- Email: [email protected]
The prescription of hormone replacement therapy in Spain: Differences between general practitioners and gynaecologists
Maturitas 55 (2006) 308–316
The prescription of hormone replacement therapy in Spain: Differences between general practitioners and gynaecologists Camil Castelo-Branco a,∗ , Javier Ferrer a,b , Santiago Palacios a,c , Sonia Cornago a a
Hospital Cl´ınic, University of Barcelona, Villarroel 170, 08036-Barcelona, Spain b University of Oviedo, Spain c Instituto Palacios, Madrid, Spain
Received 12 January 2006; received in revised form 11 April 2006; accepted 11 April 2006
Abstract Objectives: The purpose of this study was to determine the frequency with which hormone replacement therapy (HRT) was prescribed and to identify physician-related factors associated with the prescription of HRT in Spain. Study design: A descriptive cross-sectional survey based on a personal interview with a structured questionnaire was conducted in April 2005 with physicians aged 25–65 years. A total of 2700 doctors were asked to participate in this prospective study (1350 GY and 1350 GP). This number included 270 gynaecologists (GY group) and 270 general practitioners (GP group). Results: Only 10% of gynaecologists and 19.4% of GPs had never prescribed HRT. The reasons given for not prescribing HRT were adverse effects and the fear of cancer among GPs and adverse effects and social alarm in the GY group. Phytoestrogens were the most commonly used alternative; however, GPs were more willing to use antidepressants and benzodiazepines than GYs. The frequency of HRT prescription in symptomatic women was significantly higher among GYs. The main reasons for prescribing HRT were climacteric complaints and improvement in life quality for GYs and, climacteric complaints and the prevention of osteoporosis for GPs. Seventy-eight percent of GYs prescribing hormones referred a high degree of satisfaction with HRT, whereas only 50% of GPs expressed a similar attitude. Conclusions: Concern for HRT prescription in Spain is high. Adverse effects and the fear of cancer are negative conditioning factors in the prescription of HRT, whereas climacteric complaints, quality of life and the prevention of osteoporosis are positive conditioning factors. GYs are more willing to use HRT than GPs. This contrast may reflect the indecision of GPs regarding the preventive value of HRT. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Hormone replacement therapy; Menopause; Drug prescription; Health care givers; Gynecologist; General practitioner
1. Introduction ∗
Corresponding author. E-mail address: [email protected] (C. Castelo-Branco).
Hormone replacement therapy (HRT) is a widespread intervention during the climacteric period,
0378-5122/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.maturitas.2006.04.023
C. Castelo-Branco et al. / Maturitas 55 (2006) 308–316
which was widely prescribed during the second half of last century despite the lack of conclusive studies on its hypothetical beneficial role. The most common arguments for the prescription of HRT are based primarily on the position assumed by few authors who consider the menopause an endocrinopathy, where the reduction of estrogen levels is a risk factor for several prevalent diseases that constitute the most frequent causes of mortality in this sector of the population; and secondly, from a more ‘natural’ perspective, HRT has been regarded as a treatment of choice to alleviate only the symptoms related to estrogen decline. However, until now, most of these prescriptions were based on the results of observational studies not supported by randomised controlled trials (RCT) [1–3]. At present, scientific controversy on this topic is particularly active, since the results of several RCTs not only fail to demonstrate any preventive role of HRT but also link it to several diseases including breast cancer, heart disease, stroke and pulmonary embolism [4–6]. The USA and Australia are the countries with the highest prescription rates followed by north-European countries. The frequency of prescription ranges from 62% in USA [7] and 14.9% in Denmark [8] to 3 per 1000 registered women in The Netherlands [9]. Additionally, few studies have been carried out on this topic in Spain with conflicting results [10,11]. The characteristics of HRT users in Spain have not been studied in depth; however, according to data published elsewhere, it is more frequent in women with early and surgical menopause, and in women with severe climacteric complaints [12,13]. Moreover, most of the women who use HRT have a high socio-economic level, with a higher level of education and work out of home [14]. In addition, they considered themselves to be healthier and to have a smaller risk for cardiovascular disease [15]. On the other hand, doctors’ attitudes towards HRT have barely been explored, even though the knowledge they have, the information from journals and their standpoint on this therapy have a real influence on final prescription [13,16]. Several studies have reported that gynaecologists feel more strongly than other physicians about the preventive role of HRT [13,17–20]. However, data comparing current HRT use in women seen by gynaecologists versus and its use with women seen
309
by general practitioners or family physicians for socio-demographics, preventive health behaviours, and co-morbidities of the patients are scant [13]. The purposes of this paper were to determine the major reasons for HRT prescription and to identify doctors’ socio-demographic factors related to the prescription of the treatment in women aged 40–65 years in Spain.
2. Materials and methods A descriptive cross-sectional survey was conducted in April 2005, with doctors aged 25–65 years from the reference population of four of the major cities in Spain (Madrid, Barcelona, Seville and Valencia). All the participants were gynaecologists or GPs. All of them were interviewed in person at their homes or by telephone by professional interviewers. The sample size was established based on the fact that the studied condition (the prescription of postmenopausal HRT) may affect different percentages of women [18–22] (for this reason and due to the high variability of the information provided in the relevant literature, additional experts from the area were consulted). Thus, using statistics software to calculate sample size with a 5% maximal acceptable error, 95% confidence level, potential of 80% and possible losses of 20%, we determined that the number of doctors estimated for the final sample was 500. Secondly, from this population, assuming that the prescription proportion among gynaecologists and general practitioners would be similar [13], we determined that 250 doctors were required in each group. Therefore, a total of 1343 gynaecologists and 1357 GPs were asked to participate in this study. Among them, 80% in both groups denied participation, leaving 270 GYs and 270 GPs for the survey. Subjects were selected at random from a list of 3124 doctors provided by a pharmaceutical studies company (Salvetti and Llompart, Barcelona, Spain) (data obtained from the health departments of different local governments, Spanish Health Annual Report 2004–2005 and phone list). Doctors with a physical incapacity to answer a questionnaire by telephone or at home, and those who had expressed their desire not to take part in the study were excluded. The selection process was by phone and, after inclusion, all doctors
310
C. Castelo-Branco et al. / Maturitas 55 (2006) 308–316
were interviewed in person at their homes or offices by professional interviewers. The information was gathered using a semistructured questionnaire specifically designed to collect information on the prescription for climactericrelated complaints. The questionnaire included 9 items to consider the subjects selectable, 12 items to evaluate socio-demographics aspects, 6 items related to perception and behaviours on climacteric complaints, 7 items related to knowledge of therapies for the climacteric, 6 items related specifically to knowledge and prescription of HRT, 9 items related to the way doctors identify pharmaceutical brand names and finally, 34 items related to the prescription of HRT for doctors who prescribe HRT, 12 for doctors who have prescribed it in the past and 8 for those who had never prescribed HRT. The questions were based on instruments used in previous studies (Salvetti and Llombart. Unpublished data) and aimed to be clear and concise so as to increase reliability. Each interview took around 30 min and if the doctor was not at home, up to three calls were made at different times of the day in order to reach him/her. Finally, the satisfaction with the different treatments for climacteric complaints was assessed by a visual analogue scale (VAS), with values from 0 (left side: absolutely unsatisfied) to 10 cm (right side: absolutely satisfied). The data were analyzed using a personal computerbased software package (SPSS 12.0, SPSS Inc. Headquarters, 233 South Wacker Drive, 11th floor, Chicago, IL 60606, USA). The outcome measure of the study was the frequency of the prescription of HRT, defined as any pharmaceutical composite that has an estrogenic or estrogenic and progestogenic action administered by any route and prescribed by a doctor, regardless of his/her speciality. The rest of the variables were considered predictor variables. For the descriptive analysis, the habitual statistics, frequencies and percentages for the qualitative variables, and mean and standard deviation for the quantitative variables, were used. Differences between the groups were evaluated using the Student’s t-test, ANOVA or the Kruskall– Wallis test, according to the homogeneity of the variance measured with the Bartlet test. Comparisons between groups for percentages were made using χ2 . A value of p less than 0.05 was considered statistically significant.
