Oxygen supplementation before or after submaximal exercise in patients with chronic obstructive pulmonary disease.

BACKGROUND: Evidence for improved exercise tolerance or relief of breathlessness by short term use of oxygen before or after exercise in patients with chronic obstructive pulmonary disease (COPD) is scant, and guidelines for this treatment are lacking despite widespread provision in the UK. METHODS: The effect of oxygenation either before or after exercise on perception of breathlessness and walk distance was studied in a group of patients with moderate to severe COPD (mean forced expiratory volume in 1 second (FEV(1)) 34% of predicted, mean 6 minute walk distance on air 283 m), all of whom desaturated by at least 4% on submaximal exercise. Oxygen (28%) or air was delivered double blind and in random order, either for 5 minutes before a standard 6 minute walk test (n=34) or for 5 minutes following the end of the test (n=18). Exercise tolerance was measured as the distance achieved and breathlessness was assessed using visual analogue scales (VAS) which were scored before and after exercise and during recovery. RESULTS: No increase in mean walk distance after oxygen (288 v 283 m) and no improvement in mean breathlessness scores (58 v 54 mm) or recovery times occurred with oxygen taken either before (177 v 184 seconds) or after exercise (182 v 151 seconds). CONCLUSIONS: This group of patients with COPD derived no physiological or symptomatic benefit from oxygen breathed for short periods before or after submaximal exercise. Domiciliary oxygen should only be prescribed for such patients if they have shown objective evidence of benefit on exercise testing.

Predictors of seropositivity to herpes simplex virus type 2 in women.

Five hundred and twenty consecutive women newly attending a genitourinary medicine clinic who participated in a study of sexual behaviour were also tested for type-specific antibody to herpes simplex virus type 2; 135 (26%) were seropositive, of whom only 29 (21.5%) had had clinical evidence of genital herpes. Seropositive women were much more likely to have a past history of genital herpes (odds ratio [OR] 173). They were also more likely to be black non-UK born (OR 14), aged 30 years or over (OR 6), to have had 6-20 sexual partners (OR 3-4), especially from abroad (OR 12), to be unemployed (OR 6) or blue collar workers (OR 4), to have smoked cigarettes (OR 2) and to have practised peno-anal penetration (OR 5). Disease predictors included a past history of pelvic inflammatory disease (OR 63) and bacterial vaginosis (OR 3). Unexpected predictors were only one sexual partner (OR 5) and no non-regular partners (OR 5). Commencing intercourse before 16 years of age showed a protective effect (OR 0.2) and so did use of oral contraception (OR 0.5). Our findings show that infection with HSV-2 is associated with a wider range of morbidity and also emphasize the role of male sexual partner selection in the transmission of infection.

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.

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.

The effects of age, body mass index, smoking and general health on the risk of venous thromboembolism in users of combined oral contraceptives.

OBJECTIVES: To investigate the factors associated with idiopathic venous thromboembolism in combined oral contraceptive users and to estimate the crude and age-specific incidence rates ofidiopathic venous thromboembolism among this population. METHODS: The UK MediPlus Database and the General Practice Research Database were searched to identify women with evidence of venous thromboembolism while exposed to combined oral contraceptives. Cohort and nested case-control studies were carried out using the same methodology on both databases. We conducted a meta-analysis using the individual data for the cases and controls from the two case-control studies to identify factors associated with idiopathic venous thromboembolism in women using combined oral contraceptives. RESULTS: The incidence rate of idiopathic venous thromboembolism among oral contraceptive users was 39.4 per 100,000 exposed woman-years. The age-specific incidence rates were found to rise sharply after the age of 39 years. Factors identified as being significantly associated with idiopathic venous thromboembolism in women using combined oral contraceptives were: body mass index of 25 kg/m2 and over, the association rising dramatically in women with a body mass index of 35 kg/m2 or more; smoking; general ill health; and asthma. CONCLUSION: We believe that, before prescribing combined oral contraceptives, the venous as well as the arterial factors need to be considered and, in addition, age, obesity and smoking are all relevant when assessing an individual patient's risk.

