Androgens, conjugates

Another example of resort to heteroatoms to obtain both oral potency and a split between androgenic and anabolic activities Ls tiomestrone (99). Trienone, 98, prepared in much the same way as 23, undergoes sequential 1,6 and 1,4 conjugate addition of thioacetic acid under either irradiation or free radical catalysis to afford the compound containing two sulfur atoms. 

Estrogen, Conjugated + Methylprogesterone (Premarin + Methylprogesterone) [Estrogen Androgen Hormones]... 

The catabolism of plasma testosterone and other androgens occurs primarily in the liver (Fig. 63.3), where they are conjugated into water-soluble compounds that are excreted by the kidney as the urinary 17-ketosteroids. 

The synthesis of adrenal steroids is illustrated in Fig. 5.3.1. Cortisol, corticosterone, and aldosterone are formed by sequential hydroxylations and oxidoreductions from pregnenolone and progesterone. 17a-Hydroxypregnenolone (17HP) is a branchpoint constituent because it can be converted to cortisol or adrenal androgens. All of the components of this pathway can be quantified by MS/MS. The steroids around the periphery are urinary metabolites and these are measured by GC-MS following hydrolysis of conjugates and derivatization. 

Estrogens can cause dose-related nausea, which is not reduced by using enteric-coated tablets. It has been claimed that there is a significantly lower incidence of nausea with estrogen + androgen than with conjugated estrogens. 

Many Anabolic/Androgenic Steroids (AAS) are available in an oral form. Unfortunately some are also quite toxic to the liver. Orally administered AAS are very susceptible to first pass liver deactivation unless chemical molecular structures are altered to make them harder to deactivate. When an oral AAS is swallowed it enters the stomach where it is partially broken down and passed to the small intestines. The small intestines contain a group of enzymes called CYP-450 s. These enzymes begin to break down the AAS further in an attempt to deactivate it. The AAS is then absorbed through intestinal mucosa cells and transferred to the liver portal vein for further deactivation into inactive chemicals such as etiocholanone. These chemicals are then conjugated with glucuronic acid and excreted in urine. Up to 100% of the original compound can be deactivated in this process which is known as first pass deactivation. 

Endogenous conjugated androgens in clinical chemistrv GC-GS and LC-MS/MS analyses of conjugated androgens—deconjugation, derivatization, and associated issues. [7]... 

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