Endocrine responses to long-term administration of the antiprogesterone RU486 in patients with pelvic endometriosis

Abstract

Objective: To examine endocrine and clinical responses to long-term administration of RU486 in patients with endometriosis.

Design: Prospective open trial.

Setting: Faculty practice of the authors.

Patients, participants: Six normally cycling women with endometriosis were recruited.

Interventions: Subjects received RU486 100 mg/d for 3 months.

Main outcome measure(s): Hormonal changes during RU486 were compared with control data obtained in the preceding cycle during the early follicular phase. Clinical responses were determined by patient assessment and second-look laparoscopy.

Results: All women became amenorrheic, and daily urinary levels of ovarian steroid metabolites remained acyclic. Mean luteinizing hormone (LH) (P less than 0.02) and LH pulse amplitude (P less than 0.05) were increased without changes in LH pulse frequency. An antiglucocorticoid effect was demonstrated by an increase in serum cortisol (P less than 0.01) and adrenocorticotropic hormone (P less than 0.05) levels. Treatment resulted in an improvement in pelvic pain in all subjects without significant change in the extent of disease as evaluated by follow-up laparoscopy.

Conclusions: Daily administration of RU486 results in acyclic ovarian function and improvement in the subjective painful symptoms of endometriosis.

PIP: Physicians recruited 6 women aged 17-40 years with cyclic pelvic pain due to endometriosis for a prospective open trial conducted at the Clinical Research Center in San Diego, California. They wanted to assess endocrine and clinical responses to daily administration of 100 mg/d of RU-486 for 3 months. They all experienced amenorrhea during treatment. Moreover, urinary ovarian steroid metabolites were acyclic indicating anovulation. Mean luteinizing hormone (LH; p.02) and LH pulse (p.05) amplitude increased after treatment with RU-486, yet the LH pulse frequency did not change. Further, serum cortisol (p.01) and adrenocorticotropic hormone (p.05) also increased indicating that RU- 486 had an antiglucocorticoid effect. Menstrual cyclicity returned immediately after terminating treatment. 2 patients even became pregnant. Further, all patients reported less pelvic pain during treatment yet the extent of endometriosis did not improve. Indeed most received alternative treatment for endometriosis prior to enrollment in this study with no reduction in pain. The researchers could not determine the mechanism of pain relief or chronic anovulation, however. Further studies using lower doses and longer term therapy with RU-486 in patients with endometriosis are needed.