Position statement on the diagnosis and management of premature/primary ovarian insufficiency (except Turner Syndrome)

Ann Endocrinol (Paris). 2021 Dec;82(6):555-571. doi: 10.1016/j.ando.2021.09.001. Epub 2021 Sep 8.

Abstract

Premature ovarian insufficiency (POI) is a rare pathology affecting 1-2% of under-40 year-old women, 1 in 1000 under-30 year-olds and 1 in 10,000 under-20 year-olds. There are multiple etiologies, which can be classified as primary (chromosomal, genetic, auto-immune) and secondary or iatrogenic (surgical, or secondary to chemotherapy and/or radiotherapy). Despite important progress in genetics, more than 60% of cases of primary POI still have no identifiable etiology; these cases are known as idiopathic POI. POI is defined by the association of 1 clinical and 1 biological criterion: primary or secondary amenorrhea or spaniomenorrhea of>4 months with onset before 40 year of age, and elevated follicle-stimulating hormone (FSH)>25IU/L on 2 assays at>4 weeks' interval. Estradiol level is low, and anti-Müllerian hormone (AMH) levels have usually collapsed. Initial etiological work-up comprises auto-immune assessment, karyotype, FMR1 premutation screening and gene-panel study. If all of these are normal, the patient and parents may be offered genome-wide analysis under the "France Génomique" project. The term ovarian insufficiency suggests that the dysfunction is not necessarily definitive. In some cases, ovarian function may fluctuate, and spontaneous pregnancy is possible in around 6% of cases. In confirmed POI, hormone replacement therapy is to be recommended at least up to the physiological menopause age of 51 years. Management in a rare diseases center may be proposed.

Keywords: FMR1 premutation; Hormonal replacement therapy; Oocyte donation; Premature ovarian insufficiency; Primary ovarian insufficiency; X chromosome.

Publication types

  • Practice Guideline

MeSH terms

  • Adult
  • Anti-Mullerian Hormone
  • Female
  • Follicle Stimulating Hormone
  • Fragile X Mental Retardation Protein
  • France
  • Hormone Replacement Therapy
  • Humans
  • Primary Ovarian Insufficiency / diagnosis*
  • Primary Ovarian Insufficiency / therapy*

Substances

  • FMR1 protein, human
  • Fragile X Mental Retardation Protein
  • Anti-Mullerian Hormone
  • Follicle Stimulating Hormone