Excessive androgen exposure in female-to-male transsexual persons of reproductive age induces hyperplasia of the ovarian cortex and stroma but not polycystic ovary morphology.

STUDY QUESTION Does administration of androgen to female-to-male transsexual persons (FTMs) of reproductive age induce polycystic ovary (PCO) morphology? SUMMARY ANSWER Administration of high-dose androgen to women causes pathognomonic changes to the ovarian cortex and stroma that resemble Stein-Leventhal syndrome but it does not induce PCO morphology. WHAT IS KNOWN ALREADY Androgen is thought to play a key role in follicular development and to be involved in the pathophysiology of polycystic ovary syndrome (PCOS). In several experimental models, animals given high-dose androgen show ovarian changes similar to those in women with PCOS. In previous human studies, the ovaries of FTMs who received androgen for long periods also exhibited PCO morphology. STUDY DESIGN, SIZE, DURATION We conducted a retrospective case-control study of women, all without PCOS, undergoing salpingo-oophorectomy. The case group consisted of 11 FTMs taking testosterone (duration range: 17 months to 14 years), while the control group consisted of 10 patients with gynaecologic malignancies who did not receive testosterone. PARTICIPANTS/MATERIALS, SETTING, METHODS Resected ovaries from both groups were compared histologically with respect to changes in the cortex and stroma, and the number of follicles at each maturation stage. MAIN RESULTS AND THE ROLE OF CHANCE Compared with controls, the FTM group had a thicker ovarian cortex (P = 0.0001), and more hyperplastic collagen (P = 0.001), ovarian stromal hyperplasia (P = 0.003) and stromal luteinization, i.e. luteinized stromal cells with a small dark central nucleus surrounded by clear cytoplasm (P = 0.004). Isolated clusters of such stromal luteinized cells were found only in the testosterone-treated ovaries of FTMs. The number of primordial follicles was similar in the two groups (P = 0.22). The numbers of early stage (primary, pre-antral and early antral) follicles, which are dependent on androgen, were also similar (P = 0.81), as were the numbers of antral follicles (P = 0.97). In contrast, significantly greater numbers of atretic follicles were seen in the FTM than that in the control group (P = 0.01). LIMITATIONS, REASON FOR CAUTION In addition to the low numbers in the study groups, the histological changes in FTMs were investigated after testosterone administration, therefore it is possible that some of the observed changes were already present, before androgen administration. WIDER IMPLICATION OF THE FINDINGS Our results are at variance with those of earlier studies and suggest that excessive androgen exposure in women of reproductive age may not be a factor in the pathogenesis of PCOS.