Competition of the Histamine H₂ Antagonist Cimetidine for Androgen Binding Sites in Man

Abstract

Gynecomastia and impotence have been described as side‐effects of cimetidine therapy. It has previously been shown that cimetidine possesses antiandrogenic properties and competes for dihydrotestosterone (DHT) binding to the cytosol and nuclear fractions of the rat prostate. Because this interaction may be relevant to the clinical findings in man, the authors analyzed the effects of cimetidine on androgen binding to the human prostate, testis, and serum. Cimetidine competed for DHT binding sites in the human prostate with a displacement curve parallel to that of nonlabeled DHT, whereas no binding to the testis or serum was apparent. Neither histamine nor the H1 antagonist diphenhydramine was capable of inhibiting androgen binding to the human prostate. Thus, androgen antagonism may be the mechanism of the endocrine side‐effects of cimetidine in man.

Ecotoxicological assessment of cimetidine and determination of its potential for endocrine disruption using three test organisms: Daphnia magna, Moina macrocopa, and Danio rerio

“…Down-regulation of cyp17 gene observed in male fish can therefore explain the decrease in T levels. Several in vitro observations also indicated that cimetidine could compete with androgens for specific receptor sites (Sultan et al, 1980;Winters et al, 1980). Androgen inhibition has been related to the side effects of cimetidine, e.g., sexual dysfunction and gynecomastia (Garcia Rodriguez and Jick, 1994).…”

“…Endocrine disrupting potential of cimetidine has also been suggested in several in vitro, and in vivo experimental and clinical studies. Cimetidine competes with androgen for binding to androgen receptors in rat ventral prostate cells and fibroblasts (Sultan et al, 1980;Winters et al, 1980). Cimetidine exposure in rats resulted in decreased serum testosterone levels as well as reduced weight of androgen-dependent tissues, e.g., testes and prostate (Baba et al, 1981;Peden et al, 1981;Anand and Van Thiel, 1982).…”