Sex differences in metabolism

Hamilton JA, Grant M Sex differences in metabolism and pharmacokinetics Effects on agent choice and dosing. NIMH Conference, Bethesda, MD, November 4, 1993... 

Strain differences in route and rate of metabolism and hence toxicity have been documented in inbred strains of mice. Species and strain differences in receptors occur. Sex differences in metabolism and toxicity are mostly confined to rodents. Generally male rats metabolize chemicals faster than female rats. These differences can be removed by castration of males and returned by treatment with androgens. 

Quinn GP, Axelrod J, Brodie BB, et al. Species, strain and sex differences in metabolism of hexobarbitone, amidopyrine, antipyrine and aniline. Biochem Pharmac 1958 1 152-159. 

Hathway DE, Brown SS, Chasseaud LF, et al. Foreign Compound Metabolism in Mammals, Vols. 1-6, London The Chemical Society, 1970-1981. (This series contains chapters on species, strain and sex differences in metabolism.)... 

Walle T, Walle U, Cowart TD, Conradi EC. 1989 Pathway selective sex differences in metabolic clearance of propranolol in human subjects. Clin. Pharm. Ther. 46(3) 257-263. 

As well as phase 1 reactions, phase 2 reactions also show sex differences. Thus glucuronic acid conjugation of 1-naphthol (figure 4,4) is greater in male than female rats and this difference is also found in microsomes in vitro. The acetylation of sulphanilamide (figure 4.64) is also greater in male than female rats. Sex differences in metabolism depend on the substrate, however. For example, the hydroxylation of aniline or zoxazolamine shows little difference between the sexes, in contrast to the three-fold greater metabolism of hexobarbital or aminopyrine in male compared with female rats. 

Sex differences in metabolism are less pronounced in species other than the rat. In humans, differences, when noted are similar to those in the rat, whereas in the mouse they are often the reverse of those in the... 

In humans too, sex differences in metabolism exist, but they are small and usually clinically not important. The clearance of benzodiazepines eliminated by metabolic conjugation (temazepam, oxazepam, lorazepam) is, for example, significantly smaller in women than in men. 

While fiver microsomes from male rats metabolise xenobiotics fast than fiver microsomes from female rats, enzyme preparations from rat lung (benzphe-tamine demethylase, p-chloro-W-methylanifine de-methylase, benzpyrene hydroxylase, UDP-glucuronyltransferase) and gut did not show sex differences in metabolism of several drug substrates (Chhabra and Pouts 1974). 

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