Evaluation of the hypothalamic-pituitary effects of digoxin

Normally menstruating young female volunteers with no evidence of cardiovascular disease participated in a controlled study of digoxin effects on serum thyroid stimulating hormone (TSH) and prolactin levels in the basal state and after stimulation with thyrotropin releasing hormone (TRH). In the first study, subjects received oral digoxin, 0.5 mg daily, or matching placebo, on days 10 through 22 of a menstrual cycle, then crossed over to placebo or digoxin for days 10 through 22 of the next cycle. Basal serum TSH and prolactin on days 7 through 9 and 20 through 22 did not differ significantly between placebo and digoxin cycles. Levels of both hormones rose after a 200-micrograms intravenous dose of TRH given on days 8 and 21, but the response to TRH did not differ between placebo and digoxin cycles. In the second study, subjects received 0.5 mg intravenous digoxin daily for days 7 through 21 of a menstrual cycle. Basal serum TRH and prolactin did not change significantly in response to digoxin. The findings suggest that hormonal changes associated with digoxin therapy, if they exist, are more likely to reflect direct effects on the target organ rather than indirect effects on the hypothalamic-pituitary axis.