Effects of long-term testosterone exposure on ovarian function and morphology in the rhesus monkey

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Abstract
This study was aimed at developing a model in the rhesus monkey for the human gynecologic disorder termed the polycystic ovary syndrome (PCOS). The effects of chronic constant androgen exposure upon quantitative ovarian morphology and ovulatory function were examined. Twenty‐five normally cycling females, aged 4–12 yr and weighing 3.3–8.2 kg, were enrolled in the study in random fashion. Seventeen animals were implanted subcutaneously (s.c.) with 10 or 25 mg testosterone‐filled silastic tubing so as to maintain steady serum levels of testosterone averaging 80 ng/dl (low‐dose group, n=8) and 115 ng/dl (high‐dose group, n = 9) for 13–16 months. Eight animals served as controls (sham implants); in these, mean serum testosterone levels averaged 24 ng/dl. No effect of androgen treatment was observed on ovulatory function as gauged by periodic luteal phase progesterone determinations and the presence of a fresh corpus luteum at laparoscopy. Menstrual cycle frequency (number of cycles over number of months of observation) was, however, slightly but significantly (P 7lt; 0.05) reduced in the high‐dose (88.9%) vs. the control (96.7%) and low‐dose (95.0%) groups. Quantitative morphology, performed by light microscopy on a single ovary obtained from 16 of the 25 animals and read in a blinded fashion, revealed no differences in ovarian weight, capsular width and numbers, size, or proportion of healthy and atretic follicles among the three groups. Although constant long‐term testosterone exposure failed to result in a picture resembling the human PCOS counterpart, factors such as higher levels, a longer duration of exposure, a different type of androgen used, or a critical peripubertal period of exposure will have to be considered in future experiments.