Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

User compliance is not a problem for the recently approved subdermal, longterm contraceptive delivery system, Norplant. It delivers 50-80 mcg of levonorgestrel/day during the 1st year and 30-35 mcg for years 2-5. The levonorgestrel is encased in 6 36 mm x 2.4 mm capsules which are placed in the upper arm in 5-10 minutes using local anesthesia. Since the implants systemically release levonorgestrel, the shock to the liver experienced in oral contraceptive (OC) users does not occur. Levonorgestrel prevents pregnancy by decreasing luteinizing hormone and follicle stimulating hormone which prevents ovulation, reducing the rate of ovum transfer in the tube, making the endometrium incompatible for implantation, and making the cervical mucus too thick and scanty for sperms to migrate if ovulation does occur. 1-year pregnancy rates for Norplant users are much lower than for women who use other contraceptives (0.6/100 users vs. 2.3/100 for OC users and 2.4/100 for IUD users). The ectopic pregnancy rate is also low (1.47/1000 Norplant users). The 1-year continuation rate is 80% compared with 50% for OC users. Fertility returns within 3 months for 50% of users and within 1 year for 80%. Because Norplant does not adversely affect lipid metabolism there is no increase in the risk of atherogenesis. Menstrual irregularities are the leading side effect of Norplant. The irregular cycles tend to occur during the 1st 3-6 months after insertion. Other side effects include headaches, acne, breast discharge, weight gain, and transient ovarian cysts. Contraindications are abnormal uterine bleeding, possible pregnancy, active liver disease, and women taking phenytoin. The cost for the initial exam and insertion of the Norplant capsules is $500 at Planned parenthood of the Rocky Mountains in Colorado (mean=$8.30/month vs. $13/month for 5 years of taking OCs). Due to the possibility of exploitation of women and involuntary infertility, nurse practitioners must thoroughly explain the system to each patient and answer all questions so the patient can give informed consent.
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PMID:New concepts in contraception: Norplant subdermal implant. 156 6

In Finland, the hormonal diaphragm Levonova was put on the market in the fall of 1990. Since that time, more than 20,000 Finnish women have been using them. The hormonal diaphragm is most suitable for women who want long-term contraception. It has a 5-year duration, and its contraceptive effectiveness equals that of sterilization. Levonova releases levonorgestrel directly into the uterus, thus its effect is local, and therefore, women who cannot take other hormonal preparations can use it. Thus, there is no upper age limit for using Levonova in contrast to oral contraceptive use. Nevertheless, hormonal diaphragms are not recommended for nulliparous women 25 years of age. This preparation is mainly recommended for women who no longer wish to have a child, yet who do not want to undergo sterilization in cases they change their mind. The hormonal diaphragm is fitted during menstruation, or at the latest on the 7th day after the beginning of menstruation. This is a simple procedure, and a follow-up examination 3 months later is recommended. In rare instances, side effects such as headache, lower abdominal tumescence, lack of appetite, and depression can occur, but these are transitory. In general it has been observed that in women who have had heavy bleeding or painful menstruation, these symptoms become ameliorated after the insertion of the hormonal diaphragm. Levonova has been tested during 10,000-use years with the participation of 3500 women using it from 1-5 years. These investigations are currently proceeding, and 50% of women are kept under observation during normal use in order to get Levonova registered in the countries of the European Common Market, the manufacturer, Leiras Pharmaceutical co., has disclosed.
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PMID:[The hormone diaphragm affords safe contraception and relief from menstrual pain]. 161 46

