Exercise Evaluation Randomised Trial (EXERT): a randomised trial comparing GP referral for leisure centre-based exercise, community-based walking and advice only.

OBJECTIVES: To evaluate and compare the effectiveness and cost-effectiveness of a leisure centre-based exercise programme, an instructor-led walking programme and advice-only in patients referred for exercise by their GPs. DESIGN: A single-centre, parallel-group, randomised controlled trial, consisting of three arms, with the primary comparison at 6 months. SETTING: Assessments were carried out at Copthall Leisure Centre in Barnet, an outer London borough, and exercise programmes conducted there and at three other leisure centres and a variety of locations suitable for supervised walking throughout the borough. PARTICIPANTS: Participants were aged between 40 and 74 years, not currently physically active and with at least one cardiovascular risk factor. INTERVENTIONS: The 943 patients who agreed to participate in the trial were assessed in cohorts and randomised to one of the following three arms: a 10-week programme of supervised exercise classes, two to three times a week in a local leisure centre; a 10-week instructor-led walking programme, two to three times a week; an advice-only control group who received tailored advice and information on physical activity including information on local exercise facilities. After 6 months the control group were rerandomised to one of the other trial arms. Assessments took place before randomisation, at 10 weeks (in a random 50% subsample of participants), 6 months and 1 year in the leisure centre and walking arms. The control participants were similarly assessed up to 6 months and then reassessed at the same intervals as those initially randomised to the leisure centre and walking groups. MAIN OUTCOME MEASURES: The primary outcome measures were changes in self-reported exercise behaviour, blood pressure, total cholesterol and lipid subfractions. Secondary outcomes included changes in anthropometry, cardiorespiratory fitness, flexibility, strength and power, self-reported lifestyle behaviour, general and psychological health status, quality of life and health service usage. The costs of providing and making use of the service were quantified for economic evaluation. RESULTS: There was a net increase in the proportion of participants achieving at least 150 minutes per week of at least moderate activity in the sport/leisure and walking categories in all three study groups: at 6 months, the net increases were 13.8% in the leisure centre group, 11.1% in the walking group and 7.5% in the advice-only group. There were significant reductions in systolic and diastolic blood pressure in all groups at each assessment point compared with baseline. There were also significant and sustained improvements in cardiorespiratory fitness and leg extensor power, and small reductions in total and low-density lipoprotein cholesterol in all groups, but there were no consistent differences between the groups for any parameter over time. All three groups showed improvement in anxiety and mental well-being scores 6 months after the beginning of the trial. Leisure centre and walking groups maintained this improvement at 1 year. There were no differences between groups. Costs to the participants amounted to pound 100 for the leisure centre scheme and pound 84 for the walking scheme, while provider costs were pound 186 and pound 92, respectively. Changes in overall Short Form 36 scores were small and advice only appeared the most cost-effective intervention. CONCLUSIONS: The results of this trial suggest that referral for tailored advice, supported by written materials, including details of locally available facilities, supplemented by detailed assessments may be effective in increasing physical activity. The inclusion of supervised exercise classes or walks as a formal component of the scheme may not be more effective than the provision of information about their availability. On cost-effectiveness grounds, assessment and advice alone from an exercise specialist may be appropriate to initiate action in the first instance. Subsidised schemes may be best concentrated on patients at higher absolute risk, or with specific conditions for which particular programmes may be beneficial. Walking appears to be as effective as leisure centre classes and is cheaper. Efforts should be directed towards maintenance of increased activity, with proven measures such as telephone support. Further research should include an updated meta-analysis of published exercise interventions using the standardised mean difference approach.

UK women doctors' use of hormone replacement therapy: 10-year follow up.

OBJECTIVES: To determine changes in the prevalence and duration of use of hormone replacement therapy (HRT) by women doctors over 10 years. METHODS: Questionnaire survey of 1234 UK women doctors (randomized, stratified sample), compared with a similar survey in 1993. RESULTS: In women aged 50-64 years, the age-standardized prevalence of ever-use of HRT had increased from 53.4% in 1993 to 66.2% in 2003 (p<0.001). There was a marked reduction in uptake by women under 50 years, while the age-standardized prevalence of current use in women aged 50-64 years was unchanged at 38.1%. The discontinuation rate in this age group had increased from 27.8% to 42.4% (p<0.001). Over 20% of women aged 65-74 years were still using HRT. The median duration of HRT use was 8.1 years by current users and 5 years by past users. The major indications were symptom relief and osteoporosis prevention. Current users of HRT tended to have more definite views about the potential risks and benefits of long-term use than past or never-users. CONCLUSIONS: The proportion of women doctors starting HRT increased after 1993, but uptake and continuation rates have now both declined, consistent with prescription data, probably reflecting the changing nature of the evidence base. However, many women doctors still intended to continue long-term HRT.

