Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007222 (cardiovascular disease)
 65,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Menopausal symptoms and signs associated with the reduction of ovarian function include an increased incidence of cardiovascular disease and loss of bone mass as well as less serious but more uncomfortable symptoms such as vasomotor flushes and atrophy of the vaginal wall. Although unopposed estrogen effectively reverses these and other menopausal symptoms, it is well established that without the addition of progestin there is an unacceptably high risk of developing hyperplasia or cancer of the endometrium. Depending on the type and dose of progestin added, however, this addition may reverse estrogen's beneficial cardiovascular effects and produce unwanted side effects. Lower doses and newer progestins, such as norgestimate, gestodene, and desogestrel, have demonstrated a decreased potential to reverse the positive cardiovascular effects of estrogen while still eradicating persisting or de novo endometrial hyperplasia.
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PMID:Introduction to steroids in the menopause. 160 88

Epidemiologic studies of breast, ovarian, and endometrial cancer and physiologic studies of epithelial tissues from which these cancers originate indicate that medical researchers can develop interventions to reduce women's risk of these 3 cancers. They already know that use of combined oral contraceptives considerably reduced the risk of endometrial and ovarian cancer. The key etiologic factors for endometrial and breast cancer are ovarian steroid hormones. Specifically, any estrogen not checked by progestogen stimulate cell division in the epithelial tissue of the endometrium thus increasing the risk of cancer. Yet estrogen and progestogen induces significantly more cell division in the epithelial tissue of the terminal duct lobular unit (from which many breast cancers originate) than does just estrogen. Ovulation damages the ovarian surface making it the leading etiologic factor for ovarian cancer. Medical researchers at the University of Southern California (USC) have designed a prototype contraceptive regimen which should prevent all 3 cancers. They re presently testing it in a clinical trial at USC. The prototype regimen consists of administration of the gonadotropin releasing hormone agonist (GnRHA) leuprolide acetate depot on day 1 of each 28-day cycle, 0.625 mg of oral conjugated equine estrogens (CEE) on Monday-Saturday (24 days) per each 28-day cycle, and 10 mg of oral medroxyprogesterone acetate (MCA) for 13 days every 4th cycle. The GnRHA reduces the risk of all 3 cancers. CEE prevents bone mineral loss, possible increase in cardiovascular disease risk, menopausal symptoms, and urogenital atrophy. MCA reverses endometrial hyperplasia and prevents increased risk of endometrial cancer. The predicted relative reduction in lifetime breast cancer risks over 5,10, and 15 years for the prototype regimen are 31%, 53%, and 70%, respectively. For endometrial cancer, they are 18%, 33%, and 45%, respectively. For ovarian cancer, they are 41%, 67%, and 84%. This regimen should also reduce the incidence or severity of hormonally mediated benign gynecologic disorders. Further research on such a regimen is needed.
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PMID:The prevention of breast cancer through reduced ovarian steroid exposure. 162 31

Estrogen therapy in women has traditionally been used for the relief of menopausal symptoms and protection from osteoporosis. Recently, there has been a growing body of evidence suggesting that estrogen therapy protects against cardiovascular disease in women. An epidemiologic review of the literature demonstrates an approximately 50% reduction in cardiovascular risk in women using estrogen. A brief review of indications, complications, and routes of estrogen administration is presented. Current areas of controversy include the effects of parenteral estrogen administration and progestin administration on the cardioprotective aspects of estrogen therapy and the risk of breast cancer in estrogen users. Further study in these areas is needed.
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PMID:Estrogen therapy and cardiovascular risk in women. 186 Oct 96

The estradiol transdermal therapeutic system is a cutaneous delivery device which delivers estradiol into the systemic circulation via the stratum corneum at a constant rate for up to 4 days. Physiological levels of estradiol (the major estrogen secreted by the ovaries in premenopausal women) can therefore be maintained in postmenopausal women with low daily doses because first-pass hepatic metabolism is avoided. In short term clinical studies, the beneficial effects of transdermal estradiol on plasma gonadotrophins, maturation of the vaginal epithelium, metabolic parameters of bone resorption and menopausal symptoms (hot flushes, sleep disturbance, genitourinary discomfort and mood alteration) appear to be comparable to those of oral and subcutaneous estrogens, while the undesirable effects of oral estrogens on hepatic metabolism are avoided. As with oral or injectable estrogen replacement therapy, concomitant sequential progestagen is recommended for patients with an intact uterus during transdermal estradiol administration, in order to reduce endometrial stimulation. Transdermal estradiol has been well tolerated in clinical trials, with local irritation at the site of application being the most common adverse effect. The incidence of systemic estrogenic effects appears to be comparable to that observed with oral therapy. Thus, transdermal estradiol offers near-physiological estrogen replacement in postmenopausal women in a convenient low-dose form which may avoid some of the complications of higher dose oral therapy. Long term epidemiological studies are warranted to determine whether transdermal estradiol therapy provides protection against osteoporosis and fractures and cardiovascular disease equivalent to that offered by oral and injectable estrogens. However, despite the importance of such data, it seems reasonable to conclude at this stage of its development that transdermal estradiol represents an important advance in hormone replacement therapy.
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PMID:Transdermal estradiol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of menopausal complaints. 208 14

