Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Recent studies have shown the predictive power of abdominal distribution of adipose tissue for the development of cardiovascular disease, stroke, diabetes as well as strong associations to the previously known risk factors for these endpoints. The reason for the accumulation of abdominal fat might be due to an imbalance between cortisol and sex steroid hormones. Cortisol receptor density seems to be particularly high in abdominal adipose tissue, leading to expression of lipoprotein lipase activity primarily here. Progesterone and testosterone seems to counteract this, the former perhaps through competition with the cortisol receptor. Accumulation of intraabdominal fat, particularly in the tissues drained by the portal circulation, probably leads to high free fatty acid concentrations in the portal vein, because of the high lipolytic sensitivity of these tissues. This in turn seems to inhibit hepatic clearance of portal insulin, leading to peripheral hyperinsulinemia, insulin resistance, perhaps hypertension as well as hyperlipidemia via drive by free fatty acids of lipoprotein synthesis in the liver. These are risk factors for diabetes, cardiovascular disease and stroke. It is of interest that subjects with abdominal adipose tissue have several factors leading to increased cortisol and low sex steroid hormone secretion, including stress, high alcohol consumption and smoking. This might provide some of the background to this syndrome.
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PMID:Obesity and adipose tissue distribution as risk factors for the development of disease. A review. 214 Jan 8

Progesterone (PROG) is a neurosteroid, possessing a variety of functions in the central nervous system. Exogenous PROG has been shown to reduce secondary neuronal loss in conjunction with attenuated brain edema after cerebral contusion and to reduce brain edema after focal cerebral ischemia. In the present study, we assessed the neuroprotective potential of PROG in a model of focal cerebral ischemia in the rat. Forty-eight male Wistar rats were randomly assigned to 4 groups, i.e. pretreatment with water soluble PROG, or dimethyl sulfoxide (DMSO) dissolved PROG, or DMSO as control or delayed treatment with DMSO dissolved PROG. Middle cerebral artery occlusion (MCAO) was induced by insertion of an intraluminal suture and reperfusion was performed by withdrawing the suture. Pretreatments were initiated 30 min before MCAO via intraperitoneal injection. Delayed treatment was initiated upon reperfusion following 2 h of MCAO. Infarct volume, body weight loss, and neurological deficit were measured 48 h after MCAO. Pre- and delayed treatment with DMSO dissolved PROG resulted in a 39% (P < 0.05) and 34% (P < 0.05) reduction in cerebral infarction, respectively, along with decreased body weight loss and improved neurological function as compared to control animals, whereas no statistically significant reduction in infarct volume by water soluble PROG was found. We demonstrated that administration of PROG to the male rat before or 2 hours after onset of MCAO reduces ischemic cell damage and improves physiological and neurological function 2 days after stroke. These results suggests potential therapeutic properties of PROG in the management of stroke.
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PMID:Progesterone is neuroprotective after transient middle cerebral artery occlusion in male rats. 890 74

Treatment of focal cerebral ischemia in the rat with intraperitoneal administration of progesterone dissolved in dimethyl sulfoxide (DMSO) has demonstrated therapeutic efficacy. In the present study we test whether iv administration of water soluble progesterone 2 h after the onset of middle cerebral artery occlusion provides therapeutic benefit for the treatment of stroke. In addition, we perform a battery of functional tests: rotarod, adhesive-backed somatosensory, and neurological score, as well as a dose-response study. The data indicate that iv administration of progesterone at a dose of 8 mg/kg significantly reduces the volume of cerebral infarction and significantly improves outcome on the array of functional measures employed. Treatment with 4 mg/kg or 32 mg/kg of progesterone failed to provide any therapeutic benefit. Progesterone, a non toxic, clinically employed, pluripotent therapeutic agent which targets both neuroprotective as well as neuroregenerative strategies, may have important therapeutic benefits for the treatment of stroke.
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PMID:Neuroprotective effects of progesterone after transient middle cerebral artery occlusion in rat. 1056 46

