STEROIDS AND GROWTH 389 



block growth-hormone eflFects on the epiphyses, are in general agree- 

 ment with our understanding of the adolescent growth response. Thus, 

 as androgens are first formed and secreted in significant amounts by 

 the testes and adrenal gland, the growth response is augmented. As the 

 output of androgens reaches a peak during the end of adolescence, 

 epiphyseal fusion occurs. Whether or not the endogenous supply of 

 androgen is sufficient to account for the epiphyseal closure at this time 

 cannot be definitely stated. At least, such a mechanism of action does 

 exist. The androgens may also act to depress the elaboration of 

 growth hormone from the pituitary gland, and this possibility requires 

 investigation. 



Panhypogonadism and growth. The term hypogonadism is used to 

 indicate that both the tubules and the interstitial cells of the testes aie 

 destroyed or absent as a result of trauma, castration, congenital defects, 

 or other causes. Aside from the absence of normal development of sec- 

 ondary sex characteristics, the fusion of skeletal epiphyses is delayed. 

 Although the adolescent spurt in growth is absent, growth in height 

 continues at an apparently normal and steady rate through the adoles- 

 cent period. With this continued growth, normal adult stature is usu- 

 ally reached at an approximately normal age. Only a few eunuchoid 

 individuals grow to an exceptionally tall height, even though the delay 

 of skeletal maturation and epiphyseal fusion presumably ofiFers an op- 

 portunity for continued growth. Because of the delayed epiphyseal 

 fusion there is, however, a tendency for eunuchs and eunuchoids to 

 develop relatively long extremities ( Talbot and Sobel, 1947 ) . 



It is apparent from such data that the increased output of andro- 

 gen from the testes that normally occurs during adolescence is not the 

 main factor that finally arrests growth. In the eunuchoid or castrate in- 

 dividual, ketosteroid excretion is below normal ( Dorfman and Shipley, 

 1956) and is derived from adrenal androgen. The adrenal androgen is 

 sufficient to produce some growth of sexual hair but insuflScient to 

 allow normal development of other secondary sex characteristics. There 

 is no evidence to implicate adrenal androgens as factors that finally 

 stop growth. 



Androgens to stimulate growth. There is ample evidence demon- 

 strating that testosterone and related steroids increase growth rate 

 (height) in children of subnormal stature (Howard et al., 1942; Tal- 

 bot, Sobel, Burke, et aJ., 1947; Talbot and Sobel, 1947. ) The rate of 

 growth is increased from subnormal to normal or above normal levels. 

 An e£Fect on growth is usually seen within three months and is pro- 

 duced by 5 mg. of methyl testosterone orally per day. Higher doses of 

 10, 20, or 30 mg. per day apparently do not produce a greater growth 

 response. Further, the androgens will not increase linear growth after 

 fusion of the skeletal epiphyses has occurred. Administration of andro- 



