Anti-androgen

Prostate cancer is the most frequently diagnosed malignancy in males and ranks second only to lung cancer in terms of annual mortality. Great efforts have been made in the past to develop novel approaches to the treatment of prostate cancer. The two main options for the treatment of prostate cancer are 

A variety of investigational anti-androgens are in development. These compounds have not yet been evaluated chnically but demonstrate potent 

Structural modifications of bicalutamide led to the discovery of the first generation of selective androgen receptor modulators (SARMs). These compounds not only bind to the AR with an affinity in the nanomolar range, but they also show tissue selectivity in animal models [206]. 

Flutamide was the first drug used in prostate cancer therapy for which the withdrawal syndrome was reported. In that study, 40% of patients showed a decline in prostate specific antigen (PSA) levels after cessation of flutamide from the therapeutic protocol. The decline in PSA levels was associated with an improvement of the clinical symptoms. Based on these paradoxical observations, the concept of sequenced androgen ablation was proposed [217]. Several phase II clinical studies were performed, demonstrating safety and tolerability, however, a direct comparison in randomised phase III trials is necessary [218]. 

Although administration of all currently available anti-androgens in most cases leads to stabilisation of the disease, survival of prostate cancer patients has still not been significantly improved. There are several mechanisms by 

---

Filby, A.L., Thorpe, K.L., Maack, G. et al. (2007b). Gene expression profiles revealing the mechanisms of anti-androgen and estrogen-induced feminization in fish. Aquatic... 

Jobling, S., Bum, R.W., and Thorpe, K.L. et al. (2008). Anti-androgens in wastewater treatment works effluents contribute to sexual disruption in wild fish living in English rivers. Proceedings of the National Academy of Science, submitted. 

Johnson, L, Hetheridge, M., and Tyler, C.R. (2004). Assessment of the (Anti-) Oestrogenic and (Anti-) Androgenic Activity of Sewage Treatment Works Effluent. R D Technical Report, Environment Agency. 

Sebire, M., Holtorf, K., and Sanders, M. et al. (2008). Fenitrothion acts as anti-androgen and disrupts the reproductive behaviour of the three-spined stickleback. Ecotoxicology (accepted). 

Sohoni, P. and Sumpter, J.P. (1998). Several environmental oestrogens are also anti-androgens. Journal of Endocrinology 158, 327-339. 

A randomized, double-blind, placebo-controlled trial evaluating the use of a monophasic OC containing 30 meg ethinyl estradiol and 3 mg drospirenone, a progesterone with anti-androgenic effects, showed improvement in the treatment arm compared with placebo.31 In particular, appetite, food cravings, and acne improved. However, active treatment was not associated with a statistically significant improvement in the overall outcome measure, the Calendar of Premenstrual Experiences (COPE) scale, perhaps because of the small sample size (n = 82). 

Anti-androgens and hormones 5a-Reductase inhibitors Progesterone and estrogen Recreational drugs Ethanol Cocaine Marijuana... 

Anti androgens GnRH analogs Steroid synthesis inhibitors f>a reductase inhibitors Testosterone receptor inhibitors... 

Yamada T, Ueda S, Yoshioka K et al (2003) Lack of estrogenic or (anti-)androgenic effects of d-phenothrin in the uterotropic and Hershberger assays. Toxicology 186 227-239... 

Kunimatsu T, Yamada T, Ose K et al (2002) Lack of (anti-)androgenic or estrogenic effects of three pyrethroids (esfenvalerate, fenvalerate, and permethrin) in the Hershberger and uterotrophic assays. Regul Toxicol Pharmacol 35 227-237... 

Vasopressin plays a major role in the control of blood pressure, which is probably essential for vasocongestion or erection. cOxytocin gene expression occurs in ovary and testes, but the exact functions remain unknown. dProgestins, such as cyproterone acetate, are used clinically as anti-androgens (Kravitz, et ah, 1995). 

Abnormalities associated with primary and secondary sex organs, systemic hormone concentrations, and thyroid resulting from anti-androgenic and thyroid activity... 

---