Thesis
Reference
Utilisation de l'hormonothérapie de substitution à la ménopause : une comparaison entre des patientes en médecine de premier recours et
la population générale
RIEDER, Arabelle Rachel
Abstract
L'objectif de ce travail de recherche était d'évaluer les pratiques de conseil concernant le traitement hormonal de substitution (THS) en médecine de premier recours. Nous avons fait une étude par questionnaire de 107 patientes péri- et post ménauposées dans un centre médical ambulatoire à Genève en 1998. Les résultats ont été comparés avec des données similaires d'un échantillon (n=241) d'une étude épidémiologique annuelle représentative de la population générale. Les résultats ont montré que l'utilisation actuelle du THS avait tendance à être moins importante chez les femmes du centre médical que dans la population générale.
Les utilisatrices du THS dans le centre avaient plus souvent une ménopause chirurgicale et utilisaient les hormones pendant une durée plus courte que dans la population. Ainsi, l'utilisation de THS dans le centre de médecine de premier recours était plus restrictive que dans la population générale et ne correspondait pas aux recommandations thérapeutiques de l'époque.
RIEDER, Arabelle Rachel. Utilisation de l'hormonothérapie de substitution à la
ménopause : une comparaison entre des patientes en médecine de premier recours et la population générale. Thèse de doctorat : Univ. Genève, 2008, no. Méd. 10553
URN : urn:nbn:ch:unige-6238
DOI : 10.13097/archive-ouverte/unige:623
Available at:
http://archive-ouverte.unige.ch/unige:623
Disclaimer: layout of this document may differ from the published version.
UNIVERSITE DE GENEVE FACULTE DE MEDECINE
Section de Médecine Clinique Département de Sante et de
Médecine Communautaires
Thèse préparée sous la direction du Professeur Jean-Michel Gaspoz
________________________________________________________________
UTILISATION DE L’HORMONOTHERAPIE DE SUBSTITUTION A LA MENOPAUSE : UNE COMPARAISON ENTRE DES PATIENTES EN MEDECINE DE PREMIER RECOURS ET LA POPULATION GENERALE
Thèse
présentée à la Faculté de Médecine de l’Université de Genève
pour obtenir le grade de Docteur en médecine par
Arabelle RIEDER NAKHLE de
Zürich Thèse n° 10553
Genève 2008
TABLE DES MATIERES
RESUME……….. p. 3 RESEARCH QUESTION……… p.8 DEFINITIONS………. p. 10 STUDY DESIGN………. p. 17 METHODS……… p. 19 RESULTS………. p. 22 DISCUSSION……….. p. 24 REFERENCES……… . p. 29 REMERCIEMENTS……… p. 33
Tables……… p. 34
Figure 1………. p. 37
RESUME EN FRANÇAIS
Question de recherche
Jusqu’au début du 21ième siècle, la prescription du traitement hormonal de substitution (THS) était un sujet controversé parmi les autorités médicales concernées. Le but de ce projet de recherche était d’évaluer la pratique médicale concernant la prescription du THS en médecine de premier recours dans un centre universitaire de formation de généralistes et d’internistes généralistes (la « policlinique »). L’hypothèse de recherche était que l’utilisation du THS par les femmes ménopausées et post-ménopausées qui fréquentaient la policlinique serait le reflet des conseils donnés par les médecins de premier recours qui y pratiquaient. Les résultats d’une enquête de ce type étaient cependant difficiles à interpréter vu la variabilité des pratiques dans les différents pays. Nous avons donc comparé les résultats de l’enquête clinique avec la même enquête menée dans la population générale de la même région. Ainsi, les différences constatées entre les deux échantillons représentaient une comparaison indirecte de la prescription du THS par les médecins de la policlinique universitaire avec celle des praticiens installés en ville.
Définitions et introduction
La ménopause est définie comme la cessation de menstruations en raison de la perte
d’activité folliculaire au niveau des ovaires et est déterminée rétrospectivement après 1 année sans menstruations. L’âge médian est entre 50 et 51 ans. La ménopause peut aussi être induite artificiellement par l’ablation chirurgicale des ovaires, par chimiothérapie antinéoplasique ou par radiothérapie. La perte des menstruations s’accompagne d’effets à court et à plus long terme. Les symptômes aigus les plus fréquents sont des bouffées de chaleur et une atrophie vaginale. A plus long terme, on relève une augmentation du risque de fractures et du risque cardiovasculaire.
L’hormonothérapie de substitution consiste en l’administration d’œstrogènes naturels à des doses 3 à 4 fois inférieures à celles qui sont utilisées pour la contraception orale. Les
œstrogènes sont associés à des progestatifs en l’absence d’hystérectomie vu le risque avéré de cancer de l’endomètre si les œstrogènes sont administrés seuls. Les doses de progestatifs sont les mêmes que pour la contraception orale combinée.
Le THS a été introduit dans les années 1940 pour le traitement des symptômes de la
ménopause. Par la suite, de nombreuses études observationnelles ont suggéré un bénéfice du THS dans la prévention des maladies cardiovasculaires et de l’ostéoporose principalement.
Les risques suspectés étaient une augmentation du risque de cancer du sein et de maladie thromboembolique. Dès les années 1990, plusieurs agences de référence de la prévention ont proposé d’étendre la prescription du THS à la majorité des femmes ménopausées et post- ménopausées. Il revenait aux praticiens de premier de recours de peser les bénéfices potentiels et les risques encore mal définis du THS.