3. Results From the list of 3124 doctors, contact was made with 2700 doctors, of whom 2160 did not meet the inclusion criteria or did not wish to answer, leaving a total of 540 interviews, and a response rate of 20%. Table 1 shows the socio-demographic characteristics of the sample. Half of the doctors were aged 45–65 years, and 50% were females. It is worthy of note that a significant percentage (33.3%) of the entire sample were not HRT prescribers. As expected, gynaecologists worked more frequently in hospitals than GPs (p < 0.000) and were more willing to prescribe HRT (p = 0.062). Only 10% of gynaecologists and 19.4% of GPs had never prescribed HRT. In addition, 23.42% (63/269) GYs and 14.17% (38/268) GPs do not prescribe HRT at present although they have prescribed it in the past. Table 2 shows the reasons given for not prescribing HRT. Adverse effects and the fear of cancer among GPs and adverse effects and social alarm in the GY group were the most common reasons. Interestingly, among doctors who had previously prescribed HRT, women’s reluctance to HRT was an increasing factor for GYs while for GPs, it was negative information from medical journals. Phytoestrogens were the most used alternative; however, GPs were more willing to use antidepressants and benzodiazepines than GYs (Table 3). Table 4 shows the main reasons for prescribing HRT among the doctors who indicate the therapy in more than 50% of subjects complaining of menopause-related symptoms. Climacteric complaints and improvement in life quality for GYs and climacteric complaints and the prevention of osteoporosis for GPs were the most important factors condition prescription. Reasons given by ≤50% of prescribing doctors prescribing in for not increasing their prescription rates are shown in Table 2. In most cases, the risk of cancer and adverse effects are again the main reasons; however, for GYs, women’s reluctance is once more a rising factor. The frequency of prescription among women with symptoms was 93% in the GY group, which was significantly higher than the frequency among those attended by GPs (85%) (OR = 1.25; CI 95%: 1.09–1.89). The reasons most associated with the prescription of HRT were surgery (55% GY, 48% GP), early menopause (56
C. Castelo-Branco et al. / Maturitas 55 (2006) 308–316
311
Table 1 Socio-demographic characteristics of the sample (N = 540) Gynaecologists
General practitioners
p-Valuea
Age <35 years old 35–45 years old 46–55 years old >55 years old
61 74 108 27
39 96 118 17
NS NS NS NS
Gender Male Female
134 136
135 135
NS NS
95 95 40 40
67 67 68 68
ND ND ND ND
81 129 125 2 1
221 70 9 1 2
59
33
27 63
52 38
NS (0.062) NS (0.062)
Prescribing HRT Rate ≤ 50% patients Rate > 50% patients Do not know % of HRT vs. no HRTb
98 81 1
115 63 2
NS (0.062) NS (0.062) NS (0.062)
THS prescription (rate THS >50% patients) Place of work Barcelona Madrid Sevilla Valencia
17 43 7 14
9 31 11 12
NS NS NS NS
81
63
NS
45 36
34 29
NS NS
81
63
NS
Place of work (location) Barcelona Madrid Sevilla Valencia Place of work (sector)a National Health Service Centers (ambulatory clinics) Private center Hospital (outpatients) Menopause unit (public) Menopause unit (private) Number of doctors working in public and private HRT prescriptions No prescribing HRT Never Former
Total rate >50% patients Gender Male Female Total rate >50% patients a b
0.0000 0.0000 0.0000 NS NS
Multiple choice (several doctors work in both public and private centres). Several doctors did not remember their prescription rates.
GY, 46 GP) and the prevention of osteoporosis (14% GY, 15% GP). It was observed that the prescription of HRT was greater if the doctor was a gynaecologist (81/179
versus 63/178) and worked in the private sector (OR = 1.51; CI 95%: 1–2.31). In contrast, no differences were observed regarding the place of work (Madrid/Barcelona/Seville/Valencia p = 0.244;
312
C. Castelo-Branco et al. / Maturitas 55 (2006) 308–316
Table 2 Reasons given for not prescribing (more) HRT Gy
GP n
p-Value
n
%
Doctors who had never prescribed HRT Adverse effects Cancer risk Other more safe therapies available Negative data from medical journals Women reluctance Social alarm Lack of specialist (GY) prescription Government restriction 5 years use limit Lack of knowledge To avoid nuisances with Government Cost Others
27 18 3 7 5 3 5 – 3 1 0 0 0 4
10* 67 11 26 19 11 19 – 11 4 0 0 0 15
52 36 24 9 10 6 4 9 3 2 4 1 1 1
% 19.26* 69 46 17 19 12 8 17 6 4 8 2 2 2
<0.01 NS 0.002 NS NS NS NS – NS NS NS NS NS 0.026
Doctors who do not prescribe HRT currently but who had previously prescribed in the past Adverse effects Cancer risk Other more safe therapies available Negative data from medical journals Women reluctance Social alarm Lack of specialist (GY) prescription Government restriction 5 years use limit Lack of knowledge To avoid nuisances with Government Cost Others
63
23.33*
38
14.07*
<0.01
33 21 11 19 26 24 – 3 5 0 1 0 5
52 33 17 30 41 38 – 5 8 0 2 0 8
21 15 6 12 3 8 2 0 1 0 1 0 0
55 39 16 32 8 21 5 0 3 0 3 0 0
NS NS NS NS 0.000 NS (0.076) – NS NS NS – NS
Doctors who prescribe HRT currently but ≤50% of cases Adverse effects Cancer risk Other more safe therapies available Negative data from medical journals Women reluctance Social alarm Lack of specialist (GY) prescription Government restriction 5 years use limit Lack of knowledge To avoid nuisances with Government Cost Others
98
36.29*
42.59*
NS
26 41 15 17 36 27 – 2 6 0 0 4 13
27 42 15 17 37 28 – 2 6 0 0 4 13
35 39 19 9 14 18 22 3 6 0 0 2 0
NS NS NS 0.059 0.000 NS – NS NS – NS 0.000
115 40 45 22 10 16 21 25 4 7 0 0 2 0
* Total numbers differ because some doctors give more than one reason. GY: gynaecologist, GP: general practice. Percentages refer to each sub-sample except those marked with an asterisk, which refer to the entire sample.
