Androgen Effects on the Reproductive Neuroendocrine Axis

July 19, 2025 updated by: Antoni Duleba, University of California, San Diego
This research study investigates whether male-level exogenous androgens inhibit the reproductive neuroendocrine axis in otherwise healthy (non-PCOS) females.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Testosterone Replacement Therapy (TRT) is the mainstay of gender affirming care for transgender men (TGM) who have male gender identity after female sex assignment at birth. TGM receiving TRT over time exhibit irregular menstrual bleeding, however, the mechanism of menstrual disruption is unknown. Therefore, the investigators propose to evaluate the effect of chronic testosterone (T) exposure on ovarian hormones and pituitary gonadotropin release that determines menstrual cyclicity. The investigators will conduct a detailed study of blood reproductive hormone secretion in TGM before and during TRT as well as in untreated cisgender female (CGF) control subjects who report female gender identity congruent with female sex assignment at birth. The investigators will also perform periodic clinical and ultrasonographic evaluations.

Study Type

Interventional

Enrollment (Actual)

2

Phase

  • Phase 4

Contacts and Locations

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

Study Locations

  • United States
    • California
      • San Diego, California, United States, 92037
        • University of California San Diego

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

Accepts Healthy Volunteers

Yes

Study Population

Transgender men/non-binary/gender non-conforming who are initiating gender-affirming testosterone replacement therapy as part of their medical care. The investigators will also study a control group of cisgender females who are not receiving testosterone.

Description

Inclusion Criteria: Transgender/Non-binary Group, Initiating Testosterone Group

  • Provision of signed and dated informed consent form
  • Stated willingness to comply with all study procedures and availability for the duration of the study
  • Aged 18-35
  • Plan to initiate testosterone therapy
  • History of regular menstrual cycles (every 24-35 days) at baseline, before beginning TRT

Inclusion Criteria: Cisgender Female Group

  • Provision of signed and dated informed consent form
  • Stated willingness to comply with all study procedures and availability for the duration of the study
  • Aged 18-35
  • Having regular menstrual cycles (every 24-35 days)

Exclusion Criteria: All

  • Pregnant
  • Incarcerated
  • Known cognitive impairment or institutionalized
  • Hemoglobin less than 11 gm/dl at screening evaluation
  • Weight less than 110 pounds
  • BMI <18 or >35
  • Current endocrine disease- including untreated thyroid abnormalities, pituitary or adrenal disease, polycystic ovary syndrome, or androgen producing tumor
  • Current or recent pregnancy within two months of study enrollment
  • Current or recent breast feeding within two months of study enrollment
  • Diabetes, or renal, liver, or heart disease
  • History of oophorectomy or hysterectomy
  • History of radiation or surgery involving brain structures and/or pelvis/pelvic organs
  • Currently taking any medications that may affect their reproductive hormones, such as contraceptive medications, androgens, estrogens, progestins, GnRH antagonists, GnRH agonists, insulinomimetics, and metformin.
  • History of prior testosterone therapy

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

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: TGM initiating TRT
Transgender men/non-binary/non-gender-conforming initiating testosterone replacement therapy
Drug: Testosterone Cypionate 50 MG/ML Injectable Solution
Participants in the initiating group will receive weekly doses of testosterone for gender-affirming care.
Other Names:
  • Testosterone Replacement Therapy
No Intervention: CGF control group
Cisgender females serving as a control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evidence of Luteal Activity (ELA)
Time Frame: Through study completion, an average of 7 months.
Evidence of Luteal Activity (ELA), as defined by serum progesterone level above 3 ng/mL in transgender men initiating testosterone replacement therapy.
Through study completion, an average of 7 months.
Determination of Pulsatile LH Secretion
Time Frame: Through study completion, an average of 7 months.
Subjects will have baseline measurement of serum LH immediately followed by frequent blood sampling at 10-min intervals for 8 h. We will measure LH pulse frequency, the number of LH pulses per 8 hours.
Through study completion, an average of 7 months.
Uterine Bleeding Pattern.
Time Frame: Through study completion, an average of 7 months.
All subjects will complete a daily uterine bleeding log using REDCap®
Through study completion, an average of 7 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate Serum Reproductive Hormones
Time Frame: Through study completion, an average of 7 months.
Measurement of serum FSH, AMH, LH, estradiol, and testosterone levels
Through study completion, an average of 7 months.

Collaborators and Investigators

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

Sponsor

University of California, San Diego

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institutes of Health (NIH)

Investigators

  • Principal Investigator: Antoni Duleba, MD, UC San Diego

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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)

February 26, 2025

Primary Completion (Actual)

February 26, 2025

Study Completion (Actual)

March 3, 2025

Study Registration Dates

First Submitted

April 30, 2024

First Submitted That Met QC Criteria

June 3, 2024

First Posted (Actual)

June 10, 2024

Study Record Updates

Last Update Posted (Actual)

July 22, 2025

Last Update Submitted That Met QC Criteria

July 19, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 808679
  • 1R01HD111650-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

We will not be sharing IPD.

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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