Descriptions of the effect of androgens on ovarian human tissues are exceptional. This opportunity was provided for us by 17 women with transsexualism--female to male transsexuals (TSX)--who had been given androgens for a mean period of 21 months before hystero-salpingo-oophorectomy took place. Twenty-nine ovaries from TSX and 14 control ovaries from 13 regularly cycling women were examined. As compared with controls, TSX ovaries were enlarged and displayed a two-fold increase in cystic follicles and a 3.5-fold increase in atretic follicles; the ovarian cortex was collagenized and three-times thicker. Theca interna hyperplasia and luteinization were uniformly observed in TSX cystic follicles. Stromal hyperplasia was a constant finding in TSX ovaries, accompanied by clusters of luteinized stromal cells in 12 cases. Eventually, these findings met the histological criteria for the diagnosis of polycystic ovaries. These observations demonstrate that androgens alone may induce polycystic changes. The assumption that the role of androgens is pivotal at the follicular level--inducing follicle growth arrest and accelerating cystic changes--in the genesis of polycystic ovaries is reinforced.

Polycystic ovary syndrome (PCOS) represents the most common cause of anovulatory infertility and affects 5-10% of women of reproductive age. The etiology of PCOS is still unknown. The current study is the first to describe consistent differences in gene expression profiles in human ovaries comparing PCOS patients vs. healthy normoovulatory individuals. The microarray analysis of PCOS vs. normal ovaries identifies dysregulated expression of genes encoding components of several biological pathways or systems such as Wnt signaling, extracellular matrix components, and immunological factors. Resulting data may provide novel clues for ovarian dysfunction in PCOS. Intriguingly, the gene expression profiles of ovaries from (long-term) androgen-treated female-to-male transsexuals (TSX) show considerable overlap with PCOS. This observation provides supportive evidence that androgens play a key role in the pathogenesis of PCOS. Presented data may contribute to a better understanding of dysregulated pathways in PCOS, which might ultimately reveal novel leads for therapeutic intervention.