Strategies to Modulate the Aromatase Enzyme

Lylen Ferris, ND | September 26, 2023

Aromatase (CYP19A1) is a cytochrome P450 enzyme expressed in the placenta, ovary, testes and adipose cells which catalyzes the synthesis of estrogens from androgens: testosterone to estradiol, and androstenedione to estrone. The activity of this enzyme, concentrated in peripheral adipose tissue such as buttocks, hips and thighs, is commonly increased due to inflammation, insulin resistance, excess alcohol, and obesity in both males and females. 

In post-menopausal women, when the ovaries cease producing estrogen, aromatase activity can become an important means of estrogen production by converting androgens into estrogens. In aging males, monitoring the activity of aromatase can prove informative as it may be clinically useful to slow the activity of this enzyme to preserve testosterone levels. 

Pharmaceutical aromatase inhibitors (AI) have become routine in the management of postmenopausal females with estrogen receptor positive (ER+) breast cancer. AIs work to block the production of aromatase and impede estrogen synthesis. In females, studies have identified higher aromatase activity in breast cancer tissues compared to healthy breast tissue. While AIs are not able to block the synthesis of estrogen from the ovaries in reproductive age women, in post-menopausal women, AIs inhibit estrogen synthesis from peripheral tissue. 

In males with hypogonadism who are utilizing testosterone replacement therapy, AIs can slow potential conversion of testosterone to estrogen. Too much conversion to estrogen could result in gynecomastia, erectile dysfunction, increased risk of cardiovascular disease, severe edema, and potentially contribute to hyperproliferation of prostate cells. AIs can help to slow this conversion. 

The most commonly used pharmaceutical AIs are anastrozole, exemestane, and letrozole.  

However, it is not only females with breast cancer and males with gynecomastia who could benefit from slowing aromatase activity. The Doctor’s Data Hormone and Urinary Metabolites Assessment Profile or HuMapTM will identify the activity of the aromatase enzyme by reporting values of testosterone and androstenedione as well as estradiol and estrone. By comparing these values, aromatase activity is highlighted. If testing indicates a need to support or slow down aromatase activity, non-pharmaceutical approaches such as lifestyle management and nutraceutical supplementation are considerations. 

Aromatase activity is increased when a patient is obese, insulin resistant, stressed, or experiencing chronic inflammation. Supporting them in weight loss, stress management, and utilizing anti-inflammatory therapies are effective ways to slow enzyme activity. Therapeutically, there are natural substances shown to slow aromatase activity including chrysin, zinc, nettles, damiana, grape seed, ECGC, resveratrol, licorice, and flavonoids. 

It is less common to find a need to increase aromatase activity. In patients with blunted aromatase activity, one might expect to see excess androgens and lower estrogens. This is typically more of a problem in females. Lifestyle strategies that can be utilized to speed up aromatase activity include Coleus forskohlii and iron (if the patient is iron deficient). 

Note: SSRIs have been shown to both increase and decrease aromatase regulation activities. 

To support providers in choosing supplementation strategies for their patients based on HuMapTM results, Doctor’s Data has created the “Hormone and Urinary Metabolites Assessment Profile: Clinical and Therapeutic Considerations” as a resource. Here you will find more research-based suggestions for supporting healthy aromatase activity and hormone metabolism in general. Providers with a Doctor’s Data account can also call our Clinical Education department to discuss specific patient results to determine potential support and treatment plans.  

 

References

Chumsri S. Clinical utilities of aromatase inhibitors in breast cancer. Int J Womens Health. 2015 May 6;7:493-9. doi: 10.2147/IJWH.S69907. PMID: 26005359; PMCID: PMC4427607. 

Hussain, Aatif; Gilloteaux, Jacques (2020-09-01). "The human testes: Estrogen and ageing outlooks". Translational Research in Anatomy. 20: 100073. doi:10.1016/j.tria.2020.100073. ISSN 2214-854X. S2CID 219001284 

Breastcancer.org. 29 October 2020. https://www.breastcancer.org/treatment/hormonal-therapy/aromatase-inhibitors 

Farnsworth, W. “Roles of estrogen and SHBG in prostate physiology”. Prostate. 1996;28:17-23.  

Miller WR. Aromatase activity in breast tissue. J Steroid Biochem Mol Biol. 1991 Nov;39(5B):783-90. doi: 10.1016/0960-0760(91)90026-2. PMID: 1954167. 

Monteiro R, Soares R, Guerreiro S, Pestana D, Calhau C, Azevedo I. Red wine increases adipose tissue aromatase expression and regulates body weight and adipocyte size. Nutrition. 2009 Jun;25(6):699-705. doi: 10.1016/j.nut.2009.01.001. Epub 2009 Mar 5. PMID: 19268535. 

