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The Migraine Cure

December 2006

By Sergey A. Dzugan, MD, PhD


While pregnenolone is the grandmother of hormones—and the precursor of dehydroepiandrosterone (DHEA)—DHEA is the mother, because it is a precursor for the estrogens and testosterone.

While low levels of DHEA are associated with aging, they also have been linked with various health problems, including but not limited to migraine, chronic inflammation, depression, rheumatoid arthritis, memory and concentration difficulties, osteoporosis, heart disease (in men), increased risk for some cancers, and complications of type II diabetes. On the positive side, taking DHEA supplements to restore the hormone to youthful levels can help treat many of these same conditions.

One of the main functions of DHEA is to counteract the stress-damaging actions of cortisol. Maintaining an optimal DHEA-to-cortisol ratio is not only a critical key to anti-aging, but also important for achieving hormone balance and eliminating migraine.

Your body's production of DHEA can be reliably identified by measuring the amount of DHEA-sulfate (DHEA-S) in a blood sample. The goal of DHEA supplementation is to restore levels to their youthful (age 20-29) range. For men, the optimal range is 500-640 ug/dL; for women, 250-380 ug/dL. The usual daily dose is 50-100 mg taken as an oral supplement.

Because DHEA is a precursor for the estrogens and testosterone, it can have some effect on increasing the levels of these hormones. That is why it is important for women to undergo periodic blood tests to have the levels of these hormones checked.

Quite often, we also recommend that individuals take 7-keto DHEA in addition to a regular DHEA supplement; 7-keto DHEA is a metabolite of DHEA (a product of DHEA metabolism). Perhaps the most important feature of 7-keto is that, unlike DHEA, it does not convert to estrogen and testos-terone. Therefore, availability of the supplement 7-keto DHEA allows you to take a lower dose of DHEA, which helps balance estrogen and testosterone levels and keeps cortisol levels in check.

Estrogen and Progesterone

Estrogen and progesterone are produced naturally by the body and typically thought of as female sex hormones. Indeed, females typically have higher levels of these two hormones than do males, but both estrogen and progesterone are found in people of both sexes and of all ages.

The roles of estrogen and progesterone in migraine are both critical and complex. I have grouped these two hormones together because they are so intimately connected, and because we have found that it is the balance between them, and not the restoration of optimal levels individually, that is critical for elimination of migraine, as well as of the many symptoms women experience during perimenopause and menopause.

A Power Trio: The Estrogens

"Estrogen" is actually a blanket term for several types of the hormone, of which three—estriol, estradiol, and estrone—are the most important.

When the three estrogens are present and in proper balance with each other and with other steroid hormones, health and well-being are maintained. All three estrogens work together to support the central nervous system, determine female physical characteristics, minimize loss of calcium from bone, enhance skin health, promote blood clotting, and support ovulation, among other functions. Although all three play critical roles in the body, they are not equal in terms of safety or benefits.

Estradiol and estrone, for example, along with their positive features, have cancer-causing abilities, and the body naturally allows for this negative characteristic by producing lower levels of these estrogens compared to the so-called "good" estrogen, estriol. In fact, estriol is believed to have cancer-reducing properties. Thus, the normal, healthy breakdown of total estrogens in women is 60-80% estriol, and 10-20% each of estradiol and estrone.

Estrogen and Migraine

The relationship between estrogen levels and the development and elimination of migraine is an intimate one. Here is what we know about estrogen and migraine:

  • The prevalence of migraine increases at menarche (when a female's menstrual cycle first begins).
  • The decline in estrogen levels just before menstruation triggers migraine in many women.
  • Migraines usually decline during the second and third trimesters of pregnancy, when estrogen levels are high.
  • Migraines commonly occur immediately after a women gives birth, as estrogen levels decline dramatically.

The form of bioidentical estrogen that I recommend is Triest gel, which I recommend be taken in a formulation that consists of 90% estriol, 7% estradiol, and 3% estrone. A compounding pharmacy can prepare this specific formulation for you. This formulation is most advantageous for women, especially those older than 35, because it provides a large percentage of safe estrogen (estriol), along with the other two types of estrogen. This gel should be applied in the morning after bathing, to areas such as the neck, forearm, or sides of the chest or abdomen.

