Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histological specimens from 150 women with liver tumors are discussed. Of the 150 patients under consideration, 85% had ingested contraceptive steroids, most for more than 3 years. Of these 64% had taken pills containing mestranol, and 18% had used ethinyl estradiol; 18% had taken both. Average age was about 30 years, and pain was the most common presenting symptom. 19 tumors were malignant (hepatoma), 57 were adenoma, 68 were focal nodular hyperplasia, and 6 were unclassified. To date, 12 of the 19 hepatoma patients have died. In addition to presenting numerous figures depicting the pathology material and a discussion of tumor differentiation difficulties, speculation between steroid ingestation and tumor appearance is considered. Since hepatomas are much more common than benign liver tumors, circumspection is in order before indicting steroids as causative. In this group of women studied, none had cirrhosis, for example, whereas cirrhosis is very common in the general population. The authors call for further investigation of estrogens and primary liver tumores.
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PMID:Relation of steroids to liver oncogenesis. 22 96

Restovar, a low dose combined oral contraceptive containing .75 mg lynestrenol and 37.5 mcg ethinyl estradiol was given to 83 women for up to 25 cycles or 1265 total. A cycle contained 22 pills begun on the first day of menstruation or withdrawal bleeding from previous pill cycles. Each woman was questioned regularly on side effects and bleeding, had weight and blood pressure taken, and received gynecologic exams before and after pill treatment. There were no pregnancies. Latency from end of the cycle to bleeding was 2-3 days in 87%; cycles lasted 28 days in 80%; bleeding lasted 3-4 days in 84%; flow was moderate in 72%; and spotting occurred in 4.2% of cylces and breakthrough bleeding in 2.4%; withdrawal bleeding was absent in 4.2% of cycles. The most common side effects were breast pain in 1.9% of cycles and headaches in 1.2%. These complaints as well as nausea, vomiting, leucorrhea, nervousness and depression were reported as less frequent or absent more often than present or aggravated. 6 women quit for drug related reasons. There was no significant weight change or hypertension (means 126/82 and 120/80 before and during Restovar. Thus this low dose pill is remarkably effective and well tolerated.
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PMID:[Clinical study of restovar, an oral contraceptive with a low estrogen content]. 114 76

A 15-year old Black teenager came to a clinic at the University of Alabama's School of Medicine in Tuscaloosa requesting oral contraceptives (OCs). The physical examination indicated that she was in good health and the physician prescribed an OC (1 mg norethindrone and .035 mg ethinyl estradiol). 21 months later she returned complaining of yellow eyes for 3 weeks. The oral mucosa was also jaundiced. She had considerably high levels of bilirubin and alkaline phosphatase. She had no hepatitis virus antibodies. 5 months later she returned for the physical examination required to renew the OC prescription. She did not have jaundice at this time. 10 months later she complained of malaise and muscular pain. Her alkaline phosphatase level was high, but her bilirubin level was normal. She had mild hepatosplenomegaly without focal defects. After reviewing her medical records, the physician diagnosed intrahepatic cholestasis and discontinued her OC prescription. Liver function tests were normal within 3 months. 14 months later, she returned complaining of malaise and reported taking OCs obtained at another clinic 3 months earlier. The physician advised her about the complications of OCs and about other contraceptive methods. The same physician also examined a 32-year-old Black woman who had intermittent epigastric and right-upper quadrant abdominal pain for 2 weeks. Eating worsened the pain, which lasted for up to 15 minutes. She had used an OC for 12 years. Ultrasound revealed a 4.2 cm hypoechoic mass in the left upper lobe of the liver. The physician discontinued the OCs. The tumor regressed over 12 months. Active liver disease is a contraindication to OC use. Women who had cholestatic jaundice while pregnant or have first degree relatives with cholestatic jaundice of pregnancy should not use OCs. Physicians may introduce OCs to closely monitored women with a history of liver disease whose liver function tests are normal. Women with a family history of biliary excretion defects should not use OCs.
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PMID:Hepatobiliary complications of oral contraceptives. 133 97

