Severity Of Flushes Research Articles

Increased Vascular Inflammation in Early Menopausal Women Is Associated With Hot Flush Severity

Context: Menopause has been related to an increased atherosclerotic risk. Presence and severity of hot flushes in menopausal women have been associated with impaired endothelial function and advanced subclinical atherosclerosis. Objective: The objective of the study was to evaluate the effect of menopausal transition on vascular inflammation indices and investigate the association of hot flush severity with these indices in early menopausal women. Design, Setting, and Participants: This was a cross-sectional study that included 120 early menopausal women (age range 42–55 yr, <3 yr in menopause) recruited from the menopause outpatient clinic of an academic hospital and 24 age-matched premenopausal women (controls). Main Outcomes: Serum high-sensitivity C-reactive protein, P-selectin, and soluble CD40 ligand (sCD40L) levels were measured. Results: P-selectin and sCD40L were increased in early menopausal compared with control women (P = 0.006 and P = 0.02 respectively), whereas high-sensitivity C-reactive pr...

Effectiveness and Safety of Laropiprant on Niacin-Induced Flushing

Extended-release niacin (ERN) improves multiple lipid parameters but is underused owing to niacin-induced flushing (NIF). Laropiprant (LRPT) reduces NIF; however, its effects on chronic flushing (>6 months) have not been studied. We examined whether after 20 weeks of treatment with ERN/LRPT, patients who continued ERN/LRPT would experience less NIF than patients who stopped LRPT and continued ERN alone. A total of 1,152 dyslipidemic patients were randomized 2:2:1 to group 1, ERN/LRPT 1 g/20 mg/day from 0 to 4 weeks and then ERN/LRPT 2 g/40 mg/day from 5 to 32 weeks; group 2, ERN/LRPT 1 g/20 mg/day from 0 to 4 weeks, ERN/LRPT 2 g/40 mg/day from 5 to 20 weeks, and then ERN 2 g/day without LRPT from 21 to 32 weeks; or group 3, placebo for the entire study. The end points included the number of days each week with a moderate or greater Global Flushing Severity Score (GFSS) ≥4 (primary end point) and the percentage of patients with a maximum GFSS of ≥4 (secondary end point) during the postwithdrawal period (weeks 21 to 32). ERN/LRPT produced significantly less NIF than ERN alone during the postwithdrawal period, as measured by the number of days each week with a GFSS of ≥4 (p <0.001) and the percentage of patients with a maximum GFSS of ≥4 (p <0.001; ERN/LRPT 19.6%; ERN 48.9%; placebo 9.2%). Compared with ERN alone, ERN/LRPT produced fewer drug-related adverse experiences during the postwithdrawal period. After 20 weeks of stable maintenance therapy, dyslipidemic patients treated continuously with ERN/LRPT experienced less NIF than did patients who had had LRPT withdrawn and had continued with ERN alone. In conclusion, the results of our study support the long-term efficacy of ERN/LRPT in reducing NIF symptoms.

Transdermal estradiol gel for the treatment of symptomatic postmenopausal women

The aim of this study was to determine the efficacy, safety, and lowest practical dose of a transdermal estradiol gel in the treatment of symptomatic postmenopausal women. Healthy postmenopausal women with seven or more moderate to severe hot flushes per day or 50 to 60 or more per week were randomized to transdermal gel containing 1.5 mg (n = 73) or 0.75 mg (n = 75) estradiol (EstroGel 0.06%) or placebo (n = 73) in a phase 3 study, or to 0.375 mg (n = 119) or 0.27 mg (n = 118) estradiol (0.03% gel) or placebo (n = 114) in a phase 4 study. The frequency of moderate to severe hot flushes and severity of all hot flushes significantly decreased versus placebo at weeks 4 and 12 with 1.5, 0.75, and 0.375 mg estradiol. Overall participant responder rates were generally lower in the phase 4 study than those in the phase 3 study with the approved 0.75-mg estradiol dose. Vaginal maturation index (VMI) shifts from baseline to week 12 were significant (P < 0.001) with 0.75 and 1.5 mg estradiol versus placebo; VMI improved (P < 0.001), superficial cells increased (P = 0.005), and parabasal cells decreased (P = 0.002) with 0.375 mg estradiol vs placebo but not with 0.27 mg estradiol. The most frequently reported treatment-emergent adverse events, although not necessarily treatment related, were headache, infection, breast pain, and nausea (phase 3 study) and insomnia and headache (phase 4 study). No serious adverse events were related to treatment; no deaths occurred. A transdermal gel with 0.75 mg estradiol was the lowest practical dose that effectively reduced the frequency and severity of moderate to severe hot flushes, improved VMI, and was well tolerated.