Balam FH, Ahmadi ZS, Ghorbani A. Inhibitory effect of chrysin on estrogen biosynthesis by suppression of enzyme aromatase (CYP19): A systematic review. Heliyon. 2020;6(3):e03557. Published 2020 Mar 7. doi:10.1016/j.heliyon.2020.e03557 

Om AS, Chung KW. Dietary zinc deficiency alters 5 alpha-reduction and aromatization of testosterone and androgen and estrogen receptors in rat liver. J Nutr. 1996;126(4):842-848. doi:10.1093/jn/126.4.842  

Zhao J, Dasmahapatra AK, Khan SI, Khan IA. Anti-aromatase activity of the constituents from damiana (Turnera diffusa). J Ethnopharmacol. 2008;120(3):387-393. doi:10.1016/j. jep.2008.09.016  

Kijima I, Phung S, Hur G, Kwok SL, Chen S. Grape seed extract is an aromatase inhibitor and a suppressor of aromatase expression. Cancer Res. 2006;66(11):5960-5967. doi:10.1158/0008- 5472.CAN-06-0053  

Chrubasik JE, Roufogalis BD, Wagner H, Chrubasik S. A comprehensive review on the stinging nettle effect and efficacy profiles. Part II: urticae radix. Phytomedicine. 2007;14(7-8):568- 579. doi:10.1016/j.phymed.2007.03.014 

Watanabe M, Nakajin S. Forskolin up-regulates aromatase (CYP19) activity and gene transcripts in the human adrenocortical carcinoma cell line H295R. J Endocrinol. 2004;180(1):125- 133. doi:10.1677/joe.0.1800125 


 

Addressing the Hidden Epidemic of Yeast Overgrowth: Test Interpretation and Treatment Options

Dan Kalish, DC, IFMCP

 September 28, 2023 at 4 PM Pacific

Each session is approximately 60 minutes with Q&A

Join Dr. Kalish for this free webinar on one of the most often overlooked health concerns, yeast overgrowth in the GI tract. The wide range of potential symptoms stemming from yeast problems, ranging from fatigue to depression, make this condition difficult to determine from patient history and symptoms alone. In the absence of obvious GI complaints, lab testing for yeast and fungal overgrowth reveals those suffering from chronic health complaints driven by hidden GI problems. We will look at the types of yeast overgrowth, and discuss the most effective treatment options for these types of problems.

 
 

Some Diseases Do Begin in the Gut: The Gut Microbiome and Chronic Disease

Julia Malkowski, ND, DC

 October 4, 2023 at 9:30AM and 12 PM Pacific

Each session is approximately 60 minutes with Q&A

Approximately half of all Americans will suffer chronic disease in their lifetime. The burden of chronic disease poses a significant impact regards to public health and individual health. There exists a connection between the gut microbiome and the pathogenesis of chronic disease. This talk will discuss this intricate link between he gut microbiome and chronic disease. Prevalent chronic diseases such as obesity, diabetes, cancer, Alzheimer's and depression will be discussed in relation to the gut microbiome. Appropriate evaluation of the GI microbiome will be discussed alongside clinical considerations. Attendees will take away an understanding of the pathogenesis of chronic disease and the gut microbiome.

Learning Objectives:

  1. Understand the significant role chronic disease plays on an individual and national level
  2. Understand the role of the gut microbiome in the pathogenesis of chronic disease
  3. Gain knowledge of appropriate gut testing
  4. Knowledge of appropriate gut microbiome evaluation and clinical considerations


 
 

Mastering the Neurotransmitter-HPA Axis Connection for Enhanced Patient Outcomes

Presented by Lylen Ferris, ND

October 11, 2023 at 11 AM Pacific

Each session is approximately 60 minutes with Q&A

Stress, driven by inflammation, circadian disruption, glycemic dysregulation, and perceived stress, affects multiple systems. In the context of stress-related concerns, the common approach of examining the Hypothalamic-Pituitary-Adrenal (HPA) axis via cortisol and DHEA assessment overlooks the intricate interplay between neurotransmitters and the HPA axis. These intertwined systems must be understood holistically.

For instance, heightened serotonin levels trigger an increase in Adrenocorticotropic Hormone (ACTH), subsequently elevating cortisol and DHEA release. Conversely, low cortisol prompts ACTH elevation, fostering serotonin release to compensate for adrenal demands. A dynamic loop exists within the HPA axis, relying on both systems' vitality for optimal function.

The fight or flight response is governed by epinephrine, norepinephrine, and cortisol. Neuroadrenal testing reveals patterns of neuroadrenal/sympathetic fatigue stages, crucial for supporting the HPA axis and stress response, including epinephrine, norepinephrine, and cortisol responsiveness.

Elevating overall health involves assessing these biochemical networks, and shedding light on effective treatment strategies. Participants will uncover how neuroadrenal imbalance influences mental and physical symptoms like energy levels, mood, focus, cognition, and sleep.

By fortifying neurotransmitters, HPA axis dysregulation can be mitigated or even reversed. As HPA axis balance is restored, we can observe neurotransmitters regain harmony. The course delves into treatment considerations utilizing lifestyle adjustments and natural interventions. Real-life case studies solidify these concepts, enabling practical clinical applications. Join Lylen Ferris, ND to comprehend these intricate systems, optimizing health by harmonizing neurotransmitters and HPA axis dynamics.

Learning Objectives:

  1. Adrenal hormones and neurotransmitters will be discussed in order to understand their role in patient health, with an emphasis on the stress response and how it contributes to chronic disease and common symptoms.
  2. Explore the NeuroAdrenal Profile as a tool to assess a patient's stress response.
  3. By assessing the HPA axis and neurotransmitter secretion, healthcare providers can offer more comprehensive and individualized care to patients with chronic stress-related conditions.
  4. Stress is pervasive. All practitioners can learn from this class.


 

Disclaimer: All information given about health conditions, treatment, products, and dosages are for educational purposes only and do not constitute medical advice.

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