The effectiveness of monophasic and multiphasic oral contraceptives (OCs) depends on their ability to suppress ovulation, change endometrial growth and ovum receptivity, and reduce cervical mucus receptivity to sperm. They are all more than 99% effective, but, depending on the type and dose of hormone components, they have different side effects. The estrogen component (ethinyl estradiol) of most new OCs is between 30 and 35 mcg, which reduces the risk of estrogen side effects, especially thromboembolism and hypertension. The Food and Drug Administration does not recommend use of an OC with an estrogen component for lactating mothers, while the American College of Obstetrics and Gynecology and the American Academy of Pediatrics believe it is fine. Estrogen may protect against coronary artery disease, yet the estrogen component of today's OCs is so low that the progestin component may cancels this beneficial effect. It also prevents breakthrough bleeding. The most frequently used progestins in OCs are norethindrone and norgestrel. They prevent ovum implantation, sperm penetration through the cervical mucus, and ovulation. Progestins, especially norgestrel, increase the risk of coronary artery disease. Other side effects include acne and weight gain. Progestin benefits are reduced menstrual blood loss, pain during menstruation, premenstrual tension, and endometrial cancer risk. The ideal estrogen-progestin balance depends on the individual, but the estrogen component should be between 30 and 35 mcg, and the progestin component should be the lowest possible dose to reduce metabolic side effects. If an OC user with a well stabilized cycle who takes another recently prescribed drug experiences unexpected breakthrough bleeding or spotting, this change may indicate a drug interaction. Absolute and/or possible contraindications of OC use are smoking after age 35, history of breast or endometrial cancer, liver disease or impaired liver function, cardiovascular risk factors, and diabetes mellitus.
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PMID:Benefits and risks of oral contraceptive use. 143 13

A placebo-controlled, double-blind study of triphasic oral contraceptives for prospectively confirmed premenstrual syndrome (PMS) was conducted with 82 subjects, 59 of whom completed the study and who were later confirmed to have moderate to severe premenstrual symptoms. 212 subjects were recruited between April 1987 - June 1988, and completed a menstrual history form and a 95-item retrospective questionnaire on premenstrual symptoms. Subjects took Synphasic (Syntex, Mississauga, Canada) containing 35 mcg ethinyl estradiol and 0.5 mg, 1.0 mg, and 0.5 mg norethindrone. Subjects were monitored for 1 menstrual cycle for baseline, then took triphasic or placebo for 3 cycles. 23 oral contraceptive taking and 36 placebo subjects completed the trial: completers had higher status occupations and lower symptom severity scores than dropouts. Both pill and placebo groups showed significant clinical improvement on every symptom except headache. Symptom scores decreased significantly between baseline and 3rd treatment cycle, and between menstrual phase scores and the variables "mood swings," "more sleep," "unhappy," and "tense" in the 2nd treatment cycle compared with the 1st treatment cycle in both groups. In the pill group ratings of premenstrual breast pain were significantly lower in the 3rd treatment cycle compared with baseline (p0.05), and to the 1st treatment cycle (p0.01). No significant changes in breast pain were found in the placebo group. Some pill cycles showed significant reduction in edema. Those in the pill group who were initially rated as "depressed" showed greater improvement in work impairment, sleep requirements, and energy level premenstrually. The pill group, however, reported significantly lower sexual interest during treatment. This is the 1st reported double-blind, placebo-controlled, prospectively confirmed study of oral contraceptives for PMS.
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PMID:A prospective treatment study of premenstrual symptoms using a triphasic oral contraceptive. 156 78

During testing new sequential preparations such as Trinordiol the weak suppression of gonadotropin and the partly increased endogenous estradiol (E2) and also partly increased progesterone were noted in the course of 30,000 checkups by contraceptive users when clinical symptoms were confirmed by ultrasound and biochemical analysis. In micropill users these were acute abdominal and breast pain, often follicular ripening in the ovaries, and cysts in the ovaries and in the breast with increased E2 values up to ovulatory values in some. The strong pain in the lower abdomen required intervention. It has been known that ethinyl estradiol (EE) and gestagens inhibit ovulation. In a study of 7 patients taking 40 mcg of gestoden there were 6 cases of ovulation inhibition (4 times along with follicular ripening) and 1 case of corpus luteum insufficiency. There were 2 instances of follicular ripening in 32 patients using Femovan containing 30 mcg of EE with 75 mcg of gestoden. With a 20 mcg preparation these signs occurred repeatedly when young girls complained of strong breast pain and breast enlargement. Shifting to a preparation containing 30 mcg of EE with the same dose of gestagen eliminated the complaints. This contradicts the hypothesis that all receptors are occupied by Ee and that endogenous E2 production cannot exercise its effect. Therefore, development of micropills with a somewhat higher gestagen dose has been suggested. There are patients whose cycle regulation is aided only by sequential preparations with 50 mcg of EE. It is concluded that ovulation inhibition is dependent on the dose and structure of gestagens, with the resorption and current metabolism of steroids in agreement with individually differing suppression of the ovaries.
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PMID:[Response to the letter by Prof. Kuhl: "Does a rise in endogenous estradiol during treatment with low-dose ovulation inhibitor signify increased risk"?]. 179 81

