The influence of estradiol and progesterone on neurocognition during three phases of the menstrual cycle: Modulating factors.

Estradiol is an ovarian steroid hormone that peaks shortly before ovulation and significantly affects various brain regions and neurotransmitter systems, with similar and differential effects with progesterone, another ovarian hormone. Studies investigating the neurocognitive processes during the menstrual cycle have focused on the early follicular phase (EFP) characterized by low estradiol and progesterone levels and the mid-luteal phase (MLP) with high estradiol and progesterone levels. However, most studies have failed to include the ovulatory phase, characterized by high estradiol and low progesterone levels. Given the various hormonal changes in the menstrual cycle, we revisited studies suggesting that the menstrual cycle did not affect verbal and spatial abilities and observed that many contain mixed results. Comparing these studies makes it possible to identify relevant modulating factors, such as sample size, participant age, accurate selection of days for testing, asymmetrical practice effects, genetic polymorphisms, and task difficulty. More robust findings are related to improved mental rotation capacity during EFP with challenging tasks and differences in brain activation among menstrual cycle phases during the execution of spatial and verbal tasks. During MLP, less robust findings were observed, possibly modulated by the complex effects of the two hormones on the brain. In conclusion, we propose that it is crucial to include all three menstrual cycle phases and consider these modulating factors to avoid confounding findings.

Sex, menstrual cycle, and hormonal contraceptives influences on global-local processing.

The effect of sex hormones on global-local tasks has rarely been studied, offering, when done, conflicting results possibly modulated by the congruency between hierarchical stimuli, and by the attentional demands. Here, we examined the global advantage (GA) effect in men (with high testosterone levels), women in the mid-luteal phase (with high levels of estradiol and progesterone), in the ovulatory phase (with high estradiol but low progesterone levels); and in the early follicular phase and with hormonal contraceptive (HC) use (with low sex hormone levels). The level of processing (global-local), the congruency (congruent vs. incongruent), and attentional demands (divided vs. selective) were manipulated. The divided-incongruent condition was sensible to estradiol and progesterone levels and, in this condition, mid-luteal women performed more locally while men performed more globally. The selective-incongruent condition was sensible to the testosterone level and, in this condition, men were faster. The HC group showed a congruency effect in the GA reaction times (RTs) during both, divided and selective conditions. Finally, the GA RTs of the ovulatory group differed from the early follicular and mid-luteal groups only in the congruent-selective condition, but the performance was not related with sex hormone levels. This result is interpreted in relation with the brain effects of estradiol in the absence but not in the presence of progesterone. Thus, sex, menstrual cycle, HC, task difficulty and sex hormones seem to modulate performance in the global-local task. These factors represent an important source of variability in studies focused on the processing of hierarchical stimuli and allow apparently inconsistent data to be explained.

Influence of sex, menstrual cycle, and hormonal contraceptives on egocentric navigation with or without landmarks.

This study examines the influence of sex, menstrual cycle, hormonal contraceptives (HC) and sex hormone levels in following egocentric navigation instructions with or without landmarks. Estradiol seem to bias the reference frame for navigation during estrous cycle of female rats. However, previous studies in humans found no differences in overall navigation between women in their early follicular and mid-luteal menstrual cycle phases, whose performance was worse than that of men. Our study hypothesis was that the performance of women would be improved during the peri-ovulatory phase and would remain the same during placebo and active phases of HC users. The study included 21 men, 62 women with natural menstrual cycle (21 during early follicular phase, 20 during peri-ovulatory phase, and 21 during mid-luteal phase), and 38 women that were receiving HC (13 during placebo phase and 25 during active phase). The men outperformed the women with a natural menstrual cycle when following egocentric instructions without landmarks. However, the women's performance varied according to the phase of their menstrual cycle, differing from men during early follicular and mid-luteal phases but not during the peri-ovulatory phase. The use of HC also improved the performance of women to the extent that the difference with men disappeared. No differences were observed between HC-placebo and HC-active user groups during egocentric navigation without landmarks and among all groups during egocentric navigation with landmarks. Analysis of salivary hormones showed that testosterone levels were higher in men and that estradiol levels in women were higher during peri-ovulatory and mid-luteal phases and also in HC users. Progesterone levels were higher in women during the mid-luteal phase. These results appear compatible with beneficial effect of testosterone and estradiol on egocentric navigation without landmarks and with a block of this effect produced by progesterone.