Androgen Effects on the Reproductive Neuroendocrine Axis

Phase 4

Recruiting

• Conditions: Transgenderism; Reproductive Issues
• Interventions: Drug: Testosterone Cypionate 50 MG/ML Injectable Solution

• Registration Number: NCT06450405
• Lead Sponsor: University of California, San Diego

Brief Summary

This research study investigates whether male-level exogenous androgens inhibit the reproductive neuroendocrine axis in otherwise healthy (non-PCOS) females.

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 Timeline

• Study First Submitted: 2024-04-30
• Study First Submitted QC: 2024-06-03
• Study First Posted: 2024-06-10
• Status Verified: 2025-02
• Study Start: 2025-02-26
• Last Update Submitted: 2025-02-26
• Last Update Posted: 2025-02-28
• Primary Completion: 2028-11-15
• Study Completion: 2028-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TGM initiating TRT	Testosterone Cypionate 50 MG/ML Injectable Solution	Transgender men/non-binary/non-gender-conforming initiating testosterone replacement therapy

Primary Outcome Measures

Name	Time	Method
Evidence of Luteal Activity (ELA)	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.
Determination of pulsatile LH secretion	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.
Uterine bleeding pattern.	Through study completion, an average of 7 months.	All subjects will complete a daily uterine bleeding log using REDCap®

Secondary Outcome Measures

Name	Time	Method
Evaluate serum reproductive hormones	Through study completion, an average of 7 months.	Measurement of serum FSH, AMH, LH, estradiol, and testosterone levels

Trial Locations

Locations (1)

University of California San Diego; 🇺🇸 San Diego, California, United States