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Although the precise mechanism by which testolactone produces its clinical antineoplastic effects has not been established, its principal action is reported to be inhibition of steroid aromatase activity and consequent reduction in estrone synthesis from adrenal androstenedione, the major source of estrogen in postmenopausal women. Based on in vitrostudies, the aromatase inhibition may be noncompetitive and irreversible. This phenomenon may account for the persistence of testolactone's effect on estrogen synthesis after drug withdrawal.
Despite some similarity to testosterone, testolactone has no in vivo androgenic effect. No other hormonal effects have been reported in clinical studies in patients receiving testolactone. In one study, testolactone administered orally (1000 mg/day) was reported to increase renal tubular reabsorption of calcium but to have no effect on serum calcium concentration. The mechanism of the hypocalciuric effect is unknown. No clinical effects in humans of testolactone on adrenal function have been reported; however, one study noted an increase in urinary excretion of 17-ketosteroids in most of the patients treated with 150 mg/day orally.
Testolactone is well absorbed from the gastrointestinal tract. It is metabolized to several derivatives in the liver, all of which preserve the lactone D-ring. These metabolites, as well as some unmetabolized drug, are excreted in the urine. Additional pharmacokinetic data in humans are unavailable.
In animals, parenteral but not oral testolactone reduced cortisone acetate induced hepatic glycogen deposits. In animal tests conducted to detect any hormonal activity for testolactone, some evidence of antiandrogenic and antiglucocorticoid activity was seen; increased growth rate in the newborn was suggested. However, there was no clear manifestation of androgenic, estrogenic or antiestrogenic, progestational or antiprogestational, gonadotropin-like or antigonadotropic effects. Testolactone did not demonstrate anti-inflammatory, mineralocorticoid-like, or glucocorticoid-like properties.
Last reviewed on RxList: 6/30/2009
This monograph has been modified to include the generic and brand name in many instances.
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