Digoxin does not alter plasma steroid levels in health men

Area of Science:

• Endocrinology
• Pharmacology

Background:

• Digoxin is a cardiac glycoside with reported feminizing effects in men.
• Previous studies suggest digoxin does not compete with estradiol receptors or cause uterotrophic effects.

Purpose of the Study:

• To investigate if digoxin alters plasma sex steroid concentrations, potentially explaining reported feminizing effects.
• To assess the impact of digoxin on the hypothalamic-gonadal feedback axis.

Main Methods:

• Six healthy men received therapeutic doses of digoxin for 43 days.
• Plasma concentrations of multiple sex steroids and hormones were measured before, during, and after digoxin treatment.
• Hormonal responses to adrenocorticotropic hormone (ACTH) and human chorionic gonadotropin (hCG) stimulation were assessed.

Main Results:

• Digoxin treatment did not significantly alter plasma levels of testosterone, androstenedione, dehydroepiandrosterone, estrone, estradiol, progesterone, 17-hydroxyprogesterone, cortisol, or aldosterone.
• Hormonal responses to ACTH and hCG stimulation remained unchanged during and after digoxin administration.
• The hypothalamic-gonadal feedback axis, assessed via luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH), was not affected by digoxin.

Conclusions:

• The estrogen-like activity attributed to digoxin cannot be explained by altered plasma sex steroid availability.
• Feminizing effects associated with digoxin may be due to co-existing conditions in cardiac patients that influence sex steroid hormones.
• Digoxin may be a preferred digitalis therapy to mitigate feminizing effects.