Sexual behaviour and sexually transmitted infection among African and Caribbean men in London.

We studied 180 black heterosexual men of whom 133 (74%) were Caribbean and 47 (26%) African. Seventy-three per cent of Caribbeans and 27% of Africans were UK born. We found no difference in age, but more Africans were married (30% cf 10%; P=0.002) and students (26% cf 10%; P=0.00008). More Caribbeans smoked 1-10 cigarettes a day (42% cf 22%; P=0.02) and more drank alcohol (89% cf 74%; P=0.002). Sixty-nine per cent of Caribbeans reported intercourse before the age of 17 compared with 48% of Africans (P=0.004), but there was no difference in the numbers of sexual partners, either in the previous year or in total. Twenty-four (18%) of the 133 Caribbeans had gonorrhoea compared with one (2%) of the 47 Africans (P=0.001). Multivariate analysis showed that coitarche under 16 years of age (odds ratio (OR) 50) and gonococcal and/or chlamydial infection (OR 12.5) were independently associated with Caribbeans. Within this group, gonorrhoea was found more often in teenagers (OR 9.5) who had commenced intercourse before the age of 16 (OR 3.3) and chlamydial infection in those with multiple partners (OR 24). New problem-orientated approaches are needed to eradicate these curable infections which facilitate infection with HIV.

The differential risk of oral contraceptives: the impact of full exposure history.

Previous discussions have indicated that the small increases of risk of venous thromboembolism (VTE) associated with newer combined oral contraceptives (third generation, containing desogestrel and gestodene) may be attributed to bias due to cohort effects. In a case-control analysis, this may produce an overestimate of risk of newer preparations. In 10 centres in Germany and the UK, the Transnational Study analysed data from 502 women aged 16-44 years with VTE, and from 1864 controls matched for 5-year age group and region. Information on lifetime exposure history from all subjects was added to the dataset used in previous analyses and entered into a Cox regression model with time-dependent covariates. Based on 17 622 continuous exposure episodes comprising 47 914 person-years of observation, the adjusted hazard ratio (equivalent to odds ratio, OR) of VTE for the comparison of current users of third-generation versus current users of second-generation (primarily levonorgestrel compounds) combined oral contraceptives was 0.8 (0.5 to 1.3). The OR obtained in standard case-control analysis had been 1.5 (1.1 to 2.1). Adjustment for past exposures includes more information and appears more valid than the standard cross-sectional analysis. Using this approach, the Transnational Study data show no evidence for an increased risk of VTE with third- compared with second-generation combined oral contraceptives.

PIP: This transnational study examined the risk of venous thromboembolism (VTE) associated with combined oral contraceptives (OCs). The study analyzed data on 502 women aged 16-44 years with VTE and 1864 controls from 10 centers in Germany and the UK from 1 January, 1993, to 20 October, 1995. Information on lifetime exposure history from all subjects was added to the data set used in previous analyses and entered into a Cox regression model with time-dependent covariates. Based on 17,622 continuous exposure episodes comprising 47914 person-years of observation, the adjusted hazard ratio of VTE for the comparison of current users of third-generation versus current users of second-generation combined OCs was 0.8 (0.5-1.3). The OR obtained in standard case-control analysis had been 1.5 (1.1-2.1). Adjustment for past exposures includes more information and appears more valid than the standard cross-sectional analysis. Using this approach, the transnational study data show no evidence for an increased risk of VTE with third-generation compared with second-generation combined OCs.

Racial origin, sexual behaviour, and genital infection among heterosexual men attending a genitourinary medicine clinic in London (1993-4).

