John R. Hilditch

A comparison of the effects of oral conjugated equine estrogen and transdermal estradiol-17β combined with an oral progestin on quality of life in postmenopausal women

OBJECTIVE To compare the effect of transdermal estradiol-17 beta and oral conjugated equine estrogen when combined with an oral progestin on quality of life in post-menopausal women. DESIGN Randomized controlled double-blind trial. A randomization error lead to the exclusion of six subjects but the soundness of the remaining randomization was confirmed. SETTING Large urban community. PATIENTS Women 2-7 years after menopause with a uterus and ovaries, and not currently using hormone replacement therapy. Seventy-four women completed the trial. INTERVENTIONS After baseline measures of quality of life, subjects were randomly assigned to either continuous oral conjugated equine estrogen 0.625 mg daily or continuous transdermal estradiol-17 beta 50 mcg twice weekly, for four 4-week cycles. Medroxyprogesterone acetate 10 mg oral tablets was administered to both groups for the last 12 days of each cycle. OUTCOMES MEASURED Quality of life was determined using the Menopause-Specific Quality of Life Questionnaire. Tolerability was determined by a specifically designed list of adverse effects. Both measures were recorded at base-line and in mid-cycle during the second, third and fourth cycles of treatment. RESULTS There were no statistically significant differences in any of the domains at baseline between the oral and transdermal treatment groups. In the vasomotor domain-scores for the oral and transdermal groups improved from baseline levels of 3.14 and 3.09, respectively, to 1.32 and 1.23; physical domain scores improved from 2.45 and 2.73 to 2.04 and 1.78; psychosocial domain scores improved from 2.72 and 3.04 to 2.21 and 1.94; sexual domain scores improved from 2.32 and 2.16 to 1.64 and 1.30. There were no statistically significant group differences or time/group interactions. Both forms of therapy were equally well tolerated. CONCLUSIONS Improvement in all domains, measured by the Menopause-Specific Quality of Life Questionnaire, was observed in both the oral and transdermal groups. In the absence of a placebo control group, the improvements observed cannot be attributed solely to the therapy. Neither form of therapy offered an advantage over the other in respect to improvement in quality of life.

A randomized controlled trial of the effect of dietary soy and flaxseed muffins on quality of life and hot flashes during menopause.

Objective: To compare the effects of daily ingestion of soy flour (S), ground flaxseed (F), or wheat flour (W) muffins, on quality of life and hot flash frequency and severity in postmenopausal women. Design: This was a double-blind, randomized, controlled, intention-to-treat trial. Ninety-nine women, 1 to 8 years after menopause, ingested muffins with 25 g of flaxseed (50 mg of lignans), 25 g of soy (42 mg of isoflavones), or wheat (control) daily for 16 weeks. Subjects completed the Menopause-specific Quality of Life instrument monthly along with daily hot flash frequency and severity diaries. Compliance measures included a 3-day food diary and urinary isoflavone and lignan analyses at weeks 0 and 16 and returned muffin counts monthly. Results: Eighty-seven women (28, ground flaxseed muffins; 31, soy flour muffins; and 28, wheat flour muffins) completed the trial. Multivariate analysis of variance of all quality-of-life domains yielded an insignificant treatment × time interaction (F46,122 = 0.92, P = 0.62) but a significant time main effect (P <.0001). Repeated-measures analyses of covariance controlling for body mass index showed no significant group × time interaction nor time nor group differences on all quality-of-life domains and hot flash measures except severity. Hot flashes were less severe with flaxseed (P = 0.001) compared to placebo; however, the group × by time interaction was not significant. Phytoestrogen excretion analysis showed treatment group exposure as allocated and no contamination. Conclusion: Neither dietary flaxseed nor soy flour significantly affected menopause-specific quality of life or hot flash symptoms in this study.

Is the ‘clinic-home blood pressure difference’ associated with psychological distress? A primary care-based study

Objective To determine whether there is an association between the ‘clinic-home blood pressure difference’ (CHBPD) and psychological distress in a sample not selected without regard to blood pressure and hypertension status. Design A cross-sectional study. Setting An academic family medicine department in Toronto, Canada. Participants Consecutive attenders (n = 214) of the primary care facility. Subjects aged less than 16 years and those being administered psychotropic or blood pressure-lowering agents were excluded. Main outcome measures The CHBPD was calculated from clinic blood pressure readings and self-measurements by subjects at home; psychological distress was measured by the 30-item version of the General Health Questionnaire (GHQ). Results No signficant association between the CHBPD and psychological distress could be shown for systolic and diastolic blood pressures. The same applied to GHQ subdomains and the CHBPD modelled on several independent variables by multiple linear regression analyses. Conclusion The results from this study, using a large sample drawn from a community, support the view that the CHBPD is not related to anxiety, depression and other forms of psychological distress, but rather is a reaction specific to the clinic setting itself.

Low blood pressure associated with low mood: A red herring?

OBJECTIVE Several reports have discussed a relationship between blood pressure (BP) and psychological well-being scales. Lower BP readings were associated with higher levels of psychological distress and fatigue. This study sought to replicate the association found by previous secondary analyses of epidemiological surveys. DESIGN Cross-sectional study. SETTING Academic Family Medicine Department in Toronto, Canada. SUBJECTS 214 practice attenders. STUDY MEASURES: Extent of psychological abnormalities with the General Health Questionnaire (GHQ), self-reported fatigue, in-clinic and home BP measurements. RESULTS No significant relationship between blood pressure levels and GHQ-score or fatigue could be demonstrated. This applies to clinic and home measurements for systolic and diastolic pressure. Neither adjustment for age or sex nor for several confounders through multiple linear regression produced significant associations in the postulated direction. No nonlinear relationship could be shown either. The study had a power of 95% to detect a correlation of r = 0.22 (alpha = 0.05, one-sided). CONCLUSION The study specifically addressing the possible link between blood pressure and psychological dysfunction/fatigue, could not confirm the previously reported association. Problems related to type-I error in epidemiological research are discussed.