European Journal of Obstetrics & Gynecology and Reproductive Elsevier
Biology, 31 (1990) 55-61
55
EUROBS 00954
General practitioners use of hormone-replacement therapy in Yorkshire F.C. Bryce and R.J. Lilford Department
of Obstetrics and Gynaecologv, St. James’s University Hospital, L.eeak, U.K. Accepted for publication 4 October 1989
Questionnaires were sent to 1000 general practitioners (GPs) in the Yorkshire Region to obtain information about their approach to the use of hormone-replacement therapy (HRT) in the menopause. A total of 310 GPs returned completed questionnaires. These showed widely varying views. The majority of GPs estimated that less than 10% of their perimenopausal patients had taken HRT at some time. There was confusion about the reported effects of HRT, on the risks of endometrial carcinoma and on ischaemic heart disease. Thus, while 86% correctly judged that HRT was protective against osteoporosis, 70% concluded against prevailing opinion that combined preparations increase the risk of endometrial cancer. In contrast to the bulk of evidence, nearly 50% of respondents believed that the risk of ischaemic heart disease was also increased by HRT. A number of GPs considered lack of an authoritive lead from epidemiology to be their greatest difficulty in forming an opinion on the desirability of HRT. The general approach to HRT was cautious in respect of both the frequency and the duration of the therapy. Less than a quarter of the GPs were sympathetic to the idea of prophylactic HRT and only 7% routinely discussed this possibility with menopausal patients, while the majority felt that the duration of therapy should be limited to 2 years or less. Most respondents also showed intuitive resistance to the idea of ‘mass therapy’ at the menopause and expressed concern at the idea of ‘interfering with nature’. Hormone replacement therapy; General practitioner
IntmductIon
Oestrogen and progesterone replacement therapy (HRT) in the menopause is effective in reducing a number of symptoms associated with the climacteric, such as
Correspondence: U.K.
F.C. Bryce, Department of Obstetrics and Gynaecology,
0028-2243/90/$03.50
St James’s Hospital, Leeds,
Q 1990 Elseviex Science. Publishers B.V. (Biomedical Division)
56
hot flushes, dry vagina and mood changes [l-5]. Many case-control studies have shown a protective effect against endometrial cancer [6,7]; ischaemic heart disease [S-14] and osteoporosis [15-181, while the risks of hypertension [lo] and venous thromobosis 19,201 are reported as unchanged. The effect on the incidence of breast cancer is the most important unknown effect although there is a suggestion that it may rise slightly after 10 years of use [21-271. It could be argued from these findings that the health of many women might be improved by a course of HRT, although our present knowledge is limited by the lack of randomised or quasi-randomised studies. The question of HRT is of great public health interest. We conducted a study to assess opinions and attitudes of general practitioners to the menopause and HRT under a wide variety of circumstances. Our clinical experience has suggested that many doctors are reluctant to prescribe HRT and that this is based on intuition and general philosophical principles rather than an analysis of costs and benefits to health. A questiomaire was designed to test this observation. Subjects and methods Lists of General Practitioners (GPs) in the region were obtained from the Family Practitioner Committee. One thousand questionnaires were sent out by three Family Practitioner Committees to GPs in their area. A total of 320 responses were received in the 4 months following distribution. Twelve responses were from GPs who did not have any post-menopausal patients on their lists (student health practitioners). This left a total of 308 completed questionnaires; a response rate of 31%. In order to encourage a response the questiomraire was made anonymous and it was therefore impossible to identify which GPs had not responded. This questionnaire consisted of a series of nine multiple-choice questions designed to assess both current practice and attitudes towards hormone-replacement therapy. Results The questionnaire first asked for an estimate of the proportion of the practice’s post-menopausal patients who had taken HRT: 70% responded that less than 10% had done so, 23% thought that lo-25% of patients had received HRT, and a further 2% estimated that 25-50% of women had taken this treatment. Only 0.66% thought that over half of their post-menopausal patients had taken HRT, while 4% of respondents were unable to answer this question. When asked whether HRT was discussed with patients around the time of the menopause, only 8% of the GPs said that this was routinely done, while the remainder said they would do so if the patient complained of menopausal symptoms or in response to a direct request for information from a patient. Contra-indications to HRT that GPs regarded as ‘absolute’ are shown in Fig. 1. The majority (94.3%) considered breast cancer, active liver disease (91.6%), thrombo-embolic disease (88.3%) and a previous cerebrovascular accident (75.3%) to be absolute contra-indications. There was less certainty about ischaemic heart disease, heavy smoking,
benign
breast
dis.
mod. hypertension obesity heavy smoking ischaemic
heart dis.
cerebrovascular
dis.
thrombo-embolic
dis.