A cette époque, la prévalence de l’utilisation du THS variait entre 2 et 38% selon la population étudiée.
C’est dans ce contexte qu’a été menée notre étude sur la prescription du THS à la policlinique. En effet les praticiens de premier recours étaient dans une position idéale quoique difficile pour conseiller leurs patientes ménopausées et post-ménopausées sur l’utilisation ou non du THS.
Il est à noter que les résultats de deux études randomisées (HERS et WHI) publiés entre 1998 et 2002 ont montré plus tard et de manière inattendue, une augmentation des événements cardiovasculaires ainsi que des attaques cérébrales. Ainsi, depuis 2002, le THS n’est plus recommandé dans la prévention de maladies chroniques et son utilisation a diminué de manière importante à partir de cette époque.
Dessein de l’étude
Nous avons comparé la prévalence et les déterminants du THS dans deux groupes de femmes de 45 à 65 ans périménopausées ou post-ménopausées. Le groupe « policlinique » comprend les femmes ayant consulté la policlinique pendant une période définie, et le groupe
« population générale » inclut un échantillon représentatif de femmes du même groupe d’âge ayant participé à une enquête annuelle des déterminants de santé dans la population générale (projet Bus Santé) de la même année.
Méthodes
Pendant deux mois en 1998, toutes les femmes péri- et post-ménopausées, résidentes de Genève et âgées de 45 à 65 ans qui consultaient la policlinique ont rempli un auto- questionnaire anonyme qui comprenait des questions sur leur vie reproductive et leur utilisation actuelle ou passée du THS. Les résultats de cette enquête ont été comparés avec des données du projet « Bus Santé ». Le groupe « population générale » a répondu aux mêmes questions que le groupe clinique dans le cadre d’un auto questionnaire sur de multiples facteurs de risque cardiovasculaire. Les participantes ont été classées selon les réponses données dans le questionnaire comme étant en « péri-ménopause », « ménopause naturelle », « ménopause chirurgicale » ou « autre cause de ménopause ». Les femmes en pré- ménopause ont été exclues de l’analyse. L’utilisation du THS était définie comme
« actuelle », « dans le passé » ou « jamais utilisée ». L’âge, la nationalité, et d’autres
caractéristiques de l’utilisation du THS ont été comparés entre les deux groupes. Nous avons fait des analyses uni- et multivariées pour mettre en évidence des associations entre
l’utilisation du THS et des caractéristiques des participantes à l’étude.
Résultats
Nous avons analysé les données de 107 patientes périménopausées ou ménopausées dans le groupe « policlinique » et de 241 femmes périménopausées ou ménopausées ayant participé à l’enquête dans la population générale. Les caractéristiques générales des participantes étaient semblables dans les deux groupes (âge moyen, utilisation antérieure de la contraception orale, type de ménopause). La seule différence significative était la proportion plus élevée de non- suisses dans le groupe « policlinique ». La prévalence de l’utilisation « actuelle » du THS avait tendance à être plus basse dans la policlinique que dans la population générale (38.3%
vs 47.7%, p=0.1). Deux caractéristiques des utilisatrices actuelles du THS étaient
significativement différentes entre les deux groupes. Premièrement, une plus forte proportion d’utilisation pour une courte durée (1-2 ans) dans le groupe « policlinique » que dans le groupe « population générale » (41.5% vs 18.3%). Deuxièmement, un taux plus élevé de ménopause chirurgicale dans la policlinique que dans la population générale (34.4% vs 16.1%) : les résultats de la régression logistique ont montré que comparées aux femmes de la population générale, les patientes de la policlinique avaient 2 fois moins de chance d’être utilisatrices « actuelles » du THS si elles avaient une ménopause naturelle ou si elles étaient citoyennes suisses.
Discussion
A la fin des années 1990, la prévalence du THS (38.3%) relevée chez les patientes de la policlinique était assez élevée comparée aux résultats de la littérature. Cependant, elle paraît plutôt basse quand elle est comparée à l’utilisation du THS dans la population genevoise.
Comme explication, nous proposons que le groupe « policlinique » pourrait être d’un niveau socio-économique moins élevé, ce qui a été associé à une moindre utilisation du THS.
D’autre part, les femmes à la policlinique pourraient avoir consulté moins souvent leur gynécologue que les femmes dans la population générale. Les gynécologues prescrivaient plus de THS que les médecins d’autres spécialités. Finalement, les médecins en formation de la policlinique pouvaient être réticents à recommander le THS au long terme car ils étaient régulièrement exposés à une approche critique et « evidence-based » de la pratique médicale enseignée dans le cadre de la formation post-graduée de l’hôpital universitaire.
Les femmes à la policlinique avaient plus souvent une ménopause chirurgicale que les utilisatrices du THS dans la population générale. Cela est en accord avec les
recommandations de l’époque des instances de prévention aux USA. Le fait que les patientes à la policlinique prenaient des hormones pour des durées plus courtes que dans la population générale dénote une approche restrictive de la prescription de la part des médecins en
formation.
