Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Ru-486”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources
PubMed1990

Accelerated dissolution of luteal-endometrial integrity by the administration of antagonists of gonadotropin-releasing hormone and progesterone to late-luteal phase women.

Sequential blockade of gonadotropin-releasing hormone (GnRH) and progesterone (P) receptors by potent antagonists (Nal-Glu GnRH antagonist and RU486) was conducted in late-luteal phase women to develop a once-a-month birth control method by timed advancement of ongoing luteolysis and endometriolysis. Hormonal dynamics and timing of uterine bleeding during the antagonists' imposed luteal-follicular transition were compared with spontaneous (1st to 2nd) and recovery (2nd to 3rd) cycles in 10 normally cycling women. Serum luteinizing hormone (LH) and follicle-stimulating hormone levels declined (47 +/- 4.3% and 24 +/- 3.0%, respectively) by 24 hours after Nal-Glu injection, which accelerated the ongoing luteolytic process, as evidenced by more rapid declines of serum concentrations of estradiol, P, and ir-inhibin, as compared with the corresponding control cycle. This was accompanied by the prompt (16 +/- 3.2 hours after RU486) onset of a single episode of uterine bleeding, which was advanced by 2 days. Whereas the luteal phase length was foreshortened by 2 days, the subsequent follicular phase duration was prolonged by 2 days with a normal sequence of follicular maturation, LH surge, and luteal function during the recovery cycle. We conclude that the late-luteal sequential administration of antagonists of GnRH and P resulted in acceleration of the ongoing luteolytic and endometriolytic processes without functional alterations of the subsequent cycle.

Adult↗
PubMed1988

Inhibition of folliculogenesis and ovulation by the antiprogesterone RU 486.

Healthy, regularly menstruating women were treated with the antiprogesterone RU 486, Mifepristone (Roussel-Uclaf, Romainville, France) during the follicular phase of the cycle. Three women were given 25 mg of RU 486 on days 1 to 14 of the cycle and five received 25 mg on days 1 to 21 of the cycle. Venous blood samples were collected three times per week during a control cycle and during one treatment cycle in each subject. Serum concentrations of estradiol (E2), progesterone (P), and RU 486 were determined by radioimmunoassays. No drug-related side effects and no spotting or bleeding during RU 486 treatment were observed. Menstrual bleeding was delayed by 8.7 +/- 3.8 days (mean +/- SD) after treatment over days 1 to 14 and by 12.6 +/- 3.2 days after treatment over days 1 to 21. During the treatment with RU 486, the serum concentrations of E2 remained low, indicating effective inhibition of folliculogenesis. After cessation of RU 486 treatment, serum E2 levels rose to similar values as in the control cycle, and subsequently serum P concentrations also reached ovulatory levels in six out of the eight volunteers. The results showed that the antiprogesterone RU 486 delayed folliculogenesis and luteinization even at low doses when given during the follicular phase of the menstrual cycle. It is speculated that this property of RU 486 could be utilized in the design of an estrogen-free combined oral contraceptives.

Adult↗
PubMed1995

Regression of uterine leiomyomata to the antiprogesterone RU486: dose-response effect.

OBJECTIVE: To study the response of uterine leiomyomata to three daily doses of RU486 (5, 25, and 50 mg). DESIGN: Prospective nonrandomized trial of women with symptomatic leiomyomata. SETTING: Patients from the clinical practice of the authors at the University of California, San Diego Medical Center. PATIENTS: Ten patients with symptomatic leiomyomata previously reported after treatment with 50 mg of RU486 daily for 3 months. Eleven patients treated with 25 mg of RU486 daily and nine patients placed on 5 mg of RU486 daily for 12 weeks. MAIN OUTCOME MEASURES: Changes in leiomyomata volume as measured with vaginal ultrasounds at baseline and monthly thereafter. Frequent blood samples for hematology, chemistry, and hormone levels were obtained. Twenty-four-hour urine collections for free cortisol and creatinine were obtained at baseline and at 12 weeks. RESULTS: All three doses induce ovarian acyclicity. Administration of 50 mg of RU486 decreases leiomyomata volume to 78.1% +/- 4.8% of baseline at 4 weeks, 60.5% +/- 6.6% at 8 weeks, and 51.0% +/- 9.2% after 12 weeks of treatment. Regressive response in patients treated with 25 mg of RU486 daily was 76.3% +/- 5.0% of baseline at 4 weeks, 54.0% +/- 5.1% at 8 weeks, and 44.0% +/- 5.0% after 12 weeks. At 5 mg of RU486 leiomyomata volume was 80.6% +/- 8.3% of baseline after 4 weeks, 63.7% +/- 14.6% after 8 weeks, and 74.4% +/- 19.8% after 12 weeks of therapy. CONCLUSIONS: Although acyclicity is seen at all three doses, an effective dose to cause a clinically significant (50%) decrease in leiomyomata volume appears to be 25 mg daily.

