Effect of characteristics of women on attendance in blind and non-blind randomised trials: analysis of recruitment data from the EPHT Trial.

OBJECTIVES: To analyse the effect of women's characteristics on their willingness to join a blind or a non-blind subtrial or to be excluded by physicians. DESIGN: Primary prevention trial of postmenopausal hormone therapy (HT). A 2×2, randomised design with a non-blind HT arm or control arm and a blind HT arm or placebo arm. SETTING: 3 clinical centres in Estonia. METHODS: Interest in joining the trial was asked in a questionnaire together with demographic and health status data. Interested and eligible women were invited to a health examination that also informed whether they belonged to a blind or to a non-blind subtrial; the arm was not revealed. Trial physicians made further exclusions when checking the women's eligibility. Thereafter, informed consent was asked as detailed in the flow chart. Comparisons were made between non-blind and blind subtrials. Analyses were carried out for each of the background variables. OUTCOME MEASURES: The proportion of willingness, eligibility and attendance. RESULTS: Women randomised to the non-blind subtrial were more willing to join (relative risk (RR) 1.17) and more likely to be found eligible by physicians (RR 1.10) than women in the blind subtrial, resulting in larger attendance (RR 1.29). Women with higher education were differentially more willing to join the non-blind trial (RR 1.29) than those with basic education (RR 1.08); the differential willingness of never-smokers (RR 1.20) was larger than that of current smokers (RR 1.07). The differential exclusion by physicians by education and smoking were small. Some subjective symptoms (eg, diarrhoea/constipation, stomach pain) had reverse differential effects on attendance in the non-blind subtrial in comparison to the blind subtrial. Menopausal symptoms did not affect the differential interest, eligibility or attendance. CONCLUSIONS: Blinding in RCT reduces attendance, due to decisions of the women and the trial physicians. Differential attendance by blinding may affect the generalisability of the results from trials. TRIAL REGISTRATION NUMBER: ISRCTN35338757.

Predictive value of exhaled nitric oxide in the management of asthma: a systematic review.

The clinical value of measuring fractional exhaled nitric oxide (FeNO) in asthma is not clear. We aimed to assess whether FeNO can reliably predict clinical outcomes in asthma treated with inhaled corticosteroids (ICS). We also evaluated whether its predictive role is influenced by different inflammatory phenotypes of asthma.We conducted a systematic review focusing on five clinically relevant questions. Two authors independently screened search results, extracted data and assessed quality of the included studies. Data were synthesised by qualitative methods.12 prospective studies were included, answering partly three of the five questions. In steroid-naïve asthma, a high FeNO level probably predicts good response to ICS. In ICS-treated asthmatics, a low FeNO level probably predicts low risk of exacerbation, and the patient is unlikely to benefit from increasing ICS dose. There were scarce data to conclude whether FeNO predicts exacerbations when ICS treatment is stopped in well-controlled asthma. Only one study reported results separately in different asthma phenotypes.The current evidence on the predictive value of FeNO and its role in the management of asthma is incomplete. Future studies should focus on clinically meaningful questions and probably target only eosinophilic phenotypes where FeNO is best associated with the activity of airway inflammation.

The effect of hormone therapy on women's quality of life in the first year of the Estonian Postmenopausal Hormone Therapy trial.

BACKGROUND: For postmenopausal women, the main reason to start hormone therapy (HT) is to reduce menopausal symptoms and to improve quality of life (QOL). The aim of this study was to analyse the impact of HT on different aspects of symptom experience and QOL during a randomised trial. A total of 1823 postmenopausal women were recruited into the Estonian Postmenopausal Hormone Therapy (EPHT) trial in 1999-2001. Women were randomised to blind HT, open-label HT, placebo or non-treatment arm. After one year in the trial, a questionnaire was mailed and 1359 women (75%) responded, 686 in the HT arms and 673 in the non-HT arms. Mean age at filling in the questionnaire was 59.8 years. The questionnaire included Women's Health Questionnaire (WHQ) to assess menopause specific QOL of middle-aged women together with a 17-item questionnaire on symptoms related to menopause, a question about painful intercourse, and a question about women's self-rated health. RESULTS: After one year in the trial, fewer women in the HT arms reported hot flashes, trouble sleeping, and sweating on the symptom questionnaire. According to WHQ, women in the HT arms had fewer vasomotor symptoms, sleep problems, and problems with sexual behaviour, but more menstrual symptoms; HT had no effect on depression, somatic symptoms, memory, attractiveness, or anxiety. A smaller proportion of women reported painful intercourse in the HT arms. There were no significant differences between the trial arms in women's self-rated subjective health. CONCLUSIONS: The results from the EPHT trial confirm that HT is not justified for treating symptoms, other than vasomotor symptoms, among postmenopausal women. WHQ proved to be a useful and sensitive tool to assess QOL in this age group of women.