Lack of response to octreotide in Cushing's syndrome due to metastatic adrenocortical carcinoma.

Functional metastatic adrenocortical carcinoma is an uncommon cause of Cushing's syndrome, which rarely responds to conventional treatment. A patient presenting with Cushing's syndrome secondary to adrenocortical carcinoma underwent surgical resection. Postoperatively, she developed metastatic disease resistant to conventional chemotherapy. Octreotide, a somatostatin analogue which is effective in the treatment of several types of neuroendocrine tumour, was tried to ameliorate her secretory symptoms, but without any therapeutic effect.

Mortality of women with polycystic ovary syndrome at long-term follow-up.

Metabolic disturbances associated with insulin resistance are present in most women with polycystic ovary syndrome. This has led to suggestions that women with polycystic ovary syndrome may be at increased risk of cardiovascular disease in later life. We undertook a long-term follow-up study to test whether cardiovascular mortality is increased in these women. A total of 786 women diagnosed with polycystic ovary syndrome in the United Kingdom between 1930 and 1979 were traced from hospital records and followed for an average of 30 years. Standardized mortality ratios (SMRs) were calculated to compare the death rates of these women with national rates. The SMR for all causes was 0.90 (95% CI, 0.69-1.17), based on 59 deaths. There were 15 deaths from circulatory disease, yielding an SMR of 0.83 (95% CI, 0.46-1.37). Of these 15 deaths, 13 were from ischemic heart disease (SMR 1.40; 95% CI, 0.75-2.40) and two were from other circulatory disease (SMR 0.23; 95% CI, 0.03-0.85). There were six deaths from diabetes mellitus as underlying or contributory cause, compared with 1.7 expected (odds ratio 3.6; 95% CI, 1.5-8.4). Breast cancer was the commonest cause of death (SMR 1.48 based on 13 deaths; 95% CI, 0.79-2.54). We conclude that women with polycystic ovary syndrome do not have markedly higher than average mortality from circulatory disease, even though the condition is strongly associated with diabetes, lipid abnormalities, and other cardiovascular risk factors. The characteristic endocrine profile of women with polycystic ovary syndrome may protect against circulatory disease in this condition.

Why do women doctors in the UK take hormone replacement therapy?

STUDY OBJECTIVES: To ascertain the determinants and experiences of hormone replacement therapy (HRT) use by menopausal women doctors. DESIGN: Postal questionnaire. SETTING: UK. PATIENTS: A randomized stratified sample of women doctors who obtained full registration between 1952 and 1976, taken from the current Principal List of the UK Medical Register. MAIN OUTCOME MEASURES: Current and previous use of HRT; reasons for and against HRT use; menopausal status; hormonal contraceptive use; lifestyle patterns; family and personal history of disease. MAIN RESULTS: While 73.2% of 471 users had started HRT for symptom relief, 60.9% cited prevention of osteoporosis and 32.7 prevention of cardiovascular disease. Altogether 18.7% had started for preventive purposes alone. Significant predisposing factors to starting HRT were the presence and severity of menopausal symptoms, surgical menopause, past use of hormonal contraception, and a family history of osteoporosis. HRT users were also more likely to use skimmed rather than full fat milk, to try to increase their intake of fruit, vegetables, and fibre, and to undertake vigorous physical activity at least once a week. They were less likely to have had breast cancer. Long duration users were more likely than short duration users to be past users of hormonal contraception and to be using HRT for prevention of osteoporosis as well as symptom relief; they were less likely to have experienced side effects. CONCLUSIONS: The high usage of HRT by women doctors reflects the fact that many started HRT on their own initiative and with long term prevention in mind. The results may become generalisable to the wider population as information on the potential benefits of HRT is disseminated and understood. However, HRT users may differ slightly from non-users in health-related behaviour and a substantial minority may never take up HRT, at least until the benefit-risk ratio is more clearly established.

Is hormone replacement therapy prescribed for postmenopausal diabetic women?

