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Chemical Compound Review

AndroGel     (8S,9S,10R,13S,14S,17S)-17- hydroxy-10,13...

Synonyms: Sustanon, Testolin, Androderm, Testoderm, Virormone, ...
 
 
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Disease relevance of AndroGel

  • Together, the above findings and the fact that T, but not Adiol, can induce transcriptional activity in a mutant AR (mtAR708), suggest that, without being metabolized into T, Adiol itself may represent a natural hormone with androgenic activity in human prostate cancer cells [1].
  • Patients with IHH were treated with hCG/human menopausal gonadotropin, whereas patients with primary hypogonadism received T treatment [2].
  • The magnitude of the serum LH and T response to iv pulses of GnRH [50 ng/kg body weight (BW)] and naloxone (1 mg/kg BW) did not differ between control and treated animals during the nonbreeding or breeding season at 6 yr of age [3].
  • Thus, single daily injection of GnRH-A and T failed to predictably induce azoospermia in normal men over the 16-week treatment period.(ABSTRACT TRUNCATED AT 400 WORDS)[4]
  • Exogenous T therapy resulted in normal virilization, whereas therapy with hCG was ineffectual [5].
 

Psychiatry related information on AndroGel

  • Chronic treatment with agonist analogs of GnRH results in reversible oligospermia in man, but leads to impotence and decreased libido due to a concomitant fall in serum testosterone (T) concentrations [4].
  • However, when B was given in combination with T, not only were the positive effects of T eliminated, but there was a reduction in activity (31%) and home-range size (72%) similar to that reported in lizards that received B implants alone [6].
  • The effect of social interaction on B and T levels was also examined by presenting territory-holding males with a size-matched male intruder [7].
  • These results indicate that betaE2 and TES ameliorate the amnesia induced by inhibition of (Na(+), K(+))-ATPase activity, and that the protective effect of betaE2 is caused by a non-genomic, rather than a genomic effect or a radical scavenging action [8].
  • The Testim(R) Study of Testosterone Androgen Response Time (START) explored the time to response in sexual activity, desire, and mood following testosterone replacement therapy with Testim for 30 days in 638 hypogonadal men [9].
 

High impact information on AndroGel

  • Moreover, as shown in many systems, castration levels of serum testosterone (T) at 0.2-0.4 ng/ml exert significant androgenic activity in target tissues [10].
  • In this review we discuss evidence indicating the existence of specific binding receptor sites for progesterone (P), estrogen (E), and testosterone (T) in neural membranes [11].
  • Second, we examine the physiological and biochemical data supporting the concept of cognate membrane receptors for P, E, and T, the so-called mPR, mER, and mTR [11].
  • Androgen resubstitution after a 10-day period of T deprivation resulted in a rise in the tumor cell proliferation index to 20% within 4 days [12].
  • Administration of supraphysiologic doses of T in intact male mice did not lead to an increase in the number of Ki-67-stained nuclei [12].
 

Chemical compound and disease context of AndroGel

 

Biological context of AndroGel

  • VT, presumably, does not simply represent one step in the biochemical cascade of events that is induced by T in the brain and leads to the expression of male sexual behavior [17].
  • Thus, this regimen, employing constant infusion of 400 micrograms GnRH agonist daily plus T led to a greater suppression of spermatogenesis than the previous regimen employing single daily injections of 200 micrograms of the same agonist plus T [18].
  • Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men [19].
  • T levels and the degree of frailty were not different in the wild-type LH group compared with the heterozygote LH variant group [20].
  • Both E and T show a significant drop immediately after ovulation; P4 does not [21].
 

Anatomical context of AndroGel

  • MATERIALS AND METHODS: In an age-stratified population sample of 314 men (age, 22-91 years), we assessed volumetric BMD (vBMD) and bone geometry by QCT at the lumbar spine, femoral neck, distal radius, and distal tibia and related these to circulating bio E(2) and bio testosterone (T) levels [22].
  • Pulsatile LH stimulation of the testes does not appear necessary to maintain T secretion [23].
  • Prior hCG/human menopausal gonadotropin therapy had resulted in high normal serum T levels and near-normal semen quality, but during subsequent hCG therapy, spermatogenesis markedly decreased [24].
  • Experimental data suggest that FSH-stimulated Sertoli cells can enhance LH-induced Leydig cell testosterone (T) production [25].
  • The ratios of the 5 alpha-saturated metabolites (DHT plus Adiol) to T or to T + Adion, respectively, parallel total androgen concentrations, whereas the Adiol to DHT ratio, a parameter of 3 alpha-reductase activity, was highest in striated muscle and thigh skin and lowest in androgen target tissues (labia majora and clitoris) [26].
 

