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The beneficial effects of combined estrogen-progestin-containing oral contraceptives (OCs) include prevention of pregnancy (less than 1 failure out of 100 regular users); the prevention of ectopic pregnancy; the reduction of preeclampsia (2.4 times lower risk compared with barrier methods); and reduction of pelvic inflammation to about one-half. The effects on menstruation include the reduction of sideropenic anemia (by lowering the incidence and duration of menstruation, OCs reduce the loss of iron to 50% or to as much as 33%); dysmenorrhea by 40% (symptoms receded in 90% of users); and premenstrual syndrome by 30%. OCs exert a favorable effect on menstrual epilepsy; reduce sports-related accidents in the premenstrual and menstrual periods; and reduce intermenstrual bleeding. The protection from cancer includes the lowering of endometrial cancer risk (every 2 years of use reduces the risk by 38%, 12 years of use by 70%, and the beneficial effects last 3-15 years); reduction of the risk of the ovarian cancer (already 3-6 months of use reduces the risk by 30%, and more than 5 years by 50% in women under 50 years of age with a longterm effect of 10 years or more, which drops sharply in women over 60 who are mostly at risk). Among other beneficial effects, they reduce benign mastopathy by 50-75%; reduce the risk of follicular ovarian cysts to 50% and the risk of corpus luteal ovarian cysts to 1/5; and they lessen bone loss which favorably affects osteoporosis. Low-dose OCs minimize the well-known risks of thrombotic and cerebrovascular accidents, myocardial infarction, hypertension, altered carbohydrate metabolism, gallbladder diseases, and liver cancer. A new OC with 30 mcg of ethinyl estradiol was tested with daily doses of 150 mcg of desogestrel. The high density lipoprotein (HDL) either increased or did not change with desogestrel: the HDL2 subfraction that protects from atherosclerosis did not change, and probably the HDL3 raised the HDL level.
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PMID:[Favorable effects of oral estrogen-progestin contraception]. 181 41

Female hormonal contraceptives, introduced commercially in 1959, contained 10 mg of norethynodrel and .15 mg of mestranol. The estrogen and progesterone doses were progressively reduced over time. In 1989, approximately 60 million couples used oral contraceptives (OCs) ranging from 1% in Japan to 40% in the Netherlands. The monophasic pill contains .01 - .04 mg of ethinyl estradiol (EE), and the biphasic pill contains increasing doses of progesterone and estroprogesterone in the course of the menstrual cycle. Triphasic combined pills contain an initially dominant estrogen dose. In oral sequential pills, estrogen is given on days 14-16 followed by a estroprogesterone for 5-7 days. Micropills with progesterone, injectables with medroxyprogesterone, and 3rd-generation OCs such as gestoden with a low progesterone dose of .04 mg/day and reduced androgenic activity are among other OCs. The OCs are administered in 21-22 day packets. Absolute contraindications include history of venous thrombosis, atherogenic lipid profile, hormone-dependent cancer, and allergy. Relative contraindications include arterial ailments, smoking, hypertension, older age, obesity, and familial history of cardiovascular and cerebrovascular accidents. Interactions with antibiotics (ampicillin and tetracycline) occur as the modified intestinal flora reduces the level of deconjugated EE. Most frequent side effects are depression, modification of libido, ocular disorders, headache, and urinary infection. Benefits include favorable modification of menstrual cycle, and reduction of endometriosis and endometrial and ovarian cancer. Systemic risks such as cardiovascular and blood coagulation effects occur mainly with high-dose OCs. Further topics addressed are the cancer risk and protective effect of OCs, postcoital OCs, traditional contraception, the IUD, RU-486, implants, vaccination with the human antigonadotropine, and the vaginal ring.
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PMID:[Family planning with different contraceptive methods]. 182 14

