This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gerhard, M. Articles by Creager, M. A. Search for Related Content PubMed PubMed Citation Articles by Gerhard, M. Articles by Creager, M. A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ESTRADIOL PROGESTERONE

(Circulation. 1998;98:1158-1163.)
© 1998 American Heart Association, Inc.

Clinical Investigation and Reports

Estradiol Therapy Combined With Progesterone and Endothelium-Dependent Vasodilation in Postmenopausal Women

Marie Gerhard, MD; Brian W. Walsh, MD; Ahmed Tawakol, MD; Elizabeth A. Haley, BA; Shelly J. Creager, BSN; Ellen W. Seely, MD; Peter Ganz, MD; ; Mark A. Creager, MD

From the Department of Medicine (M.G., A.T., E.A.H., S.J.C., E.W.S., P.G., M.A.C.) and the Department of Obstetrics and Gynecology (B.W.W.), Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Background—Epidemiological studies indicate that estrogen replacement therapy decreases the risk of cardiovascular events in postmenopausal women. Estrogen may confer cardiovascular protection by improving endothelial function because it increases endothelium-dependent vasodilation. It is not known whether progesterone attenuates the beneficial effects of estrogen on endothelial function.

Methods and Results—Seventeen postmenopausal women with mild hypercholesterolemia were enrolled in a placebo-controlled, crossover trial to evaluate the effect of transdermal estradiol, with and without vaginal micronized progesterone, on endothelium-dependent vasodilation in a peripheral conduit artery. Brachial artery diameter was measured with high-resolution B-mode ultrasonography. To assess endothelium-dependent vasodilation, brachial artery diameter was determined at baseline and after a flow stimulus induced by reactive hyperemia. To assess endothelium-independent vasodilation, brachial artery diameter was measured after administration of sublingual nitroglycerin. During estradiol therapy, reactive hyperemia caused an 11.1±1.0% change in brachial artery diameter compared with 4.7±0.6% during placebo therapy (P<0.001). Progesterone did not significantly attenuate this improvement. During combined estrogen and progesterone therapy, flow-mediated vasodilation of the brachial artery was 9.6±0.8% (P=NS versus estradiol alone). Endothelium-independent vasodilation was not altered by estradiol therapy, either with or without progesterone, compared with placebo. There was a modest decrease in total and LDL cholesterol during treatment both with estradiol alone and when estradiol was combined with progesterone (all P<0.001 versus placebo). In a multivariate analysis that included serum estradiol, progesterone, total and LDL cholesterol concentrations, blood pressure, and heart rate, only the estradiol level was a significant predictor of endothelium-dependent vasodilation.

Conclusions—The addition of micronized progesterone does not attenuate the favorable effect of estradiol on endothelium-dependent vasodilation. The vasoprotective effect of hormone replacement therapy may extend beyond its beneficial actions on lipids.

Key Words: endothelium • hormones • vasodilation • women

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Epidemiological studies indicate that estrogen replacement therapy decreases the risk of cardiovascular death in postmenopausal women.^{1 2 3} Yet, many postmenopausal women require the use of progesterone in addition to estrogen to reduce the risk of endometrial cancer.⁴ A recent observational report from the Nurses Health Study, which included >63 000 women, suggested that progesterone, when added to estrogen replacement therapy, decreases the risk of cardiovascular events, as does estrogen replacement therapy alone.⁵ Other, smaller studies have found that progesterone in combination with estrogen had no adverse effect, compared with estrogen alone, on the risk of myocardial infarction and stroke.^{6 7 8}

An important postulated mechanism whereby estrogen may confer cardiovascular protection is by improving the function of vascular endothelium, specifically by increasing the bioavailability of endothelium-derived nitric oxide.⁹ Nitric oxide may slow atherogenesis and limit the adverse effects of atherosclerosis by modulating vascular tone; by inhibiting platelet aggregation, synthesis of monocyte chemotactic factors, and monocyte adhesion to the endothelial surface; and by reducing vascular smooth muscle cell proliferation.^{10 11 12 13} Indeed, estrogen administration improves endothelium-dependent vasodilation in coronary and peripheral vessels of ovariectomized animals and postmenopausal women.^{14 15 16 17 18 19 20 21 22} Addition of medroxyprogesterone acetate decreases the beneficial effects of estrogen on endothelium-dependent vasodilation in atherosclerotic coronary arteries of cynomolgus monkeys.²³ It is not known whether progesterone diminishes the favorable endothelial effects of estrogen on the endothelium in postmenopausal women. A counterregulatory action would be inconsistent with the available epidemiological studies.

Oral estrogen also may decrease cardiovascular risk by lowering LDL cholesterol and lipoprotein (a) levels and by raising HDL cholesterol.^{24 25} The Postmenopausal Estrogen-Progesterone Intervention (PEPI) trial found that neither medroxyprogesterone acetate nor oral micronized progesterone significantly changed the beneficial effects of conjugated equine estrogen on LDL cholesterol levels.²⁶ Transdermal administration of estradiol, with or without micronized progesterone, however, has not been shown to significantly alter plasma lipoprotein composition.^{24 27}

The objective of this study was to determine whether progesterone, when added to estrogen replacement therapy, attenuates the favorable effects of estrogen on endothelium-dependent vasodilation in postmenopausal women with mild hypercholesterolemia. Specifically, we studied the effect of chronic transdermal estradiol treatment alone and in combination with vaginal micronized progesterone, each administered to achieve physiologically relevant premenopausal levels, on peripheral endothelium-dependent vasodilation in a placebo-controlled, crossover trial.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Seventeen postmenopausal women 48 to 75 years old (mean, 60 years) with mild hypercholesterolemia were recruited via advertisement for participation in the study. Menopause was confirmed by follicle-stimulating hormone levels >40 IU/L and absence of menses for at least 1 year. Exclusion criteria included hypertension, diabetes, cigarette smoking, clinical manifestations of atherosclerosis (coronary artery disease, peripheral artery disease, and cerebrovascular disease), venous thromboembolism, liver disorders, unexplained vaginal bleeding, and personal or family history of breast cancer. All subjects provided a medical history and underwent a physical examination, including gynecological evaluation, and mammography before enrollment. This study was a substudy of a larger trial evaluating the metabolic effects of the restoration of premenopausal hormone levels in postmenopausal women and was approved by the Human Research Committee of Brigham and Women's Hospital. Each subject gave written informed consent.

