5-alpha reductase deficiency

Related: 5-alpha reductaseImperato-McGinley • GuevedocesInvention of finasteride

General reference

Kumar G, Barboza-Meca JJ. 5 alpha reductase deficiency – NCBI Bookshelf. StatPearls Publishing. 2020 Jan.

MedlinePlus. National Library of Medicine (US). 5-alpha reductase deficiency.

Sources on guevedoces & early history of finasteride. Finasteride Watch.

Technical reference

Conte FA, Grumbach MM. Chapter 14. Disorders of sex determination and differentiation. In: Gardner DG, Shoback D, eds. Greenspan’s Basic & Clinical Endocrinology, 9e. The McGraw-Hill Companies; 2011. Full text at McGraw-Hill Medical

Imperato-McGinley J. 5alpha-reductase-2 deficiency and complete androgen insensitivity: lessons from nature. Adv Exp Med Biol. 2002. doi:10.1007/978-1-4615-0621-8_8PubMed

Case series & case reports

See also: Psychological & cultural studies

Armeni AK, Vasileiou V, Georgopoulos NA. When genotype prevails: sexual female-to-male transformation in classical antiquity, recorded by Gaius Plinius Secundus and Phlegon. Hormones (Athens). 2014. doi:10.1007/BF03401331 • PubMed [See also: Stamou et al, 2024]

Cai LQ, Fratianni CM, Gautier T, Imperato-McGinley J. Dihydrotestosterone regulation of semen in male pseudohermaphrodites with 5 alpha-reductase-2 deficiency. J Clin Endocrinol Metab. 1994. doi:10.1210/jcem.79.2.8045956 • PubMed

Cai LQ, Zhu YS, Katz MD, et al. 5 alpha-reductase-2 gene mutations in the Dominican Republic. J Clin Endocrinol Metab. 1996. doi:10.1210/jcem.81.5.8626825PubMed

Cantu J, Hernández-Montes H, del Castillo V, et al. Potential fertility in incomplete male pseudohermaphroditism type 2. Rev Invest Clin (Méx). 1976 Apr-Jun;28(2):177-182. PubMed

Carpenter TO, Imperato-McGinley J, Boulware SD, et al. Variable expression of 5 alpha-reductase deficiency: presentation with male phenotype in a child of Greek origin. J Clin Endocrinol Metab. 1990. doi:10.1210/jcem-71-2-318 • PubMed

Cheng T, Wang H, Han B, et al. Identification of three novel SRD5A2 mutations in Chinese patients with 5α-reductase 2 deficiency. Asian J Androl. 2019. doi:10.4103/aja.aja_113_18PubMed

Deeb A, Al Suwaidi H, Ibukunoluwa F, Attia S. Phenotype, sex of rearing, gender re-assignment, and response to medical treatment in extended family members with a novel mutation in the SRD5A2 gene. J Clin Res Pediatr Endocrinol. 2016. doi:10.4274/jcrpe.2782 • Via journal site • PubMed • PMC full text

[Conference abstract] Imperato-McGinley J. Guerrero L, Gautier T, Peterson RE. 93. An unusual inherited form of male pseudohermaphroditism. A model of 5α-reductase deficiency in man. Journal of Steroid Biochemistry. 1974. doi:10.1016/0022-4731(74)90238-6

Gajdusek DC. Urgent opportunistic observations: the study of changing, transient and disappearing phenomena of medical interest in disrupted primitive human communities. In: Elliott K, Whelan J, eds. Novartis Foundation Symposia. John Wiley & Sons, Ltd.; 2008. doi:10.1002/9780470715406.ch5

Herdt GH, Davidson J. The Sambia “Turnim-Man”: sociocultural and clinical aspects of gender formation in male pseudohermaphrodites with 5-alpha-reductase deficiency in Papua New Guinea. Arch Sex Behav. 1988. doi:10.1007/BF01542051

Herdt GH, Stoller RJ. Sakulambei—a hermaphrodite’s secret: an example of clinical ethnography. The Psychoanalytic Study of Society. 1985;11:117-158. doi:10.4324/9781315791920-4

Hernandez LO, Inchaustegui S, Arguello CN. Los casos de pseudo-hermafroditismo en la Sección de las Salinas, Prov. de Barahona. Revista médica dominicana. 1951;6(2):114–136.

