Female fertility and pregnancy in autoimmune Addison's disease - a mini review

Autoimmune Addison's Disease (AAD) is by far the most common cause of primary adrenal insufficiency in developed countries, occurring more commonly in women compared with men. The condition is associated with a spectrum of disorders affecting fertility and reproductive health. Premature ovarian insufficiency (POI) is a clinical condition defined by cessation of menstrual cycles and menopausal range gonadotrophins before the age of 40 years. This occurs with a prevalence of 1-2% in the general population, but has been estimated at 6-10% for women with AAD. One registry study demonstrated that one-third of those with AAD who develop POI, do so before the age of thirty. The onset of POI precedes or is contemporaneous with the diagnosis of AAD in the majority. It has also been demonstrated that women with AAD are more likely to use hormone replacement therapy. The pathophysiology of POI in this cohort is thought to be primarily through autoimmune mediated inflammation of the ovarian theca cells. In particular, cross-reacting autoantibodies to steroid-producing cells (StCA) have been identified which are present in AAD and POI. That said, when women with POI are excluded, fertility remains significantly reduced. Impaired adrenal androgenesis and resulting sex-hormone deficiency have also been implicated in subfertility in AAD. These lead to suboptimal follicular development. This, in turn, may also affect libido. Despite physiological glucocorticoid replacement therapy, patients with AAD consistently report reduced quality of life compared to matched controls. These factors may affect fecundity and likelihood of conception. Other autoimmune conditions such as hypothyroidism and type 1 diabetes occur with increased prevalence in those with AAD. These conditions have been shown to independently affect reproductive health. This review focuses on the current understanding of the factors and mechanisms impacting fertility in women with autoimmune Addison's disease.