Assessment of women's treatment preferences for vasomotor symptoms due to menopause.

BACKGROUND: Several therapies for vasomotor symptoms (VMS) due to menopause are available. Treatment preferences and willingness-to-pay for VMS treatment among US women with VMS were evaluated. METHODS: An online survey of women with perimenopausal or postmenopausal VMS was conducted (3/15/21-4/23/21). A discrete choice experiment quantified the impact of 7 treatment attributes on VMS treatment choice: VMS frequency/severity reduction, sleep improvement, risk of breast cancer/cardiovascular events in 6 years, risk of short-term side effects, and out-of-pocket costs. Preference weights (PWs) with 95% confidence intervals (CIs) were estimated and reported. RESULTS: Among 467 women, 86.5% and 87.8% reported moderate to very severe VMS and sleep problems during the preceding month, respectively. Sleep improvement (PW: 0.843; 95% CI: 0.721, 0.965) and reduction in VMS frequency (PW: 0.658; 95% CI: 0.520, 0.796) and severity (PW: 0.628; 95% CI: 0.500, 0.756) most influenced treatment preference; risk of cardiovascular events (PW: 0.150; 95% CI: 0.069, 0.232) or breast cancer (PW: 0.401; 95% CI: 0.306, 0.496) in 6 years had lesser effect. Willingness-to-pay was an additional $35-$46/month for substantially improved sleep, 80% VMS frequency reduction, and reduction from severe to mild VMS. CONCLUSIONS: Sleep improvement and reductions in VMS frequency/severity were the most important treatment attributes.

Hormone and non-hormone treatments are available to reduce vasomotor symptoms (hot flashes and night sweats) due to menopause. We conducted an online survey of 467 women with moderate to very severe vasomotor symptoms during perimenopause or postmenopause to learn what treatment attributes are most important to women when selecting from among the available therapies and how much women were willing to pay for the attributes. Women were shown 14 cards, each with a side-by-side comparison of 2 treatments with varying descriptions of the following 7 treatment attributes: reduction in frequency of vasomotor symptoms, reduction in severity of vasomotor symptoms, improvement in sleep, risk of breast cancer in 6 years, risk of cardiovascular events in 6 years, risk of short-term side effects, and out-of-pocket costs. Women picked their preferred treatment on each card. Results showed that improvement in sleep was the most important attribute to women, and they were willing to pay an extra $46/month for a treatment that substantially improved sleep. The next most important attributes were reduction in frequency and reduction in severity of vasomotor symptoms. Women were willing to pay $36/month more for a treatment that reduced symptom frequency by 80% compared with one that reduced frequency by 50%, and they were willing to pay $35/month more for treatment that reduced symptoms from severe to mild compared with one that did not reduce symptom severity. These results may help guide development of new treatment options and may help physicians recommend treatments that best fit women's preferences.

A critical appraisal of vasomotor symptom assessment tools used in clinical trials evaluating hormone therapy compared to placebo.

OBJECTIVE: Vasomotor symptoms (VMS) have been consistently reported as the leading predictor of health-related quality of life (HRQOL) among menopausal women, and the strongest indication for treatment. The North American Menopause Society endorses the use of oral estrogen for the treatment of VMS based on a Cochrane meta-analysis. The Cochrane review concludes that oral hormone therapy reduces the frequency and severity of VMS. The objective of this review is to critically appraise the outcome measures used in these clinical trials to evaluate whether there is adequate evidence that oral hormone therapy improves HRQOL. METHODS: Each trial in the 2004 Cochrane review of oral hormone therapy for the management of VMS was evaluated with respect to study design, outcome measures, and method of analysis. RESULTS: Twenty-four randomized, double-blind, placebo-controlled clinical trials were appraised. Six trials were excluded from the Cochrane meta-analysis due to inadequate reporting of outcome measures. Of the remaining trials, 15 trials assessed only symptom frequency and/or severity. One trial used a subscale of the General Health Questionnaire. Two trials used the Greene Climacteric Scale, a validated outcome measure in menopausal women, to directly assess the impact of hormone therapy on HRQOL. Both studies showed an improvement in HRQOL in the hormone-treated group, although the sample size was small (n = 118) and the effect was modest. CONCLUSION: Although oral hormone therapy improves VMS scores, there is a paucity of evidence on whether it improves HRQOL in menopausal women. Future studies using validated, patient-reported outcome measures that directly assess HRQOL are needed.

