Systemic lupus erythematosus prevalence in the UK: methodological issues when using the General Practice Research Database to estimate frequency of chronic relapsing-remitting disease.

PURPOSE: The purpose of this study was to calculate the prevalence of systemic lupus erythematosus (SLE) between 1992 and 1998 using the General Practice Research Database (GPRD) METHODS: We identified all individuals who had contributed at least 3 years of data to the GPRD and who had a diagnosis of SLE with supporting evidence of their diagnosis. We calculated the annual age- and sex-specific prevalence of SLE. Additionally, we stratified the prevalence by years of data contributed to the GRPD. RESULTS: In males the point estimate of the prevalence of SLE increased from 7.5/100,000 (CI(95) 6.3, 8.8) to 10.1/100,000 (CI(95) 7.8, 12.2) but this rise was not statistically significant. However, prevalence appeared to increase significantly amongst females from 42.6/100,000 (CI(95) 39.6, 45.6) in 1992 to 70.8/100,000 (CI(95) 65.1, 76.6) in 1998. This increase was mainly amongst women aged 50-79 and in those contributing more than 5 years of data and could not be explained by increasing incidence of SLE or decreasing mortality during the study period. CONCLUSIONS: We found an increasing prevalence of SLE that could not be explained by increasing incidence or decreasing mortality. This is almost certainly an artefact caused by the increased likelihood of detecting or confirming cases of chronic relapsing-remitting diseases with increasing time contributed to the GPRD.

Myocardial infarction risk and hormone replacement: differences between products.

OBJECTIVES: To establish the risk of myocardial infarction (MI) in users of hormone replacement therapy (HRT) compared with non-users and to compare the risk between different HRT regimens. METHODS: A population-based cohort and case-control study, and a case-control study nested within a cohort of HRT users, using the UK General Practice Research Database. Differences between HRT regimen, mode of administration and duration and recency of use were examined whilst adjusting for confounding. RESULTS: In the cohort and case-control study, 4537 cases of MI were identified in 2.62 million observed women years, cases were age-matched to 27,220 controls. In both studies, current and past HRT use were associated with reduced risk estimates for MI compared with no prior use. MIs were less likely to be fatal amongst women who had used HRT than amongst never users (OR(adj) 0.58; 95% CI 0.45-0.75). No difference in risk was seen between current and past use, oral and transdermal HRT or between different regimens (p>0.44). In the nested study, no difference was found in the association with MI risk between different oestrogen-progestogen combinations or between different combinations and tibolone. Unopposed oestrogen use was not associated with a decrease in risk compared with combined HRT. CONCLUSIONS: These results are consistent with previous observational studies in supporting the hypothesis that use of postmenopausal HRT is associated with a decrease in risk of acute myocardial infarction (AMI). Case fatality differed between HRT users and non-users, suggesting a protective effect of HRT. This study does not demonstrate a difference between regimens.

Venous thromboembolism associated with cyproterone acetate in combination with ethinyloestradiol (Dianette): observational studies using the UK General Practice Research Database.

PURPOSE: To derive risk estimates for venous thromboembolism (VTE) in women prescribed cyproterone acetate combined with ethinyloestradiol (CPA/EE), a drug licensed in the UK for the treatment of women with acne or hirsutism. CPA/EE provides a treatment option for women with polycystic ovary syndrome (PCOS). CPA/EE has been associated with an increased risk of VTE. METHODS: Using the General Practice Research Database, we conducted cohort and case-control analyses in all women aged 15-39 and then nested in a population of women of the same age with acne, hirsutism or PCOS. RESULTS: The incidence rate ratio (IRR) for VTE in women exposed to CPA/EE versus conventional combined oral contraceptives (COCs) was significantly raised (all women: 1.92; 95% CI: 1.22,2.88; nested: 2.51; 95% CI: 1.07,5.75). Using exposure to conventional COCs as the reference, the adjusted odds ratio (ORadj) for VTE associated with CPA/EE was 1.45 (95% CI: 0.80,2.64) in all women and 1.71 (95% CI: 0.31,9.49) in women with acne, hirsutism or PCOS. CONCLUSIONS: The risk of VTE associated with CPA/EE use does not differ significantly from that associated with the use of conventional COCs. These data are reassuring and together with knowledge of the risks associated with other treatments for acne, in particular, should influence prescribing practice.

