Championing the role of estrogen in brain biochemistry.

As a neurochemist, I am dismayed (again) to see a reference in Tori Hudson's column, on migraine this time, to the recommendation of significantly low doses of 17 beta-estradiol. In over ten years of researching women's brain biochemistry and mood disorders, we have seen that not having enough E2 is the critical distinction for many disorders, including headaches. Certainly not E2 dominance. Specifically, enough estradiol must be present in order to stabilize Ca+ + intracellular signaling, which is suggested by laboratory data to be dependent on "E2 mediated neuroprotection" (Nilsen J, Brinton RD. Estrogen regulation of mitochondrial function. Proc Natl Acad Sci. 2003).

Many women are not responsive to estradiol until they get enough: this is a dismal side effect we have seen from "holistic" laboratory protocols, such as saliva tests for gender hormones, which do not coordinate with symptoms and have told many women they were estrogen-dominant when, in fact, all key symptoms pointed to the opposite, which serum tests confirmed.

Much of the cascade of "neurologic symptomology," which Tori Hudson, ND asserts is fundamental to migraine, may well be triggered by the initial and precipitous decline in E2, which dampens the cholinergic basal forebrain function, which is primary to cognitive function. Progesterone is a critical secondary molecule but is not as good in oral form because of the way it is metabolized. Therefore, women who need the calming effect of progesterone during the day get sleepy instead of calm. Compounded topical hormones, properly dosed, have the best chance to help individual women without using a myriad of pills, patches, and creams. Many women have reported that they feel agitated on the patch--be it Vivelle or Climara--because they are out of balance and need proper dosing and other hormones and, most significantly, proper amounts of 17 beta-estradiol or E2 and progesterone.

The Journal of Orthomolecular Medicine has just published "In Defense of Estrogen." That article can be ordered through The International Society of Orthomolecular Medicine in Toronto.

Phyllis J. Bronson, PhD

Biochemical Consulting Company

Biochemical Research Foundation, Aspen

Associate Professor, University of Denver: Department of Chemistry/Biochemistry

Aspen Clinic Internal Medicine

100 E. Main Street, Aspen, Colorado 81611; 970-920-2523

Tori Hudson responds:

I think we are in agreement here, and I think my article states the important role of estrogen quite clearly. I state the following in my article on migraines:

  For women, proper management of migraines may also need to include the
  consideration of their hormonal situation. Migraines can be related in
  timing to the menstrual cycle, when there are fluctuations in our
  hormones that then affect the brain chemistry and vasculature. Some
  women may find their migraines are worse before or during or after
  their menses. This then may require altering or balancing their
  hormonal environment to get the best results. My best results come
  with using an estradiol patch (for example, Climara 0.05 mg patch)
  applied one week before the onset of menses and left on the whole
  week.

Further in the article, I state and support your position:

  As with menstrual migraines, migraines at perimenopause may require
  altering or balancing or stabilizing the hormonal environment. In
  perimenopause, this may require using a compounded estrogen with
  progesterone formulation, cycling it, three weeks on and one week off.
  Or the patient may need her estrogen in very steady doses, in which
  case, give the estrogen daily and then cycle the progesterone because
  the patient is still having a menses (for example: Estriol 1 mg/
  Estradiol 0.25 mg/ Progesterone 50 mg, one cap twice daily, three
  weeks on and one week off; or Estriol 1 mg/ Estradiol 0.25 mg, one cap
  twice daily, continuously, and then oral micronized progesterone, 200
  mg before bed, days 15-26.)

I'm surprised you brought up the issue of estrogen dominance and saliva testing as I did not mention or advocate either of those and, again, I agree with you. For our readers, let me restate that the concept of estrogen dominance is not a cause of migraines but, in fact, the opposite: unstable and low estrogen is involved in the etiology of migraines in a significant number of women. I have had excellent experience using estrogen in premenopausal and perimenopausal women with premenstrual/perimenstrual migraines. I did not at all discuss laboratory testing in my article, but again, we would agree, it seems, as I also do not advocate for saliva testing of estrogen or progesterone as a useful tool in symptom management.

In my 23 years of experience in women's health and my study of the literature on migraines in women, I've found it quite clear that estrogen very much affects brain chemistry involved in migraines. I find great benefit in the use of estrogen for migraines in women, much more so than progesterone, but not at the exclusion of progesterone. The dose and delivery system is very individual to each case--based on symptoms, cost, compliance, patient's personal preference, and other medical considerations.

It seems as though, rather than your proposed disagreement as to the role of estrogen in the etiology of migraines in women, we actually agree. I hope that with a second read of my article, you will find comfort in my mention of that and confirmation of your work and research. A detailed article from you on the role of estrogen and women's brain biochemistry and mood disorders would be a great contribution.