Associations of AndroGel with other chemical compounds

  • Castration markedly decreases the immunoreactivity in both the VT-immunopositive elements of the BSTm and the innervation of the SL and POM, whereas T-replacement therapy restores the VT immunoreactivity to a level typical of intact birds [17].
  • Castration reduces prostate size and causes intraprostatic testosterone (T) and dihydrotestosterone (DHT) to fall to very low levels [27].
  • Reflecting their intact gonadal status, vBMD/structural parameters were not related to sex steroid levels in young men, whereas bio E(2) levels were associated consistently with vBMD and variably with bone geometric parameters in the elderly men; middle-aged men showed associations with bio E(2) and bio T at some sites [22].
  • The dissociation of E2 from T responses to nafarelin during puberty suggests that aromatase activity does not fully mature in males until puberty is complete [28].
  • At baseline, PCOS women had higher T, free T, androstenedione, and estrone [29].
 

Gene context of AndroGel

  • Alterations in immunostaining patterns for TGFalpha and EGFR were exclusively detected in the dysplastic lesions in the DLPs of T + E2-treated rats [30].
  • This dose of T, however, had little effect on LH in mice with a blank pellet in the AH [31].
  • Melatonin in the AH markedly increased the content of gonadotropin-releasing hormone (GnRH) in the mediobasal hypothalamus (P less than 0.05) in mice treated with T; however, there was little effect of melatonin and/or T in any other region examined [31].
  • T and delta 4A levels returned to normal with elevation to normal of SHBG [32].
  • At 0 hour, compared with baseline, significant increases were observed in the plasma concentrations of testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), cortisol (F), free T index (T/SHBG), and prolactin (PRL) [33].
 

Analytical, diagnostic and therapeutic context of AndroGel

  • Mean serum T and E(2) levels were significantly lower and higher, respectively, in the obese men than in the control group [serum T, 13.5 +/- 2.4 vs. 19.4 +/- 1.4 nmol/L (mean +/- SEM; P: = 0.01); serum E(2), 0.184 +/- 0.01 vs. 0.153 +/- 0.01 nmol/L (P: < 0.05)] [34].
  • Plasma FSH, LH, PRL, T, and estradiol levels were also determined before and 3 months after treatment [2].
  • A regimen of two Testoderm TTS testosterone patches (Alza Corp., Mountain View, CA) daily can maintain serum concentrations of total and free testosterone and its metabolites dihydrotestosterone and estradiol in the midnormal range in healthy hypogonadal men and men on hemodialysis [35].
  • We conclude that continued application of AndroGel resulted in beneficial effects similar to those with injectables and other transdermal preparations [19].
  • Determination of AF levels of T would appear to be a valuable screening test for antenatal diagnosis of sex (predictive error, less than or equal to 15%), but not in the presence of steroidogenic enzyme defects [36].

