Cardiovascular responses of perimenopausal women to hormonal replacement therapy

doi:10.1016/S0002-9378(00)70485-6

American Journal of Obstetrics and Gynecology

Volume 182, Issue 1, January 2000, Pages 17-22

https://doi.org/10.1016/S0002-9378(00)70485-6 Get rights and content

Abstract

Objective: This study was undertake to test the hypothesis that hormone replacement therapy alters cardiovascular function during the first several months of therapy. Study Design: Serial estimates of blood pressure, heart rate, stroke volume, and venous capacitance were obtained before and at 1, 5, 9, and 21 weeks after the beginning of hormone replacement therapy with daily estradiol and intermittent norethindrone. Measurements were performed by means of electrocardiography, automated blood pressure measurement (Dynamap; Critikon Company LLC, Tampa, Fla), echocardiography, and plethysmography. Results: Hormone replacement therapy did not alter heart rate, blood pressure, or venous capacitance. End-diastolic volume and stroke volume were unchanged after 1 week of hormone replacement therapy but rose thereafter. After 5 weeks of hormone replacement end-diastolic volume and stroke volume were increased by 13 ± 5 mL and 9 ± 2 mL, respectively, and after 9 weeks the increases totaled 23 ± 5 mL and 17 ± 3 mL, respectively. As a result cardiac output rose progressively to a level 1.1 ± 0.3 L/min (18%) greater than pretreatment values and systemic vascular resistance fell 15%. These changes were associated with a 3-fold increase in serum estradiol levels. Conclusion: The studied regimen of hormone replacement therapy produces progressive cardiac remodeling and peripheral vasodilatation during the first 2 months of therapy. (Am J Obstet Gynecol 2000;182:17-22.)

Section snippets

Study population

The protocol was approved by the institutional review committee, and all subjects gave informed consent at the time of enrollment. Thirty healthy perimenopausal women were recruited by newspaper solicitation. After initial screening, however, only 8 of these subjects met all the inclusion criteria. The inclusion criteria included good health, an adequate echocardiographic image, no previous estrogen use, a normal result of mammography within the previous 6 months, ≥3 perimenopausal symptoms

Subject characteristics

On the basis of their occupations all women were classified as coming from middle and upper socioeconomic classes. All women were in good health. The average subject was 52 years old (range, 50-55 years), had a height of 159 ± 5 cm (range, 150-165 cm), and weighed 67 ± 6 kg (range, 53.0-92.6 kg). Body mass index values ranged between 20.5 and 33.7 kg/m² (mean, 26.4 kg/m²; median, 25.3 kg/m²), and estimates of percentage of body fat from skinfold thicknesses ranged from 21% to 36% (mean, 28%;

Comment

As mentioned earlier, most previous studies demonstrated that hormone replacement therapy has direct structural or functional cardiovascular effects, whereas a recent study that used a randomized, blinded, crossover design did not agree.11, 12, 13, 14, 15, 20, 21, 22 The findings of this study support the former point of view and indicate that both the structural changes (end-diastolic volume and peripheral resistance) and the functional changes (stroke volume and cardiac output) begin in the

Acknowledgements

We thank the companies Kranzbuehler and PeroMed (Dr Fischbach) for their technical support. We also thank the chairman of our department, Dr W. Künzel, for his support to implement a cardiovascular laboratory in the Department of Obstetrics and Gynecology at the University of Giessen.

