Reproductive Issues, Transgenderism
Conditions
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.
Interventions
DRUGTestosterone Cypionate 50 MG/ML Injectable Solution
Participants in the initiating group will receive weekly doses of testosterone for gender-affirming care.
Sponsors
National Institutes of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of California, San Diego
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Evaluate Serum Reproductive Hormones | Through study completion, an average of 7 months. | Measurement of serum FSH, AMH, LH, estradiol, and testosterone levels |
Countries
United States
Participant flow
Recruitment details
The researchers enrolled 2 cisgender female participants before the study was terminated. Enrolled CGFs signed consent forms, but did not participate in any study activities. There is no analyzable data.
Participants by arm
| Arm | Count |
|---|---|
| TGM Initiating TRT Transgender men/non-binary/non-gender-conforming initiating testosterone replacement therapy
Testosterone Cypionate 50 MG/ML Injectable Solution: Participants in the initiating group will receive weekly doses of testosterone for gender-affirming care. | 0 |
| CGF Control Group Cisgender females serving as a control group | 0 |
| Total | 0 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study funding terminated. | 0 | 2 |
Baseline characteristics
| Characteristic | — |
|---|---|
| Region of Enrollment United States | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Determination of Pulsatile LH Secretion
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.
Time frame: Through study completion, an average of 7 months.
Population: The study sponsor terminated the grant funding before any data, besides names and signatures on consent forms, were collected. There are no data to analyze. No data will be analyzed in the future.
Primary
Evidence of Luteal Activity (ELA)
Evidence of Luteal Activity (ELA), as defined by serum progesterone level above 3 ng/mL in transgender men initiating testosterone replacement therapy.
Time frame: Through study completion, an average of 7 months.
Population: The study sponsor terminated the grant funding before any data, besides names and signatures on consent forms, were collected. There are no data to analyze. No data will be analyzed in the future.
Primary
Uterine Bleeding Pattern.
All subjects will complete a daily uterine bleeding log using REDCap®
Time frame: Through study completion, an average of 7 months.
Population: The study sponsor terminated the grant funding before any data, besides names and signatures on consent forms, were collected. There are no data to analyze. No data will be analyzed in the future.
Secondary
Evaluate Serum Reproductive Hormones
Measurement of serum FSH, AMH, LH, estradiol, and testosterone levels
Time frame: Through study completion, an average of 7 months.
Population: The study sponsor terminated the grant funding before any data, besides names and signatures on consent forms, were collected. There are no data to analyze. No data will be analyzed in the future.