Increasing evidence has demonstrated striking sex differences in the pathophysiology of and outcome after acute neurological injury. Lesser susceptibility to postischemic and posttraumatic brain injury in females has been observed in experimental models. Additional evidence suggests this sex difference extends to humans as well. The greater neuroprotection afforded to females is likely due to the effects of circulating estrogens and progestins. In fact, exogenous administration of both hormones has been shown to improve outcome after cerebral ischemia and traumatic brain injury in experimental models. The neuroprotection provided by periinjury administration of these hormones extends to males as well. The mechanisms by which estrogen and progesterone provide such neuroprotection are likely multifactorial, and probably depend on the type and severity of injury as well as the type and concentration of hormone present. Both genomic and nongenomic mechanisms may be involved. Estrogen's putative effects include preservation of autoregulatory function, an antioxidant effect, reduction of A beta production and neurotoxicity, reduced excitotoxicity, increased expression of the antiapoptotic factor bcl-2, and activation of mitogen activated protein kinase pathways. It is hypothesized that several of these neuroprotective mechanisms can be linked back to estrogen's ability to act as a potent chemical (i.e., electron-donating) antioxidant. Progesterone, on the other hand, has a membrane stabilizing effect that also serves to reduce the damage caused by lipid peroxidation. In addition, it may also provide neuroprotection by suppressing neuronal hyperexcitability. The following review will discuss experimental and clinical evidence for sex differences in outcome after acute brain trauma and stroke, review the evidence implicating estrogens and progestins as mediators of this neuroprotection following acute neurological injury, and finally, address the specific mechanisms by which these hormones may protect the brain following acute neurological injury.
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PMID:Gender differences in acute CNS trauma and stroke: neuroprotective effects of estrogen and progesterone. 1083 57

In every year since 1984, cardiovascular disease has claimed the lives of more females than males. More than 450,000 women succumb to heart disease annually, and 250,000 die of coronary artery disease. Despite the proportions, most women believe they will die of breast cancer. The perception that heart disease is a man's disease and that women are more likely to die of breast cancer is alarming. Although women develop heart disease about 10 years later than men, they are likely to fare worse after a heart attack. The poorer outcomes are due, in part, to the failure to identify heart attack symptoms. Approximately 35% of heart attacks in women are believed to go unnoticed or unreported. However, because of increased age, women are more likely to have co-morbid diseases such as diabetes and hypertension. In women, not only is "tightness" or discomfort in the chest a warning sign, but in addition, nausea and dizziness are common indicators of myocardial ischemia. Other symptoms include breathlessness, perspiration, a sensation of fluttering in the heart, and fullness in the chest. In comparison to men, women are less likely to undergo tertiary care interventions such as cardiac catheterization, angioplasty, thrombolytic therapy, and bypass surgery; to participate in cardiac rehabilitation; and to return to work full-time after myocardial infarction. In the past, most research about treatments for heart disease focused on men, and gender differences have been ignored. Recent studies are enrolling enough women to test if there are differences between men and women in outcomes. One of the major areas of research relates to estrogen and hormonal replacement therapy to reduce the relative risk of heart attack and stroke. The Women's Health Initiative is a major NIH-sponsored trial that addresses the issue of primary prevention of cardiac disease by hormonal replacement therapy. The results will be available in 2004. The Heart Estrogen/Progestin Replacement Study (HERS), disappointingly, did not show a significant reduction of coronary events in women taking hormonal replacement therapy, nor did the Estrogen Replacement and Atherosclerosis (ERA) trial of 309 postmenopausal women who underwent coronary angiography. New insight into the role of vitamins, phytoestrogens and other natural sources, and selective estrogen receptor modulators may provide other options for management. Until then, modification of risk factors and healthy life style choices are recommended for reducing the risk of cardiac disease. In fact, the key to a healthy heart in the year 2000 appears closely tied to life style choices. Prevention of disease is the key, and current recommendations are simply to stop smoking, or do not start; treat and control blood pressure >140/90 mm Hg; manage elevated lipids by diet, exercise, and cholesterol-lowering medications (if necessary); treat diabetes; lose weight so that BMI is <25; walk for 20-30 minutes at least three times a week; and take an aspirin tablet daily.
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PMID:Heart disease in women. 1114 May 44