Randomization to Treatment
This was a double-blind, crossover trial in which subjects received 2 therapeutic regimens, each for a duration of 14 weeks. Nineteen women were enrolled; 17 participated in the vascular reactivity studies. Eight women were randomized to placebo treatment first and received 14 weeks of placebo therapy followed by a 1-month washout period. Then, they crossed over to receive active therapy for 14 weeks. This included estradiol alone for the first 8 weeks, followed by estradiol in combination with 2-week cycles of progesterone during weeks 9 to 10 and 13 to 14. The other 9 women received the opposite treatment order. Estradiol was administered as 0.2 mg estradiol transdermal (two 0.1-mg patches, Estraderm, CIBA-Geigy) placed 2 times per week or corresponding placebo (CIBA-Geigy). The transdermal route of estrogen administration was selected to minimize changes in lipid levels.^{24 27} Progesterone was given daily as 300 mg vaginal micronized progesterone (Upjohn) in a nonliquefying base (Unibase, Warner Chilcott Laboratories) to achieve sustained physiological levels.²⁸ The vaginal route of administration was chosen to administer natural progesterone. Patch and creme medications were administered in the evening, and vascular reactivity studies were performed in the morning. Review of treatment effects was undertaken at each visit by 1 of the authors (B.W.W.). Treatment effects were not made known to the individuals performing and analyzing the vascular reactivity studies.

Vascular Reactivity Studies
Vascular reactivity was evaluated during placebo treatment (week 8), during estradiol therapy (week 8), and during estradiol plus progesterone therapy (week 10). Subjects were evaluated at the same time of day for each study in a quiet, temperature-controlled room after resting supine for 15 minutes. To assess vascular reactivity, high-resolution ultrasonography of the brachial artery was performed with a Toshiba 270 SSA ultrasound machine equipped with a 7.5-MHz linear array probe. In brief, as previously described and validated,^{21 29 30 31 32} the brachial artery was imaged longitudinally at a site just proximal to the antecubital fossa, with the arm abducted 80° from the body and the forearm semipronated. The transducer position was adjusted to obtain optimal images of the anterior and posterior intima. The image was recorded on x-ray film to ensure that the brachial artery was imaged at the identical site and position for each study. All images were recorded on super VHS videotape. After baseline images were recorded, a sphygmomanometric cuff on the upper arm was inflated to suprasystolic pressures for 5 minutes. To determine endothelium-dependent vasodilation, the brachial artery was imaged during reactive hyperemia 1 minute after cuff release. Brachial artery blood flow typically increases 5- to 10-fold during reactive hyperemia, and this is followed by peak brachial artery vasodilation.²⁰ Flow-mediated vasodilation of the brachial artery is largely an endothelium-dependent process, mediated by nitric oxide and inhibited by the nitric oxide synthase antagonist N^G-monomethyl-L-arginine.³⁰ Moreover, flow-mediated, endothelium-dependent vasodilation of the brachial artery correlates with endothelium-dependent vascular responsiveness of the coronary arteries to acetylcholine in individuals who have undergone both types of testing.³¹ After a minimum of 10 minutes from the time of cuff release and reestablishment of baseline conditions, including baseline diameter, the brachial artery was imaged again. Then, to determine endothelium-independent vasodilation, subjects received 0.3 mg of sublingual nitroglycerin. The brachial artery image was recorded 3 minutes later, a time corresponding to peak vasodilation to nitroglycerin. Forearm blood flow during reactive hyperemia was measured by venous occlusion plethysmography with calibrated mercury-in-Silastic strain gauges as previously described.³³

Biochemical Assays
Serum 17ß-estradiol, progesterone level, and lipid concentrations were measured during each treatment period on the day of the vascular reactivity study. An enzymatic method was used to determine total cholesterol and triglyceride levels (Dax 96 analyzer, Bayer). HDL cholesterol was measured by precipitation of apoB-containing lipoproteins by the addition of phosphotungstic acid and magnesium ions. After centrifugation, only HDL cholesterol remained in the supernatant. The cholesterol concentration of the supernatant was measured by the enzymatic method. LDL cholesterol was calculated according to the Friedewald formula.³⁴ Estradiol and progesterone concentrations were determined by chemiluminescent immunoassays (Bayer).

Image Analysis
For each condition (baseline, reactive hyperemia, repeat baseline, nitroglycerin) during each treatment period, 3 end-diastolic frames were selected and digitized for subsequent analysis. Each image was assigned a code. Subject name, date, and time were then removed from the image. Image analysis of the coded frames was then performed by 2 blinded investigators using software that searched for the shortest distance between the points on the arterial wall as previously described.^{20 29} This resulted in 20 paired measurements along a 10- to 15-mm length of artery. Arterial diameter was measured from the intima-lumen interface along the posterior wall to the media-intima interface of the anterior wall. Pixels were converted to millimeters by use of calibration factors from real-time ultrasonography. The average of 3 measurements was used for each determination of brachial artery diameter.

Statistical Analysis
All data are reported as mean±SEM. The effects of estrogen alone and combined with progesterone were analyzed by repeated-measures ANOVA. Post hoc comparisons between the different treatments were made with the Student-Newman-Keuls test. Side effects during treatment were evaluated with the McNemar test. The Spearman rank correlation coefficient was determined for endothelium-dependent vasodilation and total and LDL cholesterol levels. A stepwise multivariate analysis was performed with flow-mediated, endothelium-dependent vasodilation as the dependent variable and 17ß-estradiol, progesterone, total cholesterol and LDL cholesterol levels, age, heart rate, and blood pressure as independent variables. Statistical significance was accepted at the 95% confidence level (P<0.05).

	Results

Top Abstract Introduction Methods Results Discussion References

 
The effect of treatment with placebo, estradiol, and estradiol combined with progesterone on heart rate, blood pressure, and serum estradiol and progesterone is described in Table 1. The serum estradiol concentration rose significantly and comparably during both drug treatment periods. The serum progesterone level increased significantly only during the period in which micronized progesterone was administered. Neither heart rate nor blood pressure was altered by active treatment.

View this table: [in this window] [in a new window]   Table 1. Effect of Treatment on Heart Rate, Blood Pressure, and Hormone Levels

During placebo therapy, total cholesterol was 223±7 mg/dL, LDL cholesterol was 141±6 mg/dL, HDL cholesterol was 62±4 mg/dL, and triglycerides were 97±12 mg/dL. Estradiol therapy alone decreased total cholesterol by 6.7±1.8% (P<0.001) and LDL cholesterol by 10.9±2.7% (P<0.001). Estradiol therapy combined with progesterone decreased total cholesterol by 5.8±1.7% (P<0.001) and LDL cholesterol by 8.4±2.4% (P<0.001). Estradiol treatment alone or combined with progesterone did not significantly alter HDL cholesterol or triglyceride concentrations.

There were no significant differences in the degree of symptoms or side effects between placebo, estradiol alone, and estradiol with progesterone therapy. Breast tenderness was noted by 9 subjects during estradiol therapy, by 7 subjects during estradiol with progesterone therapy, and by 5 subjects during placebo therapy. Vaginal bleeding was reported by 4 subjects during estradiol therapy, by 5 subjects during estradiol plus progesterone therapy, and by 2 subjects during placebo therapy. Hot flashes were present in 5 subjects during placebo therapy and were reported by 2 subjects during estradiol therapy. One or 2 subjects reported fatigue, mood change, leg cramps, headache, rash, sweating, insomnia, nausea, urinary frequency, and insomnia during each of the 3 treatment periods.