C. Castelo-Branco et al. / Maturitas 55 (2006) 308–316
313
Table 3 Complementary and alternative therapies to HRT
Phytoestrogens-phytotherapy Raloxifene Veralipride Bisphosphonates Healthy life styles Benzodiazepines Relaxation response/guided techniques Antidepressants Oil therapy Homeopathic remedies Herbal therapy Other alternatives
Gya (n = 27)
Gyb (n = 63)
GPa (n = 52)
GPb (n = 38)
n
%
n
%
n
%
n
%
21 10 13 14 5 0 2 1 2 2 3 0
78 37 48 52 19 0 7 4 7 7 11 0
58 34 26 32 9 3 0 2 4 0 4 0
92 54 41 51 14 5 0 3 6 0 6 0
43 19 17 17 15 12 8 9 5 3 2 2
83 37 33 33 29 23 15 17 10 6 4 4
32 16 12 14 4 8 2 4 2 0 1 0
84 42 32 37 11 21 5 11 5 0 3 0
p-Valuea
p-Valueb
NS NS NS NS NS 0,006 NS NS (0,087) NS NS NS NS
NS NS NS NS NS 0,011 NS (0,067) NS NS – NS –
a
Doctors who had never prescribed HRT. Doctors who do not prescribe HRT at present but have prescribed HRT in the past. Data are in percentages. Total numbers differ because some doctors give more than one reason. b
Table 4 Reasons for prescribing HRT GY (n = 81)
Climacteric symptoms Osteoporosis prevention Improvement in quality of life Higher efficacy than alternatives therapies Prescribed by a specialist Easier control than other therapies Improve sexuality Cardiovascular disease prevention Uncomplicated use Less expensive than alternative therapies Others
GP (n = 63)
p-Value
n
%
n
%
66 11 27 23 – 6 8 5 5 0 1
81 14 33 28 – 7 10 6 6 0 1
54 20 13 15 12 11 6 6 4 2 0
86 32 21 24 19 17 10 10 6 3 0
NS 0.008 NS NS – NS (0.064) NS NS NS NS NS
Data from doctors (GY: gynaecologist, GP: general practice) who prescribe HRT in more than 50% of subjects with menopause-related complaints.
OR = 0.70; CI 95%: 0.46–1.06) or gender (p = 0.182; OR = 1.40; IC 95%: 0.92–2.14). Finally, using the VAS, 78% of GYs prescribing hormones referred a high level of satisfaction with HRT (VAS ≥ 8), whereas only 50% of GPs expressed a similar attitude (p < 0.0000).
4. Discussion Before taking into consideration the results of this survey, one must keep in mind a potential problem of validity in this study since the impact of our results
may be severely hampered by the low response proportion. Moreover, as it is a survey based on the opinions of interviewed doctors, the subjects’ memory may be diminished, particularly regarding the information given by doctors who visit menopausal patients sporadically or who did so some time ago. To reduce this error, questions in the survey referred to very specific information which was, in general, easy to remember. Furthermore, doctors were requested to supply the trademark of the drug and the administration route. In addition, as the interview was a semi-structured questionnaire, it was possible for the interviewer to compare the answers given by the subjects. Another limitation to
314
C. Castelo-Branco et al. / Maturitas 55 (2006) 308–316
this study was the fact that it was a relatively small survey with doctors recruited from the four largest cities in Spain, and results may not be representative of the doctor population as a whole. Clinical trials show that hormone therapy is an effective treatment for vasomotor symptoms and vaginal dryness. HRT improves other symptoms, including sleep and mood disturbances, in women who have menopause symptoms. In the Women’s Health Initiative (WHI) controlled clinical trial, estrogen plus progestin therapy reduced fracture risk and colon cancer risk, neither reduced the risk of heart disease, and increased the risk of breast cancer, stroke and deep vein thrombosis [6]. The WHI clinical trial found overall harm rather than benefit from medication. This surprised professionals, made newspaper headlines, and changed prescription practices. Thus, after WHI publication, with the reduced popularity of HRT [16], physicians may encounter women who are experiencing somatic symptoms or psychological disorders that worsen at the time of menopause. A significant decrease in the number of HRT prescriptions was associated with a statistically significant increase in prescriptions of psychoactive drugs (mainly benzodiazepines and antidepressants) [21] and phytoestrogens [22]. In this survey, phytoestrogens were the most used alternative; however, GPs were more willing to use antidepressants and benzodiazepines than GYs. Accordingly, Reynolds et al. have noted associations between changes in HRT and antidepressant prescription patterns [23]. The increase in prescriptions of benzodiazepines and antidepressants among GPs suggests that such drugs are being prescribed for (psychological and physical) symptoms previously controlled with the use of HRT [24]. It is worthy of note that in this survey 19% of GYs and 14% of GPs prescribed HRT for other indications, which may indicate a preventive attitude and a minor impact of the negative information published in the media on this topic. In addition, 6% of GYs and 10% of GPs also prescribed HRT for cardiovascular prevention. This fact is remarkable since most recent reviews support the hypothesis that in relatively healthy women, HRT significantly increased cardiovascular risk, including the risk of venous thromboembolism or coronary event (after 1 year’s use) and stroke (after 3 years) and that HRT is not indicated for the routine management of chronic disease [25,26]. This prevailing opinion has been denied by those
doctors under the assumption that cardioprotection is possible. Factors influencing a physician’s decision to prescribe medication for the climacteric have not been widely studied. The results of the current study suggest that climacteric complaints and improved life quality for GYs and climacteric complaints and the prevention of osteoporosis for GPs as well as differing HRT tolerability profiles are important factors. Several studies have reported that gynaecologists feel more strongly than other physicians about the preventive role of HRT [17–20]. These prescribers may have emphasized the prevention and treatment of chronic conditions such as osteoporosis in younger groups with a greater life expectancy [27]. In contrast to this attitude and even though the literature suggests that with HRT treatment, this group still benefits from increased bone mineral density [28] and reduced fracture risk [6], some practitioners, based on published guidelines and negative information in the media may emphasize other treatments. In our study, adverse effects and the fear of cancer among GPs and adverse effects and social alarm in the GY group were the most common reasons for this attitude. Although these data are in agreement with previous studies of our group in other countries [16], unfortunately, it is not clear, whether different demands of the patients to GY respect GP could explain the observed differences. Having the menopause and going to the gynaecologist, mainly in the private sector, are factors related to the prescription of HRT in this survey. On the other hand, in our study, we did not find variations in HRT prescription rates related to where doctors live; however, others have found striking differences in patterns of HRT prescription depending on geographical location [29]. The fact that gynaecologists prescribe hormone replacement therapy more frequently than general practitioners may be explained by the better access they have to the complementary tests the users of HRT have to undergo, and by their having more specific information on this particular issue. Nevertheless, this does not clarify the increasing number of prescriptions in the private sector. In this sense, practice variation has been found in a number of clinical areas, especially when there is uncertainty concerning the value of a treatment [30]. Both GYs and GPs have been advised to consider many aspects in this decision, including recent scien-
C. Castelo-Branco et al. / Maturitas 55 (2006) 308–316
tific evidence and women’s thoughts, concerns, and individual risk factors [30,31]. Part of the practice variation between GYs and GPs may be explained by differences in the perception of the value of HRT, given the puzzling excess of evidence regarding the effectiveness of HRT. Further studies on the prescription of HRT should explore how physicians evaluate the existing evidence for individual patients.