A 22-year old unmarried healthy woman was admitted to the Swedish department with low fever, tiredness, SR 75 mm, positive uricult, but no urinary tract symptoms. Urinary tract infection was suspected and treatment was started with norfloxacin. Nevertheless, the urine culture proved to be negative. A few weeks later she had increasing trouble with stiff knee and shoulder joints and the left foot became swollen. The subfebrile status continued, and tonsillitis was suspected and diagnosed. V-penicillin and cefaklor treatment was applied. She was transferred to the infectious diseases ware, where fever was confirmed with leukocytosis (19 x 1 billion/1), C-reactive protein at 66 (normal value 10) mcg/ml, pronounced blood pressure increase (160/130 mm Hg), anemic signs, and pathological liver status with increased transaminases (ASAT 6.3-10.4 and ALAT 8.,8-16 ukat/1). ALP increased slightly to 6 ukat/1. The symptoms of weight loss indisposition, and muscles and joints aches, especially in foot ache continued. Collagen disease was suspected, and she was transferred to the internal medicine department. She regularly had tachycardia and high blood pressure. She had to use crutches for mobility because of the pain. S-albumin was 32 (normal 36- 50) g/l and S-hepatoglobin was 2.7 (normal value .4-1.8) g.l. Various others tests were normal. Ulnaris neuropathy was suspected on the left hand. Intensive blood pressure reducing combination treatment was started with 200 mg x 1 of metoprolol, 10 mg x 2 nifedipin, and 20 mg x 1 enalapril. The Desolett oral contraceptive (containing 30 mcg of ethinyl estradiol and 150 mcg of desogestrel) she had been taking for a few months were discontinued. Quick improvement of clinical and laboratory parameters followed. SR and leukocytosis became normal. The values of ALP, ASAT, and ALAT became normal some days later. She was discharged shortly thereafter, and blood pressure medication was gradually discontinued. In the 1940s there were reports about the hepatotoxic effects of synthetic estrogens followed by carbohydrate, lipid, and protein metabolism alterations. Jaundice has also been reported, and the Swedes have an ethnic susceptibility to it. The global incidence rate is 1/10.000 vs. 1/100 and 1/4000 in Sweden induced by high-dose OCs containing more than 50 mcg ethinyl estradiol, but with low-dose OCs this rate is much lower. Both estrogens and gestagens can increase blood pressure. A 1969 study reported that 22 young women developed arthritis, arthralgia, and myalgia after taking pills for 3- 12 months. Rheumatic symptoms were also recorded with pill use. Thus, it is very likely that OCs were responsible for the patient's symptoms, especially since her status rapidly improved after discontinuing them.
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PMID:[Were the severe adverse effects on several organs and the marked blood pressure increase caused by oral contraceptives?]. 182 62

A 19 year old female and a 21 year old female visited their physicians in Jerusalem, Israel because of pain in the esophagus and in the chest. Both were otherwise healthy and not taking any medication except for oral contraceptives (OCs) containing levonorgestrel and ethinyl estradiol. They would swallow the OCs without any fluids before lying down. Both physicians used an endoscope to view the esophagus. 1 physician saw 3 round esophageal ulcers 1-1.5 cm in diameter whereas the other physician saw 1 round esophageal ulcer 2.5 cm in diameter. The ulcers of 1 woman were 30 cm from the incisors and the other woman's ulcer was 25 cm from the incisors. Neither patient stopped taking the OCs. 1 physician advised his patient to take the OCs with plenty of fluids while in a vertical position. The symptoms stopped within 4 days. The other physician treated his patient with sucralfate suspension and ranitidine. Her symptoms subsided within 5 days. The ulcer of 1 patient and the ulcers of the other patient were completely healed by the time of the 2nd endoscopy 2 weeks later. The esophageal ulcers were probably caused by the uncoated and acidic OCs lodging in the esophagus. Even though the size of the OC is 0.5 cm and thought to be easy to swallow, peristalsis cannot effectively move such a small bolus. Moreover, many OCs are taken at night when salivation levels are reduced and swallowing occurs less often than during the day. In conclusion, physicians should stress to OC users the importance of swallowing them with plenty of fluids and not while lying down to prevent OC induced esophageal ulcers.
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PMID:Oral contraceptive-induced esophageal ulcer. Two cases and literature review. 191 75