OBJECTIVES: To compare variables of sexual behaviour and incidence of genital infections among heterosexual men of different racial origins. DESIGN: A prospective cross sectional study of sexual behaviour reported by a standardised self administered questionnaire in new patients who presented for screening and diagnosis. SETTING: A genitourinary medicine clinic in west London. SUBJECTS: 1212 consecutive heterosexual men newly attending in 1993-4. MAIN OUTCOME MEASURES: Variables relating to sociodemographic status, sexual behaviour, condom use, sexually transmitted diseases, and other genital infections stratified by racial origin. RESULTS: There were 941 evaluable heterosexual men of whom the majority were white (79%) and 17% were black. The black men comprised more teenagers (11% cf 2%; p < 0.00001), were more likely to be unemployed (26% cf 12%; p < 0.00001), to have commenced intercourse much earlier (45% cf 22% before aged 16: p < 0.0001), and to have had intercourse with an African woman (14% cf 6%; p < 0.001). Both fellatio (64% cf 96%; p < 0.00001) and cunnilingus (40% cf 92%; p < 0.00001) were practised less frequently by the black men and so too was anal intercourse (11% cf 27%; p < 0.00001). Similar proportions from both groups were non-smokers (53% cf 57%), but a significantly higher proportion of the black men did not drink alcohol (13% cf 5%; p < 0.001). Gonorrhoea (15% cf 1%; p < 0.00001), chlamydial infection (17% cf 8%; p < 0.001), and non-gonococcal urethritis (37% cf 24%; p = 0.001) were diagnosed more frequently in the black men. These findings remained significant after logistic regression and are therefore independently associated with black race. However, there was no significant difference in numbers of sexual partners in the preceding year (median 2), nor in condom use with regular and non-regular partners. The Asian men had commenced intercourse later (mean 19.1 years) than both the black men (mean 15.9 years) and the white men (mean 17.3 years). CONCLUSIONS: Compared with white men, black men attending a genitourinary medicine clinic were much more likely to be unemployed, to have commenced intercourse earlier and to have urethral infection. They were much less likely to practice fellatio, cunnilingus, or anal intercourse. However, there was no difference between the two racial groups in respect of numbers of sexual partners and condom use.

Racial origin, sexual lifestyle, and genital infection among women attending a genitourinary medicine clinic in London (1992).

OBJECTIVES: To compare variables of sexual behaviour and incidence of genital infections among women of different racial origins and lifestyles. DESIGN: A prospective cross sectional study of sexual behaviour reported by a standardised self administered questionnaire in new patients who presented for screening and diagnosis. SETTING: A genitourinary medicine clinic in west London. SUBJECTS: 1084 consecutive women newly attending in 1992. MAIN OUTCOME MEASURES: Variables relating to sociodemographic status, sexual lifestyle, condom use, sexually transmitted diseases, and other genital infections stratified by racial origin. RESULTS: There were 948 evaluable women, of whom 932 (98.3%) were heterosexual and 16 (1.7%) were lesbian. Previous heterosexual intercourse was reported by 69% of lesbian women and their most frequent diagnosis was bacterial vaginosis (38%). The majority of heterosexual women were white (78%) and 16% were black. The black women were more likely to be teenagers (18% cf 8%; p = 0.0004) or students (28% cf 15%; p = 0.0008), and to have had an earlier coitarche (48% cf 38% before aged 17; p < 0.004). They also had a higher proportion of pregnancies (58% cf 38%; p < 0.00001) and births (38% cf 20%; p < 0.00001). The white women showed significantly more sexual partners during the preceding year (p = 0.004) and in total (p < 0.00001) and more reported non-regular partners (48% cf 35%; p = 0.004) with whom they were more likely to use condoms (p = 0.009). However, the black women were more likely to have gonorrhoea (7% cf 2% p < 0.0003), chlamydial infection (12% cf 5% p < 0.002), trichomoniasis (10% cf 2% p < 0.00001), or to sexual contacts of men with non-gonococcal urethritis (19% cf 12% p < 0.02). They were less likely to have genital warts (3% cf 12% p = 0.002). Logistic regression showed that all these variables were independently associated with the black women. The Asian women (2%), none of whom had a sexually transmitted disease, had commenced intercourse later (mean 19.7 years) than both black women (mean 16.8 years) and white women (mean 17.6 years). CONCLUSIONS: Sexual intercourse commenced approximately 1 year earlier in the black women, who were more likely to have become pregnant, had children, and to have acquired a bacterial sexually transmitted infection than were the white women.

