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Biomedical subjects

P M Sarrel

Publications and source records attributed to P M Sarrel.

At least 19 recordsLinked to original sources
PubMed2001

A clinical trial of estrogen-replacement therapy after ischemic stroke.

BACKGROUND: Observational studies have suggested that estrogen-replacement therapy may reduce a woman's risk of stroke and death. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of estrogen therapy (1 mg of estradiol-17beta per day) in 664 postmenopausal women (mean age, 71 years) who had recently had an ischemic stroke or transient ischemic attack. Women were recruited from 21 hospitals in the United States and were followed for the occurrence of stroke or death. RESULTS: During a mean follow-up period of 2.8 years, there were 99 strokes or deaths among the women in the estradiol group, and 93 among those in the placebo group (relative risk in the estradiol group, 1.1; 95 percent confidence interval, 0.8 to 1.4). Estrogen therapy did not reduce the risk of death alone (relative risk, 1.2; 95 percent confidence interval, 0.8 to 1.8) or the risk of nonfatal stroke (relative risk, 1.0; 95 percent confidence interval, 0.7 to 1.4). The women who were randomly assigned to receive estrogen therapy had a higher risk of fatal stroke (relative risk, 2.9; 95 percent confidence interval, 0.9 to 9.0), and their nonfatal strokes were associated with slightly worse neurologic and functional deficits. CONCLUSIONS: Estradiol does not reduce mortality orthe recurrence of stroke in postmenopausal women with cerebrovascular disease. This therapy should not be prescribed for the secondary prevention of cerebrovascular disease.

Aged↗
PubMed2001

Effects of oat and wheat cereals on endothelial responses.

BACKGROUND: This study was undertaken to determine the effects of month-long whole grain oat and wheat cereal supplementation on endothelial function following a fatty meal as measured by brachial artery reactivity studies. METHODS: Fifty healthy adult subjects underwent brachial artery reactivity studies before and after a high-fat meal along with alpha-tocopherol (vitamin E), oats, or a comparable bowl of wheat cereal and were again tested after the high-fat meal following month-long supplementation with oat or wheat cereal in a random crossover with interim washout. RESULTS: In the acute phase, the fatty meal attenuated the hyperemic brachial artery flow response when administered concurrently with wheat cereal (-13.4%; P = 0.02), whereas hyperemic flow was maintained by concurrent administration of either oatmeal or alpha-tocopherol. Following month-long supplementation, postprandial peak flow (wheat +3.88 +/- 5.62%; oat -10.78 +/- 7.15%), and peak diameter (wheat -1.40 +/- 0.96%; oat -0.86 +/- 0.88%) did not differ from preprandial values. Oat and wheat treatments did not differ when directly compared. CONCLUSIONS: Month-long, daily supplementation with either whole-grain oat or wheat cereal may prevent postprandial impairment of vascular reactivity in response to a high-fat meal.

Adult↗
PubMed2001

Acute effects of oats and vitamin E on endothelial responses to ingested fat.

OBJECTIVE: To assess the effects of oats and vitamin E on endothelial function following a high-fat meal in healthy adults as measured by brachial artery reactivity studies (BARS). METHODS: A total of 25 men and 25 women (N=50) were recruited from a community population to participate in this randomized, crossover study. All subjects were free of known vascular disease, and female subjects were postmenopausal. Subjects underwent BARS before and after a high-fat meal (50 gm fat) on three occasions 1 week apart, one each with vitamin E 800 IU, oatmeal containing 3 gm beta-glucan, or a comparable bowl of wheat cereal serving as a placebo, in random sequence. The ultrasonographer was blinded to treatment status. RESULTS: Endothelial function, as measured by brachial artery peak flow during one minute of post-occlusive hyperemia, declined significantly from baseline when the high-fat meal was consumed with the wheat cereal (-13.4%; p=0.02). There was no difference in brachial artery flow change before and after a high-fat meal with oats (+0.37%; p=0.77) or a high-fat meal with vitamin E (+1.87%; p=0.42). No significant differences in flow-mediated vasodilation before and after the high-fat meal were detected among the three supplements. CONCLUSIONS: Endothelial dysfunction induced by acute fat ingestion in healthy adults is apparently prevented by concomitant ingestion of oats or vitamin E, but not wheat. Nutrient distribution and meal composition may have important implications for cardiovascular health.

Adult↗
PubMed2000

Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women.

