Androgen Effects on the Reproductive Neuroendocrine Axis

NCT06450405 | Terminated Phase 4 Results FDA Drug

• 2 other identifiers: 8086791R01HD111650-01
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Transgenderism; Reproductive Issues

Outcome Measures

Primary Outcomes (3)

• 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.

  Through study completion, an average of 7 months.

• 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.

• Uterine Bleeding Pattern.

  All subjects will complete a daily uterine bleeding log using REDCap®

  Through study completion, an average of 7 months.

Secondary Outcomes (1)

• Evaluate Serum Reproductive Hormones

  Through study completion, an average of 7 months.

Study Arms (2)

TGM initiating TRT

ACTIVE COMPARATOR

Transgender men/non-binary/non-gender-conforming initiating testosterone replacement therapy

Drug: Testosterone Cypionate 50 MG/ML Injectable Solution

CGF control group

NO INTERVENTION

Cisgender females serving as a control group

Interventions

Testosterone Cypionate 50 MG/ML Injectable Solution DRUG

Participants in the initiating group will receive weekly doses of testosterone for gender-affirming care.

Also known as: Testosterone Replacement Therapy

TGM initiating TRT

Eligibility Criteria

• Age: 18 Years - 35 Years
• Gender Eligibility Details: Cisgender females; Transgender males/non-binary/gender non-conforming initiating testosterone replacement therapy
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Diego: lead
• National Institutes of Health (NIH): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of California San Diego

San Diego, California, 92037, United States

Location

Related Publications (35)

• Coleman E, Radix AE, Bouman WP, Brown GR, de Vries ALC, Deutsch MB, Ettner R, Fraser L, Goodman M, Green J, Hancock AB, Johnson TW, Karasic DH, Knudson GA, Leibowitz SF, Meyer-Bahlburg HFL, Monstrey SJ, Motmans J, Nahata L, Nieder TO, Reisner SL, Richards C, Schechter LS, Tangpricha V, Tishelman AC, Van Trotsenburg MAA, Winter S, Ducheny K, Adams NJ, Adrian TM, Allen LR, Azul D, Bagga H, Basar K, Bathory DS, Belinky JJ, Berg DR, Berli JU, Bluebond-Langner RO, Bouman MB, Bowers ML, Brassard PJ, Byrne J, Capitan L, Cargill CJ, Carswell JM, Chang SC, Chelvakumar G, Corneil T, Dalke KB, De Cuypere G, de Vries E, Den Heijer M, Devor AH, Dhejne C, D'Marco A, Edmiston EK, Edwards-Leeper L, Ehrbar R, Ehrensaft D, Eisfeld J, Elaut E, Erickson-Schroth L, Feldman JL, Fisher AD, Garcia MM, Gijs L, Green SE, Hall BP, Hardy TLD, Irwig MS, Jacobs LA, Janssen AC, Johnson K, Klink DT, Kreukels BPC, Kuper LE, Kvach EJ, Malouf MA, Massey R, Mazur T, McLachlan C, Morrison SD, Mosser SW, Neira PM, Nygren U, Oates JM, Obedin-Maliver J, Pagkalos G, Patton J, Phanuphak N, Rachlin K, Reed T, Rider GN, Ristori J, Robbins-Cherry S, Roberts SA, Rodriguez-Wallberg KA, Rosenthal SM, Sabir K, Safer JD, Scheim AI, Seal LJ, Sehoole TJ, Spencer K, St Amand C, Steensma TD, Strang JF, Taylor GB, Tilleman K, T'Sjoen GG, Vala LN, Van Mello NM, Veale JF, Vencill JA, Vincent B, Wesp LM, West MA, Arcelus J. Standards of Care for the Health of Transgender and Gender Diverse People, Version 8. Int J Transgend Health. 2022 Sep 6;23(Suppl 1):S1-S259. doi: 10.1080/26895269.2022.2100644. eCollection 2022.

  PMID: 36238954 BACKGROUND

• Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH, Rosenthal SM, Safer JD, Tangpricha V, T'Sjoen GG. Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017 Nov 1;102(11):3869-3903. doi: 10.1210/jc.2017-01658.

  PMID: 28945902 BACKGROUND

• Deutsch MB, Bhakri V, Kubicek K. Effects of cross-sex hormone treatment on transgender women and men. Obstet Gynecol. 2015 Mar;125(3):605-610. doi: 10.1097/AOG.0000000000000692.