Acknowledgements The present study was supported by a grant from Organon Spain. The opinions reflected in the manuscript are solely those of the authors.
References [1] Michels KB. Hormone replacement therapy in epidemiologic studies and randomized clinical trials—are we checkmate? Epidemiology 2003;14:3–5. [2] Giannakakis IA, Haidich AB, Contopoulos-Ioannidis DG, Papanikolaou GN, Baltogianni MS, Ioannidis JP. Citation of randomized evidence in support of guidelines of therapeutic and preventive interventions. J Clin Epidemiol 2002;55:545–55. [3] Laine C. Postmenopausal hormone replacement therapy: how could we have been so wrong? Ann Intern Med 2002;137:290. [4] Speroff L. The impact of the Women’s Health Initiative on clinical practice. J Soc Gynecol Investig 2002;9:251–3. [5] Humphrey LL, Chan B, Sox H. Postmenopausal hormone replacement therapy and the primary prevention of cardiovascular disease. Ann Intern Med 2002;137:273–84. [6] Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321–33. [7] Carney PA, Tosteson AN, Titus-Ernstoff L, et al. Hormone therapies in women aged 40 and older: prevalence and correlates of use. Maturitas 2006;53:65–76. [8] Olesen AV, Johnsen SP, Mortensen JT, Boggild H, Olsen J, Sorensen HT. Socioeconomic status and use of postmenopausal hormone replacement therapy among Danish women. Acta Obstet Gynecol Scand 2005;84:639–44. [9] Donker GA, Spreeuwenberg P, Bartelds AI, van der Velden K, Foets M. Hormone replacement therapy: changes in frequency and type of prescription by Dutch GPs during the last decade of the millennium. Fam Pract 2000;17:508–13. [10] Jolleys JV, Olesen F. A comparative study of prescribing of hormone replacement therapy in USA and Europe. Maturitas 1996;23:47–53. [11] Bermejo MJ, Perez IR. Physicians and the prescription of hormone replacement therapy in Spain. Health Policy 2005; 73:58–65.
315
[12] Li C, Samsioe G, Lidfelt J, Nerbrand C, Agardh CD. Important factors for use of hormone replacement therapy: a populationbased study of Swedish women The Women’s Health in Lund Area (WHILA) Study. Menopause 2000;7:273–81. [13] Levy BT, Ritchie JM, Smith E, Gray T, Zhang W. Physician specialty is significantly associated with hormone replacement therapy use. Obstet Gynecol 2003;101:114–22. [14] Blumel JE, Castelo-Branco C, Riquelme R, et al. Use of hormone replacement therapy among Chilean women: a comparison between socioeconomic levels. Menopause 2002;9:377–80. [15] Blumel JE, Castelo-Branco C, Kerrigan N, et al. Influences of hormone replacement therapy on postmenopausal women’s health perceptions. Menopause 2003;10:235–40. [16] Blumel JE, Castelo-Branco C, Chedraui PA, et al. Patients’ and clinicians’ attitudes after the Women’s Health Initiative study. Menopause 2004;11:57–61. [17] Grisso JA, Baum CR, Turner BJ. What do physicians in practice do to prevent osteoporosis? J Bone Miner Res 1990;5:213–9. [18] Greendale GA, Carlson KJ, Schiff I. Estrogen and progestin therapy to prevent osteoporosis: attitudes and practices of general internists and gynecologists. J Gen Intern Med 1990;5:464–9. [19] Rolnick SJ, Kopher RA, Compo RB, Kelley ME, DeFor TA. Provider attitudes and self-reported behaviors related to hormone replacement therapy. Menopause 1999;6:257–63. [20] Saver BG, Taylor TR, Woods NF, Stevens NG. Physician policies on the use of preventive hormone therapy. Am J Prev Med 1997;13:358–65. [21] McIntyre RS, Konarski JZ, Grigoriadis S, et al. Hormone replacement therapy and antidepressant prescription patterns: a reciprocal relationship. CMAJ (Journal de L’Association Medicale Canadienne) 2005;172:57–9. [22] Kaplan B, Aschkenazi-Steinberg S, Yogev Y, Nahum R, Sulkes J, Phisher M. Gynecologists’ trends and attitudes toward prescribing hormone replacement therapy during menopause. Menopause 2002;9:354–9. [23] Reynolds RF, Walker AM, Obermeyer CM, Rahman O, Guilbert D. Discontinuation of postmenopausal hormone therapy in a Massachusetts HMO. J Clin Epidemiol 2001;54:1056– 64. [24] Stearns V, Beebe KL, Iyengar M, Dube E. Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial. JAMA 2003;289:2827–34. [25] Gabriel SR, Carmona L, Roque M, Sanchez GL, Bonfill X. Hormone replacement therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst Rev 2005 [CD002229]. [26] Farquhar CMMJ, Lethaby A, Lamberts Q, Suckling JA, Cochrane HT, Study Group. Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev 2005 [CD004143]. [27] Redelmeier DA, Tan SH, Booth GL. The treatment of unrelated disorders in patients with chronic medical diseases. N Engl J Med 1998;338:1516–20 [see comment]. [28] Castelo-Branco C, Figueras F, Sanjuan A, et al. Long-term compliance with estrogen replacement therapy in surgical postmenopausal women: benefits to bone and analysis of fac-
316
C. Castelo-Branco et al. / Maturitas 55 (2006) 308–316
tors associated with discontinuation. Menopause 1999;6:307– 11. [29] Keating NL, Cleary PD, Rossi AS, Zaslavsky AM, Ayanian JZ. Use of hormone replacement therapy by postmenopausal women in the United States. Ann Intern Med 1999;130:545–53 [see comment].
[30] Eddy DM. Variations in physician practice: the role of uncertainty. Health Aff 1984;3:74–89. [31] Mort EA. Clinical decision-making in the face of scientific uncertainty: hormone replacement therapy as an example. J Fam Pract 1996;42:147–51.
