Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00691 (EE2)
 7,802 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

63 pregnant women (aged 20-35 years) with a parity range from 0-3 (average 1.6+-.8) were treated in vaginal suppository form with ONO-802 at either .5 or 1 mg. Pregnancy-stage range was from 11-66 days beyond last expected menstrual period. Patients were instructed to insert 1 suppository every 3 hours for a maximum of 5 applications. Estradiol and progesterone levels were assayed from venous blood samples before (control) administration and 3, 6, and 24 hours postadministration. No changes were present at onset of contractions, but all fractions decreased by 48 hours postadministration. 63/63 responded with hemorrhage. 54/63 (86%) had complete abortions (89% with 1 mg, 84% with .5 mg). 9/63 were incomplete (14%), but there was sufficient dilatation for subsequent uterine content removal. With the 1-mg dose, uterine contractions and hemorrhage occurred about 1.5 hours sooner. 1/63 (1.6%) complained of nausea and vomiting, and 3 (4.8%) complained of headache. No other side effects were observed.
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PMID:Termination of early pregnancy by ONO-802 suppositories (16,16-dimethyl-trans-delta2-PGE1 methyl ester). 70 15

A clinical review of the oral contraceptive Ovral (.5 mg norgestrel, .05 mg ethinyl estradiol), representing 6806 users over 9836 woman-years of use, is presented. 19 pregnancies occurred (.19 per 100 woman-years), though none were attributable to failure of the drug. Menstrual periods were regular and predictable in at least 80% of the patients. The incidence of intermenstrual bleeding was low (2.5% of the cycles). 306 patients (4.5%) discontinued medication for medical reason s, the most prevalent of which were headache, nausea and vomiting, weight gain, and nervousness. Breast masses developed in 19 women, carcinoma in situ of the cervix in 16 patients, and thrombophlebitis in 9 women. Hepatic and thyroid functions were slightly altered, though there was no evidence of abnormal adrenal function or neuro-ophthalmologic effects related to the medication. Fertility promp tly returned after cessation of treatment in most cases, and no infant a bnormalities were attributable to the drug. The contraceptive effect of Ovral is suggested to be due primarily to gonadotropin suppression with subsequent inhibition of ovulation.
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PMID:Eight years of fertility control with norgestrel-ethinyl estradiol (Ovral): an updated clinical review. 118 25

At this time 3 triphasics are widely used in the US: Ortho-Novum 7/7/7, Tri-Norinyl, and Triphasil. Ethinyl estradiol is the preferred estrogenic agent for the triphasic products. Torethindrone and levonorgestrel were chosen as the progestins for the triphasic products. It is the combined effects of estrogen and progestin in the triphasics that provide their contraceptive action. Triphasil increases both the estrogen and the progestin at midcycle; Tri-Norinyl and Ortho-Novum 7/7/7 elevate the progestin only. The midcycle surges of estrogen and luteinizing hormone are dampened, and ovulation is inhibited. The triphasics represent a 98.7% reduction in total steroid content since oral contraceptives (OCs) were introduced. An estrogen dose of 30-50 mcg will inhibit ovulation, and side effects with such a dose are considered tolerable. The triphasic OCs are in this range. An estrogen dose of 20 mcg has been tested but is slightly less effective and is not recommended. Contraceptive failures have occurred with the triphasic products. In 1486 women studied, 6 pregnancies have occurred. Of these failures, one may have been because of a drug interaction with a barbituate. 1 pregnancy was due to patient failure; 3 consecutive pills were missed. Only 2 pregnancies were certain drug failures. Because of the gentle suppression of ovarian function, it has been observed that the menstrual flow is less affected than by standard OCs. Due to the fact that less total steroid is delivered and more endometrial shedding occurs, it is hoped that the triphasic preparations will have less of a "lingering" effect on the return to functional fertility. Most of the published data on side effects is available from the UK, North America, and Europe on the formulation known in the US as Triphasil. Nausea, vomiting, breakthrough bleeding, weight gain, and breast tenderness appear to be the most common side effects. The major medical reasons for triphasic discontinuation include breast tenderness, weight gain, breakthrough bleeding, nausea and vomiting, headache, and increased bleeding during the 1 week of withdrawal. Rifampin and phenobarbital are examples of drugs found to decrease pill efficiency, including triphasics. Also, a triphasic may interfere with the action of another drug. The new triphasics are appropriate when starting new patients on OCs. Patient counseling is essential. Due to the low margin of error as a consequence of lesser suppression of ovarian function, the patient needs to be well instructed in how to take the pill and advised of the consequences of missed tables.
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PMID:The triphasics: insights for effective clinical use. 382 67