[HTA and non-hormonal menopause treatment]. / HTA et traitements non-hormonaux de la ménopause.

Serotonin reuptake inhibitors, clonidine, gabapentin and pregabalin have shown moderate efficacy in menopausal disorders. The effect of phytoestrogens is reported to be modest, but the side effects are not well known.

Conjugated estrogens and bazedoxifene in minority populations: pooled analysis of four phase 3 trials.

OBJECTIVE: The aim of the study was to compare efficacy of conjugated estrogens (CE)/bazedoxifene (BZA) for treatment of menopausal symptoms and prevention of postmenopausal osteoporosis in minorities (black/Hispanic) versus whites. METHODS: In a post hoc analysis, data were pooled from 3,424 white or minority nonhysterectomized postmenopausal women randomized to CE 0.45 or 0.625 mg/BZA 20 mg or placebo in four double-blind, phase 3 Selective Estrogens, Menopause, and Response to Therapy (SMART) trials. Outcomes included hot flush frequency/severity (daily diary) in women with at least seven moderate-to-severe hot flushes per day (SMART-1, -2), vaginal cytology in women with at most 5% superficial cells (SMART-1, -3), lumbar spine and total hip bone mineral density (BMD) (SMART-1, -5), and the Menopause-Specific Quality of Life (MENQOL) questionnaire (SMART-1, -2, -3, -5). RESULTS: The analysis included 2,907 white (84.9%), 315 black (9.2%), and 202 Hispanic (5.9%) women. The reduction in hot flush frequency/severity versus placebo (P < 0.05; week 12) was similar in white and minority women. In both populations, both doses significantly (P < 0.05 vs placebo) improved MENQOL vasomotor function, sexual function, and total scores at 3 months; decreased the percentage of parabasal cells at 2 years; and increased the percentage of BMD responders at 12 and 24 months. Significant differential treatment effects by race/ethnicity were observed only for effects on vaginal superficial cells at month 24 and vaginal pH at month 3. CONCLUSIONS: Notwithstanding a limited sample size, CE/BZA had a similar and beneficial impact on hot flushes, MENQOL, and BMD in minorities and whites.

Quantitative efficacy of soy isoflavones on menopausal hot flashes.

AIM: This study aimed to quantitate the efficacy of soy isoflavones in the treatment of menopausal hot flashes. METHODS: Model based meta-analysis (MBMA) was used to quantitate the efficacy of soy isoflavones. We conducted a systemic literature search to build a time-effect model for placebo and soy isoflavones in treating menopausal hot flashes. Studies were identified, subjected to inclusion and exclusion criteria, and reviewed. RESULTS: From 55 articles, 16 studies of soy isoflavones met the inclusion criteria, and contained 65 and 66 mean effect values in placebo and soy isoflavone groups, respectively, from about 1710 subjects. Interestingly, the developed model was found to describe adequately the time course of hot flashes reduction after administration of placebo and soy isoflavones. Using this model, we found that the maximal percentage change of hot flashes reduction by soy isoflavones was 25.2% after elimination of the placebo effect, accounting for 57% of the maximum effects of estradiol (Emax-estradiol = 44.9%). However, a time interval of 13.4 weeks was needed for soy isoflavones to achieve half of its maximal effects, much longer than estradiol, which only required 3.09 weeks. These results suggest that treatment intervals of 12 weeks are too short for soy isoflavones, which require at least 48 weeks to achieve 80% of their maximum effects. CONCLUSIONS: Soy isoflavones show slight and slow effects in attenuating menopausal hot flashes compared with estradiol.

Design and methods of a multi-site, multi-behavioral treatment trial for menopausal symptoms: the MsFLASH experience.

BACKGROUND: Behavioral strategies are recommended for menopausal symptoms, but little evidence exists regarding efficacy. PURPOSE: Describe design and methodology of a randomized controlled 3 by 2 factorial trial of yoga, exercise and omega-3 fatty acids. METHODS: Women from three geographic areas with a weekly average of ≥14 hot flashes/night sweats, who met exclusion/inclusion criteria, were randomized to 12weeks of: 1) yoga classes and daily home practice; 2) supervised, facility-based aerobic exercise training; or 3) usual activity. Women in each arm were further randomized to either omega-3 supplement or placebo. Standardized training, on-going monitoring, and site visits were adopted to ensure consistency across sites and fidelity to the intervention. Participant adherence to the intervention protocol was monitored continuously, and retention was actively encouraged by staff. Information on adverse events was systematically collected. RESULTS: Of 7377 women who responded to mass mailings, 355 (4.8%) were randomized; mean age was 54.7 (sd=3.7), 26.2% were African American, 81.7% were post-menopausal, and mean baseline frequency of daily hot flashes/night sweats was 7.6 (sd=3.8). Adherence of ≥80% was 59% for yoga, 77% for exercise training, and 80% for study pills. Final week 12 data were collected from 95.2% CONCLUSIONS: Conducting a multi-site, multi-behavioral randomized trial for menopausal symptoms is challenging but feasible. Benefits included cost-effective study design, centralized recruitment, and methodologic standardization.

A pilot 'cohort multiple randomised controlled trial' of treatment by a homeopath for women with menopausal hot flushes.

INTRODUCTION: In order to address the limitations of the standard pragmatic RCT design, the innovative 'cohort multiple RCT' design was developed. The design was first piloted by addressing a clinical question " What is the clinical and cost effectiveness of treatment by a homeopath for women with menopausal hot flushes?". METHODS: A cohort with the condition of interest (hot flushes) was recruited through an observational study of women's midlife health and consented to provide observational data and have their data used comparatively. The 'Hot Flush' Cohort were then screened in order to identify patients eligible for a trial of the offer of treatment by a homeopath (Eligible Trial Group). A proportion of the Eligible Trial Group was then randomly selected to the Offer Group and offered treatment. A "patient centred" approach to information and consent was adopted. Patients were not (i) told about treatments that they would not be offered, and trial intervention information was only given to the Offer Group after random selection. Patients were not (ii) given prior information that their treatment would be decided by chance. RESULTS: The 'cohort multiple RCT' design was acceptable to the NHS Research Ethics Committee. The majority of patients completed multiple questionnaires. Acceptance of the offer was high (17/24). DISCUSSION: This pilot identified the feasibility of an innovative design in practice. Further research is required to test the concept of undertaking multiple trials within a cohort of patients and to assess the acceptability of the "patient centred" approach to information and consent.

A pilot phase II trial of magnesium supplements to reduce menopausal hot flashes in breast cancer patients.

BACKGROUND: We tested if magnesium would diminish bothersome hot flashes in breast cancer patients. METHODS: Breast cancer patients with at least 14 hot flashes a week received magnesium oxide 400 mg for 4 weeks, escalating to 800 mg if needed. Hot flash score (frequency × severity) at baseline was compared to the end of treatment. RESULTS: Of 29 who enrolled, 25 women completed treatment. The average age was 53.5 years; six African American, the rest Caucasian; eight were on tamoxifen, nine were on aromatase inhibitors, and 14 were on anti-depressants. Seventeen patients escalated the magnesium dose. Hot flash frequency/week was reduced from 52.2 (standard error (SE), 13.7) to 27.7 (SE, 5.7), a 41.4% reduction, p = 0.02, two-sided paired t test. Hot flash score was reduced from 109.8 (SE, 40.9) to 47.8 (SE, 13.8), a 50.4% reduction, p = 0.04. Of 25 patients, 14 (56%) had a >50% reduction in hot flash score, and 19 (76%) had a >25% reduction. Fatigue, sweating, and distress were all significantly reduced. Side effects were minor: two women stopped the drug including one each with headache and nausea, and two women had grade 1 diarrhea. Compliance was excellent, and many patients continued treatment after the trial. CONCLUSIONS: Oral magnesium appears to have helped more than half of the patients and was well tolerated. Side effects and cost ($0.02/tablet) were minimal. A randomized placebo-controlled trial is planned.

