Estrogen levels are associated with extinction deficits in women with posttraumatic stress disorder.

Biol Psychiatry. 2012 Jul 1;72(1):19-24. Epub 2012 Apr 12.

Glover EM, Jovanovic T, Mercer KB, Kerley K, Bradley B, Ressler KJ, Norrholm SD.

Abstract

BACKGROUND:
Women are twice as likely to develop posttraumatic stress disorder (PTSD) than men. As shown in our previous work, the inability to suppress fear responses in safe conditions may be a biomarker for PTSD. Low estrogen in naturally cycling women is associated with deficits in fear extinction. On the basis of these findings, we have now examined the influence of estrogen levels on fear extinction in women with and without PTSD.

METHODS:
We measured fear-potentiated startle during fear conditioning and extinction in women. The study sample (N = 81) was recruited from an urban, highly traumatized civilian population at Grady Memorial Hospital in Atlanta, Georgia. We assayed serum estrogen levels and used a median split to divide the sample into high and low estradiol (E(2)) groups. Seventeen of 41 women (41.5%) in the low E(2) group and 15 of 40 women (37.5%) met criteria for PTSD in the high E(2) group.

RESULTS:
The results showed that all groups had equivalent levels of fear conditioning. However, we found significant interaction effects between high versus low E(2) groups and PTSD diagnosis [F(1,71) = 4.55, p < .05] on extinction. Among women with low estrogen levels, fear-potentiated startle was higher during extinction in the PTSD group compared with traumatized control women [F(1,38) = 5.04, p < .05]. This effect was absent in the High E(2) group.

CONCLUSION:
This study suggests that low estrogen may be a vulnerability factor for development of PTSD in women with trauma histories. Research on the role of estrogen in fear regulation may provide insight into novel treatment strategies for PTSD.

PMID: 22502987

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The lowest levels of estrogen production are generally in the follicular phase of the menstrual cycle. Much of the estrogen at that time is produced by the adrenal glands. Thus low estrogen level predicts hypothalamic-pituitary-adrenal dysregulation, co-occuring with low production of other adrenal cortex hormones in response to stress.

I would predict these low-estrogen women also have low cortisol, DHEA-s, progesterone, testosterone, etc. in response to stress.

Estrogen – via its ability to act as an MAOI inhibitor – helps reduce norepinephrine signaling and the fear response.  Estrogen also promotes neuronal growth and development. Outside of the other deficits in adrenal hormones, a deficit of estrogen predisposes a woman to impairment in stress / fear response and adaptation.