The clinical presentation of POI is variable. Very early onset in adolescence leads to complete delay of puberty with primary amenorrhoea. After menarche the presentation is with symptoms of oestrogen deficiency and secondary amenorrhoea or as part of a work up for infertility. In addition POI can be part of rare syndromic conditions that can be genetic or autoimmune.
Frustratingly, the cause of POI remains unknown in the majority of cases. As genetic screening for causal mutations has become more widely performed so new insights are gained not only into the pathogenesis of POI but also into the regulation of the lifespan of the ovary. Mutations in POLG, STAG3 and genes affecting the control of meiosis have been identified in our clinic through the investigation of consanguineous pedigrees.
Oestrogen replacement regimens for young women with POI have gradually changed over the past 10 years with increasing emphasis on transdermal oestrogen and away from the use of ethinylestradiol. Traditionally, the dose of oestrogen replacement has been influenced by the HRT preparations available for use in older women after the natural menopause. Of particular focus is the timing of induction of puberty where evidence is sparse but delay can have long lasting effects in life. It may be that earlier start of treatment and maintenance of higher dose oestrogen would improve outcomes for women with POI.