Validation of a 5-year risk score of hip fracture in postmenopausal women. The Danish Nurse Cohort Study.

SUMMARY: We evaluated the Women's Health Initiative (WHI) hip fracture risk score in 15,648 postmenopausal Danish nurses. The algorithm was well calibrated for Denmark. However, the sensitivity was poor at common decision making thresholds. Obtaining sensitivity better than 80% led to a low specificity of 61.4%. INTRODUCTION: A new score based on data from the WHI has been designed to predict 5-year risk of hip fracture in postmenopausal women. The performance of the algorithm has not been validated in populations with different lifestyle characteristics and ethnicity. The aim of this study was to test the clinical performance of the algorithm in a large Danish cohort of postmenopausal Caucasian women against hip fracture. METHODS: The Danish Nurse Cohort is a prospective risk factor and hormone therapy (HT) study established in 1993. Participants in the present analysis were 15,648 postmenopausal nurses. The calibration and diagnostic performance of the WHI algorithm was evaluated using fracture events captured in the Danish National Hospital Registry. RESULTS: During 5 years of follow-up, 122 participants suffered a hip fracture (1.8/1,000 person years). The WHI algorithm predicted that 107 hip fractures would occur, indicating an underestimation of the number of fractures by 12%. To obtain sensitivity better than 80%, the cut-off value for 5-year risk was set to 0.5%, which was accompanied by a low positive predictive value of 1.9% and a low specificity of 61.4%. The algorithm predicted too many fractures in HT-users (12 observed, 22 expected) and too few in non HT-users (107 observed, 81 expected). CONCLUSIONS: While the WHI algorithm was well calibrated on the Danish population, the clinical utility of the WHI algorithm in Danish postmenopausal women was limited by poor sensitivity at common decision-making thresholds and suboptimal in non-HT-users.

Breast cancer with different prognostic characteristics developing in Danish women using hormone replacement therapy.

The aim of this study is to investigate the risk of developing prognostic different types of breast cancer in women using hormone replacement therapy (HRT). A total of 10 874 postmenopausal Danish Nurses were followed since 1993. Incident breast cancer cases and histopathological information were retrieved through the National Danish registries. The follow-up ended on 31 December 1999. Breast cancer developed in 244 women, of whom 172 were invasive ductal carcinomas. Compared to never users, current users of HRT had an increased risk of a hormone receptor-positive breast cancer, but a neutral risk of receptor-negative breast cancer, relative risk (RR) 3.29 (95% confidence interval (CI): 2.27-4.77) and RR 0.99 (95% CI: 0.42-2.36), respectively (P for difference=0.013). The risk of being diagnosed with low histological malignancy grade was higher than high malignancy grade with RR 4.13 (95% CI: 2.43-7.01) and RR 2.17 (95% CI: 1.42-3.30), respectively (P=0.063). For breast cancers with other prognostic characteristics, the risk was increased equally for the favourable and non favourable types. Current users of HRT experience a two- to four-fold increased risk of breast cancer with various prognostic characteristics, both the favourable and non favourable types. For receptor status, the risk with HRT was statistically significantly higher for hormone receptor-positive breast cancer compared to receptor-negative breast cancer.

Relation between hormone replacement therapy and ischaemic heart disease in women: prospective observational study.

OBJECTIVE: To investigate the risk of ischaemic heart disease and myocardial infarction among women using hormone replacement therapy, especially the potential modifying effect of cardiovascular risk factors. DESIGN: Prospective observational study. SETTING: Denmark. PARTICIPANTS: 19 898 nurses aged 45 and over completing a questionnaire on lifestyle and use of hormone replacement therapy in 1993. MAIN OUTCOME MEASURES: All cases of death and incident cases of ischaemic heart disease and myocardial infarction until the end of 1998. RESULTS: Current users of hormone replacement therapy smoked more, consumed more alcohol, had lower self rated health, but were slimmer and had a lower prevalence of diabetes than never users. In current users compared with never users, hormone replacement therapy had no protective effect on ischaemic heart disease (hazard ratio 1.2, 0.9 to 1.7) or myocardial infarction (1.0, 0.6 to 1.7), whereas current users with diabetes had an increased risk of death (3.2, 1.4 to 7.5), ischaemic heart disease (4.2, 1.4 to 12.5), and myocardial infarction (9.2, 2.0 to 41.4) compared with never users with diabetes. CONCLUSION: Hormone replacement therapy showed no protective effect on ischaemic heart disease, but there was a significantly increased risk of death from all causes and ischaemic heart disease among women with diabetes.