The prescription of hormone replacement therapy in Spain: Differences between general practitioners and gynaecologists Camil Castelo-Branco a,∗ , Javier Ferrer a,b , Santiago Palacios a,c , Sonia Cornago a a
Hospital Cl´ınic, University of Barcelona, Villarroel 170, 08036-Barcelona, Spain b University of Oviedo, Spain c Instituto Palacios, Madrid, Spain
Received 12 January 2006; received in revised form 11 April 2006; accepted 11 April 2006
Abstract Objectives: The purpose of this study was to determine the frequency with which hormone replacement therapy (HRT) was prescribed and to identify physician-related factors associated with the prescription of HRT in Spain. Study design: A descriptive cross-sectional survey based on a personal interview with a structured questionnaire was conducted in April 2005 with physicians aged 25–65 years. A total of 2700 doctors were asked to participate in this prospective study (1350 GY and 1350 GP). This number included 270 gynaecologists (GY group) and 270 general practitioners (GP group). Results: Only 10% of gynaecologists and 19.4% of GPs had never prescribed HRT. The reasons given for not prescribing HRT were adverse effects and the fear of cancer among GPs and adverse effects and social alarm in the GY group. Phytoestrogens were the most commonly used alternative; however, GPs were more willing to use antidepressants and benzodiazepines than GYs. The frequency of HRT prescription in symptomatic women was significantly higher among GYs. The main reasons for prescribing HRT were climacteric complaints and improvement in life quality for GYs and, climacteric complaints and the prevention of osteoporosis for GPs. Seventy-eight percent of GYs prescribing hormones referred a high degree of satisfaction with HRT, whereas only 50% of GPs expressed a similar attitude. Conclusions: Concern for HRT prescription in Spain is high. Adverse effects and the fear of cancer are negative conditioning factors in the prescription of HRT, whereas climacteric complaints, quality of life and the prevention of osteoporosis are positive conditioning factors. GYs are more willing to use HRT than GPs. This contrast may reflect the indecision of GPs regarding the preventive value of HRT. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Hormone replacement therapy; Menopause; Drug prescription; Health care givers; Gynecologist; General practitioner
1. Introduction ∗
Corresponding author. E-mail address: [email protected] (C. Castelo-Branco).
Hormone replacement therapy (HRT) is a widespread intervention during the climacteric period,
0378-5122/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.maturitas.2006.04.023
C. Castelo-Branco et al. / Maturitas 55 (2006) 308–316
which was widely prescribed during the second half of last century despite the lack of conclusive studies on its hypothetical beneficial role. The most common arguments for the prescription of HRT are based primarily on the position assumed by few authors who consider the menopause an endocrinopathy, where the reduction of estrogen levels is a risk factor for several prevalent diseases that constitute the most frequent causes of mortality in this sector of the population; and secondly, from a more ‘natural’ perspective, HRT has been regarded as a treatment of choice to alleviate only the symptoms related to estrogen decline. However, until now, most of these prescriptions were based on the results of observational studies not supported by randomised controlled trials (RCT) [1–3]. At present, scientific controversy on this topic is particularly active, since the results of several RCTs not only fail to demonstrate any preventive role of HRT but also link it to several diseases including breast cancer, heart disease, stroke and pulmonary embolism [4–6]. The USA and Australia are the countries with the highest prescription rates followed by north-European countries. The frequency of prescription ranges from 62% in USA [7] and 14.9% in Denmark [8] to 3 per 1000 registered women in The Netherlands [9]. Additionally, few studies have been carried out on this topic in Spain with conflicting results [10,11]. The characteristics of HRT users in Spain have not been studied in depth; however, according to data published elsewhere, it is more frequent in women with early and surgical menopause, and in women with severe climacteric complaints [12,13]. Moreover, most of the women who use HRT have a high socio-economic level, with a higher level of education and work out of home [14]. In addition, they considered themselves to be healthier and to have a smaller risk for cardiovascular disease [15]. On the other hand, doctors’ attitudes towards HRT have barely been explored, even though the knowledge they have, the information from journals and their standpoint on this therapy have a real influence on final prescription [13,16]. Several studies have reported that gynaecologists feel more strongly than other physicians about the preventive role of HRT [13,17–20]. However, data comparing current HRT use in women seen by gynaecologists versus and its use with women seen
309
by general practitioners or family physicians for socio-demographics, preventive health behaviours, and co-morbidities of the patients are scant [13]. The purposes of this paper were to determine the major reasons for HRT prescription and to identify doctors’ socio-demographic factors related to the prescription of the treatment in women aged 40–65 years in Spain.
2. Materials and methods A descriptive cross-sectional survey was conducted in April 2005, with doctors aged 25–65 years from the reference population of four of the major cities in Spain (Madrid, Barcelona, Seville and Valencia). All the participants were gynaecologists or GPs. All of them were interviewed in person at their homes or by telephone by professional interviewers. The sample size was established based on the fact that the studied condition (the prescription of postmenopausal HRT) may affect different percentages of women [18–22] (for this reason and due to the high variability of the information provided in the relevant literature, additional experts from the area were consulted). Thus, using statistics software to calculate sample size with a 5% maximal acceptable error, 95% confidence level, potential of 80% and possible losses of 20%, we determined that the number of doctors estimated for the final sample was 500. Secondly, from this population, assuming that the prescription proportion among gynaecologists and general practitioners would be similar [13], we determined that 250 doctors were required in each group. Therefore, a total of 1343 gynaecologists and 1357 GPs were asked to participate in this study. Among them, 80% in both groups denied participation, leaving 270 GYs and 270 GPs for the survey. Subjects were selected at random from a list of 3124 doctors provided by a pharmaceutical studies company (Salvetti and Llompart, Barcelona, Spain) (data obtained from the health departments of different local governments, Spanish Health Annual Report 2004–2005 and phone list). Doctors with a physical incapacity to answer a questionnaire by telephone or at home, and those who had expressed their desire not to take part in the study were excluded. The selection process was by phone and, after inclusion, all doctors
310
C. Castelo-Branco et al. / Maturitas 55 (2006) 308–316
were interviewed in person at their homes or offices by professional interviewers. The information was gathered using a semistructured questionnaire specifically designed to collect information on the prescription for climactericrelated complaints. The questionnaire included 9 items to consider the subjects selectable, 12 items to evaluate socio-demographics aspects, 6 items related to perception and behaviours on climacteric complaints, 7 items related to knowledge of therapies for the climacteric, 6 items related specifically to knowledge and prescription of HRT, 9 items related to the way doctors identify pharmaceutical brand names and finally, 34 items related to the prescription of HRT for doctors who prescribe HRT, 12 for doctors who have prescribed it in the past and 8 for those who had never prescribed HRT. The questions were based on instruments used in previous studies (Salvetti and Llombart. Unpublished data) and aimed to be clear and concise so as to increase reliability. Each interview took around 30 min and if the doctor was not at home, up to three calls were made at different times of the day in order to reach him/her. Finally, the satisfaction with the different treatments for climacteric complaints was assessed by a visual analogue scale (VAS), with values from 0 (left side: absolutely unsatisfied) to 10 cm (right side: absolutely satisfied). The data were analyzed using a personal computerbased software package (SPSS 12.0, SPSS Inc. Headquarters, 233 South Wacker Drive, 11th floor, Chicago, IL 60606, USA). The outcome measure of the study was the frequency of the prescription of HRT, defined as any pharmaceutical composite that has an estrogenic or estrogenic and progestogenic action administered by any route and prescribed by a doctor, regardless of his/her speciality. The rest of the variables were considered predictor variables. For the descriptive analysis, the habitual statistics, frequencies and percentages for the qualitative variables, and mean and standard deviation for the quantitative variables, were used. Differences between the groups were evaluated using the Student’s t-test, ANOVA or the Kruskall– Wallis test, according to the homogeneity of the variance measured with the Bartlet test. Comparisons between groups for percentages were made using χ2 . A value of p less than 0.05 was considered statistically significant.
