Regression of uterine leiomyomata in response to the antiprogesterone RU 486.
Uterine leiomyomata are steroid hormone dependent tumors which possess receptors for estrogen (ER) and progesterone (PR). We reasoned that an antiprogesterone (RU 486) may induce regression of leiomyomata by withdrawal of progesterone action and/or by its interference of estrogen action. Accordingly, we examined the effects of daily administration of RU 486 (50 mg) for a period of 3 months in 10 patients with uterine leiomyomata and regular menstrual cycles. Baseline ultrasound examinations were obtained and repeated monthly during treatment as a measure of leiomyomata volume. Hormonal parameters were monitored by blood samples obtained prior to treatment and daily for 7 days, weekly for 4 weeks and monthly for the duration of therapy. Myomectomy or hysterectomy was performed in 6 of 10 patients at the end of treatment. Leiomyomata and myometrial tissue was obtained for immunocytochemical analysis of ER and PR protein. Amenorrhea was induced in all patients during treatment. Leiomyomata volume (mean +/- SE) decreased 21.9 +/- 4.8% after 4 weeks, 39.5 +/- 6.6% (P < 0.001) after 8 weeks, and 49.0 +/- 9.2% (P < 0.001) after 12 weeks of treatment compared to pretreatment measurements. Serum LH levels (P < 0.005), but not FSH levels, more than doubled during the first 3 weeks of treatment with a concomitant increase in serum androstenedione (P < 0.006) and testosterone (P < 0.0001) levels. These elevated hormonal levels returned to baseline at 4 weeks without further changes during the remainder of treatment. A significant rise in serum dehydroepiandrosterone sulfate (P < 0.0001) and cortisol (P < 0.01) was seen at 12 weeks, suggesting an antiglucocorticoid effect of RU 486 has occurred. Serum estradiol, estrone, progesterone, sex hormone binding protein, thyroid-stimulating hormone, and PRL were unchanged from early follicular phase values. PR but not ER immunoreactivity was significantly reduced in both leiomyomata and myometrium after RU 486 treatment compared with tissues from untreated patients, suggesting that regression of tumors may be attained through a direct antiprogesterone effect. However, an alteration in ER functionality cannot be excluded. We conclude that RU 486 is well tolerated, safe, and effective; thus, it may prove to be a novel mode of management for uterine leiomyomata.
Murphy
A A
AA
Department of Reproductive Medicine, University of California, San Diego School of Medicine, La Jolla 92093-0802.
Kettel
L M
LM
Morales
A J
AJ
Roberts
V J
VJ
Yen
S S
SS
D000293:Adolescent; D000328:Adult; D000735:Androstenedione / Q000097:blood; D015519:Bone Density; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007044:Hysterectomy; D007150:Immunohistochemistry; D007889:Leiomyoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D015735:Mifepristone / Q000009:adverse effects / Q000627:therapeutic use*; D009215:Myometrium / Q000737:chemistry / Q000601:surgery; D011374:Progesterone / Q000097:blood; D011959:Receptors, Estradiol / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013739:Testosterone / Q000097:blood; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D011959:Receptors, Estradiol; D011980:Receptors, Progesterone; D015735:Mifepristone; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D011374:Progesterone; D019314:Dehydroepiandrosterone Sulfate; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone