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Postmenopausal Hormone Replacement Therapy and Cardiovascular Mortality in Central-Eastern Europe

^a Departments of Obstetrics/Gynecology, Semmelweis Medical School, Budapest, Hungary
^b Departments of Medicine II, Semmelweis Medical School, Budapest, Hungary
^c Section of Endocrinology, VA Medical Center, Phoenix, Arizona

Zoltan Vajo, VA Medical Center, Section of Endocrinology, 650 E. Indian School Road, 111E, Phoenix, AZ 85012 E-mail: zvajo{at}usa.net.

Decision Editor: William B. Ershler, MD

	Abstract

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Background. The leading cause of death among elderly women is cardiovascular (CV) disease in the United States and in Western Europe as well. The protective effect of postmenopausal hormone replacement therapy (HRT) on coronary heart disease has been verified in epidemiologic studies. There are no data available on the rate of HRT use in Eastern Europe. Our goals were to study the rates of HRT in Eastern Europe, to compare them to those of the United States and Western Europe, as well as to compare their CV mortality rates.

Methods. The use of HRT in Eastern Europe was calculated from sales records obtained from all pharmaceutical companies that ship HRT preparations to the given area. Data on HRT in Western countries were taken from the literature. Mortality rates were obtained from the World Health Organization.

Results. The rate (mean ± SD) of HRT in Eastern Europe was 2.88 ± 2.67%, whereas 12.67 ± 9.97% in Western Europe and the United States, p < .05. The cardiovascular mortality rate per 100,000 women older than 45 years in Eastern Europe was higher (1766 ± 158.3) than in the Western countries (1155 ± 164.1, p < .001).

Conclusions. The rate of HRT is markedly lower, whereas CV mortality rates are notably higher in Eastern Europe than in the United States or Western Europe. Because HRT seems to be underutilized in Eastern Europe, to increase its use might be an important tool to improve CV mortality rates. However, due to the risks associated with HRT, other measures to prevent coronary heart disease, such as smoking cessation programs, and other efforts should also be considered in Eastern Europe.

THE leading cause of death among women is cardiovascular (CV) disease in the United States and in Western Europe as well ^(1)(2)(3)(4).

Cardiovascular deaths in females occur almost only after menopause. Besides aging, this is at least in part due to the dramatic decrease of estrogen levels. The protective effect of postmenopausal hormone replacement therapy (HRT) on coronary heart disease and perhaps to some extent on cerebrovascular disease has been verified in epidemiologic studies ⁽⁵⁾⁽⁶⁾. The relative risk of cardiovascular diseases decreases by about 50% in women currently using HRT as compared with postmenopausal women without estrogen treatment ⁽⁶⁾. Therefore, the use of HRT can have a significant impact on the overall mortality rates in this subpopulation.

Unfortunately, there are little or no data available on the spread of HRT use in Eastern European countries. Our goals were to study the rates of HRT in Eastern European countries, to compare them to those of the United States and Western Europe, as well as to compare their CV mortality rates.

	Methods

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Data on prescribing hormone replacement therapy in the Czech Republic, Bulgaria, Romania, Hungary, and Poland were measured indirectly. All drug manufacturers who ship HRT products to these countries were contacted and asked to provide their shipment records. The records were then used to estimate the number of women on HRT for the year 1996. These figures are total national costs of each product based on annual sales. The number of original packs of an HRT product used in each country was calculated by dividing the total national sales of the product by the local unit cost of the product pack. Then the number of women treatment years of the HRT preparation was calculated by dividing the number of original packs used by the number of original packs which would be required to treat a woman continuously for 1 year. The number of women treated by individual preparations was summed up to calculate the total number of women currently on HRT. Finally, the proportion of women taking HRT was calculated by dividing the number of women treatment years by the eligible population and expressing the result as a percentage. This method has been validated and the details of this calculation are described elsewhere ⁽⁷⁾. Because this study focused on hormone replacement therapy and cardiovascular mortality rates, only the use of systemic HRT preparations (oral and transdermal products) was evaluated, ignoring data on locally active HRT (vaginal creams, ovules, and low-dose oestriol tablets). The cardiovascular mortality rates and the number of women aged 45–70 were obtained from national mortality statistics of these countries, provided by World Health Statistics Annuals (World Health Organization [WHO] Geneva) ⁽²⁾. Data on HRT in Western European countries (Italy, the Netherlands, United Kingdom, Sweden, and West Germany) and the United States were taken from the literature ^{(1)(7)(8)(9)(10)(11)(12)(13)}. Data for West Germany were obtained for the last year before it was reunited with East Germany.