E. rel. liver dis. breast cancer 0
10 20
30
40
50
60
70
80
90100
c/o
Fig. 1. Pre-existing HRT. Percentage
medical disorders considered of respondents who regarded
by general the disorder
practitioners to be a contra-indication to as an absolute contraindication to HRT.
obesity and moderate hypertension. Only 6% felt that benign breast disease was an absolute contra-indication. Table I shows the investigations which GPs consider necessary before starting HRT. Measurement of blood pressure was almost always performed, whereas endometrial biopsy was virtually never deemed necessary. Routine examination of the breasts was always performed by 43% sometimes by 43% and never by 13% despite 94.3% of respondents indicating that breast cancer was an absolute contraindication to treatment. Preparations prescribed most frequently for patients who had retained or lost their uterus are listed, in order of frequency, in Table II; the combined preparations (Prempak and Cycloprogynova) were the most frequently prescribed. Unopposed oestrogens were still prescribed by 9% of practitioners for patients who had retained their uterus and by 38.5% of general practitioners for those patients who had had a hysterectomy. Most GPs reviewed patients at regular intervals: 73% at 6 monthly intervals, 23% at 3 monthly intervals, and only 4% saw patients at yearly intervals or not at all. When questioned about the how long HRT should usually be continued once it had been started, 32% of respondents felt that 2 years was adequate, 21% favoured 1 year and 18% felt that 5 years was optimal, 6.6% would treat forever, 4.0% for 10 years and the remainder could not specify a time period.
TABLE
I
Routine
examinations
Weight Blood pressure Cervical smear Pelvic examination Breast examination Endometrial biopsy
performed
before commencing
hormone
replacement
therapy
Always
Sometimes
Never
@I
(V
@I
40.6 94 63.3 52.6 43.3 0
48.3 5.3 33.3 42.3 43.3 8.0
11 0.66 3.3 5.0 13.3 92
58 TABLE II Hormone replacement preparation most frequently prescribed by general practitioners In the patient with a uterus Cycloprogynova Prempak Prempak C. Menophase Harmogen Trisequens Mixogen Premarin Estraderm patches (with progesterone)
In the hysterectomised patient 55% 54.6% 16.3% 9% 8% 7% 1.6% 0.66% 0.33%
Cycloprogynova Prempak Prempak C. Harmogen Premarin Ethinyloestradiol Menophase Trisequens Mixogen Cyclogest
61% 36% 3% 25% 12% 6.3% 4% 2.6% 1.66% 0.66
Footnote: Some general practitioners used more than one preparation consequently percentages add up to more than 100%.
The questionnaire then asked the effect GPs considered their chosen HRT preparation had on selected important diseases. Almost 70% thought the risk of endometrial cancer was increased, and only 8.3% thought this risk was decreased. Of those who thought HRT increased the risk of endometrial cancer, 80% were using ‘opposed’ therapy. 20% of doctors who recognised the increased risk of endometrial cancer with unopposed oestrogens nevertheless preferred this treatment for patients who had not had an hysterectomy. The doctors’ opinions about the effects of HRT on the risks of hypertension, myocardial infarction, breast cancer and osteoporotic fracture were sought. 87% of practitioners responded that the risk of hypertension was increased. 47% felt that the risk of myocardial infarction was also increased, 21% recognised that the risk may be decreased and 25% thought that HRT had no effect on the incidence of myocardial infarction. The risk of breast cancer was also considered to be increased by 68% of practitioners; 4% thought the risk was decreased while 22% thought HRT had no effect on the incidence and 6% had no opinion. The beneficial effect of HRT in the prevention of osteoporotic fracture was correctly recognised by the majority of GPs, with 86% indicating that HRT reduces the incidence of fracture. It was rather surprising to see that 11% of respondents indicated that HRT might increase the risk of fracture. The final question asked practitioners their opinion about offering HRT to all women who had no specific contra-indication to treatment. 15% strongly disagreed with this idea, 29.6% disagreed, 31.3% were neutral, 16.3% agreed and 7% strongly agreed. Respondents were also encouraged to enlarge upon their responses. The most frequent concerns were long-term effects of treatment, financial cost, patient compliance, time for supervision of treatment of a philosophical dislike of the concept of treating all patients regardless of symptoms. 60% of those who were against offering HRT routinely to all patients with no specific contra-indications invoked the principle of ‘primum non nocere’ and 40% made remarks to the effect that it was a mistake to prescribe for a natural process on a large scale. There were also comments voiced concerning lack of a clear lead from specialists.
