NEW YORK—Endometriosis, uterine fibroids and breast cancer are usually considered separate disorders, but physiologically they share a common pathogenic root: chronic, systemic estrogen toxicity, said Joel Evans, MD, at the third annual CAM Expo East.

All three conditions are related to increased adiposity, especially visceral adiposity, and arise in a context of insulin resistance and chronic inflammation. Rather than focusing on the lesions, physicians should work with patients to try and reduce adiposity, increase insulin sensitivity and decrease inflammation.

A comprehensive nutrition and lifestyle-based strategy aimed at achieving healthy weight, normal glucose metabolism, and reduced inflammation can help many women with fibroids or endometriosis avoid surgery. It will also go a long way toward reducing the risk of breast cancer as well.

Estrogen & Inflammation

These disorders are characterized by maladaptive tissue responses to circulating free estrogen. Excessive estrogen production, inadequate estrogen clearance, and impaired glucose metabolism all contribute to the pathogenesis.

“Estrogen causes more inflammation. Inflammation causes more insulin release, and insulin causes more total estrogen as well as free estrogen. Visceral fat causes both more estrogen and more inflammation. To reduce these estrogen-related disorders, we need to reduce insulin levels, inflammation, and visceral adipose tissue,” said Dr. Evans, a holistic gynecologist, and founder of the Center for Women’s Health, Stamford, CT.

Fibroids—benign tumors of the myometrium—are highly sensitive to hormonal influences. Lesional tissue typically shows many more estrogen and progesterone receptors than surrounding myometrium. These tumors are rare before menarche and usually shrink or totally disappear after menopause. Typically, they enlarge during pregnancy or oral contraceptive use.

Endometriosis affects between 3% and 10% of all reproductive-age women. Among those seeking infertility treatment, prevalence is as high as 35%. Though it is defined by presence of endometrial tissue outside the uterus (usually on the peritoneal lining), it is not so much the presence of the tissue itself but the cyclic inflammation—usually around menstruation—that makes it such a bane.

Process of Elimination

The first step in evaluating a woman with fibroids or endometriosis is to look at how her body functions, both qualitatively and quantitatively, in response to estrogen and progesterone. Pay close attention to circulating estrogen and especially her ability to eliminate it. “If the body isn’t eliminating estrogen properly, then it is extremely difficult to shrink fibroids.”

Estrogen is removed from circulation by the liver, and requires both Phase 1 and Phase 2 detoxification. Phase 1 involves hydroxylation of the estrogen molecule, while phase 2 involves glucuronidation, sulfation, and methylation. The end product is an inactive complex excreted in bile and eliminated in the feces.

The efficiency of the hepatic detox is determined in part by genetics—some women have inherent deficiencies in one or the other phase—and also by nutritional factors. Deficiencies of folic acid, magnesium, zinc, and manganese will impair enzymes involved in hepatic detox.

Pay attention to GI function as well. Impaired bowel function, especially constipation, will increase re-uptake of excreted estrogen.

The big culprit here is β-glucuronidase, a bacterial enzyme that de-conjugates the β-glucuronide molecules attached to estrogen during hepatic detox. This renders the estrogen active again. “I always test patients for β-glucuronidase. It’s a simple stool test. You want to see β-glucuronidase as low as possible,” said Dr. Evans. “This is an inducible enzyme, upregulated by a high animal fat diet.”

Flax & Other Friendly Foods

Reducing animal fat, and increasing dietary fiber, especially cruciferous vegetables, are important first steps in optimizing bowel function, reducing β-glucuronidase, and reducing estrogen. Flax is a valuable ally: it provides much dietary fiber, has an excellent fatty acid balance, and is anti-estrogenic. Other friendly foods include artichokes, pomegranates, apples, watercress, onions, garlic, and green tea.

Helpful supplements include n-acetyl cysteine, glutamine, vitamin C, and calcium-d-glucarate. The latter is a great choice because, at 200 mg twice daily, it inhibits β-glucuronidase, thus improving estrogen elimination. Many patients will also benefit from a good probiotic, to ensure the gut flora is healthy, and to minimize organisms that produce β-glucuronidase.

Adi-posing Problems

Fibroids, endometriosis and breast cancer are all strongly linked with obesity, especially visceral adiposity. This is because adipocytes are a major source of aromatase, a rate-limiting enzyme for estrogen production. The more aromatase, the more estrogen a woman is able to produce. Dr. Evans pointed out that endometriosis tissue shows very high levels of aromatase activity, though normal endometrium inside the uterus shows no detectable aromatase activity. Likewise, fibroid tissue shows high aromatase activity, while normal myometrium shows none (Shozu M, et al. Sem Repr Med. 2004; 22(1): 51).