Effective and cost-effective clinical trial recruitment strategies for postmenopausal women in a community-based, primary care setting.

INTRODUCTION: Little evidence exists to guide investigators on the effectiveness and cost-effectiveness of various recruitment strategies in primary care research. The purpose of this study is to describe the effectiveness and cost-effectiveness of eight clinical trial recruitment methods for postmenopausal women in a community-based setting. METHODS: A retrospective analysis of the yield and cost of eight different recruitment methods: 1) family physician (FP) recruiters, 2) FP referrals, 3) community presentations, 4) community events, 5) newsletters, 6) direct mailings, 7) posters, and 8) newspaper advertisements that were used to recruit postmenopausal women to a randomized clinical trial (RCT) evaluating the effectiveness of gabapentin in treating hot flashes. RESULTS: We recruited 197 postmenopausal women from a total of 904 screened, with 291 of the remainder being ineligible and 416 declining to participate. Of the 904 women screened, 34 (3.8%) were from FP recruiters and 35 (3.9%) were from other FP referrals while 612 (67.7%) resulted from newspaper advertisements. Of the 197 women enrolled, 141 (72%) were from newspaper advertisements, with 26 (13%) following next from posters. Word of mouth was identified as an additional unanticipated study recruitment strategy. Metropolitan newspaper advertising at $112.73 (Canadian) per enrolled participant and posters at $119.98 were found to be cost-effective recruitment methods. CONCLUSION: Newspaper advertisements were the most successful method to recruit postmenopausal women into a community-based, primary care RCT.

Assessment of the clinical effect of Chinese medicine therapy combined with psychological intervention for treatment of patients of peri-menopausal syndrome complicated with hyperlipidemia.

OBJECTIVE: To observe the effect of Chinese medicine therapy combined with psychological intervention (combined therapy) on the clinical symptoms and levels of blood lipids and sex hormones of patients of peri-menopausal syndrome complicated with hyperlipidemia. METHODS: With the use of a randomizing digital table method, 185 patients that fit the registration standard were randomly assigned to three groups. The 59 cases in Group A were treated with two Chinese patents, Kunbao Pill and Modified Xiaoyao Pill; the 63 in Group B received psychological intervention alone; and the 63 in Group C were treated with both (the combined therapy), with the treatment course for all six months. The items of observation included: (1) scoring by SCL-90 on eight factors and seven symptoms; (2) scoring on Chinese medicine symptoms by Kupermann scale, including anxiety and bad temper, scorching sense action with sweating, dizziness, tinnitus, soreness and weakness of the loin and knees, palpitation, insomnia, lassitude, weakness, and hyposexuality; (3) blood contents of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apoprotein AI (ApoAI) and B (ApoB); (4) levels of sex hormones, including estradiol (E(2)), progesterone (P), pituitary prolactin (PRL), follicular stimulating hormone (FSH), and), luteinzing hormone (LH) in some randomly selected patients; (5) adverse reaction; and (6) one-year follow-up study on long-term effect. RESULTS: A total of 21 patients (6, 8, and 7 cases in Groups A, B, and C, respectively) dropped out; the drop-out rate was insignificant among groups. (1) The markedly effective rates in Group A, B, and C were 26.42% (14/53), 18.18% (10/55), and 53.57% (30/56), respectively, and the total effective rates in them were 64.15% (34/53), 50.91% (28/55), and 87.50% (49/56), respectively, suggesting the therapeutic efficacy in Group C was significantly better than that in Groups A and B (P<0.01). (2) SCL-90 scoring showed that the total scores decreased significantly after treatment in Group C (P<0.01), but remained unchanged in Groups A and B (P>0.05). (3) Scoring on Chinese medicine symptoms showed the same results as shown by SCL-90 scoring in terms of total scores and individual symptoms, except that menstrual disorder and amenorrhea were unchanged in all three groups (P>0.05). (4) Levels of HDL-C, ApoAI, and E(2) increased and those of TG, TC, LDL-C, ApoB, FSH, and LH decreased after treatment in Group C, reaching near normal levels; similar trends of blood lipids were shown in Group A, but the level of sex hormones was unchanged. In Group B all the above-mentioned indices were unchanged (P>0.05). (5) A one-year follow-up study showed the markedly effective rate and the total effective rate in Group C were higher than those in the other two groups respectively (P<0.01). (6) No adverse reaction was found. CONCLUSION: Chinese medicine therapy combined with psychological intervention could not only improve the nervous symptoms, but also regulate the blood levels of lipids and sex hormones in patients of peri-menopausal syndrome complicated with hyperlipidemia.