Utilisation of hormone replacement therapy in the United Kingdom. A descriptive study using the general practice research database.

OBJECTIVE: To determine prevalence and patterns of hormone replacement therapy (HRT) utilisation in women in the UK. DESIGN: Prospective observational study. SETTING: UK general practice. POPULATION: Women from general practices throughout the UK. METHODS: The study period was 1 January 1992 to 31 December 1998. Age-specific prevalence was calculated for each year. Trends in prescribing patterns were described over time. A sub-cohort of 'new starters' on HRT was identified to establish patterns of use, including duration of use and switching of preparations. Characteristics of the sub-cohort were compared with a reference group of non-HRT users. MAIN OUTCOME MEASURES: Prevalence, prescribing patterns and differences in characteristics between HRT users and non-HRT users. RESULTS: Among women aged 45-64, prevalence of HRT use increased from 18.6% in 1992 to 27.7% in 1998. Secular trends were observed away from prescribing combined-sequential preparations and towards use of combined-continuous preparations. Among the prescriptions for combined HRT products, only 4.3% contained medroxyprogesterone acetate (MPA). A total of 45.7% of women without a record of a hysterectomy and 53.8% of women with a record of a hysterectomy used HRT for at least three years. When women were partitioned by year of starting HRT, there was a trend of increasing duration of use across the seven years. Some women without a record of a hysterectomy were receiving unopposed oestrogen without progestogen supplementation. CONCLUSIONS: Within the past decade, use of HRT has increased among women in the UK with large numbers of women using HRT for long periods and treatment often tailored to the individual.

The risk of liver disorders in women prescribed cyproterone acetate in combination with ethinyloestradiol (Dianette): a nested case-control study using the GPRD.

PURPOSE: To explore the risk of liver disorders associated with cyproterone acetate combined with ethinyloestradiol (CPA/EE). CPA/EE is licensed in the UK for the treatment of women with acne and hirsutism and is a treatment option for polycystic ovary syndrome (PCOS). It acts as a contraceptive also. METHODS: Using the General Practice Research Database, we conducted a cohort analysis and case-control study in women aged 15-39 with acne, hirsutism or PCOS to estimate the risk of liver disorders associated with CPA/EE. RESULTS: Compared with cases exposed to conventional combined oral contraceptives (COCs), the age-adjusted incidence rate ratio for liver disorders in women using CPA/EE was 1.7 (95% CI: 0.9, 3.4) and compared with no use it was 1.5 (95% CI: 0.8, 2.8). In the case-control study, the adjusted odds ratio (OR) for liver disorders in women exposed to CPA/EE was 1.6 (95% CI: 0.7, 3.5) and 0.8 (95% CI: 0.5, 1.3) for exposure to conventional COCs, compared with no use. The risk of liver disorders in women prescribed CPA/EE was not significantly greater than that in women prescribed conventional COCs (OR: 2.1 [95% CI: 0.9, 4.8]). CONCLUSION: Our results do not indicate an increased risk for liver disorders associated with CPA/EE use in women with acne, hirsutism or PCOS after adjusting for potential confounding. This may be due to lack of statistical power.

Differences in the use of combined oral contraceptives amongst women with and without acne.

BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) provides a treatment option for women with acne, hirsutism or polycystic ovary syndrome (PCOS). CPA/EE may be prescribed as an oral contraceptive (OC), but is not licensed as such in the UK. The use of CPA/EE steadily increased after its introduction to the UK market in 1987, but there was a marked increase in its share of the OC market after 1995. METHODS: Using the General Practice Research Database, utilization patterns of CPA/EE and conventional oral contraceptives were compared in women aged 15-39 years, with or without acne or PCOS. RESULTS: Between 1994 and 1998, CPA/EE accounted for an increasing proportion of all OC use. The proportion of CPA/EE prescribed to women with acne declined between 1994 and 1998, whereas that prescribed to women with PCOS remained constant. The age-specific use of CPA/EE by women with acne or PCOS almost doubled. After 1995, there was a marked increase in the use of products containing levonorgestrel by women with acne or PCOS. CONCLUSIONS: A large proportion of CPA/EE is prescribed to women with acne and/or PCOS, although this proportion decreased between 1992 and 1998. This has important implications in CPA/EE risk assessment studies.

