|
|
Estrogen Metabolism and Prostate Health: Treatment Approaches for Functional Medicine Providers
|
Lylen Ferris, ND | May 28, 2024
|
|
|
|
|
|
|
Approximately 1 in 8 men will be diagnosed with prostate cancer over the course of their lifetime. The risk of developing prostate cancer varies among individuals, influenced by factors such as age, race/ethnicity, and other variables. Recent research has identified estrogen metabolism as a potential risk factor for prostate cancer. Evaluating hormone metabolism and enzyme activity offers a comprehensive understanding of patient health. Similar to a fingerprint, hormone metabolism is distinct to each individual.
Estrogen metabolism primarily occurs in the liver and involves a two-step process beginning with phase I hydroxylation mediated by the cytochrome P450 enzyme family. The CYP1A1 gene regulates this metabolic activity within the liver, whereas the CYP1B1 gene is responsible for estrogen metabolism in peripheral tissues, including the prostate, breasts, ovaries, and uterus.
Phase I hydroxylation produces three estrogen metabolites with significantly different biological activities: 2-hydroxyestrone/estradiol (2-OH, catalyzed by the CYP1A1 enzyme), 16-hydroxyestrone/estradiol (16-OH, catalyzed by the CYP3A4 enzyme), and 4-hydroxyestrone/estradiol (4-OH, catalyzed by the CYP1B1 enzyme). The 2-OH metabolites are considered "beneficial" estrogens due to their weaker and potentially less harmful estrogenic activity. In contrast, the 16-OH and 4-OH metabolites exhibit persistent estrogenic activity, which may promote detrimental tissue growth if not regulated. Notably, individuals who predominantly metabolize estrogen via the 4-OH pathway may have a significantly increased risk of developing prostate cancer.
The CYP1B1 enzyme, as driver of 4-OH metabolism, is prevalent in hormone-responsive tissues including prostate, breast, ovary, and endometrium. Abundant levels are also found in tumor tissue compared to healthy tissue, and particularly high levels are observed in estrogen-mediated diseases which may also contribute to prostate cancer.
In a study conducted by Carnell and colleagues, no CYP1B1 activity was detected in normal prostate tissue. However, CYP1B1 was overexpressed in prostate carcinoma and was also detectable in associated premalignant and benign hyperplastic tissues, suggesting a potential link with malignant progression and indicating CYP1B1 as a potential therapeutic target. Other studies have even indicated prostate cancer patients with high CYP1B1 expression have lower survival rates.
If testing reveals a preference for 4-OH metabolism, two therapeutic approaches are considerations: support less movement down the CYP1B1 pathway and more movement down the CYP1A1 pathway, and support phase II metabolism via the COMT enzyme to render these reactive 4-OH metabolites less dangerous.
Research has found these natural products can boost CYP1A1.
-
DIM (diindolylmethane) – phytonutrient found in cruciferous vegetables
-
I3C (requires stomach acid to convert to DIM)
-
Coffee
-
Resveratrol
-
Andrographolide, from the Andrographis paniculata plant
-
Astaxanthin (antioxidant found in shrimp and some algae)
-
Fish oil and garlic oil
-
Green and black tea
-
Hops
Phase I metabolism in and of itself can generate free radicals. Because of this, the following antioxidants are a consideration to help further reduce additional harm to the tissues:
-
Vitamins A, C, E
-
Carotenoids
-
Selenium
-
Copper
-
Zinc
-
Manganese
-
CoQ10
-
Alpha lipoic acid
-
Thiols (garlic, onions, cruciferous vegetables)
-
Bioflavonoids
-
Silymarin
-
Oligomeric proanthocyanins
-
Glutathione
-
Melatonin
Phase II metabolism involves methylation of phase I metabolites into more water-soluble versions that can be excreted and ideally be rendered inactive, via the COMT enzyme. This is an extremely important step. If 4-OH metabolites are not inactivated, they have the potential to form quinones and or semiquinones, which are highly carcinogenic and genotoxic, capable of inducing and potentiating prostate cancer. To decrease this risk, it is critical to optimize the function of COMT. The following have been shown to increase COMT activity:
-
Nutrient cofactors: cruciferous vegetables, soy foods, resveratrol, citrus foods, teas (rooibos, dandelion), and spices (rosemary, curcumin)
-
Methyl donors: methionine, methylcobalamin, pyridoxyl-5-phosphate, betaine, folate, and magnesium
For those who have lower COMT activity and thus greater potential for quinone activity, two supplements may offer some additional protection:
Resveratrol
-
Can reduce catechol estrogen semiquinones back to catechol estrogens
-
Can induce the estrogen-protective enzyme quinone reductase
-
Modulates CYP1B1, thereby reducing its activity and minimizing the potential for the formation of 4-OH metabolites
NAC
-
Can reduce estrogen semiquinones back to catechol estrogens
-
Primary effect is to react with quinones to form conjugates preventing the formation of estrogen-DNA adducts
The Doctor’s Data HuMaP™ (Hormone and Urinary Metabolites Assessment Profile) test can provide insight into a patient’s unique hormone fingerprint. This innovative test provides an in-depth analysis of your patient’s hormone profile, empowering practitioners to precisely adjust enzymes and target estrogen metabolites. This customized approach effectively reduces prostate health risks. Experience the future of personalized prostate health management with HuMaP™.
|
|
|
|
|
|
|
References
https://www.cancer.org/cancer/types/prostate-cancer/about/key-statistics.html. Accessibility verified 5/17/2024.
