PubMed Health⌕ Search

Biomedical subjects

R A Wild

Publications and source records attributed to R A Wild.

At least 19 recordsLinked to original sources
PubMed2001

Estrogens, progestins, selective estrogen receptor modulators, and the arterial tree.

We reviewed studies of the effects of different estrogens, progestins, and selective estrogen receptor modulators at the coronary and carotid arterial sites to help determine their likely effects on cardiovascular morbidity and mortality. All English-language studies published between 1997 and 2000 on MEDLINE, Current Contents, and Best Evidence were reviewed, including in vitro, other animal, human physiologic, and clinical trial studies. We synthesize, assess limitations, and integrate across systems with the in vivo experience in humans to evaluate the clinical context. Estrogens have favorable direct effects in most circumstances, progestins oppose these effects, and early studies suggest that selective estrogen receptor modulators are protective. In some systems the dosage, route of delivery, and type of progestin may be important and risk factors may modulate hormone effects. The evaluation of endothelial dysfunction gives a unique in vivo opportunity to assess the vascular properties of hormones, although the relationship between the in vivo physiologic effects of hormones and clinical outcomes remains to be determined.

Animals↗
PubMed2000

The effects of hormone replacement therapy and raloxifene on C-reactive protein and homocysteine in healthy postmenopausal women: a randomized, controlled trial.

C-Reactive protein and homocysteine are independent risk factors for the development of cardiovascular disease. This study compared the effects of hormone replacement therapy (HRT) and raloxifene on serum C-reactive protein and homocysteine levels as markers of cardiovascular risk in healthy postmenopausal women. Healthy postmenopausal women (n = 390) were enrolled in a double blind, randomized, placebo-controlled, 6-month trial at eight out-patient sites in the United States. Women were randomly assigned to receive continuous combined HRT (0.625 mg/day conjugated equine estrogen and 2.5 mg/day medroxyprogesterone acetate), raloxifene (60 or 120 mg/day), or placebo for 6 months. C-Reactive protein and homocysteine were measured in baseline and 6-month serum samples. HRT increased C-reactive protein levels by 84% (P<0.001), whereas raloxifene (60 and 120 mg/day) had no significant effect (-6% and -4%;, respectively; P>0.2). Raloxifene (60 and 120 mg/day) significantly lowered serum levels ofhomocysteine by 8% (P = 0.014) and 6% (P = 0.024), respectively, similar to the 7% (P = 0.014) reduction obtained with HRT. We conclude that HRT and raloxifene lower serum homocysteine levels to a comparable extent in postmenopausal women. Whereas cardiovascular risk predicted by C-reactive protein in healthy postmenopausal women is not influenced by raloxifene, the relationship between elevated C-reactive protein levels with HRT and cardiovascular disease events requires further study.

Aged↗
PubMed1998

Effects of raloxifene on serum lipids and coagulation factors in healthy postmenopausal women.

CONTEXT: Raloxifene is a selective estrogen receptor modulator that has estrogen-agonistic effects on bone and estrogen-antagonistic effects on breast and uterus. OBJECTIVE: To identify the effects of raloxifene on markers of cardiovascular risk in postmenopausal women, and to compare them with those induced by hormone replacement therapy (HRT). DESIGN: Double-blind, randomized, parallel trial. SETTING: Eight sites in the United States. PARTICIPANTS: 390 healthy postmenopausal women recruited by advertisement. INTERVENTION: Participants were randomized to receive 1 of 4 treatments: raloxifene, 60 mg/d; raloxifene, 120 mg/d; HRT (conjugated equine estrogen, 0.625 mg/d, and medroxyprogesterone acetate, 2.5 mg/d); or placebo. MAIN OUTCOME MEASURES: Change and percent change from baseline of lipid levels and coagulation parameters after 3 months and 6 months of treatment. RESULTS: At the last visit completed, compared with placebo, both dosages of raloxifene significantly lowered low-density lipoprotein cholesterol (LDL-C) by 12% (P < .001), similar to the 14% reduction with HRT (P < .001). Both dosages of raloxifene significantly lowered lipoprotein(a) by 7% to 8% (P < .001), less than the 19% decrease with HRT (P<.001). Raloxifene increased high-density lipoprotein-2 cholesterol (HDL2-C) by 15% to 17% (P < .05), less than the 33% increase with HRT (P < .001). Raloxifene did not significantly change high-density lipoprotein cholesterol (HDL-C), triglycerides, or plasminogen activator inhibitor-1 (PAI-1); whereas HRT increased HDL-C by 11% and triglycerides by 20%, and decreased PAI-1 by 29% (for all, P < .001). Raloxifene significantly lowered fibrinogen by 12% to 14% (P < .001), unlike HRT, which had no effect. Neither treatment changed fibrinopeptide A or prothrombin fragment 1 and 2. CONCLUSIONS: Raloxifene favorably alters biochemical markers of cardiovascular risk by decreasing LDL-C, fibrinogen, and lipoprotein(a), and by increasing HDL2-C without raising triglycerides. In contrast to HRT, raloxifene had no effect on HDL-C and PAI-1, and a lesser effect on HDL2-C and lipoprotein(a). Further clinical trials are necessary to determine whether these favorable biochemical effects are associated with protection against cardiovascular disease.

