OBJECTIVE: To assess the safety and health-related quality of life (HRQOL) of continuous combined hormone replacement therapy (ccHRT) with estradiol valerate/medroxyprogesterone acetate (E(2)V/MPA) over nine years and at follow-up one year after discontinuation. Study design: A total of 419 women were randomized to one of four treatments: once-daily 1 mg E2V/2.5 mg MPA (1 + 2.5 group); 1 mg E2V/5 mg MPA daily (1 + 5 group); 2 mg E2V/2.5 mg MPA daily (2 + 2.5 group); 2 mg E2V/5 mg MPA daily (2 + 5 group) (Indivina, Orion Pharma). For the last six months, all received the 1 + 2.5 dosage. The 2 + 2.5 dosage was discontinued at the end of year 7. A total of 198 women continued after year 7. RESULTS: Annualized percentage rates for cardiovascular events [corrected] and endometrial cancers [corrected] were below national rates for Finland and those reported for the Women's Health Initiative. There were no serious events with the 1 + 2.5 dosage or after ccHRT discontinuation. Climacteric symptoms remained significantly below baseline values after dosage reduction; some symptoms recurred after discontinuation of ccHRT. HRQOL ratings improved with ccHRT, irrespective of dosage, including depressed mood, anxiety, health perception and sexual interest. Scores on a scale assessing daily functioning and enjoyment (Q-LES-Q) improved from year 7 to year 9. They deteriorated during follow-up in women not continuing ccHRT. CONCLUSIONS: Lower dosages of HRT were as effective as higher doses in improving climacteric symptoms and HRQOL ratings and had fewer safety concerns. Following discontinuation of ccHRT, patient satisfaction was variable, with 15% electing to continue or restart HRT and 7% resuming at follow-up. This supports the need for an individualized approach to therapy recommendations.
To explore the extent to which biochemical testing is used to diagnose androgen deficiency before initiating treatment and to learn whether recommendations for clinical monitoring of men taking androgen therapy are being followed.
Population-based retrospective cohort study.
A total of 902 men who filled at least 2 prescriptions for androgen therapy.
Whether men had had baseline prostate-specific antigen (PSA) and testosterone testing before initiation of therapy and whether men had been monitored during the first year of treatment.
Of the 902 men who filled first-time prescriptions during the study period, only 475 (52.7%) had ever had PSA or testosterone tests. Before starting therapy, 315 men (34.9%) had had PSA tests, and 152 men (16.9%) had had testosterone tests. Less than 1% of the entire sample had had 3 or more tests during the year following initiation of therapy.
Indications for androgen therapy in this population appear to be based on clinical symptoms rather than on demonstrated biochemical androgen deficiency. Recommendations for clinical monitoring of men taking androgen therapy are not followed consistently.
OBECTIVE: To investigate the relationship between hormone replacement therapy (HRT), smoking, and cancer incidence. METHODS: Baseline interviews were conducted from 1990 to 1992 in a population-based cohort of 29,508 Swedish women aged 25-65 years with no history of cancer. Cancer incidence in the cohort was assessed through December 31, 1999, with the Swedish Cancer Registry, the Population Census Registry, and the Cause of Death Registry. RESULTS: When follow-up ended, the cohort included 226,611 person-years. A total of 1145 malignancies were diagnosed (observed), and 1166.6 were expected (standardized incidence ratio 0.98; 95% confidence interval [CI] 0.93, 1.04). Women who had experienced a natural menopause and had ever used HRT had no increased incidence of cancer overall (standardized incidence ratio 1.03; 95% CI 0.88, 1.19). Long-term HRT users who smoked had a decreased incidence of smoking-related cancers, such as the oral cavity, pharynx, hypopharynx, larynx, esophagus, lung, cervix, and bladder (standardized incidence ratio 0.24; 95% CI 0.08, 0.76). The effect was seen regardless of the type of HRT (progestin versus non-progestin-containing preparations) used and number of cigarettes smoked. The protective role of HRT for colon cancer was evident among both smokers and nonsmokers. An increased incidence of endometrial cancer was seen only for nonsmokers who used HRT. CONCLUSION: Our data indicate that HRT use protects women against smoking-associated cancers. This effect occurs regardless of the type of HRT and the amount of smoking.
OBJECTIVE: To assess attitudes and beliefs about the menopausal transition in a population of peri- and postmenopausal women, and if these attitudes differed before and after publication of studies on risks and benefits with hormone therapy (HT). MATERIALS AND METHODS: In 1999 and 2003 all women aged 53 and 54 years in the community of Linköping, Sweden, were sent a questionnaire about use of HT, menopausal status and attitudes regarding menopause and HT. RESULTS: Most women regarded menopause as a natural process characterized by both hormonal deficiency and aging and these views did not differ between 1999 and 2003. A majority of women thought that significant climacteric symptoms were a good reason to use HT, but not that women without symptoms should use HT. The fraction of women who supported HT use was, however, significantly lower in 2003 than in 1999. Most women agreed that menopause leads to increased freedom and that it is a relief not to have to think about contraception and pregnancies. CONCLUSIONS: Most Swedish women had a mainly biological view on menopause but nevertheless they thought that only women with climacteric symptoms should use HT. Women's attitudes towards HT have changed after recent reports on risks from long-term use of HT whereas the attitudes towards the menopausal transition were stable. Other factors than attitudes towards menopause affect women's actual use of HT. Probably women's and health care provider's apprehension of the risk-benefit balance of HT use is one such factor.