The ability of various estrogen antagonists and agonists to compete with [3H]spiroperidol, [3H]domperidone, [3H]dihydroalprenolol, [3H]dihydroergocryptine, [3H]dopamine or [3H]5-hydroxytryptamine for binding to membrane preparations from rat brain tissue was tested. The non-steroidal triphenylethylene-type antiestrogens with an amine side chain--enclomiphene, nitromifene, tamoxifen and zuclomiphene--were found to be competitive inhibitors of [3H]spiroperidol (Kd = 0.12 nM; Bmax = 101 fmol/mg protein) and [3H]domperidone (Kd = 0.62 nM; Bmax = 86 fmol/mg protein) binding to striatal membranes. The Ki values ranged from 4-12 microM. Estradiol-17 beta (Ki = 480 microM) or diethylstilbestrol (Ki = 63 microM) were much less effective inhibitors exhibiting noncompetitive interaction with the in vitro binding of [3H]spiroperidol. The pharmacological relevance of the antiestrogen interactions with dopamine receptor binding is discussed with respect to adverse effects of the in vivo administered compounds such as nausea and vomiting.
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PMID:Interaction of non-steroidal antiestrogens with dopamine receptor binding. 609 84

Following the development of hormonal interception after coitus the post-coital insertion of an intrauterine contraceptive device was proposed by Tatum . The advantage of this treatment is the avoidance of the ingestion of large doses of estrogen which causes much nausea and vomiting although it is a very effective post-coital method of contraception. The recently proposed alternative administration of 200 micrograms Ethynol Estradiol combined with 2 mg of DL norgesterol in 2 equal doses at 12 hour intervals has the same disadvantage of a high percentage of side effects. The post-coital insertion of an intrauterine contraceptive device is the first method which is effective up to five days following unprotected intercourse which is three days longer than treatment by estrogen. In addition the method can be offered to women who would want to continue to wear the intrauterine contraceptive device for long term contraception. The disadvantage of the post-coital insertion of an intrauterine contraceptive device is the ability of serious complications if the patient has a vaginal or venereal infection or an asymptomatic cervicitis or salpingitis. Following appropriate physical examination women who present themselves for post-coital treatment are selected. Cases of rape are usually not suitable for treatment with intrauterine contraceptives devices. However, when cases of rape are seen early enough the appropriate investigations may be done and the treatment with the intrauterine device started within five days. The potential risk of future infertility must be considered since salpingitis is 7 times more common in nulliparous wearers of intrauterine devices than in nulliparous non-wearers. Young sexually active nulliparous women especially of lower socio economic background are patients with a high risk. Over 70% of the women who present themselves for interception treatment are nulliparous.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Postcoital IUD insertion, a review]. 637 83