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Cited by (25)

Aerobic training abolishes ambulatory blood pressure increase induced by estrogen therapy: A double blind randomized clinical trial
2011, Maturitas
Citation Excerpt :
In regard to the cardiovascular system, the post-menopausal period is accompanied by an increase in blood pressure (BP) [5]. Estrogen therapy produces controversial results in this aspect, increasing [6,7], decreasing [8,9] or not affecting [10,11] BP. Part of this variability is attributable to women's ages.
Emerging data reveal that oral estrogen therapy can increase clinic blood pressure (BP) in post-menopausal women; however, it is important to establish its effects on ambulatory BP, which is a better predictor for target-organ damage. Besides estrogen therapy, aerobic training is widely recommended for post-menopausal women, and it can decrease ambulatory BP levels. This study was designed to evaluate the effect of aerobic training and estrogen therapy on the ambulatory BP of post-menopausal women. Forty seven healthy hysterectomized women were randomly divided (in a double-blind manner) into 4 groups: placebo–control (PLA–CO = 12), estrogen therapy–control (ET–CO = 14), placebo–aerobic training (PLA–AT = 12), and estrogen therapy–aerobic training (ET–AT = 09). The ET groups received estradiol valerate (1 mg/day) and the AT groups performed cycle ergometer, 3×/week at moderate intensity. Hormonal status (blood analysis), maximal cardiopulmonary exercise test (VO₂ peak) and ambulatory BP (24-h, daytime and nighttime) was evaluated before and 6 months after interventions. A significant increase in VO₂ peak was observed only in women who participated in aerobic training groups (+4.6 ± 1.0 ml kg⁻¹ min⁻¹, P = 0.00). Follicle-stimulating hormone was a significant decreased in the ET groups (−18.65 ± 5.19 pg/ml, P = 0.00), and it was accompanied by an increase in circulating estrogen (56.1 ± 6.6 pg/ml). A significant increase was observed in the ET groups for daytime (P = 0.01) and nighttime systolic BP (P = 0.01), as well as nighttime diastolic BP (P = 0.02). However, daytime diastolic BP was increased only in the ET–CO group (+3.4 ± 1.2 mmHg, P = 0.04), and did not change in any other groups. No significant effect was found in ambulatory heart rate. In conclusion, aerobic training abolished the increase of daytime ambulatory BP induced by estrogen therapy in hysterectomized, healthy, normotensive and postmenopausal women.
Comparison of the effects of tibolone and estrogen replacement therapy on echocardiographic basic cardiac functions in post-menopausal women: A randomized placebo controlled study
2004, Maturitas
Objectives: This study is designed to investigate and compare the effects of synthetic steroid tibolone and HRT on systolic and diastolic heart functions in post-menopausal women. Methods: This prospective, randomized placebo controlled double blind study was conducted in a university clinic. Fifty-eight non-smoking, otherwise healthy post-menopausal women who did not receive any kind of HRT at least for 3 years within the onset of menopause were included in the study. The patients were randomly allocated to either 2.5 mg per day tibolone (OD, n=18), daily combined 0.625 mg of conjugated estrogens 2.5 mg⁻¹ of medroxy progesterone acetate pill (EP, n=20) or a vitamin pill (n=20) in a double blinded fashion. Their basic systolic and diastolic functions were investigated with HP Sonos-1000 echocardiography using standard positions and windows before and 6 months after the initiation of HRT. Results: Mean age, weight, length of post-menopausal period, heart rate, systolic and diastolic pressures were similar between the groups. At the initiation of the study all groups had similar echocardiographic measurements. However, at the end of 6 months, left ventricular end-systolic and -diastolic volumes were decreased significantly compared to pretreatment and placebo in both EP and OD treated groups. (55.5±18.4 and 53.7±19.1.8 ml; 109.9±19.9 and 110.7±20.8 ml versus 74.5±14.9 and 142.7±19.1 ml, respectively; P<0.05). Improvement in diastolic functions was significant in EP/OD groups compared to pre-treatment period and the placebo groups (E/A 1.34±0.1 and 1.38±0.1 versus 1.18±0.09, deceleration time 204±11.1 and 202.8±27.1 ms versus 237.6±26.9 ms, respectively). Besides increase in left ventricular mass adjusted for height, decrease in left ventricular relative wall thickness, and systemic vascular resistance were significant in EP and OD treated groups than placebo and the pre-treatment measurements. Although improved in both OD and EP groups, the changes in systolic and diastolic functions were significantly higher in the OD treated group. Based on our preliminary results, we may conclude that both EP and OD regimens may improve cardiac performance and age related dysfunctions. Conclusion: The present results may further support that both OD and EP exert many direct effects on cardiovascular system other than metabolic changes regarding lipoproteins. The greater improvement in the OD group may be explained by its weak androgenic activity which is consistent with the in vitro data that androgens are potent relaxing agents on coronary arteries and restores cardiac myosin isoenzyme and ATPase patterns which mandates further clinical studies.
Effects of combined use of sildenafil citrate (Viagra) and 17β-estradiol on ovine coronary and uterine hemodynamics
2004, American Journal of Obstetrics and Gynecology
This study was undertaken to determine whether Viagra (Pfizer, New York, NY), a type 5 phosphodiesterase (PDE-5) inhibitor, increases baseline coronary and uterine blood flow or potentiates estrogen-induced increases in blood flow.
Seven nonpregnant ovariectomized ewes were chronically instrumented to measure blood pressure, heart rate, cardiac output, and coronary and uterine blood flow. Estradiol-17β (E2, 0.3 μg/kg) (Sigma Chemical Co, St Louis, Mo) and Viagra (50 mg) were intravenously administered separately or together and hemodynamic responses monitored.