3. Results From the list of 3124 doctors, contact was made with 2700 doctors, of whom 2160 did not meet the inclusion criteria or did not wish to answer, leaving a total of 540 interviews, and a response rate of 20%. Table 1 shows the socio-demographic characteristics of the sample. Half of the doctors were aged 45–65 years, and 50% were females. It is worthy of note that a significant percentage (33.3%) of the entire sample were not HRT prescribers. As expected, gynaecologists worked more frequently in hospitals than GPs (p < 0.000) and were more willing to prescribe HRT (p = 0.062). Only 10% of gynaecologists and 19.4% of GPs had never prescribed HRT. In addition, 23.42% (63/269) GYs and 14.17% (38/268) GPs do not prescribe HRT at present although they have prescribed it in the past. Table 2 shows the reasons given for not prescribing HRT. Adverse effects and the fear of cancer among GPs and adverse effects and social alarm in the GY group were the most common reasons. Interestingly, among doctors who had previously prescribed HRT, women’s reluctance to HRT was an increasing factor for GYs while for GPs, it was negative information from medical journals. Phytoestrogens were the most used alternative; however, GPs were more willing to use antidepressants and benzodiazepines than GYs (Table 3). Table 4 shows the main reasons for prescribing HRT among the doctors who indicate the therapy in more than 50% of subjects complaining of menopause-related symptoms. Climacteric complaints and improvement in life quality for GYs and climacteric complaints and the prevention of osteoporosis for GPs were the most important factors condition prescription. Reasons given by ≤50% of prescribing doctors prescribing in for not increasing their prescription rates are shown in Table 2. In most cases, the risk of cancer and adverse effects are again the main reasons; however, for GYs, women’s reluctance is once more a rising factor. The frequency of prescription among women with symptoms was 93% in the GY group, which was significantly higher than the frequency among those attended by GPs (85%) (OR = 1.25; CI 95%: 1.09–1.89). The reasons most associated with the prescription of HRT were surgery (55% GY, 48% GP), early menopause (56
C. Castelo-Branco et al. / Maturitas 55 (2006) 308–316
311
Table 1 Socio-demographic characteristics of the sample (N = 540) Gynaecologists
General practitioners
p-Valuea
Age <35 years old 35–45 years old 46–55 years old >55 years old
61 74 108 27
39 96 118 17
NS NS NS NS
Gender Male Female
134 136
135 135
NS NS
95 95 40 40
67 67 68 68
ND ND ND ND
81 129 125 2 1
221 70 9 1 2
59
33
27 63
52 38
NS (0.062) NS (0.062)
Prescribing HRT Rate ≤ 50% patients Rate > 50% patients Do not know % of HRT vs. no HRTb
98 81 1
115 63 2
NS (0.062) NS (0.062) NS (0.062)
THS prescription (rate THS >50% patients) Place of work Barcelona Madrid Sevilla Valencia
17 43 7 14
9 31 11 12
NS NS NS NS
81
63
NS
45 36
34 29
NS NS
81
63
NS
Place of work (location) Barcelona Madrid Sevilla Valencia Place of work (sector)a National Health Service Centers (ambulatory clinics) Private center Hospital (outpatients) Menopause unit (public) Menopause unit (private) Number of doctors working in public and private HRT prescriptions No prescribing HRT Never Former
Total rate >50% patients Gender Male Female Total rate >50% patients a b
0.0000 0.0000 0.0000 NS NS
Multiple choice (several doctors work in both public and private centres). Several doctors did not remember their prescription rates.
GY, 46 GP) and the prevention of osteoporosis (14% GY, 15% GP). It was observed that the prescription of HRT was greater if the doctor was a gynaecologist (81/179
versus 63/178) and worked in the private sector (OR = 1.51; CI 95%: 1–2.31). In contrast, no differences were observed regarding the place of work (Madrid/Barcelona/Seville/Valencia p = 0.244;
312
C. Castelo-Branco et al. / Maturitas 55 (2006) 308–316
Table 2 Reasons given for not prescribing (more) HRT Gy
GP n
p-Value
n
%
Doctors who had never prescribed HRT Adverse effects Cancer risk Other more safe therapies available Negative data from medical journals Women reluctance Social alarm Lack of specialist (GY) prescription Government restriction 5 years use limit Lack of knowledge To avoid nuisances with Government Cost Others
27 18 3 7 5 3 5 – 3 1 0 0 0 4
10* 67 11 26 19 11 19 – 11 4 0 0 0 15
52 36 24 9 10 6 4 9 3 2 4 1 1 1
% 19.26* 69 46 17 19 12 8 17 6 4 8 2 2 2
<0.01 NS 0.002 NS NS NS NS – NS NS NS NS NS 0.026
Doctors who do not prescribe HRT currently but who had previously prescribed in the past Adverse effects Cancer risk Other more safe therapies available Negative data from medical journals Women reluctance Social alarm Lack of specialist (GY) prescription Government restriction 5 years use limit Lack of knowledge To avoid nuisances with Government Cost Others
63
23.33*
38
14.07*
<0.01
33 21 11 19 26 24 – 3 5 0 1 0 5
52 33 17 30 41 38 – 5 8 0 2 0 8
21 15 6 12 3 8 2 0 1 0 1 0 0
55 39 16 32 8 21 5 0 3 0 3 0 0
NS NS NS NS 0.000 NS (0.076) – NS NS NS – NS
Doctors who prescribe HRT currently but ≤50% of cases Adverse effects Cancer risk Other more safe therapies available Negative data from medical journals Women reluctance Social alarm Lack of specialist (GY) prescription Government restriction 5 years use limit Lack of knowledge To avoid nuisances with Government Cost Others
98
36.29*
42.59*
NS
26 41 15 17 36 27 – 2 6 0 0 4 13
27 42 15 17 37 28 – 2 6 0 0 4 13
35 39 19 9 14 18 22 3 6 0 0 2 0
NS NS NS 0.059 0.000 NS – NS NS – NS 0.000
115 40 45 22 10 16 21 25 4 7 0 0 2 0
* Total numbers differ because some doctors give more than one reason. GY: gynaecologist, GP: general practice. Percentages refer to each sub-sample except those marked with an asterisk, which refer to the entire sample.