Adolescent↗
PubMed1995

Endometrial effects of long-term low-dose administration of RU486.

OBJECTIVE: To examine endometrial response to long-term low-does RU486 administration. DESIGN: Retrospective controlled study of women with endometriosis treated for 6 months with 50 mg RU486 daily for 6 months. Controls consisted of women in the follicular phase of a spontaneous cycle undergoing endometrial biopsy. SETTING: Patients from the clinical practice of the authors at the University of California, San Diego Medical Center. PATIENTS AND INTERVENTIONS: Nine patients treated with long-term low-dose RU486 and nine normal cycling controls undergoing hysterectomy or endometrial biopsy for benign disease. MAIN OUTCOME MEASURES: Changes in endometrial morphology and immunohistochemical analysis for estrogen receptor (ER) and progesterone receptor (PR) protein. RESULTS: All patients treated with RU486 exhibited abnormal endometrial morphology. The endometrial glands were irregular in size and shape. The stroma was varied but consisted predominantly of dense cellular stroma with frequent mitotic figures. The glands were lined by a combination of epithelial types some of which were secretory. No cytologic atypia was seen. Levels of ER immunoreactivity, as determined by image analysis, were greater in the stroma with no difference in PR immunoreactivity compared with controls. No difference in ER and PR immunoreactivity were seen in the glands compared with normal controls. CONCLUSION: The generalized cystic changes demonstrated are consistent with a chronic unopposed estrogen effect and are concordant with hormonal data showing early to midfollicular phase levels of estrogens. They also are consistent with our findings of increased ER immunoreactivity in the stroma. Evidence of minimal P agonist effect was noted.

Adolescent↗
PubMed1994

RU486 exerts antiestrogenic activities through a novel progesterone receptor A form-mediated mechanism.

The human progesterone receptor (hPR) exists in two distinct forms in most cells, hPR-A and hPR-B. Both receptor isoforms exhibit distinct biological functions and demonstrate a cell- and promoter-specific ability to regulate gene transcription. Interestingly, in cell contexts where PR-A is transcriptionally inactive, it acts as a progesterone-dependent inhibitor of estrogen receptor function. Coexpression of the human estrogen receptor with the A form (but not the B form) of the human progesterone receptor resulted in a ligand-dependent inhibition of estrogen receptor-mediated gene transcription. The antiprogestins RU486 (MIfepristone) and ZK98299 (Onapristone) and related antiprogestins were all effective "noncompetitive" inhibitors of the estrogen receptor in this assay as none of these compounds interacted directly with the estrogen receptor. This observation may explain in part the observed tissue-specific antiestrogenic effects of RU486 and further indicates that the antiestrogenic activities of antiprogestins may be intrinsic to their biological function. This important new information defines novel activities of progesterone receptor ligands and may alter the way in which we define progesterone receptor modulators for future clinical applications. In addition, these data reveal that the A form of the progesterone receptor plays a key role in modulating estrogen receptor function in cells where both receptors are expressed.

Animals↗
PubMed1994

The effects of RU 486 and leuprolide acetate on uterine artery blood flow in the fibroid uterus: a prospective, randomized study.

OBJECTIVE: Our purpose was to examine the effects of RU 486 and leuprolide acetate on uterine artery blood flow and uterine volume. STUDY DESIGN: Patients were randomly assigned to group A (eight patients) receiving 25 mg of RU 486 daily for 3 months or group B (six patients) receiving 3.75 mg of leuprolide acetate monthly for 3 months. Uterine artery blood flow change was determined by resistive index by means of vaginal color Doppler ultrasonography. Uterine volume was measured before and during the study with abdominal ultrasonography. RESULTS: Both groups showed an increase in resistive index. Patients receiving RU 486 had uterine artery blood flow decreased by 40%, and those receiving leuprolide acetate had a 21% decrease. We noted a significant decrease in uterine volume compared with pretreatment in both groups at 3 months. There was no significant decrease between groups. CONCLUSION: Both RU 486 (25 mg daily) and leuprolide acetate (3.75 mg monthly) are effective in decreasing blood flow to the uterus (increasing resistive index) and decreasing uterine volume at 3 months. A significant decrease in uterine artery blood flow may provide a mechanism for the decrease in uterine size and the decrease in uterine blood loss at the time of surgery.

