1 CLIMACTERIC 2012;15: Attitude of German gynecologists towards prescribing HRT before and after the WHI study K. J. Buhling, F. S. G. von Studnitz, A. Jantke *, C. Eulenburg and A. O. Mueck Department of Gynecological Endocrinology, Clinic of Gynecology, Universit ä tsklinikum Hamburg-Eppendorf, Hamburg; * Clinic for Gynecology, Charit é Universit ä tsmedizin Berlin, Berlin; Institute for Medical Biometry and Epidemiology, Universit ä tsklinikum Hamburg-Eppendorf, Hamburg; Universit ä ts-frauenklinik, Department of Endocrinology and Menopause, T ü bingen, Germany Key words: HORMONE REPLACEMENT THERAPY, GYNECOLOGISTS, SURVEY, WOMEN S HEALTH INITIATIVE ABSTRACT Objective The publication of the Women s Health Initiative (WHI) randomized, controlled trial in 2002 resulted in a critical discussion on the risks and benefits of hormone replacement therapy (HRT). The present study aims to evaluate the attitude of German gynecologists regarding changes in the prescription of HRT over recent years. Method A questionnaire was sent to all 9589 German gynecologists in private practice in November Results The response rate was 2548 (26.6%). Whereas 82.2% of the responders stated that their advice for primary hormone therapy and alternative agents depended on the severity of symptoms, 9.1% of the responders would recommend HRT in the first place (male: 14.3%; female: 6.1%; p 0.001). An age limit for hormone prescription was stated by 26.2%, with a mean age limit of years. An increasing number of patients and becoming more critical about HRT after the WHI was mentioned by 79.8%. Of the responding doctors, 43.9% found that their patients were badly informed by the media, 44.5% stated they were moderately or well (10.1%) informed, whereas only 1% considered their patients to be very well informed. HRT was prescribed for the relief of vasomotor symptoms by 97.4% of responders, making this the primary indication. This percentage decreased slightly to 92.6% between 2003 and 2008 ( p 0.001) and increased again to a similar level at the beginning of 2010 (96.7%, p 0.05). Conclusion German gynecologists generally have a positive attitude towards HRT, but find it important to focus on the evaluation of the risk benefit ratio. The major barriers to prescription are multiple concerns of the patients resulting from non-objective media. INTRODUCTION The publication of the Women s Health Initiative (WHI) randomized, controlled trial in July 2002 induced a huge discussion between physicians, but also in the public, on the health benefit ratio of hormone replacement therapy (HRT), sometimes also called hormone therapy (HT) 1. Two years after the publication of the first results, another paper on the estrogen-mono arm was published, showing some cardiovascular health benefits in women who started with estrogen treatment (ET) at an earlier age 2. Variable results and the ongoing discussion in the lay press have led to scepticism and insecurity, even in the group of gynecologists. Additionally, in 2010 the German S3-guidelines were introduced, which constrain the indications for HRT to hot flushes and as a second choice for osteoporosis 3. Yet, 9 years since the publication of the results of the WHI study, it would be interesting to know the data regarding HRT in Germany in the past year and the attitude of gynecologists towards it. Both K. J. Buhling and F. S. G. von Studnitz contributed equally to this publication. Correspondence: Dr K. J. Buhling, Clinic for Gynecology, Universit ä tsklinikum Hamburg-Eppendorf, Martinistra ß e 52, Hamburg, Germany ORIGINAL ARTICLE Received International Menopause Society Revised DOI: / Accepted
2 METHODS Survey A self-administered, anonymous questionnaire was sent to all 9589 gynecologists working in private practice in Germany. Gynecologists in private practice are the exclusive health-care givers for all German patients since the hospitals are only responsible for obstetric and surgical management. The questionnaires were sent by mail at the beginning of November 2010 and the doctors were asked to return them by the end of the year via fax or mail. The questionnaire was designed to include 15 questions following two open questions. At the beginning, we asked about personal information, including age, gender and work experience as an established specialist. Subsequently, we questioned the quality of the information regarding HRT and an appraisal of uncertainty among patients and doctors. Then, we asked about prescription habits before, immediately after and 8 years after the WHI study results were published, including the type of application and age limit for HRT. We questioned the indications leading to the hormonal treatment of climacteric symptoms. Statistics Data entry and data analysis were performed using SPSS Statistics version The results are presented as n (%) and mean standard deviation. For categorical information (e.g. gender, quality of information and uncertainty), we