The Norplant System consists of 6 capsules each containing 36 mg of crystal line levonorgestrel (LNG), for a total dose of 216 mg LNG. The capsules are inserted subdermally in the mid-upper arm, and LNG diffuses continuously through the capsule walls for 5 years. In the United States the Norplant System was approved in December 1990. The initial rate of hormone delivery is about 85 mcg/day, then decreases over the next 9 months to 5 mcg/day, and over the ensuing 9 months to 35 mcg/day. Thereafter, the diffusion rate levels off for the next 3.5 years, averaging around 30-35 mcg/day. Removal results in a drop in the plasma concentration of levonorgestrel to below contraceptive levels within 24 hours and below the detectable limit of .1 pg/ml at 96 hours. Preliminarily data from 402 users over 5 years show improvements of Norplant produced better efficacy in all weight classes and a lowered cumulative rate of 1.1 pregnancies of 100 users. The pregnancy rate for the first year of use is 02., better than for oral contraceptives. Side effects include headache, nervousness, nausea, dizziness, dermatitis, acne, change of appetite, breast tenderness, minimal weight gain, some change in hair distribution, and adnexal enlargement. Adverse reactions include breast discharge, possible cervicitis, musculoskeletal pain, abdominal discomfort, leukorrhea, and vaginitis. More than the usual number of bleeding days occurred in slightly more than one fourth of the patients, prolonged bleeding in 27.6% spotting in 17.1% and amenorrhea in 9.4% of patients. Hyperlipidemic users should be observed for possible low-density lipoprotein elevations. The cumulative discontinuation rate for pregnancy was 3.9 per 100 users; for bleeding irregularities the rate was 25.1 per 100 users, and for other medical results it was about 22.4 per 100 users. Personal reasons for discontinuation accounted for 38.7 per 100 users, equivalent to a cumulative continuation rate of about 30 per 100 users over the 5-year duration.
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PMID:The NORPLANT system of contraception. 168 4

A comparison of the triphasic Triphasil and the combined oral contraceptive Diane 50 for treatment of acne for 6 cycles showed significant improvement in both groups. Triphasil (Wyeth-Ayerst) contains 50 mcg levonorgestrel and 30 mcg ethinyl estradiol, 75 mcg levonorgestrel and 40 mcg ethinyl estradiol for 5 days and 125 mcg levonorgestrel and 30 mcg ethinyl estradiol for 10 days. Diane 50 (Schering Ag) contains 2 mg cyproterone acetate and 50 mcg ethinyl estradiol for 21 days per cycle. 10 women in each group had physical, pelvic, ophthalmologic and neurologic exams, hematologic and biochemical screens, assays of free testosterone, sex hormone binding globulin (SHBG), androstenedione, dehydroepiandrosterone SO4 (DHEAS), progesterone, and computations of acne and hirsutism scores. Subjects had used tetracyclines, isotretinoin, erythromycin, topical clindamycin and benzoyl peroxide previously, but were withdrawn from medication in the cycle before the intervention. The mean acne scores, derived from grading and counting lesions and comedones, fell from 63.3 to 6 in the Diane 50 and from 64.2 to 4.5 in the Triphasil group. Subjective results were excellent for 6, good for 2 and unsatisfactory for 2 in the Diane 50 group, and excellent for 8 and good for 2 in the Triphasil group. In both groups mean free testosterone, androgen index, androstenedione and DHEAS, and an increase in SHBG were documented. 5 Triphasil and 5 Diane 50 subjects had increased cholesterol levels during the trial, the only abnormality detected. Side effects reported were recurrence of varicose veins and hemorrhoids in 1 women who withdrew, and complaints of mastalgia, nausea, dysmenorrhea, migraine, headache, backache and vaginal discharge.
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PMID:An open study of Triphasil and Diane 50 in the treatment of acne. 183 45

