Estrogen replacement therapy and breast cancer survival in a large screening study.
BACKGROUND: Hormone replacement therapy has been associated in some studies with reductions in breast cancer mortality among women who develop this disease. It is unclear whether this association reflects the biologic activity of the hormones or the earlier detection of tumors among hormone users. We examined breast cancer mortality among women who were diagnosed with axillary lymph node-negative and node-positive breast cancer according to the currency of estrogen use at diagnosis. METHODS: Vital status through June 1995 was determined for 2614 patients with postmenopausal breast cancer diagnosed during the period from 1973 to January 1981. We estimated adjusted hazard-rate ratios (adjusting for tumor size, age, race, Quetelet [body mass] index, and number of positive lymph nodes in women with node-positive disease) and unadjusted cumulative probabilities of breast cancer death over time since diagnosis. RESULTS: Among patients with node-negative disease, rate ratios for breast cancer mortality associated with current use compared with nonuse at diagnosis were 0.5 (95% confidence interval [CI] = 0.3-0.8) until 144 months after diagnosis and 2.2 (95% CI = 0.9-5.2) thereafter. Mortality was not statistically significantly lower in past users. The cumulative probabilities of breast cancer mortality at the end of follow-up were 0.14, 0.14, and 0.09 in nonusers, past users, and current users, respectively. Among women with node-positive disease, the rate ratios associated with current and past use were both 0.5 until 48 months after diagnosis (95% CI = 0.3-0.8 for current users; 95% CI = 0.3-0.9 for past users) and were 1.1 (95% CI = 0.7-1.7) and 1.8 (95% CI = 1.2-2.7), respectively, thereafter. The cumulative probabilities of breast cancer mortality were 0.32, 0.39, and 0.27 in nonusers, past users, and current users, respectively. CONCLUSIONS: Patients with breast cancer who were using replacement estrogens at the time of diagnosis experienced reductions in breast cancer mortality, which waned with the time since diagnosis. (+info)
Breast carcinoma developing in patients on hormone replacement therapy: a histological and immunohistological study.
AIM: To study the histopathological features of breast carcinoma developing in postmenopausal patients on hormone replacement therapy (HRT). METHODS: The sample comprised 60 patients with invasive breast carcinoma including 31 who had received HRT at or shortly before presentation, and 29 who had not. Details concerning their tumour size, histological type and grade, lymph node status, and oestrogen and progesterone receptor status were compared. Immunoperoxidase staining for Bcl-2, p53, and E-cadherin was carried out on paraffin sections of all 60 patients. The results were then statistically analysed. RESULTS: Tumours detected in HRT patients were significantly smaller (mean 17 mm v 25 mm; p = 0.0156) and of a lower histological grade (p = 0.0414) than those detected in non-HRT patients. The incidence of invasive lobular carcinoma was slightly higher in HRT patients (19% v 14%). Immunohistologically, 87% of HRT tumours were Bcl-2 positive (compared with 79% in the control group), 29% were p53 positive (45% in the control), and 48% were E-cadherin positive (72% in the control group). Although the differences were not statistically significant there was a trend towards higher incidence of p53 negative and E-cadherin negative tumours in HRT patients. CONCLUSIONS: Breast carcinomas detected in patients on HRT have a significantly higher incidence of two favourable prognostic features (small size and a low histological grade). They also show a trend, statistically not significant, of being p53 negative and E-cadherin negative; this may be related to the slightly higher incidence of invasive lobular tumours in these patients. (+info)
The relationship between a polymorphism in CYP17 with plasma hormone levels and breast cancer.