Clinically, it is known that: (1) magnesium (Mg) supplementation relieves premenstrual problems (e.g., migraine, bloating and edema) occurring in the late luteal phase of the menstrual cycle; and (2) migraine syndromes, particularly in women, are associated with deficits in brain and serum ionized Mg levels. We investigated whether concentrations of sex steroid hormones, found in the serum during the menstrual cycle of women, are associated with changes in the levels of cytosolic free magnesium ions ([Mg2+]i in single cultured canine cerebral vascular smooth muscle cells. The resting level of [Mg2+]i in these cells was 645 +/- 89 microM before exposure to sex steroid hormones. Exposure of these vascular cells to a low concentration of estrogen (10 pg/ml) failed to interfere with the levels of [Mg2+]i. However, exposure to estrogen, at concentrations ranging from 40 to 200 pg/ml, induced significant loss of [Mg2+]i in a concentration-dependent manner. At a concentration of 200 pg/ml estrogen, the level of [Mg2+]i decreased approximately 30% in comparison with controls. Progesterone produced biphasic effects on the levels of [Mg2+]i, depending on its concentration. Exposure of the cultured cells to a low concentration of progesterone (0.5 ng/ml) resulted in an increased level of [Mg2+]i (from 690 +/- 50 microM to 753 +/- 56 microM, p < 0.05). However, when these cells were exposed to higher concentrations of progesterone (i.e., from 5.0 to 20 ng/ml), the cellular levels of [Mg2+]i were decreased significantly. The higher the estrogen or progesterone concentration, the lower the levels of [Mg2+]i. In contrast, testosterone, a male hormone, didn't produce any significant alteration in [Mg2+]i levels in these cerebral vascular smooth muscle cells. These data indicate that low, physiological concentrations of female sex hormones, estrogen and progesterone, help cerebral vascular smooth cells sustain normal concentrations of [Mg2+]i, which are beneficial to vascular function, whereas high levels of estrogen and progesterone deplete, significantly, [Mg2+]i in cerebral vascular smooth muscle cells, possibly resulting in cerebrovasospasms and reduced cerebral blood flows related to premenstrual syndromes, migraine and stroke risk. Our findings could provide new insight into the mechanism whereby migraine occurs frequently in the late luteal phase in the premenstrual syndrome. In addition, our results demonstrate that female sex steroids but not testosterone (in physiologic concentrations) can exert direct effects on [Mg2+]i in cerebral vascular cells.
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PMID:Sex steroid hormones exert biphasic effects on cytosolic magnesium ions in cerebral vascular smooth muscle cells: possible relationships to migraine frequency in premenstrual syndromes and stroke incidence. 1122 17

Progestin only birth control pills appeared on the US market in 1973. As there is no estrogen in these mini pills, they may have fewer dangerous side effects than the combined pills. Some clinics suggest mini pills for women who suffer from estrogen excess side effects. The 3 mini pills available in the U.S. are called Micronor, NOR-QD, and Ovrette. Instructions are presented for patients who are interested in using mini pills. The mini pills most likely work by affecting a women's fertility in several ways: act as a messenger to the woman's ovaries and uterus to prevent the release of an egg; thicken the mucous on the cervix, making it difficult for the sperm to "get through" the cervix and reach the egg; and change the lining of the uterus so that it may not develop properly for the fertilized egg to grow. The mini pills can be 97% effective is used perfectly. The mini pills are only effective for as long as a woman takes them. A woman must take a pill every day to prevent pregnancy. A woman should not use the mini pill if she has or ever has had any of these problems: blood clotting problems in veins; stroke; cancer of the breast or reproductive parts of the body; suspected pregnancy, current pregnancy; and undiagnosed, abnormal genital bleeding. Possible benefits for a woman using mini pills include: an effective method of birth control; a method for nursing mothers since it does not seem to affect the amount of their breast milk; and a possible reduction in premenstrual cramps. Possible risks for a woman using mini pills include: irregular periods; and a less effective method if the patient does not take a pill every day. The danger signals to look for are abdominal pain, chest pain, headaches, eye problems, and severe leg pain. A patient should revisit a clinic in the following situations: has not had a period within 45 days of the last period; severe abdominal pains while taking mini pills; experiences a warning signal; any time one thinks the pills are causing trouble; and once a year for a pap smear, breast examination, and laboratory tests.
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PMID:How to use mini-pills: helpful patient instructions. 1226 79

