Dehydroepiandrosterone Enhances Decidualization in Women of Advanced Reproductive Age

Abstract Objective: To investigate the impact of the androgen precursor dehydroepiandrosterone on decidualization of human endometrial stromal cells isolated from women of advanced reproductive age. Design: In vitro study. Setting: University Research Institute. Patients: Proliferative phase primary human endometrial stromal fibroblasts (hESF) were isolated from women of advanced reproductive age (n=16, mean age 44.7 +/- 2.3). None of the women were receiving hormonal therapy or suffering from endometriosis. Interventions: Isolated hESF were decidualized in vitro by incubation with progesterone (1µM) and cAMP (0.1mg/ml) in the presence, or absence, of DHEA (10nM, 100nM). Main outcome measures: Secretion of androgens was assessed by ELISA. Expression of decidualization markers and endometrial receptivity markers was assessed by qPCR and ELISA. Results: Decidualization responses were retained in hESF isolated from women of advanced reproductive age. Supplementation with DHEA increased androgen biosynthesis and concentrations of testosterone (p<0.0001) and dihydrotestosterone (p<0.0001) were ~3x greater following co-incubation with DHEA compared to hESF stimulated with decidualization alone. Addition of DHEA to decidualized hESF increased expression of the decidualization markers IGFBP1 (p<0.01) and PRL (p<0.001) and the endometrial receptivity marker SPP1 (p<0.0001). DHEA enhanced secretion of IGFBP1 (p<0.05), prolactin (p<0.01) and SPP1 (p<0.01) proteins maximally by day 8 of the decidualization time course concomitant with peak androgen concentrations. Conclusion: These novel results demonstrate DHEA can enhance in vitro decidualization responses of hESF from women of advanced reproductive age. Supplementation with DHEA during the receptive phase may augment endometrial function and improve pregnancy rates in natural or assisted reproductive cycles.