Evidence for a Role of Progesterone in Menstrual Cycle-Related Variability in Prepulse Inhibition in Healthy Young Women

Abstract

Prepulse inhibition (PPI) of the startle response is sensitive to sex, with healthy young women showing less PPI compared with age-matched men, and varies according to the menstrual cycle phase in women. Relatively less is known regarding sex and hormonal influences in prepulse facilitation (PPF). Menstrual phase-related variability in PPI is suggested to be mediated by fluctuating estrogen level, based on the observations of more PPI in women during the follicular, relative to the luteal, phase. No study has directly assessed the relationship between fluctuating hormones and PPI or PPF levels over the human ovarian cycle. To examine the roles of circulating ovarian hormones in PPI and PPF, 16 non-smoking regularly menstruating healthy women were tested during both the follicular and luteal phases on PPI and PPF and provided saliva samples for measurement of 17b-estradiol (estrogen), progesterone and testosterone. The results showed higher levels of 17b-estradiol and progesterone during the luteal, relative to the follicular, phase; and more PPI during the follicular phase and more PPF during the luteal phase with comparable startle amplitude and habituation during the two phases. A larger increase in progesterone was associated with a smaller decrease in PPI from the follicular to the luteal phase. No significant associations were found between changes in PPI/PPF and estrogen levels. The findings confirm lower PPI during the luteal, compared with the follicular, phase and suggest a role for progesterone, more specifically an antipsychotic-like PPI-restoration action of progesterone, during the luteal phase in PPI of young women.

The impact of sex and menstrual cycle on the acoustic startle response

“…Contrary to our findings, no differences in ASR between follicular and luteal phase were reported in healthy women in several studies [43,45,46]. However, in some of these studies the investigated samples were comparatively small which would have made it harder to detect a rather minor effect.…”

“…However, in another study PMDD patients showed heightened ASR during both the follicular and the luteal phase compared to healthy women while there was no difference in ASR between the two cycle phases within the PMDD or the healthy control group [44]. Similarly, Jovanovic et al [45] and Kumari et al [46] found no differences in ASR magnitudes during follicular vs. luteal cycle phase in healthy samples although a significant effect of menstrual cycle phase was found on PPI [45]. Jovanovic et al also investigated the influence of menstrual cycle phase in a longitudinal approach in 14 women.…”

Sensorimotor gating in healthy adults tested over a 15 year period

“…Kumari et al 2011), with some less common exceptions in human reports, perhaps attributable to the fact that these sex differences are moderated by menstrual phase (Swerdlow et al 1997; Jovanovic et al 2004) and other factors potentially related to reproductive hormones (e.g. Bannbers et al 2010; Kumari et al 2010; Comasco et al 2015, 2016). Male > female PPI was evident in the present sample, and this group difference increased modestly when samples were limited to women of child-bearing years and to non-smokers.…”

Heritability of startle reactivity and affect modified startle

“…It has been previously shown that females tend to rate negative-valence pictures as more unpleasant than males and have greater defensive reactivity to negatively-valence pictures, as measured by a number of autonomic responses (Bradley, Codispoti, Sabatinelli, & Lang, 2001). In studies of pre-pulse inhibition, females display lesser inhibition in comparison to males (Kumari, 2003; Swerdlow, et al, 1993) and this effect has also shown to be sensitive to the menstrual phase (Kumari, et al, 2010). Considering the notable differences in defensive reactivity and sensorimotor gating between males and females, it is plausible that the relative contributions of genetic and environmental influences to startle reactivity and AMS also differ between the two sexes.…”