Erik B. Obel

Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe.

Epidemiologic studies have shown an increased risk of breast cancer following hormone replacement therapy (HRT). The aim of this study was to investigate whether different treatment regimens or the androgenecity of progestins influence the risk of breast cancer differently. The Danish Nurse Cohort was established in 1993, where all female nurses aged 45 years and above received a mailed questionnaire (n = 23,178). A total of 19,898 women returned the questionnaire (86%). The questionnaire included information on HRT types and regimens, reproductive history and lifestyle‐related factors. Breast cancer cases were ascertained using nationwide registries. The follow‐up ended on 31 December 1999. Women with former cancer diagnoses, women with missing information on HRT, surgical menopause, premenopausal, as well as hysterectomized women were excluded, leaving 10,874 for analyses. Statistical analyses were performed using Cox proportional hazards model. A total of 244 women developed breast cancer during follow‐up. After adjustment for confounding factors, an increased risk of breast cancer was found for the current use of estrogen only (RR = 1.96; 95% CI = 1.16–3.35), for the combined use of estrogen and progestin (RR = 2.70; 95% CI = 1.96–3.73) and for current users of tibolone (RR = 4.27; 95% CI = 1.74–10.51) compared to the never use of HRT. In current users of combined HRT with testosterone‐like progestins, the continuous combined regimens were associated with a statistically significant higher risk of breast cancer than the cyclical combined regimens (RR = 4.16, 95% CI = 2.56–6.75, and RR = 1.94, 95% CI = 1.26–3.00, respectively). An increased risk of breast cancer was noted with longer durations of use for the continuous combined regimens (p for trend = 0.048). The European traditional HRT regimens were associated with an increased risk of breast cancer. The highest risk was found for the use of continuous combined estrogen and progestin.

Preoperative wound infiltration with bupivacaine reduces early and late opioid requirement after hysterectomy.

We conducted a randomized, double-blind trial to evaluate the early and late analgesic effect of preoperative wound infiltration with bupivacaine 0.25% (40 mL) compared to placebo (NaCl 0.9%, 40 mL) in patients undergoing major surgery. Forty-one patients scheduled for elective hysterectomy during general anesthesia were included. The pain management focused on pain prevention, including preoperative administration of nonsteroidal antiinflammatory drugs (NSAIDs), and peroperative administration of opioids. Postoperatively patients received buprenorphine and/or acetaminophen on demand. A significant difference between treatments was evident in the 3-day postoperative trial period. With identical pain scores in the two groups, the requested total amount of buprenorphine was greater in the placebo group (2.0 [0-5.1] mg) (median and [range]) than in the bupivacaine group (0.8 [0-2.8] mg) (P < 0.05). The demand for analgesics occurred earlier in those who received placebo (225 min) than in those who received bupivacaine (345 min), but did not reach the level of significance. In conclusion, preoperative wound infiltration with bupivacaine improved immediate and late postoperative pain management after hysterectomy compared to placebo. (Anesth Analg 1996;83:376-81)

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

Abstract 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. What is already known on this topic Observational studies have shown that hormone replacement therapy protects women against ischaemic heart disease Randomised clinical trials found no such effect Little attention has focused on identifying subgroups of women who would or would not benefit from treatment What this study adds Hormone replacement therapy does not protect against ischaemic heart disease Women with diabetes who use hormone replacement therapy are at an increased risk of death from all causes and ischaemic heart disease

The validity of self-reported fractures among Danish female nurses: comparison with fractures registered in the Danish National Hospital Register

Background: The authors compared self-reported non-spine fractures obtained from a cohort of Danish female nurses with fracture diagnoses registered in the Danish National Hospital Register (DNHR). Method: The self-reported fracture history was obtained from a questionnaire and was related to fracture information registered with the DNHR by means of the unique person identification code of Danish citizens. A total of 166 self-reported hip fractures, 391 self-reported wrist fractures, and 121 self-reported upper arm fractures were available for the comparison. The self-reported fractures were initially compared with the anatomic specific fracture diagnoses registered in the DNHR. Second, the comparison also included fracture diagnoses of adjacent skeletal sites (unspecific fracture diagnoses). Results: The positive predictive value of a positive report of hip fracture was 89%. Inclusion of unspecific registered hip fractures increased the positive predictive value to 94%. The same figures for wrist fractures were 75% and 84%, respectively, and for upper arm fractures 54% and 83%, respectively. The predictive value of a negative report of hip fracture was 99.5%. The fracture year was correctly reported in 76% of the hip fracture cases, 81% of the wrist fracture cases, and 82% of the upper arm fracture cases. Predictors of false-positive report of fractures were young age (<60 years), report of indoor falls in the previous year, and use of hormone replacement therapy (HRT). Conclusion: The authors conclude that self-report of hip, wrist, or upper arm fractures among Danish nurses is relatively accurate but varies by the site of fracture. False positive reports of fracture introduce only modest bias fracture risk estimates and tend to dilute the association between exposures and fracture.