References

  1. Delta5-androstenediol is a natural hormone with androgenic activity in human prostate cancer cells. Miyamoto, H., Yeh, S., Lardy, H., Messing, E., Chang, C. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  2. Daytime plasma melatonin levels in male hypogonadism. Ozata, M., Bulur, M., Bingol, N., Beyhan, Z., Corakci, A., Bolu, E., Gundogan, M.A. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
  3. Neonatal treatment of male monkeys with a gonadotropin-releasing hormone agonist alters differentiation of central nervous system centers that regulate sexual and skeletal development. Mann, D.R., Akinbami, M.A., Gould, K.G., Tanner, J.M., Wallen, K. J. Clin. Endocrinol. Metab. (1993) [Pubmed]
  4. Hormonal effects of gonadotropin-releasing hormone (GnRH) agonist in the human male. III. Effects of long term combined treatment with GnRH agonist and androgen. Bhasin, S., Heber, D., Steiner, B.S., Handelsman, D.J., Swerdloff, R.S. J. Clin. Endocrinol. Metab. (1985) [Pubmed]
  5. A syndrome of gonadotropin resistance possibly due to a luteinizing hormone receptor defect. David, R., Yoon, D.J., Landin, L., Lew, L., Sklar, C., Schinella, R., Golimbu, M. J. Clin. Endocrinol. Metab. (1984) [Pubmed]
  6. Effects of steroid hormone interaction on activity and home-range size of male lizards. DeNardo, D.F., Sinervo, B. Hormones and behavior. (1994) [Pubmed]
  7. Steroid correlates of territorial behavior in male jacky dragons, Amphibolurus muricatus. Watt, M.J., Forster, G.L., Joss, J.M. Brain Behav. Evol. (2003) [Pubmed]
  8. Effects of steroid hormones on (Na+, K+)-ATPase activity inhibition-induced amnesia on the step-through passive avoidance task in gonadectomized mice. Sato, T., Tanaka, K., Ohnishi, Y., Teramoto, T., Irifune, M., Nishikawa, T. Pharmacol. Res. (2004) [Pubmed]
  9. Early Response Time in Sexual Activity and Mood Following Testosterone Gel Replacement in Hypogonadal Males from the Testim(R) START Study. Loizides, E., Swierzewski, M.J., O'neill, C., Griesser, J., Smith, T. Reviews in urology. (2004) [Pubmed]
  10. Treatment of prostate cancer with gonadotropin-releasing hormone agonists. Labrie, F., Dupont, A., Bélanger, A., St-Arnaud, R., Giguère, M., Lacourcière, Y., Emond, J., Monfette, G. Endocr. Rev. (1986) [Pubmed]
  11. Membrane sex-steroid receptors in the brain. Ramirez, V.D., Zheng, J. Frontiers in neuroendocrinology. (1996) [Pubmed]
  12. Determination of the proliferative fraction of a transplantable, hormone-dependent, human prostatic carcinoma (PC-82) by monoclonal antibody Ki-67: potential application for hormone therapy monitoring. Gallee, M.P., van Steenbrugge, G.J., ten Kate, F.J., Schroeder, F.H., van der Kwast, T.H. J. Natl. Cancer Inst. (1987) [Pubmed]
  13. Puberty in the chimpanzee: somatomedin-C and its relationship to somatic growth and steroid hormone concentrations. Copeland, K.C., Eichberg, J.W., Parker, C.R., Bartke, A. J. Clin. Endocrinol. Metab. (1985) [Pubmed]
  14. Steroid secretion by masculinizing and "feminizing" Hilus cell tumors. Mandel, F.P., Voet, R.L., Weiland, A.J., Judd, H.L. J. Clin. Endocrinol. Metab. (1981) [Pubmed]
  15. Effect of a novel steroid (PM-9) on the inhibition of 5alpha-reductase present in Penicillium crustosum broths. Flores, E., Cabeza, M., Quiroz, A., Bratoeff, E., García, G., Ramírez, E. Steroids (2003) [Pubmed]
  16. Protection by gonadal steroid hormones against procarbazine-induced damage to spermatogenic function in LBNF1 hybrid rats. Parchuri, N., Wilson, G., Meistrich, M.L. J. Androl. (1993) [Pubmed]
  17. Steroid-induced plasticity in the sexually dimorphic vasotocinergic innervation of the avian brain: behavioral implications. Panzica, G.C., Aste, N., Castagna, C., Viglietti-Panzica, C., Balthazart, J. Brain Res. Brain Res. Rev. (2001) [Pubmed]
  18. Hormonal effects of gonadotropin-releasing hormone (GnRH) agonist in men: effects of long term treatment with GnRH agonist infusion and androgen. Bhasin, S., Yuan, Q.X., Steiner, B.S., Swerdloff, R.S. J. Clin. Endocrinol. Metab. (1987) [Pubmed]
  19. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. Wang, C., Cunningham, G., Dobs, A., Iranmanesh, A., Matsumoto, A.M., Snyder, P.J., Weber, T., Berman, N., Hull, L., Swerdloff, R.S. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  20. Luteinizing hormone and different genetic variants, as indicators of frailty in healthy elderly men. van den Beld, A., Huhtaniemi, I.T., Pettersson, K.S., Pols, H.A., Grobbee, D.E., de Jong, F.H., Lamberts, S.W. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  21. Steroid levels in follicles and the plasma of hens during the ovulatory cycle. Shahabi, N.A., Norton, H.W., Nalbandov, A.V. Endocrinology (1975) [Pubmed]
