• Impact of dose, frequency of administration, and equol production on efficacy of isoflavones for menopausal hot flashes: a pilot randomized trial

      Crawford, Sybil L.; Jackson, Elizabeth A.; Churchill, Linda C.; Lampe, Johanna W.; Leung, Katherine; Ockene, Judith K. (2013-04-22)
      OBJECTIVE: The relatively modest benefit of vasomotor symptom relief in clinical trials of isoflavones may reflect once-daily dosing and low percentages of participants who are able to metabolize daidzein into equol, a potentially more biologically active isoflavone. This pilot study examined whether symptom reduction was greater with more frequent administration and with higher daily doses. In addition, we explored possible effect modification by equol producer status. METHODS: We randomized 130 perimenopausal (no menses in the past 3 mo) and postmenopausal (≥12 mo of amenorrhea) women with a mean of five or more moderate/severe hot flashes per day to treatment arms with varying total daily isoflavone doses and dosing frequency, separately for equol producers and nonproducers. Participants recorded the daily frequency and severity of hot flashes. Analyses compared mean daily hot flash intensity scores (sum of hot flashes weighted by severity) by total daily dose and by dosing frequency. Dose- and frequency-related differences were also compared for equol producers and nonproducers. RESULTS: Hot flash intensity scores were lowest in women randomized to the highest total daily dose (100-200 mg) and in women randomized to the highest dosing frequency (twice daily to thrice daily), with greater benefits on nighttime scores than on daytime scores. Dose- and frequency-related differences were somewhat larger in equol producers than in nonproducers. CONCLUSIONS: These results suggest that a twice-daily to thrice-daily dosing frequency may improve the benefit of isoflavones for vasomotor symptom relief, particularly in equol producers and for nighttime symptoms. Larger studies are needed to confirm these findings.
    • Lifestyle and demographic factors in relation to vasomotor symptoms: baseline results from the Study of Women's Health Across the Nation

      Gold, Ellen B.; Block, Gladys; Crawford, Sybil L.; Lachance, Laurie; FitzGerald, Gordon; Miracle, Heidi; Sherman, Sheryl (2004-06-12)
      Results of recent trials highlight the risks of hormone therapy, increasing the importance of identifying preventive lifestyle factors related to menopausal symptoms. The authors examined the relation of such factors to vasomotor symptoms in the multiethnic sample of 3,302 women, aged 42-52 years at baseline (1995-1997), in the Study of Women's Health Across the Nation (SWAN). All lifestyle factors and symptoms were self-reported. Serum hormone and gonadotropin concentrations were measured once in days 2-7 of the menstrual cycle. After adjustment for covariates using multiple logistic regression, significantly more African-American and Hispanic and fewer Chinese and Japanese than Caucasian women reported vasomotor symptoms. Fewer women with postgraduate education reported vasomotor symptoms. Passive exposure to smoke, but not active smoking, higher body mass index, premenstrual symptoms, perceived stress, and age were also significantly associated with vasomotor symptoms, although a dose-response relation with hours of smoke exposure was not observed. No dietary nutrients were significantly associated with vasomotor symptoms. These cross-sectional findings require further longitudinal exploration to identify lifestyle changes for women that may help prevent vasomotor symptoms.
    • Longitudinal changes in hypothalamic and ovarian function in perimenopausal women with anovulatory cycles: relationship with vasomotor symptoms

      Skurnick, Joan H.; Weiss, Gerson; Goldsmith, Laura T.; Santoro, Nanette; Crawford, Sybil L. (2009-04-01)
      OBJECTIVE: To determine whether the transition to menopausal status is unidirectional and predictable with aging. DESIGN: Longitudinal evaluation of the menstrual cycle hormone patterns and experience of vasomotor symptoms in an anovulatory, perimenopausal cohort, during cycles that occurred 1 and 2 years after an anovulatory cycle. SETTING: Academic center. PATIENT(S): One hundred fifty-nine of 840 women in the Daily Hormone Study, a substudy of the Study of Women's Health across the Nation (SWAN), had anovulatory cycles. Their menstrual cycle patterns were previously described. This report describes their cycle patterns and vasomotor symptoms in the subsequent 2 years. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Daily urinary hormone levels of FSH, LH, and estrogen and P metabolites and reports of daily occurrence of vasomotor symptoms. RESULT(S): While a tendency to develop cycles having a loss of negative feedback of estrogen on LH secretion was seen before menopause, there is no clear progression of cycle patterns in anovulatory women. Anovulation did not predict menopause within 2 years. Vasomotor symptoms occur before menopause, as experienced by 73% of the women. Vasomotor symptoms were not related to cycle pattern. CONCLUSION(S): Any cycle pattern may be related to vasomotor symptoms. The best predictor of vasomotor symptoms is a prior history of vasomotor symptoms.
    • Sensitivity and specificity of recalled vasomotor symptoms in a multiethnic cohort