Challenges and opportunities to manage depression during the menopausal transition and beyond.

Women are at a higher risk than men of developing depression and anxiety and such increased risk might be particularly associated with reproductive cycle events. Recent evidence suggests that the transition to menopause may constitute a window of vulnerability for some women for the development of new onset and recurrent depression. Several biological and environmental factors seem to be independent predictors or modulating factors for the occurrence of depression in menopausal women; they include the presence and severity of hot flushes, sleep disturbances, history of severe premenstrual syndrome or postpartum blues, stressful life events, history of depression, socioeconomic status, and use of hormones and psychotropic agents. The regulation of monoaminergic systems by ovarian hormones might explain, at least in part, the emergence of depressive symptoms and/or anxiety in biologically predisposed subpopulations. The use of transdermal estradiol, as well as serotonergic and noradrenergic antidepressants, is an efficacious strategy in the treatment of depression and vasomotor symptoms in symptomatic women in midlife. In this review, the authors discuss the existing evidence of a greater risk for the development of depression during the menopausal transition and the putative underlying mechanisms contributing to this window of vulnerability. Hormonal and nonhormonal treatment strategies for depression and anxiety in this particular population are critically examined, although more tailored treatment options are still needed.

Desvenlafaxine: application withdrawal. Desvenlafaxine: withdrawal of marketing application for depression also.

A welcome move! This psychoactive agent has an unfavourable risk-benefit balance in both hot flushes and depression.

Costs of hormonal and nonhormonal prescription medications for hot flashes.

Hot flashes are the cardinal symptom of menopause and can be treated with hormonal and nonhormonal prescription medications. However, considering that 6000 women enter menopause daily in the USA, and many of these women are symptomatic, the costs of these treatments can be a significant public health issue. We evaluated annual individual and population costs of hormonal and nonhormonal prescription treatments for hot flashes. Cost information may be helpful to clinicians and consumers in making treatment decisions.

Is a shorter hot flash diary just as good as a 7-day diary?

OBJECTIVE: In randomized trials, the most common way to measure the effect of treatment on the frequency and severity of menopausal hot flashes is a 7-day self-reported diary. However, adherence with completing the hot flash diary in real time may be poor, and completing a diary is cumbersome for study participants. Our objective was to determine if a shorter diary for recording self-reported hot flashes is as accurate and precise as the traditional 7-day diary. METHODS: Using cross-sectional data from a multicenter randomized clinical trial of an herbal preparation (MF101, an estrogen receptor beta-selective agonist for treatment of menopausal hot flashes), we compared findings based on shorter diaries with findings based on a 7-day diary. RESULTS: With 3 days of diary keeping, the mean number of hot flashes per day and mean severity were almost identical to the means based on the 7-day diary, the SDs of the means were almost identical, and the intraclass correlations were almost perfect. The difference in the mean number of hot flashes per day compared with the 7-day diary was only 12% of one hot flash. Data from a different clinical trial revealed similar correspondence between the findings of a 3- and 7-day diary. CONCLUSIONS: In our study, the optimal duration of diary keeping to record menopausal hot flashes seems to be 3 days. In addition to being as good as a 7-day diary, a 3-day diary would be less burden on study participants and research staff and less expensive.