[Insertion of intrauterine device in general practice. Which women choose the IUD, and how is the procedure done?]. / Spiraloplaegning i almen praksis. Hvem får oplagt spiral, og hvordan er proceduren?

INTRODUCTION: In Denmark most IUDs are inserted by general practitioners (GPs). The aim of this study was to throw light on which women choose IUD, the procedure used, and difficulties associated with insertion. MATERIAL AND METHODS: All 232 GPs in Frederiksborg County were invited to participate and 88 agreed. The GP filled in a questionnaire concerning the type of IUD, the age, parity, etc, of the woman and information about the insertion. RESULTS: Eighty-eight GPs contributed with 562 IUD insertions. IUD was mostly used by women above 25 years of age and by women who had given birth to a child. There were no differences in the insertion procedures used by the doctors. Fifty-nine per cent of the women were previous IUD users. Of the former users, 37% reported problems with the previous use of the IUD. Twenty-five per cent of the women in this study reported that they had had heavy or long-lasting menstruation before insertion. Fifty-five per cent of the women had a test for chlamydia before insertion. Twenty-three (4.1%) insertions were abandoned. 26 (4.6%) insertions were described as difficult. The highest frequency was in women using gestagen-releasing IUDs. CONCLUSION: IUD was mainly used by women, who had given birth to a child. The gestagen releasing IUD was mostly used by the elder group and by women with heavy bleedings before insertion. The procedure was very identical and the number of abandoned and difficult insertions were low and only related to the type of IUD. More female than male doctors participated. Doctors working in partnerships participated more frequently than doctors working alone.

Use of hormone replacement therapy among Danish nurses in 1993.

BACKGROUND: To describe the prevalence of women using systemic hormone replacement therapy in various age groups. To identify their reasons for choosing or not choosing the therapy, reasons for discontinuing the treatment, the prevalence of side effects among current users, and to estimate the duration of treatment. METHODS: The study is based on postal questionnaires sent to 23,000 female Danish nurses above the age of 44 years. Out of these 19,953 (86%) responded. The questionnaire gave information on age, use of hormone replacement therapy, use of oral contraceptives, family predisposition and diseases. Duration of hormone replacement therapy was calculated by Cox regression analysis. Chi square tests were used to evaluate differences and 5% was used as the level of significance. RESULTS: Overall, 6673 (33%) had ever used hormone replacement therapy. The prevalence was highest in the age group 55-59, where 29.3% were currently using hormones. The most cited reasons for choosing hormone replacement therapy were vasomotor symptoms (62%) and prevention of osteoporosis (44%). Among never users 43% had not experienced climacteric symptoms, 24% found the therapy unnatural, and 22% were afraid of side effects. It was estimated that 70% still were using hormones five years after the start of therapy, 57% after ten years, and 48% after fifteen years. Women with a family history of osteoporosis used hormones longer than women without this predisposition. CONCLUSIONS: One third of all the women had ever used hormone replacement therapy and more than half of ever users used the therapy for more than ten years.

Combined versus sequential hormonal replacement therapy: a double-blind, placebo-controlled study on quality of life-related outcome measures.

BACKGROUND: To compare combined and sequential hormonal replacement therapies to each other as well as placebo in patients suffering from the postmenopausal syndrome. Clinical outcomes were measured concerning both the specific postmenopausal symptoms (using the Kupperman scale) and health or well-being dimensions (using subscales of the General Health Questionnaire and specific depression and anxiety scales). METHODS: A prospective randomized double-blind study over 12 months of 105 normal early postmenopausal women in the setting of a general hospital. RESULTS: Both hormone replacement therapies were superior to placebo on the Kupperman scale (sweating, hot flushing, myalgia and vertigo). The psychic symptoms on the Kupperman scale were psychometrically invalid. However, psychic symptoms as measured by the Beck Depression Inventory and the General Health Questionnaire were significantly improved by the hormonal replacement therapies. No differences were observed when combined therapy was compared to sequential therapy. CONCLUSION: One-year treatment with hormonal replacement therapy is superior to placebo in measuring the somatic and psychic symptoms of the menopausal syndrome. No differences were found in this respect between combined and sequential replacement therapy.

Continuous combined and sequential estradiol and norethindrone acetate treatment of postmenopausal women: effect of plasma lipoproteins in a two-year placebo-controlled trial.