used the χ 2 test to evaluate associations between variables. Student s t -test was utilized to identify differences between groups concerning continuous data (e.g. age, age limit for treatment). To compare the differences for indications between the time ranges, McNemar s test was utilized. Values of p 0.05 were considered statistically significant, and values as statistically highly significant. RESULTS Study population By the end of January 2011, 2548 questionnaires were received via fax or mail and were eligible for evaluation (response rate: 26.6%); 1612/5769 (27.9%) of them were completed by female and 933/3820 (24.4%) by male gynecologists. The mean age of the participants was years. On average, men were 6 years older than women ( vs years; p 0.001). According to this difference, the men had 6 years more experience compared to their female colleagues ( vs years; p 0.001). To gain a better impression of the variety in attitudes, participants were divided into six groups according to age; 252 (9.9%) of the gynecologists had completed a 3-year subspecialization in gynecological endocrinology and reproductive medicine (no gender difference). These are referred to as endocrinologists as opposed to regular gynecologists. The average work experience as a resident was years. Quality of information and level of security To detect the quality of information among German gynecologists regarding the WHI study and the observation of publications, 36.9% stated they had followed the literature regarding those items exactly (male 44.1%, female 32.8%; p 0.001), 45.4% had followed it closely, 16.9% regularly, 0.5% lightly and 0.1% not at all. Among endocrinologists, participants considered themselves better informed: 82.4% were in the two highest informed groups ( p value vs. regular gynecologists 0.001). Furthermore, we examined the insecurity regarding the risk benefit ratio of HRT. The majority of respondents stated they were only slightly unsure (41.9%) or had not experienced an unsafe feeling at any time (33.8%), while 21.5% acknowledged some insecurity. Overall, 69 (2.7%) respondents declared that they were highly unsure about the risk value ratio. There was no significant difference between genders, except for the group that declared HRT to be highly unsafe (4.5% male and 1.7% female, p 0.001). There was no significant difference in the insecurity between gynecological endocrinologists and regular gynecologists, nor was there coherence between the level of insecurity and the years of work experience. Hormone therapy attitudes Of all the responders, 14.3% of males and 6.1% of females ( p 0.001, total 9.1%) would recommend HRT to a woman complaining about climacteric disorders for the first time (Table 1). The majority (2098/2548, 82.2%) stated that their advice for primary therapy depended on the characteristics and severity of symptoms (78.5% of male and 84.5% of female doctors agreed, p 0.001). However, 18.2% (16.1% of males and 19.6% of females, p 0.029) advocated for alternative therapeutic agents as the primary course of treatment. An age limit for hormone prescription was stated by 26.2% of the participants (17.6% of male and 31.2% of female doctors, p 0.001). Among them, the mean age limit was years (no gender difference). Changes since the WHI Of the responding gynecologists, 79.8% approved the thesis of an increasing amount of patients becoming more critical of HRT after the WHI; 14.7% said the amount had reached that level prior to the WHI. In this context, it should be mentioned Climacteric 327
3 Table 1 Attitudes towards hormone replacement therapy (HRT). Response to the question: What do you recommend to a woman who is complaining about climacteric disorders for the first time? (multiple answers accepted). Data are given as number of gynecologists giving each response (%) Depends on characteristics and severity of symptoms Directly prescribe HRT Directly prescribe alternative therapeutic agents Total 2098 (82.3%) 231 (9.1%) 465 (18.2%) Among men 732 (78.5%) 133 (14.3%) 150 (16.1%) Among women 1362 (84.5%) 98 (6.1%) 315 (19.6%) p value (gender) Among endocrinologists 208 (82.5%) 37 (14.7%) 42 (16.7%) Among gynecologists 1880 (82.3%) 193 (8.5%) 418 (18.3%) p value (subspecialization) Among aged 40 years 137 (77.4%) 12 (6.8%) 50 (28.2%) Among aged years 307 (82.5%) 22 (5.9%) 81 (21.8%) Among aged years 480 (83.8%) 24 (4.2%) 120 (20.9%) Among aged years 448 (83.1%) 55 (10.1%) 83 (15.4%) Among aged years 386 (85.0%) 55 (12.1%) 62 (13.7%) Among aged 61 years 327 (78.6%) 61 (14.7%) 63 (15.1%) p value (age) * * * *, Overall χ 2 test for comparisons between age groups that 43.9% of doctors found that their patients were badly informed by the media; 44.5% stated that they were moderately or well (10.1%) informed, whereas 1% considered their patients to be very well informed. A total of 1775 (72%) informants reported a decrease in prescription for HRT since the discontinuance