Carnell DM, Smith RE, Daley FM, Barber PR, Hoskin PJ, Wilson GD, Murray GI, Everett SA. Target validation of cytochrome P450 CYP1B1 in prostate carcinoma with protein expression in associated hyperplastic and premalignant tissue. Int J Radiat Oncol Biol Phys. 2004 Feb 1;58(2):500-9. doi: 10.1016/j.ijrobp.2003.09.064. PMID: 14751521.
Cavalieri E, Rogan E. The 3,4-quinones of estrone and estradiol are the initiators of cancer whereas resveratrol and N-acetylcysteine are the preventers. International Journal of Molecular Sciences. 2021;22(15):8238. doi:10.3390/ijms22158238
Gajjar K, Martin-Hirsch PL, Martin FL. CYP1B1 and hormone-induced cancer. Cancer Lett. 2012 Nov 1;324(1):13-30. doi: 10.1016/j.canlet.2012.04.021. Epub 2012 May 2. PMID: 22561558.
Hodges RE, Minich DM. Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application. J Nutr Metab. 2015;2015:760689. doi:10.1155/2015/760689
Lin, Q., Cao, J., Du, X. et al. CYP1B1-catalyzed 4-OHE2 promotes the castration resistance of prostate cancer stem cells by estrogen receptor α-mediated IL6 activation. Cell Commun Signal 20, 31 (2022). https://doi.org/10.1186/s12964-021-00807-x
Ragavan N, Hewitt R, Cooper LJ, Ashton KM, Hindley AC, Nicholson CM, Fullwood NJ, Matanhelia SS, Martin FL. CYP1B1 expression in prostate is higher in the peripheral than in the transition zone. Cancer Lett. 2004 Nov 8;215(1):69-78. doi: 10.1016/j.canlet.2004.06.051. PMID: 15374634.
Romilly E. Hodges, Deanna M. Minich, "Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application", Journal of Nutrition and Metabolism, vol. 2015, Article ID 760689, 23 pages, 2015. https://doi.org/10.1155/2015/760689
Yager JD. Mechanisms of estrogen carcinogenesis: The role of E2/E1–quinone metabolites suggests new approaches to preventive intervention – A Review. Steroids. 2015;99:56-60. doi:10.1016/j.steroids.2014.08.006
Yao HT, Hsu YR, Lii CK, Lin AH, Chang KH, Yang HT. Effect of commercially available green and black tea beverages on drug-metabolizing enzymes and oxidative stress in Wistar rats. Food Chem Toxicol. 2014;70:120-127. doi:10.1016/j.fct.2014.04.043
|
|
|
|
|
|
|
|
Women's Hormone Homeostasis: A Guide to Health Through Testing, Treatment, and Lifestyle Solutions
|
|
|
|
|
|
|
Presented by Laura Neville, ND
June 5, 2024 at 9:30 AM and 12 PM Pacific
Each session is approximately 60 minutes with Q&A
Learning Objectives:
-
Identify the role of major hormones and pertinent metabolites
-
Match hormone testing method options (serum, saliva, urine) to clinical goals
-
Recognize unique approaches to PMS, PCOS, and endometriosis
-
Develop peri-menopause support for an easier transition through menopause
-
Compile botanical and nutritional, and lifestyle support of hormones
-
Understand hormonal controversy & hormone safety
-
Predict how tachyphylaxis relates to hormone replacement
-
Discuss new study findings on HRT past the age of 65
|
|
|
|
|
|
|
|
Rupa Lab Essentials Bootcamp:
Integrative Approaches to Migraines and Pain Management
|
|
|
|
|
|
|
Starting June 10, join Dr. Asare Christian, MD and members of the Doctor's Data clinical team for a 6-week deep dive into managing chronic pain and migraines!
This 6-week bootcamp covers a wide array of topics regarding pain management, including:
-
Defining pain types and function: Explain pain's concept, distinguishing its forms and role in bodily protection.
-
Exploring pain pathophysiology: Examine biological processes generating pain signals in the body.
-
Analyzing neuroanatomy and neurochemistry: Delve into nervous system structures and chemical messengers transmitting and modulating pain.
-
Understanding chronic pain as a neurological disorder: Present chronic pain as a brain disease, its development, impact on neural pathways, and treatment strategies.
This bootcamp includes GI360 and HuMap tests (over $1000 retail value). Some restrictions apply; see the Registration Page for more details.
The first class is on Monday, June 10, 2024. We hope to see you there!
|
|
|
|
|
|
|
Disclaimer: All information given about health conditions, treatment, products, and dosages are for educational purposes only and do not constitute medical advice.
|
|
|
|
|
|
|
800.323.2784 (US and Canada)
+1.630.377.8139 (Global)
|
|
|
|
|
|