Using bazedoxifene plus conjugated estrogens for treating postmenopausal women

The objective of this article was to review clinical outcomes reported with the tissue selective estrogen complex containing bazedoxifene (BZA) and conjugated estrogens (CE) in postmenopausal women. PubMed was searched from inception to June 2011 using the key words bazedoxifene and conjugated estrogens. We reviewed six published articles reporting the clinical efficacy and safety outcomes of three different level I evidence, multicenter, blind, randomized, placebo-controlled studies. BZA/CE reduced hot flush frequency and severity, prevented loss of bone mass, and treated vulvar-vaginal atrophy and its symptoms without endometrial stimulation and provided amenorrhea and breast tenderness rates similar to those with placebo. Overall safety was not different from that observed with placebo, and no unexpected findings were reported. The tissue selective estrogen complex composed of BZA/CE is a new progestin-free therapy that alleviates hot flushes and prevents the loss of bone mass in postmenopausal women with endometrial hyperplasia and amenorrhea rates comparable with those of placebo.

Increased Vascular Inflammation in Early Menopausal Women Is Associated with Hot Flush Severity

Menopause has been related to an increased atherosclerotic risk. Presence and severity of hot flushes in menopausal women have been associated with impaired endothelial function and advanced subclinical atherosclerosis. The objective of the study was to evaluate the effect of menopausal transition on vascular inflammation indices and investigate the association of hot flush severity with these indices in early menopausal women. This was a cross-sectional study that included 120 early menopausal women (age range 42-55 yr, <3 yr in menopause) recruited from the menopause outpatient clinic of an academic hospital and 24 age-matched premenopausal women (controls). Serum high-sensitivity C-reactive protein, P-selectin, and soluble CD40 ligand (sCD40L) levels were measured. P-selectin and sCD40L were increased in early menopausal compared with control women (P = 0.006 and P = 0.02 respectively), whereas high-sensitivity C-reactive protein levels did not differ (P = 0.4) between the groups. Hot flush severity was the most important independent predictor of P-selectin levels (P = 0.011) in early menopausal women. Women with moderate/severe/very severe hot flushes had increased P-selectin compared with women with no/mild hot flushes or controls (P < 0.05 for both). The sCD40L levels were also higher in menopausal women with moderate/severe/very severe hot flushes compared with controls (P = 0.03) but did not differ significantly compared with women with no/mild hot flushes (P = 0.2). Increased indices of vascular inflammation in early menopausal compared with age-matched premenopausal women may indicate a higher atherosclerotic risk. Increased severity of hot flushes was associated with adverse changes in vascular inflammation, further supporting the emerging role of hot flushes in cardiovascular prognosis in these women.

Luteinizing hormone–releasing hormone receptor antagonist may reduce postmenopausal flushing

Hormone therapy (HT) is the most effective treatment of postmenopausal (PMP) flushing; however, its use is often contraindicated. As an alternative option, we explored the efficacy of the luteinizing hormone-releasing hormone (LHRH) receptor antagonist cetrorelix in women with severe PMP flushing. We conducted an open-label treatment with cetrorelix 250 μg twice a day on 10 women with a baseline daily flush score of 15 or higher for a period of 4 to 6 weeks. The response to treatment was evaluated through monitoring serum gonadotropin levels, flush scores, and quality of life. At baseline, the mean (SEM) daily flush score was 36.1 ± 1.8 (mean ± SEM range, 29-44). All women demonstrated a decrease in serum luteinizing hormone and follicle-stimulating hormone during treatment, but the premenopausal levels of both gonadotropins were reached in only two women. The mean daily flush score decreased by 42.0% ± 7.7% (P < 0.001). This was caused by a decrease in flush frequency of 26.2% ± 6.0% (P < 0.01) and by a decrease in flush severity of 21.2% ± 7.7% (P < 0.05). In an open-label setting, luteinizing hormone-releasing hormone receptor blockade reduced PMP flushing by at least 25% in 8 of 10 women with severe flushing. A placebo-controlled study will be needed to demonstrate the true benefit of this approach. The present data suggest that the treatment period must be longer than 6 weeks to capture the maximal effect.