of the WHI trial in 2002 (no gender difference). Gynecologists aged years stated a higher decrease than those aged under 40 years (77% vs. 53%; p 0.001). Gynecologists with a subspecialization reported less of a decrease in prescriptions compared to regular gynecologists (64.7% vs. 72.8%; p 0.007). A decline in the perception of HRT was most visible among those who had said they felt highly unsure about the risk benefit ratio of HRT (86.4%; p 0.008). This decline decelerated with increasing security in the risk benefit ratio, leading to a 62.8% decrease among those who did not admit any insecurity ( p 0.001). Participants also recorded a change in the type of application over the years; 75% reported a shift towards more transdermal application, whereas the others did not detect a change. Just 17 (0.7%) stated that they prescribed more oral hormones than in the past (no gender difference; see Table 2). HRT was prescribed for the relief of vasomotor symptoms by 97.4% of responders, making this the primary indication. This percentage decreased slightly to 92.6% between 2003 and 2008 ( p 0.001) and increased again to a similar level in the beginning of 2010 (96.7%; p 0.001). The changes were more obvious for other indications, such as osteoporosis and the prevention of cardiovascular diseases. The indications for prescription are shown in Table 3. DISCUSSION The response rate of 27% was in the medium range for surveys, but the sample size of 2548 is one of the largest ever published on this topic. This fact, and the fact that we questioned only medical specialists (who had completed their residency) in private practice with a mean work experience of years, are the strengths of our study. Since physicians working in private practice are the main doctors dealing with HRT (hospitals only deal with surgical and obstetric management), we addressed the correct collective of physicians who participate in the debate on HRT. Several studies have described a change in the prescription habits of gynecologists after the publication of the WHI trial Additionally, some observational studies in patients have shown similar results 8, In a 7-month, post-whi survey among British, French, Spanish and German women, Germany showed the highest ever use rate of 40%, but, in total, the percentage of current users among women in those countries had fallen to 16% 17. The absolute decrease ranged from 5.6% in a western region of Germany 12, to 6.8% nationwide 15, and up to 12.9% in a recent Berlin population-based cohort 16. International surveys showed a decline in prescriptions by 32% (ET) in a Canadian study 11, by 45.9% (HRT) and by 27.8% (ET) in two studies done in the US in Other investigations from Brazil 5, Lebanon 4, Israel 6, Chile 8 and New Zealand 13 do not state actual numbers referring to the decline in use, but only refer to the fact that the majority of physicians had changed their prescription habits since Only Spain produced a survey in which 61.1% of the gynecologists 328 Climacteric
4 Table 2 Changes in the type of application. Response to the question: Regarding your prescription behavior, have you modified the type of application?. Data are given as number of gynecologists giving each response (%) More transdermal More oral No change Total 1872 (75.0%) 17 (0.7%) 606 (24.3%) Among men 662 (72.3%) 6 (0.7%) 247 (27.0%) Among women 1208 (76.6%) 11 (0.7%) 357 (22.7%) p value (gender) Among age 40 years 145 (83.8%) 3 (1.7%) 25 (14.5%) Among age years 297 (81.1%) 3 (0.8%) 66 (18.0%) Among age years 436 (77.9%) 1 (0.2%) 123 (22.0%) Among age years 142 (26.8%) 5 (0.9%) 142 (26.8%) Among age years 135 (30.6%) 3 (0.7%) 135 (30.6%) Among age 61 years 110 (26.9%) 2 (0.5%) 110 (26.9%) p value (age) * * * *, Overall χ 2 test for comparisons between age groups stated that they did not change their prescription habits until Our findings of 72% of respondents admitting to prescribing less HRT since the WHI trial are more than consistent with the results from other studies. Even more, it shows that the highest decrease occurred prior to 2002, compared to other countries. Many physicians have stated that the reduction in prescription was not always due to their personal opinion, but a result of their patients reluctance toward hormone therapy. Even if only 9.1% of informants would prescribe HRT to a woman complaining of climacteric disorders for the first time, a positive attitude towards HRT cannot be ruled out. This percentage reflects the security and accuracy of physicians when deciding on the optimal therapy for their patients. Respectively, almost 80% of patients seemed to be more critical towards HRT, according to their doctor s opinion. Here, the important role of the media should be mentioned. The fact that the majority of our respondents found their patients were poorly (44%) or only moderately (44.6%) informed shows how immensely media coverage affects patient opinion. It remains uncertain if this