Effect of Hormonal Treatment on Vascular Reactivity
The baseline brachial artery diameter was 3.61±0.80 mm during placebo treatment, 3.59±0.70 mm during estradiol treatment, and 3.62±0.90 mm during the estradiol plus progesterone treatment (each P=NS versus placebo). Peak reactive hyperemic forearm blood flow, the stimulus for brachial artery flow-mediated vasodilation, was similar for each treatment period (19.5±1.4, 19.7±1.6, and 24.0±1.8 mL · 100 mL^-1 · min^-1 during placebo, estradiol alone, and estradiol plus progesterone treatment periods, respectively, P=NS). Flow-mediated, endothelium-dependent vasodilation was greater during estradiol therapy than during placebo therapy. During estradiol therapy, reactive hyperemia caused an 11.1±1.0% increase in brachial artery diameter compared with 4.7±0.6% during placebo therapy (P<0.001) (Figure 1). Flow-mediated endothelium-dependent vasodilation of the brachial artery also was greater during combined estradiol and progesterone treatment (9.6±0.8%) than during placebo treatment (P<0.001 versus placebo) (Figure 1). Progesterone combined with estradiol did not change the magnitude of endothelium-dependent vasodilation compared with treatment with estradiol alone (9.6±0.8 versus 11.1±1.0%, P=NS). Endothelium-independent vasodilation to sublingual nitroglycerin was not affected by treatment (Figure 2). The change in brachial artery diameter after nitroglycerin was 12.7±1.3% during placebo treatment, 12.1±1.0% during estradiol treatment alone, and 11.3±1.2% during the combination of estradiol and progesterone (P=NS).

View larger version (11K): [in this window] [in a new window]   Figure 1. Flow-mediated, endothelium-dependent vasodilation of brachial artery during placebo therapy, estradiol therapy, and estradiol plus progesterone therapy. Values are mean±SEM. *P<0.001 vs placebo.

View larger version (12K): [in this window] [in a new window]   Figure 2. Endothelium-independent vasodilation of brachial arteries during placebo, estradiol therapy, and estradiol plus progesterone therapy. Values are mean±SEM.

Factors Associated With Endothelium-Dependent Vasodilation
Stepwise multiple logistic regression was performed with flow-mediated, endothelium-dependent vasodilation as the dependent variable (Table 2). Estradiol concentration was the only significant predictor of endothelium-dependent vasodilation. A significant correlation between the change in total cholesterol or LDL cholesterol and flow-mediated, endothelium-dependent vasodilation was not detected by rank correlation testing.

View this table: [in this window] [in a new window]   Table 2. Stepwise Multivariate Analysis

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
The novel observation made in this study is that the addition of micronized vaginal progesterone to transdermal estradiol does not diminish the benefits of estradiol on endothelium-dependent vasodilation in postmenopausal women. This effect of estradiol therapy, with or without progesterone, on vascular reactivity appears to be independent of its lipid-lowering effect.

Estrogen and Endothelium-Dependent Vasodilation
The beneficial effect of estrogen on endothelium-dependent vasodilation was initially elucidated in animal models and subsequently confirmed in postmenopausal women. Replacing estrogen after ovariectomy restores endothelium-dependent relaxation of arteries isolated from rabbits, dogs, and cholesterol-fed swine.^{14 15 35} Short-term and long-term estrogen administration also improves endothelium-dependent vasodilation of coronary arteries to acetylcholine in vivo in cholesterol-fed ovariectomized monkeys.^{16 17 23} In postmenopausal women, acute administration of estrogens increases endothelium-dependent vasodilation of coronary arteries and forearm resistance vessels,^{18 19 21 22} and chronic oral estradiol administration increases flow-mediated vasodilation of the brachial artery.²⁰ Studies in animal models have examined the effect of progestin on endothelial function. Miller and Vanhoutte³⁵ studied canine coronary artery rings and reported that progesterone combined with estrogen attenuated the improvement in endothelium-dependent relaxation seen with estrogen alone. Williams et al²³ found that medroxyprogesterone acetate diminished the endothelium-dependent vasodilator effect of conjugated equine estrogen by up to 50% in coronary arteries of cholesterol-fed monkeys. Recently, Miyagawa et al³⁶ compared the effects of 2 types of progestin on coronary vasoreactivity in ovariectomized monkeys. Intracoronary administration of serotonin and a thromboxane mimetic induced coronary vasospasm in monkeys treated with 17ß-estradiol and medroxyprogesterone acetate but not in monkeys treated with 17ß-estradiol and progesterone.³⁶ Taken together, these studies suggest that the vascular effects of progestins combined with estrogen may be different between synthetic and natural progesterone.

The present study demonstrates that the addition of micronized vaginal progesterone, in a dose that achieved physiological serum concentrations of progesterone, does not attenuate the beneficial effects of estradiol on endothelium-dependent vasodilation in postmenopausal women. Our findings are consistent with those observed in premenopausal women, in whom similar enhancement of endothelium-dependent vasodilation of the brachial artery occurred during the follicular and luteal phases of the menstrual cycle compared with the time of menses.³⁷ In our study, we achieved estradiol and progesterone levels during active treatment comparable to those found in the follicular (estradiol administration) and luteal (estradiol plus progesterone administration) phases of the menstrual cycle.³⁸ The use of micronized progesterone, which is less androgenic than medroxyprogesterone acetate, and/or species differences may explain, in part, the findings in women compared with those seen in experimental studies.

Lipoprotein Effects
The decrease in total and LDL cholesterol concentrations with both active treatments in this study was modest. This differs from a previous study in which transdermal estradiol concentration used at a lower dose (0.1 mg twice each week) had no effect on these lipoprotein measurements.²⁴ We chose to use 0.2 mg twice each week to more closely approximate physiological concentrations of estrogen that occur during the menstrual cycle. The higher dose may account for the disparate results on lipoprotein fraction between these 2 studies.

Lowering LDL cholesterol has been shown to improve endothelium-dependent vasodilation in coronary arteries.^{39 40 41 42} Therefore, a question has arisen as to whether the effect of estrogen on endothelium-dependent vasodilation is indirect and related to its lipid-lowering properties.⁴³ If so, this approach would be less appealing than the use of moderate lipid-lowering drugs, which are more potent and more free of side effects. Our findings suggest that improved endothelium-dependent vasodilation with transdermal administration of estradiol is independent of the change in lipid concentration. In a multivariate analysis, reduction in total and LDL cholesterol did not correlate with improvement in brachial artery endothelial function. Moreover, in previous studies, intracoronary or intravenous estrogen restored endothelium-dependent vasodilation in the coronary arteries in a matter of minutes, a time duration in which lipid changes could not have occurred.^{17 18 19 21 22}

Conclusions
The addition of micronized vaginal progesterone does not attenuate the improvement in endothelium-dependent vasodilation that occurs with estradiol treatment. These findings suggest that the increased bioavailability of endothelium-derived nitric oxide achieved with estradiol therapy is not reduced by progesterone. This observation provides insight into a mechanism whereby hormone replacement therapy reduces the risk of cardiovascular events in postmenopausal women and may allay fears about abrogating cardiovascular risk reduction with the addition of progesterone. Moreover, the vasoprotective effects of estradiol and progesterone replacement therapy appear to extend beyond its favorable actions on lipids. Therefore, hormone replacement and lipid-lowering therapies may be complementary, a concept that needs to be explored in future studies.

