Antiglucocorticoid effects

An adolescent girl with Cushingoid features and osteoporosis took mifepristone 400 mg/day for its antiglucocorticoid effect in an attempt to prevent further bone loss (16). Her striae, weight gain, and buffalo hump markedly improved, and further bone loss was halted. However, with each of the two 6-month courses of mifepristone (9 months apart) she developed massive simple endometrial hyperplasia and a markedly enlarged uterus. This reverted to normal after withdrawal of mifepristone. 

Information is only available for mifepristone since there is very limited clinical experience with other PAs and SPRMs. Owing to its specific action at the PR and GR, serious untoward effects are rare and mifepristone is well tolerated. Antiglucocorticoid effects are usually only seen with doses exceeding 200 mg daily [59]. Chronic administration of mifepristone has been associated with the development of biochemical hypothyroidism which requires observation and follow-up [115]. 

Compounds of this type have been shown to retain antiprogestational effects and to have reduced antiglucocorticoid activity (136). 

SAR analyses revealed that unwanted endocrine side effects such as antiglucocorticoid activities were reduced by modifying position C-17. Among a variety of modifications, the 17Q -pentaliuoroethyl side chain (Fig. 15) led... 

Duval D, Durant S, Homo-Delarche F. Effect of antiglucocorticoids on dexamethasone-induced inhibition of uridine incorporation and cell lysis in isolated mouse thymocytes. J Steroid Biochem 1984 20 283-287. 

---