The risks of venous thromboembolic disease among German women using oral contraceptives: a database study.

This study investigated the risk of venous thromboembolic disease (VTE) between second and third generation combined oral contraceptives, using the German MediPlus database of patient records. Women studied included 42 patients between the ages of 18 and 49 years, with a diagnosis of VTE treated with an anticoagulant, who were exposed to an oral contraceptive (OC). Four controls per patient (168), matched by year of birth and exposure to an OC on the even day, were identified. More women were users of second generation than third generation OC, and none were using progestogen-only pills. There was no significant difference between patients and control subjects with respect to the type of OC used on the event day (unadjusted odds ratio for third versus second generation users was 0.77; 95% confidence interval [CI] 0.38-1.57). There was no significant age difference between second and third generation users among patients or control subjects. Between January 1 and the event date, there was no significant difference between the patients and control subjects in terms of the number of oral contraceptive prescriptions, number of consultations for psychotherapeutic complaints, or mixed physical and psychotherapeutic consultations; however, patients did demonstrate significantly more consultations for purely physical complaints compared with control subjects (p < 0.0001). There were no significant consultation differences between patients with pulmonary emboli (n = 6) and other VTE patients (n = 36). No significant differences with respect to VTE risk between users of second and third generation oral contraceptives were found in this study. Consultations (physical) for patients were higher than for control subjects before the VTE event. If consultation rate relates to the general health status of a person, this might indicate that VTE risk is higher among women of poorer health, but that this is not related to the type of progestogen in the oral contraceptive that they use.

PIP: The German MediPlus database of patient records from 451 practices was used to investigate the risk of venous thromboembolism (VTE) in users of second- and third-generation combined oral contraceptives (OCs). Cases included 42 women 18-49 years of age with a diagnosis in 1992-95 of a VTE treated with an anticoagulant and with a history of OC use. Also enrolled were 168 controls (4 per case), matched to cases by year of birth and exposure to an OC on the event day. 64.3% of cases and 53.0% of controls had used a second-generation OC; use of a third-generation OC was reported by 35.7% of cases and 38.1% of controls. No significant differences in terms of VTE risk factors were identified between users of second- and third-generation OCs. The odds ratio for VTE among users of third-generation compared to second-generation OCs was 0.77 (95% confidence interval, 0.38-1.57). There were no significant differences between cases and controls in terms of the type of OC used, age, the total number of OC prescriptions issued, number of consultations for psychotherapeutic complaints, and number of consultations for mixed psychotherapeutic and physical complaints. Although cases had more consultations for physical complaints before the VTE (presumed to be a proxy for poor general health), this was not related to the type of progestogen in the OC.

Heterosexual behaviour, risk factors and sexually transmitted infections among self-classified homosexual and bisexual men.

Our study of men presenting at a genitourinary medicine clinic shows that self-classification into homosexual or bisexual does not accurately define behaviour. We found that 8.5% of self-defined homosexual men had had heterosexual intercourse in the past year and that 26% of self-defined bisexual men had not. Overall, 19% of homosexual/bisexual men reported vaginal intercourse in the past year and a further 42% in their lifetime. Compared with heterosexual men attending our clinic, the practising bisexual men were significantly more likely to come from a white ethnic group (P < 0.003) and to use condoms invariably with regular female partners (P = 0.0001). There was no significant difference in consent for HIV testing between homosexual (43%), practising bisexual (49%) and heterosexual (42%) men despite significantly different perceptions of risk. None of the practising bisexual men was seropositive for HIV infection (P = 0.06) or for syphilis (P = 0.02), or had chlamydial infection, which was found infrequently among homosexual men in general (P = 0.00001). HIV infection found in 19.4% of the exclusively homosexual men was associated with more frequent alcohol consumption (P=0.06).

The value of forced expiratory volume in 1 s in screening subjects with stable COPD for PaO2 < 7.3 kPa qualifying for long-term oxygen therapy.

