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CLINICAL STUDY: CORONARY BLOOD FLOW

Modulation of coronary flow velocity reserve by gender, menstrual cycle and hormone replacement therapy

Kumiko Hirata, MD^*, Kenei Shimada, MD^*,*, Hiroyuki Watanabe, MD^*, Takashi Muro, MD^*, Minoru Yoshiyama, MD^*, Kazuhide Takeuchi, MD^*, Takeshi Hozumi, MD and Junichi Yoshikawa, MD, FACC^*

^* Department of Internal Medicine and Cardiology, Graduate School of Medicine, Osaka City University Medical School, Osaka, Japan
Division of Cardiology, Department of Medicine, Columbia University, New York, New York, USA

Manuscript received April 13, 2001; revised manuscript received July 18, 2001, accepted August 22, 2001.

^* Reprint requests and correspondence: Dr. Kenei Shimada, Department of Internal Medicine and Cardiology, Graduate School of Medicine, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
shimadak{at}med.osaka-cu.ac.jp

OBJECTIVES

The purpose of this study was twofold: 1) to examine the relationship between menstrual cycle and coronary flow velocity reserve (CFVR) in young healthy women, and 2) to evaluate the effect of hormone replacement therapy by estrogen on CFVR in postmenopausal women, using transthoracic color Doppler echocardiography (TTCDE).

BACKGROUND

Although the incidence of cardiovascular disease is lower in women before menopause compared with men, postmenopausal women have an incidence of coronary artery disease similar to that of men of the same age. This is mainly dependent upon estrogen deficiency. However, no clinical report has yet examined the effect of estrogen on CFVR, which is one index of coronary microcirculation.

METHODS

We examined 15 male and both 15 premenopausal and 10 postmenopausal female healthy volunteers. We measured coronary flow velocity of the left anterior descending coronary artery at baseline and hyperemic conditions during adenosine triphosphate infusion by TTCDE and determined CFVR. Each premenopausal woman was studied two times (menstrual [M] and follicular [F] phases) in one menstrual cycle. Fifteen men were also studied at a time corresponding to women’s menstrual cycle. The postmenopausal women were studied before and two hours after oral administration of conjugated estrogen (CE).

RESULTS

Serum 17ß-estradiol level in premenopausal women increased in the F phase and decreased to the same levels as in men, as in the M phase and as in postmenopausal women (123 ± 9 pg/ml vs. 28 ± 6 pg/ml, 25 ± 9 pg/ml and 19 ± 11 pg/ml; p < 0.0001, respectively). The CFVR increased in the F phase compared with that in the M phase (4.8 ± 0.4 vs. 3.7 ± 0.8, p < 0.0001). We found that CFVR in men remained unchanged (3.7 ± 0.6 vs. 3.8 ± 0.5). After CE administration, CFVR increased compared with baseline in postmenopausal women (4.1 ± 0.8 vs. 3.4 ± 0.8, p < 0.005).

CONCLUSIONS

In premenopausal women, CFVR determined by TTCDE varied during the menstrual cycle, and in postmenopausal women, CFVR increased after acute estrogen replacement.

Abbreviations and Acronyms   ANOVA = analysis of variance   ATP = adenosine triphosphate   CE = conjugated estrogen   CFVR = coronary flow velocity reserve   F = follicular   HDL = high-density lipoprotein   LAD = left anterior descending coronary artery   LDL = low-density lipoprotein   M = menstrual   MDV = mean diastolic velocities   NO = nitric oxide   TTDE = transthoracic color Doppler echocardiography

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