Changes of the prescription of hormone therapy in menopausal women: An observational study in Taiwan

Menopausal hormone therapy (MHT), estrogen with or without progestin, has been commonly used to treat symptoms of menopause and prevent chronic conditions such as cardiovascular disease and osteoporosis since the late 1960s [1]. Evidence on the potential risks and benefits of combined estrogen/progestin has slowly accumulated and has suggested that the combination of the two acts differently than estrogen alone [2‐4]. Evidence from secondary prevention trials and observational studies has also shown that using combined estrogen/progestin therapy comes with an increased risk of coronary heart disease [5, 6].

In 2002, the Women's Health Initiative (WHI) report [7] demonstrated that the risks outweighed the benefits for women undergoing continuous estrogen and progestin treatment [5]. The WHI report findings prompted the U.S. Food and Drug Administration to require new warning labels be placed on all estrogen products [8], and prompted the U.S. Preventive Services Task Force to recommend that estrogen and progestin not be used routinely in the prevention of chronic post-menopausal conditions [9]. Although WHI results may not apply to other types of estrogen and progesterone therapies, different dosages, and various methods of administration, the results were, nevertheless, significant enough to lead to a substantial decline in the use of MHT by many postmenopausal women [10‐17].

Consequently, the WHI report affected drug approval policy. The FDA (U.S.) now only approves estrogen for the relief of menopause symptoms alone regardless of formulation, dosage, or route of administration. Furthermore, it has been recommended that only women at a significant risk of osteoporosis consider hormone therapy, at recommended dosage decreased from 0.625 mg conjugated estrogens to 0.3 mg [36]. Because the impact of the WHI report may demonstrate that what some studies have claimed- the dissemination and availability of health care information influence consumer perception and demand for medical care [10, 18‐20], we believe that a closer examination of the effect of WHI report on the use of MHT treatment might lead to a better understanding of the role of "information" in the demand and supply of medical services.

Certain consumer characteristics including age, educational level, working status, and marital status, influence whether or not a woman seeks and accepts MHT [1, 15, 21‐24]. Also, possession of information or knowledge, largely obtained through medical and social contacts, has a great influence on the acceptance of MHT [[15, 23, 25], and [26]]. Furthermore, the opinion of a woman's health care provider has also been found to strongly influence her decision to undergo MHT [27].

Which medical interventions health care providers decide to use depend on their access to technical information, recommended procedures and regimen, and reported "uncertainties" about the effectiveness of the intervention [28]. Incomplete information, as being one of the main reasons, is often cited that physicians vary in how they treat a particular medical condition and in their patterns of practice [29]. Preference of medical intervention can also depend on medical specialty of the physician. Women treated by gynecologists have been reported to be 2.6 times more likely to receive MHT than women being treated by family physicians [30], which is understandable in light of the finding that gynecologists have a more favorable attitude toward MHT as a preventive measure than other physicians [31‐33].

Forty to 60-year-old women in Taipei, Taiwan increased their use of MHT from 8.8% to 19% between 1991 and 1997 [34]. Most of these women were encouraged to seek this therapy by their social contacts, medical professionals and the media. The government even had a television advertisement promoting MHT in 1999. However, four months after the release of WHI report, the government formed an ad hoc committee that later announced new guidelines for the use of MHT, though the television promotion of MHT was withdrawn much earlier. [35].

With regard to WHI report's impact over physician and patients, it is not clear whether it affected their willingness to prescribe or use MHT in Taiwan. Using the results of a national health interview survey administered between August 2001 and January 2002 and linking them with the National Health Insurance (NHI) outpatient claims for women with menopausal conditions, we examined the changes of prescription of MHT to treat menopausal outpatients in Taiwan before and after the publication of WHI report as well as to what extent certain patient or health care provider characteristics influenced the decision to use MHT.

The NHI records of 504 participants indicated that they had sought treatment for menopause related problems during the study period starting six months before and ending six months after the WHI report was published (Table 2). Of these 504 women, 28.6% (n = 144) had NHI outpatient records for menopause only during the six-month period leading up the release of WHI report, 51.2% (n = 258) before and after, and 20.2% (n = 102) during the 6-month period following the WHI period only (Table 2). Of the 402 women who had outpatient visits for menopause related problems both before the WHI report, 361 (89.8%) of them had at least one outpatient record with MHT prescription, 288 (80%) of 360 women, who had NHI outpatient visits for menopause six months after the WHI report, had at least one outpatient record with a MHT prescription.

Most of the 504 study participants, who had outpatient visits for menopause during our study period, were aged 45 – 55 years old (57.9%), had elementary school educations or lower (48.6%), were married (81.8%), were not employed (66.5%) or had no personal income (39.1%). Of these 504 females, most (84.9%) had experienced an illness during the six-month period leading up to the interview, and most (70.0%) had no NHI outpatient records for osteoporosis. In total, these 504 women made 2549 outpatient visits for menopause-related symptoms, 50.8% were being treated by either an obstetrician or gynecologist and 79.3% had been prescribed MHT. The proportion of outpatient visits in which MHT was prescribed dropped from 83.0% (n = 1392) before WHI to 73.0% (n = 1157) after WHI.

