|
16-OH E1: A Key Player in Bone Density
|
Ruth Hobson, ND | June 26, 2023
|
|
|
|
|
|
|
Most of the clinical focus surrounding estrogen metabolism is directed toward the balance between the more protective 2-hydroxy (2-OH) and more proliferative 4-hydroxy (4-OH) metabolites of estrone (E1) and estradiol (E2).The metabolite 16-hydroxy estrone (16-OH E1) on the other hand, may represent a grey area when it comes to the risk- reward calculator of bone health.
16-OH E1, a major metabolite of estrone and intermediate in the synthesis of estriol (E3), has been shown to possess estrogenic activity due to its ability to bind to estrogen receptors in hormonally sensitive tissues such as uterine and breast. Women with a higher proportion of 16-OH E1 metabolites may be at higher risk of developing breast cancer. Yet, emerging research indicates 16-OH E1 may be beneficial to other processes such as the retention of bone density in aging males and females.
Bone loss in the postmenopausal female:
The peri and postmenopausal periods naturally result in significant fluctuations in estrogen levels leading to an array of symptoms including those that are well-known such as hot flashes and mood instability, to lesser-known structural issues related to the loss of collagen, elastin, and bone. After menopause, when ovarian production ceases, estrogen is produced to a small degree in the adrenal glands and via aromatase in peripheral tissue to assist with the maintenance of cardiovascular, bone, and brain health. It is during this time that the primary circulating form of estrogen shifts from the more potent estradiol (E2) to the less potent estrone (E1). Studies also suggest that certain estrogen metabolites may influence bone mineral density (BMD). But what is the mechanism?
E1 and E2 are hydroxylated via the enzyme CYP1A1 to enter the 2-OH pathway; and via CYP1B1 toward the 4-OH pathway. The enzyme CYP3A4 metabolizes E1 to 16-OH E1, and E2 to E3. It has been shown that 2-OH metabolites have a low affinity for estrogen receptors. Thus, they are considered safer when it comes to proliferative effects. 16-OH E1, on the other hand, has been shown to have estrogenic effects similar to, but less potent than, estradiol, resulting in its reputation as an unsafe metabolite due to its proliferative effects on breast and uterine tissues
Interestingly, when it comes to bone health, 16-OH E1 may have a protective function in its similar action to estradiol with the ability to decrease cortical bone loss and enhance bone mineral density (BMD). Studies of 16-OH E1 have also shown a cholesterol lowering effect. Some researchers have suggested that females with higher 16-OH E1 levels may have a decreased risk for post-menopausal osteoporosis than those with lower levels. Additionally, those with a genetic defect in the CYP1A1 enzyme, leading to a higher rate of metabolism of 2-OH, appear to have a greater risk for development of osteoporosis due to the lack of estrogenic effects via 2-OH metabolites.
In females with postmenopausal osteopenia, one study showed reduced activity of 16-OH-E1 and/or increased activity of 2-OH, leading researchers to conclude that these alterations may contribute to accelerated bone loss in this population. Ginkgo Biloba and St John’s Wort have been shown to increase the activity of CYP3A4 in vitro, and Vitamin D in vivo, potentially contributing to healthy 16-OH E1 levels to support bone health.
Bone loss in males:
Some studies have suggested that estrogen is an important hormone for BMD in males, perhaps even having more osteoblastic properties than testosterone. In fact, fracture risk has been linked to lower circulating free E2, calculated via the free estrogen index. However, little research is available regarding the relationship between BMD and estrogen metabolism. Researchers conducted a study to evaluate the hypothesis that male bone loss, similar to postmenopausal females, may be the result of altered estrogen metabolites. Their small study involved 61 Caucasian males around the age of 50. Results demonstrated higher levels of both 16-OH E1 and E3 associated with higher BMD; this was seen in vertebral bone and to an even greater extent, femoral bone. While research in this area continues to emerge, authors suggest that since estrogen metabolism is something that happens throughout a male’s life, shifting metabolism toward 16-OH E1 may be beneficial or even preventive for those at risk of bone loss. A word of caution: shifting metabolism to favor 16-OH E1 may include risk to prostatic tissue due to the potential for 16-OH E1’s estrogenic influence.