Conclusion
La prévalence relativement basse du THS parmi les patientes de la policlinique pouvait être expliquée par des facteurs socio-économiques et médicaux. Comparée aux caractéristiques d’utilisation du THS dans la population générale, l’utilisation du THS dans la policlinique n’était pas totalement en accord avec les recommandations des instances de référence de l’époque. Il s’agit d’une étude innovante qui compare l’application pratique d’une
recommandation clinique concernant le THS avec l’utilisation du THS par les femmes d’âge ménopausique dans la population générale. Cela a été rendu possible par une harmonisation de la méthodologie en ce qui concerne le questionnaire sur la vie reproductive utilisé dans les deux enquêtes.
RESEARCH QUESTION
Physicians are expected to provide excellent medical care which is based on the best level of evidence available. To assist doctors, recognised medical authorities provide
recommendations in many fields of medicine such as preventive medicine (cardiovascular risk factors, early cancer detection, screening for alcohol abuse etc), workup of suspected disease (pulmonary embolus, acute coronary syndrome, streptococcal pharyngitis etc) and treatment regimens (endocarditis prophylaxis, treatment of hypertension, myocardial infarction, peptic ulcer disease, osteoporosis etc). The task is particularly challenging when there is controversy regarding the best approach to a particular medical issue. This was the case with the use of hormone replacement therapy (HRT) at and after the menopause during the nineties and the first years of the 21st century.
Assessment of physicians’ interventions in general practice is an important issue. This is necessary to adapt post-graduate education to the specific needs of practitioners, but remains a difficult task especially when the medical issue is complex.
For this research project, I wanted to assess trainee general internists’ and general practitioners’ counselling practice in relation to HRT use.
My hypothesis was that patterns of HRT measured in menopausal and post-menopausal women in a University outpatient clinic would reflect advice and recommendations given by doctors who practice in the clinic. However, the information provided by a single
questionnaire survey in the clinic would be difficult to interpret since prevalence and patterns
of use vary considerably between regions and countries. Comparison of HRT use in the clinic with patterns of HRT in the general population in the same region would provide a “control”
group of women. Women in the study group and in the general population would be similar in relation to their average cultural and social context. The main difference between the two groups would be consultation of a physician for the clinic group. Therefore, differences in the pattern of HRT use between the two study groups would reflect counselling by physicians-in- training who worked at the primary care policlinic.
DEFINITIONS
Menopause
The menopause is defined as the permanent cessation of cyclical menstruation due to loss of ovarian follicular activity. The median age at menopause is 50 to 51 years. It is therefore determined in retrospect, conventionally after a period of 1 year without menstruation. It is important to note that the average age at menopause has remained constant throughout recorded history and does not appear to be related to the age at menarche, socioeconomic conditions, race, parity, heath, or weight. However, menopause may occur earlier in women who smoke (McKinlay et al. 1985)(Wilson 1998).
Although the age of menopause is approximately 51 years, for 5 percent of women, it occurs after age 55 (late menopause), and for another 5 percent, between ages 40 to 45 years (early menopause). When menopause occurs prior to age 40 years, it is considered to be premature ovarian failure.
During the reproductive years, successive cycles of ovulation and atresia deplete the ovary of its follicles. The principal endocrine change of the menopause is a decrease in estrogen secretion as a result of the loss of ovarian follicles.
Between two and eight years before the cessation of menstruation (the menopausal transition), responsiveness of the ovary to gonadotropins begins to decrease. The term
“perimenopause” is used to cover this transition and the first year after the menopause and may last 3 to 5 years. This period is also called the “climacteric” from the Greek “klimakter”
which means “critical period”(Taffe et al. 2002).
Women who are perimenopausal but still experiencing ovulatory menstrual cycles have increased levels of follicle-stimulating hormone (FSH) and luteinising hormone (LH) compared with younger women and their levels of estrogen and progesterone are lower. The cessation of follicular development leads to decreased secretion of estradiol-17β and inhibin (a regulatory ovarian hormone), with consequent loss of negative feedback to the
hypothalamus and pituitary. The levels of gonadotropins increase, with FSH rising earlier and to a greater extent than LH. The plasma levels of gonadotropins may remain elevated or may decrease somewhat during the later decades of life (Wilson 1998)
This transition period may be characterised by a change from regular menstrual cycles to irregular menstrual cycles and dysfunctional uterine bleeding. Fertility is much reduced compared with the early reproductive years.
Circulating estrogens in premenopausal ovulatory women are derived from two sources.
More than 60% is estradiol secreted directly by the ovaries, and the remainder is estrone derived from extraglandular conversion of androstenedione. After the menopause, the ovarian contribution is reduced, and extraglandular formation of estrone from adrenal
androstenedione predominates. Because adipose tissue is a major site of extraglandular estrogen production, estrogen production is greater in obese than in thin postmenopausal women.
Menopause is diagnosed when FSH is greater than 40mU per ML and estradiol falls bellow 20 pg per mL.
The menopause may also be induced by surgical removal of both ovaries, or sometimes by antineoplastic drugs or radiotherapy.
The decline in oestrogen concentrations during the perimenopause may be associated with both acute and long-term effects. However, some of these may be difficult to differentiate from the effects of ageing and there are geographical variations.
Acute symptoms include vasomotor instability (hot flushes, night sweats), vaginal atrophy and dyspareunia.