Aged↗
PubMed1998

Effects of different hormone replacement regimens on postmenopausal women with abnormal lipid levels. Menopause Study Group.

OBJECTIVES: A retrospective, subset analysis of the prospective Menopause Study Group data was performed to determine the effects of four conjugated estrogens (CE) + medroxyprogesterone acetate (MPA) regimens and one unopposed CE regimen on the lipid profiles of women with abnormal lipid levels (n = 525). Previously unpublished data on the entire study population were also reviewed to determine the effects of these hormone replacement regimens on blood pressure and weight (n = 1368, 1374, respectively). METHODS: During a 1-year, prospective trial, all patients took CE. Groups A and B also took continuous MPA 2.5 and 5 mg, respectively, C and D took MPA 5 and 10 mg for the last 14 cycle days of each 28-day cycle, and E took matching placebo tablets to replace MPA. RESULTS: After 1 year, all five regimens were directly associated with significant elevations in high density lipoprotein-2 (HDL2) cholesterol and significant reductions in low density lipoprotein (LDL) cholesterol (p < 0.05), although unopposed estrogen produced the greatest increase in HDL2 cholesterol. The CE + MPA regimens were also associated with significant decreases in total cholesterol. Triglyceride levels did not change significantly from baseline in any treatment group (baseline values > 1.808 mmol/l (> 160 mg/dl)), although the CE + MPA regimens were associated with a mean triglyceride decrease and CE-only women (n = 8) had a mean triglyceride increase. No regimen produced significant weight or blood pressure changes. CONCLUSIONS: This analysis suggests that hormone replacement therapy (CE + MPA), used in appropriate dosages, may alter the HDL2 cholesterol and LDL cholesterol lipoproteins in postmenopausal women with borderline lipid levels (a higher-risk population) in a cardioprotective manner.

Blood Pressure↗
PubMed1997

Metabolic aspects of polycystic ovary syndrome.

The metabolic aberrations in patients with polycystic ovary syndrome (PCOS) demand a shift in clinical care from symptom driven to the prevention of chronic disease. The onset of carbohydrate intolerance or diabetes may be accelerated. The lipoprotein lipid profiles are compatible with the effects of insulin resistance. Disturbed cholesterol and triglyceride metabolism may eventuate in premature cardiovascular disease.

Androgens↗
PubMed1996

Estrogen: effects on the cardiovascular tree.

My objective is to review the current literature with respect to basic science aspects concerning the effects of both endogenous and exogenous sex steroids on the vascular system. For simplification in this complex, burgeoning field, generalizations are made and mechanisms are highlighted. Major landmark studies in the English language over the past 25 years are reviewed. Cardiovascular, endocrinologic, and gynecologic references are targeted. Investigations by leading authorities are emphasized with an intent to bridge clinical significance with in vitro studies, in vivo data (both animal and human), and current epidemiologic information. Study results indicate that atherosclerotic lesions can stabilize, and occlusion can regress. The combined effects of estrogen in preventing atherosclerosis and maintaining arterial tone and integrity indicate that the circulatory system is a major target for estrogen action. A number of direct and indirect effects of estrogen have been shown to be beneficial.

Arteriosclerosis↗
PubMed1996

Antibodies to carbonic anhydrase in endometriosis: prevalence, specificity, and relationship to clinical and laboratory parameters.

