Estrogen Dominance

Estrogen Dominance Overview:

Estrogen dominance is a term used to describe a dysfunctional disparity between estrogen and progesterone. It doesn't specifically mean high estrogen. it can involve HIGH estrogen, with LOW/NORMAL progesterone, or NORMAL estrogen, with LOW progesterone.

It's important to differentiate this relationship because simply reducing estrogen or boosting progesterone can push the balance further out of order if an incorrect assumption is made.

 

Aetiology:

+ Estrogen Excess

Estrogen excess causes symptoms such as fluid retention (through changes to fluid osmolarity threshold through mechanisms involving ADH and ACTH), extended menstrual cycle and spotting in the luteal phase.

Estrogen excess is a condition involving a high estrogen to progesterone ratio. It can occur for many reasons, and can change depending on the timing in the menstrual cycle. Estrogen dominance can involve high or normal estrogen and low or normal progesterone.

Estrogen is converted from C19 steroids to estrogen via aromatase. This enzyme is encoded in the liver by the CYP19 gene [9]. E1 and E2 are metabolised by the phase 1 liver detoxification enzyme CYP1A1 into 2-hydroxy catechol metabolites with weak binding capacity and oestrogenic activity (potentially even antiestrogenic) [10].

Another set of enzymes encoded by the CYP3A4 and CYP3A7 convert E1 and E2 into 16-hydroxy catechols that are reported to have strong oestrogenic activity and binding capacity and are associated with increased proliferation of endometrial tissue [11]. CYP1B1 converts E1 and E2 into 4-hydroxy catechol oestrogen [12], which is also an active metabolite.

Therefore, shifting the ratio between 2-hydroxy, 4-hydroxy, and 16-hydroxy catechol oestrogens is an important therapeutic mechanism when addressing concerns over estrogen dominance.

This is achieved through inhibition of the 16-hydroxy catechol producing CYP3A4, and 4-hydroxy catechol producing CYP3B1, and inducing the 2-hydroxy catechol oestrogen producing CYP1A1.

High Xenoestrogen Exposure

Exposure to xenoestrogens in the environment may cause symptoms of estrogen excess. Removal of these factors is the first line of treatment if this is suspected.

Poor Liver Metabolism

Estrogen is broken down in the liver, and eliminated through the digestive tract. There are 3 main reasons why the liver may have difficulty eliminating estrogen, allowing it to gradually increase in concentration, or remain elevated for longer than it should.

  1. Nutrient deficiencies (vitamin B6, magnesium, copper, and zinc are all needed for metabolising estrogen)
  2. Liver disease, such as NAFLD, AFLD, or hepatitis may interfere with liver function
  3. Increased demand on the liver, reducing clearance of estrogens

+ Progesterone Deficiency

Progesterone has a negative feedback effect on the hypothalamus to reduce the effects of the HPG, while estrogen has a (mostly) positive feedback effect on the HPG. This means that estrogen is more likely to become in excess than progesterone is, however, it's crucial that this differentiation is made in order to provide effective treatment.

Low Dopamine

Low dopamine results in elevated prolactin levels, which can reduce progesterone levels. There are several causes for lowered dopamine levels:

  1. Nutrient deficiencies (such as tyrosine, magnesium, B6)

High Stress

Stress is thought to be a major cause for lowered progesterone levels through a theory called the "progesterone steal". this is a theory, and has not yet been proven. it suggests that the manufacture of cortisol during stressed states takes priority over progesterone production by robbing a common precurser, progesterone, from the cycle in order to make cortisol.

Screenshot 2018-06-09 17.54.40.png
 

+ Symptoms of High Estrogen

  • Fluid retention
  • Breast tenderness/Swelling

+ Symptoms of Low Progesterone

  • Poor concentration
  • Fluid retention
  • Clotting
  • Spotting
  • Depression/anxiety
  • Burnign throat
  • Cysts in breasts
  • Swollen breasts
  • Dry skin
  • Hair loss
  • Menorrhagia

General Symptoms:

Symptom

Symptom

Symptom

Symptom

Symptom

Symptom

Symptom

 

Diagnostic Considerations:

 

Therapeutic Aims:

1. Address Nutrient Deficiencies

  • Magnesium(Magnesium glycinate, Magnesium orotate, Magnesium threonate, Magnesium citrate)
  • Iron
  • Fatty Acids(Omega 3 fatty acids, omega 9 fatty acids)

2. Improve Estrogen Clearance

If estrogen levels are in excess

  • Choleretics(Gentiana lutea, Taraxicum officinale radix, Cynara scolymus, Schisandra chinensis, Rosmarinus officinalis)
  • Nutritional Considerations(DIM, increase fiber intake, Magnesium, B6, Zinc)
  • Alteratives(Taraxicum officinale folia)
  • Specific CYP3A1 Inducers(Rosmarinus officinalis, Silybum marianum)
  • Specific CYP3A4 Inhibitors(Turnera diffusa, Paeonia lactiflora, Rosmarinus officinalis, Silybum marianum)
  • Nutritional Considerations(DIM, increase fiber intake, Magnesium, B6, Zinc)

3. Increase Progesterone Production

If progesterone is low

  • Dopaminergics(Trichilia catigua, Vitex agnus-castus, Cimicifuga racemosa)
  • Nutritional Considerations(Magnesium, vitamin B6, fatty acids)
  • Prolactin Inhibitors(Withania somnifera)