The obstetrician-gynecologist clinic should provide easy access for the disabled patient such as a hydraulic pelvic examination table. In most cases, disability does not affect sexuality, menstruation, or fertility but may change the level of interest and activity. Thus the physician should include sexual counseling even for abled patients with disabled partners. He/she should document the informed consent process to make sure it is legal and ethical. He/she must do a thorough evaluation of each disabled patient and her needs and develop a special protocol for each patient. The physician must know those disabled conditions that limit pelvic examination ability an contraindicate some contraceptives. Oral contraceptives (OCs) and progestin implants are contraindicated in women with spinal cord injury (SCI), disabled by a stroke, and with neurologic disorders that inhibit mobility in the lower extremities and cause circulatory disorders. Depending on individual circumstances, physicians should not advise OC use for women who are mentally retarded, mentally ill, or are drug abusers since they either do not understand, cannot remember, or are not motivated to take OCs regularly. Progestin implants may be a viable option for drug abusers, the mentally ill, and mentally retarded women. Once the US Food and Drug Administration approves injectable progestational agents, they could be another option for these women. The IUD is contraindicated in women who have no sensory capabilities and could not notice an ectopic pregnancy and pelvic infection. This may include women with some neurologic disorders, stroke, SCI, and multiple sclerosis. It is also contraindicated in women who have a blood disease, use anticoagulants, or have AIDS. Barrier methods could be used if a disabled patient or a partner is able to put them in place. In some cases, sterilization may be justified on medical grounds.
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PMID:Contraception for the disabled. 1228 20

The bulk of the experimental data suggest beneficial effects of estrogen (both premenopausal use of OCs and postmenopausal use of ERT-HRT). An intriguing finding from the monkey studies is that social subordination, which induces estrogen deficiency in female monkeys, accelerates atherosclerosis premenopausally and predicts extent of postmenopausal atherosclerosis. This effect can be inhibited by exogenous estrogen, premenopausally. The results suggest that more effort on detecting and regulating premenopausal ovarian dysfunction may be justified. A complication in understanding estrogen action may be the result of varying extents of arterial damage. For example, primary prevention studies in both postmenopausal animals and women have provided strong evidence of atheroprotection with a variety of estrogens. In contrast, the results of secondary prevention studies [10,12] have in general suggested little cardioprotection with either ERT or HRT. Studies in rabbits suggest the antiatherogenic effect of estrogen may not be present when the endothelium is damaged [64]. The state of the endothelium may be critical for some estrogen actions. For those effects of estrogen that require the ER, be it ERalpha or ERbeta, the presence of the receptor may vary with age, disease state, or type of hormone therapy. If continuous combined HRT therapy decreases ER in the artery as it does in the uterus, this may eliminate those estrogen actions requiring the ER, but not others. Older women who have not been exposed to estrogens for many years may be more sensitive to some estrogen effects, and may need lower doses of ERT-HRT. Recent reports suggest that lower doses of estrogens maintain beneficial effects on lipoproteins and coagulation factors [95], while also requiring lower doses of progestogens to protect the uterus [96]. These beneficial findings are very promising in light of the improvements in CHD risk and decreased stroke risk reported with low-dose estrogens [5]. It ill be interesting to see if CRP is increased with lower doses of estrogens and whether these changes are associated with increased early risk of CHD. Perhaps older women with CHD are also more obese, may have diabetes, and may be more susceptible to inflammatory and thrombotic effects of higher doses of estrogens. There are many questions left unanswered. It is hoped that some of the answers may come from the WHI, which is a large prospective trial assessing ERT and HRT. The age range is also relatively large and may be able to determine if older women respond differently than younger women. Some initial data from the WHI have been made available suggesting a small increased risk in the first 2 years and a trend for decreasing risk in the last months of the first 2 years [34]. Just recently, the CEE + MPA arm of the study was stopped early by the data and-safety monitoring board as the overall health risks exceeded benefits with increases in both breast cancer and CVD [97]. The remainder of the study groups including an estrogen-only arm, are expected to continue until 2005.
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PMID:Reproductive hormones and cardiovascular disease mechanism of action and clinical implications. 1235 69


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