Guidelines on the management of chronic obstructive pulmonary disease (COPD) issued by the European Respiratory Society (ERS), British Thoracic Society (BTS), American Thoracic Society (ATS), and Department of Health for England and Wales (DoH) suggest differing values of forced expiratory volume in 1 s (FEV1) below which arterial blood gas analysis should be performed to determine the presence of severe hypoxaemia and possible long-term oxygen therapy (LTOT) requirement. This study aimed to determine the value of FEV1 at these different levels in screening for LTOT requirement defined as PaO2 < 7.3 kPa in subjects with stable COPD. Comparative measures were taken against other lung function tests of volume and diffusing capacity. A retrospective analysis of paired lung function and arterial oxygen measurements in 491 subjects was made. The positive and negative predictive values, sensitivity and specificity of FEV1 < 70% predicted (ERS), FEV1 < 50% predicted (ATS), FEV1 < 40% predicted (BTS) and FEV1 < 1.51 (DoH) were determined for fulfilling LTOT criteria (PaO2 < 7.3 kPa). The correlation between lung function variables and PaO2 was established. Logistic regression analysis was used to classify subjects with PaO2 < 7.3 kPa and PaO2 > or = 7.3 kPa. Using FEV1 to screen for LTOT requirement produced a high negative predictive value at all four suggested limits (FEV1 < 70% 100%, FEV1 < 50% 96%, FEV1 < 40% 95%, FEV1 < 1.51 97%). However, the positive predictive values were low (FEV1 < 70% 13%, FEV1 < 50% 16%, FEV1 < 40% 19%, FEV1 < 1.51 15%) as were sensitivities. No single lung function variable was a strong determinant of PaO2. FEV1 % pred (r = 0.40), FVC % pred (r = 0.34) and TLCO % pred (r = 0.27) had the strongest relationships. Logistic regression also placed FEV1 % pred and TLCO % pred as the best predictors of PaO2 < 7.3 kPa. We conclude no lung function variable correlates well with PaO2 in subjects with stable COPD. The best predictor of PaO2 < 7.3 kPa was FEV1 % pred. Whilst a low FEV1 is a poor predictor of LTOT requirement in an individual, PaO2 < 7.3 kPa is only found in subjects with a low FEV1. A high FEV1 may be used to exclude subjects from further investigation for LTOT and prevent unnecessary arterial sampling.

The use of oral contraceptives and the occurrence of acute myocardial infarction in young women. Results from the Transnational Study on Oral Contraceptives and the Health of Young Women.

The objective of this study was to assess the risk of myocardial infarction (MI) associated with the use of new and old combination oral contraceptives (OC). A matched case-control study in 16 centers in Germany, the United Kingdom, France, Austria, and Switzerland explored the association of current use of combination OC with the occurrence of MI. Our subjects were 182 women aged 16-44 years with MI; the controls were 635 women without MI (at least one hospital control and one community control per case) matched for 5-year age group and region. The main outcome measures were odds ratios comparing current use of a specific group of OC against current use of other groups or against no current use. The adjusted overall odds ratio (OR; 95% confidence intervals) for MI for second generation OC versus no current use was 2.35 (1.42 to 3.89) and 0.82 (0.29 to 2.31) for third generation OC (low dose ethinyl estradiol, gestodene, and desogestrel). A direct comparison of third generation users with second generation users yielded an OR of 0.28 (0.09 to 0.86). In subgroup analyses, the odds ratio for the UK alone was 1.25 (0.36 to 4.29), while for continental Europe it was 0.10 (0.02 to 0.48). For hospital controls, the risk estimated was 0.98 (0.22 to 4.44), and 0.18 (0.04 to 0.65) for community controls. The independent risk of MI among current smokers adjusted for OC use was 7.21 (4.58 to 11.36). Among users of third generation OC, the OR for current smokers was 3.75 (0.65 to 21.74) and among users of second generation it was 9.50 (2.93 to 30.96). A comparison of OC use in the UK for the time before and after regulatory action was taken in October 1995 shows that the likelihood of a control (last control accrued June 1996) being treated with second generation OC is seven times higher after 1 November 1995 than it was before. Third generation OC are the first to be associated with no excess risk of MI. A significantly lower risk of MI is found when comparing use of third generation OC with use of second generation OC. There seems to be an impressive amelioration of risk among smokers using newer OC. An impact of regulatory action in the UK was found in the OC use spectrum of controls.