The most common acute change during menopause is the hot flash, which occurs in up to 75 percent of women in some cultures. This symptom typically begins as the sudden sensation of heat centred on the face and upper chest that rapidly becomes generalized. The sensation of heat lasts from two to four minutes, is often associated with profuse perspiration and occasionally palpitations, and is often followed by chills and shivering. Episodes can occur several times per day. Hot flushes represent thermoregulatory dysfunction: there is
inappropriate peripheral vasodilatation with increased digital and cutaneous blood flow and perspiration. These changes result in rapid heat loss and a decrease in core body temperature below normal. Shivering then occurs as a normal mechanism to restore the core temperature (Casper et al. 1985).
Sleep disturbance is often associated with hot flashes, which can occur as often as once per hour even during the night. A continuing sleep disturbance may lead to fatigue, irritability, depression and difficulty concentrating, which have been attributed to menopause.
A large prospective cohort study of women ages 40 to 55 years showed that 13.1 percent of women had vaginal dryness which causes symptoms of itching and often dyspareunia (Gold et al. 2000). This is due to the thinning of the vaginal epithelium which in turn results from estrogen deficiency. The prevalence of vaginal dryness increases over the transition.
Symptoms related to genitourinary atrophy are exquisitely responsive to estrogen therapy, in particular vaginal estrogen therapy.
Non-specific symptoms that occur during the menopause include palpitations, headache, backache, and psychological symptoms such tiredness, lack of concentration, loss of libido, irritability, insomnia and depression. However, studies that have investigated the relationship between depression, for example, and menopause have been conflicting (Pearlstein et al.
1997). “Mood symptoms”, that have been attributed to the menopause transition may also be related to nonhormonal events. Examples of stressful events around the time of menopause include mid-life adjustment and children leaving home.
An established long-term consequence of the decline in oestrogen concentrations is an increased risk of bone fractures resulting from an increase in the rate of bone resorption. An imbalance of formation and resoprtion occurs in the early postmenopausal years and results predominantly in trabecular bone loss. Trabecular bone predominates in the vertebral body, which accounts for the vertebral osteoporosis and compression fractures which appear in many women during the decade or two after menopause(Wark 1996). The frequency and severity of these fractures and their associated complications are a major public health problem, especially as the population continues to age. In addition, decline in oestrogen concentrations is associated with adverse effects on blood lipoproteins and this may be a risk factor for cardiovascular disease (Wilson 1998).
Hormone Replacement Therapy
Since the perimenopause and the menopause are characterized by a relative oestrogen’
deficit, oestrogen was approved in the USA in the 1940’s as a supplement to treat
menopausal symptoms. The most commonly used oestrogens in menopause HRT are natural oestrogens such as estradiol and conjugated oestrogens (0.625 mg/day is effective in most women). Doses of oestrogens used in HRT are generally lower (3-4 times less) than those used in combined oral contraceptives and do not therefore provide contraception. Various dosage forms of the different oestrogen compounds used for HRT are available, including oral tablets, intranasal sprays, subcutaneous implants, topical application for vulvovaginal use, transdermal patches and gels.
During the ensuing years, observational studies indicated additional health benefits for oestrogen users such as the prevention of chronic diseases like cardiovascular disease and osteoporosis (Ettinger et al. 1985)(Nelson 2002).
Reports based on use in the 1960’s and 1970’s established that unopposed estrogens caused endometrial carcinoma (Shapiro et al. 1985). Since these studies have been published, estrogens have been used with progestins (if the patient hasn’t had a hysterectomy).
Generally, if prolonged therapy (for more than 2 to 4 weeks) with an oestrogen was envisaged in a woman with an intact uterus, a progestogen was required to prevent
endometrial proliferation. This was administered by mouth cyclically for 10 to 14 days per cycle or continuously. Transdermal preparations were also available. Both progesterone derivatives such as medroxyprogesterone and dydrogesterone and 19-nortestosterone analogues such as norethisterone and norgestrel were used. Doses of progestogens for HRT were similar to those used in combined oral contraceptives (Martindale 2002).
In the nineties, widespread use of HRT was proposed by several North American preventive agencies predominantly for the prevention of cardiovascular disease and the prevention of or treatment of osteoporosis (American College of Physicians 1992; Report of the
U.S.Preventive Service Task 1996). Improved cognitive function was another topic which led doctors to advocate the treatment despite insufficient evidence.
Physicians were in the difficult position of having to advise middle-aged women on therapy with potential (but yet unproven) important benefits, which they had to offset against the risks that weren’t well defined. Such as increased breast cancer and venous
thromboembolism. Faced with these uncertainties, some medical authorities were more conservative in their recommendations pending the results of clinical trials (Barett-Connor 1998; Hannaford 1998: Crosignani et al. 1997).
HRT use tended to steadily increase through the eighties and nineties (Morabia et al. 2006;
Derby et al.1993; Johannes et al. 1994; Moorhead et al. 1997; Mueller et al. 2002; Bromley et al. 1994).In the USA, use in the general population ranged between 11% and 38% with the highest pre-valence among menopausal women who lived on the West Coast (Brett &
Madans 1997; Johannes et al. 1994; Harris et al.1990; Derby et al.1993; Cauley et al. 1990;
Derby et
al.1995; Brown et al.1999; Keating et al.1999). Uptake was lower in Europe ranging between 2% (Crosignani, 1996; Moorhead et al., 1997; Oddens et al., 1994; Oddens and Boulet, 1997) and 33% in Britain (Million Women StudyCollaborators, 2002) and Norway (Bakken et al., 2001). Comparisons are difficult since studies were conducted at different periods, however HRT use tended to steadily (Derby et al., 1993; Johannes et al., 1994; Moorhead et al., 1997;
Mueller et al., 2002).