OBJECTIVE: Our purpose was to examine the effects of postmenopausal estrogen therapy supplemented with progestogen on plasma lipoprotein levels. STUDY DESIGN: One hundred thirteen women were randomized to receive either placebo or a combination of 17 beta-estradiol and norethindrone acetate administered continuously (Kliogest) or sequentially (Trisequens). Plasma lipoprotein levels were measured at baseline and after 2 years of treatment and compared by analysis of variance. RESULTS: Hormone therapy lowered plasma cholesterol levels (p < 0.001) and low-density lipoprotein cholesterol (Kiogest, p < 0.001; Trisequens, p < 0.01), whereas high-density lipoprotein cholesterol levels were unchanged (Trisequens) or reduced (Kliogest, p < 0.01), primarily because of a decrease in the high-density lipoprotein-2 subfraction (p < 0.05). Low-density lipoprotein/high-density lipoprotein cholesterol ratios remained unchanged. CONCLUSIONS: Although hormonal replacement therapy with estradiol combined with norethindrone acetate eliminated the increase in high-density lipoprotein cholesterol levels observed with estrogen monotherapy, the reductions in low-density lipoprotein cholesterol concentrations still suggest reduced cardiovascular risk, according to the National Cholesterol Education Program and to recent observations indicating that risk is not necessarily inversely proportional to high-density lipoprotein cholesterol levels.

[Use of oral contraceptives and smoking among Danish women]. / P-pillebrug og rygevaner blandt danske kvinder.

PIP: Oral contraceptive (OC) pills have a very high rate of acceptability among Danish women in spite of the possible risks associated with their use referred to in the daily press. Every fourth woman prefers OCs. Half of the women under 25 use OCs as well as every tenth one over 35. There is hardly any doubt that the use of OCs can increase the risk of blood clot in the heart, and the more cigarettes are smoked the higher the risk. Today increasing doses of gestagens are used with minor effect on the lipid system. The risk of deep venous thrombosis of the lower extremities and the risk of cerebral thrombosis or embolism is elevated even with low-dose OCs, but regarding cerebral thrombosis, research is inconclusive. The risk of cerebral thrombosis is very low among young women and it increases with age. Considering that masses of young women use OCs, and increased incidence of breast cancer has been found under 45 years of age among those who had used OCs before the birth of their first child, a risk that seems to correspond to perhaps a higher number of breast cancer cases in the following years. This can be explained by the fact that OC users do not have an increased risk of breast cancer, but may undergo checkups more often than others, giving a higher chance of early diagnosis of this disease. Based on this it would be unwise to advise against OCs for women under 25, but the issue has to be examined in the context of the risks of other contraceptive methods and AIDS. It is reasonable to restrict OC use in women over 35-40 who smoke more than 5-10 cigarettes daily, or who have other known risk factors for cardiovascular disease.^ieng

[Course of pregnancies and labors in a department of general surgery. A prospective study of pregnancies during a 1-year period at Hørsholms hospital]. / Graviditets- og fødselsforløb på en almenkirurgisk afdeling. En prospektiv opgørelse af en fødselsårgang på Hørsholm Sygehus.

The complications of pregnancy and delivery in a material consisting of 841 women without obstetric risk factors were investigated. The deliveries were planned to take place in a department of general surgery with a specialist obstetrician. Seventy-five women (8.9%) were transferred to a specialized obstetric department before delivery, 14 women (1.7%) because of imminent premature delivery. In addition, 69 women were transferred because of removal or their own wish for transfer. A total of 631 patients (90.5%) were delivered vaginally and 66 (9.5%) were delivered abdominally. In thirty-five of these, caesarean sections were performed during the course of delivery. In 34 deliveries (5.1%) vacuo extraction was used. Among 181 women (27.1%), unexpected complications occurred, 80 of these women (12.0%) requiring emergency treatment. A total of 697 infants were delivered. One infant died before delivery because of placental separation. Twenty-two infants (3.2%) were transferred to a paediatric department during the neonatal period, three because of asphyxia. Three of the liveborn infants (0.4%) had Apgar scores at 1 minute between 0 and 3, 40 infants (5.7%) had scores between 4 and 6. After 5 minutes, no infants had Apgar scores between 0 and 3, but three infants had scores between 4 and 6. It is concluded, that the low perinatal mortality and morbidity might indicate, that deliveries in a department of general surgery are safe, provided a specialist obstetrician is available and the rules of referral strictly observed.

A two-year double-blind controlled study of the clinical effect of combined and sequential postmenopausal replacement therapy and steroid metabolism during treatment.

