Androgen ester

In the case of androgens as with estrogens there is occasionally need for treatment of patients with chronic sustained doses of these drugs. Resort is made to esters of the androgen with long-chain fatty acids in order to provide oil-soluble agents ... 

Figure 25-5. Metabolism of high-density lipoprotein (HDL) in reverse cholesteroi transport. (LCAT, lecithinxholesterol acyltransferase C, cholesterol CE, cholesteryl ester PL, phospholipid A-l, apolipoprotein A-l SR-Bl, scavenger receptor B1 ABC-1, ATP binding cassette transporter 1.) Prep-HDL, HDLj, HDL3—see Table 25-1. Surplus surface constituents from the action of lipoprotein lipase on chylomicrons and VLDL are another source of preP-HDL. Hepatic lipase activity is increased by androgens and decreased by estrogens, which may account for higher concentrations of plasma HDLj in women.

Endogenous and exogenous androgens can be derivatized with trimethylsilyl (TMS) for hydroxy functions and by 0-methylation for ketones, and analyzed with GC-FID or GC-MS (Shimada et al., 2001). MS is more prevalent due to unequivocal identification and greatly increased sensitivity but FID is still used in laboratories for some steroids. Sterols have typically been analyzed by GC-FID and GC-MS with derivatization to optimize peak shape (Shimada et al., 2001), and bile acids can be derivatized with M-butyl ester-TMS ether and analyzed by GC-FID from plasma samples (Batta et al., 1998). Juricskay and Telegdy (2000) reported an assay capable of analyzing 28 steroids in urine samples using GC-FID. 

Testosterone (T.) derivatives for clinical use. T. esters for im. depot injection are T. propionate and T. heptanoate (or enanthate). These are given in oily solution by deep intramuscular injection. Upon diffusion of the ester from the depot, esterases quickly split off the acyl residue, to yield free T. With increasing lipophilicity, esters will tend to remain in the depot, and the duration of action therefore lengthens. A T. ester for oral use is the undecanoate. Owing to the fatty acid nature of undecanoic acid, this ester is absorbed into the lymph, enabling it to bypass the liver and enter, via the thoracic duct, the general circulation. 17-0 Methyltestosterone is effective by the oral route due to its increased metabolic stability, but because of the hepatotoxicity of Cl 7-alkylated androgens (cholestasis, tumors) its use should be avoided. Orally active mesterolone is 1 a-methyl-dihydrotestosterone. Trans-dermal delivery systems for T. are also available. 

In applied medicine, testosterone esters (propionate, cypionate, and enantate) and a synthetic analog, methyltestosterone, are widely used. In many tissues, testosterone s androgenic... 

Catalytic hydrogenation of the formyl derivative (36-4) proceeds as usual from the more open a face of the molecule to afford the axial 2 3 methyl derivative (37-1). Treatment with a strong base leads to epimerization to the more stable equatorial 2a methyl isomer. There is thus obtained the androgen, dromostanolone (37-2) [35]. The compound is used clinically as its 17-propionate ester. Direct reaction of the formyl ketone (36-4) with hydrazine leads to the formation of a fused pyrrazole ring [36] this product is the widely used androgenic and anabohc drug, stanazole (37-3). 

Estradiol-17 is given to animals in form of a subcutaneous implant in the ear, alone or in combination with other hormonally active compounds such as progesterone or trenbolone acetate. Estradiol-17 is used in steers, to best advantage, but also exhibits some anabolic effects in heifers and veal calves. It works best in lambs in conjunction with androgens, but is not effective as an anabolic agent in pigs. It has been used in many forms in the past including the benzoate, dipropionate, hemisuccinate, heptanoate, propionate, undecanoate, and valerate esters. 

Hirsutism is common in patients taking androgens, and is often irreversible (62,63). In contrast, in women, loss of scalp hair can occur (64). Of 81 female-to-male transsexual subjects, mean age 37 years (range 21-61), treated with testosterone esters (n = 61 250 mg intramuscularly every 2 weeks) or testosterone undecanoate (n = 20 160-240 mg/day orally), 31 developed male-pattern baldness thinning of the hair was related to the duration of androgen administration and was present in about half of the transsexuals after 13 years (65). 

Both men and women produce androgens and estrogens. Women s dominant production is estrogens, and men s dominant production is androgens. Reverse this and each will take on their counter-parts characteristic to quite some extent. Our main focus for the following chapters is the male androgen testosterone and its almost endless derivatives and esters. 

Suspension is more androgenic and anabolic than either Enanthate or Cypionate only because it is not testosterone joined to an ester. This simply means lOOmg of suspension actually has lOOmg of active testosterone that enters the circulatory system at a fairly rapid rate. (More testosterone = more activity )... 

Testosterone This agent is ineffective orally because of inactivation by first-pass metabolism. As with the other sex steroids, testosterone is rapidly absorbed by the liver and other tissues, and is metabolized to relatively or completely inactive compounds that are excreted primarily in the urine but also in the feces. Testosterone and its C-17-esters (for example, testosterone cypi-onate or enanthate) are administered intramuscularly. [Note The addition of the esterified lipid makes the hormone more lipid-soluble, thereby increasing its duration of action.] Testosterone and its esters demonstrate a 1 1 relative ratio of androgenic to anabolic activity. 

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