Estrogen is a life-giving hormone with which modern humans, both men and women, have a love-hate relationship. Several factors contribute to this complicated relationship: 1) estrogen is a proliferative hormone that contributes to and exaggerates growth; 2) because women outlive their estrogen production, they need safe forms of exogenous supplementation for bone, brain and cardiovascular health; 3) the mode of delivery is essential to preventing or contributing to some of the harms associated with estrogen; 4) because many modern chemicals mimic estrogen (xenoestrogens), increasing the estrogen burden; and 5) adipose tissue has the ability to aromatize testosterone into estrogen in both men and women. Clearly, the chemicals and diet of modern living play an influential role in estrogen’s effects. Research has shown that returning to a simpler, earth-derived (whole foods) diet emphasizing more fruits and vegetables, can counterbalance some of those effects by encouraging safer estrogen metabolism contributing to better overall estrogen balance.
While appropriate levels of estrogen are essential for promoting and maintaining blood sugar balance, fertility, bone, cardiovascular, and brain health; estrogen is also at the center of many autoimmune, infectious, metabolic and degenerative pathologies. Several studies have concluded that as inappropriate exposure to estrogen increases, so does the risk of breast, ovarian, prostate and thyroid cancers. Disproportionate exposure to estrogen has been associated with other health syndromes including PCOS, PMS, endometriosis, fibrocystic breast tenderness and mastalgia. Conversely, depletion is not a safer option, as low estrogen is associated with digestive problems, osteoporosis, cognitive decline, joint dysfunction, vasomotor symptoms, insomnia, urogenital issues, and cardiovascular complications.
There are several mediums with which to test hormone levels including saliva, serum and urine. Urine is the only commercially available testing method for monitoring the metabolism of both endogenous and supplemented hormones. Much like a fingerprint, hormone metabolism is unique to each individual. Assessment of hormone metabolism as well as enzyme activity provides a rare glimpse into patient health.
Estrogen metabolism takes place primarily in the liver via phase I hydroxylation via the cytochrome P450 family of enzymes. The CYP1A1 gene regulates metabolism in the liver while the CYP1B1 gene does so outside the liver, mainly in the breasts, ovaries, and uterus. In phase II, these metabolites are conjugated through sulfation via steroid sulfotransferases, or glucuronidation, requiring catechol-O-methyltransferase (COMT) and glutathione S-transferase (GST) enzymes.
Phase I hydroxylation yields three estrogen metabolites that vary greatly in biologic activity: 2-hydroxyestrone/estradiol (2-OH), 16-hydroxyestrone/estradiol (16α-OH), and 4-hydroxyestrone/estradiol (4-OH). The 2-OH metabolite is generally termed the “good” estrogen because it generates weaker and potentially less harmful estrogenic activity. In contrast, the 16α-OH and 4-OH metabolites show persistent estrogenic activity which could promote dangerous tissue growth if unchecked. In fact, women who metabolize a larger proportion of estrogen via the 16α-OH and 4-OH metabolites may be at significantly higher risk of developing breast cancer.
In phase II metabolism, the 2-OH and 4-OH estrogen metabolites are further detoxified via methylation and COMT. This is an important pathway, because it renders the harmful 4-OH metabolite significantly less active, and also activates the protective 2-OH into the stable 2-methoxyestrone (2-M-E2). If the 2-OH and 4-OH estrogens are not methylated, they can become highly reactive molecules with the potential to damage DNA.
Furthermore, the activity of the aromatase enzyme plays an important role in estrogen’s story. The level of aromatase activity in breast adipose tissue containing a tumor is strikingly increased when compared with breast tissue from disease-free women. The level of estradiol in the breast cancer tissue of postmenopausal women is reported to be 10 times higher than the level in their serum. For postmenopausal women without breast cancer, the level of estradiol in their breast tissue is approximately four times higher than their serum level. Reducing the activity of aromatase is fundamental to estrogen modulation.
The take-home? Estrogen’s overall effects on the human body are greatly impacted by how it’s metabolized. Some of the most potent agents for supporting methylation and the enzymes that support healthy estrogen metabolism come from plants. According to the 2015 Behavioral Risk Factor Surveillance System, only 9% of American adults met the recommendations for vegetable consumption and only 12% for fruit. Ouch! The following are herbs and foods that can be beneficial to estrogen metabolism:
Berries:
Reduces CYP1A1 overactivity (this may be desired if phase II detoxification is not efficient)
Broccoli and cruciferous vegetables/DIM:
Induces CYP1A1 enzyme - encouraging the 2-OH pathway
Kale inhibits CYP1B1 pathway (this pathway drives 4-OH estrogen metabolite)
Chrysin (i.e. honey and propolis):
Inhibits aromatase
Citrus Foods:
Supports COMT
Fiber:
Promotes diversity of the gut microbiome
Inhibits estrogen reabsorption via control of beta-glucuronidase
Flavonoids from plant matter:
Inhibits aromatase
Inhibits CYP3A4 (this enzyme drives 16-OH estrogen metabolite)
Grapefruit:
Inhibits CYP1B1 pathway
Green tea:
Inhibits aromatase
Induces CYP1A1
Lowers estrone levels
Lycopene rich foods (i.e. tomatoes, carrots, watermelon):
Inhibits CYP1B1
Resveratrol containing foods (i.e. grapes, peanuts, cocoa, blueberries, biliberries, cranberries):
Induces CYP1A1– encouraging the 2-OH pathway
Reduces CYP1B1
Inhibits aromatase
Reverses semi-quinone formation/Promotes quinone reductase
Supports COMT
Rooibos tea and Apeacea vegetables (i.e. celery, carrots, coriander, fennel, cumin)
Chrysoerial inhibits CYP1B1
Rosemary:
Induces CYP1A1
Supports COMT
Turmeric/Curcumin:
Supports COMT
Anti-inflammatory
Conclusion:
Healthcare providers can help tip the scales of this complicated relationship to estrogen through the encouragement of a whole-foods diet. In this way, estrogen gets more love and less hate.
The Doctor’s Data HuMap (Hormone and Urinary Metabolites Assessment Profile) test can provide a patient’s hormone fingerprint. Practitioners can then specifically modulate enzymes and metabolites to create a healthier environment for estrogen and its metabolism.
