Research on teratogenicity (birth abnormalities)

Teratogenicity (birth abnormalities)

IN BRIEF: There are several scenarios where exposure to 5-alpha reductase inhibitors (5ARI) might result in birth abnormalities:

If a pregnant woman takes a 5ARI, the fetal environment has reduced levels of dihydrotestosterone (DHT). This hormone is crucial for the differentiation of male genitals, especially during a critical period early in pregnancy. If the fetus is male, a low-DHT environment could result in ambiguous or otherwise atypical genitals at birth (see case reports).
When a man taking a 5ARI inseminates a pregnant woman, his semen may contain the drug. Insemination could expose the fetus to the drug (see Zakhem et al, 2019). Merck ran animal experiments to assess the risk of such an exposure (see Precautions in Prescribing Information).
Pregnant women could be exposed to 5ARIs through blood donation (see the section ‘Blood donation’).
A pregnant woman could be exposed to a 5ARI by handling the pills. A warning about this appears in the finasteride label.

Animal studies have shown other effects on the offspring of male or female parents exposed to finasteride (see the section ‘Animal studies’).

Case reports

AlSaad D, Lee BH, Al-Obaidly S. Finasteride use during pregnancy and early neonatal outcome: a case report. Int J Clin Pharm. 2018. doi:10.1007/s11096-018-0661-5 • PubMed

Ibarra Vilar P, Marín Pérez A, Hernández Peñalver AI, et al. Genitales ambiguos tras toma de finasteride [Ambiguous genitalia after taking finasteride]. Abstract presented at: XXVII Reunión de la Sociedad Ginecológica Murciana: Laparoscopia ginecológica. March 4, 2017; Hospital Comarcal del Noroeste, Caravaca de la Cruz, Spain. Spanish. Content warning: includes a sensitive image of a fetus. Abstract (Spanish) • English translation

Levy B, Teplitsky S, Kalaitzoglou E, Kahler S, Matheny JP, Saltzman AF. “Exogenous” 5 alpha reductase deficiency: a case report. Urology. 2023. doi:10.1016/j.urology.2023.05.001 • PubMed

Sallout BI, Al Wadi KA. Aphalangia possibly linked to unintended use of finasteride during early pregnancy. Ann Saudi Med. 2009. doi:10.4103/0256-4947.51805 • PubMed • PMC full text

Exposure of women

Iamsumang W, Leerunyakul K, Suchonwanit P. Finasteride and its potential for the treatment of female pattern hair loss: evidence to date. Drug Des Devel Ther. 2020. doi:10.2147/DDDT.S240615 • PubMed

Teichert M, van Puijenbroek E, Stricker BH. Contraindicated use of 5-alpha-reductase inhibitors in women. Br J Clin Pharmacol. 2017. doi:10.1111/bcp.13118 • PubMed

Townsend KA, Marlowe KF. Relative safety and efficacy of finasteride for treatment of hirsutism. Ann Pharmacother. 2004 Jun;38(6):1070-3. doi:10.1345/aph.1D461 • PubMed

Exposure of men

Ritchie HE, Oakes DJ, Hegedus E, Hill M, Kennedy D. Counselling regarding paternal exposures: Can we do better? Aust N Z J Obstet Gynaecol. 2017. doi:10.1111/ajo.12584 • PubMed

Zakhem GA, Motosko CC, Mu EW, Ho RS. Infertility and teratogenicity after paternal exposure to systemic dermatologic medications: a systematic review. J Am Acad Dermatol. 2019. doi:10.1016/j.jaad.2018.09.031 • PubMed

Blood donation

Becker CD, Stichtenoth DO, Wichmann MG, Schaefer C, Szinicz L. Blood donors on medication – an approach to minimize drug burden for recipients of blood products and to limit deferral of donors. Transfus Med Hemother. 2009. doi:10.1159/000203355 • PubMed • PMC full text

Shin SY, Shin YH, Lee SW, Shin JY, Kim CH. Blood donors on teratogenic drugs and donor deferral periods in a clinical situation. Vox Sang. 2012. doi:10.1111/j.1423-0410.2011.01566.x • PubMed

Wambier CG, Pereira CS, Prado Júnior Bde P, Foss NT. Brazilian blood donation eligibility criteria for dermatologic patients. An Bras Dermatol. 2012. doi:10.1590/s0365-05962012000400012 • PubMed

Animal studies

Anderson CA, Clark RL. External genitalia of the rat: normal development and the histogenesis of 5 alpha-reductase inhibitor-induced abnormalities. Teratology. 1990. doi:10.1002/tera.1420420505 • PubMed

Bowman CJ, Barlow NJ, Turner KJ, Wallace DG, Foster PM. Effects of in utero exposure to finasteride on androgen-dependent reproductive development in the male rat. Toxicol Sci. 2003. doi:10.1093/toxsci/kfg128 • PubMed