OBJECTIVES: We sought to compare the effects of estrogen/transvaginal progesterone gel with estrogen/medroxyprogesterone acetate (MPA) on exercise-induced myocardial ischemia in postmenopausal women with coronary artery disease or previous myocardial infarction, or both. BACKGROUND: Estrogen therapy beneficially affects exercise-induced myocardial ischemia in postmenopausal women; however, women with an intact uterus also take progestin to protect against uterine malignancies. The effects of combination estrogen/progestin therapy on myocardial ischemia are unknown. METHODS: Eighteen postmenopausal women (mean +/- SD age 59+/-7 years) were given 17-beta-estradiol in single-blinded manner for four weeks (1 mg/day for three weeks then 2 mg/day for one week). Estradiol (2 mg/day) was then continued, and the patients were randomized (double-blind) for 12 days to either transvaginal progesterone gel (90 mg on alternate days) and oral MPA placebo (10 mg/day), or vice versa. After another two weeks on estradiol alone, the patients crossed over to progestin treatment and repeated the protocol on the opposite treatment. Patients underwent treadmill exercise testing after each estradiol phase and at day 10 of each progestin phase. RESULTS: Exercise time to myocardial ischemia increased after the first estrogen phase as compared with baseline (mean difference with 95% confidence interval [CI]: 72 s [34 to 110], p = 0.001), and was increased by combination estradiol/progesterone therapy as compared with estradiol/MPA therapy (92 s [35 to 149], p = 0.001)). Two patients (11%) were withdrawn while taking estradiol/MPA owing to unstable angina. CONCLUSIONS: Combination estrogen/transvaginal progesterone gel increases exercise time to myocardial ischemia, as compared with estrogen/MPA. These results imply that the choice of progestin in women at higher cardiovascular risk requires careful consideration.

Cross-Over Studies↗
PubMed2000

Effects of hormone replacement therapy on sexual psychophysiology and behavior in postmenopause.

Investigators continue to define the exact relationship between sexual function and changes in hormonal status during menopause. The availability of different preparations that could replace estrogens and androgens has led to many studies of the use of hormone replacement therapy (HRT) for sexual dysfunction. Dyspareunia due to vaginal dryness appears to be most responsive to estrogen replacement therapy (ERT) via restoration of vaginal cells, pH, and blood flow. Progestins, to a certain extent, can oppose these changes and lead to a recurrence of dryness and dyspareunia. ERT has also been reported to enhance sexual desire in a significant percent of women. Although treatment with ERT has been shown to be efficacious for many women, there are others whose sexual difficulties remain unresponsive. There also appears to be a significant subgroup of women whose sexual difficulties respond initially to ERT but who subsequently revert to their initial problems, especially when the problem has been loss of libido. For these women, the addition of androgen has proved helpful.

Androgens↗
PubMed2000

Blood pressure exceeding national guidelines among women after stroke.

BACKGROUND AND PURPOSE: After a transient ischemic attack or stroke, the risk for recurrence may be reduced by treatment of hypertension. The purpose of this study was to determine how commonly blood pressure exceeds national guidelines among patients who have had one of these events. METHODS: Subjects were 644 women participating in a randomized trial of estrogen for secondary stroke prevention. We measured blood pressure 1 month after the stroke or TIA while patients were under the care of their personal physicians. Among 536 patients, a second measure was made at an average of 2.9 years after the first. RESULTS: The mean age of participants was 71 years, and 73% reported a history of hypertension. At baseline, only 44% (280/644) of the women had blood pressure values within national guidelines (<140/90 mm Hg). With separate guidelines used for diabetics (<130/85 mm Hg) and nondiabetics (<140/90 mm Hg), the proportions of women within the guidelines were 27% and 44%, respectively. Overall, 39% of patients were within the diabetes-adjusted guidelines. Among patients whose blood pressure exceeded 140/90 mm Hg at first examination, 55% were still in excess at follow-up. Features associated with severe hypertension at first examination (>160/100 mm Hg) were history of hypertension, education less than college, and higher cognitive functioning. CONCLUSIONS: Blood pressure values in excess of national guidelines are common after stroke and TIA, especially among diabetic patients. Efforts to lower blood pressure control may enhance secondary prevention.

Aged↗
PubMed2000

The stroke prognosis instrument II (SPI-II) : A clinical prediction instrument for patients with transient ischemia and nondisabling ischemic stroke.