The risk of venous thromboembolism in women prescribed cyproterone acetate in combination with ethinyl estradiol: a nested cohort analysis and case-control study.

BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) is licensed in the UK for the treatment of women with acne and hirsutism and is also a treatment option for polycystic ovary syndrome (PCOS). Previous studies have demonstrated an increased risk of venous thromboembolism (VTE) associated with CPA/EE compared with conventional combined oral contraceptives (COCs). We believe the results of those studies may have been affected by residual confounding. METHODS: Using the General Practice Research Database we conducted a cohort analysis and case-control study nested within a population of women aged between 15 and 39 years with acne, hirsutism or PCOS to estimate the risk of VTE associated with CPA/EE. RESULTS: The age-adjusted incidence rate ratio for CPA/EE versus conventional COCs was 2.20 [95% confidence interval (CI) 1.35-3.58]. Using as the reference group women who were not using oral contraception, had no recent pregnancy or menopausal symptoms, the case-control analysis gave an adjusted odds ratio (OR(adj)) of 7.44 (95% CI 3.67-15.08) for CPA/EE use compared with an OR(adj) of 2.58 (95% CI 1.60-4.18) for use of conventional COCs. CONCLUSIONS: We have demonstrated an increased risk of VTE associated with the use of CPA/EE in women with acne, hirsutism or PCOS although residual confounding by indication cannot be excluded.

Incidence and prevalence of lower urinary tract symptoms suggestive of benign prostatic hyperplasia in primary care--the Triumph project.

OBJECTIVE: Benign prostatic hyperplasia (BPH) is one of the most common conditions associated with ageing in men. BPH often presents as lower urinary tract symptoms (LUTS) due to difficulties in voiding and irritability of the bladder. We conducted a retrospective cohort study within the Integrated Primary Care Information (IPCI) database, a general practitioners database in The Netherlands, to assess the incidence of LUTS suggestive of BPH (LUTS/BPH) in the general population. MATERIALS: Our study population comprised all males, 45 years or older who were registered for at least 6 months prior to start of follow-up. The study period lasted from 1 January 1995 to 31 December 2000. Cases of LUTS/BPH were defined as persons with a diagnosis of BPH, treatment or surgery for BPH, or urinary symptoms suggestive of BPH that could not be explained by other co-morbidity. RESULTS: The study cohort comprised 80,774 males who contributed 141,035 person-years of follow-up. We identified 2181 incident and 5605 prevalent LUTS/BPH cases. The overall incidence rate of LUTS/BPH was 15 per 1000 man-years (95% CI: 14.8-16.1). The incidence increased linearly (r(2) = 0.99) with age from three cases per 1000 man-years at the age of 45-49 years (95% CI: 2.4-3.6) to a maximum of 38 cases per 1000 man-years at the age of 75-79 years (95% CI: 34.1-42.9). After the age of 80 years, the incidence rate remained constant. For a symptom-free man of 46 years, the risk to develop LUTS/BPH over the coming 30 years, if he survives, is 45%. The overall prevalence of LUTS/BPH was 10.3% (95% CI: 10.2-10.5). The prevalence rate was lowest among males 45-49 years of age (2.7%) and increased with age until a maximum at the age of 80 years (24%). CONCLUSIONS: The incidence rate of LUTS/BPH increases linearly with age and reaches its maximum at the age of 79 years.

Study of the association between ischemic heart disease and use of alpha-blockers and finasteride indicated for the treatment of benign prostatic hyperplasia.

OBJECTIVE: Given the high possibility of co-occurrence of benign prostatic hyperplasia (BPH) and cardiovascular disease, we evaluated whether patients using BPH drugs are at an increased risk of acute hospital admission for ischemic heart disease (IHD). METHODS: A nested case control study within a cohort of 4414 men (aged > or =30 years) who had a history of using BPH products between 1992 and 1998 was conducted. Cases were defined as men with a first record of an acute hospital admission for IHD during the study period; three controls were matched to each case on year of birth, pharmacy and calendar time (index date). RESULTS: The study population comprised 220 cases and 515 controls. Current use of alpha-blockers (adjusted odds ratio 1.0, 95% confidence interval: 0.5-2.2) or finasteride (adjusted odds ratio 0.3, 95% CI: 0.1-1.4) was not associated with hospital admission for IHD. Furthermore, current use of BPH drugs was not associated with IHD in patient subgroups (age, history of cardiovascular disease, diabetes), nor with duration of use prior to hospitalization. CONCLUSION: Although the power of the study was low, we found no evidence for an association between current use of BPH drugs and hospital admission for IHD. Therefore, our study seems to confirm the good cardiovascular safety profile of modern BPH drugs.

