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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Therapeutic potential for the selective progesterone receptor modulator asoprisnil in the treatment of leiomyomata.

Asoprisnil is a novel selective progesterone receptor modulator that exhibits partial agonist and antagonist activities in animals and humans. It demonstrates a high degree of progesterone receptor specificity and tissue selectivity. Although asoprisnil at high doses exhibited some antiglucocorticoid activity in animal models, no antiglucocorticoid effects were observed at therapeutic doses in humans. In male rats, asoprisnil showed mixed androgenic and antiandrogenic properties. Unlike antiprogestins, asoprisnil at high doses exhibited only marginal labor-inducing activity in guinea pigs during midpregnancy and was completely ineffective in inducing preterm parturition. In nonhuman primates, asoprisnil completely eliminated menstrual cyclicity and induced endometrial atrophy. Early clinical studies of asoprisnil in healthy volunteers demonstrated a dose-dependent suppression of menstruation, irrespective of the effects on ovulation, with no change in basal estrogen concentrations and no breakthrough bleeding. Phase 2 studies in subjects with uterine fibroids demonstrated that asoprisnil induced amenorrhea and reduced the volume of the dominant leiomyoma in a dose-dependent manner without altered basal estrogen and with virtually no clinical symptoms of estrogen deprivation. Asoprisnil seems to exhibit a direct inhibitory effect on both the endometrium and leiomyoma. In all studies to date, asoprisnil has maintained a favorable safety and tolerability profile. Thus, asoprisnil has the potential to target the major clinical symptoms of leiomyomata related to both menorrhagia and the size of the tumors and may, therefore, reduce or eliminate the need for surgery.[1]

References

  1. Therapeutic potential for the selective progesterone receptor modulator asoprisnil in the treatment of leiomyomata. Chwalisz, K., DeManno, D., Garg, R., Larsen, L., Mattia-Goldberg, C., Stickler, T. Seminars in reproductive medicine. (2004) [Pubmed]
 
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