Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
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Changes in body weight and the incidence of estrogen-related side effects with low-dose oral contraceptives (OCs) containing 20 microg ethinyl estradiol (EE) have not been demonstrated in placebo-controlled trials. Two placebo-controlled, randomized trials demonstrated the efficacy of a low-dose OC for the treatment of acne in healthy females (n = 704; >or=14 years old) with regular menstrual cycles and moderate facial acne. Patients were randomized to receive 20 microg EE/100 microg levonorgestrel (LNG) or placebo for six cycles. Body weight was measured at baseline and during Cycles 1, 3, and 6. The occurrence of adverse events was recorded at each visit. Mean changes in weight from baseline were similar with 20 microg EE/100 microg LNG [0.72 kg +/- 2.64 (SD; n = 349)] and placebo [0.56 kg +/- 2.64 (SD; n = 355; p > 0.05)] for the last measured weight of each patient. Rates of headache, nausea, weight gain, and breast pain, side effects commonly attributed to OCs, were also similar between groups (p > 0.05). No serious, unexpected, drug-related adverse events occurred during the study. The low-dose OC containing 20 microg EE/100 microg LNG is safe, well tolerated, and does not cause weight gain.
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PMID:Weight change and adverse event incidence with a low-dose oral contraceptive: two randomized, placebo-controlled trials. 1167 50

Pseudotumor cerebri or benign intracranial hypertension is a syndrome of raised intracranial pressure without obvious explanation. Most patients are obese women at childbearing age. Symptoms and signs usually include headache, nausea, vomiting, edema of the papilla, visual obscurations and rarely palsy of the nervus abducens. The prognosis is generally good, but progressive visual loss and eventual blindness are major risks. We report the case of a 21-year-old non-obese young woman who developed pseudotumor cerebri while taking minocycline for acne therapy. Identical symptoms occurred upon inadvert rechallenge with minocycline for the second time.
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PMID:[Pseudotumor cerebri in minocyline treatment]. 1168 Jan 22

Reactions to oral contraceptive therapy tend to be maximal during the first few months of use. They include nausea or epigastric discomfort, malaise, dizziness, nervousness, fatigue, weakness, leg cramps, headache, and depression. The estrogenic component is thought to be the cause. There may also be a psychogenic basis reflecting apprehension. Breast tenderness is an occasional complaint and intermenstrual spotting or breakthrough bleeding is often reported. Increasing dosage has reduced this symptom. Dysmenorrhea prior to treatment may be improved but occasionally it is aggravated. Drug-induced amenorrhea presents a double problem in that failure to resume medication 7 days after completion of a cycle results in a risk of conception. Episodes of severe uterine bleeding in patients discontinuing use after several months or years have been reported. Other side effects include a skin reaction resembling acne, pruritus, hirsutism, thinning of scalp hair, increased skin pigmentation, and weight gain or loss. Serious vascular complications and hepatic dysfunction have been shown and deviation of thyroid function may be shown by increase of serum protein-bound iodine (PBI). Clinical signs of hyperthyroidism have not been described. Oral contraception is associated with elevated plasma cortisol (hydrocortisone) levels and decreased urinary levels of 17-hydroxycorticosteroids (17-OCHS). Suppression of ovarian activity by oral contraceptives is rapidly reversible. Fear of carcinogenesis has caused much alarm but no proof as of the present time. Safety of long term use will require additional years of experience.
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PMID:Side-effects and possible complications of oral contraceptive drugs. 1225 41

100 women used the sequential preparation Physiostat for a total of 1029 cycles. 65 were between 20 and 40 years of age, 24 were nulliparae, and 59 were workers or employees. No pregnancies were reported. After 6-12 cycles of use, very few menstrual irregularities were reported, and 99% had no spotting after the first cycle of use. In one case, the preparation had to be discontinued due to vascular disorders. There were 5 cases of headaches, one of nausea. 9% reported no change in weight. 6 women reported improvement of an acne condition. 2 women discontinued Physiostat use due to a reduction in libido; 18 reported that their libido increased during Physiostat use.
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PMID:[Physiostat: normophasic oral contraceptive]. 1226 83