59
Discussion This is the first survey to determine the attitudes of family doctors to HRT. This issue is of great public health interest since virtually half the population will experience the menopause and their subsequent mortality and morbidity could be influenced by medical practice. Most doctors were reluctant to use HRT. The majority of GPs estimated that less than 10% of their perimenopausal patients had taken HRT at some time. Once therapy had been commenced it was generally given for as short a time as possible. Only 29% of practitioners who replied were prepared to prescribe treatment for longer than 5 years. GPs had accurate knowledge of some effects of HRT, e.g. the protective effect against osteoporosis was recognised, as was the effect of unopposed oestrogens on endometrial cancer, We were, therefore, surprised by the finding that, of those practitioners who indicated that HRT increased the risk of developing endometrial carcinoma, 20% were not using combined oestrogen and progesterone preparations. Possibly they wished to avoid the effects of some progestagens on blood lipids and regarded this as the greater evil. Only 8.3% correctly recognised that the risk of developing endometrial cancer is probably reduced by cyclical HRT. GPs were correctly concerned about the effect of HRT on carcinoma of the breast, since this is one of the major concerns regarding long-term treatment. The current evidence suggests a small increase in risk after 10 years of continuous unopposed oestrogen therapy [21,24-261. Only one study [22] has examined the effect of current combined low dose oestrogen and progesterone preparations on this disease. Also awaited is evidence that HRT influences the incidence of ovarian carcinoma. Retrospective studies in America and Italy suggest a possible increase in the incidence of endometrial and clear cell carcinoma of the ovary, but the figures are not statistically significant [28-301. Prolonged use of the combined oral contraceptive decreases the risk of ovarian carcinoma by at least 50% so it might be hoped that HRT may provide similar protection against non-endometroid ovarian cancer [31]. An effect of HRT on the cardiovascular system was recognised by the majority of GPs - although the fact that this was beneficial was not! The bulk of the evidence now suggests that in contrast to the combined oral contraceptive, HRT does not cause or aggrevate essential hypertension [32,33]. Over half the practitioners indicated that HRT would increase the risk of ischaemic heart disease, whereas epidemiological evidence suggests that oestrogens may actually give up to 50% protection against this major cause of mortality and morbidity [10,12-14,251. Reactions to the concept of routine prophylactic HRT produced a widely varying response; 45% against, 24% in favour and 31% were neutral. The main concerns about treatment were concern about unknown long-term effects, particularly breast cancer and cardiovascular disease. Although GPs showed poor knowledge of current literature, their cautious approach can be defended on the basis that there are no random&d or quasi-randomised studies of hormone replacement therapy. Our knowledge is based mainly on case control studies, a small number of prospective studies and a knowledge of the pharmacological effects of sex steroids. Furthermore, even if it could be ‘proved’ that prophylactic HRT substantially diminished heart
60
disease, endometrial cancer and osteoporosis, while slightly increasing the risk of breast cancer, we do not know how women would perceive this trade-off. Financial cost, cost in time for supervision and monitoring and likely poor patients compliance were mentioned as further reasons against more widespread use of this treatment. Many practitioners indicated that their views were strongly influenced by intuition and general philosophical considerations, rather than a formal appraisal of likely risks versus benefits. The general principle of primum non nocere was held important; in other words many respondents seemed to feel that failure to realise potential net benefit was not as harmful as causing potential net harm of equal magnitude. There was also a strong general concern about a pharmacological approach to what is seen as a natural process in humans. There is no unambiguous evidence that all women should be offered HRT, and this study shows that: (1) general practitioners need more information about this therapy; (2) general practitioners are cautious about widespread use of HRT and will not offer this therapy to most women until there is more compelling evidence of net long-term benefit. References 1 Utian WH. Transdermal oestradiol. GveraII safety profile. Am J Obstet Gynaecol1987;156:1335-1338. 2 Dennerstein L, Burrows GD. A review of studies of the psychological symptoms found at the menopause. Maturitas 1978;1:55-64. 3 Whitehead MI. The Climacteric. Progress in Obsterics and Gynaecology 5. Edinburgh: Churchill Livingstone 1986;332-361. 4 Smith P. Age changes in the female urethra. Br J Urol 1972;44:667-676. 5 Holmes MM, Rooner DR, Rothert ML, Elstein AS, Holzman CP, Hoppe RB, Methny WD, Ravitch. Women and physicians utilities for health outcomes in oestrogen replacement therapy. J Gen Intern Med 1987;2:178-182. 6 Studd JWW, Thorn MH, Paterson MEL, Wade Evans T. The prevention and treatment of endometrial pathology in postmenopausal women receiving exogenous oestrogens. In: Pasetto N, Paoletti R, Ambrus JL, eds. The Menopause Postmenopause. Lancaster: MTP Press 1980;127-139. 7 Cramer DW, Knapp RC. Review of epidemiologic studies of endometrial cancer and exogenous estrogen. Obstet Gynecol 1979;54:521-526. 8 Wilson PWF, Garrison RJ, Castelh WP. Post-menopausal estrogen use, cigarette smoking and cardiovascular morbidity in women over 50. N Eng J Med 1985;313:1036-1040. 9 Rosenburg L, Armstrong B, Jick H. Myocardial infarction and estrogen therapy in postmenopausal women. New Eng J Med 1976;294:1256-1259. 10 Pfeffer RJ, Whipple GH, Kuroski TT, Chapman J. Coronory risk and estrogen use in postmenopausal women. Am J Epidemiol 1978;107:467-487. 11 Ross RK, Paganini-Hill A, Mack TM, Henderson BE. Estrogen use and cardiovascular disease. In: Mishell DR, ed. Menopause, physiology and pharmacology. Chicago Year Book Medical Publishers 1986;203-209. 12 Bush TL, Cowan LD, Barrett-Connor E, Criqui MH, Karon JM, Wallace RB et al. Estrogen use and all-cause mortality. J Am Med Assoc 1983;249,903-909. 13 Stampfer MJ, Willet WC, Colditz GA, Rosner B, Speizer FE, Hemrek CH. A prospective study of postmenopausal estrogen use, cigarette smoking and cardiovascular morbidity in women over 50. N Eng J Med 1985;316:1105-1110. 14 Colditz GA, WiIIet WC, Stampfer MJ, Rosner B, Speizer FE, Hennekens CH. Menopause and the risk of coronary heart disease in women. N Eng J Med 1987;316:1105-1110.
