Effect of Progesterone on Testosterone Concentrations and Breast Development in Transwomen

• Purpose. The purpose of this research is study the effect of progesterone therapy on testosterone levels in transwomen who are currently on gender affirming treatment with estradiol.
• Duration. It is expected that participation will last for 6 months (24 weeks).
• Study Procedures. Participants will be asked to sign an informed consent, complete a medical history, have a physical exam conducted, have a fasting blood sample taken and asked to take a study drug once daily.
• Risks. Some of the foreseeable risks or discomforts include temporary discomfort, bleeding, bruising and/or swelling in the arm from blood draw. There are no known direct risks with the use of Progesterone in Transwomen for gender affirming therapy.
• Benefits. Some of the possible benefits that may be expected include increase in fat mass, increase in breast size/fullness, decrease in masculine hair patterns.

Study Overview

• Status: Terminated
• Conditions: Transgender Persons
• Intervention / Treatment: Drug: Progesterone 200 MG; Drug: Placebo

Detailed Description

The number of individuals with gender incongruence who present to their physician for hormone therapy has increased manifold in the last decade. Testosterone therapy in transgender men (also known as female-to-male transgender or transmen) and estrogen therapy in transgender women (also known as male-to-female transgender or transwomen) respectively is the mainstay of hormone regimen.Transwomen, who are genetically men, receive estradiol replacement with the aim of suppressing serum testosterone and achieving serum estradiol concentrations that mimic the serum concentrations of biological women. This leads to an increase in fat mass, breast growth and decreases in lean mass and masculine pattern hair. However, the results of these changes are often less than satisfactory and additional therapy is required.

Breast development is a major concern for transgender females. There is a great deal of variability among individuals, as evidenced during pubertal development.Transgender women do not achieve the same level of breast development as cisgender women do after puberty. Typically, transgender women plateau at Tanner stage III and half of the transgender women have a AAA cup size or less.Investigators plan to conduct a randomized, placebo controlled double blind study evaluating the effect of adding progesterone for 6 months to transwomen who are being treated with estradiol. The hypothesis is that progesterone will decrease serum testosterone concentrations as compared to placebo and increase breast size. Investigators will also assess its role in mood, sleep, scalp hair and androgenic hair growth.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sandeep Dhindsa, MD; Phone Number: 3149774911; Email: sandeep.dhindsa@health.slu.edu

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Saint Louis University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Transwomen, currently on treatment with estradiol therapy for at least 6 months (as their standard of care gender affirming therapy)
• Has achieved serum estradiol >100 pg/ml at least once, based on clinical labs in past.

Exclusion Criteria:

1. Treatment with progesterone in the last 2 months
2. HIV
3. Planning to go for breast enhancement or gender reassignment surgery in the next 6 months
4. Known history of peanut allergy (because the study drug contains peanut oil)
5. Active deep vein thrombosis, pulmonary embolism or history of these conditions
6. Active arterial thromboembolic disease or history of these conditions
7. Active cardiovascular disorders or history of these conditions (e.g. myocardial infarction, uncontrolled hypertension >150/90 mmHg)
8. Known, suspected, or history of breast cancer
9. Known liver dysfunction or disease
10. Known or history of gallbladder disease. This does not apply to subjects who have undergone cholecystectomy
11. Known or history of hypertriglyceridemia (>400 mg/dl)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: progesterone; subjects on active drug (progesterone)	Drug: Progesterone 200 MG; Subjects will be randomized to receive generic micronized progesterone 200 mg or placebo tablets, to be taken at bedtime daily.
Placebo Comparator: placebo; subjects on placebo	Drug: Placebo; Subjects will be randomized to receive generic micronized progesterone 200 mg or placebo tablets, to be taken at bedtime daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy: Testosterone	Change from baseline till 24 weeks in serum testosterone concentrations between progesterone and placebo groups. Calculated as testosterone levels at 24 weeks minus baseline	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum luteinizing hormone (LH) concentrations		24 weeks
Serum follicle stimulating hormone (FSH) concentrations		24 weeks
Breast size		24 weeks
Hair growth		24 weeks
Efficacy: sleep	sleep quality will be assessed in the two groups via single-item sleep quality scale (SQS)	24 weeks
Efficacy: mood	Subjects will complete two psychometric tests:-; Body-image concern questions of Body-uneasiness test (BUT-BIC): This questionnaire has 9 questions and is meant to capture worries related to physical appearance. Responses are recorded on a 6 point Likert scale. The mean of all 9 questions is presented as the global severity index.; Symptom-Checklist-K-9 (SCL-K-9) to measure psychological distress level: This questionnaire has 9 questions and is meant to assess overall psychological distress. Responses are recorded on a 5 point Likert scale. The mean of all 9 questions is presented as the global severity index.	24 weeks

Collaborators and Investigators

• Sponsor: St. Louis University
• Investigators: Principal Investigator: Sandeep Singh Dhindsa Dhindsa, MD, St. Louis University

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2020
• Primary Completion (Actual): January 18, 2023
• Study Completion (Actual): January 18, 2023

Study Registration Dates

• First Submitted: August 17, 2020
• First Submitted That Met QC Criteria: August 27, 2020
• First Posted (Actual): September 1, 2020

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Testosterone, breast
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: 31144

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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