A total of 151 postmenopausal women were randomly allocated to 3 groups for treatment with hormone replacement therapy. One group received combined therapy (2 mg oestradiol (E2) and 1 mg norethisterone acetate (NETA) daily), the second group was placed on sequential therapy (2 mg E2 for 12 days, 2 mgE2 and 1 mg NETA for 10 days and 1 mg E2 for 6 days), while the third was given placebo. Treatment was administered over 24 cycles of 28 days. The two active treatments were equally effective in relieving climacteric symptoms. In the combined therapy group, 62% of the women experienced spotting and/or breakthrough bleeding during the first 3 cycles; thereafter this proportion decreased to between 3 and 18% in each of the following three-cycle periods. Sixty-four percent (64%) of these women had no more bleeding after the first 3 cycles. Endometrial atrophy was detected in 93% of the women in this group after 24 cycles of therapy. Bleeding irregularities occurred during the first 3 cycles in 27% of the patients treated with sequential therapy and in 21% of those receiving placebo. In the subsequent 3-cycle periods these figures fell to below 10% in the 2 groups. In all 3 groups weight remained stable but blood pressure increased equally in the actively treated groups and the placebo group. The levels of follicle-stimulating hormone (FSH), sex-hormone-binding globulin (SHBG) and the free fraction of E2 in serum were significantly lower in the combined therapy group than in the sequential therapy group. The higher level of free E2 in the latter group may have been caused by a decrease in metabolism associated with the increased SHBG concentration. It was concluded that combined treatment with E2 and NETA might provide an alternative to sequential treatment in postmenopausal women willing to tolerate the initial high risk of breakthrough bleeding/spotting in order to avoid subsequent regular bleeding. In the subgroup of women in whom bleeding irregularities continue, sequential treatment should be considered.

Frequency of curettage in middle-aged women treated with sequential preparations versus untreated women.

Over a 2-month period a register was kept of all dilatation and curettage procedures performed in Frederiksborg County, Denmark, involving women aged 40-59 years. The total recorded was 284. In the same period, questionnaires were sent out to 1200 women in the county who fell within the same, randomly selected age group, to establish the number of women treated with sequential oestrogen/progestogen and those who had been hysterectomized. Based on the results and the total female population in the county, it was calculated that the frequency of the procedure in sequentially-treated women as compared with untreated women was 3.1 times higher in the 55-59 age group. In the 40-54 age group no difference in the incidence of curettage in the sequentially-treated women could be demonstrated.

[Long-term follow-up of patients after a single-freezing treatment of ectocervical intraepithelial neoplasms]. / Langtidsopfølgning af enkeltfrysebehandling af ektocervikale intraepiteliale neoplasier.

Fifty-five women aged 21-51 years were treated in 1977 and 1978 with cryocoagulation (single-freezing technique) for cervical intraepithelial neoplasia (CIN I-III). 92% of these patients were followed up 7-8 years after this treatment. The primary success rate i.e. the proportion between the number of women in whom dysplastic changes were not re-encountered within the first 15 months after treatment and the total number of women treated was 94.5%. After the period of observation of 7-8 years, the success rate was 100% for CIN I + II and 79.5% for CIN III.

Reversal of postmenopausal vertebral bone loss by oestrogen and progestogen: a double blind placebo controlled study.

Because of uncertainty about the place of hormones in the treatment of postmenopausal bone loss vertebral and forearm bone loss was measured by absorptiometry in early postmenopausal women before and after continuous or sequential treatment with combined oestrogen and progestogen in a double blind placebo controlled trial. Treatment with hormones significantly reversed the vertebral bone loss. The net gain in vertebral bone density amounted to 6.4% a year with continuous supplementation and 5.4% a year with sequential supplementation; the net gain in forearm bone density was lower (3.6% with continuous and 3.7% with sequential supplementation). Before a policy of supplementation with hormones can be recommended to all postmenopausal women with the aim of reducing the incidence of vertebral crush fractures further studies with different doses and combinations of hormones, administered over several years, are needed.

Randomised controlled trial of genetic amniocentesis in 4606 low-risk women.

Outcome of pregnancy after amniocentesis was studied in a randomised controlled trial of 4606 women, age-range 25-34 years, without known risk of genetic disease. Spontaneous abortion rate was 1.7% in the study group after amniocentesis and 0.7% in the control group after ultrasound (relative risk 2.3). In the study group, increased levels of maternal serum alpha-fetoprotein before amniocentesis, perforation of the placenta during amniocentesis, and withdrawal of discoloured amniotic fluid were associated with an increased risk of spontaneous abortion. In the first six weeks after amniocentesis/ultrasound scan, amniotic fluid leakage occurred more often in the study group but there was no difference in the rate of vaginal bleeding. Frequency of postural malformations in the infants in the two groups was the same. In the study group, respiratory distress syndrome was diagnosed more often (relative risk 2.1) and more babies were treated for pneumonia (relative risk 2.5).