Primary Amenorrhea Due to Anatomical Abnormalities of the Reproductive Tract: Molecular Insight

Int J Mol Sci. 2021 Oct 25;22(21):11495. doi: 10.3390/ijms222111495.

Abstract

Congenital anomalies of the female reproductive tract that present with primary amenorrhea involve Müllerian aplasia, also known as Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS), and cervical and vaginal anomalies that completely obstruct the reproductive tract. Karyotype abnormalities do not exclude the diagnosis of MRKHS. Familial cases of Müllerian anomalies and associated malformations of the urinary and skeletal systems strongly suggest a complex genetic etiology, but so far, the molecular mechanism in the vast majority of cases remains unknown. Primary amenorrhea may also be the first presentation of complete androgen insensitivity syndrome, steroid 5α-reductase type 2 deficiency, 17β-hydroxysteroid dehydrogenase type 3 deficiency, and Leydig cells hypoplasia type 1; therefore, these disorders should be considered in the differential diagnosis of the congenital absence of the uterus and vagina. The molecular diagnosis in the majority of these cases can be established.

Keywords: DSD; MRKH syndrome; Müllerian aplasia; congenital absence of uterus and vagina; primary amenorrhea.

Publication types

  • Review

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases / deficiency
  • 17-Hydroxysteroid Dehydrogenases / genetics
  • 46, XX Disorders of Sex Development / pathology*
  • Amenorrhea / genetics*
  • Amenorrhea / pathology*
  • Androgen-Insensitivity Syndrome / genetics
  • Androgen-Insensitivity Syndrome / pathology
  • Cervix Uteri / abnormalities*
  • Cervix Uteri / embryology
  • Cholestenone 5 alpha-Reductase / deficiency
  • Cholestenone 5 alpha-Reductase / genetics
  • Congenital Abnormalities / diagnosis
  • Congenital Abnormalities / pathology*
  • Disorder of Sex Development, 46,XY / genetics
  • Disorder of Sex Development, 46,XY / pathology
  • Female
  • Humans
  • Male
  • Mullerian Ducts / abnormalities*
  • Mullerian Ducts / pathology
  • Testis / abnormalities
  • Testis / pathology
  • Vagina / abnormalities*
  • Vagina / embryology

Substances

  • 17-Hydroxysteroid Dehydrogenases
  • Cholestenone 5 alpha-Reductase

Supplementary concepts

  • Leydig Cell Hypoplasia
  • Mullerian aplasia