This may be the first article on male pseudohermaphrodites in Las Salinas, Dominican Republic, where Imperato-McGinley et al. investigated the condition in the 1970s (see Imperato-McGinley et al., 1974 and subsequent papers).

Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE. Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science. 1974. doi:10.1126/science.186.4170.1213PubMed

Jong D, Pulungan A, Tridjaja B, Batubara JRL. 5-alpha-reductase deficiency: a case report. 2016. doi:10.14238/pi43.6.2003.234-40

Katz MD, Kligman I, Cai LQ, et al. Paternity by intrauterine insemination with sperm from a man with 5alpha-reductase-2 deficiency. N Engl J Med. 1997. doi:10.1056/NEJM199704033361404 • PubMed

Khorashad BS, Aghili Z, Kreukels BPC, et al. Mental health and disorders of sex development/intersex conditions in Iranian culture: congenital adrenal hyperplasia, 5-α reductase deficiency-type 2, and complete androgen insensitivity syndrome. Arch Sex Behav. 2018. doi:10.1007/s10508-017-1139-6 • PubMed

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

Maimoun L, Philibert P, Cammas B, et al. Phenotypical, biological, and molecular heterogeneity of 5α-reductase deficiency: an extensive international experience of 55 patients. J Clin Endocrinol Metab. 2011. doi:10.1210/jc.2010-1024 • PubMed

Mannan MA, Rahman MH, Hoque MA. Male pseudohermaphroditism due to 5 alpha reductase-2 deficiency- an uncommon etiology. J Medicine. 2009. doi:10.3329/jom.v10i2.2834

Noroozi Asl S, Ibrahimi R, Bagheri S, Lotfi M. 5-Alpha reductase deficiency; an important cause of 46, XY DSD: Report of three cases within a family. Clin Case Rep. 2023. doi:10.1002/ccr3.7269PubMed • PMC full text

Okon E, Livni N, Rösler A, et al. Male pseudohermaphroditism due to 5 alpha-reductase deficiency. Ultrastructure of the gonads. Arch Pathol Lab Med. 1980. PubMed

Palui R, Ravichandran L, Kamalanathan S, et al. Clinical, hormonal, and genetic spectrum of 46 XY disorders of sexual development (DSD) patients. Indian J Pediatr. 2024. doi:10.1007/s12098-024-05144-8 • PubMed

Putri Susilo AF, Tjandraprawira KD, Bayu P, Bayuaji H. Disorders of sex development (DSD) 46.XY due to type 2 5-α reductase deficiency in three siblings: case report from a low-resource setting. Ann Med Surg (Lond). 2022. doi:10.1016/j.amsu.2022.104577 • PMC full text

Ruiz Martín M, Alcalá RL, Martín MA. Pseudo hermafroditismo masculino: presentación de un caso. [Journal unknown]. 1979. PDF at Universidad de la Rioja

Pekkolay Z, Kiling F, Tuzcu S, Soylu H, Tuzcu A. 5-alpha reductase deficiency: a review of five cases diagnosed with ambiguous genitalia. Turk J Endocrinol Metab. 2017. doi:10.25179/tjem.2017-56481. Article page via archive.org

Peterson RE, Imperato-McGinley J, Gautier T, Sturla E. Male pseudohermaphroditism due to steroid 5-alpha-reductase deficiency. Am J Med. 1977. doi:10.1016/0002-9343(77)90313-8 • PubMed