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

The metabolic effects of sex steroids pertinent to cardiovascular risk are described. These effects are discussed for estrogen inducible proteins, coagulation and fibrinolysis, blood pressure and hypertension, carbohydrate metabolism, lipids and lipoproteins, and vessel walls and local prostaglandins. Also described is the cardioprotection from estrogens and estrogen/progesterone treatment and cardiovascular risk. Oral contraceptive (OC) and cardiovascular risk are also discussed with the following effects identified: the influence on many of the multiple risk factors involved in the development of cardiovascular diseases (i.e., lipids, carbohydrate metabolism, and hemostasis), an association between OC use and thromboembolic accidents, a state of hypercoagulability counterbalanced by increased fibrinolytic activity, venous thrombosis, a relationship with the dosage of androgenic progestogens. no atherogenic origin, no age limit for prescribed, healthy, nonsmoking women, and an increased peripheral insulin resistance. It is concluded that it is rarely inadvisable to prescribe low dose natural estrogens in postmenopausal hormone replacement therapy. Factors contraindicating such use are undiagnosed genital bleeding, an active thrombolic or cardiovascular process, carcinoma of the breast or endometrium, and acute liver failure. Estrogen replacement therapy may exert some cardioprotective effect. When progestogens are added to prevent endometrial carcinoma development, the benefits might be reduced. Low estrogen and low progesterone OC use among healthy, nonsmoking women even in middle age poses no risk of death from cardiovascular disease. Premenopausal women may even be protected from coronary atherosclerosis with estrogen-containing OCs. However, it is advisable that OCs be used with the least possible impact on lipid and carbohydrate metabolism, as well as on hemostasis. For those with some prior cardiovascular risk, there are theoretical advantages at present for use of the new, less, or nonandrogenic progestins in OCs; however, caution is urged and informed consent must be obtained until epidemiological studies support this position.
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PMID:Sex hormones and cardiovascular risk. 192 64

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

Predisposing factors to cervical cancer development are age, smoking, socioeconomical status, parity, and number of sex partners. Long-term oral contraceptive (OC) use and less than 50 mg estrogen dose have been weakly linked to increased cancer risk. Regular examination and switching to other contraception in case of cervical intraepithelial neoplasia is recommended. Estrogen in sequential pills (Ovacon) increases the risks of uterine cancer by affecting the mucosa. Predisposing factors are: absence of pregnancy (nulliparity), postmenopause, hypertension, and diabetes. Parity reduces the risk. The risk is reduced in combined pills and after use of 1 year. Protection is offered by the progesterone component for 10-20 years after cessation of use. Ovarian cancer is prevented by parity and OC use even 10 years later. High estrogen levels inducing frequent ovulation damage the ovaries. Promoting factors are: old age, avoidance of breast feeding, and overweight. Breast cancer promoters are 1st pregnancy in older age, early menarche, and no pregnancy at all. OC use under age 25 and before 1st pregnancy are significant risk factors. High progesterone levels are associated with increased mitotic activity in the breast. Rare benign fibrocysts can develop into breast cancer. OC use is connected to hepatoma development mainly estrogen-induced. Liver cancer was found twice as high in OC users. Hepatoma often ruptures causing hemorrhage. 8% of liver tumors are malignant with a survival rate of 50% of patients to 4.8 years. The possible association of OCs to skin melanoma and hypophysial tumors could not be confirmed. OCs regulate menstruation, reduce bleeding, protect against uterine and ovarian cancer, but cervical and breast cancers have been influenced by them.
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PMID:[The contraceptive pill and cancer]. 207 68

Oral contraceptives (OCs, long-acting progestins (LAPs), and IUDS are reviewed in terms of new information on safety and efficacy. OC formulations are described and their mechanism of action and efficacy indicated. Reports are provided for thromboembolism, hemorrhagic and thrombotic stroke, ischemic heart diseases, alterations in lipid and hypoprotein and carbohydrate metabolism, hypertension, coagulation changes, breast and cervical cancers, and such minor side effects as menstrual irregularities, nausea, headaches, weight gain, premenstrual syndrome effects, and mood and libido changes. Noncontraceptive health benefits and clinical considerations are discussed. Norplant, as the only long acting progestin available in the US is described in terms of its formulations, mechanism of action, sequelae and metabolic effects, menstrual irregularities, metabolic effects, nuisance side effects, candidates for insertion, method of insertion and removal, and continuation rates. 2 IUD types are identified as the only ones available in the US, Progestasert T and T-Cu-380A (Paragard). Mechanism of action, efficacy, candidates, major sequelae such as salpingitis, infertility, and uterine perforation, minor sequelae such as metrorrhagia and dysmenorrhea, and other considerations are indicated. OCs in the US contain an average of 35 mg of ethinyl estradiol and assorted progestins e.g.s, ethynodiol diacetate, norethindrone acetate, nortestosterone derivatives with a complex mechanism of action. The failure rate for use effectiveness is 6 pregnancies/100 woman years. Modern formulations have combined rates of no more than 50 to 100 adverse events/100,000 users. Some of the effects are indicated as follows: Thromboembolism accounts for 60% of adverse effects and appears to be declining along with hemorrhagic and thrombotic stroke, however, modern use studies are only partially available. Myocardial infarction related to OC use may be embolic, and has a low risk at 7/100,000 users. Low-dose contraceptives substantially reduce the associated risks. Those with risk factors need close monitoring. Norplant is useful for those not wanting to take a daily regimen and is commonly accompanied by menstrual irregularity and sometimes headaches. Continuation is 80% after the 1st year and 40% after 5 years. Candidates for IUDs are parous women in monogamous relationships, who are not at risk for salpingitis, which is related to IUD use, or sexually transmitted diseases. Continuation is 70% after 1 year compared with 50% of OC users.
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PMID:Modern trends in contraception. 212 11

