The sex ratio at birth (SRB), representing the biological male-to-total live births ratio, is a crucial marker of fetal development and population health [1]. Declines in SRB have been linked to natural disasters [2], war [3], socioeconomic [4], and psychological stressors [5]. However, findings are inconsistent. For example, one study found lower-than-expected SRB (more female births) in California after the 9/11 terrorist attacks [6], while research on World War I and II found increased SRBs (more males) in eight of ten countries experiencing war [3]. Stress influences fertility and SRB through maternal-fetal neuro-hormonal interactions [7], [8], [9], but the direction of these effects remains unclear. A systematic review of studies tracking maternal stress and SRB found 16 studies reporting declines in SRB, three reporting increases, four reporting no change, and two showing an initial decline followed by an increase [10]. Differences in study designs, stress measures, and sample sizes likely contribute to these discrepancies [10].

Biomarkers like salivary cortisol and alpha-amylase have been used to explore stress effects on SRB [5]. Bae et al. [7] found declines in male births among women with the highest salivary cortisol levels, while another study reported both a decline in SRB with high cortisol and an inverse relationship (more males) with high alpha-amylase [5]. However, salivary cortisol and similar measures are influenced by short-term stressors and temporal factors, such as time of day and food intake, making them less reliable for assessing chronic stress. Hair cortisol has emerged as a stable biomarker, reflecting long-term HPA axis activity without daily fluctuations [11], [12], [13], [14]. Retrospective assessments using hair cortisol have been successfully implemented in epidemiological studies [12]. Despite its advantages, research linking hair cortisol to SRB is sparse. One study examined first-trimester hair cortisol and offspring sex but did not explore preconception stress [15].

To address these gaps and limitations—such as reliance on short-term markers, small sample sizes, and studies largely restricted to global north populations [16], [17]—we examined preconception glucocorticoids (cortisol and cortisone) measured in hair and their association with SRB in a large Peruvian cohort. We hypothesized that elevated preconception glucocorticoids, indicative of HPA axis dysregulation, would predict a lower SRB (more female births).