Hysteroscopic tubal sterilization: a systematic review of the Essure system.

OBJECTIVE: To update the evidence of the efficacy and safety of the Essure system. Female sterilization has undergone changes in the last decade. Besides laparoscopic tubal occlusion, the Essure system is now a viable option, with about 200,000 women sterilized using this method. DESIGN: The review is based on the report of the Alberta Heritage Foundation for Medical Research and completed with systematic literature searches up to April 8, 2008. SETTING: The Managed Uptake of Medical Methods program of the Finnish National Research and Development Center for Health and Welfare. PATIENT(S): Women over 30 years, who had been sterilized by the Essure method. INTERVENTION(S): Hysteroscopic tubal sterilization using Essure system. MAIN OUTCOME MEASURE(S): Efficacy/effectiveness, adverse events, costs. RESULT(S): Sterilization by Essure can be performed under local anesthesia or with oral analgesics in ambulatory settings. However, sterilization is not immediate and women must use additional contraception for 3 months until permanent tubal occlusion is verified by transvaginal ultrasound, hysterosalpingosonography, hysterosalpingography, or pelvic radiography. The evidence on efficacy and safety is mainly available from short follow-up case series but shows good efficacy and safety of the Essure system. Only a few small risks are associated with the procedure. Two economic studies, one of which implemented Essure as an in-office procedure, suggest that Essure could be more cost-effective than laparoscopic sterilization, but more information on the total cost is needed. CONCLUSION(S): The Essure system appears to be safe, permanent, irreversible, and a less invasive method of contraception compared with laparoscopic sterilization.

The effects of postmenopausal hormone therapy on social activity, partner relationship, and sexual life - experience from the EPHT trial.

BACKGROUND: With the exception of sexual functioning and weight, social and behavioural effects of postmenopausal hormone therapy (HT) have not been reported from trials. This paper reports such results from the EPHT-trial in Estonia. METHODS: A randomized trial, with a blind and non-blind sub-trial in Estonia. From 1999-2001, 1778 women were recruited. The mean follow-up was 3.6 years. Women's experiences were asked in the first and final study year by mailed questionnaires (74 and 81% response rates). Comparisons of the groups were made by cross-tabulation and logistic regression, adjusting for age. RESULTS: There were no differences between the HT and non-HT groups in regard to being employed, the extent of social involvement or marital status or opinions on aging. There was no difference in the frequency of free-time exercise, or overweight. Some of the indicators suggested less sexual inactivity, but the differences were small. CONCLUSION: In a trial setting, postmenopausal hormone therapy did not influence work or social involvement or health behaviour.

Experiences of a long-term randomized controlled prevention trial in a maiden environment: Estonian Postmenopausal Hormone Therapy trial.

BACKGROUND: Preventive drugs require long-term trials to show their effectiveness or harms and often a lot of changes occur during post-marketing studies. The purpose of this article is to describe the research process in a long-term randomized controlled trial and discuss the impact and consequences of changes in the research environment. METHODS: The Estonian Postmenopausal Hormone Therapy trial (EPHT), originally planned to continue for five years, was planned in co-operation with the Women's International Study of Long-Duration Oestrogen after Menopause (WISDOM) in the UK. In addition to health outcomes, EPHT was specifically designed to study the impact of postmenopausal hormone therapy (HT) on health services utilization. RESULTS: After EPHT recruited in 1999-2001 the Women's Health Initiative (WHI) in the USA decided to stop the estrogen-progestin trial after a mean of 5.2 years in July 2002 because of increased risk of breast cancer and later in 2004 the estrogen-only trial because HT increased the risk of stroke, decreased the risk of hip fracture, and did not affect coronary heart disease incidence. WISDOM was halted in autumn 2002. These decisions had a major influence on EPHT. CONCLUSION: Changes in Estonian society challenged EPHT to find a balance between the needs of achieving responses to the trial aims with a limited budget and simultaneously maintaining the safety of trial participants. Flexibility was the main key for success. Rapid changes are not limited only to transiting societies but are true also in developed countries and the risk must be included in planning all long-term trials. The role of ethical and data monitoring committees in situations with emerging new data from other studies needs specification. Longer funding for preventive trials and more flexibility in budgeting are mandatory. Who should prove the effectiveness of an (old) drug for a new preventive indication? In preventive drug trials companies may donate drugs but they take a financial risk, especially with licensed drugs. Public funding is crucial to avoid commercial biases. Legislation to share the costs of large post-marketing trials as well as regulation of manufacturer's participation is needed. [ISRCTN35338757].

