Maintaining hormonal balance is now recognized as an important goal in women's health.

Using the diet to beneficially influence estrogen metabolism is a safe approach to resisting age-related hormonal changes. DIM supplements actively promote a desirable estrogen metabolism that produces more of the good estrogen metabolites. Use of microencapsulated DIM supplements by thousands of women has demonstrated benefits for painful breasts, improvement in painful menstruation, and improvement in uterine and cervical health. Hormonal balance also involves benefits from the small amount of free testosterone present in women. DIM's specific benefits for women are covered in this chapter.

What makes optimal estrogen metabolism so important for women?

Q. Optimal estrogen metabolism in women is defined by the ample production of good estrogen metabolites. These metabolites help to lower the risk of cancer and to decrease the symptoms of estrogen overstimulation, or dominance-symptoms of which include breast tenderness, rapidly growing uterine fibroid tumors, uterine cervix problems (as seen with abnormal Pap smears), and endometriosis, a painful condition caused by persistent uterine tissue growing in abnormal locations within the abdomen. Having higher levels of the good estrogen metabolites is also important for sustaining an active fat-burning metabolism. Good metabolites help fat cells release stored fat. They are also important in preserving the activity of the small amount of testosterone present in all women. This provides additional support for fat utilization, as well as support for mood and libido.

Healthy levels of testosterone in women also may help to reduce the symptoms of premenstrual syndrome. Finally, the good estrogen metabolites have important antioxidant activity exceeding the potency of vitamin E. The antioxidant activity of the good estrogen metabolites may explain why estrogen in women can slow the course of some age-related diseases. These include heart disease, atherosclerosis (also known as “narrowing of the arteries"), arthritis, and cancer.

Q. What happens to hormonal balance as a woman ages?

A. Hormonal balance begins to falter as early as the late twenties, as shown by diminishing progesterone

production with some monthly menstrual cycles. Eventually, usually in the early forties, menstrual cycle length becomes less regular. During this time period, known as perimenopause, estrogen production by the ovaries fluctuates. Excess production of estrogen accompanies multiple early ovarian follicles during some months, while estrogen is deficient in other months when ovulation doesn't occur. Higher levels of unmetabolized, active estrogen and faltering progesterone production during this time of life are associated with the symptoms of estrogen dominance. Many of these conditions, including breast tenderness, endometriosis, uterine fibroids, and cervical dysplasia, have been observed to improve with DIM supplementation.

With further aging, women may experience a lack of another natural steroid, dehydroepiandrosteroneDHEA). DHEA, which comes from the adrenal glands, is another source of estrogen and testosterone in women besides the ovaries. Low DHEA levels can hamper the estrogen-to-testosterone balance during perimenopause. Supplemental DHEA has been shown to support bone health and to improve systemic lupus erythematosus (SLE)-an autoimmune condition-which has been associated with low levels of good estrogen metabolites.

Moreover, in perimenopausal women, fluctuating estrogen levels and a failure to ovulate can contribute to reduced progesterone production. In fact, progesterone deficiency has been used as a hallmark of perimenopause. Interestingly, the good estrogen metabolites can boost production of progesterone from ovarian cells. This implies that much of the effects during perimenopause can be attributed to a slowed estrogen metabolism. The use of "natural” progesterone, especially through skin creams, has become a popular means of restoring progesterone. But, adding progesterone will not serve to improve estrogen metabolism or bring higher estrogen levels back into balance.

Q. Can DIM replace the use of progesterone during perimenopause?

A. Although DIM-induced good estrogen metabolites have been shown to increase the production of progesterone by ovarian cells, this effect has not yet been demonstrated to sufficiently correct progesterone deficiency in perimenopausal women. Therefore, DIM use cannot replace the use of progesterone. The deficiency of progesterone during perimenopause is progressive and eventually needs support. Thus, the use of both DIM and progesterone is recommended for women in their forties who have evidence of progesterone deficiency, such as irregular periods.