Stellate-ganglion block as a treatment for severe postmenopausal flushing

ABSTRACTObjective Hormone replacement therapy is the most effective treatment for postmenopausal flushing. Unfortunately, its use is often contraindicated. A limited amount of uncontrolled data suggests that stellate-ganglion block (SGB) may be useful for the treatment of hot flushes. In the present study, we examined whether previously reported results could be reproduced in women with severe postmenopausal flushing.Methods Twenty postmenopausal women with a baseline hot flush score ≥ 15 were treated with SGB in an open, uncontrolled setting. This mean daily hot flush score was calculated as the product of flush frequency and flush severity over a period of 1 week. The response to treatment was evaluated by flush scores and assessment of quality of life at baseline and 4 weeks after SGB.Results The per-protocol analysis included 19 women. One woman was excluded because of lack of Horner syndrome after SGB. Four weeks after SGB, the mean flush score had decreased by 34 ± 7.4% (95% confidence interval (CI) 18–49%; p < 0 .005). Nine women had a decrease in flush score between 40 and 90%, with a mean response of 65 ± 4.9% (95% CI 53–76%). The other ten women were non-responders with a decrease in flush score between 0 and 11%. Quality of life and sleep, both assessed by questionnaire, improved significantly.Conclusions The results of this study support the observation that SGB may be a useful therapy for a subset of women with severe postmenopausal flushing. A sham-controlled, single-blinded study is warranted to improve the evidence of efficacy.

Acupuncture for Hot Flushes in Perimenopausal and Postmenopausal Women: A Randomised, Sham-Controlled Trial

To determine the effect of acupuncture in treating hot flushes in perimenopausal or postmenopausal women. The study was a randomised single-blind sham-controlled clinical trial. Perimenopausal or postmenopausal women with moderate or severe hot flushes were randomised to receive real or sham acupuncture. Both groups underwent a 4-week run-in period before the treatment. The real acupuncture group received 11 acupuncture treatments for 7 weeks, and the control group underwent sham acupuncture on non-acupuncture points during the same period. Both groups were followed for 8 weeks after the end of treatment period. Changes from baseline in the hot flush scores at week 7, measured by multiplying the hot flush frequency and severity, were the primary outcome. Hot flush frequency, severity and menopause-related symptoms measured with the Menopause Rating Scale Questionnaire were regarded as secondary outcomes. 54 participants were randomised into the real acupuncture group (n=27) and the sham acupuncture group (n=27). The mean change in hot flush scores was -6.4±5.2 in the real acupuncture group and -5.6±9.2 in the sham group at week 7 from values at the start of the acupuncture treatment (10.0±8.1 vs 11.7±12.6), respectively (p=0.0810). No serious adverse events were observed during the whole study period. Compared to sham acupuncture, acupuncture failed to show significantly different effects on the hot flush scores but showed partial benefits on the hot flush severity. Further consideration is needed to develop appropriate strategies for distinguishing non-specific effects from observed overall effectiveness of acupuncture for hot flushes. Whether acupuncture has point-specific effects for hot flushes should be also considered in designing future researches.

Abstract 8824: Following Stable Therapy with Extended Release Niacin/Laropiprant, Continued Extended Release Niacin/Laropiprant Use Reduced Flushing versus Extended Release Niacin Alone in Dyslipidemic Patients

