testing 
services for Wisconsin Diagnostic Laboratories. Serum levels of estradiol and estrone will be 
measured by LC-MS (liquid chromatography mass spectrometry). Liquid chromatography-mass 
spectrometry is a lab technique used to make measurements in many types of samples, 
including blood and urine. Liquid chromatography is used to separate different components of 
the sample. Then, mass spectrometry is used to measure a chemical "signature" unique to 
individual compounds and determine their concentration. In this study, liquid chromatography-
mass spectrometry will be used to measure the concentration of estrogen in the blood.  
 
B2. HOW LONG WILL I BE IN THE PROJECT? 
 You will be in this research project for about two weeks, with two days of study procedures 
in the A-TRU. 
 You will take the estradiol a total of two times: Day 1, and about one week later on Day 2  
 
B3. CAN I STOP BEING IN THE PROJECT?   
You are free to withdraw from the project at any time. If you leave, your regular medical care will 
not change. If you are thinking about leaving, please tell the research doctor.  
The research doctor may take you out of this project at any time. This would happen if: 
 
They think it is in your best interest. 
 
You do not follow the project rules. 
 
The whole project is stopped. 
If this happens, the research doctor will tell you. 
 
C1. WHAT HEALTH RISKS OR PROBLEMS CAN I EXPECT FROM THE PROJECT? 
There are risks to taking part in any research project. There is a risk that you may experience 
unexpected effects during the blood draws that will not help your condition or may make it 
worse.  There also may be problems (side effects) we do not know about yet, from estradiol 
itself, or how it combines with other drugs you are taking. If we learn about new important side 
effects, we will tell you.  
 
We watch everyone in the project for problems (side effects). You need to tell the research 
doctor or a member of the research team immediately if you experience any problems, 
side effects, or changes in your health. 
 
 
C2. RISKS OF ESTRADIOL 
The research drug, estradiol, may cause problems (side effects).  Side effects may be mild or 
very serious.  Some can last a long time or never go away.   


Medical College of Wisconsin & Froedtert Hospital 
Informed Consent for Research 
Clinical Interventions template - Version: March 30, 2018 
 
IRB Protocol Number: PRO 00035015 
IRB Approval Period: 6/8/2020 – 6/7/2021 
Page 8 of 13 
Version: 2 
 
 
EFFECTIVE 
 
6/8/2020 
 
MCW/FH IRB
Systemic estradiol is associated with many adverse effects including, but not limited to swelling, 
hypertension, blood clots, headache, mood changes, skin rash, weight gain and GI disturbance. 
These effects may occur by many routes of estradiol administration, including oral and 
sublingual. Many go away soon after you stop taking the estradiol, and it is important to note 
that drugs can affect individuals in many different ways.  
 
The side effects that other people have experienced so far with the sublingual estradiol are 
minimal. In the Price et al study from 1997, one of the only studies to examine sublingual 
estradiol dosing, subjects tolerated sublingual administration well. Subjects reported no taste or 
other sensation, and the tablet dissolved quickly, within approximately 1-2 minutes.  
 
Washout Period: This study will involve a washout period of 7 days between the first dose of 
estradiol (oral) and the second dose of estradiol (sublingual). A washout period is the time that 
you go without medicine in order to get all of the medicine out of your body. This is done to 
make sure the previous dose of estradiol does not impact the results of the second dose.  
 
C3. OTHER RISKS OF THIS RESEARCH PROJECT 
The frequency of blood draws during this project may pose some risk to you. If you are anxious 
around needles, this may cause you emotional or psychological distress. You may experience 
some pain in the region of the venipuncture during or after the blood draw, as well as bruising or 
hematoma. Despite proper sterilization and precautionary measures, it is also possible to 
acquire an infection as a result of peripheral intravenous catheters. 
 
Additional risks include loss of confidentiality.  
 
C4. REPRODUCTIVE RISKS 
We do not anticipate any reproductive risks from participating in this study. 
 
