O'Murchadha Liam, Pazderska Agnieszka
Department of Endocrinology, St James's Hospital, Dublin, Ireland.
School of Medicine, Trinity College Dublin, Dublin, Ireland.
Front Endocrinol (Lausanne). 2025 Jun 18;16:1510815. doi: 10.3389/fendo.2025.1510815. eCollection 2025.
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.
自身免疫性 Addison 病（AAD）是发达国家原发性肾上腺功能不全最常见的病因，女性发病率高于男性。该疾病与一系列影响生育和生殖健康的疾病相关。卵巢早衰（POI）是一种临床病症，定义为 40 岁之前月经周期停止且促性腺激素水平处于绝经范围。在普通人群中，其患病率为 1% - 2%，但据估计，AAD 女性患者中该患病率为 6% - 10%。一项登记研究表明，三分之一发生 POI 的 AAD 患者在 30 岁之前就出现了 POI。大多数情况下，POI 的发病先于或与 AAD 的诊断同时出现。研究还表明，AAD 女性更有可能使用激素替代疗法。该队列中 POI 的病理生理学被认为主要是通过自身免疫介导的卵巢膜细胞炎症。特别是，已鉴定出与产生类固醇细胞（StCA）发生交叉反应的自身抗体，这些抗体存在于 AAD 和 POI 患者体内。也就是说，排除 POI 女性患者后，生育率仍显著降低。肾上腺雄激素生成受损及由此导致的性激素缺乏也被认为与 AAD 患者的生育力低下有关。这些会导致卵泡发育欠佳。这反过来也可能影响性欲。尽管进行了生理剂量的糖皮质激素替代治疗，但与匹配的对照组相比，AAD 患者始终报告生活质量下降。这些因素可能会影响生育能力和受孕几率。其他自身免疫性疾病，如甲状腺功能减退和 1 型糖尿病，在 AAD 患者中的患病率也有所增加。这些疾病已被证明会独立影响生殖健康。本综述重点关注目前对影响自身免疫性 Addison 病女性生育力的因素和机制的理解。
