The Role of Lifestyle and Dietary Factors in the Development of Premature Ovarian Insufficiency

Abstract

Premature ovarian insufficiency (POI) is a condition that arises from dysfunction or early depletion of the ovarian follicle pool accompanied by an earlier-than-normal loss of fertility in young women. Oxidative stress has been suggested as an important factor in the decline of fertility in women and POI. In this review, we discuss the mechanisms of oxidative stress implicated in ovarian ageing and dysfunction in relation to POI, in particular mitochondrial dysfunction, apoptosis and inflammation. Genetic defects, autoimmunity and chemotherapy, are some of the reviewed hallmarks of POI that can lead to increased oxidative stress. Additionally, we highlight lifestyle factors, including diet, low energy availability and BMI, that can increase the risk of POI. The final section of this review discusses dietary factors associated with POI, including consumption of oily fish, mitochondria nutrient therapy, melatonin, dairy and vitamins that can be targeted as potential interventions, especially for at-risk women and in combination with personalised nutrition. Understanding the impact of lifestyle and its implications for POI and oxidative stress holds great promise in reducing the burden of this condition.

Keywords: diet; early menopause; infertility; lifestyle; ovarian ageing; oxidative stress; premature ovarian insufficiency.

Figure 1

Simplified diagram of reactive oxygen species (R˙)-induced apoptosis. Exogenous pathway: Free radicals induce death receptors such as the TNF receptor (TNFR) or FAS receptor, as well as inducing the production of their ligands TNFα and FasL (respectively) from neighbouring cells. The death receptors stimulate caspase-8, which activates apoptosis. Intrinsic pathway: cellular free radicals, such as H₂O₂, result in mitochondrial dysfunction via the Bax/Bak leaking of cytochrome-c from the mitochondria, which activates apoptosis via the caspase complex. Cellular free radicals also result in the phosphorylation of JNK (P-JNK) and P53, which leads to further activation of apoptosis.

Figure 2

Oestrogen antioxidant structure. Oestrogen chemical structure [52] contains a phenolic ring capable of scavenging free radicals (R˙) by transferring a hydrogen atom to the free radical.