Symptom reporting and quality of life in the Estonian Postmenopausal Hormone Therapy Trial.

BACKGROUND: The aim of the study was to determine the effect of postmenopausal hormone therapy on women's symptom reporting and quality of life in a randomized trial. METHODS: 1823 women participated in the Estonian Postmenopausal Hormone Therapy (EPHT) Trial between 1999 and 2004. Women were randomized to open-label continuous combined hormone therapy or no treatment, or to blind hormone therapy or placebo. The average follow-up period was 3.6 years. Prevalence of symptoms and quality of life according to EQ-5D were assessed by annually mailed questionnaires. RESULTS: In the hormone therapy arms, less women reported hot flushes (OR 0.20; 95% CI: 0.14-0.28), sweating (OR 0.56; 95% CI: 0.44-0.72), and sleeping problems (OR 0.66; 95% CI: 0.52-0.84), but more women reported episodes of vaginal bleeding (OR 19.65; 95% CI: 12.15-31.79). There was no difference between the trial arms in the prevalence of other symptoms over time. Quality of life did not depend on hormone therapy use. CONCLUSION: Postmenopausal hormone therapy decreased vasomotor symptoms and sleeping problems, but increased episodes of vaginal bleeding, and had no effect on quality of life. TRIAL REGISTRATION NUMBER: ISRCTN35338757.

Postmenopausal hormone therapy increases use of health services: experience from the Estonian Postmenopausal Hormone Therapy Trial [ISRCTN35338757].

OBJECTIVE: This study was undertaken to compare utilization of health services and health care costs in a randomized hormone therapy trial. STUDY DESIGN: A total of 1823 healthy postmenopausal women aged 50 to 64 years at the time of sampling were allocated to combined continuous hormone therapy or placebo or no treatment. The analysis was based on routinely collected electronic data in the Estonian Health Insurance Fund database during a follow-up period from 2 to 5 years. RESULTS: In the nonblind subtrial, the number of all health care visits was 10% higher and the number of visits to family practitioners 16% higher per person-year in the hormone therapy arm. Per person-year, the number of vaginal sonograms was 14% and the number of electrocardiograms 19% higher in the nonblind hormone therapy arm. Outpatient health care costs and drug expenses were higher in the nonblind hormone therapy arm. In the blind subtrial, the number of gynecologic operations, vaginal sonograms and total health care costs was higher in the hormone therapy arm. CONCLUSION: Hormone therapy caused additional expenses on health care.

Results from the Estonian postmenopausal hormone therapy trial [ISRCTN35338757].

OBJECTIVES: At present the Women's Health Initiative trial is the only reported randomised controlled trial studying the effects of hormone therapy among healthy postmenopausal women. The Women's Health Initiative reports have been criticized for lacking in generalisability, due to the characteristics of the trial population. We aimed to compare the health effects of oral continuous combined hormone therapy with a placebo and non-treatment among healthy Estonian women. METHODS: Eligible women were randomised into a blind group of hormone therapy versus placebo and into a non-blind group of open label hormone therapy versus non-treatment. One thousand seven hundred and seventy-eight postmenopausal women aged 50-64 at the time of sampling were recruited in 1999-2001 at three clinical centers in Estonia. Participants received conjugated equine oestrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5mg/d, or conjugated equine oestrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 5mg/d, if less than 3 years had passed since menopause at recruitment, or matched placebo or non-treatment. Trial treatment was stopped gradually from 1 January 2004 to 31 May 2004. RESULTS: After a follow-up period from 2.0 to 5.0 years the combined hazard ratio, stratified by blinding and adjusted for age at recruitment and former oral contraceptive use was 1.12 (95% confidence interval [CI]: 0.90-1.40) for coronary heart disease, 1.24 (95% CI: 0.85-1.82) for cerebrovascular disease, 1.36 (95% CI: 0.73-2.52) for total cancer, and 0.61 (95% CI: 0.42 to 0.89) for bone fractures. CONCLUSIONS: The results from the Estonian Postmenopausal Hormone Therapy randomised trial are consistent with the Women's Health Initiative findings.

