Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002453 (amenorrhea)
 6,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

147 stage II pre- and perimenopausal breast cancer patients were treated with cyclophosphamide-methotrexate-5-fluorouracil (CMF)- based adjuvant regimens. 103 (72%) patients became amenorrheic during or immediately after the end of the chemotherapy program. Univariate analyses for age, menstrual status, nodal involvement, grading, estrogen and progesterone receptor status indicated no correlation between induction of amenorrhea and a significant prolongation of overall and disease-free survival. Multivariate analyses confirmed that young age at diagnosis, increasing number of infiltrated nodes, negative progesterone receptor status and grade 3 tumors are associated with a worse prognosis. Our results suggest that no benefit is expected in women with drug induced amenorrhea after CMF adjuvant treatment.
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PMID:Chemotherapy-induced amenorrhea and other clinical and pathological parameters in the prognosis of breast cancer patients. 147 23

Seventy women requesting first trimester abortion and with amenorrhea of less than 42 days were treated with a single 600-mg dose of mifepristone. Mifepristone is a synthetic 19-norsteroid with strong progesterone receptor antagonist properties. Complete abortion was achieved in 56 women (80%), 2 women (3%) had an incomplete abortion and 12 women (17%) had a continuing pregnancy. No relationship between rate of success and gestational age could be demonstrated. There was no serious side effects and the treatment was favorably received by the women concerned. It is concluded that this treatment is a safe and very acceptable alternative to vacuum aspiration for termination of early pregnancy.
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PMID:Induction of abortion in early pregnancy with mifepristone. 235 30

The relation between tumour oestrogen and progesterone receptor status, menstrual status, relapse-free survival, and overall survival was analysed in 411 patients with early breast cancer randomised to receive either postoperative adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF) or no additional treatment (control). Prolongation of time to recurrence and survival was seen predominantly in premenopausal patients; these effects were seen only with tumours positive for steroid receptors, particularly progesterone. Chemotherapy led to permanent amenorrhoea in 61% of premenopausal patients. The therapeutic effects of chemotherapy were seen only when CMF induced permanent amenorrhoea in premenopausal patients. These findings support the hypothesis that the effect of adjuvant chemotherapy in early breast cancer may be mediated by ovarian suppression.
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PMID:Mechanism of action of adjuvant chemotherapy in early breast cancer. 287 11

This review of the literature on antiprogesterone steroids considers the following aspects: the clinical history of antiprogesterones, clinical pharmacology, nonhuman primate experiments, human physiology studies, clinical studies, obstetric and gynecologic applications, bioethical issues, future directions. Antiprogesterone drugs are expected to be available soon for prescription in various obstetric and gynecologic circumstances. The aim is to develop progesterone receptor antagonists of such specificity that these agents do not bind to the glucocorticoid receptor. Antiprogesterones steroids have particular potential as a medical therapy applicable to the early stages of pregnancy. Unlike the prostaglandin derivatives, they act on the endometrium; they can induce menstruation from the time of implantation and should continue to be effective if prescribed up to 6-7 weeks of amenorrhea. In clinical studies, antiprogesterones have been used to dislodge the pregnancy and prostaglandins prescribed to evacuate the uterus. More study is needed before it can be determined whether repeated administration of antiprogesterone steroids for 3-4 days each month will provide reliable contraception. These agents can also be used in women whose menses are overdue, but in whom a pregnancy test would not yet bepositive. A further potential use of antiprogesterone drugs is in late pregnancy for the induction of labor. These agents can be expected to raise important bioethical issues, most notably the point at which contraception becomes abortion.
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PMID:Clinical status of antiprogesterone steroids. 300 2