	Acknowledgments

 
This research was supported by a grant from the National Institutes of Health (NIH R01-HL-50890) as well as a National Institutes of Health Program Project Grant in Vascular Biology and Medicine (HL-48743). Dr Gerhard is a recipient of a Harvard/MIT Health Sciences and Technology–Beth Israel fellowship and the Cardiac Care Award of Excellence from the Alpha Phi Foundation. The authors gratefully acknowledge Dr Arnold Barnett for assistance with statistical analysis and Joanne Normandin for expert assistance in the preparation of this manuscript.

	Footnotes

 
Reprint requests to Mark A. Creager, MD, Vascular Medicine and Atherosclerosis Unit, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115.

Received January 30, 1998; revision received May 6, 1998; accepted May 16, 1998.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Stampfer JM, Colditz GA. Estrogen replacement therapy and coronary heart disease: a quantitative assessment of the epidemiologic evidence. Prev Med. 1991;20:47–63.[Medline] [Order article via Infotrieve]

2. Stampfer MJ, Colditz GA, Willett WC, Manson JE, Rosner B, Speizer FE, Hennekens CH. Postmenopausal estrogen therapy and cardiovascular disease: ten-year follow-up from the Nurse's Health Study. N Engl J Med. 1991;325:756–762.[Abstract]

3. Bush TL, Barrett-Connor E, Cowan LD, Criqui MH, Wallace RB, Suchindran CM, Tyroler HA, Rifkind BM. Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the Lipid Research Clinics Program Follow-up Study. Circulation. 1987;75:1102–1109.[Abstract/Free Full Text]

4. Grady D, Rubin SM, Petitti DB, Fox CS. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med. 1992;117:1016–1037.

5. Grodstein F, Stampfer MJ, Manson JE. Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. N Engl J Med. 1996;335:453–461.[Abstract/Free Full Text]

6. Falkeborn M, Persson I, Terent A, Adami HO, Lithell H, Bergstrom R. Hormone replacement therapy and risk of stroke: follow-up of a population based cohort in Sweden. Arch Intern Med. 1993;153:1201–1209.[Abstract/Free Full Text]

7. Falkeborn M, Persson I, Adami HO, Bergstrom R, Eaker E, Lithell H, Mohsen R, Naessen T. The risk of acute myocardial infarction after oestrogen and oestrogen-progestogen replacement. Br J Obstet Gynaecol. 1992;99:821–828.[Medline] [Order article via Infotrieve]

8. Psaty BM, Heckbert SR, Atkins D, Lamaitre R, Kvepsell TD, Wahl PW, Siscovick DS, Wagner EH. The risk of myocardial infarction associated with the combined use of estrogens and progestins in postmenopausal women. Arch Intern Med. 1994;154:1333–1339.[Abstract/Free Full Text]

9. Meredith IT, Yeung AC, Weidinger FF, Anderson TJ, Uehata A, Ryan TJ Jr, Selwyn AP, Ganz P. Role of impaired endothelium-dependent vasodilation in ischemic manifestations of coronary artery disease. Circulation. 1993;87(suppl V):V-56–V-66.

10. Radomski MW, Palmer RM, Moncada S. Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet. 1987;2:1057–1058.[Medline] [Order article via Infotrieve]

11. De Caterina R, Libby P, Peng HB, Thannickal VJ, Rajavashisth TB, Gimbrone MA Jr, Shin WS, Liao JK. Nitric oxide decreases cytokine-induced endothelial activation: nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Invest. 1995;96:60–68.

12. Bath PM, Hassall DG, Gladwin AM, Palmer RM, Martin JF. Nitric oxide and prostacyclin: divergence of inhibitory effects on monocyte chemotaxis and adhesion to endothelium in vitro. Arterioscler Thromb. 1991;11:254–260.[Abstract/Free Full Text]

13. Garg UC, Hassid A. Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest. 1989;83:1774–1777.

14. Gisclard V, Miller VM, Vanhoutte PM. Effect of 17ß estradiol on endothelium-dependent responses in the rabbit. J Pharmacol Exp Ther. 1988;244:19–22.[Abstract/Free Full Text]

15. Keaney JF, Shwaery GT, Xu A, Nicolosi RJ, Loscalzo J, Foxall TL, Vita JA. 17ß-Estradiol preserves endothelial vasodilator function and limits low-density lipoprotein oxidation in hypercholesterolemic swine. Circulation. 1994;89:2251–2259.[Abstract/Free Full Text]

16. Williams JK, Adams MR, Klopfstein HS. Estrogen modulates responses of atherosclerotic coronary arteries. Circulation. 1990;81:1680–1687.[Abstract/Free Full Text]

17. Williams JK, Adams MR, Herrington DM, Clarkson TB. Short-term administration of estrogen and vascular responses of atherosclerotic coronary arteries. J Am Coll Cardiol. 1992;20:452–457.[Abstract]

18. Reis SE, Gloth ST, Blumenthal RS, Resar JR, Zacur HA, Gerstenblith G, Brinker JA. Ethinyl estradiol acutely attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women. Circulation. 1994;89:52–60.[Abstract/Free Full Text]

19. Gilligan DM, Quyyami AA, Cannon RO. Effects of physiological levels of estrogen on coronary vasomotor function in postmenopausal women. Circulation. 1994;89:2545–2551.[Abstract/Free Full Text]

20. Lieberman EH, Gerhard MD, Uehata A, Walsh BW, Selwyn AP, Ganz P, Yeung AC, Creager MA. Estrogen improves endothelium-dependent flow mediated vasodilation in postmenopausal women. Ann Intern Med. 1994;121:936–941.[Abstract/Free Full Text]

21. Gilligan DM, Badar DM, Panza JA, Quyyumi AA, Cannon RO III. Acute vascular effects of estrogen in postmenopausal women. Circulation. 1994;90:786–791.[Abstract/Free Full Text]

22. Collins P, Rosano GMC, Sarrell PM. 17ß-Estradiol attenuates acetylcholine-induced coronary arterial constriction in women but not men with coronary heart disease. Circulation. 1995;92:24–30.[Abstract/Free Full Text]

23. Williams JK, Honore EK, Washburn SA, Clarkson TB. Effects of hormone replacement therapy on reactivity of atherosclerotic coronary arteries in cynomolgus monkeys. J Am Coll Cardiol. 1994;24:1757–1761.[Abstract]

24. Walsh BW, Schiff I, Rosner B, Greenberg L, Ravnikar V, Sacks FM. Effects of postmenopausal estrogen replacement on concentration and metabolism of plasma lipoproteins. N Engl J Med. 1991;325:1196–1204.[Abstract]

25. Sacks FM, McPherson R, Walsh BW. Effect of postmenopausal estrogen replacement on plasma Lp(a) lipoprotein concentrations. Arch Intern Med. 1994;154:1106–1110.[Abstract/Free Full Text]

