Androgen Effects on the Reproductive Neuroendocrine Axis

Transgenderism Clinical Trial

Official title:

Androgen Effects on the Reproductive Neuroendocrine Axis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06450405
• Other study ID #: 808679
• Secondary ID: 1R01HD111650-01
• Status: Not yet recruiting
• Start date: June 1, 2024
• Est. completion date: June 1, 2029

Study information

• Verified date: June 2024
• Source: University of California, San Diego
• Contact: Antoni Duleba, MD
• Phone: 619-804-4765
• Email: aduleba[@]health.ucsd.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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 urinary and 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. Furthermore, the investigators will monitor menstrual cycles and reproductive hormones in TGM who make the personal decision to discontinue TRT, whether it is to pursue fertility or for other reasons.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: June 1, 2029
• Est. primary completion date: June 1, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

All

1. Provision of signed and dated informed consent form

2. Stated willingness to comply with all study procedures and availability for the duration of the study

3. Aged 18-35

Transgender/Non-binary Group - Initiators

4. Plan to initiate testosterone therapy

5. History of regular menstrual cycles (every 24-35 days) at baseline, before beginning TRT

Transgender/Non-binary Group - Discontinuers 4. Plan to discontinue testosterone therapy 5. History of regular menstrual cycles (every 24-35 days) before beginning TRT

Cisgender Female Group 4. Having regular menstrual cycles (every 24-35 days)

Exclusion Criteria:

All

1. Pregnant

2. Incarcerated

3. Known cognitive impairment or institutionalized

4. Hemoglobin less than 11 gm/dl at screening evaluation

5. Weight less than 110 pounds

6. BMI <18 or >35

7. Current endocrine disease- including untreated thyroid abnormalities, pituitary or adrenal disease, polycystic ovary syndrome, or androgen producing tumor

8. Current or recent pregnancy within two months of study enrollment

9. Current or recent breast feeding within two months of study enrollment

10. Diabetes, or renal, liver, or heart disease

11. History of oophorectomy or hysterectomy

12. History of radiation or surgery involving brain structures

13. Currently taking any medications that may affect their reproductive hormones, such as contraceptive medications, androgens, estrogens, progestins, GnRH antagonists, GnRH agonists, insulinomimetics, and metformin.

For TRT Initiation Group and Cisgender Female group:

14. History of prior testosterone therapy

Related Conditions & MeSH terms

• Reproductive Issues
• Transgenderism

Intervention

Drug:
• Testosterone Cypionate 50 MG/ML Injectable Solution
Participants in the initiating group will receive weekly doses of testosterone for gender-affirming care. Participants in the discontinuing group will receive testosterone during their first month of enrollment and then will cease receiving testosterone. Participants in the discontinuing group will receive testosterone during their first month of enrollment and then will cease receiving testosterone.

Locations

Country	Name	City	State
United States	University of California San Diego	San Diego	California

Sponsors (3)

Lead Sponsor	Collaborator
University of California, San Diego	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (35)

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* Note: There are 35 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evidence of Luteal Activity (ELA)	Evidence of Luteal Activity (ELA), as defined by a 3-fold increase in urinary pregnanediol glucuronide (PdG) level over baseline. Basal urinary PdG levels, normalized to urinary creatinine excretion, will be determined based upon the minimum daily PdG level detected per cycle or 4-wk interval. PdG will be measured via enzyme-linked immunosorbent assay (ELISA).	Through study completion, an average of 7 months.
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.	Through study completion, an average of 7 months.
Primary	Uterine bleeding pattern.	All subjects will complete a daily uterine bleeding log using REDCap®	Through study completion, an average of 7 months.
Secondary	Determination of gonadotropin levels	Measurement of of serum FSH and LH levels, in IU/mL	Through study completion, an average of 7 months.
Secondary	Determination of serum FSH, AMH and testosterone	During testing of LH pulses (Primary outcome 2), FSH, AMH and testosterone levels will be measured hourly.	Through study completion, an average of 7 months.
Secondary	Determination of ovarian/uterine morphology: Presence of corpus luteum	TGN will undergo weekly ultrasound (US) following TRT initiation for confirmation of corpus lutes (CL) formation (Yes/No).	Through study completion, an average of 7 months.
Secondary	Determination of ovarian/uterine morphology: Thickness of endometrium	TGN will undergo weekly ultrasound (US) following TRT initiation to measure endometrial thickness (mm).	Through study completion, an average of 7 months.
Secondary	Determination of ovarian/uterine morphology: Ovarian astral follicle count.	TGN will undergo weekly ultrasound (US) following TRT initiation to measure astral follicle count (AFC).	Through study completion, an average of 7 months.
Secondary	Determination of ovarian/uterine morphology: volume of uterus and ovaries	TGN will undergo weekly ultrasound (US) following TRT initiation to measure volume of uterus and ovaries (mL).	Through study completion, an average of 7 months.

External Links

•   Pfizer Inc. Depo®-Testosterone (testosterone cypionate injection, USP0 [package insert]. U.S. Food and Drug Administration website.