The validity of self-reported use of hormone replacement therapy among Danish nurses

Background.  Recent findings from randomized clinical trials on the effects of hormone replacement therapy (HRT) among postmenopausal women contradict findings from observational studies indicating a protective effect on the development of cardiovascular disease. Most observational studies on HRT are based on self‐reported data, although data on the validity of HRT in postmenopausal women are sparse.

Pregnancy complications following conization of the uterine cervix (i)

Abstract. The literature on the course of pregnancies following conization of the uterine cervix has been studied. It is demonstrated that an evaluation of the possible effect of conization upon subsequent pregnancy should be based upon a comparison of either pregnancies before and after conization or upon a comparison between pregnancies in women with a previous conization and in a control group of women without conization. In both cases the possible influence of conization can be evaluated only if the patient material is described as regards age, parity, number of previous pregnancies, smoking habits, etc., factors which may all influence the course of pregnancy. None of the previous publications have described the patient material sufficiently, and most studies have not tried to set up control groups.

Intentional weight loss and mortality among initially healthy men and women

Most prospective observational studies suggest that weight loss increases the risk of premature death among obese individuals. This is surprising because clinical studies show that weight loss generally leads to overall improvements in cardiovascular risk factors. It is sometimes argued that the increased mortality observed with weight loss must depend on confounding or poor study designs. This review was conducted to summarize results from studies on intentional weight loss and mortality among healthy individuals, while carefully considering the designs and problems in these studies. Evaluation criteria with a rating scale were developed. Of the studies evaluated, two found decreased mortality with intentional weight loss, three found increased mortality, and four found no significant associations between intentional weight loss and total mortality. Thus, it is still not possible for health authorities to make secure recommendations on intentional weight loss. More studies designed to specifically address this issue are warranted.

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.

Cohort Profile: The Danish nurse cohort

From the 1970s to the mid-1990s, 20–30% of Danish women between 55 and 65 years of age used hormone replacement therapy (HRT). It was primarily used to alleviate climacteric symptoms, but from 1980s the therapy was also used for prevention of osteoporosis and from the 1990s for prevention of cardiovascular diseases. The literature based on observational studies, primarily US studies, suggested a considerable risk reduction of osteoporotic fractures and coronary heart disease, whereas findings on the effect of HRT on breast cancer were inconsistent. In 1976, the US Nurses’ Health Study was established, comprising 121 700 female registered nurses, who were between 30 and 55 years of age. This cohort was originally established to assess risk factors for cancer and cardiovascular diseases, with a particular interest in effects of oral contraceptives, use of hormones, cigarette smoking and other lifestyle factors. Ever since, the participants have been followed every other year with a mailed questionnaire to update exposure information and information on illnesses diagnosed since the previous questionnaire. Inspired by this US cohort of nurses, the Danish Nurse Cohort was established to examine the benefits and risks associated with HRT use in a European population.

Altered progesterone/estrogen receptor ratios in endometriosis: A comparative study of steroid receptors and morphology in endometriosis and endometrium

In a comparative study of endometriosis and endometrium, specimens were taken from both endometriotic and endometrial tissue in 14 patients. Receptor assays and histological examinations were performed on both specimens. Cy‐tosolic estrogen receptors (ERc) as well as cytosolic progesterone receptors (PRc) were detected in 9/14 and 12/12 cases of endometriosis respectively. Nuclear estrogen receptors (ERn) were detected in 4/4 cases of endometrosis. Expressed as fmol/mg cytosol protein, significantly higher values of both ERc and PRc were found in endometrium than endometriosis (p<0.01). However, when the ratio between PRc and ERc was considered, significantly higher PRc/ERc ratios were found in the cytosol of endometriotic tissue (p<0.01). Thus the lower receptor concentrations found in endometriosis cannot be explained solely as ectopic endometrium being diluted by non‐receptor‐containing tissue. In spite of high PRc/ERc ratios in endometriosis, secretory changes similar to those found in endometrium were observed in only one of 7 cases (p<0.05).