The role of androgens and the androgen receptor in cycling endometrium.

Androgens and the androgen receptor (AR) are not only required for male reproductive function, they are also essential for female reproductive physiology. Widely expressed in female reproductive tissues, AR levels fluctuate in a regulated manner in the cycling endometrium. Female androgen production depends on the adrenal glands and expression of key enzymes in the endometrium that facilitate local androgen biosynthesis and conversion. Moreover, levels of circulating androgens, in women of reproductive age, fluctuate in a cycle-dependent manner and a mid-cycle peak is associated with conception. AR and androgen signalling have a decisive role in the differentiation of human endometrial stromal cells into decidual cells. Compelling evidence for androgen signalling in the regulation of endometrial function pertaining to implantation and pregnancy is provided by epidemiological studies demonstrating a strong association between polycystic ovary syndrome, premature ovarian failure or advanced maternal age and adverse pregnancy outcome. Thus, androgen signalling is an essential component of normal endometrial physiology and its perturbation is associated with reproductive failure.