For women still having menstrual cycles, the practical step of increasing progesterone levels during the second half of the cycle with the use of creams containing progesterone is often of benefit. Together with DIM, maintaining a youthful cycle of progesterone may have a protective effect that reduces the risk of breast cancer. The good estrogen metabolites promoted by DIM can help support natural progesterone production but only through the period in which ovulation occurs. DIM and transdermal progesteroneprogesterone cream) are logical partners in maintaining a healthy balance of progesterone-to-estrogen once ovulation is irregular. A combination of DIM and progesterone are eventually needed to support hormonal balance during perimenopause and after menopause.

Q. Is DIM supplementation and hormonal replacement therapy (HRT) a good combination?

A. One of the changes in the modern woman's life cycle is a more continuous and intense exposure to estrogen during her life span. Compared to her ancestors, a modern woman's long life expectancy means that at least a third of her life will be spent in the postmenopausal years. Maintaining hormonal balance during these added years with estrogen replacement produces many benefits. However, studies have shown that there are certain women who tolerate hormonal replacement poorly, suffering from symptoms of estrogen excess, or estrogen dominance. There is also a small but clear increase in the risk of breast and uterine cancers with prolonged HRT. Since estrogen metabolism is not being tested routinely in women, it is not possible to identify which women are at the greatest risk of developing cancer.

DIM supplementation improves estrogen metabolism and reduces symptoms of estrogen dominance. For women who are troubled by the estrogen paradox, discussed on page 26, DIM offers a desirable option. The proven scientific benefits of DIM make it a logical choice as a dietary supplement for use with HRT. In a study of five thousand women in Italy, those with the highest ratio of good to bad estrogen metabolites were shown to be protected from breast cancer when followed over a period of years.

Q. Is testosterone really important in women's health?

A. Many of the benefits attributed to estrogen in women may actually relate to the presence of testosterone, which as you learned, is found in lower amounts in women than in men. The importance of testosterone was demonstrated by a study of women who had complete hysterectomies, in which the ovaries were removed, as well as the uterus. Study subjects received estrogen, an estrogen-testosterone combination, or a placebo (an inert substance). The estrogen-testosterone group experienced improved mood and increased libido. While the exact contribution of testosterone to mood and sexual health has been more difficult to define in women who have intact ovaries, it has been shown that testosterone supports physiologic responses in sexual arousal. In studies of mood and depression, testosterone alone or with estrogen was most effective in reducing depression.

Q. Why is "free" testosterone so important?

A. When women with premenstrual syndrome, a common mood disorder of perimenopause, were studied with regard to testosterone, low levels of total and free testosterone were identified. Low free testosterone levels are always seen when there is an increase in the levels of SHBG proteins. An increase in these binding proteins accompanies estrogen excess and results from the use of oral contraceptives, most HRT, and in certain women during perimenopause with estrogen dominance. Careful studies have shown that women experienced significant drops in testosterone starting as early as their late twenties. By the time a woman enters her forties, levels of free testosterone can drop 50 percent.

In addition to improved mood and increased libido, higher levels of free testosterone also contribute to a greater fat-burning metabolism. As proven with former East German female athletes given androstenedione (a testosterone precursor, or prohormone), support for testosterone can increase lean body mass in young active women.

Q. How does DIM "unlock" testosterone?

A. DIM promotes a consistent rise in the levels of good estrogen metabolites, which are the only known natural metabolites of any hormone to have a greater affinity for testosterone-binding proteins than testosterone itself. These metabolites become bound in place of testosterone, so even a small increase in the concentration of good estrogen metabolites results in higher levels of free testosterone. Even tiny increases in amounts of free testosterone are capable of influencing mood and behavior, since the brain is home to a multitude of hormone receptors that can be influenced by testosterone. The same situation applies to fat cells, where free testosterone is able to induce more of a response to the signals that release stored fat.

Since adjusting testosterone activity with DIM does not excessively elevate testosterone levels, it is a

safe way for every woman to return her free testosterone levels to a more youthful hormonal balance.

Q. What's the difference between DIM and the phytoestrogens found in soy, red clover, and black cohosh?

A. Phytoestrogens include all those substances produced in plants that resemble estrogen in their structure and can partially substitute or mimic estrogen's action. Unlike phytoestrogens, DIM has no estrogen-like activity and does not mimic estrogen. DIM is not a plant estrogen. Instead, DIM interacts with estrogen only by promoting estrogen's beneficial metabolism.

