8 a-Testosterone

A testosterone microsphere system for treatment of hypogonadol males has been developed and clinically evaluated (61,78). This formulation is based on a glycolide/DL-lactide copolymer and natural testosterone (Fig. 6). Because testosterone is not a very potent compound, about 600 mg of the drug is needed in adult males over a 90-day period. The performance of the testosterone system in baboons is shown in Fig. 7. Similar formulations have also been used in the control of the wild horse population of the western United States. Stallions were injected with a testosterone microsphere formulation designed to inhibit sperm production over a 6-month period (79). 

Novotny, M., Schwende, F.J., Wiesler, D., Jorgenson, J.W. and Carmack, M. (1984) Identification of a testosterone-dependent unique volatile constituent of male mouse urine 7-exo-ethyl-5-methyl-6,8-dioxabicyclo[3.2.1]-3-octene. Experientia 40, 217-219. 

Thresholds of the olfactory receptors of male goldfish are 35 pg/ml water for the prostaglandin F2a, and 100 times less for its 15-keto-derivative. The males receptor threshold for 17,20-progesterone (from females) is a tiny fraction of 1 pg/ml water. Three grams (one teaspoonful) would provide an abovethreshold stimulus when diluted in 500 x 500 x 500 m water (Bjerselius and Olsen, 1993). In lampreys, testosterone from males attracts females at a concentration of 29 pg/ml water but urine with a testosterone concentration of 29 X 10 pg/ml is active (Adams etal., 1987). 

The synthesis and degradation of muscle proteins are regulated by hormones. Cortisol leads to muscle degradation, while testosterone stimulates protein formation. Synthetic anabolics with a testosterone-like effect have repeatedly been used for doping purposes or for intensive muscle-building. 

Metabolism/Excretion-There are considerable variations in the reported half-life of testosterone, ranging from 10 to 100 minutes. The half-life of testosterone cypionate IM is approximately 8 days for oral fluoxymesterone, it is approximately 9.2 hours and for methyltestosterone it is 2.5 to 3 hours. Inactivation of testosterone occurs primarily in the liver. About 90% of a testosterone dose is excreted in the urine as conjugates of testosterone and its metabolites about 6% of a dose is excreted in the feces. 

Mechanism of Action A testosterone derivative that suppresses the pituitary-ovarian axis by inhibiting the output of pituitary gonadotropins. Causes atrophy of both normal and ectopic endometrial tissue in endometriosis. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are depressed in fibrocystic breast disease. Inhibits steroid synthesis and binding of steroids to their receptors in breast tissues. Increases serum levels of esterase inhibitor. Therapeutic Effect Produces anovulation and amenorrhea, reduces the production of est rogen, corrects biochemical deficiency as seen in hereditary angioedema. 

A 20-year-old man with idiopathic hypogonadotrophic hypogonadism receiving a testosterone ester in a dose of 250 mg intramuscularly every 2 weeks developed priapism (68). 

Braunstein GD, Sundwall DA, Katz M, Shifren JL, Buster JE, Simon JA, Bachman G, Aguirre OA, Lucas JD, Rodenberg C, Buch A, Watts NB. Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women a randomized, placebo-controlled trial. Arch Intern Med 2005 165 1582-9. 

Korbonits M, Slawik M, Cullen D, Ross RJ, Stalla G, Schneider H, Reincke M, Bouloux P.M, Grossman AB. A comparison of a novel testosterone bioadhesive buccal system, Striant, with a testosterone adhesive patch in hypogonadal males. J Clin Endocrinol Metab 2004 89 2039-43. 

Dobs AS, Matsumoto AM, Wang C, Kipnes MS. Shortterm pharmacokinetic comparison of a novel testosterone buccal system and a testosterone gel in testosterone deficient men. Curr Med Res Opin 2004 20 729-38. 

Of 247 men with prostate cancer who received goser-elin 3.6 mg subcutaneously every 28 days or 10.8 mg every 84 days, 27% and 18% respectively had a rise in serum testosterone concentration to above the castrate range [24]. Only 1.7% had a testosterone concentration within the age-specific reference range. There were no clinical symptoms of tumor flare reaction. 

Krause W, Mueller U, Mazur A. Testosterone supplementation in the aging male which questions have been answered Aging Male. 2005 8 31-38. 

Morales A. Testosterone treatment for the aging man the controversy. Curr Urol Rep. 2004 5 472-477. 

Epimedium, a Chinese herb, has a testosterone-like substance and enhances a woman s sexual desire... 

As previously mentioned, degradable microspheres have gained attention as promising delivery vehicles for steroids in postmenopausal therapy. Copolymers of CL and d,l-LA were used to prepare microspheres for prolonged release of progesterone and [5-estradiol. The system offered a constant release for up to 40 days in vitro and 70 days in vivo [226]. Similarly, PCL copolymers have been considered useful for androgen replacement therapy in the treatment of aging men with a testosterone deficiency. Micelles of PCL-block-poly(ethylene oxide) released dihydrotestosterone in a controlled fashion over 30 days. The biocompatibility was confirmed in vitro in a HeLa cell culture [227]. 

Nayebi AR, Rezazadeh H (2004) Involvement of serotonineigicic mechanism in analgesia by castration and flutamide, a testosterone antagonist, in the rat formalin test. Phaimacol Biochem Behav 77 9-14... 

A sensitive enzyme-immunoassay for plasma or saliva testosterone uses testosterone-lla-hemisuccinate antiserum, bound to cellulose to provide a solid phase for convenient separation. Testosterone-horseradish peroxidase conjugate was employed as the label.Another enzyme-immunoassay for testosterone employs a testosterone-3-(0-carboxymethyloxime)-pencillinase conjugate for competitive binding to the testosterone antiserum. 21-Amino-ll/3,17o -dihydroxypregn-4-ene-3,20-dione ( Cortisol 21-amine ) linked to alkaline phosphatase has been used ° in an effective enzyme-immunoassay for cortisol. 

Ring C aromatization of steroids Treatment of 17a-methyl-A - " "-testosterone (1) with 90%, formic acid under rdlux for 15 hr. results in formation of the rearranged 17,17 -dimethylandrosta-4,8,ll,13-tetraene-3-one (2) in 45% yield. 

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