Cost-effectiveness of hormone replacement therapy for menopausal symptoms in the UK.

OBJECTIVE: To estimate the cost-effectiveness of five-year treatment of hormone replacement therapy (HRT) compared with no treatment for women with menopausal symptoms in the UK. METHOD: A Markov cohort simulation model with tunnel techniques was used to assess the cost-effectiveness of HRT in women aged 50 years. For the clinical effects of HRT we used, where possible, results taken from the Women's Health Initiative (WHI). The model had a life-time horizon with cycle lengths of one year and contained the following disease states: hip fracture, vertebral fracture, wrist fracture, breast cancer, colorectal cancer, coronary heart disease, stroke and venous thromboembolic events. An intervention was modelled by its impact on the disease risks during and after stopping treatment. The model was populated with UK-specific data on risks, mortality rates, quality-of-life weights and costs. The main outcome of the model was cost per quality-adjusted life year (QALY) gained of HRT compared with no treatment. RESULTS: The results indicated that it was cost-effective to treat women with menopausal symptoms with HRT in the UK. The severity of menopausal symptoms was the single most important determinant of cost-effectiveness, but HRT remained cost-effective even where symptoms were mild or effects on symptom relief were small. CONCLUSIONS: Treatment of women with menopausal symptoms with HRT is cost-effective.

Recent epidemiological evidence relevant to the clinical management of the menopause.

BACKGROUND: The 2003 Workshop of the International Menopause Society considered the epidemiological evidence collected up to that time on the effects of female hormone therapy (HT). New evidence relevant to the clinical management of the menopause has since been published. OBJECTIVES: To summarize the new evidence, to offer critiques of important recently published studies, and to consider the implications for clinical practice. CARDIOVASCULAR DISEASE: Recent evidence from two studies, the Women's Health Initiative (WHI) clinical trial, and an observational component of the WHI, suggests that combined hormone therapy (estrogen plus progestin) (CHT) initially increases the risk of coronary heart disease (CHD), stroke, and venous thromboembolism (VTE), followed by a decline. For CHD, the hazard ratio exceeds 1.0 during the first year of follow-up, followed by a progressive decline to <1.0 after >5 years. Other studies show the same trend. BREAST CANCER: In the WHI data, recent evidence suggests that estrogen therapy (ET) reduces the overall risk of breast cancer, predominantly ductal and localized cancer. Evidence from the Million Women Study (MWS) now suggests that the previously reported association of HT with breast cancer is concentrated on tumors with lobular or tubular histology; the risk of ductal cancer is also increased, but to a lesser degree. The risks of these outcomes are higher for CHT than for ET. Other recent studies broadly accord with the MWS observations. OTHER OUTCOMES: Among CHT recipients, the WHI findings of reduced risks of fractures and colorectal cancer, and an increased risk of VTE, remain unchanged. Evidence from other studies now suggests that protracted exposure to CHT may increase the risk of ovarian cancer, and reduce the risk of endometrial cancer. INTERPRETATION: The recently published WHI findings for CHD and breast cancer are of major importance. For CHD, detection bias may have resulted in systematic overestimation of the duration-dependent hazard ratios. If so, there may be no initial increase in the risk, and prolonged use may be associated with a decreased risk. The hypothesized protective effect of HT may have been missed in the WHI study. For breast cancer, the WHI evidence now suggests a protective effect of ET. Tumors with lobular or tubular histology tend to be small, slow-growing, low-grade, and well differentiated. Such tumors may be more susceptible to detection bias, and that bias has not been ruled out as an alternative explanation of the higher risks among CHT recipients, observed in the MWS. The possibility of detection bias in that study, and in other observational studies, is supported by the decreased risk of breast cancer observed among ET recipients in the WHI clinical trial. Based on the present evidence, it is impossible to determine whether HT, or specific forms of HT, increase, decrease, or have no effect on the overall risk of breast cancer, or of specific types of breast cancer. Other evidence raises the possibility that prolonged CHT may increase the risk of ovarian cancer, and decrease the risk of endometrial cancer. Additional studies are needed to confirm those findings. If, as now seems possible, CHT in fact reduces the risk of CHD, and has little or no effect on the risk of breast cancer, or if ET decreases the risk, the clinical and public health implications would be major. However, the picture is confused. In view of new, but uncertain, findings concerning CHD and breast cancer, clinicians will have to continue to use clinical judgment, informed by a critical evaluation of the epidemiological evidence, in the management of the menopause.