  PMID: 25730222 BACKGROUND

• McFarland J, Craig W, Clarke NJ, Spratt DI. Serum Testosterone Concentrations Remain Stable Between Injections in Patients Receiving Subcutaneous Testosterone. J Endocr Soc. 2017 Jul 21;1(8):1095-1103. doi: 10.1210/js.2017-00148. eCollection 2017 Aug 1.

  PMID: 29264562 BACKGROUND

• Nakamura A, Watanabe M, Sugimoto M, Sako T, Mahmood S, Kaku H, Nasu Y, Ishii K, Nagai A, Kumon H. Dose-response analysis of testosterone replacement therapy in patients with female to male gender identity disorder. Endocr J. 2013;60(3):275-81. doi: 10.1507/endocrj.ej12-0319. Epub 2012 Oct 27.

  PMID: 23117148 BACKGROUND

• Conron KJ, Scott G, Stowell GS, Landers SJ. Transgender health in Massachusetts: results from a household probability sample of adults. Am J Public Health. 2012 Jan;102(1):118-22. doi: 10.2105/AJPH.2011.300315. Epub 2011 Nov 28.

  PMID: 22095354 BACKGROUND

• Clark TC, Lucassen MF, Bullen P, Denny SJ, Fleming TM, Robinson EM, Rossen FV. The health and well-being of transgender high school students: results from the New Zealand adolescent health survey (Youth'12). J Adolesc Health. 2014 Jul;55(1):93-9. doi: 10.1016/j.jadohealth.2013.11.008. Epub 2014 Jan 14.

  PMID: 24438852 BACKGROUND

• Kuyper L, Wijsen C. Gender identities and gender dysphoria in the Netherlands. Arch Sex Behav. 2014 Feb;43(2):377-85. doi: 10.1007/s10508-013-0140-y. Epub 2013 Jul 16.

  PMID: 23857516 BACKGROUND

• Van Caenegem E, Wierckx K, Elaut E, Buysse A, Dewaele A, Van Nieuwerburgh F, De Cuypere G, T'Sjoen G. Prevalence of Gender Nonconformity in Flanders, Belgium. Arch Sex Behav. 2015 Jul;44(5):1281-7. doi: 10.1007/s10508-014-0452-6. Epub 2015 Jan 15.

  PMID: 25588709 BACKGROUND

• Meerwijk EL, Sevelius JM. Transgender Population Size in the United States: a Meta-Regression of Population-Based Probability Samples. Am J Public Health. 2017 Feb;107(2):e1-e8. doi: 10.2105/AJPH.2016.303578.

  PMID: 28075632 BACKGROUND

• Meyer IH, Brown TN, Herman JL, Reisner SL, Bockting WO. Demographic Characteristics and Health Status of Transgender Adults in Select US Regions: Behavioral Risk Factor Surveillance System, 2014. Am J Public Health. 2017 Apr;107(4):582-589. doi: 10.2105/AJPH.2016.303648. Epub 2017 Feb 16.

  PMID: 28207334 BACKGROUND

• De Cuypere G, Van Hemelrijck M, Michel A, Carael B, Heylens G, Rubens R, Hoebeke P, Monstrey S. Prevalence and demography of transsexualism in Belgium. Eur Psychiatry. 2007 Apr;22(3):137-41. doi: 10.1016/j.eurpsy.2006.10.002. Epub 2006 Dec 26.

  PMID: 17188846 BACKGROUND

• Zucker KJ, Lawrence AA. Epidemiology of Gender Identity Disorder: Recommendations for the Standards of Care of the World Professional Association for Transgender Health. Int J Transgenderism. 2009;11(1):8-18. doi:10.1080/15532730902799946

  BACKGROUND

• Coleman E, Bockting W, Botzer M, et al. Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People, Version 7. Int J Transgenderism. 2012;13(4):165-232. doi:10.1080/15532739.2011.700873

  BACKGROUND

• Spinder T, Spijkstra JJ, van den Tweel JG, Burger CW, van Kessel H, Hompes PG, Gooren LJ. The effects of long term testosterone administration on pulsatile luteinizing hormone secretion and on ovarian histology in eugonadal female to male transsexual subjects. J Clin Endocrinol Metab. 1989 Jul;69(1):151-7. doi: 10.1210/jcem-69-1-151.