Triphasil, a low-dose combination oral contraceptive containing levonorgestrel and ethinyl estradiol, was tested in four Planned Parenthood clinics on 317 women between 18 and 34 years of age (mean, 23) for a total of 4,692 cycles, or 361 woman-years of usage. Approximately half these volunteers (165) were nulligravidas, and 309 (97.5%) were white. Despite instructions on proper tablet usage, there were 416 cycles (8.9%) in which one or more tablets were missed. Only one pregnancy occurred, in a cycle in which a total of four tablets was missed, for an uncorrected Pearl index of 0.28 pregnancies per 100 woman-years of usage. No pregnancy resulted from method failure, indicating a 100% efficacy rate for Triphasil when taken properly. The mean length of the menstrual cycle with Triphasil was 27.9 days; the mean length of menses, 4.4 days; and the mean latency period, 2.1 days. Menstrual flow was average in 64.1% of the subjects, light in 34.1%, heavy in 1.3% and variable in 0.5%. Amenorrhea during the tablet-free interval occurred in only 0.6% of the 4,692 cycles in which Triphasil was used. Breakthrough bleeding occurred in 6.9% of first cycles and 3.2% of total cycles; spotting, in 10.7% of first cycles and 4.4% of total cycles. Other symptoms that occurred with an incidence of greater than or equal to 1% were acne (1.0%), appetite increase (1.2%), breast discomfort (2.8%), breast enlargement (1.3%), gastrointestinal symptoms (1.7%), simple headache (1.4%) and nausea (1.1%). A total of 44 women (13.9%) discontinued treatment for medical reasons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Planned Parenthood experience with triphasil. 365 99

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

Drug companies have been at work throughout the 1960s, 1970s, and 1980s trying to reduce the steroid content of their oral contraceptives (OCs). Researchers have been successful in reducing steroid content while maintaining effectiveness, thereby making OCs safer. In the 1st half of the natural menstrual cycle, a woman secretes estrogen as the dominant steroid product. In the 2nd half, estrogen is the principal reproductive hormone. Estrogens inhibit ovulation, possibly by inhibiting implantation, altering ovum transplant, or in some way preventing corpus luteum function, which is necessary to maintain early pregnancies and the endometrium. There are still only 2 estrogens and 6 progestins on the market today. They are probably the most thoroughly studied chemical ever seen in the history of pharmacy or medicine. 1 of the estrogens, mestranol, is really a drug of the past. In the body, mestranol is converted to ethinyl estradiol, the other estrogen on the market. Consequently, there is no reason to use mestranol itself. Within the dose range of 50-100 mcg, there's little difference in contraceptive effect. Progestins are the other active ingredient in the combination OC. Their principal action is the thickening of the cervical mucus, which prevents sperm penetration. Also, with sufficient progesterone, ovulation is inhibited, but this happens in only 40% of those patients taking, for instance, the "mini-pill" (which consists of progesterone only). The progestins and the estrogens work in concert to make OCs a highly effective contraceptive method. Recent surveys conducted by the Centers for Disease Control and National Cancer Institute looked into the relative effectiveness of OCs. Nordette had a use effectiveness failure rate of 3.5; Ovral, 3.6. Loestrin 1/20 -- norethindrone acetate, 1 mg, and estinyl estradiol, 20 mcg -- shows a failure rate of 4.5. This indicates that the threshold for an effective dose of estinyl estradiol in OCs is 30 mcg. For 1 mini-pill, Ovrette, the failure rate is 9.5 -- much higher. Depo-Provera has a failure rate of 0.7. The primary complaint from women taking OCs is spotting and breakthrough bleeding during the cycle. 30-50% of women given OCs stop taking them within a year. OC side effects include nausea, fluid retention, breast tenderness, leukorrhea, hypomenorrhea, headaches, spotting around the face, hypertension, and visual changes. 1 of the risks of birth control pills may be cervical dysplasia -- changes in the cells of the cervix. The relative risk of cervical cancer with OCs after 5-9 years is approximately 1.8. Clinical cases of deep vein thrombosis number 1/1000 per year among nonusers of OCs. Among users, the rate is 3 times as high: 3/1000. The most serious potential adverse effect is myocardial infarction. Of the excess deaths attributed to OCs (23.3 total per 100,000 users), 22.7 are due to myocardial infarctions and hemorrhage. The discussion also briefly reviews other methods of contraception -- Depo-Provera, male contraceptives, implants, the diapragm, and IUDs.
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PMID:Prescription contraceptives: countering the risks. 405 Jun 70