Viagra alone rapidly decreased mean arterial pressure and cardiac output while increasing heart rate and uterine blood flow. Viagra tended to decrease coronary blood flow but not significantly. E2 by itself increased coronary and uterine blood flow over a 2-hour time course, whereas mean arterial pressure, cardiac output, and heart rate remained unchanged. Administration of E2 to animals pretreated with Viagra reversed Viagra-related decrease in cardiac output and coronary blood flow, resulting in a time-related increase in both parameters over baseline values. Viagra significantly augmented estradiol-related increases in uterine blood flow.
In our surgically menopausal ovine model, Viagra alone has a tendency to decrease baseline coronary blood flow, but the reduction does not reach statistical significance. The presence of estradiol reverses this Viagra-related negative trend and results in a net increase in coronary blood flow and cardiac output. Furthermore, Viagra significantly augments baseline and estrogen-induced increases in uterine blood flow suggesting the presence of PDE-5 in the ovine uterine vasculature.
Impact of HRT on the arterial carotid vascular tree
2004, Presse Medicale
Traitement hormonal substitutif (THS) et retentissement artériel, le sujet prête à controverse tant il n’est aujourd’hui encore qu’une vaste terre à défricher, un thème où de nouvelles questions surgissent à la croisée des différentes études jusqu’ici réalisées, et où l’incertitude est peut-être une des seules, voire la seule certitude sur laquelle s’accordent les différents spécialistes de la question.
Dans ce climat de polémique, il nous a semblé important de souligner 3 points :
- •
  les études américaines, aussi fiables soient-elles, ont été réalisées avec des estrogènes conjugués et la généralisation des résultats à d’autres types d’hormones telles que celles prescrites en Europe est peut-être hâtive;
- •
  d’autres facteurs de risque sont à prendre en considération dans l’éventuelle potentialisation du risque induit par tel ou tel traitement;
- •
  les risques vasculaires veineux et artériels ne reposent pas sur les mêmes mécanismes physiopathologiques. Dès lors, le risque accru dans l’un ou l’autre de ces réseaux n’est peut-être pas à fusionner non plus.
Hormone replacement therapy (HRT) and arterial impact, this is a controversial subject since it is still a large field that needs weeding, a theme in which new questions are raised by the cross results of various studies conducted, and in which doubt is perhaps one of, or even the only, certitude that all the various specialists agree on.
In this controversial climat, we feel that three important points should be underlined:
- •
  the American studies, however reliable they may be, have been conducted with conjugated estrogens and the generalisation to the results of other types of hormones such as those prescribed in Europe is perhaps a little hasty
- •
  other factors of risk should be taken into consideration in the eventual potentialisation of the risk induced by such treatment
- •
  the venous and arterial vascular risks are not based on the same physiopathological mechanisms. Hence the increased risk in one or the other network system should perhaps not be amalgalmated either.
Managing menopausal symptoms after the women's health initiative
2004, Journal of Midwifery and Women's Health
Until the results of the Women’s Health Initiative (WHI) were released in July 2002, hormone replacement therapy (HRT) had been thought to be the most effective way to manage unwanted menopausal symptoms and to prevent long-term health problems associated with aging. The results of the WHI, showing that HRT is less beneficial and associated with more risks than previously thought, has complicated the management of unwanted menopausal symptoms. This article discusses the effectiveness of HRT and other modalities used to relieve menopausal symptoms and discusses how to choose an HRT product to match specific menopausal complaints and provide maximum safety.
Effect of postmenopausal hormone replacement therapy on cardiovascular performance
2004, Maturitas
Summary: Postmenopausal hormone replacement therapy (HRT) has usually been evaluated the relationship with atherosclerotic disease, whereas its effect on direct cardiac functions hasn't been investigated in detail. This study was planned to investigate the long-term effects of HRT on cardiac functions and exercise performance. Methods: Thirty-six postmenopausal women (mean age: 51±4 years, 39–60 years) were prospectively analyzed with pulsed wave Doppler echocardiography and symptom-limited exercise stress test before HRT (oral 0.625 mg conjugated estrogen and 2.5 mg medroxyprogesteron acetate/day), and at the third and the sixth months. The effect of HRT on left ventricular ejection fraction (EF), early filling velocity (E wave) and late filling velocity (A wave), E wave deceleration time (EDT), E/A ratio, myocardial performance index (MPI), exercise duration and METS changes were examined. Results: HRT did not significantly alter the left ventricular EF. At the third month of HRT, there was an insignificant increase in E wave, EDT, and E/A ratio, whereas an insignificant decrease was noted in MPI (P>0.05). However, at the sixth month of HRT, these changes became significant (68±12 vs. 75±13 cm/s, P<0.01; 171±24 vs. 184±14 ms, P<0.01; 1.01±0.23 vs. 1.11±0.27, P<0.01, and 44±9 vs. 39±8%, P<0.001, respectively). On the other hand, exercise duration and exercise METS values showed significant improvements at the third month of HRT (423±104 vs. 482±104 s, P<0.001; 8.2±1.7 vs. 9.1±2 METS, P<0.001). These improvements also continued at the sixth month of HRT. In conclusion, postmenopausal HRT leads to a progressive improvement on left ventricular function parameters, and in parallel, in exercise performance.