      Crawford, Sybil L.; Avis, Nancy E.; Gold, Ellen B.; Johnston, Janet M.; Kelsey, Jennifer L.; Santoro, Nanette; Sowers, Mary Fran R.; Sternfeld, Barbara (2008-12-15)
      Many epidemiologic studies include symptom checklists assessing recall of symptoms over a specified time period. Little research exists regarding the congruence of short-term symptom recall with daily self-reporting. The authors assessed the sensitivity and specificity of retrospective reporting of vasomotor symptoms using data from 567 participants in the Study of Women's Health Across the Nation (1997-2002). Daily assessments were considered the "gold standard" for comparison with retrospective vasomotor symptom reporting. Logistic regression was used to identify predictors of sensitivity and specificity for retrospective reporting of any vasomotor symptoms versus none in the past 2 weeks. Sensitivity and specificity were relatively constant over a 3-year period. Sensitivity ranged from 78% to 84% and specificity from 85% to 89%. Sensitivity was lower among women with fewer symptomatic days in the daily assessments and higher among women reporting vasomotor symptoms in the daily assessment on the day of retrospective reporting. Specificity was negatively associated with general symptom awareness and past smoking and was positively associated with routine physical activity and Japanese ethnicity. Because many investigators rely on symptom recall, it is important to evaluate reporting accuracy, which was relatively high for vasomotor symptoms in this study. The approach presented here would be useful for examining other symptoms or behaviors.
    • Symptom experience after discontinuing use of estrogen plus progestin

      Ockene, Judith K.; Barad, David H.; Cochrane, Barbara B.; Larson, Joseph C.; Gass, Margery; Wassertheil-Smoller, Sylvia; Manson, JoAnn E.; Barnabei, Vanessa M.; Lane, Dorothy S.; Brzyski, Robert G.; et al. (2005-07-13)
      CONTEXT: Little is known about women's experiences after stopping menopausal hormone therapy. OBJECTIVE: To describe women's symptoms and management strategies after stopping the intervention in a large estrogen plus progestin trial. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional survey of 8405 women (89.9%; N = 9351) at 40 clinical centers who were still taking study pills (conjugated equine estrogens plus medroxyprogesterone [CEE + MPA] or placebo) when the estrogen plus progestin intervention (Women's Health Initiative) was stopped. Surveys were mailed 8 to 12 months after the stop date. Logistic regression was used to model vasomotor symptoms and pain or stiffness symptoms as functions of former treatment and baseline symptoms, adjusted for appropriate covariates. MAIN OUTCOME MEASURES: Symptoms (vasomotor or pain and stiffness) and management strategies. RESULTS: Respondents' mean (SD) age at trial stop date was 69.1 (6.7) years. They averaged 5.7 years of taking study pills. Moderate or severe vasomotor symptoms after discontinuing study pill use were reported by 21.2% of former CEE + MPA and 4.8% of placebo group respondents overall and by 55.5% and 21.3%, respectively, with these symptoms at baseline (randomization). Compared with respondents in the former placebo group, moderate or severe vasomotor symptoms (adjusted odds ratio [AOR] 5.82; 95% confidence interval [CI], 4.92-6.89) and pain or stiffness symptoms (AOR, 2.16; 95% CI, 1.95-2.40) were more likely in respondents in the former CEE + MPA group. Both vasomotor symptoms (AOR, 5.36; 95% CI, 4.51-6.38) and pain or stiffness symptoms (AOR, 3.21; 95% CI, 2.90-3.56) also were more likely in women with these symptoms at baseline. Women reported a wide range of strategies to manage symptoms. CONCLUSIONS: More than half of the women with vasomotor symptoms at randomization to active CEE + MPA also reported these symptoms after discontinuing use of the study pills. However, these participants did not include women who were unwilling to be randomized or who had stopped taking the study pills earlier. These findings should be considered when advising women to treat menopausal symptoms with hormone therapy for as short duration as possible. Investigation of alternative strategies to manage menopausal symptoms is warranted.