Epidemiological evidence, including the greater incidence of female patients, a positive association with pregnancy, and a positive association with
breast cancer suggested a role for female
sex hormones (and hormonal modulation) in regulating the growth of
meningioma. The detection of
hormone receptors on
meningioma specimens provided a mechanism for this effect. However, unlike
breast cancer,
progesterone receptors (not oestrogen receptors) predominate in
meningioma. Clinical trials with anti-oestrogens have shown little effect while trials with
progesterone agonists have shown no effect or possible stimulation of
meningioma growth. Three trials have now indicated an inhibitory activity of the antiprogestational agent
mifepristone. In the largest of these trials, 28 patients received daily oral
mifepristone for up to 62 months with a suggestion of response in eight patients. Long-term
therapy has been well tolerated. Adverse events include
fatigue, hot flushes, gynaecomastia/breast tenderness,
skin rash, cessation of menses and decrease in libido. Increases in
cortisol and
thyroid-stimulating hormone are the most striking endocrine changes. A randomized double-blind placebo-controlled phase III trial is underway to confirm the activity of
mifepristone in unresectable
meningioma.