The best methods of contraception for women with insulin-dependent diabetes mellitus and gestational diabetes are discussed, with results of clinical trials in both types of patients. Women with IDDM require effective contraception since there are serious risks both to the mother and the fetus in case of unplanned pregnancy. For women reliable enough to use them consistently, barrier methods are satisfactory. IUDs are the choice for most diabetic women. In a trial of copper-T 200 IUDs in 103 diabetics compared to 119 normal controls, the effectiveness, expulsion rate, removals for bleeding and pain, and continuation rates were comparable. It was noted that there were no added infections in the diabetic group, who have an increased risk for infection generally. Oral contraceptives may worsen glucose tolerance, due to the effect of the progestogen decreasing diabetes, except in women with history of gestational diabetes. The authors found that a triphasic pill, with lower progestin dose, decreased insulin sensitivity more than did a combined pill, in both normal women and in those with previous gestational diabetes. Since natural estrogens, as used in estrogen replacement therapy in climacteric women, do not affect glucose tolerance as much as synthetic alkylated estrogens (i.e., ethinyl estradiol), the authors tried a combination of 4 mg estradiol, 2 mg estriol and 3 mg norethisterone for contraception in diabetic women. This experimental combination was compared with a low dose ethinyl estradiol-norethisterone monophasic, a progestin only pill, and an ethinyl estradiol-levonorgestrel triphasic. There were no differences among the groups in fasting plasma glucose, 24-hour insulin requirements, HbA1C levels, LDL, or free fatty acids. VLDL and HDL cholesterol and total cholesterol decreased in the natural estrogen group. There was a small, significant increase in LDL, VLDL and total cholesterol in the combined group. The authors also have preliminary results of a trial of a low-dose monophasic with ethinyl estradiol and gestodene, showing no adverse effects on glycemic control in IDDM patients. Thus low dose progestin, triphasic and natural estrogen-progestagen combination oral contraceptives can be recommended as safe to diabetics.
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PMID:Contraception for women with diabetes: an update. 195 24

From August 1988-June 1989, 983 physicians participated in a phase IV trial by following 7759 women using the monophasic oral contraceptive (OC), Demulen 1/35 (1 mg ethynodiol diacetate and 35 ug ethinyl estradiol) to evaluate its efficacy and safety. The total number of cycles for the study stood at 21,440. In addition, the total woman-years stood at 1787. Only 6382 patients could be evaluated for safety. 4.4% of the patients had adverse reactions to the OC, but only 1.7% of all patients stopped taking it. The leading side effects included nausea (67 cases), headache (45), amenorrhea (42), emotional changes (30), breast pain (19), dysmenorrhea (12), and 11 cases of weight gain, abdominal/pelvic pain, and bloating. Of the 280 reported adverse reactions, only 87 (31%) were considered severe. The leading serious adverse reactions were depression (10) and hypertension (6). Only 5412 patients could be used to determine efficacy. The physicians initially reported 121 (2.2%) pregnancies during the study. The researchers learned that 33 of the 84 returned 2nd questionnaires (response rate, 70%) reported that the women conceived after enrollment but before taking the OC. 36 conceived while taking it, but 8 did not take it daily. Noncompliance may have contributed to pregnancy for the remaining 28 cases. Therefore the 36 confirmed pregnancies made for a failure rate of .7%. 85.7% of the pregnancies happened in the 1st 3 months of taking the OC. Either patient noncompliance or true medication failure accounted for treatment failure. Therefore it is important for physicians to instruct patients on how to take OCs correctly.
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PMID:Efficacy and safety of ethynodiol diacetate, 1 mg, with ethinyl estradiol, 35 micrograms, with an emphasis on contraceptive efficacy. A phase IV trial. 204 81


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