Table 3 shows the results of logistic regressions of random effect. Model 1 included the dummy variable of WHI effect without interaction terms; Model 2 included the interaction of WHI and women education; and Model 3 included the interaction of WHI and the accreditation level of medical institution. Overall, based on Model 1, the likelihood that MHT would be prescribed during an outpatient visit decreased after the WHI report (OR 0.36, 95%CI 0.25 to 0.52). Hospitals not classified as academic medical centers were more likely to prescribe MHT than academic medical centers (OR from 14.87 for metropolitan hospital to 26.42 for physician clinic). Obstetricians or gynecologists were more likely to prescribe MHT than physicians of other specialties (OR 5.34, 95% CI 3.45–8.26). Marital status, employment status, personal income, the diagnosis of osteoporosis, or illness was not found to be associated with the prescription of MHT the six months leading up to the interview. The impact of the WHI report on the prescription of HRT analyzed by level of education and the accreditation level of medical care institution was estimated in the two interaction models, Model 2 and Model 3. Women with college level educations or higher were less likely to be prescribed MHT after the WHI report than before (Model 2; OR 0.30; 95% CI 0.11–0.83). Academic medical centers were less likely to prescribe MHT than other medical care institutions after the release of WHI report (Model 3; OR 0.15; 95% CI 0.34–0.63).

MHT was once widely thought to be an effective treatment for menopause-related symptoms. In year 2002, the WHI trial of estrogen plus progestin in postmenopausal women found that overall health risks of this therapy outweighed the benefits for these women [7]. The release of that report provides us the opportunity to study to what extent publicizing new scientific evidence changes public acceptance of certain modes of therapy and health care provider's choice of therapeutic regimens, in this case menopausal hormone therapy.

In this study, as other studies have indicated, the WHI report led to a significant decline on the use of MHT for menopausal difficulties [12‐16]. Like other studies [29‐32], we found that gynecologists were more likely to prescribe MHT than physicians with other medical specialties, but we also found that the decision whether MHT would be prescribed was not totally decided by physicians alone, but had also to do with who was seeking therapy. Women with college level educations or higher were less likely to be prescribed MHT than the women with high-school level educations or lower and health care providers were found to vary considerably in whether MHT was prescribed.

One of the limitations of this study is its focus on the MHT for the treatment of menopausal-related symptoms. We did not take into account that some women might stop seeking western medicine treatment at outpatient visits for menopausal-related symptoms and start searching for other non-pharmacological treatments (e.g. herbal products or health supplements). Since our data source was obtained from the NHI outpatient visit records, no information on over-the counter herbal products or nutritional supplements for menopausal symptoms was included. Thus, our findings may underestimate women's reaction to the WHI report. Nevertheless, our sample was drawn from a nationwide interview survey and linked to NHI claim data, allowing us to obtain real utilization information and identify the co-existing condition of osteoporosis. Data collected this way is superior to self-reported information, which can be subject to recall bias. 98.3% of the people we surveyed were insured under the NHI program, with almost all of their medical costs covered through this program. This lends credence to our findings, in that financial barriers to MHT were non-existent.

Another limitation of our study is potential selection bias. The sample base for this study was drawn from the women who were interviewed in the 2001 National Health Interview Survey and aged 45 years or above. Only those who signed the inform consent for linking NHI claim data would be included in this study. Those who did not sign the inform consent were more likely to be older, less educated, unmarried, unemployed, have lower personal income and be healthier. Our logistic regression predicted that women who were unemployed and less educated women were more likely to be prescribed MHT. Thus, we would suspect that those women who were not included in this paper were those who were more likely to be prescribed MHT. After the WHI report, women with undergraduate or graduate (higher education) were less likely to receive MHT OR = 0.30 (0.11–0.83). Again, we suspect that the effect of WHI on reducing prescription of MHT may be somewhat over-estimated, because lower-educated women were more likely to be excluded and less responsive to WHI report than higher-educated women.

Finally, this study was undertaken only six months following publication of the WHI report. In order to keep track of stable changes in the patterns of practice patterns that take place after publication of such an article, longer follow-up periods may be necessary, especially of subgroups of women such as women with previous hysterectomies, those older than 65, and women living in areas of high social deprivation. Future research should consider factors leading to the effective dissemination of new clinical trial findings for women.

The WHI report brought about a substantial decline in the prescription of MHT to treat menopause-related symptoms in Taiwan. The decision whether to prescribe MHT for menopause-related symptoms was not purely dominated by the physician. Women with college level educations or higher were less likely to be prescribed MHT than the women with high-school level education or lower after the release of WHI report, and academic medical centers were less likely and metropolitan hospitals more likely to prescribe MHT than medical providers with different accreditations after the release of WHI report.