Extended-release niacin (ERN) produces improvements across the lipid profile in patients with dyslipidemia, but is underutilized due to flushing, a process primarily mediated by prostaglandin D 2 (PGD 2 ). The PGD 2 receptor antagonist, laropiprant (LRPT), reduces ERN-induced flushing in patients with dyslipidemia. This study tested the hypothesis that, after 20 weeks of the fixed-dose combination ERN/LRPT, patients who continued on ERN/LRPT would have less flushing than patients who had LRPT withdrawn, but continued on ERN alone. After a 2-week placebo run-in, 1152 patients with dyslipidemia were randomized 2:2:1 to one of three daily treatment groups: (1) ERN/LRPT 1g/20mg from 0 to 4 weeks, then ERN/LRPT 2g/40mg for the remainder of the study; (2) ERN/LRPT 1g/20mg from 0 to 4 weeks, then ERN/LRPT 2g/40mg from 5 to 20 weeks, then ERN 2g without laropiprant from 21 to 32 weeks; or (3) placebo for the duration of the study. The key endpoints were based on the Global Flushing Severity Score (GFSS) from the previously validated Flushing Symptom Questionnaire: the number of days/week with moderate or greater GFSS ≥4 (primary) and the percentage of patients with maximum GFSS ≥4 (secondary) during the post-withdrawal period of the study (weeks 21 to 32). ERN/LRPT produced significantly less flushing relative to ERN alone during the post-withdrawal period, as measured by the number of days/week with GFSS ≥4 (p&lt;0.001; see fig) and the percentage of patients with maximum GFSS ≥4 (ERN/LRPT: 19.6%; ERN: 48.9%; Placebo: 9.2%). There were fewer drug related adverse experiences during the post-withdrawal period comparing the ERN/LRPT to the ERN treatment groups. In summary, following 20 weeks of stable maintenance therapy, dyslipidemic patients treated continuously with ERN/LRPT experienced less flushing than patients who had LRPT withdrawn, and continued with ERN alone. This study supports the long-term efficacy (&gt; 24 weeks) of ERN/LRPT in reducing flushing symptoms.

Factors relating to insomnia during the menopausal transition as evaluated by the Insomnia Severity Index

Background Although the menopause associates to poor sleep quality, insomnia severity data in the menopausal transition is scarce or lacking. Objective To assess insomnia prevalence, severity and related factors in mid-aged women. Methods In this cross-sectional study 340 women (40 to 59 years) completed the Insomnia Severity Index (ISI) and a general questionnaire containing personal/partner data. Hot flush presence and intensity was also assessed with the Menopause Rating Scale (MRS). Results Median age of the sample was 48.0 years, with 63.5% having lower education and 52.9% being postmenopausal. At the moment of the survey 7.1% were on hormone therapy, 8.2% on phytoestrogens and 2.1% on psychotropic drugs. A 63.8% were abdominally obese (waist circumference > 88 cm) and 65.5% sedentary. According to item 1 of the MRS, 60.9% presented hot flushes, graded in 17.4% as severe-very severe. Regarding the partner ( n = 255), erectile dysfunction was present in 23.9%, premature ejaculation 37.6%, 35.3% abused alcohol and 42.4% were faithful. The ISI tool displayed a high internal consistency (alpha Cronbach coefficient = 0.87), identifying 41.5% of women with some degree of insomnia (Total ISI score ≥8) further categorized as sub-threshold or mild (32.0%), moderate (7.4%) and severe (2.1%). Multiple linear regression analysis obtained two best fit models predicting total ISI scores, one not including and one including partner data. In the first model, hot flush severity, psychotropic use and sedentarism displayed significant positive correlations with total ISI scores. In the second, hot flush intensity, psychotropic drug use and male erectile dysfunction positively correlated whereas partner faithfulness inversely with ISI scores. Conclusion In this mid-aged series insomnia severity was related to female and partner factors; several of which are susceptible of intervention.

Modeling hot flushes and quality of life in breast cancer survivors

Objectives To evaluate the relationships among measures of hot flushes, perceived hot flush interference, sleep disturbance, and measures of quality of life while controlling for potential covariates (patient and treatment variables).Methods Breast cancer survivors (n == 395) due to receive aromatase inhibitor therapy provided demographic information, physiological hot flush data via sternal skin conductance monitoring, hot flush frequency via written diary and electronic event marker, hot flush severity and bother via written diary, and questionnaire data via the Hot Flash Related Daily Interference Scale, Pittsburgh Sleep Quality Index, the EuroQOL, Hospital Anxiety and Depression Scale and the Center for Epidemiologic Studies Depression Scale.Results Confirmatory factor analysis supported a two-factor model for hot flush symptoms (frequency and severity). Although there was strong convergence among self-reported hot flush measures, there was a high degree of unexplained variance associated with physiological measures. This suggests that self-report and physiological measures do not overlap substantially. The structural model showed that greater hot flush frequency and severity were directly related to greater perceived interference with daily life activities. Greater perceived interference, in turn, directly predicted greater sleep disruption, which predicted lower perceived health state and more symptoms of anxiety and depression.Conclusions Findings suggest hot flush interference may be the most appropriate single measure to include in clinical trials of vasomotor symptom therapies. Measuring and ameliorating patients' perceptions of hot flush interference with life activities and subjective sleep quality may be the most direct routes to improving quality of life.

