Queen Esther's Fight or Flight Reaction

אסתר 4:4

וַ֠תָּבוֹאינָה נַעֲר֨וֹת אֶסְתֵּ֤ר וְסָרִיסֶ֙יהָ֙ וַיַּגִּ֣ידוּ לָ֔הּ וַתִּתְחַלְחַ֥ל הַמַּלְכָּ֖ה מְאֹ֑ד וַתִּשְׁלַ֨ח בְּגָדִ֜ים לְהַלְבִּ֣ישׁ אֶֽת־מָרְדֳּכַ֗י וּלְהָסִ֥יר שַׂקּ֛וֹ מֵעָלָ֖יו וְלֹ֥א קִבֵּֽל׃

When Esther’s maidens and eunuchs came and informed her, the queen was greatly agitated. She sent clothing for Mordecai to wear, so that he might take off his sackcloth; but he refused.

The meaning of the verse seems straightforward enough. Esther learned that throughout the empire, Jews were fasting, weeping and wailing, (although she did not yet know why). This greatly upset or"agitated" her.  But in the Talmud, Rav (d. ~247) and his student Rabbi Yirmiyah are not content with this straightforward reading. 

מגילה טו, א

ותתחלחל המלכה מאי ותתחלחל אמר רב שפירסה נדה ור' ירמיה אמר שהוצרכה לנקביה 

What is the meaning of the word ותתחלחל? Rav said: It means that she started to menstruate. R. Yirmiyah said: that her bowels were loosened.
   Esther before Ahasuerus   by Jacopo Tintoretto (1519-94). From The Royal Academy of Arts, London.

Esther before Ahasuerus by Jacopo Tintoretto (1519-94). From The Royal Academy of Arts, London.

FIGHT OR FLIGHT

Any of us who have have experienced moments of intense fear or anxiety can understand R. Yermiah's explanation. In moments of sudden severe stress, the body's sympathetic nervous system ("fight or flight") goes into overdrive and releases epinephrine (AKA adrenaline). This prepares us for battle: our heart rate increases, blood is diverted away from the digestive system and towards the muscles, and our pupils dilate, to allow for better vision. At the same time the  parasympathetic nervous system ("rest and digest") is partially activated, which results in urination and defecation (or at least the urge to do so). 

  Brain circuits involved in fear and anxiety.  A schematic view of major brain circuits involved in fear and anxiety. External auditory, visual, olfactory, or somatosensory stimuli are relayed by the thalamus to the amygdala and cortex. The basolateral complex (BLA) of the amygdala is the input side of the system, which also receives contextual information from the hippocampal formation (entorhinal cortex, hippocampus, and ventral subiculum). After intra-amygdala processing of the emotional stimuli, the central nucleus of the amygdala (CeA), on the output side, activates the locus ceruleus (LC) and central and peripheral noradrenaline systems (via corticotropin-releasing factor [CRF] neurons), and the hypothalamus (paraventricular nucleus [PVN] and lateral hypothalamus [LH]). The bed nucleus of the stria terminalis (BNST, part of the “extended amygdala”) is also a control center for the neuroendocrine system by integrating information originating from both the hippocampus and the amygdala. In addition, the CeA directly activates various midbrain regions or nuclei responsible for different aspects of the fear/anxiety response: freezing or escape (periaqueductal gray [PAG]), increased respiratory rate (parabrachial nucleus [PBN]), startle (caudal reticulopontine nucleus of the reticular formation [RPC]), and the dorsal motor nucleus of the vagus (DMN) in the medulla, which (together with the lateral hypothalamus) is responsible for the increase in heart rate and blood pressure associated with emotional events. The prefrontal cortex (PFC) processes more elaborate (“cognitive”) information; it modulates the physiological, neuroendocrine, and behavioral responses (via the amygdala), and it is also involved in the extinction of fear- and anxiety-related conditional responses. ACTH, adrenocorticotropic hormone; ANS, autonomous nervous system; BP, blood pressure; GABA, γ-aminobutyric acid; Glu, glutamate; NA, noradrenaline (neurotransmitter) or nucleus ambiguus (structure); NTS, nucleus tractus solitarius. From Steimer, T. The biology of fear- and anxiety-related behaviors.   Dialogues in Clinical Neuroscience  -  Vol 4 . No. 3 . 2002, 231-249.