RU 486 steroid, the 1st antiprogesterone which may be used in human therapy, prevents the hormone action by taking its place at the receptor level in target cells. It is a norethindrone derivative of the historical progestagen of oral contraception. Its affinity for the progesterone receptor is high, it is orally active, and toxicology studies fail to show any other effects than the endocrine consequences which may be expected from an antihormone. Consequently, it can be tested as a "contragestive" agent, putting emphasis on the fact that a few hours interruption of the progesterone action prevents pregnancy. At the Department of Obstetrics and Gynecology at the Geneva Hospital Cantonal, women who had asked to terminate 6-10 week pregnancies were administered 200 mg RU 486 to be taken orally for 4 days. The present results concern several hundred pregnancy terminations. With RU 486 alone, a unique dose of less than 400-600 mg, given in the evening, was more efficient than 50-200 mg/day for 3-7 days as in the initial trials. The results were particularly satisfactory when the compound was administered within the days following the assumed date of menstruation (5th week of amenorrhea). Several cases of normal pregnancies have been reported after using RU 486, including 1 as early as the following month. The analysis of the RU 486 mechanism of action showed that the blockage of the progesterone activity on decidualized endometrium causes the detachment of the embryo, resulting in a drop in hCG and secondary luteolysis. Then, prostaglandins are produced, as in laboratory animals, thus increasing contractility of the uterine muscles, such property already being used in pregnancy interruption. Thus, the fact of adding on the 4th day of the RU 486 treatment a weak dosage of synthetic prostaglandin equal to 1/6 of that used alone when inducing abortions made a clear improvement in the results possible. Trials have shown the feasibility of using RU 486 as a means of postcoital contraception. The monthly use of RU 486, at each cycle, of RU 486 as a menses-inducer for women who have regular coitus, is still under study. A study as to how much and for how long RU 486 is to be prescribed should make it possible to define conditions for maintaining a regular menstrual cycle. Conversely, other trials may lead to the use of RU 486 to monitor or suppress ovulation. RU 486 also makes it possible to provoke the therapeutic abortion of dead or abnormal fetuses, even at a late date. It is better tolerated than the oxytocic drugs now used.
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PMID:Fertility control in women: results with RU 486 by the end of 1985. 380 66

This review of fertility control focuses on recent prospects for fertility control, perspectives on fertility control drugs under investigation (established drugs and novel structure and biological activities), and future prospects for fertility control. Most of the research being conducted on new contraceptive devices is concentrated on 2 progestational steroids--norethisterone and its ester norethisterone enanthate, and levonorgestrel. Norethisterone is no longer under patent protection, and levonorgestrel, while still protected by patent, has been the benchmark as far as potent progestational steroids are concerned. Its potency allows the use of smaller daily quantities to be released to achieve the same biological action. This enables the life span of the device to be prolonged. In the IUD field, the devices being developed are able to release either copper progestational steroids. A new derivative of levonorgestrel, called desogestrel has recently been described and is reported to be twice as potent as levonorgestrel. If this proves to be the case, it might supplant levonorgestrel as the contraceptive steroid of choice for new device development. New developments are under way to produce both better and more acceptable barrier contraceptive methods. An area that has immediate promise for development of new contraceptive or fertility control methods is the development of nonsurgical methods for female sterilization. There are 3 candidate chemicals which seem to be effective and have been widely used clinically. The chemical used most extensively has been quinacrine, but it is known to have toxic properties. It has caused amenorrhea, intrauterine adhesions, chemical vaginitis, skin rash, and central nervous system excitation in women. There are 3 main classes of chemical compounds which fall into the general category of established drugs. For these drugs there are data from clinical studies which include both Phase 1 studies and efficacy studies. These agents, which can be classified into the groupings of steroids, prostaglandins, and analogs of luteinizing hormone releasing hormone (LRH, LHRH, LRF), are reviewed. It does appear that without some fresh impetus, such as the elucidation of certain physiological control processes, identification of the structure of native hormones like inhibin, and characterization of the structure of the progesterone receptor, further progress will be slow and limited.
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PMID:Fertility control. 675 97

A total of 60 women with 6-7 weeks' amenorrhoea were randomly allocated to three groups. The women in the first group (control) took a placebo 24 h before undergoing vacuum aspiration. The subjects in the second and third groups were given orally 200 mg of RU 486, 12 or 24 h before surgical interruption of their pregnancy. Villi and decidua were collected and frozen in liquid nitrogen. There were no significant differences in villous cytosolic steroid concentrations between the control and RU 486-treated groups. The RU 486 concentration was lower in villous cytosol than in decidua and serum. The immunostaining of progesterone receptor in villous and extravillous trophoblast was weak and localized in both cytoplasm and nucleus. RU 486 treatment had no effect on the immunostaining of progesterone receptors in trophoblast populations except in the placental bed giant cells, where the weak and diffuse progesterone receptor staining in the cytoplasm of controls seemed to be concentrated in the nucleus after RU 486 treatment. In conclusion, RU 486 might have no effect on the immunostaining of progesterone receptor and on steroid concentrations in villi in vivo.
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PMID:The effect of RU 486 on progesterone receptor in villous and extravillous trophoblast. 768 81

