Polycystic Ovary Syndrome (PCOS), a prevalent endocrine disorder, affects 6–22% of women globally, with higher rates in South Asian populations and potentially in African groups like the Igbo of Nigeria. This paper applies James V. Neel’s thrifty gene hypothesis (1962), which suggests genetic and epigenetic adaptations to ancestral famines predispose modern populations to metabolic disorders in calorie-abundant environments. We examine India’s ancient and colonial famines (e.g., the Bengal Famine of 1770) and the Nigerian Civil War (also known as the Biafran War, 1967–1970) as case studies, hypothesising their role in increasing PCOS susceptibility in South Asian and Igbo women, respectively. In India, millennia of monsoonal droughts and colonial famines selected for thrifty genotypes, amplified by epigenetic reprogramming, contributing to urban PCOS prevalence (8–22%). For Igbo women, the Biafran famine’s severe undernutrition likely induced thrifty epigenotypes, with a projected 20–30% relative increase in PCOS risk in famine-exposed women and 10–15% in descendants, driven by insulin resistance and hyperandrogenism. These risks are exacerbated by urbanisation and high-glycemic diets, paralleling India’s post-liberalisation metabolic surge. Due to limited direct PCOS data in Biafran cohorts, these estimates are extrapolated from global famine studies. I propose lifestyle interventions, metformin, and targeted screening (e.g., IGF2 methylation) to mitigate this transgenerational burden, urging further research in famine-affected populations.