The A2 allele of CYP17 has been associated with polycystic ovarian syndrome, elevated levels of certain steroid hormones in premenopausal women, and increased breast cancer risk. We prospectively assessed the association between the A2 allele of CYP17 and breast cancer risk in a case-control study nested within the Nurses' Health Study cohort. We also evaluated associations between this CYP17 genotype and plasma steroid hormone levels among postmenopausal controls not using hormone replacement to assess the biological significance of this genetic variant. Women with the A2 allele were not at an increased risk of incident breast cancer [OR (odds ratio), 0.85; 95% CI (confidence interval), 0.65-1.12] or advanced breast cancer (OR, 0.84; 95% CI, 0.54-1.32). We did observe evidence that the inverse association of late age at menarche with breast cancer may be modified by the CYP17 A2 allele. The protective effect of later age at menarche was only observed among women without the A2 allele (A1/A1 genotype: for age at menarche > or =13 versus <13; OR, 0.57; 95% CI, 0.36-0.90; A1/A2 and A2/A2 genotypes: OR, 1.05; 95% CI, 0.76-1.45; P for interaction = 0.07). Among controls, we found women with the A2/A2 genotype to have elevated levels of estrone (+14.3%, P = 0.01), estradiol (+13.8%, P = 0.08), testosterone (+8.6%, P = 0.34), androstenedione (+17.1%, P = 0.06), dehydroepiandrosterone (+14.4%, P = 0.02), and dehydroepiandrosterone sulfate (+7.2%, P = 0.26) compared with women with the A1/A1 genotype. These data suggest that the A2 allele of CYP17 modifies endogenous hormone levels, but is not a strong independent risk factor for breast cancer. (+info)
Hormone replacement therapy increases isometric muscle strength of adductor pollicis in post-menopausal women.
A randomized open trial of hormone replacement therapy was used to assess changes in adductor pollicis muscle strength during 6-12 months of treatment with Prempak C 0.625(R) in comparison with an untreated control group. Muscle strength (maximal voluntary force; MVF), muscle cross-sectional area and bone mineral density were measured. Women entering the trial had oestrogen levels below 150 pmol.l-1, confirming their post-menopausal hormonal status. In the treated group, MVF increased by 12.4+/-1.0% (mean+/-S.E.M.) of initial MVF over the duration of treatment, while it declined slightly (2.9+/-0.9%) in the control group. This increase in strength could not be explained by an increase in muscle bulk, there being no significant increase in cross-sectional area during the study. Those subjects who were weakest at enrolment showed the greatest increases in muscle strength after treatment. Bone mineral density in total hip, Ward's triangle and total spine increased in the treated group, in agreement with previous studies. There was no correlation between the individual increases in bone mineral density and those in MVF. (+info)
Osteoporosis: review of guidelines and consensus statements.
This activity is designed for physicians, pharmacists, nurses, health planners, directors of managed care organizations, and payers of health services. GOAL: To understand current guidelines and consensus statements regarding the prevention, diagnosis, and treatment of osteoporosis. OBJECTIVE: List four national or international organizations involved in the development of consensus statements regarding the prevention, diagnosis, and treatment of osteoporosis. 2. Discuss the significant differences among different countries regarding the prevention and treatment of osteoporosis. 3. List the major risk factors for osteoporosis. 4. Describe the differences in the application of bone mineral density scans, biochemical markers, and ultrasound in evaluating patients with suspected osteopenia and osteoporosis. 5. Distinguish between and briefly discuss therapeutic modalities used in primary prevention, secondary prevention, and treatment of osteoporosis. 6. Discuss the advantages and disadvantages of estrogen/hormone replacement therapy. 7. Describe alternatives to estrogen/hormone replacement therapy. (+info)
Low use of long-term hormone replacement therapy in Denmark.
AIMS: To examine individual use of hormone replacement therapy (HRT) in a defined population of Danish women during a 5-year period. HRT may reduce osteoporosis and cardiovascular disease in postmenopausal women, but may also have side-effects. Little is known about the use of HRT in most populations. METHODS: A Pharmacoepidemiological Prescription Database was used to identify all reimbursed prescriptions for HRT in the county during the period 1991 to 1995. The Danish retail pharmacies' drug subsidy system made it possible to identify prescriptions by individual use. RESULTS: We examined 255797 HRT prescriptions issued during the period in the County of North Jutland. Total sales reached 16.5 million defined daily doses (DDDs), purchased by 31653 women, which corresponds to 26.9% of the female population above the age of 39 years. The annual prevalence proportion of current users rose from 10.4% to 14.8% during the study period, and the therapeutic intensity (DDD/1000 women/day) increased from 20.6 to 32.0. The mean DDD sum of systemic HRT per user was 73.4 in 1991; it and the proportion of users who received less than 90 DDD per year (83.4% in 1991) remained almost constant during the study period. The amount of oestrogen unopposed by progestin was high, 28.1% of all prescriptions. CONCLUSIONS: Less than one-fifth of the study population used HRT for more than 3 months per year, and only 32.8% of the women who were new users of HRT in 1992 continued this therapy throughout the study period. (+info)
Differential effect of transdermal estrogen plus progestagen replacement therapy on insulin metabolism in postmenopausal women: relation to their insulinemic secretion.