However, at the end of the nineties and the beginning of the 21st century, two randomised controlled trials, the HERS and Womens Health Initiative (WHI trials) (Hulley et al. 1998;
Rossouw et al. 2002) showed that HRT was associated with an increased risk of CHD events, stroke, venous thromboembolism and a slight increase in the risk of breast cancer after 5 years. Medical Authorities reached a consensus at last and guidelines were changed in
recognition of the negative effects of HRT on cardiovascular disease and the increased risk of cancer and thromboembolic disease. Thus, since 2002, HRT use has declined (Hersch et al.
2004).
The US Food and Drug Administration recently ordered estrogen safety warnings on product labels referring to WHI finding and altered approved indications for its use (Stephenson J.
2003). Package inserts indicate that treatment of menopausal symptoms remains an indication for estrogens use, although now physicians are advised to use the smallest effective dose for the shortest duration possible. The US Preventive Services Task Force as well as professional organizations updated their recommendations and now advise against using estrogens for prevention of chronic conditions (US Preventive Services Task Force 2005).
STUDY DESIGN
Primary care physicians are in an ideal, even if difficult, position when it comes to counselling menopausal patients on hormone replacement among other health issues (Stafford et al. 1997).
The first step in defining a study group was to choose an age-group. At the time of the study, HRT was used for menopause symptoms and for expected long-term benefits. A majority of other studies had defined the age-group 45-65 years as the most representative period of HRT use: at the start of menopause symptoms (45 to50 years), at the menopause (on average 50 years) and after the menopause (51 to 65 years). I decided to include women in that age bracket which made future comparisons with other studies on prevalence and patterns of use more meaningful.
We defined two study groups: the “clinic” group which comprised middle-aged patients of primary care physicians in the outpatient clinic and the “general population” group which was a selected subgroup of participants in a epidemiological survey in the same geographical area as the clinic.
The clinic group
This is the group that we wanted to observe: middle-aged patients who consult a physician in the University outpatient clinic who live in the canton of Geneva. There may be a selection towards lower socio-economic status based on historical rather than administrative reasons.
In the past, the clinic catered for the health needs of impoverished citizens of the city who could receive free treatment. This has changed gradually over the years, especially since the
introduction of compulsory medical insurance for all residents in Switzerland. Geneva canton’ residents who seek medical advice in the University outpatient clinic probably closely resemble residents who choose a doctor in private practice in the canton of Geneva.
The general population group
In the context of medical controversy that surrounded the use of HRT by menopausal women, doctors were advised to provide as much information as possible to their female patients on risks and benefits. Women had then to make their own decision whether to take HRT or not.
Therefore, non-medical factors such as level of education, socio-economic status, cultural background, nationality, influence of media, local public health policy etc played an important role in patterns of HRT.
For the reasons stated above, we needed to compare the clinic group of with a “control group” that would allow for all the non-medical factors that influence middle-aged women’
decision to use HRT in the Geneva canton area.
The second group is taken from a representative sample of the general population, the “Bus Santé” project (Galobardes et al. 2004), which is an-going epidemiological survey of health determinants. We defined a comparable group of menopausal and postmenopausal women who had answered question on HRT as part of a larger questionnaire on health and life-style.
METHODS
We studied HRT use in two samples of peri- and postmenopausal women aged 45-65 years who are residents in the canton of Geneva, Switzerland.
In November and December 1998, all female patients aged 45-65 years who consulted at the General Internal Medicine outpatient clinic of Geneva University Hospital were asked to complete an anonymous self-administered questionnaire about reproductive history and HRT use. The clinic is an ambulatory care unit of the University Hospital. Residents have 3 to 5 years of clinical experience in internal medicine. They remain 1-2 years. The unit is open to all patients in the population. In principal, characteristics should be similar to that of any other general practice in the area.
The results were compared with data obtained in 1998 from the “Bus Santé” project. This is an ongoing annual community-based survey of cardio-vascular risk factors among men and women aged 35-74 resident in the canton of Geneva, which is described in detail elsewhere (Galobardes et al. 2004). In brief, randomly selected residents received a mail questionnaire and were invited to bring the completed questionnaire to the “Health Mobile Unit” or to offices at Geneva University Hospital.
The self-completed questionnaire included closed questions, which were identical for both samples. Figure 1 illustrates the questionnaire that was given to the participants in the clinic (the questions are identical to the questions in the Bus Santé project expect the two questions on residence status). Participants answered questions on reproductive history and use of oral contraception (OC) and HRT. Participants in the outpatient clinic were also asked to state the
Participants were defined as perimenopausal if they reported menstruation in the last twelve months but not in the last two months (adapted from Brambilla’s definition (Brambilla et al.