61 15 Hutchinson TA, Polansky SM, Feinstein A. Post-menopausal oestrogens protect against fractures of hip and distal radius. Lancet 1979;ii:706-709. 16 Lindsay R, Hart DM, Aitken JM, MacDonald EB, Anderson JB, Clarke C. Long-term prevention of postmenopausal osteoporosis by oestrogens. Lancet 1976;i:1038-1041. 17 Weis NS, Lyon JL, Krishnamurthy S, Dietert SE, Liff JM, Daling JR. Noncontraceptive estrogen use and the occurance of ovarian cancer. J Natl Cancer Inst 1982;114:95-98. 18 Paganini Hill A, Ross RR, Gerkins VR, Henderson BE, Arthur M, Mack TM. A case control study of menopausal oestrogen therapy and hip fractures. AM Intern Med 1981;95:28-31. 19 Rosenburg L, Hennekens CH, Rosner B, Berlanger C, Rothman KJ, Speizer FE. Early menopause and the risk of myocardial infarction. Am J Obstet Gynecol 1981;139:47-51. 20 Bain C, Willett W, Hennekens CH, Rosner B, Bellinger C, Speizer FE. Use of postmenopausal hormones and risk of myocardial infarction. Circulation 1981;64:42-46. 21 Hoover R, Gray LA, Cole P, MacMahon B. Menopausal estrogens and breast cancer. N Engl J Med 1976;295:401-405. 22 Gambrel1 RD, Maier RC, Saunders BI. Decreased incidence of breast cancer in postmenopausal estrogen progestogen use. Obstet Gynecol 1983;62:435-443. 23 McDonald JA. Menopausal oestrogen use and risk of breast cancer. Breast Ca Res Treat 1986;7:193199. 24 Brinton LA. Menopausal oestrogens and breast cancer risk, an expanded case control study. Br J Cancer 1986;54:825-832. 25 Ross RR, Paganini-Hill A, Gerkins VR. A case control study of menopausal estrogen therapy and breast cancer. JAMA 1980;243:1635-1639. 26 Buring JE, Hennekens CH. Prospective cohort study of postmenopausal hormone use and risk of breast cancer in US women. Am J Epidemiol 1987;125:939-947. 27 Wingo PA. The risk of breast cancer in postmenopausal women who have oestrogen replacement therapy. JAMA 1987;257:209-215. 28 Cramer DW, Hut&son GB, Welch WR, Scully RE, Ryan KJ. Determinants of ovarian cancer risk. 1. Reproductive experiences and family history. J Nat1 Cancer Inst 1982;68:95-98. 29 Cramer DW, Devesa SS, Welch WR. Trends in the incidence of endometroid and clear-cell cancers of the ovary in the United States. Am J Epidemiol 1981;114:201-208. 30 La Vecchia C, Liberati A, Frances&i S. Noncontraceptive estrogen use and the occurrance of ovarian cancer. J Nat1 Cancer Inst 1982;69:1207. 31 The Cancer and Steroid Hormone Study of the centers for disease control. National Institute of Child Health and Human Development. The reduction in risk of ovarian cancer associated with oral contraceptive use. N Eng J Med 1987;316:650-781. 32 Laragh JH, Sealey JE, Ledingbam JG, Newton MA. Oral contraceptives; renin, aldosterone and high blood pressure. JAMA 1967;201:918-922. 33 Eggerssen R. Influence on blood pressure of oestrogen substitution therapy in the menopause. Stand J Prim Health Care 1987;5:51-53.