Nevertheless, the supplemental use of phytoestrogens may have a protective effect against cancer and heart disease. Phytoestrogens are being used increasingly, but their use alone is not enough to match all the benefits that come with estrogen replacement especially with regard to a healthier brain and protection from age-related disorders such as AIzheimer's disease. While phytoestrogens may reduce the severity of menopausal symptoms, including hot flashes, their use alone cannot replace the body's eventual need for natural estrogen and progesterone.

 Unlike DIM, phytoestrogens require digestion in order to be converted into their active forms. Supplemental DIM requires no digestion but does depend on a special microencapsulated formulation to be adequately absorbed by the body.

Q. Can DIM be used with phytoestrogens?

A. The combined actions of DIM and phytoestrogens work well together. These substances produce both independent and overlapping actions that promote women's health. Like estrogen, phytoestrogens increase bone mineral metabolism. Phytoestrogens also can protect blood proteins from oxidation, overlapping with the action of the good estrogen metabolites increased by DIM. This effect has been seen in the phytoestrogens known as isoflavones, which are found in soybeans, especially the isoflavone genestein. Phytoestrogen supplements are being used increasingly in combination with natural estrogen and DIM.

The use of DIM and phytoestrogens together poses no unwanted interactions: taking the supplements together will not block the beneficial activity of either one. With or without phytoestrogens, the use of

DIM is still necessary to improve the metabolism of estrogen.

Q. What about DHEA for women's hormonal balance?

A. Many women today take supplemental dehydroepiandrosterone (DHEA). Some women choose to take DHEA instead of traditional HRT. This popular over-the-counter substance is a prohormone-once in the body, it is converted to estrogen and testosterone, helping to replenish levels of those hormones.

The role of DHEA as a beneficial component of healthy hormonal balance has been established by the fact that replacing DHEA in women has been shown to support mood, improve immune function, support bone health, and reduce menopausal symptoms. Monitored, long-term use of DHEA was shown to increase bone density and support a healthier vaginal mucosa in women. In addition, DHEA has been shown to reduce the symptoms of systemic lupus erythematosus-an autoimmune disease.

DHEA is also produced naturally in the body and, like other hormones, its production tapers off dramatically with age. In clinical studies, DHEA has been shown to promote healthy bones as well as to protect breast tissue from cancer. DHEA also contributes to the activity of our thyroid hormones. This occurs by DHEA making our cells more responsive to the thyroid hormone, which supports healthy fat metabolism. DHEA is also known to be critical for maintaining optimal energy levels and mood, and is needed to support the serotonin system. Serotonin is a brain hormone derived from the indole amino acid tryptophan and is responsible for positive mood. (Imbalances in the serotonin system are often treated with the antidepressant Prozac.) DHEA has also been shown to support memory and a sense of well-being in some studies. However, although the DHEA-promoted hormonal balance is beneficial to women, some women are concerned that DHEA supplements might be converted into too much estrogen and, therefore, may present the same risk that taking estrogen does.

Q. Is DIM and DHEA a good combination for older women?

A. DIM's action ensures that the estrogen produced from DHEA is metabolized into good estrogen metabolites. This shift in estrogen metabolism is associated with lower cardiac risk, better fat metabolism, and a more efficient insulin system, considered an important measure of overall health in women. In women, DHEA supplements help support healthy levels of testosterone-like metabolites that fall during aging. Using DIM with DHEA also helps to ensure that a healthy testosterone-to-estrogen ratio is maintained, which correlates with a low risk of heart disease and a better sensitivity to insulin. Use of DHEA in combination with DIM can begin during perimenopause and continue through and past the menopausal years.

Q. Can DIM be a substitute for hormone replacement therapy (HRT)?

A.DIM has no estrogenic activity itself. Although it helps to convert estrogen to useful metabolites, it does not directly mimic or replace estrogen. Using DIM will promote a more desirable estrogen metabolism, but it will not make up for estrogen deficiency.