OBJECTIVE: To investigate the presence and clinical association of serum autoantibodies to carbonic anhydrase (CA) in women with and without endometriosis. DESIGN: Sera were tested in an ELISA against human and bovine CAI and/or CAII isoenzymes and by Western immunoblotting of trypsin-digested fragments of human CAII as antigens. The ELISA positivity was defined as mean + 2 SD of 100 control sera. Positive sera also were tested for the presence of antiendometrial antibodies and antinuclear antibodies (ANA) by indirect immunofluorescence assays (IFA) on endometrial (ECC) and HEp-2 cells, antibodies to single-stranded (ss) and double-stranded (ds) DNA by the Farr-type RIA and Crithidia IFA, and extractable nuclear antigens (Sm, nRNP, Ro, and La) by an ELISA. PATIENTS: Sera from 319 patients with laparoscopic diagnosed pelvic endometriosis (100 stage I, 95 stage II, 67 stage III, and 57 stage IV), 100 with other gynecologic disorders, and 100 control women were used. RESULTS: In the ELISA, 113 of 319 (35.4%) endometriosis sera had elevated immunoglobulin G antibodies against nondenatured CA isoenzymes. The reactivity of sera from the endometriosis group was significantly higher (35%) in all four subgroups of patients than each of the nonendometriosis sera (< 12% and < 6%, respectively). No stage-dependent variation of an autoantibody pattern was evident. However, anti-CA autoantibodies were present in 66.3% of women with endometriosis-associated infertility. The frequency of anti-CA autoantibodies was significantly higher (by 51.7%) in women with antiendometrial antibodies detectable by IFA. In addition, in sera positive for anti-CA antibodies, the frequency of ANA also was increased (20/113 [17.6%]) with titers of 1:40 to 1:1,080. The ANA-positive sera were negative for anti-ssDNA, anti-dsDNA, anti-Sm, anti-nRNP, and anti-La. However, three sera were positive for anti-Ro antibodies. Immunoblotting study of autoantibody reactivity with trypsin-digested subfragments of human CAII revealed consistent immunoreactivity with 14 to 6.2-kd range CAII peptides. CONCLUSIONS: [1] A subgroup of patients with endometriosis have autoantibodies directed to native and linear epitopes of the CA protein. [2] Prevalence of anti-CA antibodies was associated with antiendometrial antibodies and ANA. [3] Anti-CA antibodies were associated with a higher predictive value of the disease when all patient subgroups were considered together.

Animals↗
PubMed1995

Obesity, lipids, cardiovascular risk, and androgen excess.

Several lines of evidence suggest that a subset of women may be at increased risk of cardiovascular disease because of unfavorable alterations in insulin action and/or production, accompanying altered apolipoprotein metabolism and altered androgenicity and/or estrogenicity. A number of cardiovascular disease risk factors, including central obesity, insulin resistance (with associated hyperinsulinemia), dyslipidemia, and/or diabetes mellitus, tend to cluster in these women. Another common ovarian morphology in women with hyperandrogenism is polycystic ovaries, which cluster with hirsutism, anovulation, infertility, gonadotropin secretion abnormalities, android fat distribution, and many important cardiovascular disease risk factors. Studies indicate that androgen excess may be a signal of increased risk for coronary artery disease, even in younger women. If androgenicity and insulin resistance are early warning signs of increasing risk of morbidity and mortality, these patients are prime candidates for preventive medicine. It is important that primary care providers begin to recognize these androgen disorders as a clue to the existence of a complex, lifelong pattern potentially placing women at risk for premature morbidity and mortality and initiate preventive treatment before irreversible thresholds are crossed.

Androgens↗
PubMed1995

The gynecologist and the prevention of cardiovascular disease.

This article reviews current concepts regarding the prevention of cardiovascular disease for women, with particular attention to modifiable risk factors. The background describes the magnitude of the problem, assesses the quality of the data with respect to risk factor reduction, and emphasizes several important concepts. Changes at menopause, states of endocrine aberration, and benefits and risks of hormone substitution need to be understood in conjunction with all other potentially modifiable and nonmodifiable cardiovascular risk factors. Primary care physicians have a window of opportunity to prevent this number one women's health problem. Integrating behavior modification is the key to prevention as part of the regular gynecologic visit.

Cardiovascular Diseases↗
PubMed1994

Contraception for patients with psychiatric or medical disorders.

The increased risk that pregnancy carries for women with medical disorders must be weighed against the risks of reversible contraception. In the absence of prospective randomized trials of various contraceptive methods and their effect on a given disease process, the clinician must use information regarding the risk of pregnancy in a woman with medical problems, the well-documented failure rates of various methods, and the probability that the patient will use the method (or any other method) effectively. The possible effects of contraceptive methods on cardiovascular, endocrinologic, neurologic, and other medical disorders are discussed as are appropriate contraceptive options and considerations for these women.

Cardiovascular Diseases↗
PubMed1994

Matriarchal model for cardiovascular prevention.