Treatment adherence in the Estonian postmenopausal hormone therapy (EPHT) trial [ISRCTN35338757].

OBJECTIVE: To investigate treatment adherence and factors related to non-adherence in the Estonian postmenopausal hormone therapy (EPHT) trial. METHODS: A total of 1823 postmenopausal women aged 50-64 years were recruited into the EPHT trial from 1999 to 2001. They were randomised into the blind group receiving continuous orally administered postmenopausal hormone therapy (PHT) or a placebo and to a non-blind group receiving open-label PHT or no drugs. A woman was classified as non-adherent, if she had stopped treatment for at least 6-month period in treatment arms or used PHT for at least 6-month period in the control group. Adherence was calculated by the Kaplan-Meier method, and factors affecting adherence were studied with Cox proportional hazard modelling. RESULTS: The rate of adherent women declined approximately 50% during the first year in all treatment arms. Less than 10% of the control group women started taking prescribed PHT. Older women, with lower education, with only one birth, never used oral contraceptives (OC), with lower physical activity or who were dissatisfied with the information received from the trial staff, were more likely to discontinue. In treatment arms, the two most often cited reasons for non-adherence were side-effects and woman's loss of interest in participation. Control group women started PHT due to the menopausal symptoms or on doctor's recommendation. CONCLUSIONS: The adherence was similar to that found for PHT use in everyday life. Higher adherence was related to younger age, higher education, previous OC use, physical activity and satisfaction with received information.

Women's views of the climacteric at the time of low menopausal hormone use, Estonia 1998.

OBJECTIVES: This study examined women's opinions about the climacteric and hormone therapy (HT) after menopause and compared women's and physicians' opinions in a country of low-HT use. METHODS: In 1998, a postal questionnaire was sent to a random sample of 2000 Estonian 45-64-year-old women; 69% (n=1312) responded. In 1999, a postal questionnaire was sent to a random sample of 500 Estonian gynaecologists and general practitioners; 68% (n=342) responded. RESULTS: Mean age at menopause was 49.8 years (S.D. 4.0), and there was no difference by socioeconomic classes or by age in self-rated health. Ten percent of women reported having used HT, with 3% currently using it. Most women reported some symptoms, with vasomotor symptoms more frequently reported by 50-54 years old; women most often reported tiredness (48%). Half of the women but under a fifth of physicians considered the climacteric a normal phase of life. Women's awareness about HT was low and about half had no opinion on its health effects. Half of the women had visited a gynaecologist, older women less so. Women with contacts with health care were more aware of HT. CONCLUSIONS: Women reported symptoms by age-group as similarly found in high-HT use countries and it verifies that many symptoms experienced were not due to menopause. As in other low-HT use countries, women were unfamiliar with HT and their attitudes were traditional, although physicians' attitudes were more positive. Estonian women seemed to have escaped the period of the preventive use of HT.

Who wants to join preventive trials?--Experience from the Estonian Postmenopausal Hormone Therapy Trial [ISRCTN35338757].

BACKGROUND: The interest of patients in participating in randomized clinical trials involving treatments has been widely studied, but there has been much less research on interest in preventive trials. The objective of this study was to find out how many women would be interested in a trial involving postmenopausal hormone therapy (PHT) and how the women's background characteristics and opinions correlated to their interest. METHODS: The data come from recruitment questionnaires (n = 2000) sent to women in Estonia in 1998. A random sample of women aged 45 to 64 was drawn from the Population Registry. The trial is a two-group randomized trial comparing estrogen-progestogen therapy with placebo or no drugs. A brief description of the study was attached to the questionnaires. Women were not told at this stage of the recruitment which group they would be assigned to, however, they were told of the chance to receive either hormone, placebo or no treatment. RESULTS: After two reminders, 1312 women (66%) responded. Eleven percent of the women approached (17% of the respondents) were interested in joining the trial, and 8% wanted more information before deciding. When the 225 women who stated clearly that they were interested in joining and the 553 women who said they were not interested were compared, it was found that interested women were younger and, adjusting for age, that more had given birth; in other respects, the sociodemographic characteristics and health habits of the interested women were similar to those of the non-interested women. The interested women had made more use of more health services, calcium preparations and PHT, they were more often overweight, and more had chronic diseases and reported symptoms. Interested women's opinions on the menopause were more negative, and they favoured PHT more than the non-interested women. CONCLUSION: Unlike the situation described in previous reports on preventive trials, in this case Estonian women interested in participating in a PHT trial were not healthier than other women. This suggests that trials involving PHT are more similar to treatment trials than to preventive trials. In a randomized controlled trial, more information should be obtained from those women who decline to participate.