PIP: The risk of myocardial infarction associated with use of second- and third-generation oral contraceptives (OCs) was investigated in a matched case-control study conducted at 16 centers in Germany, the UK, France, Austria, and Switzerland. 182 women 18-44 years old with myocardial infarction were matched for 5-year age group and region with 635 controls (at least 1 hospital control and 1 community control per case). 57 cases and 156 controls reported exposure to OCs, of whom 7 cases and 49 controls had taken third-generation formulations. The adjusted overall odds ratio (OR) for myocardial infarction was 2.35 (95% confidence interval [CI], 1.42-3.89) for second-generation OC use versus no use but only 0.82 (95% CI, 0.29-2.31) for third-generation OC use versus no use. A direct comparison of third-generation and second-generation OC users yielded an OR of 0.28 (95% CI, 0.09-0.86). 80% of cases, compared with 37% of controls, were current smokers. The independent risk of myocardial infarction among current smokers adjusted for OC use was 7.21 (95% CI, 4.58-11.36). The OR for current smokers was 3.75 (95% CI, 0.65-21.74) among users of third-generation OCs and 9.50 (95% CI, 2.93-30.96) among users of second-generation formulations. These Transnational Study findings indicate that third-generation formulations are the first OCs to be associated with no excess risk of myocardial infarction; moreover, they substantially reduce this risk among smokers. The reduced risk of myocardial infarction associated with OCs containing desogestrel and gestodene compared with levonorgestrel may reflect the failure of third-generation progestins to inhibit the estrogen-related increase in sex hormone binding globulin.

Oestrogen increases S-phase fraction and oestrogen and progesterone receptors in human cervical cancer in vivo.

Although cancer of the cervix is traditionally considered not to be responsive to steroid hormones, an in vitro study has reported that the addition of oestrogen increased cellular proliferation in a cervix cancer cell line that was inhibited by progesterone. We investigated whether the reported in vitro effects of oestrogen and progesterone on cellular proliferation can be replicated in locally advanced cervical cancer in vivo and whether these effects, if any, are related to oestrogen and progesterone receptor (ER and PgR) content of the tumour. One hundred post-menopausal patients with locally advanced cervical cancer were systematically allocated by rotation to the four treatment groups: (1) control group receiving no treatment; (2) ethinyl oestradiol 50 micrograms: (3) norethisterone 5 mg: (4) a combination of ethinyl oestradiol and norethisterone. Hormone treatment (five doses) was given orally every 12 h. Tissue biopsies were taken before and 12 h after the last hormone treatment. S-phase fraction (SpF) was measured by flow cytometry, and ER and PgR were measured by enzyme immunoassay. Results were analysed using two-factor analysis of variance, the factors being oestrogen-absent or present- and progesterone-absent or present. The main effects of oestrogen were increases in SpF, ER and PgR, which were statistically significant (P = 0.0056, 0.0009 and 0.01 respectively), indicating that there is much greater change in these three parameters in the presence of oestrogen (mean changes 7.808%, 6.258 fmol mg-1 and 12.716 fmol mg-1 for SpF, ER and PgR respectively) than in its absence (mean change -1.986%,-3.041 fmol mg-1 and 1.736 fmol mg-1 respectively). The progestogen main effect and the oestrogen-progestogen interaction were not significant. The rise in SpF, ER and PgR in the presence of oestrogen had a correlation coefficient with the initial ER values of -0.0565, -0.2863 and -0.1230 respectively, none being statistically significant, suggesting that the oestrogen actions were not strictly related to baseline ER concentrations. The combined median baseline ER and PgR values of the four groups were 1.48 fmol mg-1 and 0.80 fmol mg-1 respectively. Our results show that oestrogen is capable of increasing SpF in locally advanced cervical cancer in vivo and may help to revive interest in the use of oestrogen as a radiosensitizing agent in the treatment of this disease.