Biology, 31 (1990) 55-61
55
EUROBS 00954
General practitioners use of hormone-replacement therapy in Yorkshire F.C. Bryce and R.J. Lilford Department
of Obstetrics and Gynaecologv, St. James’s University Hospital, L.eeak, U.K. Accepted for publication 4 October 1989
Questionnaires were sent to 1000 general practitioners (GPs) in the Yorkshire Region to obtain information about their approach to the use of hormone-replacement therapy (HRT) in the menopause. A total of 310 GPs returned completed questionnaires. These showed widely varying views. The majority of GPs estimated that less than 10% of their perimenopausal patients had taken HRT at some time. There was confusion about the reported effects of HRT, on the risks of endometrial carcinoma and on ischaemic heart disease. Thus, while 86% correctly judged that HRT was protective against osteoporosis, 70% concluded against prevailing opinion that combined preparations increase the risk of endometrial cancer. In contrast to the bulk of evidence, nearly 50% of respondents believed that the risk of ischaemic heart disease was also increased by HRT. A number of GPs considered lack of an authoritive lead from epidemiology to be their greatest difficulty in forming an opinion on the desirability of HRT. The general approach to HRT was cautious in respect of both the frequency and the duration of the therapy. Less than a quarter of the GPs were sympathetic to the idea of prophylactic HRT and only 7% routinely discussed this possibility with menopausal patients, while the majority felt that the duration of therapy should be limited to 2 years or less. Most respondents also showed intuitive resistance to the idea of ‘mass therapy’ at the menopause and expressed concern at the idea of ‘interfering with nature’. Hormone replacement therapy; General practitioner
IntmductIon
Oestrogen and progesterone replacement therapy (HRT) in the menopause is effective in reducing a number of symptoms associated with the climacteric, such as
Correspondence: U.K.
F.C. Bryce, Department of Obstetrics and Gynaecology,
0028-2243/90/$03.50
St James’s Hospital, Leeds,
Q 1990 Elseviex Science. Publishers B.V. (Biomedical Division)
56
hot flushes, dry vagina and mood changes [l-5]. Many case-control studies have shown a protective effect against endometrial cancer [6,7]; ischaemic heart disease [S-14] and osteoporosis [15-181, while the risks of hypertension [lo] and venous thromobosis 19,201 are reported as unchanged. The effect on the incidence of breast cancer is the most important unknown effect although there is a suggestion that it may rise slightly after 10 years of use [21-271. It could be argued from these findings that the health of many women might be improved by a course of HRT, although our present knowledge is limited by the lack of randomised or quasi-randomised studies. The question of HRT is of great public health interest. We conducted a study to assess opinions and attitudes of general practitioners to the menopause and HRT under a wide variety of circumstances. Our clinical experience has suggested that many doctors are reluctant to prescribe HRT and that this is based on intuition and general philosophical principles rather than an analysis of costs and benefits to health. A questiomaire was designed to test this observation. Subjects and methods Lists of General Practitioners (GPs) in the region were obtained from the Family Practitioner Committee. One thousand questionnaires were sent out by three Family Practitioner Committees to GPs in their area. A total of 320 responses were received in the 4 months following distribution. Twelve responses were from GPs who did not have any post-menopausal patients on their lists (student health practitioners). This left a total of 308 completed questionnaires; a response rate of 31%. In order to encourage a response the questiomraire was made anonymous and it was therefore impossible to identify which GPs had not responded. This questionnaire consisted of a series of nine multiple-choice questions designed to assess both current practice and attitudes towards hormone-replacement therapy. Results The questionnaire first asked for an estimate of the proportion of the practice’s post-menopausal patients who had taken HRT: 70% responded that less than 10% had done so, 23% thought that lo-25% of patients had received HRT, and a further 2% estimated that 25-50% of women had taken this treatment. Only 0.66% thought that over half of their post-menopausal patients had taken HRT, while 4% of respondents were unable to answer this question. When asked whether HRT was discussed with patients around the time of the menopause, only 8% of the GPs said that this was routinely done, while the remainder said they would do so if the patient complained of menopausal symptoms or in response to a direct request for information from a patient. Contra-indications to HRT that GPs regarded as ‘absolute’ are shown in Fig. 1. The majority (94.3%) considered breast cancer, active liver disease (91.6%), thrombo-embolic disease (88.3%) and a previous cerebrovascular accident (75.3%) to be absolute contra-indications. There was less certainty about ischaemic heart disease, heavy smoking,
benign
breast
dis.
mod. hypertension obesity heavy smoking ischaemic
heart dis.
cerebrovascular
dis.
thrombo-embolic
dis.
