19-nortestosterone derivatives

Chemical Analysis. Chemically, the various progestogens belong to one of three classes. Estranes are 19-nortestosterone derivatives (Fig. 1) gonanes are 19-nortestosterone derivatives with a C-13 ethyl group (Fig. 2) and pregnanes are 17-alpha-OH progesterone derivatives similar in stmcture to progesterone itself. 

Adverse effects include flushes, weight gain, mood changes, vaginal dryness, decreased libido, breast enlargement and tenderness and in some patients the prolonged time required for the return of normal ovulatory function. Androgen side-effects like acne and hirsutismus can occur with the 19-nortestosterone derivatives. 

Anabolic activities of testosterone, such as increases in amino acid incorporation into protein and in RNA polymerase activity, have been demonstrated in skeletal muscle. Apart from the direct anabolic effects in specific tissue, androgens antagonize the protein catabolic action of glucocorticoids. The androgen compounds with the greatest ratio of protein anabolic effects to virilizing effects are the 19-nortestosterone derivatives. Compounds that are used clinically (Table 63.3) include nandrolone phenpropionate (Durabolin), nandrolone decanoate... 

Hirsutism may also be aggravated by the "19-nortestosterone" derivatives, and combinations containing nonandrogenic progestins are preferred in these patients. 

Many studies have shown that lactation is not adversely affected by depot medroxyprogesterone acetate and that breast-milk production may even be increased (35). Because of the low binding affinity of medroxyprogesterone to sex hormone binding globulin, the concentration of steroids in the milk is close to that in the maternal plasma, unlike the 19-nortestosterone derivatives. 

Hershberger et al. [187] discovered in 1953 that although 19-nor-testosterone and other 19-nor analogs exhibit only relatively weak androgenic properties the protein anabolic effects and myotrophic effects were of the same order of magnitude as those of testosterone. Since the anabolic-androgenic ratio of the 19-nortestosterone derivatives was very favorable, this discovery opened a new field of anabolic agents. 

In addition to the above-described compounds, there are a few other 19-nortestosterone derivatives which display a favorable anabolic-androgenic ratio by having lower androgenic activities and maintaining the anabolic activity of the standard compound 17a-methyl-l 7j8-hydroxy-19-norandrost-2-ene (N-29), 2-cyano-17/3-acetoxy-19-norandrost-2-ene acetoxy-19-norandrost-4-eno[2,3-c ]isoxazole (N-70), 17a-methyl-17/3-hydroxy-19-norandrost-4-eno[2,3-fii]isoxazole (N-76), and I7a-methyl-17/3-hydroxy-5a-estran-3-one (N-90). 

Norethindrone, norgestrel (19-nortestosterone derivatives) with some androgenic activity... 

The estrogenic component of the oral contraceptive agents is almost exclusively ethynylestradiol or mestranol, while currently available progestational steroids are either progesterone derivatives, containing the typical C21 structure, or 19-nortestosterone derivatives. Removal of the C19 methyl group of testosterone and introduction of the... 

---