The Effects of Clomiphene in Impotence a Clinical and Endocrine Study

Hormone treatment for impotence and impotentia ejaculandi (delayed or absent ejaculation in the presence of normal erections and desire) (Johnson, 1965) is based on two assumptions: namely—that (1) potency in the male is androgen dependent and (2) impotency is due to relative androgen deficiency (Miller, 1968; Margolis et al., 1967; Sobotka, 1969). The synthetic preparations most frequently used are methyl testosterone, various esters, including the propionate, deconate, enanthate, etc. (Tuthill, 1955; Kupperman, 1967) and more recently a number of testosterone- ‘aphrodisiac’ combinations (Margolis et al., 1967; Cooper et al., 1971, etc.). Despite some claims of therapeutic success for the various regimes, the administration of exogenous hormones has several pharmacologic disadvantages. For instance methyl testosterone, which has to be taken sublingually or bucally, may be associated with severe toxic effects such as cholestatic jaundice, etc. (Goodman and Gilman, 1965). Parenterally administered testosterone esters, although less toxic and more certainly absorbed than methyl testosterone, have all the drawbacks of the intramuscular route; also their rate(s) of tissue release may not be optimal for metabolism. Additionally, all these synthetic compounds may inhibit endogenous testosterone formation and spermatogenesis by suppressing pituitary gonadotrophins. Long term administration may result in Leydig cell inactivity and even disuse atrophy. Recently Harkness et al. (1964, 1968) have observed that clomiphene (Fig. 1), a non-steroid triethylene derivative which in females stimulates the anovulatory ovary to secrete oestrogens (Bishop, 1970), significantly raised the levels of urinary steroid metabolites, including testosterone, in a proportion of ‘normal’ and corticosteroid deficient males. This unexpected testosterone elevating effect suggested its possible ‘experimental’ use as an alternative drug treatment in impotence. Accordingly a limited pilot study on five ‘primary’ (non-organic) impotent males was conducted: its main aims were (a) to assess the potential clinical utility of the drug and (b) to study its effects on the ‘pituitary-testes-axis' as reflected by plasma testosterone levels.