E. rel. liver dis. breast cancer 0
10 20
30
40
50
60
70
80
90100
c/o
Fig. 1. Pre-existing HRT. Percentage
medical disorders considered of respondents who regarded
by general the disorder
practitioners to be a contra-indication to as an absolute contraindication to HRT.
obesity and moderate hypertension. Only 6% felt that benign breast disease was an absolute contra-indication. Table I shows the investigations which GPs consider necessary before starting HRT. Measurement of blood pressure was almost always performed, whereas endometrial biopsy was virtually never deemed necessary. Routine examination of the breasts was always performed by 43% sometimes by 43% and never by 13% despite 94.3% of respondents indicating that breast cancer was an absolute contraindication to treatment. Preparations prescribed most frequently for patients who had retained or lost their uterus are listed, in order of frequency, in Table II; the combined preparations (Prempak and Cycloprogynova) were the most frequently prescribed. Unopposed oestrogens were still prescribed by 9% of practitioners for patients who had retained their uterus and by 38.5% of general practitioners for those patients who had had a hysterectomy. Most GPs reviewed patients at regular intervals: 73% at 6 monthly intervals, 23% at 3 monthly intervals, and only 4% saw patients at yearly intervals or not at all. When questioned about the how long HRT should usually be continued once it had been started, 32% of respondents felt that 2 years was adequate, 21% favoured 1 year and 18% felt that 5 years was optimal, 6.6% would treat forever, 4.0% for 10 years and the remainder could not specify a time period.
TABLE
I
Routine
examinations
Weight Blood pressure Cervical smear Pelvic examination Breast examination Endometrial biopsy
performed
before commencing
hormone
replacement
therapy
Always
Sometimes
Never
@I
(V
@I
40.6 94 63.3 52.6 43.3 0
48.3 5.3 33.3 42.3 43.3 8.0
11 0.66 3.3 5.0 13.3 92
58 TABLE II Hormone replacement preparation most frequently prescribed by general practitioners In the patient with a uterus Cycloprogynova Prempak Prempak C. Menophase Harmogen Trisequens Mixogen Premarin Estraderm patches (with progesterone)
In the hysterectomised patient 55% 54.6% 16.3% 9% 8% 7% 1.6% 0.66% 0.33%
Cycloprogynova Prempak Prempak C. Harmogen Premarin Ethinyloestradiol Menophase Trisequens Mixogen Cyclogest
61% 36% 3% 25% 12% 6.3% 4% 2.6% 1.66% 0.66
Footnote: Some general practitioners used more than one preparation consequently percentages add up to more than 100%.
The questionnaire then asked the effect GPs considered their chosen HRT preparation had on selected important diseases. Almost 70% thought the risk of endometrial cancer was increased, and only 8.3% thought this risk was decreased. Of those who thought HRT increased the risk of endometrial cancer, 80% were using ‘opposed’ therapy. 20% of doctors who recognised the increased risk of endometrial cancer with unopposed oestrogens nevertheless preferred this treatment for patients who had not had an hysterectomy. The doctors’ opinions about the effects of HRT on the risks of hypertension, myocardial infarction, breast cancer and osteoporotic fracture were sought. 87% of practitioners responded that the risk of hypertension was increased. 47% felt that the risk of myocardial infarction was also increased, 21% recognised that the risk may be decreased and 25% thought that HRT had no effect on the incidence of myocardial infarction. The risk of breast cancer was also considered to be increased by 68% of practitioners; 4% thought the risk was decreased while 22% thought HRT had no effect on the incidence and 6% had no opinion. The beneficial effect of HRT in the prevention of osteoporotic fracture was correctly recognised by the majority of GPs, with 86% indicating that HRT reduces the incidence of fracture. It was rather surprising to see that 11% of respondents indicated that HRT might increase the risk of fracture. The final question asked practitioners their opinion about offering HRT to all women who had no specific contra-indication to treatment. 15% strongly disagreed with this idea, 29.6% disagreed, 31.3% were neutral, 16.3% agreed and 7% strongly agreed. Respondents were also encouraged to enlarge upon their responses. The most frequent concerns were long-term effects of treatment, financial cost, patient compliance, time for supervision of treatment of a philosophical dislike of the concept of treating all patients regardless of symptoms. 60% of those who were against offering HRT routinely to all patients with no specific contra-indications invoked the principle of ‘primum non nocere’ and 40% made remarks to the effect that it was a mistake to prescribe for a natural process on a large scale. There were also comments voiced concerning lack of a clear lead from specialists.