Female↗
PubMed1993

Possible use of glucocorticoid receptor antagonists in the treatment of major depression: preliminary results using RU 486.

The rationale for the use of anti-glucocorticoids in the treatment of major depression has been reviewed. Four patients with chronic severe depression who were resistant to conventional therapies were given RU 486 (200 mg/day) for periods up to eight weeks. Substantial levels of RU 486 were achieved within the first few days, and the levels fell gradually over the week after the treatment was discontinued. In three cases, treatment was stopped before the eight weeks were completed: in one case because of the appearance of a rash, in the others because of side-effects, which, in retrospect, were likely unrelated to the drug. The mean scores on the Hamilton Rating Scale for Depression of three patients decreased. Levels of adrenocorticotrophin, dehydroepiandrosterone and cortisol rose during treatment. These preliminary results suggest that glucocorticoid antagonists may be effective in the treatment of major depression and merit further exploration.

Adrenocorticotropic Hormone↗
PubMed1993

Reversal of activity profile in analogs of the antiprogestin RU 486: effect of a 16 alpha-substituent on progestational (agonist) activity.

16 alpha-Ethyl-17 beta-acetyl substitution in the D-ring of steroids having an 11 beta-aryl-4,9-dien-3-one structure resulted in compounds with strong progestational activity. These compounds caused endometrial proliferation in the uterus of estrogen-primed rabbits with a potency greater than that of progesterone and had no detectable antiprogestational activity in this model. This is in stark contrast with the marked antiprogestational activity in rabbits, rats and humans reported for most 11 beta-aryl-4,9-diene-3-keto steroids such as RU 486 and its 17 beta-acetyl-17 alpha-acetoxy analog, 17 alpha-acetoxy-11 beta-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-diene- 3,20-dione. Examination of structure activity relationships in combination with computer aided molecular modelling suggests that a binding interaction of the 16 alpha-ethyl group with the progesterone receptor (PR) or the PR-progestin response element complex may play the major role in this reversal of activity profile.

Animals↗
PubMed1993

[Pregnancy, contraception and epilepsy].

Epilepsy is the most common neurological disease of females in reproductive age. Problems concerning contraception, reproduction, teratogenicity and antiepileptic therapy preceding and during pregnancy are discussed and recommendations made. We underline the advantages of a planned pregnancy with optimal adjustment of antiepileptic drug therapy and recommend prophylactic treatment with folic acid before and during, and with vitamin K towards the end of pregnancy.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Conscientious objection and abortifacient drugs.

The legal right to assert a conscientious objection is reviewed, using as an example the dispensing of abortifacient drugs by pharmacists. The three areas of law that most significantly concern the right to assert a conscientious refusal are employment law, conscience clauses, and religious discrimination law. Each of these is reviewed, with descriptions of recent cases. It is concluded that employment law protects refusals that are consistent with public policy, but does not permit an employee's personal policy to determine how a business will be run; that conscience clauses appear to provide protection for pharmacists who object to dispensing abortifacients, but that the precise meanings of critical words and phrases in some clauses need to be defined; and that even though laws of religious discrimination require that employers accommodate religious beliefs, they may not protect a pharmacist who objects to dispensing abortifacients if the accommodation becomes unreasonably burdensome.

Abortifacient Agents↗
PubMed1993

Response to intermittent RU486 in women.

OBJECTIVE: To determine the effects of intermittent administration of the antiprogestin RU486 on ovarian function. DESIGN: Three different regimens of RU486 were tested. PARTICIPANTS: Nine healthy regularly menstruating volunteers protected by an intrauterine device or surgical sterilization. INTERVENTIONS: Two groups of three women each received 10 mg or 50 mg RU486 at weekly intervals for 5 weeks. Another three women received 50 mg RU486 for 3 consecutive days at 10-day intervals for 80 days. MAIN OUTCOME MEASURES: Serum E2, P and RU486 levels. Ovarian ultrasound (US) and serum LH and FSH in select subjects. RESULTS: The predominant effect was partial inhibition of E2 secretion and suppressed P levels. During a total aggregate of 16 treatment months, there were seven episodes of elevated P levels; however, US did not always indicate the occurrence of normal ovulation. CONCLUSION: Intermittent RU486 administration can interfere with normal follicular development and function, but its clinical application may require a more effective dose and/or timing of administration.

Administration, Oral↗