OBJECTIVE: To evaluate the impact on glucose and insulin metabolism of transdermal estrogen patches before and after the addition of cyclic dydrogesterone in postmenopausal women. DESIGN: We studied 21 postmenopausal women seeking treatment for symptomatic menopause. All patients received transdermal 50 micrograms/day estradiol for 24 weeks. After 12 weeks of treatment, 10 mg/day dydrogesterone were added. METHODS: During both regimens, insulin and C-peptide plasma concentrations were evaluated after an oral glucose tolerance test (OGTT); insulin sensitivity was evaluated by a hyperinsulinemic euglycemic clamp technique. Insulin and C-peptide response to OGTT were expressed as area under the curve (AUC) and as incremental AUC; insulin sensitivity was expressed as mg/kg body weight. Fractional hepatic insulin extraction (FHIE) was estimated by the difference between the incremental AUC of the C-peptide and insulin divided by the incremental AUC of the C-peptide. Plasma hormone and lipid concentrations were assessed at baseline and at 12 and 24 weeks of treatment. RESULTS: Nine patients proved to be hyperinsulinemic and 12 were normoinsulinemic. Transdermal estrogen treatment significantly decreased the insulin AUC (P < 0.05) and the insulin incremental AUC in hyperinsulinemic patients; addition of dydrogesterone further decreased both the AUC and incremental AUC of insulin. Estrogen alone and combined with dydrogesterone evoked a significant increase in C-peptide AUC in hyperinsulinemic (79.2%) and normoinsulinemic (113%) patients. The treatment increased the values for FHIE and insulin sensitivity in all patients (P < 0.04) and in the hyperinsulinemic group (P < 0.01), whereas it did not affect such parameters in normoinsulinemic patients. CONCLUSIONS: Transdermal estrogen substitution alone and combined with cyclical dydrogesterone may ameliorate hyperinsulinemia in a selected population of postmenopausal women. (+info)
Combined oestrogen-progestogen replacement therapy does not inhibit low-density lipoprotein oxidation in postmenopausal women.
AIMS: The use of oestrogen containing hormone replacement therapy (HRT) is related to a significantly reduced atherosclerotic cardiovascular risk in postmenopausal women. Oestrogen is thought to be antioxidant and may inhibit low-density lipoprotein (LDL) oxidation in vitro. We investigated the effect of combined oestrogen and progestogen HRT on LDL oxidation in postmenopausal women. METHODS: Eighteen healthy women were given oestrogen/progestogen, and the susceptibility of LDL to oxidation was measured as the level of autoantibody to oxidative modified LDL and the production of conjugated dienes during copper-dependent oxidation after 3 and 6 months HRT. The levels of vitamin E, the major antioxidant in LDL, were also measured. RESULTS: After HRT, the anti-oxidatively modified LDL antibody level remained unchanged [1.58+/-0.16, 0.10 (-0.10, 0.26), and 0.08 (-0.09, 0.19), mean+/-s.d. at baseline, and mean change with 95% confidence intervals for differences at 3 and 6 months, respectively, P>0.05] as did the production of conjugated dienes when determined as lag phase [51.2+/-7.5, -0.3 (-3.9, 3.3), and 1.5 (-3.4, 6.4) min, P>0.05]. The LDL vitamin E content, measured as alpha-tocopherol, was also not altered [2.34+/-0.54, -0.07 (-0.27, 0.13), and -0.07 (-0.33, 0.16) nmol mg(-1) LDL, P>0.05] by treatment. CONCLUSIONS: Combined oestrogen and progestogen therapy for 6 months in postmenopausal women does not protect LDL against oxidation. (+info)