The risk of liver damage associated with minocycline: a comparative study.

Using the General Practice Research Database, the authors performed (1) a cohort analysis comparing the incidence of liver dysfunction in new users of minocycline with new users of oxytetracycline/tetracycline and (2) a case control study assessing antibiotic exposure in new cases of liver dysfunction and controls without liver dysfunction. In new users, the incidence of liver dysfunction in those exposed to minocycline was 1.04 cases/10,000 exposed person months (EPM) and 0.69 cases/10,000 EPM in those exposed to oxytetracycline/tetracycline (relative risk 1.51 [CI95: 0.63, 3.65]). The risk in both groups was greatest in the first month of use. The adjusted odds ratio (ORadj) of liver dysfunction associated with exposure to minocycline compared with nonuse was 2.10 (CI95: 1.30, 3.40); for oxytetracycline/tetracycline, the ORadj was 1.46 (CI95: 0.81, 2.64); and for exposure to erythromycin, the ORadj was 1.64 (CI95: 0.71, 3.80). The authors thus support a weak association between the use of oral antibiotics and liver dysfunction in patients with acne. The risk associated with exposure to minocycline appears to be very small. The cohort analysis demonstrated that any risk associated with minocycline was not significantly greater than that associated with oxytetracycline/tetracycline exposure.

Evaluating adverse cardiovascular effects of drug treatment for benign prostatic hyperplasia (BPH): methodological considerations.

When studying the effects of drug exposure in diseases with a long asymptomatic clinical course, exposure classification may be biased by the gradually developing "visibility" of the disease. Benign prostatic hyperplasia (BPH) is such a disease. We found that cardiovascular morbidity is two times more prevalent in patients starting drug treatment for BPH when compared to age-matched population controls. This resulted in a difference of cardiovascular prognostic factors between the exposed and non-exposed. This feature can jeopardize the validity of non-randomized comparisons of drug effects. Moreover, the existence of non-treatment strategies, disease under-reporting, and an elderly population with a high baseline risk of experiencing (cardiovascular) outcome events were encountered as methodological problems. When studying adverse cardiovascular effects in patients using BPH products in a non-randomized fashion, an important question is whether we can measure in the database all relevant prognostic factors and use the information for statistical adjustment. This question is an important challenge to observational research and once again stresses the need for control of possible biases in choosing an appropriate study design.

Lower urinary tract symptoms suggestive of benign prostatic obstruction--Triumph: the role of general practice databases.

The Triumph project aims to document the current management of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) in general practice and to assess the effectiveness of the initial treatment options used. The first phase of the project will consider existing data sources in primary care. A patient's medical record will contain most, if not all, clinically relevant information, and databases combining the records from a network of computerised general practices can provide longitudinal data for complete populations, linking prescribing records to clinical information on disease progression and outcomes for individual patients. Database research can provide rapid information and offers the ability to conduct studies on a scale that would previously have been prohibited by both time and expense. Within the Triumph project, the THALES, General Practice Research Database (GPRD) and Integrated Primary Care Information (IPCI) databases are, or will be, used to examine the current management of LUTS/BPH in France, the UK and the Netherlands respectively. Preliminary results from the UK General Practice Research Database (GPRD) showed that LUTS/BPH incidence increased linearly from the ages of 45 to 85 years (r(2) = 0.992) and prevalence increased from 3.5% to 35% for men in their late 40s and 80s respectively. With treatment failure defined as a change to another medical therapy, catheterisation or prostatic surgery, and accounting for age and year variation, patients receiving the older alpha(1)-blockers (indoramin and prazosin) appeared to fail significantly earlier than those receiving finasteride. There was no significant difference between finasteride and the newer alpha(1)-blockers (tamsulosin, alfuzosin, terazosin and doxazosin). Patterns of changes between products from the THALES database in France were broadly similar to those seen in the UK.