26. The Writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA. 1995;273:199–208.[Abstract/Free Full Text]

27. Moorjani S, Dupont A, Labrie F, De Lignieres B, Cusan L, Dupont P, Mailloux J, Lupien PJ. Changes in plasma lipoprotein and apolipoprotein composition in relation to oral versus percutaneous administration of estrogen alone or in cyclic association with utrogestan in menopausal women. J Clin Endocrinol Metab. 1991;73:373–379.[Abstract/Free Full Text]

28. Kimzey LM, Gumowski J, Merriam GR Jr, Nelson LM. Absorption of micronized progesterone from a nonliquefying vaginal cream. Fertil Steril. 1991;56:995–996.[Medline] [Order article via Infotrieve]

29. Uehata A, Lieberman EH, Gerhard MD, Anderson TJ, Ganz P, Polak JF, Creager MA, Yeung AC. Noninvasive assessment of endothelium-dependent flow mediated vasodilation. Vasc Med. 1997;2:87–92.[Medline] [Order article via Infotrieve]

30. Lieberman EH, Gerhard MD, Uehata A, Selwyn AP, Ganz P, Yeung AC, Creager MA. Flow mediated vasodilation of the brachial artery is impaired in patients less than 40 years of age with coronary artery disease. Am J Cardiol. 1996;78:1210–1214.[Medline] [Order article via Infotrieve]

31. Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D, Lieberman EH, Ganz P, Creager MA, Yeung AC, Selwyn AP. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol. 1995;26:1235–1241.[Abstract]

32. Sorensen KE, Celermajer DS, Spiegelhalter DJ, Georgakopolous P, Robinson J, Thomas O, Deanfield JE. Non-invasive measurement of endothelium-dependent arterial responses in man: accuracy and reproducibility. Br Heart J. 1995;74:247–253.[Abstract/Free Full Text]

33. Creager MA, Gallagher SJ, Girerd XJ, Coleman SM, Dzau JV, Cooke JP. L-Arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans. J Clin Invest. 1992;90:1248–1253.

34. Friedewald WT, Levy RT, Fredrickson DS. Estimation of the concentration of low density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502.[Abstract]

35. Miller VM, Vanhoutte PM. Progesterone and modulation of endothelium-dependent responses in canine coronary arteries. Am J Physiol. 1991;261:R1022–R1027.[Abstract/Free Full Text]

36. Miyagawa K, Rosch J, Stanczyk F, Hermsmeyer K. Medroxyprogesterone interferes with ovarian steroid protection against coronary vasospasm. Nat Med. 1997;3:324–327.[Medline] [Order article via Infotrieve]

37. Hashimoto M, Akishita M, Eto M, Ishikawa M, Kozaki K, Toba K, Sagara Y, Taketani Y, Orimo H, Ouchi Y. Modulation of endothelium-dependent flow-mediated dilation of the brachial artery by sex and menstrual cycle. Circulation. 1995;92:3431–3435.[Abstract/Free Full Text]

38. Roseff SJ, Bangah ML, Kettel LM, Vale W, Rivier J, Burger HG, Yen SS. Dynamic changes in circulating inhibin levels during the luteal-follicular transition of the human menstrual cycle. J Clin Endocrinol Metab. 1989;69:1033–1039.[Abstract/Free Full Text]

39. Anderson TJ, Meredith IT, Yeung AC, Frei B, Selwyn AP, Ganz P. The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. N Engl J Med. 1995;332:488–493.[Abstract/Free Full Text]

40. Treasure CB, Klein JL, Weintraub WS, Talley JD, Shillabower ME, Kosinski AS, Zhang J, Boccuzz SI, Cedarholm JC, Alexander RW. Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. N Engl J Med. 1995;332:481–487.[Abstract/Free Full Text]

41. Leung WH, Lau CP, Wang CK. Beneficial effect of cholesterol-lowering therapy on coronary endothelium-dependent relaxation in hypercholesterolemic patients. Lancet. 1993;341:1496–1500.[Medline] [Order article via Infotrieve]

42. Egashira K, Hirooka Y, Kai H, Sugimachi M, Suzuki S, Inou T, Takeshita A. Reduction in serum cholesterol with pravastatin improves endothelium-dependent vasomotion in patients with hypercholesterolemia. Circulation. 1995;89:2519–2524.[Abstract/Free Full Text]

43. Guetta V, Cannon RO III. Cardiovascular effects of estrogen and lipid lowering therapies in postmenopausal women. Circulation. 1996;93:1928–1937.[Free Full Text]

This article has been cited by other articles:

				M. Abu-Taha, C. Rius, C. Hermenegildo, I. Noguera, J.-M. Cerda-Nicolas, A. C. Issekutz, P. J. Jose, J. Cortijo, E. J. Morcillo, and M.-J. Sanz Menopause and Ovariectomy Cause a Low Grade of Systemic Inflammation that May Be Prevented by Chronic Treatment with Low Doses of Estrogen or Losartan J. Immunol., July 15, 2009; 183(2): 1393 - 1402. [Abstract] [Full Text] [PDF]

				K. Kublickiene, X.-D. Fu, E. Svedas, B.-M. Landgren, A. R. Genazzani, and T. Simoncini Effects in Postmenopausal Women of Estradiol and Medroxyprogesterone Alone and Combined on Resistance Artery Function and Endothelial Morphology and Movement J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1874 - 1883. [Abstract] [Full Text] [PDF]

				P. D. Patel and R. R. Arora Review: Endothelial dysfunction: A potential tool in gender related cardiovascular disease Therapeutic Advances in Cardiovascular Disease, April 1, 2008; 2(2): 89 - 100. [Abstract] [PDF]

				J. R. Meendering, B. N. Torgrimson, N. P. Miller, P. F. Kaplan, and C. T. Minson Estrogen, medroxyprogesterone acetate, endothelial function, and biomarkers of cardiovascular risk in young women Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1630 - H1637. [Abstract] [Full Text] [PDF]

				A. Sherwood, J. K. Bower, J. McFetridge-Durdle, J. A. Blumenthal, L. K. Newby, and A. L. Hinderliter Age Moderates the Short-Term Effects of Transdermal 17{beta}-Estradiol on Endothelium-Dependent Vascular Function in Postmenopausal Women Arterioscler. Thromb. Vasc. Biol., August 1, 2007; 27(8): 1782 - 1787. [Abstract] [Full Text] [PDF]

				B. N. Torgrimson, J. R. Meendering, P. F. Kaplan, and C. T. Minson Endothelial function across an oral contraceptive cycle in women using levonorgestrel and ethinyl estradiol Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2874 - H2880. [Abstract] [Full Text] [PDF]

				A. Rickenlund, M. J. Eriksson, K. Schenck-Gustafsson, and A. L. Hirschberg Oral Contraceptives Improve Endothelial Function in Amenorrheic Athletes J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3162 - 3167. [Abstract] [Full Text] [PDF]