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^☆: Supported by the Alexander von Humboldt Foundation and the German Society for Obstetrics and Gynecology (Nourypharma-Förderungsstipendium 1992 and 1994).

^☆☆: Reprint requests: Parvis Kamali, MD, Abt. für Gynäkologie und Geburtshilfe, Justus-Liebig-Universität Giessen, Klinikstr. 32, D-35392 Giessen, Germany.

^★: 0002-9378/2000 $12.00 + 06/1/102705

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Cardiovascular responses of perimenopausal women to hormonal replacement therapy☆,☆☆,★

Abstract

Section snippets

Study population

Subject characteristics

Comment

Acknowledgements

Am J Obstet Gynecol

Arteriosclerosis

Eur J Obstet Gynecol Reprod Biol

Am J Cardiol

Am J Cardiol

Obstet Gynecol

Am J Obstet Gynecol

Chest

The epidemiology of cardiovascular disease in postmenopausal women

Ann N Y Acad Sci

Increased incidence of coronary heart disease in women castrated prior to menopause

Arch Intern Med

Hormone therapy to prevent disease and prolong life in postmenopausal women

Ann Intern Med

Decreased mortality in users of estrogen replacement therapy

Arch Intern Med

Effect of postmenopausal estrogen replacement on the concentration and metabolism of plasma lipoproteins

N Engl J Med