Clark RL, Antonello JM, Grossman SJ, et al. External genitalia abnormalities in male rats exposed in utero to finasteride, a 5 alpha-reductase inhibitor. Teratology. 1990. doi:10.1002/tera.1420420111 • PubMed

Hib J, Ponzio R. The abnormal development of male sex organs in the rat using a pure antiandrogen and a 5 alpha-reductase inhibitor during gestation. Acta Physiol Pharmacol Ther Latinoam. 1995. PubMed

[⚠️ Lead author was involved in finasteride development with Merck] Imperato-McGinley J, Sanchez RS, Spencer JR, Yee B, Vaughan ED. Comparison of the effects of the 5 alpha-reductase inhibitor finasteride and the antiandrogen flutamide on prostate and genital differentiation: dose-response studies. Endocrinology. 1992 Sep. doi:10.1210/endo.131.3.1324152 • PubMed

Kolasa A, Rogińska D, Rzeszotek S, Machaliński B, Wiszniewska B. Paternal finasteride treatment can influence the testicular transcriptome profile of male offspring-preliminary study. Curr Issues Mol Biol. 2021. doi:10.3390/cimb43020062 • PubMed

Kolasa-Wolosiuk A, Misiakiewicz-Has K, Baranowska-Bosiacka I, Gutowska I, Wiszniewska B. Androgen levels and apoptosis in the testis during postnatal development of finasteride-treated male rat offspring. Folia Histochem Cytobiol. 2015. doi:10.5603/fhc.a2015.0025 • PubMed

Kolasa-Wołosiuk A, Tarnowski M, Baranowska-Bosiacka I, Chlubek D, Wiszniewska B. Antioxidant enzyme expression of mRNA and protein in the epididymis of finasteride-treated male rat offspring during postnatal development. Arch Med Sci. 2019. doi:10.5114/aoms.2017.68528 • PubMed • PMC full text

Kur P, Kolasa-Wołosiuk A, Grabowska M, et al. The postnatal offspring of finasteride-treated male rats shows hyperglycaemia, elevated hepatic glycogen storage and altered GLUT2, IR, and AR expression in the liver. Int J Mol Sci. 2021. doi:10.3390/ijms22031242 • PubMed • PMC full text

Kurzrock EA, Jegatheesan P, Cunha GR, Baskin LS. Urethral development in the fetal rabbit and induction of hypospadias: a model for human development. J Urol. 2000. PubMed

Maldarine JS, Sanches BDA, Santos VA, et al. Low-dose in utero exposure to finasteride promotes developmental changes in both male and female gerbil prostates. Environ Toxicol. 2020. doi:10.1002/tox.22838 • PubMed

[⚠️ Based on Merck-sponsored studies] Merck & Co., Inc. Prescribing Information: PROPECIA (finasteride) Tablets, 1 mg – PRECAUTIONS section. December 8, 2001.

Paris JJ, Brunton PJ, Russell JA, Walf AA, Frye CA. Inhibition of 5α-reductase activity in late pregnancy decreases gestational length and fecundity and impairs object memory and central progestogen milieu of juvenile rat offspring. J Neuroendocrinol. 2011. doi:10.1111/j.1365-2826.2011.02219.x • PubMed • PMC full text

[⚠️ 10 of 13 authors were Merck researchers] Prahalada S, Tarantal AF, Harris GS, et al. Effects of finasteride, a type 2 5-alpha reductase inhibitor, on fetal development in the rhesus monkey (Macaca mulatta). Teratology. 1997 Feb. doi:10.1002/(SICI)1096-9926(199702)55:2<119::AID-TERA1>3.0.CO;2-Z • PubMed

Ribeiro CM, Pereira OC. 5alpha-reductase 2 inhibition impairs brain defeminization of male rats: reproductive aspects. Pharmacol Biochem Behav. 2005. doi:10.1016/j.pbb.2005.08.015 • PubMed

Rzeszotek S, Kolasa A, Pilutin A, Misiakiewicz-Has K, Sielatycka K, Wiszniewska B. The interplay between finasteride-induced androgen imbalance, endoplasmic reticulum stress, oxidative stress, and liver disorders in paternal and filial generation. Biomedicines. 2022. doi:10.3390/biomedicines10112725

Spencer JR, Torrado T, Sanchez RS, Vaughan ED Jr, Imperato-McGinley J. Effects of flutamide and finasteride on rat testicular descent. Endocrinology. 1991 Aug;129(2):741-8. doi:10.1210/endo-129-2-741

Suzuki H, Suzuki K, Yamada G. Systematic analyses of murine masculinization processes based on genital sex differentiation parameters. Dev Growth Differ. 2015. doi:10.1111/dgd.12247 • PubMed