750 cycles of treatment with a new triphasic oral contraceptive (OC), (WL-49(50), Trinordiol), containing the lowest quantity of steroids of all available preparations were evaluated in 75 healthy young women (mean age 19.6 years). 70% of all young women had normal, regular menstrual cycles. 65% had not used contraception previously, and the others had previously taken combined or progestogen only OCs or had an IUD. The mean length of treatment with the triphasic preparation was 10 cycles. Routine clinical evaluation, including gynecological examination, weight and blood pressure measurement, assessment of cycle events, and recording of spontaneously reported side effects, was performed every 3 months. Cycle control during triphasic OC use was very good. There was a statistically significant trend of the cycles toward more regularity than prior to this type of contraception, with an increased frequency of 28-day cycles. Duration of menses was significantly reduced and menstrual volume was more frequently rated by the women as normal. Spotting and breakthrough bleeding showed a very low frequency, the latter accounting for less than 10% of intermenstrual bleeding during triphasic OC medication. Frequency of side effects was 53.3% (40 women) during triphasic OC use. 20% of the population reported side effects among the reasons for stopping triphasic OC use. Breast tenderness was the most frequent side effect recorded in almost 9% of the total number of treatment cycles. It affected 21% of the women under study, a significantly more frequent occurrence than before triphasic OC use in these individuals. The tendency of this symptom to improve was observed in more than half of the cases within 3 months use of triphasic OC use. Other signs of estrogenic dominance such as gastrointestinal disturbances, vaginal discharge, pelvic congestion, and leg cramps were also present but much less prominent than breast tenderness. 16 (21.3%) patients presented with breast tenderness for 67 (8.9%) cycles. Nausea and vomiting were experienced by 6 (8%) patients for 28 (3.7%) cycles. Vaginal discharge was present in 10 (13.3%) patients for 33 (4.4% cycles). Spotting and breakthrough bleeding occurred in 6 (8%) women for 14 (1.9% cycles). Absence of change in weight was recorded in 1/3 of the women studied; another 1/3 experienced a weight reduction of 1-4 kg and the last 1/3 gained 1-4 kg. There were no statistically significant variations in either systolic or diastolic blood pressure values.
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PMID:Clinical experience with a triphasic oral contraceptive ('Trinordiol') in young women. 640 57

This study was aimed at assessing a new low dose combined estrogen-progestogen sustained release system in which the steroids were formulated as a microcrystalline aqueous suspension and injected throug a 19-gauge needle. The control of crystal size of norethisterone (NET) and ethinyl estradiol (EE2) produced sustained dissolution in both in vitro and in vivo studies. In vitro dissolution profiles revealed an inverse relationship between the percentage of NET and EE2 dissolved and size range of crystals, with complete dissolution of the miconized steroid achieved at 1 hour. A dose-response experiment carried out in healthy women indicated that intramuscular injection of 10 mg of NET with 1 mg of EE2 maintained NET serum levels above 1 ng/ml for at least 25 days. Systemic side effects such as nausea and vomiting were experienced by all 7 volunteers after the injection, suggesting that EE2 was rapidly absorbed. A less soluble system such as mestranol could be used instead of EE2 to improve the performance of the present system. There were no signs of local irritation. These findings indicate that the dosages of currently available injectable contraceptive compounds can be substantially reduced without loss of anovulatory potency. Clinical studies to assess the pharmacokinetics and pharmacodynamics of 10 mg of NET with 1 mg of EE2 or mestranol as monthly injectable are currently under way.
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PMID:Development of a low-dose monthly injectable contraceptive system: I. Choice of compounds, dose and administration route. 650 88

102 patients using Trinordiol, a triphasic oral contraceptive (OC) containing ethinyl estradiol and d-norgestrel, were followed for 932 cycles in a study of secondary effects. Follow-up visits were scheduled after 1,3, and 6 months and every 6 months thereafter. 26 patients discontinued use of the pills during the study after using them for a total of 159 cycles. 5 discontinued because of abdominal pain, 1 for breast tenderness, and 1 because of headaches or migraines. 7 discontinued because of metrorrhagia, 4 for weight gain, 3 for amenorrhea, 2 for nausea and vomiting, and 1 each for nervousness, water retention, acne, desire for pregnancy, leaving the country, hypertension, and unknown motivation. the average age of patients was 23.6 years, with a range from 14-48. 76% were aged 15-29 years. 52.9% were nulliparas. 58.8% were Belgian, 21.6% were from Mediterranean Europe, 10.8% were Moroccan, and 7.9% were from black Africa. Only 1 patient, a 37 year old, developed hypertension. 15 patients gained more than 2 kg and 17 lost more than 2 kg. 15.8% complained of spotting during the 1st cycle compared to 3.1% during the 6th cycle, 5.2% during cycle 7-12, and 9.1% during cycle 13-30. Among 35 patients who did not discontinue treatment, 7 complained of amenorrhea and 1 of scanty menstrual bleeding, 14 of pain including 7 cases of pelvic pain, 2 of dysmenorrhea, 3 of breast tenderness, and 2 of headaches, 15 of leukorrhea, 3 of nausea, 2 of dizziness, and 1 each of fatigue, acne, galactorrhea, and cutaneous pruritus. 1 case of myoma at the level of the uterine cornu was identified after 24 cycles of treatment. In all, 61 patients had some complaint, while 41 were totally satisfied. No patient became pregnant during the study.
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PMID:[Clinical study of the secondary effects associated with taking a triphasic anti-ovulatory contraceptive]. 670 4

