Mimicking women’s endocrine milieu in mice for women’s health-related studies

To improve preclinical studies and their translation, patient-derived xenografts (PDXs) are increasingly used. They have human-specific tumor characteristics and reflect intra and inter-tumor heterogeneity. However, the endocrine milieu differs between humans and host mice. In light of sex-specific cancer biology and a rise in endocrine-related cancers there is an urgent need to correctly reflect the hormonal milieu in PDX models. We show that female mice of <i>NOD.Cg-Prkdc</i> ^<i>scid</i> <i>Il2rg</i> ^{<i>tm1Wjl</i>} <i>/SzJ (NSG)</i> strain widely used for PDXs has 17-β-estradiol (E2) and testosterone (T) levels comparable to <i>C57Bl6</i> females but higher progesterone (P4) levels. E2 levels are comparable, T levels are lower and P4 levels higher than those observed in postmenopausal women. Ovariectomy increases T to levels observed in postmenopausal women. Subcutaneous E2 and combined E2/P4 silicon pellets provide <i>NSG</i> females with premenopausal ovarian hormone levels. These procedures humanize the endocrine environment of experimental animals, improving PDX relevance in women's health-related research.