BACKGROUND AND PURPOSE: In 1991 we developed the Stroke Prognosis Instrument (SPI-I) to stratify patients with transient ischemic attack or ischemic stroke by prognosis for stroke or death in 2 years. In this article we validate and improve SPI-I (creating SPI-II). METHODS: To validate SPI-I, we applied it to 4 test cohorts and calculated pooled outcome rates. To create SPI-II, we incorporated new predictive variables identified in 1 of the test cohorts and validated it in the other 3 cohorts. RESULTS: For SPI-I, pooled rates (all 4 test cohorts) of stroke or death within 2 years in risk groups I, II, and III were 9%, 17%, and 24%, respectively (P<0.01, log-rank test). SPI-II was created by adding congestive heart failure and prior stroke to SPI-I. Each patient's risk group was determined by the total score for 7 factors: congestive heart failure (3 points); diabetes (3 points); prior stroke (3 points); age >70 years (2 points); stroke for the index event (not transient ischemic attack) (2 points); hypertension (1 point); and coronary artery disease (1 point). Risk groups I, II, and III comprised patients with 0 to 3, 4 to 7, and 8 to 15 points, respectively. For SPI-I, pooled rates (3 cohorts excluding the SPI-II development cohort) of stroke or death within 2 years in risk groups I, II, and III were 9%, 17%, and 23%, respectively. For SPI-II, pooled rates were 10%, 19%, and 31%, respectively. In receiver operator characteristic analysis, the area under the curve was 0.59 (95% CI, 0.57 to 0.60) for SPI-I and 0.63 (95% CI, 0.62 to 0.65) for SPI-II, confirming the better performance of the latter. CONCLUSIONS: Compared with SPI-I, SPI-II achieves greater discrimination in outcome rates among risk groups. SPI-II is ready for use in research design and may have a role in patient counseling.

Aged↗
PubMed1999

Psychosexual effects of menopause: role of androgens.

Ovarian hormones-estrogens, androgens, and progesterone-produce a myriad of effects in the nervous system. The effects of androgens in the brain are mediated through androgen-specific receptors and by the aromatization of testosterone to estradiol. Alterations in the circulating levels of androgens play an important role in psychologic and sexual changes that occur after menopause. The effects of short-term estrogen therapy in improving psychologic symptoms, maintaining vaginal lubrication, decreasing vaginal atrophy, and increasing pelvic blood flow in postmenopausal women are well documented. However, some patients require more than estrogen alone to improve psychologic dysfunction, decreased sexual desire, or other sexual problems associated with menopause. Results from clinical studies show that hormone replacement therapy with estrogen plus androgens provides greater improvement in psychologic (eg, lack of concentration, depression, and fatigue) and sexual (eg, decreased libido and inability to have an orgasm) symptoms than does estrogen alone in naturally and surgically menopausal women.

Affect↗
PubMed1999

Improving adherence to hormone replacement therapy with effective patient-physician communication.

Surgically menopausal women are 5 times more likely to begin hormone replacement therapy than are naturally menopausal women, and they continue therapy for longer periods. The primary reasons that women refuse hormone replacement are fear of cancer and perceived side effects. In contrast, withdrawal bleeding is the major reason that women discontinue hormone replacement therapy. Physician-patient communication plays an important role in a woman's decision to use hormone replacement therapy, to fill her prescription, and to adhere to the regimen. The first visit at which hormone replacement therapy is discussed is crucial to establishing an effective patient-physician relationship. At least 15 minutes, and preferably 45 minutes, should be reserved for this visit. Patient follow-up-either by phone or in person-during the first month can help improve adherence because this is when many women may have nuisance side effects and discontinue therapy.

Communication Barriers↗
PubMed1999

Risks and benefits of hormone replacement therapy for the prevention of cardiovascular disease.

Study of the circulatory effects of ovarian hormones has become a subject of increasing interest with the promise of new treatment approaches for the prevention of cardiovascular disease. Work with estrogens is the most extensive and does indicate the benefits outweigh the risks albeit we continue to await the findings of several large, prospective randomized trials. The addition of progestins does appear to be compromising but it is possible that an approach will be developed that is cardioprotective without increasing the cancer risk.

Cardiovascular Diseases↗
PubMed1998

Cardiovascular aspects of androgens in women.

A review of the literature of androgen actions affecting the circulatory system indicates early enthusiasm for use of testosterone in cardiac patients, subsequent disenchantment with androgens due to negative effects on lipid metabolism, and recent renewed interest as new technologies and understandings of the cardio-protective effects of estrogens has led to re-examination of the beneficial and adverse effects of androgens. Ovarian steroids, including androgens, have effects on lipid metabolism in the liver and direct effects in the arterial wall, which influence the development and progress of atherosclerosis. Androgens lower total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides but also decrease high-density lipoprotein (HDL) cholesterol levels. Androgen arterial-wall effects help maintain the mechanisms involved in vasodilation. Androgens alone appear to promote atherosclerosis but when administered with estrogens have the opposite effect in the arterial wall. Recognition of the cellular actions of androgens and the decrease in androgen production as women age after the menopause has led to increased use of androgen replacement therapy for postmenopausal women. Preliminary clinical findings in women using postmenopausal estrogen/androgen treatment indicate a good safety profile. However, in comparison to the many years and experience in evaluating the effects of estrogens, studies of androgen effects must be considered to be at a preliminary stage.

