Congenital adrenal hyperplasia, disorders of sex development, and infertility in patients with POR gene pathogenic variants: a systematic review of the literature

J Endocrinol Invest. 2023 Jan;46(1):1-14. doi: 10.1007/s40618-022-01849-9. Epub 2022 Jul 17.


Background: P450 oxidoreductase (POR) deficiency (PORD) is characterized by congenital adrenal hyperplasia (CAH) and disorders of sex development (DSD) in both sexes. PORD can also associate with skeletal defects. However, the prevalence of these phenotypes is unknown.

Aim: To evaluate the prevalence of CAH, DSD, and infertility of patients with POR gene pathogenic variants by a systematic review of the literature.

Methods: The literature search was performed through PubMed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases. All studies reporting information on CAH, DSD, testicular adrenal rest tumor (TARTs), and fertility in patients with POR gene pathogenic variants were included. Finally, the prevalence of abnormal phenotypes was calculated.

Results: Of the 246 articles initially retrieved, only 48 were included for a total of 119 (46 males and 73 females) patients with PORD. We also included the case of a male patient who consulted us for CAH and TARTs but without DSD. This patient, found to be a carrier of combined heterozygous POR mutation, reached fatherhood spontaneously. All the patients found had CAH. The presence of DSD was found in 65.2%, 82.1%, and 82.1% of patients with compound heterozygosity, homozygosity, or monoallelic heterozygous variants, respectively. The prevalence was significantly higher in females than in males. The prevalence of TARTs in patients with PORD is 2.7%. Only 5 women with PORD became pregnant after assisted reproductive techniques and delivered a healthy baby. Except for the recently reported proband, no other studies focused on male infertility in patients with POR gene variants.

Conclusion: This systematic review of the literature reports the prevalence of CAH, DSD, and TARTs in patients with PORD. The unknown prevalence of POR gene pathogenetic variants and the paucity of studies investigating fertility do not allow us to establish whether PORD is associated with infertility. Further studies on both women and men are needed to clarify this relationship.

Keywords: CAH; Congenital adrenal hyperplasia; DSD; Disorders of sex development; Fertility; POR; Sperm parameters; TART; Testicular adrenal rest tumor.

Publication types

  • Systematic Review
  • Review

MeSH terms

  • Adrenal Hyperplasia, Congenital* / complications
  • Adrenal Hyperplasia, Congenital* / epidemiology
  • Adrenal Hyperplasia, Congenital* / genetics
  • Female
  • Heterozygote
  • Humans
  • Infertility, Male* / epidemiology
  • Infertility, Male* / genetics
  • Male
  • Mutation
  • Phenotype
  • Pregnancy