The clinical use of estrogens and progestogens for menopausal women is reviewed, discussing the indications, results of studies on effectiveness of various agents o each target organ, contraindications, risk-benefit ratio, and types of drug preparations available and used in European countries. The indications for menopausal hormone replacement are primarily to prevent myocardial infarction and osteoporosis, and also to treat early menopause, urogenital atrophy, and severe skin, mucous membrane and psychic disorders. Mechanisms of action of estrogens and progestins, and anticipated results are detailed for each of the indications. Contraindications typical of oral contraceptives usually do not apply for hormone replacement. For example, only severe acute liver disease, current thromboembolism, endometrial cancer other than I, and breast cancer within 3-5 years of primary treatment are contraindications. Neither cervical, ovarian or vulvar cancer, diabetes, varicose veins, hypertension, nor history of liver disease or thromboembolism are contraindications: in some cases progestins or transdermal estrogens are recommended. Estrogen side effects suggest overdosage. Progesterone or its derivatives rather than oral contraceptive progestins are prescribed. There is a clear benefit, comparing cost of medication to that of treating consequences of estrogen deficiency. The preparations currently used in Europe include oral micronized estradiol, conjugated estrogens, transdermal patches, local vaginal estrogens, and injectable estradiol esters for those who cannot tolerate oral or transdermal agents. Preparations should contain progesterone unless the woman has had a hysterectomy. Combinations designed to avoid withdrawal bleeding are available.
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PMID:Clinical use of oestrogens and progestogens. 221 69

Spironolactone (Aldactone) appears to have potential as a treatment for androgen-excess syndromes, including hirsutism. In both men and women, spironolactone decreases the rate of testosterone production and increases its metabolic clearance. The 1st indication that this agent has an effect on hirsutism was serendipitous--an incidental finding in a patient who was being treated for hypertension. Subsequent studies have largely confirmed that women who are administered spironolactone exhibit no further progression in hair darkening and coarsening, a slowed growth rate of existing hair, and decreased hair shaft diameter. When combined with dexamethasone or an oral contraceptive, spironolactone seems to increase the intervals between hair growth treatments. It has been suggested, but not documented, that spironolactone could correct hyperandrogenic ovulation. This use should be avoided, however, due to potential anti-androgenic effects on the fetus. Minor side effects of treatment with spironolactone include time-limited lethargy, stomach upset, and menstrual irregularity. There is concern, however, that this agent may stimulate the breast and contribute to the development of breast cancer. Thus, it should not be used by patients with a family history of breast malignancies. In addition, the drug should not be used in pregnancy and users of reproductive age should be supplied with an effective contraceptive method. The present dosage recommendation is 100-200 mg of spironolactone/day in 2 divided doses combined with either 35 mcg ethinyl estradiol and 0.5 mg of norethindrone or with 50 mg of ethinyl estradiol and 1 mg of ethynodiol diacetate.
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PMID:Use of spironolactone in treatment of hirsutism. 235 84

The effect of oral contraceptives (OCs) on changes in arterial pressure (AP) was studied in 160 healthy women, 22-35 years of age, with ovulatory menstrual cycles. They took Ovidan and Non-ovlon for 12 months to prevent unwanted pregnancy. These steroidal preparations contain equal doses (.05 mg) of ethinyl estradiol and different doses of gestagenic components: .25 mg of levonorgestrel in Ovidan and 1 mg of norethisterone acetate in Non-ovlon. Measurements of AP parameters were taken with a mercury sphygmomanometer, and complications caused by OCs were recorded. Results were processed by the usual methods of variational statistics. With Ovidan, a significant increase (p .05) in systolic and diastolic AP was recorded after 3 and 6 months. Systolic and diastolic APs exceeded the initial levels by 7 and 6 mm Hg, respectively. Non-ovlon caused a less pronounced effect; a significant increase (p .05) of systolic and diastolic AP was recorded during the 12th month of contraception only. Thus, the results indicate that OCs can cause an increase in AP, and the gestagenic component increases the risk of hypertension. Levonorgestrel causes a more marked effect than norethisterone. Periodic AP measurements (every 3 months) are recommended for women using OCs. In cases of a steady increase in AP, use of this contraceptive method should be terminated.
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PMID:[Indicators of arterial blood pressure during hormonal contraception]. 241 29


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