Hormone therapy use and prescription durations of menopausal women in Taiwan: a 5 years' National Cohort study.

OBJECTIVES: To describe the prevalence and associated factors of hormone replacement therapy (HRT)-related utilization in a national representative fixed cohort in Taiwan. METHOD: The study population are women aged 40 years and over in Taiwan. Our data, provided by National Health Research Institutes, are the sampled registry information of 37,315 beneficiaries of National Health Insurance from 2000 to 2004. The dependent variables were HRT-related utilizations, including physician contact, HRT utilization rate/duration/patterns (new, prevalent and discontinue users). The independent variables were age, time, prior co-morbidities and prior utilization pattern. We used generalized estimating equation (GEE) model for repeated measurement analysis. RESULTS: The outpatient contact rates for menopause syndrome were low, though the HRT prescription rate among those who have contact were high. GEE shows that age, time, prior co-morbidities/HRT utilization patterns were significantly associated with all types of HRT-related utilizations, which all declined significantly following the publications of Women's Health Initiative (WHI) in 2002. The magnitudes of reduction, though similar in 2003-2004, were greater for physician contact and HRT durations than that of HRT prescription rate for those have contacts in 2002. Besides, the percentages of new (discontinue) users have already declined (increased) since 2001 although it had not declined until 2003 for the continued users. CONCLUSIONS: WHI publications have great impact on HRT-related utilizations. However, the response of the women was quicker and much drastic than that of the physicians in 2002. Besides, the efforts of the various women's associations before WHI might have some contribution to the declined (increased) of new (discontinued) users.

Economic impact of Tibolone compared with Continuous-Combined Hormone Replacement Therapy in the management of climacteric symptoms in postmenopausal women.

BACKGROUND: Deciding whether to treat postmenopausal women suffering from climacteric symptoms with Continuous Combined Hormone Replacement Therapy (CCHRT) has become increasingly difficult after the release of the Women's Health Initiative results. As a result, development of alternatives to CCHRT is required. Tibolone, which is a synthetic steroid that has estrogenic, progestogenic and androgenic properties, is reported to be a promising alternative. It has been used in Europe, in the same indication as CCHRT, for approximately 20 years but is not yet available in Canada. OBJECTIVE: We carried out a cost-utility analysis comparing a 3-year-treatment course with Tibolone 2.5mg and conjugated equine estrogens (CEE)/medroxyprogesterone acetate (MPA) (0.625 mg/2.5 mg) in the management of postmenopausal women with climacteric symptoms. METHODS: A Markov model, considering persistence, vaginal bleeding and climacteric symptoms, was elaborated to compare the different options in terms of cost and Quality Adjusted Life Years (QALYs), according to a public third-party payer perspective. RESULTS: Compared with CEE/MPA, Tibolone led to an increase in cost (dollars 485 for Tibolone versus dollars 232 for CEE/MPA) and a slight increase in QALYs (2.08 for Tibolone versus 2.05 for CEE/MPA). Consequently, the incremental cost per QALY gained ratio was dollars 9198. CONCLUSION: According to the results, Tibolone seems to be a cost-effective alternative to CEE/MPA. However, those results should be interpreted with caution insofar as the difference in terms of QALY is clinically difficult to value and taking into account the limited data on Tibolone's long-term innocuity.