Brain circuits involved in fear and anxiety. A schematic view of major brain circuits involved in fear and anxiety. External auditory, visual, olfactory, or somatosensory stimuli are relayed by the thalamus to the amygdala and cortex. The basolateral complex (BLA) of the amygdala is the input side of the system, which also receives contextual information from the hippocampal formation (entorhinal cortex, hippocampus, and ventral subiculum). After intra-amygdala processing of the emotional stimuli, the central nucleus of the amygdala (CeA), on the output side, activates the locus ceruleus (LC) and central and peripheral noradrenaline systems (via corticotropin-releasing factor [CRF] neurons), and the hypothalamus (paraventricular nucleus [PVN] and lateral hypothalamus [LH]). The bed nucleus of the stria terminalis (BNST, part of the “extended amygdala”) is also a control center for the neuroendocrine system by integrating information originating from both the hippocampus and the amygdala. In addition, the CeA directly activates various midbrain regions or nuclei responsible for different aspects of the fear/anxiety response: freezing or escape (periaqueductal gray [PAG]), increased respiratory rate (parabrachial nucleus [PBN]), startle (caudal reticulopontine nucleus of the reticular formation [RPC]), and the dorsal motor nucleus of the vagus (DMN) in the medulla, which (together with the lateral hypothalamus) is responsible for the increase in heart rate and blood pressure associated with emotional events. The prefrontal cortex (PFC) processes more elaborate (“cognitive”) information; it modulates the physiological, neuroendocrine, and behavioral responses (via the amygdala), and it is also involved in the extinction of fear- and anxiety-related conditional responses. ACTH, adrenocorticotropic hormone; ANS, autonomous nervous system; BP, blood pressure; GABA, γ-aminobutyric acid; Glu, glutamate; NA, noradrenaline (neurotransmitter) or nucleus ambiguus (structure); NTS, nucleus tractus solitarius. From Steimer, T. The biology of fear- and anxiety-related behaviors. Dialogues in Clinical Neuroscience - Vol 4 . No. 3 . 2002, 231-249.

Queen Esther's Stress

As we saw in Megillah, Rav opined that fear can induce menstrual bleeding. In Sotah, the Talmud further delineates the effect of stress on menstruation.

סוטה כ, ב

למימרא דבעיתותא מרפיא אין דכתיב ותתחלחל המלכה מאד ואמר רב שפירסה נדה והא אנן תנן חרדה מסלקת דמים פחדא צמית ביעתותא מרפיא

Does fright loosen the womb [and causes a woman to menstruate]? Yes, as the verse states (Esther 4:4) "...and the Queen [Esther] became very afraid" about which Rav explained:" she began to menstruate."
But haven't we learned elsewhere in a Mishnah (Niddah 39a) that fear suspends the discharge of menstrual blood? In fact, fear that is not sudden contracts [the womb and prevents bleeding], but sudden fear loosens [the womb and causes early menstrual bleeding].

Here are some of the things that the rabbis of the Talmud believed could induce menstruation:

  1. Carrying a heavy load (Tosefta Niddah 9:1)
  2. Jumping (ibid)
  3. Sudden fright (Niddah 71a, and Niddah 39a)
  4. Yearning for intercourse (Niddah 20b)
  5. Garlic, onions and peppers (Niddah 63b)

Let's take a look at the medical literature and see whether or not it supports Rav's assertion.

Data from both animal and human research indicate that psychological stress is associated with altered menstrual function.
— Barsom S, et al. Association between psychological stress and menstrual cycle characteristics in perimenopausal women. Women’s Health Issues 14 (2004) 235-241

The Effect of Stress on Menstrual Function

In a review from the Department of Biological Sciences at Ohio University, researchers acknowledged that stress is difficult to define. However, one final common pathway of stressors is the low availability of dietary energy. Ovulation - which is the first part of the cascade that leads to menstruation - has been blocked in hamsters "by food restriction, pharmacological blockers of carbohydrate and fat metabolism, insulin administration (which shunts metabolic fuels into storage), and cold exposure (which consumes metabolic fuels in thermogenesis)." Women athletes frequently experience a lack of menstruation, which is found in up to 65% of competitive young runners. But what about psychogenic causes of a disturbed menstrual cycle - after all, Rav taught that it was fear that caused Esther's presumably early onset of menstruation? While not adressing this directly, the Ohio University researchers had this to say about the relationship between psychological stressors and amenorrhea (the lack of menstruation. Remember that word - it will come up again):

