Hormone therapy (HT) can prevent development of depressive symptoms among initially euthymic perimenopausal and early postmenopausal women, according to results of a study published in JAMA Psychiatry. Researchers performed a randomized clinical trial that looked at the efficacy of transdermal estradiol plus intermittent micronized progesterone (TE+IMP) compared to placebo.
The trial included 172 women aged 45 to 60 who were medically healthy and perimenopausal or postmenopausal. They were self-referred in response to community advertisements. The study used a randomized, double-blind, placebo-controlled design in which the participants were separated into two groups: a TE+IMP and a placebo group. The TE+IMP group was given 0.1mg of 17b-estradiol for 12 months and the placebo group received a placebo patch for the same amount of time. The TE+IMP group also received oral micronized progesterone (200 mg/d for 12 days) every 2 to 3 months. The placebo group received a placebo pill congruent with the TE+IMP schedule. Post-randomization study visits occurred at months 1, 2, 4, 6, 8, 10, and 12. Depressive symptoms were assessed at each study visit during the trial. The symptoms were measured using the Center for Epidemiologic Studies-Depression Scale (CES-D).
Of the 172 participants, 86 patients were randomized to placebo and 86 patients were randomized to TE+IMP. Sixty-nine patients in the placebo patients and 63 in the TE+IMP group completed treatment. The mean age of the patients was 51 and 43 patients developed clinically significant depressive symptoms. Women assigned to the placebo group were 32% more likely to develop a clinically significant depressive symptom than women in the TE+IMP group (32.3% vs 17.3%; odds ratio [OR], 2.5; 95% CI, 1.1-5.7; P = 0.03). A baseline reproductive stage moderated the effect of the hormone treatment (b, -1.97; SEM, 0.80, P = 0.03) and women who were in the early stages of menopause saw the greatest mood benefits between TE+IMP and placebo. Women in the late menopausal period (β, −0.9; SEM, 0.3; P = .23) and postmenopausal women (β, −0.3; SEM, 1.1; P = .92) did not have as strong benefits. The researchers also asked participants about stressful life events in the 6 months prior to the study. These events also moderated the effect of treatment on mean CES-D scores so that the mood benefits of TE+IMP increased with the greater number of events (β, 1.22; SEM, 0.40; P = .003).
The researchers said the strengths of the study were the comprehensive assessment of multiple psychosocial variables, its 12-month duration and bimonthly assessment of symptoms, and the fact that it was the first study to assess TE+IMP as a preventative measure. Weaknesses were identified as infrequent assessments of estradiol before and during treatment and that the active and placebo patches were not identical. The researchers believe the data show that 12 months of TE+IMP therapy is more effective than placebo in preventing clinically significant depressive symptoms among initially euthymic perimenopausal and early postmenopausal women. They note that if the findings are confirmed in future research, clinicians may consider using transdermal HT as a preventative measure to mitigate increased risk of depression during the menopausal transition and early postmenopausal period.
Does prenatal choline exposure promote cognition in infants?
According to research published in the Journal of the Federation of American Societies for Experimental Biology, when expectant mothers consume foods with high amounts of the nutrient choline, their offspring gain lasting cognitive benefits. Foods rich in choline include egg yolks, lean red meat, fish, poultry, cruciferous vegetables, legumes, and nuts.
The study included 29 pregnant women who were recruited through maternity clinics in Ithaca, NY. Eligible participants were at least 21 years old, entering their third trimester (self-reported) and were willing to comply with the study protocol, which required them to eat at least 5 meals per week on site and to consume only study-provided food and beverages. Of the 29 women recruited, 26 (90%) completed the protocol and 24 (83%) gave written, informed consent to have their infants participate in the cognitive-assessment part of the study.
The study participants were randomized to either 480 or 930 mg choline per day. They consumed at least one meal and drink per week under the supervision of study personnel, while the rest of their meals were provided as take-away food and eaten off-site.
After birth, maternal and newborn information was obtained from medical charts at the time of delivery. Following the choline intake part of the study, the mothers and infants met with the researchers for cognitive testing at ~4, 7, 10, and 13 months of age for the infant. The infants were given a visual attention task to measure latency of saccadic eye movement to locations on a display screen, in which animated pictures appeared. Saccades are quick simultaneous movements of the eyes that change the point of fixation and focus. The researchers tracked two types of saccades in this task: visually guided reactive saccades and memory-guided, anticipatory saccades. The study’s primary outcome was the mean saccade for infant saccade reaction time (RT) for the stimulus-guided fixation shifts. The secondary outcome was the number of predictive saccades.
For mean saccade RT, data were available for 139 of 192 (72%) possible participant visits and a total of 1477 stimulus presentation trials. Unadjusted regression analyses showed that, when averaged across all ages, the estimated mean saccade RT for infants in the group given 930 mg choline per day was 22.6 ms faster (CI 1.3-43.8 ms; P = 0.03) than the mean saccade RT for infants in the group given 480 mg per day of choline. Adjusted analyses from the a priori model showed a greater beneficial effect (33.8 ms; CI: 2.7-54.8 ms) when compared with the unadjusted model estimate.
The unadjusted model also revealed that infants produced more predictive saccades during predictable sequence than they did during the unpredictable baseline sequence (mean difference = 1.14; P < 0.0001). No significant effect of maternal choline intake during pregnancy was detected for the number of predictive saccades (mean difference =0.08l P = 0.07). Adjustment for covariates in the a priori model did not change the results (mean difference = 0.08; P = 0.06).
According to the researchers, reactive saccades provide an early measure of information processing speed, while anticipatory saccades do not generally provide reliable index of age-related changes during infancy, though they have been shown to predict IQ scores in childhood. Infrared corneal reflection videography was used to track and record the infants’ eye movements during the test.
The authors noted a few strengths and limitations of this study. The primary strengths of the study were the consistency and conformity of the food the participants were consuming. This kept the data clean and unblemished of external nutrients consumed outside the study. Another strength identified was that the participants were consuming at least one meal per week under supervision, which ensured that the two groups differed substantially in choline intake. Some weaknesses identified were the small sample size and the lack of cognitive assessments beyond infancy. In addition, the authors note that their choline implementation in the final trimester makes it impossible to predict the effects of a longer period of supplementation. However, the authors believe their findings suggest that since processing speed was much faster among infants in the higher choline intake group, choline intake should be recommended to mothers in the third trimester at a level exceeding the current adequate intake level recommendation.