C5. ARE THERE ANY BENEFITS TO TAKING PART IN THE PROJECT? 
This study is not likely to help you, but we hope the information from this study will help us 
develop a better understanding of how sublingual estradiol is metabolized in transgender 
individuals. The data that we collect on the pharmacokinetics of estradiol from your participation 
may contribute to the limited body of research in transgender medicine. Furthermore, from the 
data we collect in this study, we will be better able to design future studies on sublingual 
estradiol and investigate whether it is an effective alternative to oral estradiol. This may lead to 
better safety and efficacy information about estrogen replacement therapy in the transgender 
population. 
 
 
D1. ARE THERE ANY COSTS TO BEING IN THE PROJECT? 
 There are no direct costs to you for any of the services you receive in this project, which 
includes time spent in the A-TRU, blood draw expenses, lab expenses, and estradiol tablets. 
If you have questions regarding costs, please contact Dr. Sarvaideo. 


Medical College of Wisconsin & Froedtert Hospital 
Informed Consent for Research 
Clinical Interventions template - Version: March 30, 2018 
 
IRB Protocol Number: PRO 00035015 
IRB Approval Period: 6/8/2020 – 6/7/2021 
Page 9 of 13 
Version: 2 
 
 
EFFECTIVE 
 
6/8/2020 
 
MCW/FH IRB
 Potential outside costs to you from being in this project are related to the time requirement 
(two 8-hour days spent in the Translational Research Unit). This may require missing work, 
school, or additional obligations on these dates. The research team will work with you to 
schedule your involvement on days that work well for you, but preferred dates are not 
guaranteed. If you have questions regarding costs, please contact Dr. Sarvaideo.  
 
If you participate in this research, the costs of any necessary emergency medical treatment in 
the event of a research-related injury will be billed to you or your health insurance. 
 
D2. WILL I BE PAID FOR PARTICIPATING IN THE PROJECT? 
 You will receive $50.00 in the form of a VISA gift card for the Day1 visit and the Day 2 visit, 
for a total of $100.00. The study team will give the gift card to you at the end of the Day 2 
visit. 
 
 
D3. WHAT OTHER HEALTHCARE CHOICES DO I HAVE? 
You do not have to join this project. You are free to say yes or no. If you do not join this project, 
your research doctor can discuss other healthcare choices with you.  
Your other choices may include: 
 
Beginning hormone replacement therapy sooner, rather than delaying until after 
participating in the study 
 
Joining a different research project 
 
The research doctor can explain both the possible benefits and the risks of other options that 
are available to you. 
 
D4. WILL I BE GIVEN NEW INFORMATION ABOUT THE PROJECT? 
If we learn any important new information estradiol that might change your mind about being in 
the project, we will tell you about it right away.  You can then decide if you want to stay in the 
project. 
 
When research biospecimens such as blood are collected and analyzed , there is the chance of 
finding something clinically relevant. There may be benefits to learning such results (such as 
early detection and treatment of a medical condition), but there are risks as well (such as feeling 
worried about a finding for which no treatment is required or appropriate).   
 
In this study, you will be informed of any findings of possible clinical significance that may be 
discovered during review of results from your research blood samples. The results of your 
research estradiol and estrone levels will not be placed in your medical record.  
 
The results from the estradiol and estrone levels we collect in this research study are the same 
quality as what you would receive as part of your health care. The estradiol and estrone levels 
will be reviewed by a physician who normally reads such results. We will provide you with this 
information so that you may discuss it with your primary care physician. This information will be 
provided only if a participant asks for their lab results, in which case both estradiol and estrone 
levels will be shared. 


Medical College of Wisconsin & Froedtert Hospital 
Informed Consent for Research 
Clinical Interventions template - Version: March 30, 2018 
 
IRB Protocol Number: PRO 00035015 
IRB Approval Period: 6/8/2020 – 6/7/2021 
Page 10 of 13 
Version: 2 
 
 
EFFECTIVE 
 
6/8/2020 
 
MCW/FH IRB
 
 
D5. WHAT HAPPENS IF I AM INJURED BECAUSE I TOOK PART IN THE PROJECT?  
Emergency medical treatment for injuries directly related to your participation in this research 
project will be provided to you. You or your health insurance will be billed for the costs of this 
emergency treatment.  MCW will decide on a case by case basis if they will reimburse you or 
your insurer for emergency treatment costs.  If your research-related injury requires medical 
care beyond this emergency treatment, you or your insurer will be responsible for the costs of 
this follow-up care.  
 