From an integrative medical approach, considering a patient’s risk potential for future pathology could inform preventive treatment approaches. For these reasons, the Hormone and Urinary Metabolites Assessment Profile (HuMap™) is an essential baseline test for any aging patient. Considering how shifts in estrogen metabolism affect different tissues, including bone, could provide valuable information for the patient care of both aging women and men.
|
|
|
|
|
|
|
References
Napoli, N., Villareal, D. T., Mumm, S., Halstead, L., Sheikh, S., Cagaanan, M., Rini, G. B., & Armamento-Villareal, R. (2004). Effect of CYP1A1 gene polymorphisms on estrogen metabolism and bone density. Journal of Bone and Mineral Research, 20(2), 232–239. https://doi.org/10.1359/jbmr.041110
Lim, S.-K. (1998). Altered hydroxylation of estrogen in patients with postmenopausal osteopenia--authors’ Responseb. Journal of Clinical Endocrinology & Metabolism, 83(11), 4171–4171. https://doi.org/10.1210/jc.83.11.4171
Leelawattana, R., Ziambaras, K., Roodman-Weiss, J., Lyss, C., Wagner, D., Klug, T., Armamento-Villareal, R., & Civitelli, R. (2000). The oxidative metabolism of estradiol conditions postmenopausal bone density and bone loss. Journal of Bone and Mineral Research, 15(12), 2513–2520. https://doi.org/10.1359/jbmr.2000.15.12.2513
Napoli, N., Faccio, R., Shrestha, V., Bucchieri, S., Rini, G. B., & Armamento-Villareal, R. (2007). Estrogen metabolism modulates bone density in men. Calcified Tissue International, 80(4), 227–232. https://doi.org/10.1007/s00223-007-9014-4
Whitten DL, Myers SP, Hawrelak JA, Wohlmuth H. The effect of St John’s wort extracts on CYP3A: a systematic review of prospective clinical trials. Br J Clin Pharmacol. 2006;62(5):512-526. doi:10.1111/j.1365-2125.2006.02755.x
Hellum BH, Hu Z, Nilsen OG. The induction of CYP1A2, CYP2D6 and CYP3A4 by six trade herbal products in cultured primary human hepatocytes. Basic Clin Pharmacol Toxicol. 2007;100(1):23-30. doi:10.1111/j.1742-7843.2007.00011.x
Wang Z, Schuetz EG, Xu Y, Thummel KE. Interplay between vitamin D and the drug metabolizing enzyme CYP3A4. J Steroid Biochem Mol Biol. 2013;136:54-58. doi:10.1016/j.jsbmb.2012.09.012
|
|
|
|
|
|
|
|
Mastering the Art of Hormone Testing and Prescribing
|
|
|
|
|
|
|
Laura Neville, ND
July 12, 2023 at 9:30 AM and 12 PM Pacific
Each session is approximately 60 minutes with Q&A
Learning Objectives:
1. Differentiate vast nomenclature that describes various hormone treatments
2. Compare hormone prescribing options including:
|
○ Routes of administration
○ Potencies
○ Schedules
3. Examine laboratory monitoring schedules
4. Evaluate best practices for hormone specimen collection
5. Gain fluency in writing prescriptions for compounded and conventional formulations
6. Analyze commonly seen cases and treatment considerations
|
|
|
|
|
|
|
|
The Mighty Microbiome and the Anti-Aging Edge
|
|
|
|
|
|
|
Presented by Cheryl Burdette, ND | July 26, 2023 at 12 PM PDT
Each session is approximately 60 minutes with Q&A
|
Biological changes in the gut microbiome as we age may be connected to overall healthy aging and increased survival rates. Learning more about the balance of our microbiome is an evolving scientific and its relationship to quality of life is becoming more and more elucidated. Current findings suggest potential connections to many health conditions including obesity, metabolic disorders, inflammation, cancer, and depression.
Throughout the human life span, gut microbiome follows some predictable patterns, with rapid change from infancy to age three, stability up until middle age, and then accelerated change starting in late adulthood. As the microbiome ages, so do we. When microbiomes change, so does the trajectory of quality of life and longevity. In this talk we will examine the association of various pathogens in the gut and their effect on longevity, as well as signaling mechanisms that are dictated by the microbiome such as activity of transcription factors, interleukins, SCFA, and gut based nitric oxide as it relates to systemic anti-aging. The heart of aging gracefully lies in being a hospitable living condition for the microbiome within.
|
Learning Objectives:
-
To review certain beneficial species as they pertain to anti-aging and therapies that increase their growth
-
To review anti-aging markers such as butyrate and bile as they relate to the aging process
-
To review nitric oxide and gut-based health as it relates to aging and a diverse microbiome
|
|
|
|
|
|
|
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)
|
|
|
|
|
|