Blinding decreased recruitment in a prevention trial of postmenopausal hormone therapy.

PURPOSE: To compare the effect of blind design (active drug and placebo) and nonblind design (active drug and no treatment) on recruitment. SETTING: A primary prevention trial with postmenopausal hormone therapy in Estonia. METHODS: Women who were eligible and willing to participate on the basis of the questionnaire survey were randomized into blind and nonblind groups. Recruitment rates are based on record keeping, and reasons for participating were requested in the first-year follow-up. RESULTS: The recruitment was 30% higher in the nonblind group: of the 4,295 women invited, 37% (95% confidence interval CI=35-39%) in the blind group and 48% (95% CI=46-49%) in the nonblind group were recruited. In both groups, once randomized, most of the losses were women who did not attend the first clinical examination: 49% (blind; 95% CI=47-51%) and 40% (nonblind; 95% CI=38-42%). The rest were found ineligible or lost their interest during clinical examinations. The reasons for joining the trial were relatively similar in the two groups. CONCLUSIONS: Blinding decreased women's interest in joining a long-term preventive trial. Women's reasons for joining the trial were not influenced by blinding.

Births and perinatal health of infants among women who have had silicone breast implantation in Finland, 1967-2000.

BACKGROUND: Potential problems with breast implants have been widely discussed, but few data exist on the childbearing and offspring of women with implants. The purpose of this study was to investigate the occurrence and conditions of pregnancies of women who have had cosmetic breast implantation (exposed women), and the health of their newborns. METHODS: Women who had breast implants for cosmetic reasons in the period 1967-1999 (n = 2236) were identified from hospital surgical records. The births of the exposed women were identified through record linkage to the Population Register. The perinatal health of the infants was studied by the data in the Medical Birth Register in 1987-1999. For each birth to an exposed woman, 20 control mothers who gave birth in the same year were chosen randomly from the Medical Birth Register. Differences in mothers' background characteristics were adjusted by logistic regression. RESULTS: The women had received their first cosmetic breast implants at young ages (mean 31 years). By year 2000, 26% of the exposed women had one or more children. Half of these women had not had a liveborn child before getting implants. Of the 1661 exposed women who had not (yet) had children, 32% were less than 35 years of age at the end of follow-up. The women had children at a mean of 4.7 years after the implants. Some of the perinatal health indicators suggested poorer health and others better health for infants of exposed women, but only transfers to other hospitals and lower birthweight among infants of exposed multipara were statistically significant. CONCLUSIONS: The study shows that pregnancy and infant health are relevant considerations with regard to breast implants; further studies on implants are needed.

Comparison of Estonian and Finnish physicians' opinions of menopause and hormone therapy.

OBJECTIVE: To compare Estonian and Finnish gynaecologists' and general practitioners' (GP) opinions on and prescribing practices in hormone treatment (HT) during and after menopause. METHODS: Data was collected using similar postal questionnaires. In 2000 in Estonia, a random sample included 212 gynaecologists and 288 GPs (68% responded); and in 1989 in Finland, 100 male and 100 female gynaecologists, 100 general practitioner specialists and 100 non-specialists (73% responded). Gynaecologists and GPs were compared to each other within the countries, and the two countries were compared within the specialities. RESULTS: Gynaecologists' opinions of benefits were positive and similar in Estonia and Finland, and more positive than those of GPs. Gynaecologists and GPs in both countries had similar opinions about harms. Gynaecologists were in favour of longer HT than GPs, and longer treatment was recommended in Finland than in Estonia. In both countries a large proportion of physicians (48% of gynaecologists in Estonia and 65% in Finland) stated that they would routinely prescribe HT to all women at menopause without contraindication, regardless of symptoms, and some (31% of gynaecologists in Estonia and 19% in Finland) favoured routine prescribing to all postmenopausal women. CONCLUSIONS: Estonian physicians' positive attitudes suggest increased use of HT. Comparisons of the two countries and specialities suggest that physicians' positive opinions may long predate increased use.