At this time, there is no plan for any additional financial payments. 
 
If you believe that you have been injured because of your participation in this project, contact 
the research doctors right away.  Contact information: Jenna Sarvaideo, (845) 548-4536,  
jsarvaideo@mcw.edu  
 
Nothing in this consent form affects any legal rights you may have nor does it release the 
investigator, the sponsor, the institution, or its agents from liability for negligence. 
 
D6. WHO CAN ANSWER MY QUESTIONS ABOUT THE PROJECT? 
If you have more questions about this project at any time, you can call Jenna Sarvaideo at 
jsarvaideo@mcw.edu, (845) 548-4536. 
 
If you have questions about your rights as a research participant, want to report any 
problems or complaints, or offer input, you can call the MCW/Froedtert Hospital Research 
Subject Advocate at 414-955-8844. 
 
E. PERMISSION TO COLLECT, USE AND SHARE HEALTH INFORMATION 
 
E1. What health information will be collected and used for this project? 
To be in this research project, the research team needs your permission to access, collect and 
use some of your health information. If you say no, you cannot be in the project. This 
information may come from questions we ask, forms we ask you to fill out, or your medical 
record, as described below. We will only collect and use information needed for the project. 
 
The protected health information (PHI) originates from services you will or have received at one 
or more of the following locations: the Medical College of Wisconsin (MCW); BloodCenter of 
Wisconsin (BCW); Children’s Hospital of Wisconsin (CHW); any Froedtert Health Affiliate- 
Froedtert Memorial Lutheran Hospital (FMLH), Inc.; Community Memorial Hospital (CMH) 
Menomonee Falls, Inc.;  St. Joseph’s Community Hospital (SJH) West Bend, Inc.;  Froedtert & 
The Medical College of Wisconsin Community Physicians Clinics, Inc. (FMCWCP); the West 
Bend Surgery Center, LLC; and the Froedtert Surgery Center, LLC.  
 
The health information to be collected and used for this project is:  
 Medical records of the care you receive for this project 
 Lab values (estradiol, estrogen serum levels) from your blood samples 


Medical College of Wisconsin & Froedtert Hospital 
Informed Consent for Research 
Clinical Interventions template - Version: March 30, 2018 
 
IRB Protocol Number: PRO 00035015 
IRB Approval Period: 6/8/2020 – 6/7/2021 
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E2. Who will see the health information collected for this project? 
The only MCW/Froedtert Hospital employees allowed to handle your health information are 
those on the research team, those on the Institutional Review Board (IRB) and those who check 
on the research activities to make sure the hospital’s rules are followed. 
 
If the costs of any necessary emergency medical treatment in the event of a research-related 
injury are billed to your health insurance, your health information may need to be disclosed to 
the insurer for billing purposes. 
 
Because this project involves the use of drugs and/or devices, the FDA also has the right to 
inspect all project records. 
 
We may record your research information, including results of tests and procedures done for 
research, in your Froedtert Hospital and/or Medical College of Wisconsin medical record. As a 
result, this research information may be seen by people allowed to see your medical records for 
healthcare operations or treatment, by those you allow to see your medical records by giving 
written permission, and by others when required by law. 
 
We will not use your personal health information for a different project without your permission 
or the permission of a hospital research review board (IRB). Once all personal identification is 
removed from your health information and biospecimens, the information and/or biospecimens 
may be used for future research or distributed to another investigator for future research without 
additional informed consent from you or your legally authorized representative. The information 
might also be used or released for other purposes without asking you. Results of the project 
may be presented in public talks or written articles, but no information will be presented that 
identifies you. 
 