1994)) or if they reported menstruation in the last two months and fulfilled at least one of three conditions: 1) declared to be menopausal, 2) stated having irregular periods, 3) were currently taking menopausal hormones and were 50 or younger. Women were classified as menopausal with a natural menopause if they reported at least 12 months of amenorrhea (McKinlay et al. 1992) or if they had a menstruation in the last two months but were currently taking HRT and were over 50. Participants who had had a hysterectomy before natural
menopause were classified as having a surgical menopause. Most participants didn’t know whether they had had bilateral oophorectomy during surgery or not. Women with > 12 months of amenorrhoea after radiotherapy or chemotherapy were classified as menopausal for “other” reason, while those without an identified reason for menopause were considered as “unknown” reason for menopause.
Current HRT use was defined as ongoing hormone replacement therapy for a duration of at least six months. Previous oral contraception (OC) was defined as use of the contraceptive pill in the past for at least six months.
Age, nationality, reproductive history and characteristics of HRT use were compared between both populations. We performed univariate and multivariate analyses to examine associations between HRT use and other characteristics. For univariate analyses, we compared categorical variables with χ2 test and continuous variables with t-test. For multivariate analyses, we used logistic regression models, adjusting for potential confounders. The odds ratios (OR)
obtained in these models measured the magnitude of the association between current HRT use and several sociodemographic and clinical characteristics in the clinic sample compared
to the general population. We used SAS software (SAS Institute, Cary, NC, USA) for the statistical analysis.
22
RESULTS
Of the 185 patients who attended the clinic, 34 recently arrived refugees were not Geneva residents. Of the 151 eligible patients, 15 women either refused to participate in the study, or could not fill in the form because of the lack of an interpreter, while another 9 patients left the clinic before they could be approached. Of the 127 patients (84% participation rate) who completed the questionnaire, 20 were excluded because they were premenopausal.
In the 1998 Bus Santé project, 337 women aged 45-65 years (56%) responded to the postal survey, of which 96 premenopausal women were excluded. We analysed the data on the reproductive history and HRT use provided by the final sample of 241 perimenopausal and postmenopausal women.
General characteristics of the participants in both populations are described in table 1. The mean age (55 years), use of oral contraception, menopause status, type of menopause and age by menopause status were similar in both samples. The higher proportion of foreigners in the clinic was the only significant difference observed. Prevalence of current HRT use tended to be lower among women of the outpatient clinic than in the general population (38.3% vs 47.7%, p=0.1).
On average, women started to take HRT at the age of fifty, which is close to the mean age of natural menopause (table 2). When analysed by age group, current HRT use was definitely not restricted to the perimenopausal period, but was distributed relatively harmoniously over the 15 years following menopause. Similar proportions of women had previously taken oral contraception. We observed 2 significant differences in HRT use between primary care
23
patients and the general population. First, a higher proportion of short-term current HRT users (1-2 years) in the clinical sample which contrasts with longer use in the community (41.5% vs. 18.3%, p=0.01). Second, a higher rate of surgical menopause among clinic patients than in the general population (34.4% vs 16.1%, p=0.04).
Table 3 shows results of a logistic regression expressed as the ratio of the odds of being a current HRT user in the clinic (versus a never user) to the odds of being a current HRT user in the general population according to known determinants of HRT use. This enables a quantification of differences in predictors of HRT use. Multivariate analysis shows that, compared to the general population, women attending the primary care clinic are
approximately twice less likely to be current HRT users if they had a natural menopause or were Swiss citizens.
DISCUSSION
Prevalence of current HRT use in the outpatient clinic was 38.3%, which was lower, although not significantly so, than in the general population. Clinic women with a surgical menopause used HRT significantly more often than women in the general population with the same characteristics. Also, current users in clinical practice used HRT for a shorter period (1-2 years) than in the community and were less likely to be Swiss.
To our knowledge, this is the first report that directly compares the prevalence and the application of a clinical preventive guideline in a clinical context with HRT use in the general population. This is possible because of the identical methodology applied in both surveys.
Characteristics of HRT use among women in medical care can therefore be directly compared with those of women living in the community, instead of solely being compared with unrelated clinical and epidemiological data.
It is important to remember that this study was conducted in the pre-WHI era when long-term HRT use was recommended for the prevention of chronic disease. Since then evidence has shown that HRT carries more risks than benefits and the U.S. Preventive services Task Force now recommends against HRT use for the prevention of chronic conditions (U.S. Preventive Services Task Force 2002).
In 1998, the prevalence of HRT in the clinical sample (38.3%) could be considered high when compared to most recent studies which showed that in clinical practice uptake was rarely higher than 30% with the exception of one study which showed a prevalence of 60% (Stafford et al 1997; Ghali et al. 1997; Wise et al. 1999; Levy et al. 2003). However, when compared to the prevalence in the population sample (47.7%), current HRT use in the clinic appeared to be rather low. The fact that prevalence in the clinical sample was not superior to prevalence in the
population is interesting since results from previous reports suggested that women in a medical setting used more hormones than the general population (Johannes et al.1994; MacLennan et al.
1993; Ringa 1999; Zhang et al. 1999).
There may be several reasons for the tendency to low HRT use in our clinical sample. For example, medical speciality plays an important part in doctors’ counselling and prescribing practices regarding HRT. In Switzerland, gynaecologists work as primary care providers for women’s health. This explains why all participants who took HRT in the outpatient clinic stated that the treatment was prescribed by their gynaecologist (results not shown). Gynaecologists were generally more favourable to HRT as a treatment for menopausal symptoms and for disease prevention than primary care physicians (Hemminki et al. 1993; Jolleys & Olesen 1996; Levy et al. 2003). Thus, the level of HRT use in the population survey could very well have reflected the high level of HRT prescribing among Swiss gynaecologists. This implies that clinic patients visited less often a gynaecologist.
