STEROID HORMONES AND AGING IN MAN 



417 



the majority of excreted urinary ll-deoxy-17-ketosteroids do not seem 

 to be markedly age-conditioned. A systematic study of the suggested 

 relative increase in 5/3 reduction does seem to be called for. Since this 

 implies that etiocholanolone is in relatively larger concentration than 

 androsterone ( Figure 4 ) , it is tempting to attribute some of the symp- 

 toms of aging to the pyrogenic activity of the former (Kappas et al., 

 1957) and its lack of androgenicity. However, the clear superiority of 

 testosterone as an androgen as well as an anabolic agent ( Dorfman and 

 Shiple\-, 1956) suggests that its diminishment may be the primary 

 factor in the reduced libido, muscle wastage, and other phenomena 

 observed in elderly subjects. Unfortunately, testosterone as such has 

 not been found in measurable amount in urine or in blood, nor do we 

 have a specific metabolite indicative of its production, unless it prove 

 to be A^^-androstene-3a-ol recently found in states characterized by 

 high androgenicity (Burstein and Dorfman, 1960). 



A number of recent studies indicate that estrogen biosynthesis 

 proceeds by the pathways indicated in Figure 5. The decline in estrone 

 and estradiol production with acU'ancing age may be due to any of a 

 number of factors. It may be simply conditioned by the reduced pro- 

 duction of A^-androstenedione. This seems not too likely, since the 

 latter is produced in milligram amounts daily, whereas the estrogens 

 are produced in microgram amounts. It is possible that the 19-hydroxy- 

 lase for androstenedione is the bottleneck in this process and that it is 

 the age-susceptible factor. However, a number of other possibilities 

 clearly exist. Any of the steps, thus far not entirely characterized, be- 



A -ANDROSTENE -3-ot-OL 



HO ^^ H 



ANDROSTERONE 



HO -- H 



ETIOCHOLANOLONE 



Figure 4. Metabolism of urinary 17-ketosteioid precursors. 