The efficacy, side effects, and biologic actions of the progestogen-only minipills marketed since February 1973 are reviewed. The preparations are: 350 mcg norethisterone (Micronor Ortho), 30 mcg d-norgestrel (Microlut Schering and Microval Wyeth), and 500 mcg lynestrenol (Exluton Organon). The efficacy of these drugs depends on motivation: Pearl indexes vary from 1.17-3.72 for norethisterone, .9-4.4 for d-norgestrel, and .8- 2.2 for lynestrenol. Some physiologic effects of minipills possibly related to their mode of action are impermeable cervical mucus and low levels of progesterone, pregnanediol, estrogen, and LH. The side effects influencing dropout most are spotting (40-55% in the first cycle), polymenorrhea (about 10%), and amenorrhea (about 5-10%). Some transient estrogenic side effects such as nausea, headaches, and breast pain may be due to estrogenic metabolites from lynestrenol and norethisterone. None of the severe estrogenic side effects, such as thrombophlebitis and impaired glucose tolerance and liver function, are characteristic of progestogen pills.
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PMID:[Minipill as the new contraceptive method]. 481 42

Contraceptive vaginal rings (CVRs), with approximate daily release rates of 250-290 mcg of levonorgestrel and 150-180 mcg of estradiol and manufactured in a shell design, were studied for effectiveness and acceptability in multicentered trials involving 1103 ring users in Brazil, Chile, Dominican Republic, Sweden, U.S., Denmark/Finland, and Nigeria. A comparison group of 533 women used the oral contraceptive Nordette. Both 1st and all segment 1 year gross pregnancy rates among CVR users were less than 3/100, rates similar to Nordette users. Continuation at 1 year was 50/100 users of the ring (all segments) and 38/100 among Nordette users, more of whom were lost to follow-up. Gross 1 year rates of termination for medical reasons ranged from 25-29/100. Ring users were more likely to terminate for vaginal problems and pill users for headache, nausea, and associated reasons. These trials indicate that CVRs of this design are as effective and have continuation rates equal to and possibly superior to Nordette under the same study conditions.
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PMID:A multicenter study of levonorgestrel-estradiol contraceptive vaginal rings. I-Use effectiveness. An international comparative trial. 645 8

75 patients with cluster headache (63 men and 12 women) and 939 with migraine headache were seen among 1260 new patients at the Princess Margaret Migraine Clinic of Charing Cross Hospital (London, England) over a 16-month period. 3 points of interest emerged from this analysis. The age of onset in women, unlike the men, appeared to be bimodal. Approximately half of the women developed the condition in early adult life, and the remainder at about the time of the menopause. These distributions were significantly different. This was not noted in Ekbom's earlier series nor in that of Pearce, although Ekbom did record a disproportionate number of old women at presentation. Atypical cases seemed more common among women and especially among those women who developed headaches later in life. There were no satisfactory criteria for the classification of less typical cases, e.g., patients with single weekly attacks typical in site and duration, or patients with bout up to 12 attacks daily but with long headache free intervals that would appear to exclude the diagnosis of chronic paroxysmal hemicrania. 6 of the 7 typical premenstrual cases had been on oral contraceptives (OCs), and 4 of these associated breaks from contraception with the start of clusters. They could not abort a cluster by immediately restarting OC. In 1 case there was a temporal association with a change from Ovulen 50 to Ovranette, and the headaches settled when she was changed back to Ovulen 50 3 months later. They recurred when she stopped the Ovulen 50 again after 4 months, and she conceived during the cluster, which ceased in the 4th week of pregnancy. She had another cluster, lasting 6 weeks, which started when she was 11 weeks pregnant but none later in the pregnancy. She had a further cluster 7 months postpartum, and hormonal treatment has been contraindicated by a postpartum thrombosis. The anecdotal nature of this observation cannot be denied, but a large scale trial is not feasible. Longterm OC use, possibly with a 50 mcg estrogen preparation, might be helpful in occasional patients. This phenomenon is the opposite of that found in migraine, emphasizing the distinction between the 2 conditions.
Cephalalgia 1982 Sep
PMID:Cluster headache in women. 715 Nov 51


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