Adult↗
PubMed1998

Ovarian hormones and vaginal blood flow: using laser Doppler velocimetry to measure effects in a clinical trial of post-menopausal women.

OBJECTIVES: To describe the use of laser Doppler velocimetry for measurement of vaginal blood flow and report the effects of estrogen compared with estrogen-androgen treatment in post-menopausal women. DESIGN: Literature review of pelvic blood flow studies and sexual function. Findings from a prospective, randomized, parallel study. SETTING: Normal human volunteers in an academic research environment. INTERVENTIONS: Laser Doppler measurements of vaginal blood flow were compared before and after the administration of oral esterified estrogens or esterified estrogens plus methyltestosterone for four and eight weeks of daily drug administration. MAIN OUTCOME MEASURES: Vaginal blood flow velocities. RESULTS: Laser Doppler velocimetry proved readily adaptable for measurement of vaginal blood flow. Although esterified estrogens plus methyltestosterone showed greater effects on blood flow than esterified estrogens alone, the results were not statistically significant. CONCLUSIONS: Vaginal blood flow is an objective measure of sexual function which can be determined with laser Doppler velocimetry. The vasodilator effects of esterified estrogens and esterified estrogens with methyltestosterone are similar.

Double-Blind Method↗
PubMed1997

Vasodilator effects of estrogen are not diminished by androgen in postmenopausal women.

OBJECTIVE: To compare the effects of estrogen with estrogen-androgen treatment on vaginal blood flow velocity and fingertip postocclusive hyperemic blood flow response. DESIGN: Prospective, randomized, parallel, double-blind study. SETTING: Healthy human volunteers in an academic research environment. PATIENT(S): Postmenopausal women receiving estrogen replacement therapy for at least 12 months and treated with placebo before this investigation. INTERVENTION(S): Esterified estrogens or esterified estrogen + methyltestosterone were administered orally; laser Doppler velocimetry was used to determine vaginal and fingertip blood flow responses at baseline and after 4 and 8 weeks of daily drug administration. MAIN OUTCOME MEASURE(S): Fingertip postocclusive area under curve (AUC); vaginal blood flow velocities. RESULT(S): The AUC for postocclusive fingertip blood flow and vaginal blood flow increased to a greater extent in the estrogen-androgen group, but changes were not statistically significant between groups. CONCLUSION(S): Estrogen-androgen treatment does not diminish the vasodilator effects of estrogen treatment in postmenopausal women.

Blood Flow Velocity↗
PubMed1996

17-beta-Estradiol therapy lessens angina in postmenopausal women with syndrome X.

OBJECTIVES: We sought to investigate the hypothesis that estrogen replacement therapy ameliorates symptoms in postmenopausal women with syndrome X. BACKGROUND: Syndrome X (angina pectoris, positive findings on exercise electrocardiography and normal results on coronary angiography) frequently occurs in menopausal women. This observation, in conjunction with the known vasoactive properties of estrogens, suggests that estrogen depletion may contribute to the pathogenesis of syndrome X in some women. METHODS: Twenty-five postmenopausal patients with syndrome X completed a double-blind, placebo-controlled study of the effect of 17-beta-estradiol cutaneous patches (100 micrograms/24 h) on the frequency of chest pain and on exercise tolerance. Patients were randomly assigned to receive either placebo or 17-beta-estradiol patches for 8 weeks and were then crossed over to the other treatment. RESULTS: During the placebo phase, patients had a mean of 7.3 episodes of chest pain/10 days. A reduction to 3.7 episodes/10 days was observed during the 17-beta-estradiol phase (p < 0.05). No significant differences were observed between the effects of 17-beta-estradiol and placebo on exercise duration or the results of other cardiologic investigations. CONCLUSIONS: Estrogen replacement reduces the frequency of chest pain and may be a useful new therapeutic option for treating postmenopausal women with syndrome X.

Cross-Over Studies↗
PubMed1996

Cyclical variation in paroxysmal supraventricular tachycardia in women.