  PMID: 2471710 BACKGROUND

• Pelusi C, Costantino A, Martelli V, Lambertini M, Bazzocchi A, Ponti F, Battista G, Venturoli S, Meriggiola MC. Effects of three different testosterone formulations in female-to-male transsexual persons. J Sex Med. 2014 Dec;11(12):3002-11. doi: 10.1111/jsm.12698. Epub 2014 Sep 24.

  PMID: 25250780 BACKGROUND

• Mueller A, Kiesewetter F, Binder H, Beckmann MW, Dittrich R. Long-term administration of testosterone undecanoate every 3 months for testosterone supplementation in female-to-male transsexuals. J Clin Endocrinol Metab. 2007 Sep;92(9):3470-5. doi: 10.1210/jc.2007-0746. Epub 2007 Jun 19.

  PMID: 17579193 BACKGROUND

• Moravek MB, Kinnear HM, George J, Batchelor J, Shikanov A, Padmanabhan V, Randolph JF. Impact of Exogenous Testosterone on Reproduction in Transgender Men. Endocrinology. 2020 Mar 1;161(3):bqaa014. doi: 10.1210/endocr/bqaa014.

  PMID: 32105330 BACKGROUND

• Wierckx K, Van Caenegem E, Pennings G, Elaut E, Dedecker D, Van de Peer F, Weyers S, De Sutter P, T'Sjoen G. Reproductive wish in transsexual men. Hum Reprod. 2012 Feb;27(2):483-7. doi: 10.1093/humrep/der406. Epub 2011 Nov 28.

  PMID: 22128292 BACKGROUND

• Cipres D, Seidman D, Cloniger C 3rd, Nova C, O'Shea A, Obedin-Maliver J. Contraceptive use and pregnancy intentions among transgender men presenting to a clinic for sex workers and their families in San Francisco. Contraception. 2017 Feb;95(2):186-189. doi: 10.1016/j.contraception.2016.09.005. Epub 2016 Sep 9.

  PMID: 27621044 BACKGROUND

• Moseson H, Fix L, Hastings J, Stoeffler A, Lunn MR, Flentje A, Lubensky ME, Capriotti MR, Ragosta S, Forsberg H, Obedin-Maliver J. Pregnancy intentions and outcomes among transgender, nonbinary, and gender-expansive people assigned female or intersex at birth in the United States: Results from a national, quantitative survey. Int J Transgend Health. 2021 Nov 17;22(1-2):30-41. doi: 10.1080/26895269.2020.1841058. eCollection 2021.

  PMID: 34796363 BACKGROUND

• Kerman HM, Pham A, Crouch JM, Albertson K, Salehi P, Inwards-Breland DJ, Ahrens KR. Gender Diverse Youth on Fertility and Future Family: A Qualitative Analysis. J Adolesc Health. 2021 Jun;68(6):1112-1120. doi: 10.1016/j.jadohealth.2021.01.002. Epub 2021 Mar 10.

  PMID: 33712381 BACKGROUND

• Rafferty J; COMMITTEE ON PSYCHOSOCIAL ASPECTS OF CHILD AND FAMILY HEALTH; COMMITTEE ON ADOLESCENCE; SECTION ON LESBIAN, GAY, BISEXUAL, AND TRANSGENDER HEALTH AND WELLNESS. Ensuring Comprehensive Care and Support for Transgender and Gender-Diverse Children and Adolescents. Pediatrics. 2018 Oct;142(4):e20182162. doi: 10.1542/peds.2018-2162. Epub 2018 Sep 17.

  PMID: 30224363 BACKGROUND

• Light A, Wang LF, Zeymo A, Gomez-Lobo V. Family planning and contraception use in transgender men. Contraception. 2018 Oct;98(4):266-269. doi: 10.1016/j.contraception.2018.06.006. Epub 2018 Jun 23.

  PMID: 29944875 BACKGROUND

• Light AD, Obedin-Maliver J, Sevelius JM, Kerns JL. Transgender men who experienced pregnancy after female-to-male gender transitioning. Obstet Gynecol. 2014 Dec;124(6):1120-1127. doi: 10.1097/AOG.0000000000000540.