Associations between psychological disturbances and amenorrhea or infertility have long been interpreted as a causal relationship, but prospective studies demonstrating that psychogenic factors contribute to reproductive dysfunction in women are almost completely lacking . Early psychoanalytic conclusions that psychological conditions underlie involuntary infertility in women have been criticized recently on several grounds: first, the same psychological conditions have been found in analyses of fertile women; second, other women with very serious psychic problems conceive with ease; and third, couples with an unfulfilled desire for a child do not show psychological disorders any more frequently than do couples without fertility disorders. Even the direction of causality is questionable, because there are grounds for believing that infertility and its medical treatment cause the depression and anxiety observed in some infertility patients. These findings have led to the recommendation that the term ‘psychogenic infertility’ should be withdrawn from use because it is simplistic and anachronistic. 

Menstruation and Incarceration

Some of the rabbis viewed Esther's association with King Achashverosh as being coerced: she was brought to his palace against her will, and remained there in a similar state. So with only a bit of a stretch, we might turn to a 2007 paper published in Women's Health Issues which addressed the influence of stress on the menstrual cycle among newly incarcerated women.  Researchers analyzed 446 non-pregnant women who answered a number of detailed questions about their menstrual cycles.  They found that 9% reported amenorrhea (I told you what that meant two paragraphs ago) and that a third reported menstrual irregularities.  

Incarcerated women have high rates of amenorrhea and menstrual irregularity and the prevalence may be associated with certain stresses. Further research on the causes and consequences of menstrual dysfunction in this underserved population is needed.
— Allsworth J. et al. The influence of stress on the menstrual cycle among newly incarcerated women. Women's Helath Issues 2007; (17) 202-209.

As might be expected, the stressors of the incarcerated women in this study included drug and alcohol problems and sexual abuse. These are not the same stressors that faced Queen Esther - who was held in such esteem by her kingly husband that he promised her (Esther 5:6) "up to half of the kingdom."  But this work does show how stress may impact the menstrual cycle.  

A Longitudinal Study of Psychological Stress and Menstruation

The final study we will review comes from a cohort of predominantly white, well educated married women of whom 505 were "invited to participate join a special survey focusing on midlife and menopause." Rather than ask about stress and current menstruation, the researchers performed a two-year analysis. Here's what they found:

In analyzing stress levels and cycle characteristics across 2 years...women with marked increases in their level of stress (n =30) are shown to have decreased length (0.2 days/cycle) of menstrual cycle intervals and decreased duration of bleed (0.1 day/cycle) compared with increases in these measures (2.9 days/cycle for cycle interval; 0.3 days/cycle for duration of bleed) among women with no marked change in stress level (n =103); t-tests indicate that these differences are significant (p < .05). 

Some of the differences that the researchers found in this group were really small - "0.3 days/cycle for duration of bleeding" but if you are into statistics this difference can be significant (that's what those t-tests are all about). But these statistical associations were not powerful, and the researchers concluded that "the results of this investigation...suggest that, in the long term, stressful life events have little relationship to the length of menstrual cycle intervals and the duration of menstrual bleeding in perimenopausal women."

The three studies we've reviewed (even that last one with its weak findings) all suggest that there is indeed some relationship between psychological stress and menstruation.  Generally, the effect of stress is to increase the length of the menstrual cycle which may result in amenorrhea.  This finding  is also mentioned in Sotah 20b:   "פחדא צמית - chronic fear contracts [the uterus and prevents menstruation]."  But according to Rav, stress caused Esther to menstruate sooner - the opposite of most modern research findings.  Single events should be used with caution when trying to build a general explanatory model, but Rav, and the other rabbis of the Talmud were onto something when they noted that both acute and chronic fear (which is of course just one type of stress) -  can effect a women's menstrual cycle.  

[Partial repost from Sotah 20.]

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