				M. D. Iafrati, O. Vitseva, K. Tanriverdi, P. Blair, S. Rex, S. Chakrabarti, S. Varghese, and J. E. Freedman Compensatory mechanisms influence hemostasis in setting of eNOS deficiency Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1627 - H1632. [Abstract] [Full Text] [PDF]

				S. Wang, F. Paris, C. S. Sultan, R. X.-D. Song, L. M. Demers, B. Sundaram, J. Settlage, S. Ohorodnik, and R. J. Santen Recombinant Cell Ultrasensitive Bioassay for Measurement of Estrogens in Postmenopausal Women J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1407 - 1413. [Abstract] [Full Text] [PDF]

				M. L. Bots, J. Westerink, T. J. Rabelink, and E. J.P. de Koning Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response Eur. Heart J., February 2, 2005; 26(4): 363 - 368. [Abstract] [Full Text] [PDF]

				S. C. Halligan, B. Murtagh, R. J. Lennon, G. M. Pumper, V. Mathew, S. T. Higano, and A. Lerman Effect of Long-term Hormone Replacement Therapy on Coronary Endothelial Function in Postmenopausal Women Mayo Clin. Proc., December 1, 2004; 79(12): 1514 - 1520. [Abstract] [PDF]

				K. K. Koh and I. Sakuma Should Progestins Be Blamed for the Failure of Hormone Replacement Therapy to Reduce Cardiovascular Events in Randomized Controlled Trials? Arterioscler. Thromb. Vasc. Biol., July 1, 2004; 24(7): 1171 - 1179. [Abstract] [Full Text] [PDF]

				C. Duvernoy, J. Martin, K. Briesmiester, A. Bargardi, O. Muzik, and L. Mosca Myocardial Blood Flow and Flow Reserve in Response to Hormone Therapy in Postmenopausal Women with Risk Factors for Coronary Disease J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2783 - 2788. [Abstract] [Full Text] [PDF]

				L. D. Kirwan, N. J. MacLusky, H. M. Shapiro, B. L. Abramson, S. G. Thomas, and J. M. Goodman Acute and Chronic Effects of Hormone Replacement Therapy on the Cardiovascular System in Healthy Postmenopausal Women J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1618 - 1629. [Abstract] [Full Text] [PDF]

				J. M. Orshal and R. A. Khalil Gender, sex hormones, and vascular tone Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2004; 286(2): R233 - R249. [Abstract] [Full Text] [PDF]

				J. Widder, T. Pelzer, C. von Poser-Klein, K. Hu, V. Jazbutyte, K.-H. Fritzemeier, C. Hegele-Hartung, L. Neyses, and J. Bauersachs Improvement of Endothelial Dysfunction by Selective Estrogen Receptor-{alpha} Stimulation in Ovariectomized SHR Hypertension, November 1, 2003; 42(5): 991 - 996. [Abstract] [Full Text] [PDF]

				M. E. Widlansky, N. Gokce, J. F. Keaney Jr, and J. A. Vita The clinical implications of endothelial dysfunction J. Am. Coll. Cardiol., October 1, 2003; 42(7): 1149 - 1160. [Abstract] [Full Text] [PDF]

				K. K. Koh, J. Y. Ahn, D. K. Jin, B.-K. Yoon, H. S. Kim, D. S. Kim, W. C. Kang, S. H. Han, I. S. Choi, and E. K. Shin Significant Differential Effects of Hormone Therapy or Tibolone on Markers of Cardiovascular Disease in Postmenopausal Women: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study Arterioscler. Thromb. Vasc. Biol., October 1, 2003; 23(10): 1889 - 1894. [Abstract] [Full Text] [PDF]

				M. E. Widlansky, D. T. Price, N. Gokce, R. T. Eberhardt, S. J. Duffy, M. Holbrook, C. Maxwell, J. Palmisano, J. F. Keaney Jr, J. D. Morrow, et al. Short- and Long-Term COX-2 Inhibition Reverses Endothelial Dysfunction in Patients With Hypertension Hypertension, September 1, 2003; 42(3): 310 - 315. [Abstract] [Full Text] [PDF]

				K. A. Griffiths, M. A. Sader, M. R. Skilton, J. A. Harmer, and D. S. Celermajer Effects of raloxifene on endothelium-dependent dilation, lipoproteins, and markers of vascular function in postmenopausal women with coronary artery disease J. Am. Coll. Cardiol., August 20, 2003; 42(4): 698 - 704. [Abstract] [Full Text] [PDF]

				B. H. Welter, E. L. Hansen, K. J. Saner, Y. Wei, and T. M. Price Membrane-bound Progesterone Receptor Expression in Human Aortic Endothelial Cells J. Histochem. Cytochem., August 1, 2003; 51(8): 1049 - 1055. [Abstract] [Full Text]

				F. M Steinberg, N. L Guthrie, A. C Villablanca, K. Kumar, and M. J Murray Soy protein with isoflavones has favorable effects on endothelial function that are independent of lipid and antioxidant effects in healthy postmenopausal women Am. J. Clinical Nutrition, July 1, 2003; 78(1): 123 - 130. [Abstract] [Full Text] [PDF]

				J. T. Kuvin and R. H. Karas Clinical Utility of Endothelial Function Testing: Ready for Prime Time? Circulation, July 1, 2003; 107(25): 3243 - 3247. [Full Text] [PDF]

				J. R. Stratton, W. C. Levy, J. H. Caldwell, A. Jacobson, J. May, D. Matsuoka, and K. Madden Effects of aging on cardiovascular responses to parasympathetic withdrawal J. Am. Coll. Cardiol., June 4, 2003; 41(11): 2077 - 2083. [Abstract] [Full Text] [PDF]

				A. Wakatsuki, Y. Okatani, T. Fukaya, M. B. Sorensen, P. Collins, P. J.L. Ong, C. M. Webb, C. S. Hayward, E. A. Asbury, P. D. Gatehouse, et al. Long-Term Use of Contraceptive Depot Medroxyprogesterone Acetate in Young Women Impairs Arterial Endothelial Function Assessed by Cardiovascular Magnetic Resonance * Response Circulation, May 27, 2003; 107 (20): e197 - e197. [Full Text] [PDF]

				J. E. Freedman High-fat diets and cardiovascular disease: Are nutritional supplements useful? J. Am. Coll. Cardiol., May 21, 2003; 41(10): 1750 - 1752. [Full Text] [PDF]

				S. Fenkci, V. Fenkci, M. Yilmazer, M. Serteser, and T. Koken Effects of short-term transdermal hormone replacement therapy on glycaemic control, lipid metabolism, C-reactive protein and proteinuria in postmenopausal women with type 2 diabetes or hypertension Hum. Reprod., April 1, 2003; 18(4): 866 - 870. [Abstract] [Full Text] [PDF]

				M. Sanada, Y. Higashi, K. Nakagawa, M. Tsuda, I. Kodama, M. Kimura, K. Chayama, and K. Ohama A Comparison of Low-Dose and Standard-Dose Oral Estrogen on Forearm Endothelial Function in Early Postmenopausal Women J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1303 - 1309. [Abstract] [Full Text] [PDF]