Stamou MI, Armeni AK, Kazantzidis G, Georgopoulos NA, Markantes GK. Poseidon and Caeneus: a case of pubertal gender inversion in Greek mythology. Hormones (Athens). 2024. doi:10.1007/s42000-023-00524-9 • PubMed [See also: Armeni et al, 2014]

Walsh PC, Madden JD, Harrod MJ, Goldstein JL, MacDonald PC, Wilson JD. Familial incomplete male pseudohermaphroditism, type 2. Decreased dihydrotestosterone formation in pseudovaginal perineoscrotal hypospadias. N Engl J Med. 1974. doi:10.1056/NEJM197410312911806PubMed

Clinical guidance & experience

Imperato-McGinley J. 5-alpha-reductase deficiency. Curr Ther Endocrinol Metab. 1994. PubMed

Imperato-McGinley J. 5 alpha-reductase-2 deficiency. Curr Ther Endocrinol Metab. 1997. PubMed.

Kyriakou A, Dessens A, Bryce J, et al. Current models of care for disorders of sex development – results from an international survey of specialist centres. Orphanet J Rare Dis. 2016. doi:10.1186/s13023-016-0534-8PubMed • PMC full text

Mendonca BB, Batista RL, Domenice S, et al. Steroid 5α-reductase 2 deficiency. J Steroid Biochem Mol Biol. 2016 Oct. doi:10.1016/j.jsbmb.2016.05.020PubMed

Mendonca BB, Inacio M, Costa EM, et al. Male pseudohermaphroditism due to steroid 5alpha-reductase 2 deficiency. Diagnosis, psychological evaluation, and management. Medicine (Baltimore). 1996. doi:10.1097/00005792-199603000-00003 • PubMed

Sasaki G, Ishii T, Hori N, et al. Effects of pre- and post-pubertal dihydrotestosterone treatment on penile length in 5α-reductase type 2 deficiency. Endocr J. 2019 Sep 28. doi:10.1507/endocrj.EJ19-0111 • PubMed

Clinical trials

Imperato-McGinley J. 5 alpha-metabolism in finasteride-treated subjects and male pseudohermaphrodites with inherited 5 alpha-reductase deficiency. A review. Eur Urol. 1991;20 Suppl 1. doi:10.1159/000471751PubMed

Imperato-McGinley J, Shackleton C, Orlic S, Stoner E. C19 and C21 5 beta/5 alpha metabolite ratios in subjects treated with the 5 alpha-reductase inhibitor finasteride: comparison of male pseudohermaphrodites with inherited 5 alpha-reductase deficiency. J Clin Endocrinol Metab. 1990. doi:10.1210/jcem-70-3-777PubMed

Original investigations

Alswailem MM, Alzahrani OS, Alghofaili L, et al. Molecular genetics and phenotype/genotype correlation of 5-α reductase deficiency in a highly consanguineous population. Endocrine. 2019. doi:10.1007/s12020-018-1767-1PubMed

Mosher LJ, Godar SC, Morissette M, et al. Steroid 5α-reductase 2 deficiency leads to reduced dominance-related and impulse-control behaviors. Psychoneuroendocrinology. 2018. doi:10.1016/j.psyneuen.2018.02.007 • PubMed • PMC full text

Sobel V, Schwartz B, Zhu YS, Cordero JJ, Imperato-McGinley J. Bone mineral density in the complete androgen insensitivity and 5alpha-reductase-2 deficiency syndromes. J Clin Endocrinol Metab. 2006. doi:10.1210/jc.2005-2809 • PubMed

Psychological & cultural studies

See also: Criticisms and context of Imperato-McGinley’s research

Bajszczak K, Szarras-Czapnik M, Walczak-Jędrzejowska R, Marchlewska K, Slowikowska-Hilczer J. The risk of mental disorders in patients with disorders/differences of sex differentiation/development (DSD) and Y chromosome. Endokrynologia Polska. 2020. doi:10.5603/EP.a2020.0005

