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At least 379 records · Page 21Linked to original sources
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↗
PubMedDate not supplied

Expanding access to emergency contraception in developing countries.

Emergency contraception has been called the best-kept contraceptive secret. Previous research shows that several regimens of postcoital contraception offer safe and effective ways for women to avoid pregnancy. Yet the methods are typically unavailable to women in developing countries. In this article, the authors review the main methods of emergency contraception and describe experience with them to date. The prevalence and urgency of the need for making these methods available to women in developing countries are assessed. The necessary elements for creating such access are described. In several developing countries, conditions for introducing the methods may be more favorable than in industrialized countries. These advantages are reviewed. Finally, the authors describe the challenges anticipated for broadening the availability of postcoital methods in the developing world. They conclude with a brief series of recommendations for policymakers.

Contraceptives, Postcoital↗
PubMed1996

RU486 suppresses prolactin production in explant cultures of leiomyoma and myometrium.

OBJECTIVE: To assess the action of RU486 (mifepristone), in the presence and absence of P, on PRL production by explant cultures of leiomyoma and myometrium. DESIGN: Explant cultures using tissue from nine premenopausal women undergoing hysterectomy in the proliferative phase of the menstrual cycle; immunohistochemical staining of tissue sections from five patients for P receptor (PR) subtype. MAIN OUTCOME MEASURES: Prolactin secretion (measured by RIA), lactate dehydrogenase secretion (measured by quantitative colorimetric assay), and immunohistochemistry for PR subtype. RESULTS: Prolactin secretion was decreased in leiomyomas by RU486 at concentrations of 10(-7) M and 10(-5)M when normal serum-containing medium was used. In experiments with all detectable P removed from serum, PRL secretion was suppressed in both leiomyomas and myometrium at an RU486 concentration of 10(-7)M. Immunohistochemistry results suggest that the A form of the PR is the dominant form in both leiomyomas and myometrium. CONCLUSIONS: Prolactin production is suppressed in both leiomyomas and myometrium after treatment with RU486 in vitro, and this suppression may serve as a marker for the clinical effectiveness of agents used in the treatment of leiomyomas.

Culture Media↗
PubMed1996

Misoprostol is as effective as gemeprost in termination of second trimester pregnancy when combined with mifepristone: a randomised comparative trial.

A prospective randomized study was conducted to compare the efficacy of misoprostol with gemeprost when combined with mifepristone for termination of second trimester pregnancy. Patients requesting termination of second trimester pregnancy were randomized into two groups. In both groups of patients, 200 mg of mifepristone was given 36 to 48 hours before the administration of prostaglandins. In Group 1, the women were given 400 micrograms of oral misoprostol every 3 hours up to 5 doses. In Group 2, patients were given 1 mg of vaginal gemeprost every 6 hours up to 4 doses. The main outcomes measured were the induction-abortion intervals (the interval between the first dose of prostaglandin and abortion) and the incidence of side effects. Altogether, 50 subjects were recruited with 25 women in each group. The mean age and parity of the women and the mean gestational age of the two groups of women were comparable. There was no significant difference in the median induction-abortion intervals (8.7 hours in Group 1 and 10.8 hours in Group 2) or the incidence of side effects between the two groups of patients. We conclude that misoprostol is as effective as gemeprost in termination of second trimester pregnancy when combined with mifepristone.

Abortifacient Agents↗