Determinants of Plasma Androgen and Estrogen Levels in Men

Abstract

The steroid hormone testosterone is responsible for the development of the primary and secondary male sex characteristics such as male pattern hair growth, deepening of the voice and increased lean body mass. Testosterone is produced in the testicular Leydig cells in response to stimulation by pituitary derived luteinizing hormone (LH). In its turn the pituitary LH secretion is regulated by the hypothalamus. Testosterone will feed back onto the pituitary and hypothalamus thereby allowing the hypothalamo-pituitary-testicular (HPG) axis to maintain the plasma testosterone concentration within close limits. The serum testosterone concentration is considered normal when within the reference range as supplied by the laboratory. The lower limit of this reference range represents the 2.5 percentile of testosterone levels of a group of apparently healthy men. However, testosterone levels may vary considerably between individuals. Older men may have signs and symptoms reminiscent oftestosterone deficiency such as lack of libido, erectile dysfunction and lower bone and lean body mass. In older men the mean testosterone concentration in blood is lower compared to young men. The question is whether the above-mentioned symptoms truly represent testosterone deficiency. For an adequate answer to this question a better understanding of the determinants ofthe serum testosterone level in men is necessary in order to better differentiate between normal and abnormal levels in a specific individual. In the body testosterone is converted to estradiol. In the past ten years it has become evident that estradiol is responsible for a number of the effects formerly attributed to testosterone. Estradiol has an important role in gaining and maintaining bone mass, closing of the epiphyses and the feedback on gonadotropin release by the pituitary. Since estradiol may be a determinant of the circulating testosterone concentrations but may also be involved in the development ofthe clinical syndrome associated with androgen deficiency, evaluation of estradiol levels in men seems appropriate. However, the interpretation of estradiol levels in men is probably even more difficult than the interpretation of testosterone concentrations. Only little is known about the determinants of the estradiol serum concentration in men, its interaction with testosterone and the minimal tissue level needed to prevent symptoms of estrogen deficiency. Therefore, the aim of the present thesis was to gain more insight into the determinants of the testosterone and estradiol concentrations in men. This information may be helpful when interpreting the serum testosterone and estradiol concentrations of men with symptoms reminiscent of androgen deficiency.