E3. What are the risks of sharing this health information? 
One risk of taking part in a research project is that more people will handle your personal health 
information collected for this project. The research team will make every effort to protect the 
information and keep it confidential, but it is possible that an unauthorized person might see it. 
Depending on the kind of information being collected, it might be used in a way that could 
embarrass you or affect your ability to get insurance. If you have questions, you can talk to the 
research doctor about whether this could apply to you.  
 
E4. How long will you keep the health information for this project? 
If you sign this form, we plan to keep your information for 10 years, as required by MCW policy, 
in case we need to check it again for this project. 
 
E5. Can I cancel my permission to share this health information? 
If you change your mind later and do not want us to collect or share your health information, you 
need to send a letter to Jenna Sarvaideo at: 
 
 


Medical College of Wisconsin & Froedtert Hospital 
Informed Consent for Research 
Clinical Interventions template - Version: March 30, 2018 
 
IRB Protocol Number: PRO 00035015 
IRB Approval Period: 6/8/2020 – 6/7/2021 
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Medical College of Wisconsin 
Division of Endocrinology  
8701 Watertown Plank Road 
Milwaukee WI 53226 
 
You can also email Dr. Sarvaideo at jsarvaideo@mcw.edu. The letter must say that you have 
changed your mind and do not want the researcher to collect and share your health information. 
At that time, we may decide that you cannot continue to be part of the project. We may still use 
the information we have already collected. 
 
F1. FOR MORE INFORMATION ABOUT THE PROJECT 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov as required by 
U.S. Law. This Web site will not include information that can identify you. At most, the Web site 
will include a summary of the results. You can search this Web site at any time. 
 
You can look up this project by referring to the ClinicalTrials.gov number (NCT04036500) or by 
asking the research team for a printed copy.    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Medical College of Wisconsin & Froedtert Hospital 
Informed Consent for Research 
Clinical Interventions template - Version: March 30, 2018 
 
IRB Protocol Number: PRO 00035015 
IRB Approval Period: 6/8/2020 – 6/7/2021 
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CONSENT TO PARTICIPATE 
 
By signing my name below, I confirm the following: 
 
I have read (or had read to me) this entire consent document.  
All of my questions have been answered to my satisfaction. 
 
The project’s purpose, procedures, risks and possible benefits have been explained to me.   
 
I agree to let the research team use and share the health information and other information 
gathered for this project. 
 
I voluntarily agree to participate in this research project. I agree to follow the procedures as 
directed. I have been told that I can stop at any time. 
 
IMPORTANT: You will receive a signed and dated copy of this consent form.  Please keep it 
where you can find it easily.  It will help you remember what we discussed today. 
 
 
 
 
 
Subject's Name please print  
Subject's Signature 
Date    
 
 
 
 
Name of person discussing/ 
obtaining consent please print  
Signature of person 
discussing/obtaining consent 
Date 
 
 
 
 
Name of Principal Investigator         
__ I participated in consent process 
__ I acknowledge enrollment of this 
subject into the project 
Signature of Principal 
Investigator 
Date 
 

Prot_000.pdf: 
Sublingual Estradiol Versus Oral Estradiol in 
Transgender Women 
NCT04036500 
Protocol last modified 3/14/2021 


Sublingual Estradiol Versus Oral Estradiol in Transgender Women 
Protocol Summary 
Primary aim. To establish the pharmacokinetics of sublingual estradiol versus oral 
estradiol. 
Secondary aim. To compare estradiol by LC-MS/MS to estradiol by immunoassay. 
Design: To illuminate the pharmacokinetic parameters of sublingual estradiol in transgender 
women, a pilot crossover study will be conducted. Ten participants, transgender male-to-female 
patients who are naïve to hormone therapy, will be recruited from the Medical College of 
Wisconsin’s Inclusion Health Clinic.  
Methods: Each participant will be dosed with 1 mg oral estradiol. Blood will be drawn via a 
percutaneous intravenous catheter 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 1 mg on the same ten patients in the same manner. 
Estradiol and estrone by LC-MS/MS will be measured, as well as estradiol by immunoassay. 
These will be sent to ARUP.