				D. Rachon, A. Wakatsuki, Y. Okatani, N. Ikenoue, and T. Fukaya The Antiinflammatory Properties of Medroxyprogesterone Acetate * Response Circulation, November 26, 2002; 106 (22): e185 - e185. [Full Text] [PDF]

				V. Stangl, G. Baumann, and K. Stangl Coronary atherogenic risk factors in women Eur. Heart J., November 2, 2002; 23(22): 1738 - 1752. [Full Text] [PDF]

				M. Sanada, Y. Higashi, K. Nakagawa, M. Tsuda, I. Kodama, M. Kimura, K. Chayama, and K. Ohama Hormone Replacement Effects on Endothelial Function Measured in the Forearm Resistance Artery in Normocholesterolemic and Hypercholesterolemic Postmenopausal Women J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4634 - 4641. [Abstract] [Full Text] [PDF]

				M. B. Sorensen, P. Collins, P. J.L. Ong, C. M. Webb, C. S. Hayward, E. A. Asbury, P. D. Gatehouse, A. G. Elkington, G. Z. Yang, A. Kubba, et al. Long-Term Use of Contraceptive Depot Medroxyprogesterone Acetate in Young Women Impairs Arterial Endothelial Function Assessed by Cardiovascular Magnetic Resonance Circulation, September 24, 2002; 106(13): 1646 - 1651. [Abstract] [Full Text] [PDF]

				K. K. Koh, J. Y. Ahn, D. K. Jin, B.-K. Yoon, H. S. Kim, D. S. Kim, M.-S. Shin, J. W. Son, I. S. Choi, and E. K. Shin Effects of Continuous Combined Hormone Replacement Therapy on Inflammation in Hypertensive and/or Overweight Postmenopausal Women Arterioscler. Thromb. Vasc. Biol., September 1, 2002; 22(9): 1459 - 1464. [Abstract] [Full Text] [PDF]

				K. K. Koh Effects of estrogen on the vascular wall: vasomotor function and inflammation Cardiovasc Res, September 1, 2002; 55(4): 714 - 726. [Full Text] [PDF]

				M. G. Modena, L. Bonetti, F. Coppi, F. Bursi, and R. Rossi Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women J. Am. Coll. Cardiol., August 7, 2002; 40(3): 505 - 510. [Abstract] [Full Text] [PDF]

				C. S. Hayward, M. Kraidly, C. M. Webb, and P. Collins Assessment of endothelial function using peripheral waveform analysis: A clinical application J. Am. Coll. Cardiol., August 7, 2002; 40(3): 521 - 528. [Abstract] [Full Text] [PDF]

				J. E Rossouw Hormones, genetic factors, and gender differences in cardiovascular disease Cardiovasc Res, February 15, 2002; 53(3): 550 - 557. [Full Text] [PDF]

				M. A. Sader and D. S. Celermajer Endothelial function, vascular reactivity and gender differences in the cardiovascular system Cardiovasc Res, February 15, 2002; 53(3): 597 - 604. [Full Text] [PDF]

				S. P. Schulman, D. R. Thiemann, P. Ouyang, N. C. Chandra, D. S. Schulman, S. E. Reis, M. Terrin, S. Forman, C. Piva de Albuquerque, R. D. Bahr, et al. Effects of acute hormone therapy on recurrent ischemia in postmenopausal women with unstable angina J. Am. Coll. Cardiol., January 16, 2002; 39(2): 231 - 237. [Abstract] [Full Text] [PDF]

				M. C. Corretti, T. J. Anderson, E. J. Benjamin, D. Celermajer, F. Charbonneau, M. A. Creager, J. Deanfield, H. Drexler, M. Gerhard-Herman, D. Herrington, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: A report of the International Brachial Artery Reactivity Task Force J. Am. Coll. Cardiol., January 16, 2002; 39(2): 257 - 265. [Abstract] [Full Text] [PDF]

				H. Kawano, T. Motoyama, M. Ohgushi, K. Kugiyama, H. Ogawa, and H. Yasue Menstrual Cyclic Variation of Myocardial Ischemia in Premenopausal Women with Variant Angina Ann Intern Med, December 4, 2001; 135(11): 977 - 981. [Abstract] [Full Text] [PDF]

				P. Voci and F. Pizzuto Coronary flow: how far can we go with echocardiography? J. Am. Coll. Cardiol., December 1, 2001; 38(7): 1885 - 1887. [Full Text] [PDF]

				J. A. Vita and J. F. Keaney Jr Hormone Replacement Therapy and Endothelial Function: The Exception That Proves the Rule? Arterioscler. Thromb. Vasc. Biol., December 1, 2001; 21(12): 1867 - 1869. [Full Text] [PDF]

				J. Levenson, F. Pessana, J. Gariepy, R. Armentano, and A. Simon Gender differences in wall shear-mediated brachial artery vasoconstriction and vasodilation J. Am. Coll. Cardiol., November 15, 2001; 38(6): 1668 - 1674. [Abstract] [Full Text] [PDF]

				M Sitges, M Heras, E Roig, M Duran, M Masotti, M.J Zurbano, M Roque, and G Sanz Acute and mid-term combined hormone replacement therapy improves endothelial function in post-menopausal women with angina and angiographically normal coronary arteries Eur. Heart J., November 2, 2001; 22(22): 2116 - 2124. [Abstract] [PDF]

				C. K. Roberts, N. D. Vaziri, and R. J. Barnard Protective effects of estrogen on gender-specific development of diet-induced hypertension J Appl Physiol, November 1, 2001; 91(5): 2005 - 2009. [Abstract] [Full Text] [PDF]

				A. Wakatsuki, Y. Okatani, N. Ikenoue, and T. Fukaya Effect of Medroxyprogesterone Acetate on Endothelium-Dependent Vasodilation in Postmenopausal Women Receiving Estrogen Circulation, October 9, 2001; 104(15): 1773 - 1778. [Abstract] [Full Text] [PDF]

				M. Imamura, S. Biro, T. Kihara, S. Yoshifuku, K. Takasaki, Y. Otsuji, S. Minagoe, Y. Toyama, and C. Tei Repeated thermal therapy improves impaired vascular endothelial function in patients with coronary risk factors J. Am. Coll. Cardiol., October 1, 2001; 38(4): 1083 - 1088. [Abstract] [Full Text] [PDF]

				M. Sanada, Y. Higashi, K. Nakagawa, S. Sasaki, I. Kodama, M. Tsuda, N. Nagai, and K. Ohama Relationship between the angiotensin-converting enzyme genotype and the forearm vasodilator response to estrogen replacement therapy in postmenopausal women J. Am. Coll. Cardiol., May 1, 2001; 37(6): 1529 - 1535. [Abstract] [Full Text] [PDF]

				K. K. Koh, D. K. Jin, S. H. Yang, S.-K. Lee, H. Y. Hwang, M. H. Kang, W. Kim, D. S. Kim, I. S. Choi, and E. K. Shin Vascular Effects of Synthetic or Natural Progestagen Combined With Conjugated Equine Estrogen in Healthy Postmenopausal Women Circulation, April 17, 2001; 103(15): 1961 - 1966. [Abstract] [Full Text] [PDF]