The drug industry and medical practice--the case of menopausal hormone therapy in Estonia.

After the dissolution of the Soviet Union, Estonia quickly adopted a market economy. In medicine this has included the uptake of western-style health care and drug promotion aimed at practising physicians. Using post-menopausal hormone therapy (HT) as an example, we studied the consequences of this natural experiment on prescribing and on physicians' opinions of HT and drug promotion. Data were obtained from a cross-sectional questionnaire survey sent to gynaecologists and family practitioners (FPs) in 2000 compared to an earlier Finnish survey, and from drug sales figures (based on defined daily doses), local medical journals and observations. The survey focussed on physicians' opinions of HT, HT information and HT education, and was sent to a random sample of 500 physicians, of whom 68% responded. The sales of HT drugs in the 1990s in Estonia were much lower than in Finland, but rapidly rose during that decade. Physicians considered drug advertising to be a factor contributing to the increased HT use. Most gynaecologists but fewer FPs reported that they had had enough continuing education on menopause and HT. For 39% of the gynaecologists and 20% of the FPs, (part of) the costs to attend their last education activity was paid by a drug firm. Respondents who wished for further education considered drug firms to be potential organisers. Gynaecologists had had more communication on HT with the drug industry, and their attitudes towards HT were more positive than those of FPs. Fears about cancer in the 1980s were not found in 2000. The study suggests that the drug industry contributed to the change in physicians' views of HT.

Causes of death among Finnish women with cosmetic breast implants, 1971-2001.

Mortality patterns among women with cosmetic breast implants have not been well characterized. We examined cause-specific mortality among women who underwent cosmetic breast implantation at major public hospitals and private clinics in Finland from 1970 through 2000. Causes of death through 2001 were identified through the national mortality register. Expected numbers of deaths were calculated on the basis of mortality rates in the general female population, and standardized mortality ratios (SMR), i.e. ratios of observed to expected deaths, and 95% confidence intervals (CI) were calculated. Among the 2166 women with cosmetic breast implants, we observed 31 deaths versus 32.1 expected. Overall disease mortality was below expectation, mainly due to low mortality from diseases of the circulatory system (SMR, 0.28; 95% CI, 0.03-1.02). Mortality from cancer was close to expectation. There was a statistically significant excess of suicide, based on 10 deaths, which was most pronounced during the first 5 years of follow-up (SMR, 4.26; 95% CI, 1.56-9.26). In conclusion, although based on small numbers, women with cosmetic breast implants did not experience higher mortality overall than women in the general population. The high suicide risk supports other studies and warrants further detailed investigation.

Incidence of breast and other cancers among Finnish women with cosmetic breast implants, 1970-1999.

Epidemiologic evidence does not point to a carcinogenic effect of silicone implants on the breast, and evidence for or against a carcinogenic effect at sites other than the breast is limited. To examine subsequent cancer risk among women with cosmetic breast implants, we conducted a cohort study of 2171 women in Finland identified from operation diaries of major hospitals and private clinics, 1970-1999. The nationwide population and health outcome registries in Finland were used to trace these women for cancer incidence through 1999. Standard statistical techniques were used to compute expected values based on general population rates. The measure of risk was taken as the ratio of observed to expected cancers, that is, the standardized incidence ratio (SIR) and its 95% confidence interval (CI). Among the 2171 women with cosmetic breast implants, 30 developed cancer against 33.7 expected (SIR = 0.9,95% CI = 0.6-1.3). There was no evidence for an increase in breast cancer risk (SIR 0.5, 95% CI, 0.2-1.0), even among those followed for more than 10 years (2 observed, 4.6 expected). Stage at breast cancer diagnosis did not differ from that expected nor did incidence of any other cancer. Although hindered by small numbers, the consistency of our results with those of other Nordic studies leads us to conclude that cosmetic breast implants are not a cause of cancer and that they do not appear to delay the detection of breast cancers.