The importance of oestrogens in males.

Abstract

For a long time oestrogens in the human male have been regarded as a mere by-product of testosterone synthesis. Only since the description of an oestrogen-resistant man (Smith et al ., 1994) has it been fully realized that oestrogens play an import role in bone homeostasis, cardiovascular health and pituitary–gonadal interactions in men. Due to a disruptive homozygous oestrogen receptor alpha (ER α ) mutation, this man was virtually insensitive to oestrogens which lead to osteoporosis, unfused epiphyses resulting in linear growth into adulthood, increased gonadotrophin levels and evidence of premature atherosclerosis (Sudhir et al ., 1997a) and endothelial dysfunction (Sudhir et al ., 1997b). Additionally, there was low viability of sperm and glucose intolerance with acanthosis nigrans. Two adult aromatase-deficient men showed, besides undetectable oestrogen levels, low bone mass, unfused epiphyses, increased gonadotrophins and a unfavourable lipid profile (Morishima et al ., 1995; Carani et al ., 1997). Earlier, Korach (1994) described similar observations in ER α knockout mice. Heterozygous mice exhibited no obvious phenotypic abnormalities. Homozygous male mice proved to be infertile, showing smaller testes with dysmorphic seminiferous tubules and a sperm count of less than 10% compared to normal mice. Finally, bone mineral density was 20–25% lower in male and female mutants compared to wild-type animals. These reports indicate that oestrogens also play a central role in several metabolic processes in men. The interrelation between testosterone and oestrogen biosynthesis makes it difficult to separate their respective biological effects. Therefore, it is not unlikely that biological effects formerly attributed to testosterone actually represent effects of oestrogens. In light of the observations in oestrogen-resistant or -deficient males, and because of the wealth of evidence for the role of oestrogens in the (patho)physiology of bone and lipid metabolism, cardiovascular disease and the hypothalamo–pituitary– gonadal axis in women, this review will discuss these areas, focusing on the clinical importance of oestrogens in males.