	Results

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Fig. 1 shows the use of hormone replacement therapy among postmenopausal women in Poland, Hungary, Romania, Bulgaria, and the Czech Republic, and, for comparison, data from Italy, the Netherlands, United Kingdom, Sweden, United States, and West Germany. The percentage of postmenopausal women using HRT was found to be 2.13% in Hungary, 6% in the Czech Republic, 5% in Poland, and less than 1% in Romania and Bulgaria. The rate of HRT among postmenopausal women was 25% in West Germany, 24% in the United States, 11% in the United Kingdom and in Sweden, while 4% in the Netherlands, and 1% in Italy (Fig. 1). The rate (mean ± SD) of HRT in Eastern Europe was 2.88 ± 2.67% and 12.67 ± 9.97% in the other group, p < .05.

View larger version (31K): [in this window] [in a new window]   Figure 1. Rate of HRT in percentage of postmenopausal women in Eastern Europe and in Western Europe and the United States. BG: Bulgaria; RO: Romania; HU: Hungary; CZ: Czech Republic; PL: Poland; I: Italy; NL: The Netherlands; GB: Great Britain; S: Sweden; US: United States; D: West Germany. *p < .05.

	Discussion

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Our study showed that the rate of HRT is markedly lower in Eastern European countries than in the United States or Western Europe. It is interesting to note that the CV mortality rate in Eastern Europe is notably higher than in Western Europe or in the United States. More importantly, the CV mortality rates in Western Europe and the United States have been declining in the last decade, whereas it remained the same or increased in Eastern Europe ^(2)(3)(4).

Discrepancies between HRT and CV mortality rates (e.g., although the HRT rate is relatively high in Sweden, the CV mortality of postmenopausal women is lower in Italy, which has a lower HRT rate) might be explained by local differences in other CV risk factors, such as smoking, animal fat intake, serum lipid levels, exercise, obesity, and others. Therefore, it is also possible that differences in the above risk factors between the West and East contribute to the differences seen in their CV mortality rates. Interestingly, the inverse correlation between HRT use and CV mortality appears to be stronger in Eastern Europe, as the countries with higher HRT usage had lower CV death rates. This may represent that Eastern Europe is more homogenous in CV risk factors than the Western populations and could underline the importance of HRT. However, investigating CV risk factors other than postmenopausal state and HRT replacement was beyond the scope of this study.

Despite contrary results from a recent interventional trial ⁽¹⁴⁾, observational studies have consistently shown that women who are on HRT have much lower rates of coronary heart disease and perhaps cerebrovascular events as well ^{(15)(16)(17)(18)}. One of the reasons for the discrepant results might be that the study by Hulley and colleagues ⁽¹⁴⁾ enrolled women with prior coronory heart disease, whereas the observational studies involved mostly healthy women.

In summary, increasing HRT use might be a useful tool in Eastern European countries to improve their poor CV mortality rates and to reverse the unfavorable trends of CV deaths in elderly women. Because using HRT seems to be easier than influencing other CV risk factors (i.e., to convince patients to change their dietary habits, quit smoking, lose weight, and exercise more is often very difficult), HRT may provide an opportunity to Eastern Europe to "break out" of this disadvantageous situation, especially as HRT is underutilized there. One should, however, note that although there are potential risks associated with HRT, such as thromboembolic events and breast cancer ^(14)(19), many other options to prevent coronary heart disease carry no risk. For example, government run antismoking efforts have been particularly successful in the United States ⁽²⁰⁾. The Eastern European area seems to be an interesting and suitable place to carry out future interventional trials of HRT, because the exposure to HRT is low, therefore, selecting patients would be easier, and because of the high coronary heart disease rates, a possible HRT effect could be more simply detected.

View larger version (40K): [in this window] [in a new window]   Figure 2. Cardiovascular mortality rates for 100,000 women aged 45 years or older in Eastern Europe (Bulgaria, Romania, Hungary, Czech Republic, Poland) and Western Europe (Italy, The Netherlands, Great Britain, Sweden) and the United States. **p < .001.

	Acknowledgments

Received May 21, 1999

Accepted August 18, 1999

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