There is considerable evidence to support an immunopathogenic basis of psoriasis. However, changes such as altered angiogenesis have also been implicated in the pathogenesis of psoriasis. AE-941 (Neovastat; Aeterna Laboratories, Quebec City Quebec, Canada) is a naturally occurring product currently in clinical investigation that blocks two main mechanisms of angiogenesis activation, namely, vascular endothelial growth factor and matrix metalloproteinase. We hypothesized that psoriasis could be modulated by inhibiting the neovascularization of psoriatic plaques. We conducted a randomized dose-comparison trial to evaluate the safety and potential therapeutic benefit of AE-941, administered orally to patients with psoriasis. Forty-nine patients with psoriasis were enrolled and assigned to receive AE-941 at 30, 60, 120, or 240 mL/d for 12 weeks. Patients were followed up for another 12-week period. Improvement in the Psoriasis Area and Severity Index (PASI) score was observed in 50%, 41.7%, and 30.8% of the patients receiving 240, 120, and 60 mL/d, respectively. No patients receiving a dosage 30 mL/d showed a PASI score improvement. A statistically significant improvement with increasing dose was observed for the PASI score, severity of itch, and the physician's global assessment. The most commonly reported nonserious drug-related adverse events affected the gastrointestinal system in 12 of 49 patients (primarily nausea, diarrhea, vomiting, flatulence, and constipation) and the skin and appendages in 4 of 49 patients (primarily acne and rash). This randomized phase I/II study provides evidence that the antiangiogenic agent AE-941 offers a new therapeutic approach to the management of psoriasis.
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PMID:Neovastat (AE-941), an inhibitor of angiogenesis: Randomized phase I/II clinical trial results in patients with plaque psoriasis. 1227 Dec 97

Fertility control by cyclic norethindrone (Norlutin), 17 alpha-ethinyl 19-nortestosterone, plus .06 mg 3-methoxy ethinyl estradiol (Ortho-Novum) was studied in 364 women over a period of 32 months for a total of 6062 cycles. No patient who followed the instructions became pregnant. 37 patients stopped the medication for various reasons. The interval between stopping medication and becoming pregnant averaged 1.6 months. 13 of these pregnancies occurred after 11-15 cycles of treatment. Children born to these mothers were normal with no virilization observed. Findings from all Papanicolaou smears and cervical biopsies were normal. The desirable effects of diminishing the menstrual flow, reducing dysmenorrhea and regulating the menstrual cycle, plus the all-important one of contraception, far outweighed minimal and infrequent undesirable side effects (in order of frequence: chloasma, hot flashes, headache, nausea, acne, abdominal pain, dizziness and urticaria). In only 4.8% of the total 6062 cycles was some complaint made.
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PMID:Long-term administration of norethindrone in fertility control. 1227 4

18 young women with an average age of 21.5 years and average duration of acne symptoms of 3.6 years were treated with Diane 35, a new antiandrogen contraceptive containing 35 mcg ethinyl estradiol in addition to 2 mg cyproteroneacetate (CPA) for 12 months. Gynecological exams were carried out prior to treatment, and 6 and 12 months later. Diane was taken for 21 days with 1 week of cessation. During monthly checkups acne lesions, seborrhea, weight, blood pressure, and side effect were examined. A recidivism follow-up of several months included 11 patients no longer taking the contraceptive. 14 patients became symptomless, and 4 of them improved indicating an effective treatment for all patients. The loss of symptoms started after 4 months (2-7) and they became completely symptomless after 7-10 months. 8 of the 11 patients in the follow-up study stayed symptomless at the end of treatment. Although relapse occurred in 7 cases, their condition was still better than before treatment. Side effects occurred in 11 patients mostly in the first months of treatment: nausea, vomiting (6), headache (4), vertigo (3), chest ache (2), bleeding (4). Treatment may exceed 12 months because after 7-10 months relapse occurred. If the treatment fails to improve the symptoms, administration of 10-20 mg CPA/day in the first 10 days of cycle is suggested.
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PMID:[Treatment of acne with an antiandrogen containing contraceptive (Diane 35)]. 1228 88