59
Discussion This is the first survey to determine the attitudes of family doctors to HRT. This issue is of great public health interest since virtually half the population will experience the menopause and their subsequent mortality and morbidity could be influenced by medical practice. Most doctors were reluctant to use HRT. The majority of GPs estimated that less than 10% of their perimenopausal patients had taken HRT at some time. Once therapy had been commenced it was generally given for as short a time as possible. Only 29% of practitioners who replied were prepared to prescribe treatment for longer than 5 years. GPs had accurate knowledge of some effects of HRT, e.g. the protective effect against osteoporosis was recognised, as was the effect of unopposed oestrogens on endometrial cancer, We were, therefore, surprised by the finding that, of those practitioners who indicated that HRT increased the risk of developing endometrial carcinoma, 20% were not using combined oestrogen and progesterone preparations. Possibly they wished to avoid the effects of some progestagens on blood lipids and regarded this as the greater evil. Only 8.3% correctly recognised that the risk of developing endometrial cancer is probably reduced by cyclical HRT. GPs were correctly concerned about the effect of HRT on carcinoma of the breast, since this is one of the major concerns regarding long-term treatment. The current evidence suggests a small increase in risk after 10 years of continuous unopposed oestrogen therapy [21,24-261. Only one study [22] has examined the effect of current combined low dose oestrogen and progesterone preparations on this disease. Also awaited is evidence that HRT influences the incidence of ovarian carcinoma. Retrospective studies in America and Italy suggest a possible increase in the incidence of endometrial and clear cell carcinoma of the ovary, but the figures are not statistically significant [28-301. Prolonged use of the combined oral contraceptive decreases the risk of ovarian carcinoma by at least 50% so it might be hoped that HRT may provide similar protection against non-endometroid ovarian cancer [31]. An effect of HRT on the cardiovascular system was recognised by the majority of GPs - although the fact that this was beneficial was not! The bulk of the evidence now suggests that in contrast to the combined oral contraceptive, HRT does not cause or aggrevate essential hypertension [32,33]. Over half the practitioners indicated that HRT would increase the risk of ischaemic heart disease, whereas epidemiological evidence suggests that oestrogens may actually give up to 50% protection against this major cause of mortality and morbidity [10,12-14,251. Reactions to the concept of routine prophylactic HRT produced a widely varying response; 45% against, 24% in favour and 31% were neutral. The main concerns about treatment were concern about unknown long-term effects, particularly breast cancer and cardiovascular disease. Although GPs showed poor knowledge of current literature, their cautious approach can be defended on the basis that there are no random&d or quasi-randomised studies of hormone replacement therapy. Our knowledge is based mainly on case control studies, a small number of prospective studies and a knowledge of the pharmacological effects of sex steroids. Furthermore, even if it could be ‘proved’ that prophylactic HRT substantially diminished heart
60
disease, endometrial cancer and osteoporosis, while slightly increasing the risk of breast cancer, we do not know how women would perceive this trade-off. Financial cost, cost in time for supervision and monitoring and likely poor patients compliance were mentioned as further reasons against more widespread use of this treatment. Many practitioners indicated that their views were strongly influenced by intuition and general philosophical considerations, rather than a formal appraisal of likely risks versus benefits. The general principle of primum non nocere was held important; in other words many respondents seemed to feel that failure to realise potential net benefit was not as harmful as causing potential net harm of equal magnitude. There was also a strong general concern about a pharmacological approach to what is seen as a natural process in humans. There is no unambiguous evidence that all women should be offered HRT, and this study shows that: (1) general practitioners need more information about this therapy; (2) general practitioners are cautious about widespread use of HRT and will not offer this therapy to most women until there is more compelling evidence of net long-term benefit. References 1 Utian WH. Transdermal oestradiol. GveraII safety profile. Am J Obstet Gynaecol1987;156:1335-1338. 2 Dennerstein L, Burrows GD. A review of studies of the psychological symptoms found at the menopause. Maturitas 1978;1:55-64. 3 Whitehead MI. The Climacteric. Progress in Obsterics and Gynaecology 5. Edinburgh: Churchill Livingstone 1986;332-361. 4 Smith P. Age changes in the female urethra. Br J Urol 1972;44:667-676. 5 Holmes MM, Rooner DR, Rothert ML, Elstein AS, Holzman CP, Hoppe RB, Methny WD, Ravitch. Women and physicians utilities for health outcomes in oestrogen replacement therapy. J Gen Intern Med 1987;2:178-182. 6 Studd JWW, Thorn MH, Paterson MEL, Wade Evans T. The prevention and treatment of endometrial pathology in postmenopausal women receiving exogenous oestrogens. In: Pasetto N, Paoletti R, Ambrus JL, eds. The Menopause Postmenopause. Lancaster: MTP Press 1980;127-139. 7 Cramer DW, Knapp RC. Review of epidemiologic studies of endometrial cancer and exogenous estrogen. Obstet Gynecol 1979;54:521-526. 8 Wilson PWF, Garrison RJ, Castelh WP. Post-menopausal estrogen use, cigarette smoking and cardiovascular morbidity in women over 50. N Eng J Med 1985;313:1036-1040. 9 Rosenburg L, Armstrong B, Jick H. Myocardial infarction and estrogen therapy in postmenopausal women. New Eng J Med 1976;294:1256-1259. 10 Pfeffer RJ, Whipple GH, Kuroski TT, Chapman J. Coronory risk and estrogen use in postmenopausal women. Am J Epidemiol 1978;107:467-487. 11 Ross RK, Paganini-Hill A, Mack TM, Henderson BE. Estrogen use and cardiovascular disease. In: Mishell DR, ed. Menopause, physiology and pharmacology. Chicago Year Book Medical Publishers 1986;203-209. 12 Bush TL, Cowan LD, Barrett-Connor E, Criqui MH, Karon JM, Wallace RB et al. Estrogen use and all-cause mortality. J Am Med Assoc 1983;249,903-909. 13 Stampfer MJ, Willet WC, Colditz GA, Rosner B, Speizer FE, Hemrek CH. A prospective study of postmenopausal estrogen use, cigarette smoking and cardiovascular morbidity in women over 50. N Eng J Med 1985;316:1105-1110. 14 Colditz GA, WiIIet WC, Stampfer MJ, Rosner B, Speizer FE, Hennekens CH. Menopause and the risk of coronary heart disease in women. N Eng J Med 1987;316:1105-1110.
