Androgen definition

Until definitive trials are published, it is appropriate to use either LHRH agonist monotherapy or combined androgen blockade as initial therapy for metastatic prostate cancer. 

Definitive evidence that dihydrotestosterone (DHT) is a potent androgen with its own important physiological and pathophysiological actions, separate from those of testosterone, was provided by two reports in 1974 of a rare inborn disorder of male phenotypic sexual differentiation caused by a deficiency in 5a-reductase, the enzyme that converts testosterone to DHT. The reduction in the conversion of testosterone to DHT by 5a-reductase, which underlies this syndrome, leads to a specific developmental defect in the formation of the male external genitalia and the prostate. Males with this genetic disorder exhibit a striking phenotype, in which the internal genitalia are normal... 

Definitive evidence of the role of 5a-reductase in androgen physiology was provided by two reports in 1974 describing subjects who had genetic mutations affecting expression of the enzyme, resulting in a reduction in DHT formation (Imperato-McGinley et al., 1974 Walsh et... 

Fig. 3. The involvement of androgens in the development of the male urogenical tract. The organs identified in heavy type in the definitive male (b) differentiate in the presence of testosterone the remainder require 5a-DHT for their correct establishment.

Isotestosterone and 8a, 1 Oa-testosterone can be considered as substituted testosterone derivatives where the 8-H is substituted by an alkyl group. In the case of 8a,10a-testosterone other structural features are prohibitive for biological activity. However, 8-isotestosterone displays decreased, but definite androgenic and anabolic properties. Nagata [160] prepared some 8/3-substituted testosterone homologs —8-methyl-testosterone (E-30) and others. In all cases decreased androgenic and anabolic potencies were observed. These facts point to the importance of /3-face attachment to the receptor at carbon-8. 

Bulky substituents in 10-positions decrease the androgenic and anabolic activities to a large extent. This definitely points to the /8-face attachment at C-10. Results obtained with 9a,10a-testosterone derivatives confirm the importance of /3-face attachment. However the steric requirement of the methyl group, as measured by the 2.0 A van der Waals radius [222], is no bar to /3-face attachment to the receptor at C-10. The steric requirements at C-10 can accommodate 10-methyl substitution (the presence of the 19-methyl group). 

Pilepich MV, Winter K, John MJ, et al. Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate. Int J Radiat Oncol Biol Phys 2001 50 1243-1252. 

Here the follicle-stimulating hormone (FSH) is definitely more increased than the luteinising hormone (LH), which leads to an inverse relation between the two gonadotrophic hormones. Furthermore, there is extraglandular synthesis of oestrogens from androgenous precursors in the ovaries and adrenal glands. 

CRYPTORCHIDISM Cryptorchidism, the failure of one or both testes to descend into the scrotum, affects up to 3% of fuU-term male infants, becoming less prevalent with advancing postnatal age. Cryptorchid testes have defective spermatogenesis and are at increased risk for developing germ cell tumors. Hence, the current approach is to reposition the testes as early as possible, typically at 1 year of age but definitely before 2 years of age. The local actions of androgens stimulate descent of the testes thus, hCG can be used to induce testicular descent if the cryptorchidism is not secondary to anatomical blockage. Therapy usually consists of injections of hCG (3000 lU/m body surface area) intramuscularly every other day for 6 doses. 

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