Some scientists added the progestin levonorgestrel to the vaginal ring which must be removed every 3 weeks to address the problem of irregular bleeding, but it adversely altered lipoprotein levels and caused too many hemorrhaging problems. On the other hand, scientists in the laboratory at Organon have conducted various studies of a vaginal ring with ethinyl estradiol and 3-keto-desogestrel at different doses which have yielded favorable results. A multicenter European study was conducted with 400 women aged 18-40 years wearing a vaginal ring with 0.120 mg keto-desogestrel and 0.015 mg ethinyl estradiol every day for 9 months. 10% had slight bleeding 15 days after insertion of the vaginal ring. In 10 women tested, the plasmal levels of progesterone and estrogen decreased by 4 nmol/l and 0.010 nmol/l, respectively. The first French study was conducted at the Gynecology College of Bordeaux and the South-West in 1988 and included 40 women followed for 9 cycles. The vaginal ring consisted of 2 compartments: the biggest compartment contained only 3-keto-desogestrel and the other also contained ethinyl estradiol. It remained in the vagina for 21 days, then was removed to be rinsed, dried, and placed in a box. It was reinserted on the 5th or 7th day of the cycle. This ring reduces the volume of blood during menses and eliminates abdominal cramps, nausea, and headaches. Women tolerate the vaginal ring better than they do oral contraceptives (OCs); for example, it does not cause them to gain weight, they tolerate glucose well, it brings about favorable changes in lipoproteins, it does not bring about conditions favorable to thrombophlebitis, and it can improve the skin for acne-sufferers. Young women accept vaginal rings enthusiastically. The efficacy of vaginal rings with 2 steroids is the same as that of OCs.
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PMID:[Vaginal contraception with steroids]. 1228

With a million adolescents becoming pregnant each year in the US, clinicians must promote delayed sexual activity and also ensure that adolescents have access to contraceptive information and counseling in the selection of a method when appropriate. Teenagers need the chance to discuss these issues in a confidential setting, and effective counseling will depend upon the clinician's understanding of adolescent psychosocial and cognitive development. In general, early adolescence is characterized by concrete thought and self-centeredness; middle adolescence by strong peer allegiances, risk-taking, and a feeling of invincibility, and late adolescence by a capacity for abstract thinking. Counselors must listen attentively and ask appropriate questions that require an interactive response. Adolescents should participate in the choice of a contraceptive method. If the teenagers choose to use oral contraceptives (OCs), it is important to counsel them in problem-solving techniques (missed pill directions, for example), the use of back-up methods, and cues for remembering to take the OCs as well as in benefits (decreased dysmenorrhea, lighter menstrual flow, more regular menses, improvement in acne and hirsutism, decreased risk of certain cancers), side effects (breakthrough bleeding, weight gain, acne, nausea, and breast tenderness), and how-to's. To help teenagers use OCs successfully, a 28-day pack is recommended as is having her agree to a cue for remembering to take the OC daily. If the patient seems likely to be unable to adhere to the regimen, she is asked to return in a month. If she missed a number of pills during the first month, another method is recommended.
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PMID:Contraceptive choices: the adolescent years. 1228 65

All medications have side effects in certain patients; none is 100% "safe" and the physicain must determine the benefit-to-risk ratio of each contraceptive method for a particular patient. 81% of white, nonCatholic women aged 20-24 who are college graduates use oral contraceptives, an extraordinary acceptance level for a method not even available in 1960. The various preparations available in the U.S, amount of estrogen and progestogen in each, and side effects are then surveyed. Estrogen irritates the gastric mucosa and diminishes rate of sodium excretion by the kidneys; this causes the nausea, edema, general bloating, tension, and headaches which most commonly cause women to discontinue the medication. The patient with full breasts who menstruates normally should not be overloaded with estrogen while a high-estrogen compound might benefit the woman with small breasts and scanty menses. Estrogens are known stimulants for the growth of uterine leiomyomas; if such lesions are present an antiestrogenic progestogen is indicated. High estrogen pills are more likely to stimulate breast growth and increase discomfort from fibrocyctic disease while a progestin-dominant combination will reduce this discomfort. The "19-nor" progestins are essentailly variants of testosterone and may produce hirsutism, alopecia, acne, hypomenorrhea, or even amenorrhea. T hey also may increase appetite and cause excessive weight gain. The total effect is complicated by such factors as the particular progestin used. The 19-norsteroid compounds are partly metabolized to estrogen and increase the estrogenic effect while norgestrel produces antiestrogenic activity. Newer marketing methods have tried to simplify administration by inserting 7 iron tablets or 7 placebos so the user takes a pill every day for 28 days. For patients who have noted side effects during the 7-day interval they are not taking the pill (undoubtedly related to temporary estrogen insufficiency) .02 mg ethinyl estradiol may be used. The sequential method more closely simulates the normal menstrual cycle and can be used to advantage in women who suffer prolonged anovulation after cessaton of combination therapy and in women past 35 in whom the increased risk of pregnancy is offset by declining fertility potential. Both serious and minor adverse reactions to various forms of therapy are detailed. These include cutaneous, nervous system, metabloic, and endocrine system changes.
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PMID:Present status of oral contraceptives: 1. effectiveness; basis for selection; side effects; metabolic changes. 1230 85


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