Flushing Profile of Extended-Release Niacin/Laropiprant at Initiation of Therapy in Asian Lipid Clinic Patients

Objective: Niacin is underutilized due to flushing, which occurs in over 90% of niacin-treated patients. Laropiprant (LRPT) reduces flushing associated with niacin. This study compared flushing with a combination tablet of extended-release (ER) niacin (ERN)/LRPT to niacin ER (N-ER; without LRPT) during the first week of therapy among patients in Asia. Methods: Following a 1-week placebo run-in, 332 patients with dyslipidemia from China, Korea and Singapore were randomized to ERN/LRPT 1 g/20 mg, N-ER 1 g (given as Niaspan®) or placebo in a 2:2:1 ratio for 1 week. Patient-reported flushing severity was assessed using the Global Flushing Severity Score (GFSS; none/mild = 0–3; moderate = 4–6; severe = 7–9; extreme = 10). Results: Compared with N-ER, the ERN/LRPT group experienced significantly less flushing (p < 0.001), as measured by maximum GFSS categorized as none/mild, moderate, severe or extreme. Overall, 23.8% of patients in the ERN/LRPT group and 50.0% in the N-ER group (p < 0.001), versus 12.1% in the placebo group, had moderate or greater flushing (GFSS ≥4). Except for flushing, which occurred more frequently in the N-ER group, ERN/LRPT had a safety/tolerability profile similar to that of N-ER. Conclusion: ERN/LRPT produced significantly less flushing than N-ER during the initiation of therapy and was generally well tolerated in Asian patients with dyslipidemia.

Flushing Profile of Extended-Release Niacin/Laropiprant Versus Gradually Titrated Niacin Extended-Release in Patients With Dyslipidemia With and Without Ischemic Cardiovascular Disease

Niacin has beneficial effects on a patient's lipid and lipoprotein profiles and cardiovascular risk, particularly at doses >2 g/day, but is underused due to flushing. Laropiprant (LRPT), a selective prostaglandin D(2) receptor-1 antagonist, decreases flushing associated with extended-release niacin (ERN). We compared flushing with ERN/LRPT dosed by a simplified 1-g --> 2-g regimen versus gradually titrated niacin extended-release (N-ER; given as NIASPAN, trademark of Kos Life Sciences LLC). Patients with dyslipidemia (n = 1,455) were randomized 1:1 to ERN/LRPT (1 g for 4 weeks advanced to 2 g for 12 weeks) or N-ER (0.5 g for 4 weeks titrated in 0.5-g increments every 4 weeks to 2 g for the final 4 weeks). Aspirin/nonsteroidal anti-inflammatory drugs were allowed to mitigate flushing. Flushing severity was assessed using the validated Global Flushing Severity Score (GFSS; none 0, mild 1 to 3, moderate 4 to 6, severe 7 to 9, extreme 10). Patients on ERN/LRPT, despite more rapid niacin titration, had less flushing than those on N-ER, as measured by number of days per week with moderate or greater GFSS across the treatment period (p <0.001). More than 2 times as many patients had no episodes of moderate, severe, or extreme flushing (GFSS > or =4) with ERN/LRPT than with N-ER (47.0% vs 22.0%, respectively) across the treatment period. Fewer patients on ERN/LRPT discontinued due to flushing than those on N-ER (7.4% vs 12.4%, p = 0.002). Other than the decrease in flushing, the safety and tolerability profile of ERN/LRPT was similar to that of N-ER. In conclusion, improvement in flushing with ERN/LRPT versus gradually titrated N-ER supports a rapidly advanced 1-g --> 2-g dosing regimen, allowing patients to start at 1 g and quickly reach and tolerate the optimal 2 g dose of ERN.