A community-based survey was undertaken to ascertain current hormone replacement therapy (HRT) prescription rates in postmenopausal diabetic women. From age/sex and disease registers linked to prescription data which covered 144,237 patients, details on 6867 women aged 50-60 years were obtained. Of this group, 1684 (24.5%) were receiving prescriptions for HRT; the comparable figures for the 537 patients with hypertension and 135 (insulin-dependent and non-insulin dependent) diabetic patients were 117 (21.8%) and 15 (11.1%) respectively. While the presence of hypertension did not affect the likelihood of being prescribed HRT (odds ratio 0.85 [95% CI 0.68-1.05], p > 0.1), women with diabetes were less than half as likely as those from the general population to be prescribed HRT (odds ratio 0.38 [95% CI 0.21-0.67], p < 0.001). These data indicate that proportionately greater numbers of postmenopausal diabetic women, even compared with those with hypertension, another group at high risk of cardiovascular disease, are denied the potential benefits of HRT.

Utilisation of hormone replacement therapy by women doctors.

OBJECTIVES: To ascertain the prevalence and duration of use of hormone replacement therapy by menopausal women doctors. DESIGN: Postal questionnaire. SETTING: General practices in the United Kingdom. SUBJECTS: Randomised stratified sample of women doctors who obtained full registration between 1952 and 1976, taken from the current principal list of the Medical Register. MAIN OUTCOME MEASURES: Prevalence and duration of use of hormone replacement therapy; menopausal status. RESULTS: Overall, 45.7% (436/954) of women doctors aged between 45 and 65 years had ever used hormone replacement therapy. When the results from women still menstruating regularly were excluded, 55.2% (428) were ever users and 41.2% (319) current users. The cumulative probability of remaining on hormone replacement therapy was 0.707 at five years and 0.576 at 10 years. CONCLUSIONS: Women doctors have a higher prevalence of use of hormone replacement therapy than has been reported for other women in the United Kingdom, and most users seem to be taking hormone replacement therapy for more than five years. The results may become generalisable to the wider population as information on the potential benefits of hormone replacement therapy is disseminated.

Driving and drug regulation.

The UK Licensing Authority, aided by advice from expert committees, has the statutory duty to evaluate new medicines in respect of quality, safety and efficacy. All drug applications in the EC must now be accompanied by a summary of product characteristics which includes a statement on the effects of the products on the ability to drive and operate machinery. Any claims or warnings made in this or other respects must be based on data resulting from scientific experiments and will appear in data sheets. Appropriate label warnings may also be required, in some cases imposed by the Labelling Regulations, such as the standard antihistamine warning. The use of package inserts to give further warning to the public is currently under study.

A clinical assessment of Modifast in U.K. general practice.

Between April and October 1983, 443 subjects were offered a month's course of Modifast by their general practitioners. Modifast is a very low calorie formula diet containing 1.7MJ (410 kcal) and 70g protein per day. Results available on 335 of these individuals indicate that 217 completed a four week course and achieved an average weight loss of 6.6 kg, whilst those that did not complete the course achieved a 2.6 kg weight loss. Concurrent disease was present in 44.5% of subjects. The product was rated on average, tolerable, but side effects, albeit generally minor and transient, were reported by one third. Nearly two-thirds of the initially hypertensive patients became normotensive. Modified fasting is an acceptable and effective initial approach to weight loss in general practice.

Giant ovarian dermoid masked by obesity.

A 37-year-old female, weighing 194.1 kg, is described. Her gross obesity was in part due to a massive ovarian dermoid cyst weighing at least 42 kg, which had been overlooked in the past. A dermoid tumour of this size has not previously been reported. The possible presence of cystic ovarian tumours should be considered in patients presenting with severe generalized obesity.

The effect of weight gain on gonadotrophins and prolactin in anorexia nervosa.

Serum levels of gonadotrophins and prolactin and their response to luteinizing hormone/follicle stimulating hormone--releasing hormone (LRH) and thyrotrophin releasing hormone (TRH) were measured in 14 females with anorexia nervosa when at low body weight and again in 6 cases during, and 12 cases after weight gain. Mean serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were low initially and whereas FSH increased significantly with weight gain, LH levels remained subnormal in most patients. LH responses to LRH were grossly impaired or absent in patients whose weight was below 75% of the ideal, but increased dramatically above this weight over-shadowing the more modest increase in FSH response. In three patients, however, impaired LH responses persisted as ideal weight was approached. Basal prolactin levels were well within the normal range in all patients. During weight gain there was no change in basal levels but the prolactin level 20 min after TRH was significantly increased.