Colon cancer risk and different HRT formulations: a case-control study

<p>Abstract</p> <p>Background</p> <p>Most studies have found no increased risk of colon cancer associated with hormone replacement therapy (HRT), or even a decreased risk. But information about the effects of different HRT preparations is lacking.</p> <p>Methods</p> <p>A case-control study was performed within Germany in collaboration with regional cancer registries and tumor centers. Up to 5 controls were matched to each case of colon cancer. Conditional logistic regression analysis was applied to estimate crude and adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Stratified analyses were performed to get an impression of the risk associated with different estrogens and progestins.</p> <p>Results</p> <p>A total of 354 cases of colon cancer were compared with 1422 matched controls. The adjusted overall risk estimate for colon cancer (ColC) associated with ever-use of HRT was 0.97 (0.71 – 1.32). No clinically relevant trends for ColC risk were observed with increasing duration of HRT use, or increasing time since first or last HRT use in aggregate.</p> <p>Whereas the overall risk estimates were stable, the numbers in many of the sub-analyses of HRT preparation groups (estrogens and progestins) were too small for conclusions. Nevertheless, if the ColC risk estimates are taken at face value, most seemed to be reduced compared with never-use of HRT, but did not vary much across HRT formulation subgroups. In particular, no substantial difference in ColC risk was observed between HRT-containing conjugated equine estrogens (CEE) or medroxyprogesterone acetate (MPA) and other formulations more common in Europe.</p> <p>Conclusion</p> <p>Ever-use of HRT was not associated with an increased risk of colon cancer. In contrary, most risk estimates pointed non-significantly toward a lower ColC risk in HRT ever user. They did not vary markedly among different HRT formulations (estrogens, progestins). However, the small numbers and the overlapping nature of the subgroups suggest cautious interpretation.</p

Hormone therapy after the Women's Health Initiative: a qualitative study

BACKGROUND: Publication of results from the Women's Health Initiative study in July 2002 was a landmark event in biomedical science related to postmenopausal women. The purpose of this study was to describe the impact of new hormone therapy recommendations on patients' attitudes and decision-making in a primary care practice. METHODS: A questionnaire including structured and open-ended questions was administered in a family practice office waiting room from August through October 2003. Rationale for taking or not taking hormone therapy was specifically sought. Women 50–70 years old attending for office visits were invited to participate. Data were analyzed qualitatively and with descriptive statistics. Chart review provided medication use rates for the entire practice cohort of which the sample was a subset. RESULTS: Respondents (n = 127) were predominantly white and well educated, and were taking hormone therapy at a higher rate (38%) than the overall rate (26%) for women of the same age range in this practice. Belief patterns about hormone therapy were, in order of frequency, 'use is risky', 'vindication or prior beliefs', 'benefit to me outweighs risk', and 'unaware of new recommendations'. Twenty-eight out of 78 women continued hormones use after July 2002. Of 50 women who initially stopped hormone therapy after July 2002, 12 resumed use. Women who had stopped hormone therapy were a highly symptomatic group. Responses with emotional overtones such as worry, confusion, anger, and grief were common. CONCLUSION: Strategies for decision support about hormone therapy should explicitly take into account women's preferences about symptom relief and the trade-offs among relevant risks. Some women may need emotional support during transitions in hormone therapy use

Changes in elderly women's health-related quality of life following discontinuation of hormone replacement therapy

