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Verhandelingen - Koninklijke Academie voor Geneeskunde van Belgie 1997

[Juvenile hormones, reality or myth?].

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A Vermeulen

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Abstract

Recently, the "discovery" of so called "rejuvenating" pills, has attracted much interest in the media and has raised irrational expectations among the elderly population. These so called "rejuvenating drugs" are dehydroepiandrosterone (DHEA), a steroid hormone secreted by the adrenal cortex, and melatonin, an indol derivative, secreted by the pineal gland, both known since many years. Dehydroepiandrosterone is quantitatively by far the most important steroid in the human organism; it is a weak androgen, a small fraction of which is aromatized to estrogens in peripheral tissues. Plasma levels of DHEA decrease with age and some authors consider these levels as a reliable parameters of biological age, the more so that some studies seem to indicate that low levels are accompanied by increased morbidity and mortality. This could not be confirmed, however, by other authors. In in vitro experiments, DHEA has anti-oxidative effects, inhibits platelet aggregation and, possibly, stimulates the immunological system. In animal experiments DHEA has some antitumoral effects. These effects were, however, observed in animal species which do not secrete DHEA. It should, moreover, be mentioned that administration of DHEA in a high dosage, induced the development of hepatic carcinoma in 14 out of 16 rats. Preliminary controlled studies, performed in 30 elderly persons, showed an improvement of general wellbeing with an increase in plasma IGF-1 levels; in women a moderate increase in plasma testosterone and estradiol was observed. Hence these studies show a moderately beneficial effect of DHEA therapy. They need to be confirmed and they warrant further well controlled studies. Melatonin is a hormone secreted by the pineal gland, the releasing stimulus of which is darkness. It synchronizes the biological rhythms as well as the seasonal biological changes induced by the photoperiod. It induces sleep and is an euphoretic. Melatonin plasma concentrations decrease with age and this decrease has been related to the impaired sleep induction in elderly. Melatonin levels are also decreased in depression. In mice, transplantation of the pineal gland of young animals to old animals increases life expectancy by +/-20%. In in vitro experiments, melatonin appears to have some anti-oxidative effects, which led to the hypothesis that it might retard the ageing process and inhibit the growth of tumor cells. In man, melatonin has been shown to be effective in preventing jet lag and in improving sleep induction in the elderly as well as disturbances of the nycthemeral rhythms in blind persons. One research group even reported favourable effects of a combined melatonin-IGF-1 treatment of metastatic carcinomas; these results were not confirmed up to now. As to the advertised effects on sexuality, it is well known that melatonin inhibits gonadotropin secretion, which causes gonadal atrophy. Hence it is evident that we can not expect a stimulation of sexuality by melatonin administration. As to prolongation of life expectancy, there are, so far, no indications for such an effect in man.

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