information can be considered objective. Many gynecologists stated, in the open-answer question at the end of the questionnaire, that distinctiveness concerning the matter of HRT could only be Table 3 Indications leading to hormone replacement therapy (HRT prescription). Response to the question: What indications have led you/ lead you to prescribe HRT?. Only respondents who gave an answer for each time period were included when calculating the p values and the reduction for each time period. Other columns show the total positive answers Time period ( n (%)) Reduction (%) Indication Prior to Prior to 2002 vs vs Prior to 2002 vs Relief of vasomotor 2070 (97.4) 2150 (92.6) 2399 (96.7) 5.1 ** 3.9 ** 1.0 * symptoms Prevention of 1737 (81.8) 1134 (49.0) 1259 (51.0) 32.7 ** 1.5 * 30.9 ** osteoporosis Achievement of overall 1053 (49.6) 607 (26.2) 743 (30.0) 23.8 ** 3.7 ** 19.8 ** well-being Cognitive disorders 895 (42.1) 547 (23.6) 673 (27.1) 18.6 ** 3.8 ** 14.6 ** On demand of patient 1217 (57.4) 957 (41.3) 1119 (45.4) 16.5 ** 3.9 ** 12.1 ** Bleeding disorders 1459 (68.7) 1411 (60.8) 1561 (63.0) 8.2 ** 2.7 ** 5.6 ** Prevention of 780 (36.7) 269 (11.6) 347 (14.0) 24.8 ** 2.6 ** 21.8 ** cardiovascular disease Reduction of libido 1132 (53.3) 834 (35.9) 968 (39.1) 17.5 ** 3.6 ** 13.7 ** Anti-aging 584 (27.5) 286 (12.3) 359 (14.5) 15.1 ** 2.7 ** 12.1 ** Atrophic colitis leading 1541 (72.7) 1477 (63.6) 1692 (68.2) 9.8 ** 4.4 ** 5.1 ** to dyspareunia Incontinence 1363 (64.2) 1259 (54.2) 1438 (58.0) 10.3 ** 3.8 ** 6.4 ** *, p 0.05; * *, p Climacteric 329
5 achieved through independent, consistent and objective education of women (data not shown). Another change over recent years lies in the shift towards more transdermal application of HRT; 75% of respondents favored transdermal use. This has to be assessed as a very important trend for the use of HRT because this is indeed in context with the result of recent observational studies suggesting a lower risk of venous thromboembolism 20 22, and possibly also of stroke 23 and myocardial infarction 24 in comparison with oral HRT. Although the special benefits of transdermal application due to the avoidance of first hepatic passage and use of low-dose physiological dosages have promoted the transdermal treatment as safer for many years 25, clinical endpoint studies have been rare. Until now, placebo-controlled studies have been lacking, but well-designed, case-control and cohort studies support the notion of reducing cardiovascular risks by the use of transdermal HRT Additionally, we wanted to evaluate the gynecologist s concerns about different indications for prescribing HRT, rather than generalizing the symptoms. As shown in Table 3, most indications experienced a decline in HRT prescription, when comparing the pre- and post-whi era. It is striking, though, that an increase in prescription rates could be seen for every indication in recent years compared to the decline between pre- and post-whi. Whereas the basic indication for HRT, the relief of vasomotor symptoms, did not show great changes, indications like achievement of overall well-being, anti-aging, cognitive disorders and prevention of cardiovascular diseases primarily showed a strong decline, but started to become more favorable as indications for HRT, beginning in This could be the result of one publication coming from the WHI study showing a reduction in cardiovascular risk with HRT in a younger-aged group 1. In a Brazilian study from , prescription rates for the purpose of preventing osteoporosis decreased from 90.2% before, to 74.9% after the WHI. In Spain, similar results were shown (90% vs. 79%) 9. The decline in the indication osteoporosis in our study is astonishing, since HRT is still a possible second-choice therapy for this condition. Therefore, the poor increase for this indication by only 1.5% is difficult to explain. A possible explanation for this phenomenon may be overall scepticism and insecurity. Nevertheless, even the WHI 1 and recommendations by members of the International Menopause Society admit the benefit of HRT regarding the prevention of osteoporosis 29. Although the response rate of this largest survey to date among German gynecologists could be influenced by a selection bias, we assume that it might be representative of the cohort of German gynecologists. The response rate, in terms of gender and age, is representative for the entire population of German gynecologists. The results of our study show that German gynecologists are actually more likely to have a positive attitude towards HRT, including an accurate risk value analysis as well as equitable education regarding the risks and supervision of patients. One of the major barriers to HRT is the multiple concerns of patients, probably resulting from non-objective media. More objective education for patients, provided by the media, remains indispensable. 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