BACKGROUND: Many women have discontinued hormone replacement therapy (HRT) in view of recent findings. The goal of this study was to determine if HRT discontinuation is associated with changes in health-related quality of life (HRQOL) in elderly women. METHODS: We studied women enrolled in Pennsylvania's Pharmaceutical Assistance Contract for the Elderly (PACE) program, linking prescription claims with data from a longitudinal mail survey. HRQOL measures included the number of days out of the last 30 that physical health was not good and analogous measures for mental health, pain, and interference with activities, as well as a composite "healthy days" measure developed by CDC. Longitudinal analyses focused on 2,357 women who completed surveys in both 2002 and 2003, and who used HRT at baseline (mean age = 75.5, range = 65–102). Propensity scores were used to match HRT continuers and discontinuers according to HRT type, demographics, and baseline HRQOL. Analysis of covariance was used to compare HRQOL change in continuers and discontinuers. RESULTS: Between 2002 and 2003, 43% of HRT users discontinued therapy. Analysis of covariance to examine HRQOL change revealed complex interactions with age. Discontinuers aged 65–74 reported greater increases in days in which mental health was not good (p < .05), fewer "healthy days" (p < .05), more days in which health interfered with activities (p < .01), and more days with pain (p < .01). Among women aged 75–84, HRT discontinuers reported more days in which physical health was not good (p < .01); no other significant effects were observed in this group. Relative to HRT continuers, discontinuers aged 85 and older experienced apparent HRQOL improvements following cessation, with fewer days in which physical health was not good (p < .01), fewer days of poor mental health (p < .05), and more "healthy days" (p < .01). CONCLUSIONS: These results suggest that there are substantial age differences in response to HRT discontinuation. While women aged 65–74 experienced apparent declines in HRQOL following HRT cessation, women aged 85 and older experienced relative improvements. The HRQOL declines observed among younger women underscore the importance of communication between clinicians and patients throughout the discontinuation process. These results also demonstrate the value of HRQOL surveillance as a component of health program administration

Pharmacokinetics of isoflavones, daidzein and genistein, after ingestion of soy beverage compared with soy extract capsules in postmenopausal Thai women

BACKGROUND: Isoflavones from soybeans may provide some beneficial impacts on postmenopausal health. The purpose of this study was to compare the pharmacokinetics and bioavailability of plasma isoflavones (daidzein and genistein) after a single dose of orally administered soy beverage and soy extract capsules in postmenopausal Thai women. METHODS: We conducted a randomized two-phase crossover pharmacokinetic study in 12 postmenopausal Thai women. In the first phase, each subject randomly received either 2 soy extract capsules (containing daidzin : genistin = 7.79 : 22.57 mg), or soy beverage prepared from 15 g of soy flour (containing daidzin : genistin = 9.27 : 10.51 mg). In the second phase, the subjects received an alternative preparation in the same manner after a washout period of at least 1 week. Blood samples were collected immediately before and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24 and 32 h after administration of the soy preparation in each phase. Plasma daidzein and genistein concentrations were determined by using high performance liquid chromatography (HPLC). The pharmacokinetic parameters of daidzein and genistein, i.e. maximal plasma concentration (C(max)), time to maximal plasma concentration (T(max)), area under the plasma concentration-time curve (AUC) and half-life (t(1/2)), were estimated using the TopFit version 2.0 software with noncompartmental model analysis. RESULTS: There were no significant differences in the mean values of C(max)/dose, AUC(0–32)/dose, AUC(0-∝)/dose, T(max), and t(1/2 )of genistein between both preparations. For pharmacokinetic parameters of daidzein, the mean values of C(max)/dose, T(max), and t(1/2 )did not significantly differ between both preparations. Nonetheless, the mean AUC(0–32)/dose and AUC(0-∝)/dose after administration of soy extract capsules were slightly (but significantly, p < 0.05) higher than those of soy beverage. CONCLUSION: The bioavailability of daidzein, which was adjusted for the administered dose (AUC/dose), following a single oral administration of soy beverage was slightly (but significantly) less than that of soy extract capsules, whereas, the bioavailability adjusted for administered dose of genistein from both soy preparations were comparable. The other pharmacokinetic parameters of daidzein and genistein, including C(max )adjusted for the dose, T(max )and t(1/2), were not different between both soy preparations

The Women's international study of long-duration oestrogen after menopause (WISDOM): a randomised controlled trial