For some women in menopause who experience dropping estrogen production and hot flashes, DIM supplements alone at low dose often ease symptoms. However, combined use of DIM with DHEA or supplemental natural estrogen in standard HRT will promote a better metabolism for the added estrogen. This means that DIM in combination with estrogen may help those women who experience side effects when HRT is taken alone. These problems include sore breasts and excessive bleeding, experienced by some women when the combination of estrogen and progesterone are stopped after each monthly cycle.

Q. Can DIM be used with all forms of HRT in women who are postmenopausal?A.  DIM is compatible with all forms of HRT. Use of DIM together with various synthetic estrogens, conjugated estrogens as found in Premarin, and with synthetic progesterone or progestins as found in Provera has not been associated with any known problems. The estrogen and progesterone-like hormones in these preparations are not the same as the estrogen and progesterone produced in our bodies. The use of DIM in combination with low doses of DHEA may offer a new solution to problems associated with both late perimenopause and menopause. Estrogen replacement using a combination of DHEA and estrogen has been in use for many years in Europe, successfully controlling the symptoms of menopause.

The approach of using individualized combinations of DIM, DHEA, and low doses of estrogen and progesterone represents the most complete support for hormonal balance in postmenopausal women. It is recommended that women, together with advice from their health care practitioners, continue to refine their personalized plans for hormonal replacement.

Many women may find that adding DHEA and DIM to their HRT program will help to further improve their mood, energy level, and weight management.

Q. Can DIM be used with birth control pills?

A. The use of DIM with birth control pills is a good combination in theory. However, some caution is in order because possible interactions have not been studied directly. Until studies are performed confirming the effectiveness of birth control pills at preventing pregnancy during DIM use, the combination of birth control pills with DIM should only be used as recommended and supervised by a health care practitioner familiar with DIM.

The use of DIM before or during pregnancy presents more unanswered questions. Even though animals receiving high doses of cruciferous phytochemicals have successfully reproduced, the formal study of DIM and reproduction is only beginning.

Therefore, the use of DIM is not recommended for women who may be pregnant or who are trying to become pregnant.

Easy Steps for Using DIM Supplements

After reading chapters 1 through 5, you probably have many questions, like "How much DIM should I take?" "How often should I take it?""Why is it necessary to take DIM in an absorption-enhancing formulation?” and probably many others. Since maintaining hormonal balance requires a personalized approach depending on age and sex, no one combination of DIM with other supplements will suit everyone. This chapter will introduce you to a basic approach to using DIM with other supplements, helping you to get the most from DIM for your personal needs.

Q. Are DIM supplements safe?

A. Dietary supplements with absorbable, microencapsulated DIM have been used safely for ten years. The earlier research on these phytochemicals as a cancer preventive in animals used huge amounts of DIM for many months. Despite the continuous use of these phytochemicals in multiple generations of animals, no safety problems were noted. Recently, DIM was again shown to be safe when it was used successfully to treat chemically induced breast cancer in animals. Continuous use of DIM supplements by adults and children for years at a time has shown improved estrogen metabolism and no side effects or safety concerns. In addition to these research studies, DIM supplements formulated for enhanced absorption have been used by thousands as a hormonal-balancing and sports-nutrition supplement.

Q. What is the best form in which to take DIM supplements?

A. Laboratory testing shows that DIM, in its pure form, is highly insoluble. Therefore, DIM must be incorporated into a special absorption-enhancing, microencapsulated formulation using patented technology in order to ensure its assimilation by the body. So far, only microencapsulated DIM supplements have been shown to have any adequate absorption.

Q. What about the other cruciferous indole, indole-3-carbinol (I3C)?

A. Though still marketed as a dietary supplement, it turns out that I3C is not active in your body until it is converted into DIM. DIM is formed as I3C combines with itself, in a process that occurs only if just the right amount of stomach acid is present. The problem is that everyone' s digestion is a little different, so taking 13C results in unpredictable amounts of DIM. In addition, I3C is highly unstable and can transform into many other substances whose actions are undesirable. Also, I3C can react with other substances in your diet, including vitamin C and many foods, making it unpredictable to use as a supplement. Heat and moisture cause I3C to break down in supplement capsules and turn into a host of other substances of which DIM is only a small portion. Because of its instability and reactivity, ten times more I3C than DIM is needed when used as a supplement in order to achieve the beneficial shift in estrogen metabolism seen with microencapsulated DIM. 