Progesterone: The "Other" Female Hormone

The balance between estrogen and progesterone is critical in the elimination of migraine, so let us look a little closer at how this important hormone works.

Progesterone levels in the body naturally rise and fall during a woman's monthly cycle. Women can begin to miss ovulations as early as their mid-thirties, and missed ovulations become more common as perimenopause approaches. The combination of missed ovulations and the approach of menopause usually results in progressively lower levels of progesterone, which contribute to an imbalance with estrogen, whose levels are also always changing. This imbalance explains why many women begin to experience symptoms of perimenopause in their mid- to late thirties and forties, and also why the peak incidence of migraine for women is between the ages of 35 and 45.

When we talk about progesterone therapy or supplementation, there are two types available: bioidentical progesterone, which is chemically the same as the progesterone produced by the human body, and thus behaves like the body's natural progesterone; and synthetic progesterone-like substances called progestogens or progestins.

One of the first people to discover the benefits of natural progesterone was Dr. John Lee. When he recommended natural progesterone cream to his patients for symptoms of menopause, they reported relief from hot flashes, insomnia, bladder problems, dry eyes, irritability, hair loss, sore breasts, night sweats, and bloating, among other symptoms.

The formulation of natural progesterone I recommend and use in The Migraine Cure is micronized progesterone USP. Micronized progesterone is also available as a gel (transdermal form), which is the form I recommend for migraine as well as for other conditions that benefit from hormone balancing.

The micronized gel I recommend is available through compounding pharmacies, delivers 50 mg/mL, and should be applied in doses that simulate a woman's monthly cycle. An alternative is an over-the-counter micronized cream product called ProFem.


Testosterone is typically characterized as the male hormone, the one responsible for the normal development of male sex and reproductive organs, and the development of secondary male sex traits, including hair growth (and loss) patterns, thickening of the vocal chord, muscle development, and other characteristics. Normal testosterone levels are necessary to maintain healthy mood, energy level, bone marrow production, fertility, and sexual desire. Females also need testosterone; their levels need not be as high as those of males, but their optimal levels should be sufficient to maintain good health. Testosterone levels need to be in balance to eliminate migraine in men and women as well.

Measurement of testosterone levels is part of the male and female hormone panels that are used to identify the levels of other steroid hormones. The optimal range for men is 650-827 ng/dL; for women, 60-76 ng/dL.

Testosterone supplements are available in oral form (capsules, pills), by injection, through a transdermal patch, and in a gel. I recommend the latter form because it allows for individualized dosing and is easy to use. Although it is necessary to balance testosterone levels with the other steroid hormones as part of The Migraine Cure, that balance is frequently achievable without an individual having to use a testosterone supplement (mostly in younger people). In women, correct levels of DHEA can convert into testosterone whenever the body recognizes that levels are low. Thus, careful use of DHEA (a precursor of testosterone) restoration can help some women reach their optimal levels, while others need a testosterone supplement, at least temporarily.

Treatment Enhancements: Zinc and Palmetto

In males, saw palmetto (Serenoa repens), an herb that grows naturally in the southeastern United States, is often used to help prevent prostate enlargement. That is because this herb blocks the conversion of testosterone to dihydrotestosterone (DHT), a substance that, among other things, stimulates growth of the prostate gland and causes hair loss. Specifically, saw palmetto inhibits the activity of 5-alpha-reductase, the enzyme that converts testosterone to DHT.

Zinc can block aromatase enzyme, the factor that converts testosterone into estrogen. The addition of zinc could help facilitate an estrogen-progesterone balance.

Most individuals who participate in The Migraine Cure need to take saw palmetto and/or zinc. When a female has symptoms that are associated with testosterone dominance, supplementing with this herb and nutrient can be beneficial. The typical dose of saw palmetto is 160 mg once daily, while the dose of zinc can range from 15 to 90 mg.