Acupuncture for treating menopausal hot flushes: a systematic review

Objective To assess the effectiveness of acupuncture as a treatment option for menopausal hot flushes.Design We have searched the literature using 17 databases from inception to October 10, 2008, without language restrictions. We included randomized clinical trials (RCTs) of acupuncture versus sham acupuncture. Their methodological quality was assessed using the modified Jadad score.Results In total, six RCTs could be included. Four RCTs compared the effects of acupuncture with penetrating sham acupuncture on non-acupuncture points. All of these trials failed to show specific effects on menopausal hot flush frequency, severity or index. One RCT found no effects of acupuncture on hot flush frequency and severity compared with penetrating sham acupuncture on acupuncture points that are not relevant for the treatment of hot flushes. The remaining RCT tested acupuncture against non-penetrating acupuncture on non-acupuncture points. Its results suggested favorable effects of acupuncture on menopausal hot flush severity. However, this study was too small to generate reliable findings.Conclusion Sham-controlled RCTs fail to show specific effects of acupuncture for control of menopausal hot flushes. More rigorous research seems warranted.

A double-blind, randomly assigned, placebo-controlled study of desvenlafaxine efficacy and safety for the treatment of vasomotor symptoms associated with menopause

The objective of the study was to assess the efficacy and safety of desvenlafaxine (administered as desvenlafaxine succinate) for menopausal vasomotor symptoms. Postmenopausal women (n = 458) experiencing 50 or more moderate to severe hot flushes per week received desvenlafaxine 100 or 150 mg/d, with titration at therapy initiation, or placebo. Hot flush number and severity were assessed at weeks 4 and 12. Safety data were collected throughout the trial. Desvenlafaxine 100 and 150 mg/d significantly reduced the number of hot flushes compared with placebo at weeks 4 and 12 (all P < or = .012), achieving 65.4% and 66.6% reductions from baseline at week 12, respectively (placebo, 50.8%). Hot flush severity and number of nighttime awakenings were significantly reduced at both time points (all P < or = .048). Desvenlafaxine groups reported significantly more adverse events compared with placebo during week 1 only. No difference in discontinuations because of adverse events was observed. Desvenlafaxine is an effective nonhormonal treatment for menopausal hot flushes. Dose titration improves initial tolerability.

Effect of raloxifene and low-dose percutaneous 17β-estradiol on menopause symptoms and endometrium—A randomized controlled trial

Objective To investigate the effects on climacteric symptoms and endometrium of percutaneous low-dose 17β-estradiol associated with raloxifene in postmenopausal women. Design randomized placebo-controlled study. Method Fifty-two postmenopausal women with moderate to severe hot flushes were randomized to receive either 60 mg raloxifene (RLX; n = 20), 0.5 mg percutaneous 17β-estradiol associated to 60 mg raloxifene (RLX + E 2; n = 16) or placebo (PLC; n = 16). Climacteric symptoms (Kupperman index) and vaginal bleeding were evaluated. At baseline and at the end of the study endometrial thickness was measured and endometrial samples were collected for histological study. Results At baseline, the mean Kupperman index was 23.7 ± 1.8 in RLX group, 22.9 ± 1.9 in RLX + E 2 group and 22.6 ± 1.9 in the placebo group (NS). After 3 months, there was a significant reduction in Kupperman index mean values in both groups, but no statistical difference was observed between groups. However, RLX + E 2 and placebo were significantly superior to RLX in reducing hot flush severity ( p < 0.05). Endometrial thickness did not change in both groups. The association of percutaneous low-dose 17β-estradiol to raloxifene was not associated with proliferation of endometrium neither in hysteroscopies nor in endometrial biopsies at the third month of treatment. No vaginal bleeding was reported during the study. Conclusions The association of percutaneous low dose of 17β-estradiol with raloxifene exerted favorable effects on hot flushes severity of postmenopausal women, providing a safe profile in endometrium at least in short-term therapy.