Menopause constitutes a sizable proportion of the adult women's life, and it is reasonable to consider that most women will benefit from hormone-replacement therapy. Also, it is important to realize that cardiovascular disease is a major cause of morbidity and death in the menopausal patient. Two regimens of hormone-replacement therapy were evaluated in postmenopausal women with 0.625 mg of conjugated equine estrogen with either 2.5 or 5 mg of medroxyprogesterone acetate taken continuously for 52 weeks in 92 patients. The data demonstrated an improvement in menopausal symptoms, a beneficial effect in lipoprotein profiles, the establishment of an atrophic endometrium, and a marked decrease in vaginal bleeding after 13 weeks and a further decrease after 26 weeks. Ideally this regimen will offer better patient compliance and, if the favorable lipoprotein profiles offer protection to the cardiovascular system, the overall health of the American woman will be markedly affected.
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PMID:Evaluation of a continuous combined low-dose regimen of estrogen-progestin for treatment of the menopausal patient. 236 May 87

Potential risks of prescribing generic drugs for oral contraception, ovulation induction and menopausal estrogen substitution are reviewed. In the U.S. all 50 states permit or require generic substitution, unless the prescription states otherwise. F.D.A. guidelines allow the bioavailability to range within 25%, i.e., the circulating level of drug in male test subjects after a single dose must be within + or - 25% of the range reported with the pioneer drug. Thus if a patient renews her prescription monthly she may receive a 50% range in dose level if different generics with both extremes in bioavailability are provided. Potential ranges for women, ill or elderly may vary even more. The potential risks for oral contraceptives are unwanted pregnancy, breakthrough bleeding, blood lipid elevation and less serious consequences such as minor side effects or confusion over package design. Risks for generic estrogen replacement include lack of protection from cardiovascular disease or osteoporosis and lack of therapeutic effect on menopausal symptoms; those from progestins are atherogenesis and failure to stop dysfunctional bleeding, ending in an unnecessary D & C. Possible sequelae of generics for ovulation induction are multiple pregnancy and ovarian hyperstimulation resulting in hospitalization for acute massive ovarian enlargement or rupture, as well as extra months of expense for treatment and monitoring. The most pressing concern is liability for the physician or pharmacist related to provision of generics. In most cases even 1 additional office visit for drug dose adjustment will obviate all savings accrued from taking generics.
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PMID:Generic drugs in reproductive medicine: is the value anticipated the value obtained? 288 23

Costs, risks, and benefits of estrogen-progestin therapy in the menopause were compared with those for estrogen alone, using techniques of cost-effectiveness analysis. With the progestin added, reduced costs of endometrial monitoring and treatment of endometrial lesions more than offset the increased cost of the drug regimen with a net saving of $230-$430 per patient, depending on the duration of treatment. An estimated gain in life expectancy with estrogen-progestin compared to estrogen alone may be partly offset by a perceived reduction in the quality of life owing to the prolongation of menstruation in women receiving progestin. Overall, based on currently available evidence, estrogen-progestin therapy appears to be cost-effective, except in women who consider the adverse effects of continued menstruation to offset the relief of menopausal symptoms. These conclusions must be viewed as tentative, pending further clarification of the roles of estrogens and progestins in cardiovascular disease and breast cancer.
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PMID:Cost-effectiveness of hormone replacement therapy in the menopause. 631 Apr 60

Hormone replacement therapy is used for both menopausal symptoms and in prevention, but for the latter to be effective there may be a need to promote its use. Suitable strategies need to be informed by current practice. A postal questionnaire was therefore sent to 1649 women aged 20-69 years in Stockton-on-Tees to assess which women consider and take hormone replacement therapy. The response rate was 74%. Therapy had been considered by 346 (28%) women of whom 164 (47%) were premenopausal. It was taken by 20% of women aged 45-65 years. Users were more likely to have taken the contraceptive pill. Use of therapy by women with osteoporosis or cardiovascular disease, or with a family history of these, was low. As women used to the idea of taking hormone replacement therapy and accustomed to taking the contraceptive pill reach menopausal age there is likely to be an increase in uptake of therapy. By targeting the 'at risk' groups of women, the primary care team may be able to make most effective use of the therapy and their own resources for the prevention of osteoporosis and cardiovascular disease.
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PMID:The use of hormone replacement therapy; results of a community survey. 758 39

The use of estrogens in postmenopausal women has been the subject of much controversy regarding hormone formulation, dosage, use in combination with progestins, duration of treatment, and contraindications. Estrogens have been prescribed to relieve menopausal symptoms for more than three decades. The hormones reduce the gynecologic and psychologic changes associated with menopause while inhibiting bone resorption and possibly reducing the risk of cardiovascular disease. Their use however has been complicated by an increased risk of endometrial cancer and possibly breast cancer. The use of estrogens as cardioprotective agents is discussed and the clinical experiences and the possible mechanisms of action are reviewed. The clinical pharmacology of estrogens and the various formulations that are available as monotherapy or in combination with progestins will also be reviewed.
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PMID:Clinical pharmacology of estrogens: cardiovascular actions and cardioprotective benefits of replacement therapy in postmenopausal women. 775 8

The use of estrogens in postmenopausal women has been the subject of much controversy regarding hormone formulation, dosage, use in combination with progestins, duration of treatment, and contraindications. Estrogens have been prescribed to relieve menopausal symptoms for more than three decades. The hormones reduce the gynecologic and psychologic changes associated with menopause while inhibiting bone resorption and possibly reducing the risk of cardiovascular disease. Their use however has been complicated by an increased risk of endometrial cancer and possibly breast cancer. The use of estrogens as cardioprotective agents is discussed and the clinical experiences and the possible mechanisms of action are reviewed. The clinical pharmacology of estrogens and the various formulations that are available as monotherapy or in combination with progestins will also be reviewed.
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PMID:Clinical pharmacology of estrogens: cardiovascular actions and cardioprotective benefits of replacement therapy in postmenopausal women. 760 24


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