Hypospadias and endocrine disruption: is there a connection?
Open accessAbstract
Hypospadias is one of the most common congenital anomalies in the United States, occurring in approximately 1 in 250 newborns or roughly 1 in 125 live male births. It is the result of arrested development of the urethra, foreskin, and ventral surface of the penis where the urethral opening may be anywhere along the shaft, within the scrotum, or in the perineum. The only treatment is surgery. Thus, prevention is imperative. To accomplish this, it is necessary to determine the etiology of hypospadias, the majority of which have been classified as idiopathic. In this paper we briefly describe the normal development of the male external genitalia and review the prevalence, etiology, risk factors, and epidemiology of hypospadias. The majority of hypospadias are believed to have a multifactorial etiology, although a small percentage do result from single gene mutations. Recent findings suggest that some hypospadias could be the result of disrupted gene expression. Discoveries about the antiandrogenic mechanisms of action of some contemporary-use chemicals have provided new knowledge about the organization and development of the urogenital system and may provide additional insight into the etiology of hypospadias and direction for prevention.
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Antiandrogens are already recognized as one of the factors responsible for the recent increase of hypospadias.
“They are already recognized as one of the factors responsible for the recent increase of hypospadias, a male reproductive disorder where the urethral opening is on the ventral surface of the penis (Baskin et al. 2001; Davis et al. 1998; Egeland et al. 1994; Jensen et al. 1995; Sharpe and Skakkebaek 1993).”
From Perinatal Exposure to Low Levels of the Environmental Antiandrogen Vinclozolin Alters Sex-Differentiated Social Play and Sexual Behaviors in the Rat (2005) · cites this paper as Baskin et al. 2001
The discussion (p. 1180) says environmental antiandrogens can disrupt male urogenital development and lead to hypospadias. But the paper describes environmental causes of the reported increase as a concern rather than an established explanation (p. 1177), and says a clear etiology has not been established. It does not support calling antiandrogens already recognized factors responsible for the recent increase. (LLM, conf=0.88)
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Cites
The hormonal-control of sexual development
Wilson, J. D., George, F. W., & Griffin, J. E. (1981) · Science · doi:10.1126/science.7010602 · Cited by 451 · see citing works
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Welsh, M., Saunders, P. T. K., Fisken, M., Scott, H. M., Hutchison, G. R., Smith, L. B., & Sharpe, R. M. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34241 · Cited by 781 · see citing works
Environmental factors in declining human fertility
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“…already recognized as one of the factors responsible for the recent increase of hypospadias, a male reproductive disorder where the urethral opening is on the ventral surface of the penis (Baskin et al. 2001; Davis et al. 1998; Egeland et al. 1994; Jensen et al. 1995; Sharpe and Skakkebaek 1993).”
BackgroundMolecular Effects of Genistein on Male Urethral Development
Ross, A. E., Marchionni, L., Phillips, T. M., Miller, R. M., Hurley, P. J., Simons, B. W., Salmasi, A. H., Schaeffer, A. J., Gearhart, J. P., & Schaeffer, E. M. (2011) · Journal of Urology · doi:10.1016/j.juro.2010.12.095 · Cited by 29 · see citing works
- Authors
- Baskin, L. S., Himes, K., & Colborn, T.
- Affiliations
- University of California, San Francisco (US)
- ORCID
- Venue
- Environmental Health Perspectives
- Publisher
- American Chemical Society (ACS)
- Published
- 2001-11-01
- Volume
- 109
- Issue
- 11
- Pages
- 1175-1183
- ISSN
- 0091-6765 (ISSN-L)
- 1552-9924
- PMC
- PMC1240480
- OpenAlex
- W2065123070
- Cited by
- 281
- References
- 1
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 5 · 2023: 1 · 2022: 6 · 2021: 13 · 2020: 5 · 2019: 5 · 2018: 9 · 2017: 13 · 2016: 16 · 2015: 8 · 2014: 11 · 2013: 17 · 2012: 15
- FWCI
- 13.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Environmental Health Perspectives (publishedVersion, cc-by)
- Environmental Health Perspectives (publishedVersion, public-domain)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Topics
- Health Sciences › Medicine › Urology › Urological Disorders and Treatments
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- hypospadias, endocrine disruption, congenital malformations, urethral malformation, multifactorial etiology, risk factors, prevention
- MeSH terms
- Androgen Antagonists, Cell Differentiation, Environmental Exposure, Humans, Hypospadias, Infant, Newborn, Male, Risk Factors, Urogenital System, Xenobiotics, Prevalence, Gene Expression Regulation, Developmental
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