Venous thromboembolism in pregnancy and the puerperium: incidence and additional risk factors from a London perinatal database.

OBJECTIVE: To determine the incidence of venous thromboembolism in pregnancy and the puerperium and to identify risk factors for pregnancy-related venous thromboembolism. DESIGN: Cohort study and case-control study. SETTING: London, UK. POPULATION: 395,335 women with live births or pregnancies of 24 or more weeks of gestation between 1988 and 1997. METHODS: Data extraction from the St Mary's Maternity Information System database. Random sample of 5% for case-control study. MAIN OUTCOME MEASURES: Incidence of venous thromboembolism; odds ratios for variables associated with venous thromboembolism. RESULTS: The incidence of venous thromboembolism was 85/100,000 maternities. There were approximately twice as many postpartum as antepartum events. Blood group A, multiple pregnancy, caesarean section, cardiac disease, delivery at gestational age of < 36 weeks, a body mass index of > or = 25, or more and maternal age of 35 or over were all found to increase incidence of venous thromboembolism. CONCLUSIONS: Although venous thromboembolism is the leading cause of maternal deaths in the UK, it is still a rare event. Most of these events are deep vein thromboses occurring in the postpartum period. Antenatally multiple birth is an important risk factor. Postnatally women who have had a caesarean section, premature delivery or history of cardiac disease should be assessed carefully for venous thromboembolism.

How do symptoms indicative of BPH progress in real life practice? The UK experience.

OBJECTIVE: Lower urinary tract symptoms (LUTS) are usually, but not exclusively associated with benign prostatic hyperplasia (BPH). Using a population identified from the UK General Practice Research Database (GPRD), we describe the changes in the management of LUTS/BPH and assess the effectiveness of medical therapy between 1992 and 1998. METHODS: 61,364 men with LUTS/BPH and without a record of prostatic cancer were identified on the database. 14,195 were treated with an alpha1-blocker or finasteride. Treatment failure was defined as prostatic surgery, catheterisation or a switch in medical therapy. RESULTS: LUTS/BPH incidence increased linearly from the age of 45 to 85 years (r2 = 0.992) and prevalence increased from 3.5% to 35% for men in their late 40s and 80s respectively. Prostatectomy rates increased linearly from the age of 50 to 80 years (r2 = 0.984). Between 1992 and 1998, total treated-patient time had increased 3-fold, patients have been medically treated earlier and have increasingly been prescribed the LUTS/BPH-specific treatments finasteride, tamsulosin and alfuzosin in comparison to older treatments (indoramin, prazosin). In parallel, there has been a progressive increase in the interval between first diagnosis and prostatic surgery, and this interval is significantly longer for medically treated patients than those receiving no medical therapy. The intervals between the start and failure of medical therapy were significantly shorter for patients receiving indoramin and prazosin than for those receiving specific LUTS/BPH treatments. CONCLUSIONS: Between 1992 and 1998 there has been a significant lengthening of the period between first diagnosis of LUTS/BPH and surgery. This postponement of surgery is associated with earlier treatment and the increased use of specific LUTS/BPH treatments that appear more effective than older products in delaying treatment failure.

Liver damage associated with minocycline use in acne: a systematic review of the published literature and pharmacovigilance data.