The bottom line is that, because of instability and unpredictable reactions, there is no such thing as pure I3C. For these reasons, and other undesirable responses to I3C, including promotion of tumors, 13C's use as a dietary supplement is not recommended.

Q. Can DIM supplements be taken along with cruciferous vegetables in the diet

A. Although you are using supplemental DIM, a generous intake of a variety of cruciferous vegetables is still recommended. DIM is but one of many beneficial phytochemicals found in these vegetables, and the full spectrum of beneficial phytochemicals is available only through regular inclusion of a variety of cruciferous vegetables in your diet. The most helpful cruciferous vegetables, listed according to their concentrations of phytochemicals, are Brussels sprouts, cabbage, broccoli, and cauliflower. Recently, studies with cruciferous vegetables have shown this type of food to have important antioxidant and heart protective activity. Certain phytochemicals, such as sulphoraphane, which has proven useful in colon cancer prevention, are best found in fresh broccoli sprouts. In all cases, eating the cruciferous vegetable as close as possible to the raw form is best. This is because the heat of cooking destroys the enzymes that are necessary to release active phytochemicals from the storage form in the plants. Only active forms of cruciferous phytochemicals, which are free of bound sugar molecules, are able to support your metabolism.

Q. What is the typical dose of microencapsulated DIM for women?

A. The usual dose of bioavailable, microencapsulated DIM for women is 100 to 200 mg per day taken with food. Postmenopausal women sometimes take just 50 or 75 mg per day. The capsules or tablets are best taken with food either once or twice a day. Improvement in breast tenderness has been reported by women at a dose of 150 to 300 mg per day. This same dose has been shown to be sufficient to consistently shift metabolism of estrogen in women to favor the good metabolites. Typical doses for premenopausal women with symptoms of estrogen dominance, which include breast pain, painful periods, excessive periods, and PMS, are from 150 to 300 mg per day. A more active fat metabolism is seen with microencapsulated DIM at 150 to 400 mg per day.

This dosage can be of benefit during the first one or two months of weight loss, especially in association with carbohydrate restriction and exercise. The dose is then reduced to 100 or 150 mg per day, to be continued indefinitely during the maintenance phase once weight-loss goals have been reached.

Q. What is the typical dose of microencapsulated DIM for men?

A. The usual dose range of bioavailable, micro-encapsulated DIM for men is 200 to 400 mg per day

taken with food. These amounts have been associated with improved hormonal balance. The same beneficial shift in estrogen metabolism as that described in women occurs at this dose. Supplementation at these levels has also been reported to improve symptoms of prostate enlargement. For men involved in a plan of physical conditioning, the dose of microencapsulated DIM should be between 150 and 400 mg per day. DIM supplements taken with a protein snack just before or after exercise are most appropriately timed. Use of DIM at these amounts in conjunction with DHEA has been associated with benefits in body composition, helping to maintain muscle and reduce fat mass. Men on testosterone replacement therapy need less microencapsulated DIM, typically using only 50 to 75 mg per day.

Q. What other dietary supplements should women consider taking along with DIM?

A. The combined use of DIM and other supplements by women varies according to your age and your personal plan for hormone replacement. For bone health, the use of bioavailable DIM at a dose of 100 to 200 mg per day is best combined with soy isoflavones and black cohosh. Starting in perimenopause, the next logical additions to this combination are progesterone and low-dose DHEA. DHEA can be added at a starting dose of 5 to 10 mg per day if taken with DIM.