Family patterns of cardiovascular risk behavior are well documented. Significant correlation exists between spouse-spouse, parent-child, and sibling-sibling for cholesterol, high- and low-density lipoprotein, diet, physical activity, and smoking. Family/environmental influences are important in how/if risk and/or preventive behavior is learned. The family matriarch commonly functions as gatekeeper, controlling eating behavior, access to health care, and other patterns. She often acts as menu planner, shopper, and preparer of meals for all family members. She provides information and verbal reinforcement about food and is a powerful model concerning dietary practices. In fact, the mother, as head of household in most single-parent families, may be the only adult model for many children. Because relevance and credibility are the most important characteristics of a behavioral model, parents (especially mothers) are strong models for observational learning by children. Risk factor information and risk reduction activities adopted by the matriarch can be generalized to the entire family if she learns the skills to act as a change agent. Initiation of this process of education and training the matriarch lies with primary care providers for women (Ob-Gyns see most women). By teaching risk reduction to the matriarch as a component of primary care, physician interaction can have a rippling effect.

Adult↗
PubMed1994

Metabolic impact of adding medroxyprogesterone acetate to conjugated estrogen therapy in postmenopausal women. The Menopause Study Group.

OBJECTIVE: To evaluate the impact of different dosages of medroxyprogesterone acetate (MPA) on metabolism and hemostasis in postmenopausal women treated with conjugated estrogens. METHODS: In this prospective, double-blind study, 525 women were randomized to five treatment groups at 26 sites in the United States and Europe. All participants received 0.625 mg conjugated estrogens daily for up to 13 cycles; four groups also received MPA, either 2.5 or 5.0 mg/day continuously or 5.0 or 10.0 mg/day for the last 14 days of each cycle. Effects on lipid and carbohydrate metabolism and coagulation were evaluated. RESULTS: Beneficial changes in plasma lipid levels occurred in all groups, but were greatest with conjugated estrogens alone (P < or = .05). Fasting glucose and insulin levels were significantly lower and the insulin response to glucose challenge was significantly blunted in all groups (P < or = .05). No major changes of clinical significance occurred in hemostatic levels. CONCLUSIONS: Metabolic levels were not affected adversely by the addition of MPA to conjugated estrogens, but some beneficial changes were greater with conjugated estrogens alone. Hemostatic levels were not affected.

Aged↗
PubMed1994

Role of endogenous estrogen in the hirsutism paradigm.

The study of women with androgen excess as a biologic experiment in nature may improve our understanding of hormonal determinants of cardiovascular risk. These women, who have androgen and estrogen excess, also have altered apolipoprotein metabolism, which correlates with insulin resistance. They often have android obesity, which appears to aggravate their metabolic alterations. Insulin resistance seems to have more of an influence on altered apolipoprotein metabolism than does endogenous ovarian androgen or estrogen, at least in hirsute women who are obese. It is hypothesized that adrenal dehydroepiandrosterone sulfate may modify the effects of insulin resistance, as reflected in androgen and apolipoprotein lipid metabolism. These hormonal interactive influences, which require further investigation, may hold clues to why men and women differ in the time of onset of the multifactorial problem of coronary vascular disease.

Adrenal Glands↗
PubMed1993

Contraceptive choices for women with endocrine complications.

Previous confusion regarding the interference by oral contraceptives in measurements of endocrine function have been largely eliminated by the advent of improved, more sensitive assays. There are few if any contraindications to oral contraceptive use in patients with thyroid disease. Patients with prolactinoma can be treated with bromocriptine to restore fertility and prevent mineral loss. However, as a less expensive alternative, oral contraceptives can be prescribed to correct mineral loss, because there is no convincing evidence of an adverse effect on prolactinomas by the steroidal content of the pill. Oral contraceptives comprise a near ideal treatment modality for women with polycystic ovary disease because, among other effects, oral contraceptives reduce synthesis of androgen by inhibiting pituitary gonadotropin secretion.

Contraception↗
PubMed1993

Effect of tumor necrosis factor-alpha on adhesion of human endometrial stromal cells to peritoneal mesothelial cells: an in vitro system.

OBJECTIVE: To assess the effects of tumor necrosis factor-alpha (TNF-alpha) on adhesion of endometrial stromal cells to peritoneal mesothelial cells, a possible step leading to endometriosis. DESIGN: Analysis of cell adhesion in vitro. SETTING: University research laboratory. PATIENTS: Peritoneal fluid and biopsies were obtained from volunteers with regular cycles without endometriosis or endometrial pathology. INTERVENTIONS: Tumor necrosis factor-alpha (0.1 to 1,000 U/mL) was added to nutrient media with the following supplements: 10% fetal calf serum, epidermal growth factor 20 ng/mL, and gentamicin 10 ng/mL. MAIN OUTCOME MEASURES: Radioactivity of chromium-51 was used as a reflection of adherent stromal cells. RESULTS: The adherence of endometrial stromal cells to mesothelial cells was significantly increased by pretreatment of mesothelial cells with TNF-alpha. CONCLUSIONS: Tumor necrosis factor-alpha may play a facilitory role in the development of endometriosis.

Cell Adhesion↗