OBJECTIVE: Minocycline is an antibacterial drug used in the treatment of acne. Concern has been expressed over the possibility of severe adverse reactions to minocycline, including hepatitis. This study set out to identify and characterise reported cases of hepatotoxicity associated with the use of minocycline. METHODS: A systematic review of the literature including a search of computerised databases and analysis of data from the Uppsala Monitoring Centre (WHO Collaborating Centre for International Drug Monitoring) was conducted. The review involved a search for original case reports involving liver damage in people using minocycline. Patients taking minocycline for reasons other than acne or those given intravenous minocycline were excluded. The search strategy involved an enquiry of computerised databases and a search for secondary references. Cases were then classified appropriately. RESULTS: 65 reported cases of hepatitis or liver damage in association with minocycline from either case reports or case series were identified from the literature review. 58% of cases occurred in females and 94% were aged under 40 years. For 20 case reports there was insufficient information to classify the type of event, but for the remaining 45, 2 types of hepatic reaction were recognised: autoimmune hepatitis associated with lupus-like symptoms occurring after a median duration of exposure to minocycline of 365 days in females (n = 20) and 730 days in males (n = 9), hypersensitivity reaction associated with eosinophilia and exfoliative dermatitis occurring within 35 days of therapy (n = 16). Reports to the WHO of hepatic adverse drug reactions associated with minocycline accounted for 6% (493) of all minocycline-related adverse drug reactions (8025). The pattern of distribution in relation to exposure demonstrated 2 groups, similar to that described by the case reports. CONCLUSIONS: Severe cases of minocycline-associated hepatotoxicity appear to be a hypersensitivity reaction and occur within a few weeks of commencing therapy. An autoimmune hepatitis usually presents after exposure to minocycline of a year or more, is more common in women and is sometimes associated with lupus-like symptoms.

Effect of 1995 pill scare on rates of venous thromboembolism among women taking combined oral contraceptives: analysis of general practice research database.

OBJECTIVE: To compare the incidence of venous thromboembolism among women taking combined oral contraceptives before and after the October 1995 pill scare. DESIGN: Analysis of General Practice Research Database. SETTING: United Kingdom, January 1993 to December 1998. SUBJECTS: Women aged 15-49 taking combined oral contraceptives. MAIN OUTCOME MEASURES: Incidence of venous thromboembolism. RESULTS: Use of so called "third generation" combined oral contraceptives fell from 53% during January 1993 to October 1995 to 14% during November 1995 to December 1998. There was no significant change in the incidence of venous thromboembolism between the two periods after age was adjusted for (incidence ratio 1.04, 95% confidence interval 0.78 to 1.39). CONCLUSIONS: The findings are not compatible with the assertion that third generation oral contraceptives are associated with a twofold increase in risk of venous thromboembolism compared with older progestogens.

PIP: In October 1995 the UK Committee on Safety of Medicines advised that combined oral contraceptives (OCs) containing either gestodene or desogestrel were associated with twice the risk of venous thromboembolism compared with older products. This study was conducted to compare the incidence of venous thromboembolism among women taking combined OCs before and after the October 1995 pill scare. Using data from the General Practice Research Database, a total of 304 practices were analyzed. Overall, results show that use of third-generation combined OCs fell from 53% during the period of January 1993 to October 1995 to 14% during the period of November 1995 to December 1998. No significant change was noted in the incidence of venous thromboembolism between the two periods after age was adjusted for (incidence ratio, 1.04; 95% confidence interval, 0.78-1.39). Based on these findings, it is concluded that third-generation OCs are not associated with a twofold increase in risk of venous thromboembolism compared with older progestogens.

Medical therapy for benign prostatic hyperplasia: a review of the literature.

OBJECTIVE: To review the existing evidence regarding the efficacy and safety of medical therapy for lower urinary tract symptoms (LUTS) indicative of benign prostatic hyperplasia (BPH). To assess randomised controlled trials investigating the six alpha-adrenergic receptor antagonists (alpha-blockers), prazosin, alfuzosin, indoramin, terazosin, doxazosin, and tamsulosin, that benefit patients by relaxing prostatic smooth muscle, and the anti-androgen, finasteride, that mediates its more long-term benefits by reducing prostate size. RESULTS: This review suggests that both classes of drug offer significant improvement in criteria used to evaluate symptomatic BPH and can be effective whilst being acceptably safe. Furthermore, the therapeutic efficacy of all contemporary alpha-blockers appear similar, both in terms of symptom relief and urodynamic improvements. Randomised controlled trials have additionally demonstrated that finasteride therapy can provide improvement in terms of quality of life indices, prostate volume, and risks of progressing to acute urinary retention or prostatic surgery. While alpha-blockers have a rapid onset of action, likely to produce a therapeutic result within weeks, regardless of whether prostatic enlargement or bladder outlet obstruction is present, finasteride appears to be effective for more long-term therapy for up to 4 years, but only in alleviating symptoms when they are associated with a significantly large prostate. Neither finasteride nor the alpha(1a)-receptor-selective blocker, tamsulosin, are associated with the lowering of blood pressure and incidence of cardiovascular side effects that are apparent with other less selective alpha-blocker therapies such as dizziness and postural hypertension. They are, however, both associated with an increased risk of sexual dysfunction, albeit less than those associated with surgical intervention. Whereas tamsulosin is associated only with ejaculatory dysfunction, finasteride is additionally linked to decreased libido and impotence.

