It has been debated for several decades, whether number magnitudes are processed global/holistically (whole number magnitudes) or in a local/decomposed fashion (digit magnitudes). However, while it has been suggested that men attend stronger to the global level, while women attend stronger to the local level, the question has never been studied with regards to sex differences. In two-digit number comparison men should engage a more holistic processing strategy, while women should engage a more decomposed strategy. To test this hypothesis, we employed number comparison stimuli of varying decade crossing and unit-decade compatibility in men (n = 16) and women (n = 16) during their early follicular and mid-luteal cycle phase. In within-decade (WD) items both numbers had the same decade digits. Non-WD items were unitdecade-compatible, if the smaller number contained the smaller unit-digit and incompatible otherwise. In incompatible items the two local features require different responses. Thus, processing of the local level should result in a compatibility effect in RT and recruitment of differential neural networks for compatible and incompatible items. The results support the view of a holistic strategy in men and a decomposed strategy in women. In men RT and BOLD-response did not differ for incompatible compared to compatible items. Women respond slower to incompatible compared to compatible items. They show a BOLD-response compatibility effect in regions of the default mode network during their follicular phase and in prefrontal areas involved in inhibitory control during their luteal phase. Furthermore, lateralization indices interacted with decade crossing and menstrual cycle phase in a way consistent with the hypothesis of progesterone-mediated interhemispheric decoupling.