  PMID: 25415163 BACKGROUND

• Taub RL, Ellis SA, Neal-Perry G, Magaret AS, Prager SW, Micks EA. The effect of testosterone on ovulatory function in transmasculine individuals. Am J Obstet Gynecol. 2020 Aug;223(2):229.e1-229.e8. doi: 10.1016/j.ajog.2020.01.059. Epub 2020 Feb 8.

  PMID: 32044312 BACKGROUND

• Dewis P, Newman M, Ratcliffe WA, Anderson DC. Does testosterone affect the normal menstrual cycle? Clin Endocrinol (Oxf). 1986 May;24(5):515-21. doi: 10.1111/j.1365-2265.1986.tb03280.x.

  PMID: 3098455 BACKGROUND

• Scheele F, Hompes PG, Gooren LJ, Spijkstra JJ, Spinder T. The effect of 6 weeks of testosterone treatment on pulsatile luteinizing hormone secretion in eugonadal female-to-male transsexuals. Fertil Steril. 1991 Mar;55(3):608-11. doi: 10.1016/s0015-0282(16)54194-6.

  PMID: 2001760 BACKGROUND

• Ropelato MG, Rudaz MC, Escobar ME, Bengolea SV, Calcagno ML, Veldhuis JD, Barontini M. Acute effects of testosterone infusion on the serum luteinizing hormone profile in eumenorrheic and polycystic ovary syndrome adolescents. J Clin Endocrinol Metab. 2009 Sep;94(9):3602-10. doi: 10.1210/jc.2009-0402. Epub 2009 Jun 30.

  PMID: 19567528 BACKGROUND

• Spinder T, Spijkstra JJ, Gooren LJ, Hompes PG, van Kessel H. Effects of long-term testosterone administration on gonadotropin secretion in agonadal female to male transsexuals compared with hypogonadal and normal women. J Clin Endocrinol Metab. 1989 Jan;68(1):200-7. doi: 10.1210/jcem-68-1-200.

  PMID: 2491861 BACKGROUND

• T'Sjoen G, Arcelus J, Gooren L, Klink DT, Tangpricha V. Endocrinology of Transgender Medicine. Endocr Rev. 2019 Feb 1;40(1):97-117. doi: 10.1210/er.2018-00011.

  PMID: 30307546 BACKGROUND

• Mwamba RN, Ekwonu A, Guimaraes PVB, Raheem OA. The efficacy, safety, and outcomes of testosterone use among transgender men patients: A review of the literature. Neurourol Urodyn. 2023 Jun;42(5):921-930. doi: 10.1002/nau.25094. Epub 2022 Nov 20.

  PMID: 36403286 BACKGROUND

• Kassam A, Overstreet JW, Snow-Harter C, De Souza MJ, Gold EB, Lasley BL. Identification of anovulation and transient luteal function using a urinary pregnanediol-3-glucuronide ratio algorithm. Environ Health Perspect. 1996 Apr;104(4):408-13. doi: 10.1289/ehp.96104408.

  PMID: 8732951 BACKGROUND

• Santoro N, Crawford SL, Allsworth JE, Gold EB, Greendale GA, Korenman S, Lasley BL, McConnell D, McGaffigan P, Midgely R, Schocken M, Sowers M, Weiss G. Assessing menstrual cycles with urinary hormone assays. Am J Physiol Endocrinol Metab. 2003 Mar;284(3):E521-30. doi: 10.1152/ajpendo.00381.2002. Epub 2002 Nov 19.

  PMID: 12441312 BACKGROUND

• Pfizer Inc. Depo®-Testosterone (testosterone cypionate injection, USP0 [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/085635s029lbl.pdf. Accessed May 30, 2022.

  BACKGROUND

Related Links

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

MeSH Terms

Conditions

Transsexualism

Interventions

testosterone 17 beta-cypionate

Condition Hierarchy (Ancestors)

Sexuality; Sexual Behavior; Behavior

Results Point of Contact

• Title: Antoni Duleba
• Organization: University of California, San Diego

aduleba@health.ucsd.edu

858-657-7000

Study Officials

• Antoni Duleba, MD

  UC San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 30, 2024
• First Posted: June 10, 2024
• Study Start: February 26, 2025
• Primary Completion: February 26, 2025
• Study Completion: March 3, 2025
• Last Updated: July 22, 2025
• Results First Posted: July 14, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)