				P. S. Jhund, N. Dawson, A. P. Davie, N. Sattar, J. Norrie, K. P. J. O'Kane, and J. J. V. McMurray Attenuation of endothelin-1 induced vasoconstriction by 17{beta} estradiol is not sustained during long-term therapy in postmenopausal women with coronary heart disease J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1367 - 1373. [Abstract] [Full Text] [PDF]

				P. Angerer, S. Stork, W. Kothny, P. Schmitt, and C. von Schacky Effect of Oral Postmenopausal Hormone Replacement on Progression of Atherosclerosis : A Randomized, Controlled Trial Arterioscler. Thromb. Vasc. Biol., February 1, 2001; 21(2): 262 - 268. [Abstract] [Full Text] [PDF]

				S. Wassmann, A. T. Baumer, K. Strehlow, M. van Eickels, C. Grohe, K. Ahlbory, R. Rosen, M. Bohm, and G. Nickenig Endothelial Dysfunction and Oxidative Stress During Estrogen Deficiency in Spontaneously Hypertensive Rats Circulation, January 23, 2001; 103(3): 435 - 441. [Abstract] [Full Text] [PDF]

				H. A. Walker, T. S. Dean, T. A. B. Sanders, G. Jackson, J. M. Ritter, and P. J. Chowienczyk The Phytoestrogen Genistein Produces Acute Nitric Oxide-Dependent Dilation of Human Forearm Vasculature With Similar Potency to 17{beta}-Estradiol Circulation, January 16, 2001; 103(2): 258 - 262. [Abstract] [Full Text] [PDF]

				G. M. C. Rosano, C. M. Webb, S. Chierchia, G. Luigi Morgani, M. Gabraele, P. M. Sarrel, D. de Ziegler, and P. Collins Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2154 - 2159. [Abstract] [Full Text] [PDF]

				K. J. Mather, E. G. Norman, J. C. Prior, and T. G. Elliott Preserved Forearm Endothelial Responses with Acute Exposure to Progesterone: A Randomized Cross-Over Trial of 17-{beta} Estradiol, Progesterone, and 17-{beta} Estradiol with Progesterone in Healthy Menopausal Women J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4644 - 4649. [Abstract] [Full Text]

				S. Vehkavaara, J. Westerbacka, T. Hakala-Ala-Pietilä, A. Virkamäki, O. Hovatta, and H. Yki-Järvinen Effect of Estrogen Replacement Therapy on Insulin Sensitivity of Glucose Metabolism and Preresistance and Resistance Vessel Function in Healthy Postmenopausal Women J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4663 - 4670. [Abstract] [Full Text]

				S. Vehkavaara, T. Hakala-Ala-Pietila, A. Virkamaki, R. Bergholm, C. Ehnholm, O. Hovatta, M.-R. Taskinen, and H. Yki-Jarvinen Differential Effects of Oral and Transdermal Estrogen Replacement Therapy on Endothelial Function in Postmenopausal Women Circulation, November 28, 2000; 102(22): 2687 - 2693. [Abstract] [Full Text] [PDF]

				L. Mosca The Role of Hormone Replacement Therapy in the Prevention of Postmenopausal Heart Disease Arch Intern Med, August 14, 2000; 160(15): 2263 - 2272. [Abstract] [Full Text] [PDF]

				D. M. Herrington, B. E. Pusser, W. A. Riley, T. Y. Thuren, K. B. Brosnihan, E. A. Brinton, and D. B. MacLean Cardiovascular Effects of Droloxifene, a New Selective Estrogen Receptor Modulator, in Healthy Postmenopausal Women Arterioscler. Thromb. Vasc. Biol., June 1, 2000; 20(6): 1606 - 1612. [Abstract] [Full Text] [PDF]

				A. Virdis, L. Ghiadoni, S. Pinto, M. Lombardo, F. Petraglia, A. Gennazzani, S. Buralli, S. Taddei, and A. Salvetti Mechanisms Responsible for Endothelial Dysfunction Associated With Acute Estrogen Deprivation in Normotensive Women Circulation, May 16, 2000; 101(19): 2258 - 2263. [Abstract] [Full Text] [PDF]

				C. S. Hayward, R. P. Kelly, and P. Collins The roles of gender, the menopause and hormone replacement on cardiovascular function Cardiovasc Res, April 1, 2000; 46(1): 28 - 49. [Full Text] [PDF]

				A. M. McNeill, N. Kim, S. P. Duckles, D. N. Krause, and H. A. Kontos Chronic Estrogen Treatment Increases Levels of Endothelial Nitric Oxide Synthase Protein in Rat Cerebral Microvessels • Editorial Comment Stroke, October 1, 1999; 30(10): 2186 - 2190. [Abstract] [Full Text] [PDF]

				G. A. Figtree, Y.-q. Lu, C. M. Webb, and P. Collins Raloxifene Acutely Relaxes Rabbit Coronary Arteries In Vitro by an Estrogen Receptor–Dependent and Nitric Oxide–Dependent Mechanism Circulation, September 7, 1999; 100(10): 1095 - 1101. [Abstract] [Full Text] [PDF]

				T. J. Anderson Assessment and treatment of endothelial dysfunction in humans J. Am. Coll. Cardiol., September 1, 1999; 34(3): 631 - 638. [Full Text] [PDF]

				D. Waters Cholesterol Lowering : Should It Continue to Be the Last Thing We Do? Circulation, June 29, 1999; 99(25): 3215 - 3217. [Full Text] [PDF]

				D. M. Herrington, B. L. Werbel, W. A. Riley, B. E. Pusser, and T. M. Morgan Individual and combined effects of estrogen/progestin therapy and lovastatin on lipids and flow-mediated vasodilation in postmenopausal women with coronary artery disease J. Am. Coll. Cardiol., June 1, 1999; 33(7): 2030 - 2037. [Abstract] [Full Text] [PDF]

				E. Barrett-Connor and C. Stuenkel Hormones and Heart Disease in Women: Heart and Estrogen/Progestin Replacement Study in Perspective J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 1848 - 1853. [Full Text]

				J. P Cooke The 1998 Nobel prize in Medicine: clinical implications for 1999 and beyond Vascular Medicine, May 1, 1999; 4(2): 57 - 60. [PDF]

				M. Belkin and M. Gerhard The Impact of Gender on Infrainguinal Arterial Occlusive Disease Perspectives in Vascular Surgery and Endovascular Therapy, January 1, 1999; 10(1): 123 - 138. [Abstract] [PDF]

				Hormone Therapy and Endothelium Function Journal Watch Women's Health, November 1, 1998; 1998(1101): 15 - 15. [Full Text]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gerhard, M. Articles by Creager, M. A. Search for Related Content PubMed PubMed Citation Articles by Gerhard, M. Articles by Creager, M. A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ESTRADIOL PROGESTERONE