In research to control human reproduction, after the discovery of the progesterone receptor, an idea emerged about a molecule that could compete with progesterone for its binding site on the receptor, and at the same time block the receptor in a non-functional conformation to prevent or even terminate pregnancy. Among new progesterone antagonists tested, Roussel-UCLAF's RU-486 or mifepristone was the most fascinating. Currently in France (in 1993), a woman pays 4 visits over a 3-week period in a licensed hospital to terminate an unwanted pregnancy. She is given 3 x 200 mg pills of RU-486. 48 hours later, she receives the oral prostaglandin Misoprostol (2 x 200 mcg). She remains for 4 hours at the center, during which time 70% of the women abort. If expulsion does not occur, a third Misoprostol 200 mcg tablet is given. A fourth control visit takes place 10-15 days later. This protocol achieved 98% efficacy in pregnancies of 49 days of amenorrhea, but it is currently not applicable to heavy smokers or women over 35 years old. Other uses for RU-486: 1) Cervical ripening in second or third trimester abortions with a dose of 200-600 mg RU-486. 2) Initiation of labor in women for medical indications. 3) Contraception: a) late luteal postcoital administration of 400 or 600 mg RU-486 once or twice for 2 days before menses, b) monthly late luteal phase, premenstrual administration of a low-dose of RU-486 plus Misoprostol 2 days before menses, c) emergency postcoital contraception in a single 600 mg dose after unprotected intercourse within 72 hours, d) once a month anti-implantation with 200 mg of RU-486 given 2 days after unprotected intercourse, e) suppression of ovulation, f) endometrial contraception. After more than 10 years of administration to more than 150,000 women, RU-486, particularly in association with Misoprostol, is an excellent and safe agent for termination of pregnancy under the mandatory supervision of a physician.
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PMID:Steroid antagonists and receptor-associated proteins. 800 31

Concentrations of progesterone receptor (PR) and oestrogen receptor (ER) were measured by radioligand assay in decidual tissue of women undergoing termination of early pregnancy (amenorrhoea up to 49 days). Pregnancies were terminated by vacuum aspiration at 12 or 36 h after oral administration of placebo or antiprogestin RU486 in different doses. Treatment with RU486 decreased decidual PR content, the effect being observed at 12 h as well as at 36 h after 600 mg RU486 and at 36 h after 3 x 25 mg RU486 given at 12 h intervals. PR concentration 12 h after a single dose of 25 mg RU486 was not affected. ER content was unchanged at 12 h after RU486 but increased 36 h after 600 mg and 3 x 25 mg RU486. Our data suggest that apart from blocking progesterone action, RU486 may exert its abortifacient effect through decreasing the PR concentration. The simultaneous decrease of PR concentration and an increase of ER concentration changes the balance between them in favour of ER, which might also play a role in the abortifacient effect of RU486.
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PMID:The effect of RU486 on progesterone and oestrogen receptor concentration in human decidua on early pregnancy. 840 29

Under the hypothesis that the antiprogesterone RU 486 may induce regression of leiomyomata by withdrawal of progesterone action and/or by its interference with estrogen action, the effects of daily administration of 50 mg RU 486 for 3 months were examined in 10 patients with uterine leiomyomata. Monthly ultrasound examinations measured volume of leiomyomata. Myomectomy or hysterectomy was performed in 6 of 10 patients at the end of the treatment. Leiomyomata and myometrial tissue were obtained for immunocytochemical analysis of estrogen receptor (ER) and progesterone receptor (PR) proteins. Amenorrhea was induced in all patients. Leiomyomata volume decreased 21.9 +or- 4.8% after 4 weeks, 39.5 +or- 6.6% (p 0.001) after 8 weeks, and 49.0 +or- 9.2% (p 0.001) after 12 weeks of treatment compared to pretreatment measurements. Serum luteinizing hormone (LH) levels (p 0.005), but not follicle-stimulating hormone (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 which returned to baseline at 4 weeks and remained unchanged afterwards. 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. PR, but not ER, immunoreactivity was significantly reduced in both leiomyomata and myometrium after RU 486 treatment compared with tissues from untreated patients, suggesting the regression of tumors through a direct antiprogesterone effect. There was a significant decrease in PR staining in both leiomyomata and myometrium of RU 486-treated patients when compared to controls. Using image analysis, significantly (p 0.05) more PR immunoreactivity was seen in leiomyomata of treated or control patients when compared to their respective myometrium. ER immunoreactivity was significantly greater (p 0.05) in control leiomyomata when compared to control myometrium, while no difference in ER immunoreactivity was seen between leiomyomata and myometrium of treated patients. RU 486 proved to be safe and effective for a novel mode of management for uterine leiomyomata.
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PMID:Regression of uterine leiomyomata in response to the antiprogesterone RU 486. 843 97


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