Bennecke E, Thyen U, Grüters A, Lux A, Köhler, B. Health-related quality of life and psychological well-being in adults with differences/disorders of sex development. Clin Endocrinol. 2017. doi:10.1111/cen.13296PubMed

Boucher NA, Alkazemi MH, Tejwani R, Routh JC. Parents of children with newly diagnosed disorders of sex development identify major concerns: a qualitative study. Urology. 2022. doi:10.1016/j.urology.2022.01.001

Herdt G. Mistaken gender: 5-alpha reductase hermaphroditism and biological reductionism in sexual identity reconsidered. American Anthropologist. 1990;92(2):433-446. doi:10.1525/aa.1990.92.2.02a00110

Herdt GH, Davidson J. The Sambia “Turnim-Man”: sociocultural and clinical aspects of gender formation in male pseudohermaphrodites with 5-alpha-reductase deficiency in Papua New Guinea. Arch Sex Behav. 1988. doi:10.1007/BF01542051

Herdt GH, Stoller RJ. Sakulambei—a hermaphrodite’s secret: an example of clinical ethnography. The Psychoanalytic Study of Society. 1985;11:117-158. doi:10.4324/9781315791920-4

Khorashad BS, Aghili Z, Kreukels BPC, et al. Mental health and disorders of sex development/intersex conditions in Iranian culture: congenital adrenal hyperplasia, 5-α reductase deficiency-type 2, and complete androgen insensitivity syndrome. Arch Sex Behav. 2018. doi:10.1007/s10508-017-1139-6. PubMed

Khorashad BS, Khazai B, Roshan GM, Hiradfar M, Afkhamizadeh M, van de Grift TC. Prenatal testosterone and theory of mind development: findings from disorders of sex development. Psychoneuroendocrinology. 2018. doi:10.1016/j.psyneuen.2017.12.008PubMed

Moreno-Begines MLN, Arroyo-Rodríguez A, Borrallo-Riego Á, Guerra-Martín MD. Intersexuality/differences of sex development through the discourse of intersex people, their relatives, and health experts: a descriptive qualitative study. Healthcare. 2022. doi:10.3390/healthcare10040671

Perez MN, Clawson AH, Baudino MN, et al. Distress trajectories for parents of children with DSD: a growth mixture model. Journal of Pediatric Psychology. 2021. doi:10.1093/jpepsy/jsab004

Traino KA, Roberts CM, Fisher RS, et al. Stigma, intrusiveness, and distress in parents of children with a disorder/difference of sex development. J Dev Behav Pediatr. 2022. doi:10.1097/DBP.0000000000001077

Reviews & commentary

Herdt, G. Mistaken gender: 5-alpha reductase hermaphroditism and biological reductionism in sexual identity reconsidered. American Anthropologist. 1990. https://doi.org/10.1525/aa.1990.92.2.02a00110

Imperato-McGinley J, Zhu YS. Androgens and male physiology the syndrome of 5alpha-reductase-2 deficiency. Mol Cell Endocrinol. 2002 Dec 30;198(1-2):51-9. doi: 10.1016/s0303-7207(02)00368-4. PMID: 12573814.

Kang HJ, Imperato-McGinley J, Zhu YS, Rosenwaks Z. The effect of 5α-reductase-2 deficiency on human fertility. Fertil Steril. 2014. doi:10.1016/j.fertnstert.2013.11.128PubMed • PMC full text

Okeigwe I, Kuohung W. 5-alpha reductase deficiency: a 40-year retrospective review. Curr Opin Endocrinol Diabetes Obes. 2014. doi:10.1097/MED.0000000000000116 • PubMed

Robitaille J, Langlois VS. Consequences of steroid-5α-reductase deficiency and inhibition in vertebrates. Gen Comp Endocrinol. 2020. doi:10.1016/j.ygcen.2020.113400PubMed