BACKGROUND: At the time of feasibility work and final design of the trial there was no randomised control trial evidence for the long-term risks and benefits of hormone replacement therapy. Observational studies had suggested that long term use of estrogen was likely to be associated, amongst other things, with reduced risks of osteoporosis and ischaemic heart disease and increased risks of breast and endometrial cancer. Concomitant use of progestogens had been shown to protect against endometrial cancer, but there were few data showing how progestogen might affect estrogen actions on other conditions. Disease specific risks from observational studies suggested that, overall, long-term HRT was likely to be beneficial. Several studies showed that mortality from all causes was lower in HRT users than in non-users. Some secondary cardiovascular prevention trials were ongoing but evidence was also required for a range of outcomes in healthy women. The WISDOM trial was designed to compare combined estrogen and progestogen versus placebo, and estrogen alone versus combined estrogen and progestogen. During the development of WISDOM the Women's Health Initiative trial was designed, funded and started in the US. DESIGN: Randomised, placebo, controlled, trial. METHODS: The trial was set in general practices in the UK (384), Australia (94), and New Zealand (24). In these practices 284175 women aged 50–69 years were registered with 226282 potentially eligible. We sought to randomise 22300 postmenopausal women aged 50 – 69 and treat for ten years. The interventions were: conjugated equine estrogens, 0.625 mg orally daily; conjugated equine estrogens plus medroxyprogesterone acetate 2.5/5.0 mg orally daily; matched placebo. Primary outcome measures were: major cardiovascular disease, osteoporotic fractures, breast cancer and dementia. Secondary outcomes were: other cancers, all cause death, venous thromboembolism and cerebro-vascular disease. RESULTS: The trial was prematurely closed during recruitment following publication of early results from the Women's Health Initiative. At the time of closure, 56583 had been screened, 8980 entered run-in, and 5694 (26% of target of 22,300) randomised. Those women randomised had received a mean of one year of therapy, mean age was 62.8 years and total follow-up time was 6491 person years. DISCUSSION: The WISDOM experience leads to some simple messages. The larger a trial is the more simple it needs to be to ensure cost effective and timely delivery. When a trial is very costly and beyond the resources of one country, funders and investigators should make every effort to develop international collaboration with joint funding

Breast cancer in young women and its impact on reproductive function

BACKGROUND: Breast cancer is the most common cancer in women in developed countries, and 12% of breast cancer occurs in women 20-34 years. Survival from breast cancer has significantly improved, and the potential late effects of treatment and the impact on quality of life have become increasingly important. Young women constitute a minority of breast cancer patients, but commonly have distinct concerns and issues compared with older women, including queries regarding fertility, contraception and pregnancy. Further, they are more likely than older women to have questions regarding potential side effects of therapy and risk of relapse or a new primary. In addition, many will have symptoms associated with treatment and they present a management challenge. Reproductive medicine specialists and gynaecologists commonly see these women either shortly after initial diagnosis or following adjuvant therapy and should be aware of current management of breast cancer, the options for women at increased genetic risk, the prognosis of patients with early stage breast cancer and how adjuvant systemic treatments may impact reproductive function. METHODS: No systematic literature search was done. The review focuses on the current management of breast cancer in young women and the impact of treatment on reproductive function and subsequent management. With reference to key studies and meta-analyses, we highlight controversies and current unanswered questions regarding patient management. RESULTS: Chemotherapy for breast cancer is likely to negatively impact on reproductive function. A number of interventions are available which may increase the likelihood of future successful pregnancy, but the relative safety of these interventions is not well established. For those who do conceive following breast cancer, there is no good evidence that pregnancy is detrimental to survival. We review current treatment; effects on reproductive function; preservation of fertility; contraception; pregnancy; breastfeeding and management of menopausal symptoms following breast cancer. CONCLUSION: This paper provides an update on the management of breast cancer in young women and is targeted at reproductive medicine specialists and gynaecologists

Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis: a cohort study

BACKGROUND: Postmenopausal hormone-replacement therapy (HRT) increases breast-cancer risk. The influence of HRT on the biology of the primary tumor, however, is not well understood. METHODS: We obtained breast-cancer gene expression profiles using Affymetrix human genome U133A arrays. We examined the relationship between HRT-regulated gene profiles, tumor characteristics, and recurrence-free survival in 72 postmenopausal women. RESULTS: HRT use in patients with estrogen receptor (ER) protein positive tumors (n = 72) was associated with an altered regulation of 276 genes. Expression profiles based on these genes clustered ER-positive tumors into two molecular subclasses, one of which was associated with HRT use and had significantly better recurrence free survival despite lower ER levels. A comparison with external data suggested that gene regulation in tumors associated with HRT was negatively correlated with gene regulation induced by short-term estrogen exposure, but positively correlated with the effect of tamoxifen. CONCLUSION: Our findings suggest that post-menopausal HRT use is associated with a distinct gene expression profile related to better recurrence-free survival and lower ER protein levels. Tentatively, HRT-associated gene expression in tumors resembles the effect of tamoxifen exposure on MCF-7 cells