Also, residents in the clinic could have been influenced by European authors who favoured HRT less strongly than their American counterparts (Posthuma et al. 1994; Khaw 1998). Furthermore, residents may have been more cautious in recommending long-term HRT use as they were
exposed to a critical and evidence-based approach to preventive interventions during their residency training. Practising physicians in the community may have been more influenced by pro-HRT Swiss gynaecological opinion leaders.
In our study, current HRT users in medical care were more likely to have a surgical menopause than current users in the general population. This result shows that counselling by residents in the outpatient clinic focused on women with a hysterectomy, which followed the American College of Physicians' recommendations of the time (American College of Physicians 1992). Surgical menopause had been universally associated with HRT use (Johannes et al. 1994;
Keating et al.1999; Moorhead et al.1997; MacLennan et al. 1993; Taffe et al. 1997; Harris et al.
1999).
The study also shows that a higher proportion of current users in the clinic took HRT for short periods than in the general population.
Current HRT users were less likely to be Swiss in the clinical sample than in the general population. It is likely that Swiss patients in the clinic came from a lower socio-economic
background and therefore presented a lower uptake than Swiss women from the general population.
This comparative study therefore shows that apart from a significantly lower proportion of Swiss patients in the clinic, the two study groups are similar in relation to age and menopause characteristics. When patterns of HRT use are compared between the two populations, patients in the clinic are taking HRT differently. They tend to use less HRT, for shorter periods and
preferably when they have a surgical menopause. The different pattern of HRT use is an indirect indicator of the residents’ clinical practice.
Our study is limited by the smaller sample in the outpatient clinic and the relatively low participation rate (56%) of women aged 45-65 years in the community sample. Since 29.3% of non-responders to the epidemiological survey were smokers versus 18.3% of participants (data not shown), the prevalence of HRT in the community sample could have been overestimated due to a selection bias towards a healthier life-style (Hemminki et al.1993). However, smoking was not associated with current HRT use in the general population (results not shown).
Another limitation could be the difficulty in assessing whether all patients who had had a hysterectomy had had a bilateral oophorectomy. It wasn’t possible to obtain more precise information on their surgical status. We have a good reason to believe that the data in the Bus Santé project and in the clinic are comparable since about 25% of women in both samples stated that they had a surgical menopause. Also, even if some of the women who claimed to have a surgical menopause still had their ovaries, that could not explain the difference in prescription between the community and the outpatient clinic.
The epidemiological survey provided data on average or “typical” behaviour in relation to HRT use in the community. We used this information to critically assess clinical practice in the same geographical area. We think that similar comparisons would be useful in other fields of medicine such as diabetes care or control of coronary heart disease risk factors.
In conclusion, our report shows that prevalence of HRT use in a Swiss academic general internal medicine outpatient clinic was relatively low compared to use in the community. This can be explained by socio-economic and medical factors. Compared to patterns of use in the community, HRT use in the clinic didn’t fully comply with prevailing recommendations on the prevention of chronic disease. Our study proposes an innovative approach to analysing clinical practice by providing a “population perspective” which gives clinicians the opportunity to critically assess their own practice. This method could be applied to other fields of prevention.
29
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REMERCIEMENTS
Je tiens à remercier toutes les personnes qui m’ont guidée et accompagnée dans ce long travail de recherche, particulièrement le Professeur Alfredo Morabia qui m’a initié à la recherche clinique et qui a quitté la Faculté de Médecine avant que la version definitive de la these soit terminée.
Bruna Galobardes a aussi été un element clé dans la réussite de ce projet, merci Bruna!
Table 1. Description of Participants in the Outpatient Clinic and in the General Population and Prevalence of Hormone Replacement Therapy and Oral Contraception, Geneva, Switzerland, 1998.
CHARACTERISTIC CLINIC
n= 107
GENERAL POPULATION
n= 241
P value
Age (mean +SD) 55.5 (+ 5.8) 55.3 (+ 5.3) 0.8
Age distribution (%) 45-49
50-54 55-59 60-65
23.4 18.7 32.7 25.2
14.1 30.3 30.3 25.3
0.06
Swiss Nationality (%) yes
no
57.0 43.0
76.4 23.6
0.001
Menopause status (%) perimenopausal
postmenopausal
29.0 71.0
22.8 77.2
0.2
Type of menopause (%)a natural menopause
surgical menopause other
unknown
70.7 25.3 2.7 1.3
75.2 22.0 2.8 0.0
0.4
Age by menopause status (mean yrs +SD)
perimenopause postmenopause
49.4 (+ 3.4) 58.0 (+ 4.5)
50.5 (+ 4.1) 56.8 (+ 4.7)
0.2 0.05 Contraceptive pill (%)
ever use 56.1 58.5 0.7
Hormone replacement therapy (%) current use
past use never use
38.3 10.3 51.4
47.7 5.8 46.5
0.1
a n= 75 in the clinic and n=182 in the population survey (postmenopausal women only) SD= standard deviation
Table 2. Characteristics of Current Hormone Replacement Therapy Users in the Clinic and in the General Population. Geneva, Switzerland, 1998.