The other compatible and important supplements to be combined include antioxidants, essential fatty acids, minerals, and vitamins. For women's health, especially with regard to bone and joint health, these

include vitamins E, D, A, and C; omega-3 fatty acids from fish; absorbable forms of magnesium and calcium; the trace elements selenium and zinc; and folic acid. Vitamin D intake is now suggested to be as high as 2,000 international units (IUs) per day. After menopause, when there are symptoms of low estrogen such as hot flashes, taking microencapsulated DIM in conjunction with isoflavones can be of benefit. In postmenopausal women using soy isoflavones, it is necessary to take enough concentrate to provide about 100 mg of genestein specifically per day. Be sure to personalize your supplement program with the help of a healthcare professional familiar with these nutrients and with your own special needs.

Breast health is specifically benefited with a supplement combination that includes microencapsulated DIM, vitamin D, vitamin E, iodine, and selenium.

Q. What other dietary supplements should men consider taking with DIM?

A. In men, the use of absorbable DIM is best combined with prostate health supplements containing saw palmetto extract, extract from the African prune(Pygeum africanum), stinging nettle extract (Urtica dioica), and zinc. DIM prevents unwanted estrogen stimulation, and saw palmetto limits the unwanted effects of testosterone. In addition, try to eat a diet rich in cooked tomatoes, which provide the vitamin A like nutrient lycopene. Limit your consumption of red meat and saturated fats, and increase your intake of Soy protein. Maintain a lean physique. And, of course, have your physician monitor your prostate's size and function. Prostate health can also be monitored with a blood test known as the prostate-specific antigen level (PSA).

The use of DIM in conjunction with DHEA replacement and prostate support should include a basic plan of antioxidants, essential fatty acids, minerals, trace elements like zinc and selenium, and vitamin D. Vitamin E at a daily dose of 800 to 1,000 IUs is also essential, since the use of DHEA without vitamin E has been shown to create oxidative stress in some experiments. Other antioxidants important for men, especially for cardiovascular health, include vitamins A and C. Fish oil concentrate containing omega-3 fatty acids, folic acid to control homocysteine levels, and proanthocyanidins from grape seed are also known to be good for cardiovascular health.

DIM use in conjunction with creatine supplementation is recommended during weight training for increased muscle mass and strength acquisition. The use of creatine is particularly helpful for older men who need to overcome normal age-related decreases in training efficiency. In addition, the use of phosphatidylserine, a fatty acid supplement, may help to reverse age-related changes in mental function as well as reduce post-workout muscle soreness. During programs for fat loss, a number of newly available dietary supplements for more efficient fat metabolism may be used in addition to DIM, such as alpha ketoglutarate. A concern for aging men is antioxidant replacement, which can be protective for exercise-induced free radicals. Here, DIM can help along with antioxidant supplements, including phosphatidylserine, glutamine, N-acetyl cysteine (NAC), vitamins E, A, and C, and selenium. Also, if you have a family history of diabetes, high blood pressure, or heart disease, lipoic acid, proanthocyanidins from grape seeds, resveratrol from grape skins, and pycnogenol are potentially important. Be sure to establish your personal dietary supplement plan with the help of a health care professional who understands your special needs.

Q. Are there any reported side effects associated with supplemental DIM?

A. No side effects have been reported by those who use DIM within standard guidelines. However, as with all dietary ingredients, intake beyond recommended limits is not advised. Children who have inadvertently taken excessive amounts of DIM have complained of stomach upset and dizziness, but these symptoms always improved shortly after discontinuing DIM.

Some people taking DIM have noticed a darkening of their urine to an amber to brownish color. This has been seen when DIM is taken with less than the recommended daily water intake. This is a normal, harmless occurrence and is not associated with any abnormalities in kidney function or health status.

This change in urine color is due to the presence of colored DIM metabolites, and is not noticeable when drinking healthy amounts of water.

Q. Are there reports of interactions associated with DIM and medicines?

A. Persons ought to consult with their physician if they are taking medicines before using DIM. Coumadin (warfarin) is one medicine used to prevent coagulation of the blood. One should not use DIM with this type of medicine as this drug is known to have interactions with many supplements and medications. Antiepileptic drugs also should not be used with DIM, since interaction studies have not been performed.

Q. How long does it take to notice benefits from supplementation with bioavailable DIM?