Adipocytes are also a major source of inflammatory mediators like TNF-α, PAI-1, and IL-6. The latter drives increases in c-reactive protein. In essence, obese women are in a state of constant, low-grade systemic inflammation (Visser M, et al. JAMA. 1999; 282(22): 2131–2135).

There’s an interesting inter-relationship between prostaglandin E2 and estrogen that’s worth keeping in mind. PGE2 stimulates aromatase, which increases estrogen production. In turn, estrogen up-regulates the COX-2 enzyme, which increases PGE2, setting up a pernicious feed-forward loop promoting chronic inflammation (Noble, et al. J Clin Endocrinol Metab. 1997; 82: 600–606). PGE2 and IL-6 are the two most potent stimulators of aromatase in fibroid cell culture (Shozu et al., ibid.).

Adding Insulin to Injury

Visceral obesity increases insulin resistance, and further drives inflammation and estrogen production. Visceral obesity is also associated with a decrease in sex-hormone binding globulin (SHBG), a transport molecule that binds and inactivates estrogen. Less SHBG means more free, active estrogen in circulation.

Pay close attention to the “apples,” women with dense abdominal fat deposition. They’re at much greater risk than the “pears,” the women who deposit fat in the hips and buttocks. “Visceral fat is the bad actor here, not subcutaneous fat.”

Obviously, reduction of abdominal fat is essential in managing these disorders and restoring better health. And no, liposuction is not a viable option. A recent study showed that despite removal of up to 20 pounds of abdominal fat, liposuction did not improve insulin sensitivity, circulating CRP, IL-6, TNF-α, or adiponectin. There’s really no way around dietary changes and exercise.

Beyond increasing intake of fresh fruit and vegetables, Dr. Evans recommends that patients reduce intake of omega-6 fatty acids, especially from corn-fed beef, cheese and shellfish, while increasing omega-3s by upping intake of oily fish, flax, and grass-fed organic beef (for those women who eat meat). Cutting trans fats as much as possible is also wise, as these are major inflammation inducers.

A low fat, high-fiber diet will increase SHBG, improve insulin sensitivity, and attenuate inflammation. Several years ago, investigators from the Center for Obesity Management, University of Naples, showed that a multidisciplinary lifestyle change program aimed at reducing body weight in obese women led to, “a reduction in all the parameters associated with inflammation” (Esposito K, et al. JAMA. 2003; 289: 1799–1804).

Estrogen: You’re Soaking In It!

Do not underestimate the impact of exogenous estrogenic compounds in the environment. Environmental scientists have discovered estrogens in waters all over the world. They’re seeing it in fresh water rivers and lakes, as well as in marine ecosystems, and it is having disturbing effects on water-dwelling critters.

In 2004, David Norris and colleagues at the University of Colorado, Boulder, discovered genetically male fish developing female sex organs. They attributed the findings to increased exogenous estrogens in the state’s rivers. “Eighty percent of the nation’s streams have estrogen in the water,” said Dr. Evans.

The exogenous hormones come, in part from agricultural/livestock runoff and in part from human sewage—consider the vast numbers of women using estrogen-based drugs, the huge volume of excreted estrogen, and expired medications being flushed down toilets across the globe.

“Chickens are fed estrogen to develop the volume of breast meat. There are lots of hormones in chicken feed,” he said. “If a woman with estrogen-sensitive lesions does eat meat or dairy, I strongly recommend organic, hormone-free meat and milk products.” Pesticides, many of which are estrogen mimics, contribute the growing burden of exogenous estrogens affecting women today.

Stress-trogen

Finally, while you focus on nutritional and biochemical aspects of estrogen metabolism, also consider psychosocial and emotional factors that contribute to the endometriosis/fibroid/breast cancer miasm.

“Stress is very pro-inflammatory. It increases cortisol, which is inflammatory,” said Dr. Evans. “A bad marriage can increase fibroid and endometriosis symptomatology. This is for real, so always ask about the relationship and the possibility of hostile interactions between a patient and her partner or close relatives. Marital discord can markedly increase inflammatory cytokines, so talk about these things before you start planning hysterectomies!”

He added that in his practice, over many years treating many women, he’s seen several common and recurrent psychological “themes” emerging among women with fibroids or endometriosis. Conflicts about childbearing represent a big one. “Either having children they didn’t really want or being unable to have children when they did want them, are very common situations.”

Likewise conflicts over creative or sexual self expression, anger issues, and histories of sexual assault, are common in women with these disorders. It is easy, in a busy clinical context, to overlook these psycho-emotional aspects in favor of the more biochemical aspects, but Dr. Evans stressed that patients tend to do much better if you can enable and empower them to work on both the physical and psychological components together.