C. Castelo-Branco et al. / Maturitas 55 (2006) 308–316
313
Table 3 Complementary and alternative therapies to HRT
Phytoestrogens-phytotherapy Raloxifene Veralipride Bisphosphonates Healthy life styles Benzodiazepines Relaxation response/guided techniques Antidepressants Oil therapy Homeopathic remedies Herbal therapy Other alternatives
Gya (n = 27)
Gyb (n = 63)
GPa (n = 52)
GPb (n = 38)
n
%
n
%
n
%
n
%
21 10 13 14 5 0 2 1 2 2 3 0
78 37 48 52 19 0 7 4 7 7 11 0
58 34 26 32 9 3 0 2 4 0 4 0
92 54 41 51 14 5 0 3 6 0 6 0
43 19 17 17 15 12 8 9 5 3 2 2
83 37 33 33 29 23 15 17 10 6 4 4
32 16 12 14 4 8 2 4 2 0 1 0
84 42 32 37 11 21 5 11 5 0 3 0
p-Valuea
p-Valueb
NS NS NS NS NS 0,006 NS NS (0,087) NS NS NS NS
NS NS NS NS NS 0,011 NS (0,067) NS NS – NS –
a
Doctors who had never prescribed HRT. Doctors who do not prescribe HRT at present but have prescribed HRT in the past. Data are in percentages. Total numbers differ because some doctors give more than one reason. b
Table 4 Reasons for prescribing HRT GY (n = 81)
Climacteric symptoms Osteoporosis prevention Improvement in quality of life Higher efficacy than alternatives therapies Prescribed by a specialist Easier control than other therapies Improve sexuality Cardiovascular disease prevention Uncomplicated use Less expensive than alternative therapies Others
GP (n = 63)
p-Value
n
%
n
%
66 11 27 23 – 6 8 5 5 0 1
81 14 33 28 – 7 10 6 6 0 1
54 20 13 15 12 11 6 6 4 2 0
86 32 21 24 19 17 10 10 6 3 0
NS 0.008 NS NS – NS (0.064) NS NS NS NS NS
Data from doctors (GY: gynaecologist, GP: general practice) who prescribe HRT in more than 50% of subjects with menopause-related complaints.
OR = 0.70; CI 95%: 0.46–1.06) or gender (p = 0.182; OR = 1.40; IC 95%: 0.92–2.14). Finally, using the VAS, 78% of GYs prescribing hormones referred a high level of satisfaction with HRT (VAS ≥ 8), whereas only 50% of GPs expressed a similar attitude (p < 0.0000).
4. Discussion Before taking into consideration the results of this survey, one must keep in mind a potential problem of validity in this study since the impact of our results
may be severely hampered by the low response proportion. Moreover, as it is a survey based on the opinions of interviewed doctors, the subjects’ memory may be diminished, particularly regarding the information given by doctors who visit menopausal patients sporadically or who did so some time ago. To reduce this error, questions in the survey referred to very specific information which was, in general, easy to remember. Furthermore, doctors were requested to supply the trademark of the drug and the administration route. In addition, as the interview was a semi-structured questionnaire, it was possible for the interviewer to compare the answers given by the subjects. Another limitation to
314
C. Castelo-Branco et al. / Maturitas 55 (2006) 308–316
this study was the fact that it was a relatively small survey with doctors recruited from the four largest cities in Spain, and results may not be representative of the doctor population as a whole. Clinical trials show that hormone therapy is an effective treatment for vasomotor symptoms and vaginal dryness. HRT improves other symptoms, including sleep and mood disturbances, in women who have menopause symptoms. In the Women’s Health Initiative (WHI) controlled clinical trial, estrogen plus progestin therapy reduced fracture risk and colon cancer risk, neither reduced the risk of heart disease, and increased the risk of breast cancer, stroke and deep vein thrombosis [6]. The WHI clinical trial found overall harm rather than benefit from medication. This surprised professionals, made newspaper headlines, and changed prescription practices. Thus, after WHI publication, with the reduced popularity of HRT [16], physicians may encounter women who are experiencing somatic symptoms or psychological disorders that worsen at the time of menopause. A significant decrease in the number of HRT prescriptions was associated with a statistically significant increase in prescriptions of psychoactive drugs (mainly benzodiazepines and antidepressants) [21] and phytoestrogens [22]. In this survey, phytoestrogens were the most used alternative; however, GPs were more willing to use antidepressants and benzodiazepines than GYs. Accordingly, Reynolds et al. have noted associations between changes in HRT and antidepressant prescription patterns [23]. The increase in prescriptions of benzodiazepines and antidepressants among GPs suggests that such drugs are being prescribed for (psychological and physical) symptoms previously controlled with the use of HRT [24]. It is worthy of note that in this survey 19% of GYs and 14% of GPs prescribed HRT for other indications, which may indicate a preventive attitude and a minor impact of the negative information published in the media on this topic. In addition, 6% of GYs and 10% of GPs also prescribed HRT for cardiovascular prevention. This fact is remarkable since most recent reviews support the hypothesis that in relatively healthy women, HRT significantly increased cardiovascular risk, including the risk of venous thromboembolism or coronary event (after 1 year’s use) and stroke (after 3 years) and that HRT is not indicated for the routine management of chronic disease [25,26]. This prevailing opinion has been denied by those
doctors under the assumption that cardioprotection is possible. Factors influencing a physician’s decision to prescribe medication for the climacteric have not been widely studied. The results of the current study suggest that climacteric complaints and improved life quality for GYs and climacteric complaints and the prevention of osteoporosis for GPs as well as differing HRT tolerability profiles are important factors. Several studies have reported that gynaecologists feel more strongly than other physicians about the preventive role of HRT [17–20]. These prescribers may have emphasized the prevention and treatment of chronic conditions such as osteoporosis in younger groups with a greater life expectancy [27]. In contrast to this attitude and even though the literature suggests that with HRT treatment, this group still benefits from increased bone mineral density [28] and reduced fracture risk [6], some practitioners, based on published guidelines and negative information in the media may emphasize other treatments. In our study, adverse effects and the fear of cancer among GPs and adverse effects and social alarm in the GY group were the most common reasons for this attitude. Although these data are in agreement with previous studies of our group in other countries [16], unfortunately, it is not clear, whether different demands of the patients to GY respect GP could explain the observed differences. Having the menopause and going to the gynaecologist, mainly in the private sector, are factors related to the prescription of HRT in this survey. On the other hand, in our study, we did not find variations in HRT prescription rates related to where doctors live; however, others have found striking differences in patterns of HRT prescription depending on geographical location [29]. The fact that gynaecologists prescribe hormone replacement therapy more frequently than general practitioners may be explained by the better access they have to the complementary tests the users of HRT have to undergo, and by their having more specific information on this particular issue. Nevertheless, this does not clarify the increasing number of prescriptions in the private sector. In this sense, practice variation has been found in a number of clinical areas, especially when there is uncertainty concerning the value of a treatment [30]. Both GYs and GPs have been advised to consider many aspects in this decision, including recent scien-
C. Castelo-Branco et al. / Maturitas 55 (2006) 308–316
tific evidence and women’s thoughts, concerns, and individual risk factors [30,31]. Part of the practice variation between GYs and GPs may be explained by differences in the perception of the value of HRT, given the puzzling excess of evidence regarding the effectiveness of HRT. Further studies on the prescription of HRT should explore how physicians evaluate the existing evidence for individual patients.