The treatment of depression in UK general practice: selective serotonin reuptake inhibitors and tricyclic antidepressants compared.

BACKGROUND: Antidepressants are commonly prescribed by general practitioners as treatment for depression. Controversy exists as to the effectiveness in everyday use of the older tricyclic antidepressants (TCAs) when compared to the newer selective serotonin reuptake inhibitors (SSRIs). AIM: To investigate the patterns of current prescribing of antidepressants for the treatment of depression and compare TCAs with the newer SSRIs. METHOD: The study population was patients attending 151 computerised general practices from throughout the United Kingdom between 1991 and 1996. Patients with new prescriptions for antidepressants and a diagnosis of depression were identified. Age and gender distributions, prescribed doses and drop-out rates were investigated. RESULTS: During the study period 9.8% of patients received a prescription for an antidepressant, there was a 40% increase in the prescribing rate of TCAs and a 460% increase in SSRI prescribing. TCAs were initially prescribed in sub-therapeutic doses. More than 50% of patients ceased taking their antidepressants within 6 weeks of starting treatment. Fluoxetine and paroxetine were more likely to be prescribed for a therapeutic period than were other antidepressants. CONCLUSIONS: General practitioners should prescribe a therapeutic dose of antidepressant for a recognised therapeutic period to ensure that patients with depression receive the most effective treatment.

A comparison of the risks of venous thromboembolic disease in association with different combined oral contraceptives.

AIMS: In October 1995 in response to the results of three studies, the Committee on the Safety of Medicines advised doctors and pharmacists that oral contraceptives containing desogestrel (DSG) and gestodene (GST) were associated with around a two-fold increase in the risk of thromboembolism compared with those containing other progestogens. The objective of this study was to estimate the risk of idiopathic venous thromboembolic disease (VTE) in users of combined oral contraceptives (COCs), to compare the risk between formulations and to examine the effect of using age banding as opposed to matching by exact year of birth. METHODS: A nested case control study was conducted using the General Practice Research Database. Women with a VTE event recorded between 1992 and 1997, who were treated with an anticoagulant, from consideration of their prescription records were likely to have been using a COC prescription on the day of the event and also had no exclusion factors, were deemed cases. For comparison with the previous studies, two nested case control studies were undertaken. Study 1 used controls matched by practice and year of birth. Study 2 used controls matched by practice and within 5 years age bands. RESULTS: We found an incidence of idiopathic VTE amongst users of combined oral contraceptives of 3.8 per 10 000 exposed women years. Incidence rates increased markedly after 35 years of age. The nested case-control study using controls matched by year of birth showed no significant difference in risk between the major COC formulations. With levonorgestrel (LNG) 150 microgram and ethinyloestradiol (EE) 30 microgram as the reference, the adjusted ORs for GST 75 microgram and EE 30 microgram was 1.3 (95% CI 0.8, 2.1), for DSG 150 microgram and EE 30 microgram it was 1.0 (95% CI 0.7, 1.7) and for DSG 150 microgram and EE 20 microgram it was 0.8 (95% CI 0.4, 1.6). Using less rigorous matching criteria, matching controls to cases within 5 years age bands, the ORs increased. When a mixed group of COCs, characterized by having LNG as the progestogen component was used as the reference category, there was an elevation in the ORs for the newer products. We found a significant association between idiopathic VTE and current smoking (OR 2.0 (1.4, 2.7)), BMI over 35 (OR 3.8 (1.8, 8.0)) and asthma (OR 1.9 (1.3, 2.9)). The OR for women who had proxy evidence of general ill health (indicated by the number of prescriptions issued) was 2.2 (1.7, 3.7). CONCLUSIONS: The results of this study indicate that a number of the characteristics of the women taking COCs affect the risk of VTE. There is no evidence to support the hypothesis that there is any difference in risk between COC formulations containing under 50 microg ethinyloestradiol.