61 15 Hutchinson TA, Polansky SM, Feinstein A. Post-menopausal oestrogens protect against fractures of hip and distal radius. Lancet 1979;ii:706-709. 16 Lindsay R, Hart DM, Aitken JM, MacDonald EB, Anderson JB, Clarke C. Long-term prevention of postmenopausal osteoporosis by oestrogens. Lancet 1976;i:1038-1041. 17 Weis NS, Lyon JL, Krishnamurthy S, Dietert SE, Liff JM, Daling JR. Noncontraceptive estrogen use and the occurance of ovarian cancer. J Natl Cancer Inst 1982;114:95-98. 18 Paganini Hill A, Ross RR, Gerkins VR, Henderson BE, Arthur M, Mack TM. A case control study of menopausal oestrogen therapy and hip fractures. AM Intern Med 1981;95:28-31. 19 Rosenburg L, Hennekens CH, Rosner B, Berlanger C, Rothman KJ, Speizer FE. Early menopause and the risk of myocardial infarction. Am J Obstet Gynecol 1981;139:47-51. 20 Bain C, Willett W, Hennekens CH, Rosner B, Bellinger C, Speizer FE. Use of postmenopausal hormones and risk of myocardial infarction. Circulation 1981;64:42-46. 21 Hoover R, Gray LA, Cole P, MacMahon B. Menopausal estrogens and breast cancer. N Engl J Med 1976;295:401-405. 22 Gambrel1 RD, Maier RC, Saunders BI. Decreased incidence of breast cancer in postmenopausal estrogen progestogen use. Obstet Gynecol 1983;62:435-443. 23 McDonald JA. Menopausal oestrogen use and risk of breast cancer. Breast Ca Res Treat 1986;7:193199. 24 Brinton LA. Menopausal oestrogens and breast cancer risk, an expanded case control study. Br J Cancer 1986;54:825-832. 25 Ross RR, Paganini-Hill A, Gerkins VR. A case control study of menopausal estrogen therapy and breast cancer. JAMA 1980;243:1635-1639. 26 Buring JE, Hennekens CH. Prospective cohort study of postmenopausal hormone use and risk of breast cancer in US women. Am J Epidemiol 1987;125:939-947. 27 Wingo PA. The risk of breast cancer in postmenopausal women who have oestrogen replacement therapy. JAMA 1987;257:209-215. 28 Cramer DW, Hut&son GB, Welch WR, Scully RE, Ryan KJ. Determinants of ovarian cancer risk. 1. Reproductive experiences and family history. J Nat1 Cancer Inst 1982;68:95-98. 29 Cramer DW, Devesa SS, Welch WR. Trends in the incidence of endometroid and clear-cell cancers of the ovary in the United States. Am J Epidemiol 1981;114:201-208. 30 La Vecchia C, Liberati A, Frances&i S. Noncontraceptive estrogen use and the occurrance of ovarian cancer. J Nat1 Cancer Inst 1982;69:1207. 31 The Cancer and Steroid Hormone Study of the centers for disease control. National Institute of Child Health and Human Development. The reduction in risk of ovarian cancer associated with oral contraceptive use. N Eng J Med 1987;316:650-781. 32 Laragh JH, Sealey JE, Ledingbam JG, Newton MA. Oral contraceptives; renin, aldosterone and high blood pressure. JAMA 1967;201:918-922. 33 Eggerssen R. Influence on blood pressure of oestrogen substitution therapy in the menopause. Stand J Prim Health Care 1987;5:51-53.