BACKGROUND: Paroxysmal supraventricular tachycardia (SVT) in premenopausal women is often judged to be related to anxiety, and may be associated with the menstrual cycle. The aim of this study was to determine whether a cyclical variation of episodes of SVT exists and to correlate such variation with cyclical variation in plasma ovarian hormones. METHODS: 26 women (mean age 36 [SD 8] years; with paroxysmal SVT were screened; those with regular menses who experienced at least three episodes of paroxysmal SVT in two consecutive 48-hour ambulatory ECG recordings were included. 13 patients (aged 32 [6] years) met these criteria. Patients underwent 48-hour ambulatory ECG monitoring and determination of plasma concentrations of oestradiol-17 beta and progesterone on day 7, 14, 21, and 28 of their menstrual cycle. FINDINGS: An increase in the number and duration of episodes of paroxysmal SVT was observed on day 28 as compared to day 7 of the menstrual cycle. A significant positive correlation was found between plasma progesterone and number of episodes and duration of SVT (5.6 [2.2] ng/mL; r=0.83, p=0.0004; and r=0.82, p=0.0005), while a significant inverse correlation was found between plasma oestradiol-17 beta and number of episodes and duration of SVT (155 [22] pg/mL; r=0.89, p<0.0001; and r=0.81, p=0.0007). INTERPRETATION: Women with paroxysmal SVT and normal menses exhibit a cyclical variation in the occurrence of the arrhythmia with their menstrual cycle. There is a close correlation between the episodes of paroxysmal SVT and the plasma concentrations of ovarian hormones. These data suggest that changes in plasma levels of ovarian hormones (and their interaction) may be of importance in determining episodes of arrhythmia in such patients. The mechanisms of these effects are unknown.

Adult↗
PubMed1995

17 beta-Estradiol attenuates acetylcholine-induced coronary arterial constriction in women but not men with coronary heart disease.

BACKGROUND: Women are protected from coronary artery disease until the menopause. Ovarian hormones are vasoactive substances that influence both hemodynamic parameters and atheroma formation. Intravenous ethinyl estradiol has been shown to reverse acetylcholine-induced vasoconstriction in cynomolgus monkeys and humans, and 17 beta-estradiol improves exercise-induced myocardial ischemia in female patients. We investigated the effect of the naturally occurring estrogen 17 beta-estradiol on the coronary circulation in postmenopausal women and men with coronary artery disease. METHODS AND RESULTS: We studied nine postmenopausal women 59 +/- 3 years old, mean +/- SEM, and seven men 52 +/- 4 years old with proven coronary artery disease. They underwent measurement of coronary artery diameter and coronary blood flow after intracoronary infusion of acetylcholine 1.6 and 16 micrograms/min before and 20 minutes after intracoronary administration of 2.5 micrograms of 17 beta-estradiol into atherosclerotic, nonstenotic coronary arteries. Changes in coronary artery diameter were measured by quantitative angiography, and changes in coronary blood flow were measured with an intracoronary Doppler catheter. In female patients, acetylcholine 1.6 and 16 micrograms/min caused constriction before the administration of 17 beta-estradiol (-6 +/- 2% and -8 +/- 5%, respectively, compared with baseline). This constrictor response was converted to dilatation after intracoronary administration of 17 beta-estradiol (+8 +/- 2% and +9 +/- 3%, respectively; P < .01 before versus after estrogen). Acetylcholine 1.6 and 16 micrograms/min increased coronary blood flow before and after the infusion of 17 beta-estradiol. However, the mean acetylcholine-induced increases in coronary flow were significantly greater (P < .009) after (126 +/- 37% and 248 +/- 89%, respectively) than before (94 +/- 31% and 143 +/- 49% mL/min, respectively) the administration of 17 beta-estradiol. 17 beta-Estradiol alone had no significant effect on coronary diameter or coronary blood flow (P > .05). Isosorbide dinitrate (1 mg) caused dilatation of the coronary arteries by 11 +/- 2% (P < .005). In men, acetylcholine 1.6 and 16 micrograms/min caused constriction both before and after the administration of 17 beta-estradiol and caused similar increases in coronary blood flow both before and after the intracoronary administration of 17 beta-estradiol. Infusion of intracoronary placebo in six female control patients 55 +/- 3 years old and six male control patients 56 +/- 3 years old did not change coronary diameter responses or coronary blood flow responses to acetylcholine. CONCLUSIONS: 17 beta-Estradiol modulates acetylcholine-induced coronary artery responses of female but not male atherosclerotic coronary arteries in vivo. These human data confirm reports from studies in cynomolgus monkeys that estrogen modulates the responses of atherosclerotic coronary arteries. An enhancement of endothelium-dependent relaxation by natural estrogen (as used in most hormone replacement therapy) may be important in postmenopausal women with established coronary heart disease and may contribute to the acute effect of 17 beta-estradiol on blood flow and its long-term protective effect on the development of coronary artery disease.

Acetylcholine↗