Longitudinal changes in menopausal symptoms comparing women randomized to low-dose oral conjugated estrogens or transdermal estradiol plus micronized progesterone versus placebo: the Kronos Early Estrogen Prevention Study.

OBJECTIVE: The objective of the present study was to compare the efficacy of two forms of menopausal hormone therapy in alleviating vasomotor symptoms, insomnia, and irritability in early postmenopausal women during 4 years. METHODS: A total of 727 women, aged 42 to 58, within 3 years of their final menstrual period, were randomized to receive oral conjugated estrogens (o-CEE) 0.45 mg (n = 230) or transdermal estradiol (t-E2) 50 µg (n = 225; both with micronized progesterone 200 mg for 12 d each mo), or placebos (PBOs; n = 275). Menopausal symptoms were recorded at screening and at 6, 12, 24, 36, and 48 months postrandomization. Differences in proportions of women with symptoms at baseline and at each follow-up time point were compared by treatment arm using exact χ tests in an intent-to-treat analysis. Differences in treatment effect by race/ethnicity and body mass index were tested using generalized linear mixed effects modeling. RESULTS: Moderate to severe hot flashes (from 44% at baseline to 28.3% for PBO, 7.4% for t-E2, and 4.2% for o-CEE) and night sweats (from 35% at baseline to 19% for PBO, 5.3% for t-E2, and 4.7% for o-CEE) were reduced significantly by 6 months in women randomized to either active hormone compared with PBO (P < 0.001 for both symptoms), with no significant differences between the active treatment arms. Insomnia and irritability decreased from baseline to 6 months postrandomization in all groups. There was an intermittent reduction in insomnia in both active treatment arms versus PBO, with o-CEE being more effective than PBO at 36 and 48 months (P = 0.002 and 0.05) and t-E2 being more effective than PBO at 48 months (P = 0.004). Neither hormone treatment significantly affected irritability compared with PBO. Symptom relief for active treatment versus PBO was not significantly modified by body mass index or race/ethnicity. CONCLUSIONS: Recently postmenopausal women had similar and substantial reductions in hot flashes and night sweats with lower-than-conventional doses of oral or transdermal estrogen. These reductions were sustained during 4 years. Insomnia was intermittently reduced compared with PBO for both hormone regimens.

Assessing comprehension of clinical research.

BACKGROUND: Comprehension and retention of study-related concepts by research subjects are understudied, particularly in certain areas of women's health such as menopausal hormone therapy (MHT). METHODS: In a multi-center trial of MHT, a 9-item participant comprehension questionnaire (PCQ) tested knowledge of key concerns relating to MHT at two study sites. The PCQ was administered at baseline. At study site1, PCQ was re-administered to assess information retention months later. Multivariable analyses assessed predictors of participant comprehension after adjusting for age, race, education, annual family income (AFI), menopausal symptoms and study site. RESULTS: 151 participants (n = 89 at site I, n = 62 at site II) completed the PCQ at baseline; 71 participants from site I completed the follow-up PCQ. Participant comprehension at baseline was influenced by age, marital status, education, symptom of dyspareunia, season of enrollment and AFI<$40,000. Significant improvement in correct responses was observed at follow-up compared to baseline (p = 0.02); season and low AFI<$20,000 were predictive of likelihood for correctly answering <5/9 at follow up. CONCLUSION: Assessing participant comprehension of research-related concepts using a PCQ identifies a need for ongoing reinforcement of relevant details, especially in symptomatic early menopausal women of lower education and income. Improved participant comprehension at follow up is reassuring and reflects success of the research team in communicating study-related concepts to participants enrolled in longitudinal studies.