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Hormone Secretion in Transgender Males

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ClinicalTrials.gov Identifier: NCT04321551
Recruitment Status : Not yet recruiting
First Posted : March 25, 2020
Last Update Posted : March 8, 2021
Sponsor:
Information provided by (Responsible Party):
Jeffrey Chang, MD, University of California, San Diego

Brief Summary:
Significant proportions of TGM report desired child-bearing and many engage in receptive vaginal intercourse with cisgender men or transgender women. Despite the frequency of desired fertility among TGM, secondary amenorrhea and associated infertility are common in those undergoing treatment with testosterone. Although testosterone is the mainstay of gender affirming care in this population, the mechanism of androgen-induced menstrual suppression is unknown due to the limited quantity of well-designed, clinical research investigating hypothalamic-pituitary-ovarian function in testosterone-treated TGM. We hypothesize that gender affirming testosterone therapy causes infertility in transgender men through impaired gonadotropin secretion, altered ovarian function, or a combination of these effects. We therefore propose to study the effect of high-dose, exogenous androgen administration on pituitary function, ovarian folliculogenesis, and ovulatory function in transgender men. Please note that administration of testosterone cyprionate, at a dose of 50 mg (T50) per week, will be done at Planned Parenthood of the Pacific Southwest by Dr. Kyle Bukowski. Who is the Associate Medical Director. In the first of our studies, in order to determine whether normal feedback mechanisms responsible for induction of gonadotropin responses to circulating steroid hormones are altered in TGM on testosterone, we will transiently administer steroid hormones and measure resultant changes in gonadotropin secretion among TGM before and during testosterone therapy, and in untreated cisgender female control subjects. In the next study, to determine whether testosterone alters ovarian follicle function and steroidogenesis, we will assess granulosa cell production of estradiol in response to FSH stimulation in TGM before and during testosterone therapy.

Condition or disease Intervention/treatment Phase
Transgenderism Healthy Drug: Recombinant follicle-stimulating hormone Drug: Estradiol Valerate Drug: Progesterone Injectable Phase 4

Detailed Description:

Thirteen transgender men (TGM) and 13 cisgender female (CGF) control subjects with congruent female gender identity and sex will be enrolled in the following studies.

i. Ovarian follicle responses to FSH stimulation All subjects in each study group will undergo assessment of follicle responsiveness to intravenous (i.v.) recombinant FSH (r-FSH) stimulation 150 IU based on our previously published studies. Prior to testosterone treatment in TGM, r-FSH stimulation will be performed in the early follicular phase (EFP) of the cycle to approximate basal serum estradiol levels observed in the testosterone-treated TGM. Blood samples will be obtained before, and at 12 and 24 hours following each i.v. r-FSH injection for measurements of gonadotropins and sex steroid hormones. Subsequent r-FSH stimulation will be conducted on a random day at three- and six- months after testosterone treatment as we expect testosterone-treated TGM to be anovulatory. Blood samples will be obtained before, and at 12 and 24 hours following each i.v. r-FSH injection for measurements of sex steroid hormones.

ii. Gonadotropin responses to steroid hormone feedback On the morning of study day 1 (t=0) of study each subject will have a blood sample drawn in the morning for baseline hormone determinations. Subsequently, an intramuscular (i.m.) injection of estradiol valerate, 5 mg, will be administered. On study day 2 (t=48 hr), each subject will be administered an i.m. injection of progesterone in oil, 50 mg. Blood samples will be obtained t=0, +24, +48, +60, and +72 hr for the assessment of gonadotropin and steroid hormone levels. Serum FSH and LH levels following steroid administration in TGM will be compared to those observed in untreated TGM and CGF.

All subjects in each study group will undergo the same intervention as described above. TGM subjects will be studied during the early follicular phase of the menstrual cycle before and after three and six months of testosterone therapy. Should amenorrhea occur during T50 therapy, then study will be performed on a random day within one week of the three- and six- month time points. Untreated CGF controls will be studied once during the early follicular phase of the menstrual cycle.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 26 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Gonadotropin and Steroid Hormone Secretion in Transgender Males
Estimated Study Start Date : January 1, 2022
Estimated Primary Completion Date : June 30, 2025
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Provocative Hormonal Testing

Recombinant follicle stimulating hormone (r-FSH) will be administered intravenously one time at a dose of 150 IU during the early follicular phase of the first menstrual cycle after enrollment (Menstrual Cycle I).

Subjects will receive no intervention during Menstrual Cycle II (washout cycle).

During the early follicular phase of Menstrual Cycle III, subjects will receive an intramuscular (i.m.) injection of estradiol valerate 5 mg on study day 1, followed by an i.m. injection of progesterone in oil 50 mg on study day 2.

Drug: Recombinant follicle-stimulating hormone
Intravenous injection of recombinant follicle-stimulating hormone 150 IU, once.
Other Names:
  • Gonal-f
  • r-FSH

Drug: Estradiol Valerate
Intramuscular injection of estradiol valerate 5 mg, once

Drug: Progesterone Injectable
Intramuscular injection of progesterone in oil 50 mg, once
Other Name: Progesterone in Oil




Primary Outcome Measures :
  1. Luteinizing Hormone (LH) Level [ Time Frame: Within 48 hours after administration of estradiol valerate and progesterone injectable ]
    Peak serum LH level

  2. Estradiol (E2) Level [ Time Frame: Within 24 hours after administration of recombinant follicle-stimulating hormone level ]
    Peak Serum E2 level


Secondary Outcome Measures :
  1. Follicle Stimulating Hormone (FSH) Level [ Time Frame: Within 48 hours after administration of estradiol valerate and progesterone injectable ]
    Peak serum FSH level



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Cisgender females Transgender males
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Cisgender Female or Transgender Male
  • Regular menstrual cycles
  • For self-identified transgender males, must plan to initiate testosterone therapy for the first time within 3 months of study enrollment

Exclusion Criteria:

  • 1. Hemoglobin less than 11 gm/dl at screening evaluation
  • Untreated thyroid abnormalities
  • Current endocrine disease- including 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
  • BMI > 35
  • Diabetes, or renal, liver, or heart disease
  • History of oophorectomy
  • History of radiation or surgery involving brain structures
  • Current hormonal medication use (including birth control pills and hormone replacement therapy)
  • History of prior testosterone therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04321551


Contacts
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Contact: Tracy N Harrison, MD 858-822-1481 tnharrison@health.ucsd.edu
Contact: Eunice Tingzon 858-534-8930 etingzon@health.ucsd.edu

Sponsors and Collaborators
University of California, San Diego
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Responsible Party: Jeffrey Chang, MD, Professor of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego
ClinicalTrials.gov Identifier: NCT04321551    
Other Study ID Numbers: 200395
First Posted: March 25, 2020    Key Record Dates
Last Update Posted: March 8, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: After data collection has been completed, the investigators plan to upload de-identified study data to clinicaltrials.gov
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Analytic Code
Time Frame: Data will become available within 6 months of study completion, and will be available for a period of 12 months.
Access Criteria: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be shared. Other documents made available include the study protocol, statistical analysis plan, informed consent form, and clinical study report. Data will be available following publication for any purpose. Data are available through proposal directed to rjchang@health.ucsd.edu. To obtain data, requestors will need to sign a data access agreement.

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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
Keywords provided by Jeffrey Chang, MD, University of California, San Diego:
Testosterone therapy
Additional relevant MeSH terms:
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Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Hormones
Estradiol
Polyestradiol phosphate
Progesterone
Follicle Stimulating Hormone
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Estrogens
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female
Progestins