Postcoital contraceptives are available for adolescent use in the US. They include combination oral contraceptives (OCs), high dose estrogens, danazol, and IUDs. Mifepristone (RU-486) is currently not available in the US but is used in France, the UK, and Sweden. Postcoital contraception is especially important for adolescents who have a very high pregnancy rate due to poor contraceptive use. Administration of 2-5 mg ethinyl estradiol (EE) for 5 days beginning within 72 hours of unprotected intercourse yields pregnancy rates ranging from 0-0.92%. EE-related side effects include nausea, vomiting, sore breasts, and irregular menstrual bleeding. DES should not be used, since it is associated with reproductive tract anomalies and vaginal cancers in exposed offspring. Conjugated estrogens have not been used in adolescents for postcoital contraception. The Yuzpe regimen consists of 2 tablets of a combined OC with 200 mg EE and 2 mg dl-norgestrel administered within 72 hours of unprotected intercourse followed by the same dose 12 hours later. Common side effects are nausea and vomiting. Its pregnancy rate is 1.8%. Levonorgestrel-containing OCs can also be used. Administration of 800-1200 mg danazol up to 120 hours after unprotected intercourse protects against pregnancy in about 98% of cases. Copper IUDs have a high efficacy rate when used as postcoital contraception (99.9%), but public opinion, medicolegal considerations, financial costs, and potential for infection impede IUD as a postcoital contraceptive in the US. RU-486 is best known as an abortifacient. It is also a potential postcoital contraceptive. Two UK studies find that RU-486 used as a postcoital contraceptive has a very low pregnancy rate and fewer side effects than the Yuzpe regimen and danazol. It is much more costly than currently used postcoital contraceptives (600 mg of RU-486 cost US$ 68, while Ovral costs US$ 0.48-2.24). Nevertheless, RU-486 may replace the higher doses of OCs as a postcoital contraceptive method.
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PMID:Postcoital contraception: present and future options. 774 40

Studies by A. Albert Yuzpe, MD, and Lee H. Schilling, MD, have shown Ovral to be an effective contraceptive after unprotected intercourse at any time in the menstrual cycle, not just in midcycle. As a morning after pill, Ovral is taken in 2 doses: 2 tablets within 72 hours after coitus; 2 tablets 12 hours later, a total of 200 mcg ethinyl estradiol and 2 mg di-norgestrel. Risk of pregnancy from a single act of unprotected midcycle coitus averages 20-30% while the risk from unprotected intercourse at other times in the cycle averages 2-4%. Young, nulliparoous, women would be the prime target for the morning after pill. 98.5% of the women in Yuzpe's study bled within 21 days. The 1.5% who do not bleed within the expected time will either be pregnant or have a delayed period. Ovral can be administered from a pack in the doctor's office. The major complaint about DES was nausea and vomiting. Only 24% of the women taking Ovral reported nausea. The episodes were mild and controlled with an antiemetic. Both doctors and patients are wary of DES because of public concern about teratogenesis. Many doctors recommend termination of pregnancy if it was conceived while the woman was using DES. Ovral use does not usually indicate abortion. The postcoital IUD insertion studies have included small numbers of patients, but the difficulties are that bleeding following insertion may suggest pregnancy, and the potential for pelvic infection is increased. Ovral should not be given to women who have contraindications to oral contraceptives, and benefits and risks should be weighed.
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PMID:Ovral touted as morning-after pill. 1226 90


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