The aim of this study was to determine bone mineral density (BMD), markers of bone metabolism, fractures, and steroids reflecting hormonal control in adult males with congenital adrenal hyperplasia (CAH). SUBJECTS, METHODS, AND DESIGN: We compared CAH males with 21-hydroxylase deficiency (n=30), 19-67 years old, with age- and sex-matched controls (n=32). Subgroups of CYP21A2 genotypes, age, glucocorticoid preparation, poor control vs overtreatment, and early vs late (>36 months) diagnosis were studied. BMD measured by dual energy X-ray absorptiometry and markers of bone metabolism and androgens/17-hydroxyprogesterone levels were investigated.
All, including older (>30 years), CAH patients had lower BMD in all measured sites compared with control subjects. The null group demonstrated lower BMD in more locations than the other groups. Osteoporosis/osteopenia was present in 81% of CAH patients compared with 32% in controls (=30 years). Fracture frequency was similar, osteocalcin was lower, and fewer patients than controls had vitamin D insufficiency. IGF1 was elevated in the milder genotypes. In patients, total body BMD was positively correlated to weight, BMI, total lean body mass, and triglycerides, and negatively to prolactin. Patients on prednisolone had lower BMD and osteocalcin levels than those on hydrocortisone/cortisone acetate. Patients with poor control had higher femoral neck BMD. There were no differences in BMD between patients with an early vs late diagnosis.
CAH males have low BMD and bone formation markers. BMD should be monitored, adequate prophylaxis and treatment established, and glucocorticoid doses optimized to minimize the risk of future fractures.
The incidence of breast cancer in Denmark has increased about 2-3% every year in the past decades. In this review the established risk factors for the disease are presented and the changes over time in these factors are described. It is concluded that a large part of the rise in incidence can be explained by changes in established risk factors. The potential measures for prevention of the disease seem to be changes in birth patterns and and increased focus on obesity and alcohol use.
While use of hormone-replacement therapy (HRT) effectively alleviates menopausal symptoms and prevents osteoporosis and possibly cardiovascular disease, there is concern of a detrimental impact on breast-cancer risk. There is a particular lack of data regarding the effect of long-term use of oestrogen-progestin combinations on breast-cancer risk. We conducted a large epidemiological study in Sweden, where combined oestrogen-progestin treatment has been predominant, to examine the influence of different regimens of menopausal hormone therapy on breast-cancer risk. In this population-based case-control study, 3,345 women aged 50 to 74 years with invasive breast cancer (84% of all eligible) and 3,454 controls of similar age (82% of all selected) were included. Mailed questionnaires and telephone interviews were used to collect detailed information on use of hormone replacement and on potential confounding factors. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through multiple logistic regression. There was a trend of increasing breast-cancer risk with duration of oestrogen/oestrogen-progestin use (OR for women treated at least 10 years, 2.43; 95% CI, 1.79-3.30, as compared to never-users), with statistically significant estimates only for women with BMI
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.
The purpose of the cohort study reported here was to investigate the association between oral contraceptive use and risk of benign breast disease (BBD), overall and by histological subtype, within the 56,537 women in the Canadian National Breast Screening Study (NBSS) who completed self-administered lifestyle and dietary questionnaires. The NBSS is a randomized controlled trial of screening for breast cancer in women aged 40-59 at recruitment. Cases were the 2,116 women in the dietary cohort who were diagnosed with biopsy-confirmed incident BBD. For comparative purposes, a subcohort consisting of a random sample of 5,681 women (including 197 subjects with incident BBD) was selected from the full dietary cohort. After exclusions for various reasons, the analyses were based on 2,116 cases and 5,338 non-cases. There was an inverse association between use of oral contraceptives and risk of all types of BBD combined. The reduction in risk was confined largely to proliferative forms of BBD (BPED), and in particular, to those forms of BPED without histological atypia, in whom there was a progressive reduction in risk with increasing duration of use (the IRR (95% CI) for use of more than 7 years was 0.64 (0.47-0.87)); risk of BPED with atypia was increased somewhat in association with oral contraceptive use (the IRR (95% CI) for use of more than 7 years was 1.43 (0.68-3.01 )), but not in a dose-dependent manner. The results were similar when examined separately in the screened and control arms of the NBSS and for screen-detected and interval-detected BPED.
OBJECTIVE: To delineate the influence of hormone therapy (HT) on features of metabolic syndrome with special reference to the composition and mode of administration of three specific HT regimens, all containing estradiol (E2) + norethisterone. DESIGN: The Women's Health in the Lund Area project screened all women (n = 10,766), born between 1935 and 1945. Complete data were obtained from 6,917 women. Those at or above defined cutoff limits were considered positively screened (n = 3,593) for metabolic syndrome. All of them were invited to undergo an oral glucose tolerance test; 2,923 women accepted. After excluding 200 women with impaired fasting glucose, 2,723 women were included in the present analysis. Serum lipids were determined by conventional standard methods at the department of clinical chemistry of Lund University Hospital. RESULTS: According to World Health Organization criteria, 2,123 women had normal glucose tolerance and 600 women had impaired glucose tolerance (IGT). IGT was less common (P = 0.001) among users of a transdermal patch [CYC-TRANS; E2 50 microg + norethisterone acetate (NETA) 250microg] compared with the two-combined oral regimen [CON-O (continuous oral E2 2 mg + NETA 1 mg) + CYC-O (sequential oral E2 2 mg + NETA 1 mg)]. Furthermore, IGT was more common among CON-O users when compared with either the CYC-O + CYC-TRANS group (P = 0.002) or the CYC-TRANS only group (P = 0.001). There were no significant differences between CYC-O versus CYC-TRANS or CON-O. Serum levels of total cholesterol were higher in the CYC-TRANS group than in the combined CON-O + CYC-O group (P