Do androgens have a direct effect on endometrial function? An in vitro study

Objective: To test the hypothesis that androgens have a direct effect on the function of endometrial epithelial cells. Design: In vitro study. Setting: Academic research center. Patient(s): Endometrial epithelial cells were prepared from biopsy samples obtained from normal fertile women. Interventions: Cells were incubated with androstenedione, testosterone, dihydrotestosterone, and DHEA. Main Outcome Measure(s): Secretion of glycodelin A into the culture fluid was used to assess secretory activity. Uptake of 3H-thymidine and immunostaining for Ki67 was used to assess cell growth. The specific action of the androgens was confirmed by incubation with an antiandrogen, cyproterone acetate. Result(s): Androstenedione (10 −6 M and 10 −7 M) caused a dose-dependent decrease in glycodelin A secretion, uptake of 3H-thymidine, and percentage of positive Ki67 cells in cultured human endometrial epithelial cells. Testosterone, dihydrotestosterone, and DHEA had no effect on glycodelin A secretion or 3H-thymidine uptake. The direct effect of androgens on endometrial function were confirmed by demonstrating the presence of androgen receptors in cultured endometrial epithelial cells and showing that the direct effects of the androgens were not observed when cyproterone acetate was added to the cultures. Conclusion(s): The results suggest that androstenedione can inhibit human endometrial cell growth and secretory activity. Infertility and miscarriage associated with high androgen levels (e.g., that caused by the polycystic ovary syndrome) may be due to an adverse effect of high androgen levels on the endometrium.