4. Symptomatic Support For PMS

Fluid retention, depression, cramping, spotting/menorrhagia

  • Diuretics(Galium aparine, Taraxicum officinale, Urtica doica)
  • Nervines(Passiflora incarnata, Scutellaria lateriflora, Piper methysticum)
  • Antispasmodics(Passiflora incarnata, Zingiber officinale, Achillea millefolium, Lavandula angustifolia, Verbascum thapsus)
  • PGE Inhibitors (Tanacetum parthenium, Zingiber officinalis)
  • Antihemorrhagic(Achillea millefolium, Capsella bursa-pastoris, Alchemilla vulgaris, Rehmannia glutinosa)
 

Differential Diagnosis:

  • Hypothyroidism
  • Menopause
  • Ovarian cysts
  • Ovarian cancer
  • PCOS
  • PCOD
 

Comorbidities:

  • Anemia
  • Ovarian cancer
  • Ovarian cysts
  • Endometriosis
  • Hyppthyroidism
 

Cautions:

It's important to differentiate between progesterone deficiency, and estrogen excess, both will often present with similar symptoms.

 

Herbs For Estrogen Dominance:

Out of all the available herbs for estrogen dominance, Vitex appears to be the safest, and has the greatest level of evidence for normalising hormones in the presence of both progesterone deficiency, and estrogen excess.

Other Herbs to Consider

  • Feverfew
  • Ginger
  • Vitex agnus-castus
  • Shatvari
  • Capsella bursa pastoris
  • yarrow
  • Ladys mantle
  • Catuaba?
  • Dandilion
  • Cleavers
  • Withania
  • American skullcap
  • Passionflower
  • Lavender
 
 

Sample Estrogen Dominance Formula

Herb Name Ratio Amount in mL
Vitex agnus-castus 1:2 15 mL
Taraxicum officinale (Leaf) 1:2 20 mL
Taraxicum officinale (Root) 1:2 20 mL
Scutellaria lateriflora 1:2 20 mL
Gallium aparine 1:2 30 mL
Total 105 mL

Author:

Justin Cooke

The Sunlight Experiment

Updated: November 2017


Recent Blog Posts:

References:

  1. Stachenfeld, N. S. (2008). Sex hormone effects on body fluid regulation. Exercise and sport sciences reviews, 36(3), 152.

  2. Fitzgerald, P., & Dinan, T. G. (2008). Prolactin and dopamine: what is the connection? A review article. Journal of Psychopharmacology, 22(2_suppl), 12-19.

  3. Bone, K., & Mills, S. Y. (2013). Principles and Practice of Phytotherapy, Modern Herbal Medicine, 2: Principles and Practice of Phytotherapy. Elsevier Health Sciences.

  4. Hoffmann, D. (2003). Medical herbalism: the science and practice of herbal medicine. Simon and Schuster.

  5. Lessey, B. A., & Young, S. L. (2014, September). Homeostasis imbalance in the endometrium of women with implantation defects: the role of estrogen and progesterone. In Seminars in reproductive medicine (Vol. 32, No. 05, pp. 365-375). Thieme Medical Publishers.

  6. Cousins, L. M., Hobel, C. J., Chang, R. J., Okada, D. M., & Marshall, J. R. (1977). Serum progesterone and estradiol-17β levels in premature and term labor. American Journal of Obstetrics & Gynecology, 127(6), 612-615.

  7. Yu, L. L., Song, P. L., Guo, Z. L., Mu, Z. X., & CHEN, M. (2003). The Therapeutic Effect of Traditional Chinese Medicine Prescription Zhuyun III on Kidney-Deficiency and Luteal Phase Defect Aborting Rat Model [J]. Reproduction and Contraception, 1, 003.

  8. Shozu, M., Sebastian, S., Takayama, K., Hsu, W. T., Schultz, R. A., Neely, K., ... & Bulun, S. E. (2003). Estrogen excess associated with novel gain-of-function mutations affecting the aromatase gene. New England Journal of Medicine, 348(19), 1855-1865.

  9. Simpson, E. R., Mahendroo, M. S., Means, G. D., Kilgore, M. W., Hinshelwood, M. M., Graham-Lorence, S., ... & Mendelson, C. R. (1994). Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocrine reviews, 15(3), 342-355.

  10. Hamilton-Reeves, J. M., Rebello, S. A., Thomas, W., Slaton, J. W., & Kurzer, M. S. (2007). Soy Protein Isolate Increases Urinary Estrogens and the Ratio of 2: 16 α-Hydroxyestrone in Men at High Risk of Prostate Cancer. The Journal of nutrition, 137(10), 2258-2263.

  11. Obi, N., Vrieling, A., Heinz, J., & Chang-Claude, J. (2011). Estrogen metabolite ratio: Is the 2-hydroxyestrone to 16α-hydroxyestrone ratio predictive for breast cancer?. International journal of women's health, 3, 37.

  12. Hanna, I. H., Dawling, S., Roodi, N., Guengerich, F. P., & Parl, F. F. (2000). Cytochrome P450 1B1 (CYP1B1) pharmacogenetics: association of polymorphisms with functional differences in estrogen hydroxylation activity. Cancer Research, 60(13), 3440-3444.