Testosterone TRANSdermal Gel for Poor Ovarian Responders Trial

Summary

Previous work indicates that 2 months androgen pre-treatment may equip preantral follicles with more FSH receptors and increase the cohort of follicles surviving to the recruitable antral stage. In this regard it may result in an increase in the oocyte yield and the reproductive outcome in women with poor ovarian response. These findings provide a strong rationale for a definitive large RCT. The TTRANSPORT study will include 400 women with poor ovarian response randomized to receive pre-treatment with transdermal testosterone gel or placebo in order to provide conclusive evidence regarding the superiority or not of transdermal testosterone pre-treatment for the management of poor ovarian responders fulfilling the Bologna criteria.

Timeline

Start

2015-04

Primary completion

2023-12

Completion

2024-02

Publications

• Background Casson PR, Lindsay MS, Pisarska MD, Carson SA, Buster JE. Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series. Hum Reprod. 2000 Oct;15(10):2129-32. doi: 10.1093/humrep/15.10.2129.
• Background Gonzalez-Comadran M, Duran M, Sola I, Fabregues F, Carreras R, Checa MA. Effects of transdermal testosterone in poor responders undergoing IVF: systematic review and meta-analysis. Reprod Biomed Online. 2012 Nov;25(5):450-9. doi: 10.1016/j.rbmo.2012.07.011. Epub 2012 Jul 26.
• Background Vendola K, Zhou J, Wang J, Famuyiwa OA, Bievre M, Bondy CA. Androgens promote oocyte insulin-like growth factor I expression and initiation of follicle development in the primate ovary. Biol Reprod. 1999 Aug;61(2):353-7. doi: 10.1095/biolreprod61.2.353.
• Background Weil S, Vendola K, Zhou J, Bondy CA. Androgen and follicle-stimulating hormone interactions in primate ovarian follicle development. J Clin Endocrinol Metab. 1999 Aug;84(8):2951-6. doi: 10.1210/jcem.84.8.5929.
• Background Kim CH, Howles CM, Lee HA. The effect of transdermal testosterone gel pretreatment on controlled ovarian stimulation and IVF outcome in low responders. Fertil Steril. 2011 Feb;95(2):679-83. doi: 10.1016/j.fertnstert.2010.07.1077.
• Background Singh AB, Lee ML, Sinha-Hikim I, Kushnir M, Meikle W, Rockwood A, Afework S, Bhasin S. Pharmacokinetics of a testosterone gel in healthy postmenopausal women. J Clin Endocrinol Metab. 2006 Jan;91(1):136-44. doi: 10.1210/jc.2005-1640. Epub 2005 Nov 1.
• Background Nathorst-Boos J, Jarkander-Rolff M, Carlstrom K, Floter A, von Schoultz B. Percutaneous administration of testosterone gel in postmenopausal women--a pharmacological study. Gynecol Endocrinol. 2005 May;20(5):243-8. doi: 10.1080/09513590500097283.
• Background Fooladi E, Reuter SE, Bell RJ, Robinson PJ, Davis SR. Pharmacokinetics of a transdermal testosterone cream in healthy postmenopausal women. Menopause. 2015 Jan;22(1):44-9. doi: 10.1097/GME.0000000000000259.
• Background Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-24. doi: 10.1093/humrep/der092. Epub 2011 Apr 19.
• Polyzos NP, Leathersich SJ, Martinez F, Blockeel C, Gosalvez A, de la Fuente L, Pinborg A, Fabregues F, Stoop D, Rodriguez I, de Geyter C, Davis SR, Humaidan P. Transdermal testosterone gel vs placebo in women with diminished ovarian reserve prior to in vitro fertilization: a randomized, clinical trial. Nat Commun. 2026 Feb 12;17(1):2713. doi: 10.1038/s41467-026-69557-z.
• Leathersich SJ, Davis SR, Garcia Martinez S, Blockeel C, Martinez F, Gosalvez A, Humaidan P, de la Fuente L, Fabregues F, Pinborg A, Stoop D, Polyzos NP. The impact of transdermal testosterone treatment on quality of life in women with diminished ovarian reserve: secondary analysis of a randomized controlled trial. Hum Reprod. 2026 Feb 1;41(2):231-238. doi: 10.1093/humrep/deaf233.

Drugs

Indications