Measuring flushing symptoms with extended-release niacin using the flushing symptom questionnaire©: results from a randomised placebo-controlled clinical trial

IntroductionNiacin is underutilised because of flushing. Lack of a quantitative tool to assess niacin-induced flushing has precluded the objective evaluation of flushing associated with extended-release (ER) niacin formulations. We developed the Flushing Symptom Questionnaire© (FSQ), a quantitative tool to assess patient-reported flushing, and assessed its ability to characterise ER niacin-induced flushing.MethodsThis study focused on the responses to one question in the FSQ, the Global Flushing Severity Score (GFSS), reported on a 0–10 scale (none = 0, mild = 1–3, moderate = 4–6, severe = 7–9 and extreme = 10) to assess flushing during ER niacin initiation (week 1) and maintenance (weeks 2–8).ResultsFlushing severity with ER niacin was greatest during week 1 and remained greater than placebo for the study duration. During weeks 2–8, 40% of patients on ER niacin vs. 8% of those on placebo had > 1 day/week with ‘moderate or greater’ GFSS.ConclusionsIn conclusion, the GFSS component of the FSQ was a sensitive and responsive quantitative measure of ER niacin-induced flushing that will aid in the objective comparison of novel strategies intended to improve tolerability and adherence to niacin, an agent proven to reduce cardiovascular risk.DisclosuresJohn F. Paolini, Yale B. Mitchel, Robert Reyes, Sally Thompson-Bell, Qinfen Yu, Eseng Lai, Douglas J. Watson, Josephine M. Norquist and Christine McCrary Sisk are employees of Merck & Co., Inc., and may own stock/hold stock options in the Company. Dr Harold Bays has served as a Clinical Investigator for (and has received research grants from) the following: Abbott, Alteon, Arena, AstraZeneca, Aventis, Bayer, Boehringer Ingelheim, Boehringer Mannheim, Bristol Myers Squibb, Ciba Geigy, Eli Lilly, Esperion, Fujisawa, GelTex, Genentech, GlaxoSmithKline, Hoechst Roussel, Hoffman LaRoche, InterMune, KOS, Kowa, Lederle, Marion Merrell Dow, Merck, Merck Schering Plough, Miles, Novartis, Parke Davis, Pfizer, Pliva, Purdue, Reliant, Roche, Rorer, Regeneron, Sandoz, Sankyo, Sanofi, Searle, Shionogi, Schering Plough, SmithKline Beacham, Takeda, TAP, UpJohn, Upsher Smith, Warner Lambert and Wyeth-Ayerst. He has also served as a consultant, speaker, and/or advisor to and for Arena, AstraZeneca, Aventis, Bayer, Bristol Myers Squibb, KOS, Merck, Merck Schering Plough, Metabasis Therapeutics, Microbia, Novartis, Nicox, Ortho-McNeil, Parke Davis, Pfizer, Roche, Sandoz, Sankyo, Sanofi Aventis, Shering Plough, SmithKline Beacham, Takeda, UpJohn and Warner Lambert.What's knownNiacin has favourable effects on the lipid profile; however, its use in clinical practice has been hampered by bothersome side effects, primarily flushing. The lack of a quantitative tool to assess flushing symptoms has precluded the objective evaluation of niacin-induced flushing.What's newThis study describes the utility of the Flushing Symptom Questionnaire© (FSQ), a quantitative tool to assess patient-reported flushing end-points. The results show that the FSQ is a useful patient-reported outcome measure to objectively assess flushing associated with extended-release niacin.

A randomized, double-blind, placebo-controlled study of the effect of a Chinese herbal medicine preparation (Dang Gui Buxue Tang) on menopausal symptoms in Hong Kong Chinese women

