Androgens contribute to the stimulation of cancellous bone formation by ovarian hormones in female rats

We investigated whether androgens, for which the ovaries are the major source in female rats, contribute to the stimulation of cancellous bone formation by ovarian hormones in female rats. Ovariectomized animals were administered 5 alpha-dihydrotestosterone (DHT; 10 and 100 mu g/kg) by daily subcutaneous injection for 13 days, after which histomorphometric analysis was performed at the proximal tibial metaphysis. To prevent ovariectomy from stimulating bone turnover, and hence complicating the interpretation of changes in bone formation, animals were also given the resorption inhibitor 3-amino-1-hydroxypropylidene-1-bisphosphonate. We found that ovariectomy markedly suppressed cancellous bone formation, which was partially prevented by DHT (100 mu g/kg). To further address whether androgens contribute to the stimulation of bone formation by ovarian hormones, we treated intact and ovariectomized female rats with the androgen antagonist flutamide (15 mg . kg(-1). day(-1)) for 28 days. Whereas flutamide had no effect in ovariectomized rats, it significantly reduced cancellous bone formation in intact animals. We conclude that, in the female rat, androgens contribute under physiological conditions to the stimulation of cancellous bone formation by ovarian hormones.