  22. Relationship of volumetric BMD and structural parameters at different skeletal sites to sex steroid levels in men. Khosla, S., Melton, L.J., Robb, R.A., Camp, J.J., Atkinson, E.J., Oberg, A.L., Rouleau, P.A., Riggs, B.L. J. Bone Miner. Res. (2005) [Pubmed]
  23. Effects of increasing the frequency of low doses of gonadotropin-releasing hormone (GnRH) on gonadotropin secretion in GnRH-deficient men. Spratt, D.I., Finkelstein, J.S., Butler, J.P., Badger, T.M., Crowley, W.F. J. Clin. Endocrinol. Metab. (1987) [Pubmed]
  24. Stimulation of spermatogenesis and biological paternity by intranasal (low dose) gonadotropin-releasing hormone (GnRH) in a male with Kallmann's syndrome: intraindividual comparison of GnRH and gonadotropins for stimulation of spermatogenesis. Oppermann, D., Happ, J., Mayr, W.R. J. Clin. Endocrinol. Metab. (1987) [Pubmed]
  25. Effects of human recombinant luteinizing hormone and follicle-stimulating hormone in patients with acquired hypogonadotropic hypogonadism: study of Sertoli and Leydig cell secretions and interactions. Young, J., Couzinet, B., Chanson, P., Brailly, S., Loumaye, E., Schaison, G. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  26. Influence of age on steroid concentrations in skin and striated muscle in women and in cardiac muscle and lung tissue in men. Deslypere, J.P., Vermeulen, A. J. Clin. Endocrinol. Metab. (1985) [Pubmed]
  27. Differential effect of 5 alpha-reductase inhibition and castration on androgen-regulated gene expression in rat prostate. Rittmaster, R.S., Magor, K.E., Manning, A.P., Norman, R.W., Lazier, C.B. Mol. Endocrinol. (1991) [Pubmed]
  28. Maturation of gonadotropin and sex steroid responses to gonadotropin-releasing hormone agonist in males. Cuttler, L., Rosenfield, R.L., Ehrmann, D.A., Kreiter, M., Burstein, S., Cara, J.F., Levitsky, L.L. J. Clin. Endocrinol. Metab. (1993) [Pubmed]
  29. Obese patients with polycystic ovary syndrome: evidence that metformin does not restore sensitivity of the gonadotropin-releasing hormone pulse generator to inhibition by ovarian steroids. Eagleson, C.A., Bellows, A.B., Hu, K., Gingrich, M.B., Marshall, J.C. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  30. Involvement of transforming growth factor alpha (TGFalpha) and epidermal growth factor receptor (EGFR) in sex hormone-induced prostatic dysplasia and the growth of an androgen-independent transplantable carcinoma of the prostate. Kaplan, P.J., Leav, I., Greenwood, J., Kwan, P.W., Ho, S.M. Carcinogenesis (1996) [Pubmed]
  31. Melatonin acts in the brain to mediate seasonal steroid inhibition of luteinizing hormone secretion in the white-footed mouse (Peromyscus leucopus). Glass, J.D., Dolan, P.L. Proc. Soc. Exp. Biol. Med. (1988) [Pubmed]
  32. The hormonal response of patients with polycystic ovarian disease to subcutaneous low frequency pulsatile administration of luteinizing hormone-releasing hormone. Hurwitz, A., Rosenn, B., Palti, Z., Ebstein, B., Har-Nir, R., Ron, M. Fertil. Steril. (1986) [Pubmed]
  33. Time-related changes in the plasma concentrations of prolactin, gonadotropins, sex hormone-binding globulin, and certain steroid hormones in female runners after a long-distance race. Mathur, R.S., Neff, M.R., Landgrebe, S.C., Moody, L.O., Kirk, R.F., Gadsden, R.H., Rust, P.F. Fertil. Steril. (1986) [Pubmed]
  34. A preponderance of circulating basic isoforms is associated with decreased plasma half-life and biological to immunological ratio of gonadotropin-releasing hormone-releasable luteinizing hormone in obese men. Castro-Fernández, C., Olivares, A., Söderlund, D., López-Alvarenga, J.C., Zambrano, E., Veldhuis, J.D., Ulloa-Aguirre, A., Méndez, J.P. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  35. Pharmacokinetics of a transdermal testosterone system in men with end stage renal disease receiving maintenance hemodialysis and healthy hypogonadal men. Singh, A.B., Norris, K., Modi, N., Sinha-Hikim, I., Shen, R., Davidson, T., Bhasin, S. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  36. Concentration of 14 steroid hormones in human amniotic fluid of midpregnancy. Forest, M.G., de Peretti, E., Lecoq, A., Cadillon, E., Zabot, M.T., Thoulon, J.M. J. Clin. Endocrinol. Metab. (1980) [Pubmed]
 
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