Objective Many complementary or alternative medicines are being used for the treatment of menopausal symptoms but most have not been properly tested for efficacy or for safety. This study examined the effect of a Chinese herbal preparation (Dang Gui Buxue Tang) on menopausal symptoms in Hong Kong Chinese women.Methods A 6-month randomized, double-blind, placebo-controlled study of the effect of Dang Gui Buxue Tang (a 1 : 5 combination of Dang Gui (Angelicae sinensis) and Huang Qi (Astragalus membranaceus)) on acute menopausal symptoms. A total of 103 symptomatic women were enrolled. Three failed to meet inclusion criteria, leaving 50 subjects for inclusion in each group.Results Overall, mild hot flushes were reported more frequently than either moderate or severe flushes. In analysis by severity of flushes, there was a significant reduction in the number of mild hot flushes per month in the treatment group but not in the placebo group (from 18.9 ± 23.5 at baseline to 8.6 ± 17.1 at 6 months in the treatment group (p < 0.01) and from 26.0 ± 43.5 to 12.4 ± 17.6 in the placebo group (p = 0.062)). For moderate flushes, there was a significant reduction in the placebo group compared with the treatment group (from 18.9 ± 28.7 at baseline to 11.1 ± 29.9 at 6 months in the placebo group (p < 0.05) and from 10.5 ± 22.3 to 6.0 ± 16.0 in the treatment group (p = 0.107)). There was no significant change in either treatment or placebo groups in the reporting of severe hot flushes. Episodes of night sweats decreased significantly in the placebo but not in the treatment group (from 6.8 ± 10.0 at baseline to 1.9 ± 5.7 at 6 months in the placebo group (p < 0.05) and from 5.4 ± 8.9 to 3.2 ± 8.5 in the treatment group (p = 0.471)). In the vasomotor domain of the Menopause Specific Quality of Life, there was a significant reduction in scoring in the placebo group (from 2.8 ± 1.6 to 1.7 ± 1.3, p < 0.01) but not in the treatment group (from 2.8 ± 2.1 to 2.3 ± 1.6, p = 0.247).Conclusions This study found overall no significant difference between Dang Gui Buxue Tang and placebo in the treatment of vasomotor symptoms in Hong Kong Chinese women. The frequency of mild, moderate and severe hot flushes decreased in both treatment and placebo groups, but Dang Gui Buxue Tang was statistically superior to placebo only in the treatment of mild hot flushes. There were no serious adverse events attributable to treatment during the study period.

CYP17 polymorphism and hot flushes in postmenopausal women

Objective To investigate the association between the CYP17α gene polymorphism and hot flushes in postmenopausal women.Methods Ninety-three non-hysterectomized, postmenopausal women were enrolled in this study. Vasomotor symptoms were assessed at the baseline visit and based on information provided by each participant. The genotypic polymorphism of CYP17α gene was analyzed by PCR-RFLP assay using genomic DNA isolated from peripheral blood lymphocytes.Results Thirty-six women reported hot flushes of mild intensity, 25 reported hot flushes of moderate intensity and 32 of severe intensity. There was no significant difference between the severity of hot flushes and the CYP17 genotype or allele frequencies, 0.58 and 0.67 respectively. No association was found between hot flush severity and the CYP17 allele (odds ratio = 1.17, p = 0.61).Conclusion The results of this study suggest that the CYP17 MspAI polymorphism was not significantly associated with an increased risk of reporting hot flushes.At the World Congress on Menopause in Madrid, May 2008, Dr Massad-Costa was awarded the Robert Greenblatt Prize for Basic Science for the study reported in this paper.

Efficacy and Tolerability of Desvenlafaxine Succinate Treatment for Menopausal Vasomotor Symptoms

To compare efficacy and safety of desvenlafaxine succinate (desvenlafaxine) with placebo for the treatment of vasomotor symptoms. This randomized, double-blind, placebo-controlled trial enrolled 707 healthy, postmenopausal women experiencing 50 or more moderate-to-severe hot flushes per week. Participants randomly received desvenlafaxine 50, 100, 150, or 200 mg or placebo daily. Trial duration was 52 weeks. Primary outcomes were change from baseline in average daily number of moderate-to-severe hot flushes and in daily hot flush severity score at weeks 4 and 12. Six hundred twenty women with an average of 11 moderate-to-severe hot flushes per day at baseline completed at least one on-therapy evaluation for primary efficacy end points; 519 participants completed 12 weeks of treatment, and 368 completed the study. Desvenlafaxine 100 mg/d achieved a significantly greater reduction compared with placebo in average daily number of hot flushes at weeks 4 (P=.013) and 12 (P=.005), reaching a 64% decrease from baseline at week 12, and the 75% responder rate was significantly higher for desvenlafaxine 100 mg (50%) compared with placebo (29%; P=.003; number needed to treat=4.7) at week 12. Average daily severity of hot flushes was significantly lower in the desvenlafaxine 100-mg group compared with placebo at week 12 (P=.020). Desvenlafaxine-treated women reported significantly more treatment-emergent adverse events than placebo-treated women during the first week of therapy only. Desvenlafaxine is an effective nonhormonal treatment for vasomotor symptoms in postmenopausal women. Its tolerability profile is consistent with that of other serotonin-norepinephrine reuptake inhibitors. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00421031 I.