Acknowledgements The present study was supported by a grant from Organon Spain. The opinions reflected in the manuscript are solely those of the authors.
References [1] Michels KB. Hormone replacement therapy in epidemiologic studies and randomized clinical trials—are we checkmate? Epidemiology 2003;14:3–5. [2] Giannakakis IA, Haidich AB, Contopoulos-Ioannidis DG, Papanikolaou GN, Baltogianni MS, Ioannidis JP. Citation of randomized evidence in support of guidelines of therapeutic and preventive interventions. J Clin Epidemiol 2002;55:545–55. [3] Laine C. Postmenopausal hormone replacement therapy: how could we have been so wrong? Ann Intern Med 2002;137:290. [4] Speroff L. The impact of the Women’s Health Initiative on clinical practice. J Soc Gynecol Investig 2002;9:251–3. [5] Humphrey LL, Chan B, Sox H. Postmenopausal hormone replacement therapy and the primary prevention of cardiovascular disease. Ann Intern Med 2002;137:273–84. [6] Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321–33. [7] Carney PA, Tosteson AN, Titus-Ernstoff L, et al. Hormone therapies in women aged 40 and older: prevalence and correlates of use. Maturitas 2006;53:65–76. [8] Olesen AV, Johnsen SP, Mortensen JT, Boggild H, Olsen J, Sorensen HT. Socioeconomic status and use of postmenopausal hormone replacement therapy among Danish women. Acta Obstet Gynecol Scand 2005;84:639–44. [9] Donker GA, Spreeuwenberg P, Bartelds AI, van der Velden K, Foets M. Hormone replacement therapy: changes in frequency and type of prescription by Dutch GPs during the last decade of the millennium. Fam Pract 2000;17:508–13. [10] Jolleys JV, Olesen F. A comparative study of prescribing of hormone replacement therapy in USA and Europe. Maturitas 1996;23:47–53. [11] Bermejo MJ, Perez IR. Physicians and the prescription of hormone replacement therapy in Spain. Health Policy 2005; 73:58–65.
315
[12] Li C, Samsioe G, Lidfelt J, Nerbrand C, Agardh CD. Important factors for use of hormone replacement therapy: a populationbased study of Swedish women The Women’s Health in Lund Area (WHILA) Study. Menopause 2000;7:273–81. [13] Levy BT, Ritchie JM, Smith E, Gray T, Zhang W. Physician specialty is significantly associated with hormone replacement therapy use. Obstet Gynecol 2003;101:114–22. [14] Blumel JE, Castelo-Branco C, Riquelme R, et al. Use of hormone replacement therapy among Chilean women: a comparison between socioeconomic levels. Menopause 2002;9:377–80. [15] Blumel JE, Castelo-Branco C, Kerrigan N, et al. Influences of hormone replacement therapy on postmenopausal women’s health perceptions. Menopause 2003;10:235–40. [16] Blumel JE, Castelo-Branco C, Chedraui PA, et al. Patients’ and clinicians’ attitudes after the Women’s Health Initiative study. Menopause 2004;11:57–61. [17] Grisso JA, Baum CR, Turner BJ. What do physicians in practice do to prevent osteoporosis? J Bone Miner Res 1990;5:213–9. [18] Greendale GA, Carlson KJ, Schiff I. Estrogen and progestin therapy to prevent osteoporosis: attitudes and practices of general internists and gynecologists. J Gen Intern Med 1990;5:464–9. [19] Rolnick SJ, Kopher RA, Compo RB, Kelley ME, DeFor TA. Provider attitudes and self-reported behaviors related to hormone replacement therapy. Menopause 1999;6:257–63. [20] Saver BG, Taylor TR, Woods NF, Stevens NG. Physician policies on the use of preventive hormone therapy. Am J Prev Med 1997;13:358–65. [21] McIntyre RS, Konarski JZ, Grigoriadis S, et al. Hormone replacement therapy and antidepressant prescription patterns: a reciprocal relationship. CMAJ (Journal de L’Association Medicale Canadienne) 2005;172:57–9. [22] Kaplan B, Aschkenazi-Steinberg S, Yogev Y, Nahum R, Sulkes J, Phisher M. Gynecologists’ trends and attitudes toward prescribing hormone replacement therapy during menopause. Menopause 2002;9:354–9. [23] Reynolds RF, Walker AM, Obermeyer CM, Rahman O, Guilbert D. Discontinuation of postmenopausal hormone therapy in a Massachusetts HMO. J Clin Epidemiol 2001;54:1056– 64. [24] Stearns V, Beebe KL, Iyengar M, Dube E. Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial. JAMA 2003;289:2827–34. [25] Gabriel SR, Carmona L, Roque M, Sanchez GL, Bonfill X. Hormone replacement therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst Rev 2005 [CD002229]. [26] Farquhar CMMJ, Lethaby A, Lamberts Q, Suckling JA, Cochrane HT, Study Group. Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev 2005 [CD004143]. [27] Redelmeier DA, Tan SH, Booth GL. The treatment of unrelated disorders in patients with chronic medical diseases. N Engl J Med 1998;338:1516–20 [see comment]. [28] Castelo-Branco C, Figueras F, Sanjuan A, et al. Long-term compliance with estrogen replacement therapy in surgical postmenopausal women: benefits to bone and analysis of fac-
316
C. Castelo-Branco et al. / Maturitas 55 (2006) 308–316
tors associated with discontinuation. Menopause 1999;6:307– 11. [29] Keating NL, Cleary PD, Rossi AS, Zaslavsky AM, Ayanian JZ. Use of hormone replacement therapy by postmenopausal women in the United States. Ann Intern Med 1999;130:545–53 [see comment].
[30] Eddy DM. Variations in physician practice: the role of uncertainty. Health Aff 1984;3:74–89. [31] Mort EA. Clinical decision-making in the face of scientific uncertainty: hormone replacement therapy as an example. J Fam Pract 1996;42:147–51.