CHARACTERISTIC CLINIC
n=41
GENERAL POPULATION
n=115
P value
Mean age (+SD) 56.4 (+5.3) 56.4 (+4.8) 0.9
Age of HRT initiation (mean+SD) 50.5 (+5.6) 50.2 (+4.2) 0.8
Swiss nationality(%) Yes
No
46.3 53.7
73.9 26.1
0.0013 HRT duration
mean (+SD) 5.5 (+ 5.4) 6.2 (+ 3.8) 0.5
HRT duration by age group (mean+SD)
45-49 years 50-54 years 55-59 years 60-65 years
1.0 (+0.6) 4.2 (+3.9) 6.4 (+4.9) 8.0 (+7.0)
2.4 (+1.4) 4.5 (+3.0) 6.0 (+3.3) 8.9 (+3.6)
0.04 0.8 0.8 0.7 HRT duration (%)
1-2 years 3-4 years
> 5 years
41.5 19.5 39.0
18.3 25.2 56.5
0.01
Menopause status (%) perimenopause
postmenopause
19.5 80.5
17.4 82.6
0.8
Type of postmenopause (%) natural menopause
surgical menopause other
59.4 34.4 6.3
81.7 16.1 2.2
0.04
Prior use of oral contraception(%)
yes 61.0 62.6 0.9
SD= Standard Deviation
36
Table 3. Prevalence and Odds Ratio of current Hormone Replacement Therapy use (versus never use) in the Clinic and in the General Population by Different Characteristics. Geneva, Switzerland, 1998.
CHARACTERISTIC CURRENT HRT USE
Clinic General
population
ORa CI95%
N % N %
Age groups 45-49 50-54 55-59 60-65
23 19 30 24
26.1 42.1 56.7 41.7
32 70 69 56
28.1 47.1 56.5 60.7
0.7 0.8 1.0 0.4
(0.2-2.5) (0.3-2.2) (0.4-2.4) (0.2-1.2) Nationality
Swiss Foreign
55 41
34.6 53.7
172 55
49.4 54.6
0.5 1.0
(0.2-0.9) (0.5-2.4) Menopausal status
postmenopausal perimenopausal
29 67
27.6 49.3
52 175
38.5 54.3
0.8 0.8
(0.4-1.4) (0.3-2.1) Type of menopause
natural menopause surgical menopause
47 16
40.4 68.8
126 40
60.3 37.5 -
0.4 3.7
(0.2-0.9) (1.0-12.9) Prior oral contraception
yes no
54 42
46.3 38.1
131 96
55.0 44.8
0.7 0.7
(0.4-1.4) (0.3-1.5)
OR= odds ratio CI=confidence interval
a simultaneously adjusted for all other variables in the table
37
Figure 1 : Questionnaire distributed to patients in the outpatient clinic
1. Date de naissance (jour). (mois). (année).
2. Initiales (les deux premières lettres de votre prénom et nom)) : (prénom) (nom) 3. Date de vos dernières règles : (mois) (année)
4. Si vous avez vos règles
a) sont-elles irrégulières ? 1ο oui 0ο non
si oui, pensez-vous être au début de la ménopause ? 1ο oui 0ο non 7ο je ne sais pas b) pensez-vous avoir des bouffées de chaleur dues à la ménopause ?
1ο oui 0ο non 7ο je ne sais pas
5. Si vous n’avez plus vos règles, pour quelle raison ?
1ο ménopause naturelle 2ο chirurgie(préciser...) 3ο autre (préciser...) 7ο je ne sais pas
6. Avez-vous déjà pris une pilule pour la contraception ?
1ο oui 0ο non 7ο je ne sais pas
Si vous av répondu oez ui à la question 6 :
Age du début de la prise de la pilule ? ans
La prenez-vous maintenant ? 1ο oui 0ο non
Age d’arrêt définitif éventuel ans
Pendant combien de temps au total en avez-vous pris ? ans Quel médecin a prescrit la pilule ? 1ο gynécologue 2ο médecin de famille
3ο autre
7. Avez-vous déjà pris des hormones pour la ménopause (comprimé, patch, gel, crème) ?
1ο oui 0ο non 7ο je ne sais pas
Si vous avez répondu oui à la question 7 :
Age du début du traitement avec les hormones ? ans
En prenez-vous maintenant ? 1ο oui 0ο non
Age d’arrêt définitif éventuel ? ans
Pendant combien de temps au total en avez-vous pris ans mois Quel médecin a prescrit les hormones ? 1ο gynécologue 2ο médecin de famille
3ο autre Si vous avez répondu non à la question 7 :
P our quelle raison n’avez-vous pas pris d’hormones pour la ménopause (plusieurs réponses possibles) ? 1ο mon médecin ne m’en a pas proposé 2ο j’ai peur des effets secondaires des
hormones
3ο ce n’est pas naturel de prendre des hormones 7ο je ne sais pas
4ο autre raison (préciser...) 8. Quelle est votre nationalité ? : ...
9. Si vous n’êtes pas Suissesse, quel est votre titre de séjour ? :
1ο permis de séjour B ou C 4ο permis frontalier ou carte de légitimation 3ο sans permis (de passage, voyage etc...) 2ο autre permis de séjour (A,F,G,L,N) 10. Si vous n’êtes pas née en Suisse, quand êtes-vous arrivée en Suisse ? 19
