Endometriosis is often a painful condition in which tissue, similar to uterine lining tissue, grows outside of the uterus. This growth forms painful adhesions that respond to hormone signals to thicken, break down, and bleed with each cycle, just as uterine lining tissue typically does. Adhesions can grow near the ovaries, fallopian tubes, bladder, rectum, stomach, and other areas of the abdominal cavity. It’s estimated that 11% of women in the U.S. ages 15-44 have endometriosis, and it’s a common contributor to infertility.
[signup]
CC: Endometriosis, Irregular Cycles, Heavy and Painful Periods, Constipation
Amber* was a 34-year-old female who had been diagnosed with endometriosis a year prior to our initial consultation. Her symptoms that led to the diagnosis - irregular menstrual cycles, severe pain around her period or when trying to have a bowel movement, heavy periods, and constipation - had not been helped by the original treatment she had been given (oral contraceptives). Amber felt worse on birth control and had tried two different forms before her OB-GYN suggested surgery to assess and remove adhesions. During the surgery, it was found that Amber had adhesions around her ovaries and outside of the uterus, which were removed, though she only had mild relief post-surgery. At this point, Amber decided to look into functional medicine to see how else she could support herself and find relief, as she did not want to try oral contraceptives again.
Amber had had varying cycle lengths for “as long as she could remember,” ranging from 25-40 days, though her periods had become heavier and painful in her 30s. She had dealt with constipation for most of her adult life and had tried various laxatives and supplements to try to resolve symptoms without much success. Amber had not really made any dietary changes to address her symptoms and was eating a Standard American Diet at the time of her initial consultation. She was taking a multivitamin and a melatonin supplement at night and was on no other supplements or medications.
Amber ran a social media management company from home and managed a team of 10 employees. She admitted her stress levels had been high for a few years since starting this business, and she often worked late nights and early mornings and felt she didn’t always have a great balance in her life.
During a review of systems, Amber also brought up that she wasn’t sleeping well and often woke up throughout the night. Additionally, she felt that her energy went up and down all day, and she relied on coffee throughout the morning and early afternoon to stay focused. She walked most mornings around her neighborhood and occasionally went to a group fitness class at her local gym, but hadn’t had a consistent exercise routine in years.
Lab Work
The following specialty labs were run:
GI-MAP Comprehensive Stool Test Results
The GI-MAP by Diagnostic Solutions resulted in:
- LOW Pancreatic Elastase
- ELEVATED Beta-glucuronidase
- ELEVATED H. pylori
- ELEVATED Opportunistic/dysbiotic bacteria species
- LOW Commensal bacterial spp.
DUTCH Hormone Testing
A DUTCH Complete Test by Precision Analytics showed high levels of estrone and estradiol, with high levels of the 16-OH-E1 estrogen metabolite as well. It’s common to see women with endometriosis favor the 2-OH and 4-OH estrogen metabolite pathways like Amber does, though elevations of 16-OH-E1 often signal that there’s ongoing inflammation in the body. Her test also showed low methylation activity, an important epigenetic process for liver detoxification of estrogen. Amber's test also showed elevated testosterone metabolites and elevated cortisol in the afternoon, evening, and morning.
Micronutrient Test Results
A micronutrient test like SpectraCell's Micronutrient Test showed low levels of zinc, magnesium, iron, vitamin D, and vitamin B12.
Additional Lab Results
Lab Analysis
Amber's lab work points to a few different problems that are contributing to her ongoing symptoms.
Dysbiosis, Malabsorption, and Other Gut Findings
Amber’s stool test showed low-normal pancreatic elastase, indicating low digestive enzyme function and potential malabsorption. This can often lead to not absorbing nutrients well from the diet and may also cause bloating, constipation, and other digestion symptoms. Her results also showed elevated beta-glucuronidase, a byproduct of bacterial metabolism that can reactivate estrogens rather than eliminate them from the digestive tract, leading to recirculation of estrogens and symptoms of excess estrogen. Amber's GI-MAP test also showed elevated opportunistic bacteria and low commensal (keystone) bacteria, indicating dysbiosis is present. A dysbiotic microbiome can cause inflammation, impaired detoxification ability, and even hormone imbalances and has been linked as a potential contributor to the development of endometriosis.
Hormone Imbalances
Amber had several patterns typical of endometriosis patients, including elevated estrogens, elevated estrogen metabolites, and elevated DHEA. Estriol (E3) and its metabolite 16-OH-E1 tend to be proliferative in nature, meaning tissues like to grow, a process that defines endometriosis. She also had elevated cortisol, indicating some dysfunction in her stress pathways that can worsen endometriosis symptoms; Amber also had low free T3, which can occur in states of chronic stress and inflammation.
Multiple Micronutrient Depletions
Amber had several vitamin and mineral depletions apparent on her micronutrient testing, including zinc, magnesium, iron, vitamin D, and vitamin B12. Zinc, potassium, and B12 deficiencies have all been linked to a higher risk of endometriosis, while low vitamin D levels have been correlated in several studies with endometriosis.
Interventions
Amber did not want to try oral contraceptives again, and her OB-GYN was supportive in co-managing her case to try a functional medicine approach to support her symptoms before considering surgery again in the future. Amber’s therapeutic plan recommendations are listed below:
- Started magnesium glycinate, 300mg, and Cortisol Manager by Integrative Therapeutics at night to help reduce stress, support cortisol levels, and aid in sleep. Additionally, we worked on creating a “winding down” ritual in the evenings to help with her sleep instead of continuing to work late into the night.
- Started vitamin D, 4000 IU/day (Apex Energetics Liqua-D)
- Started comprehensive digestive enzyme (Thorne) to help support food breakdown and nutrient absorption.
- Added in digestive bitters before larger meals to help stimulate stomach acid and digestive enzyme production.
- For 8 weeks, followed a protocol to help address dysbiosis, H. Pylori, and Amber’s gut testing results:
- Gi-Microb-X, an antimicrobial blend to help eradicate opportunistic microbes in the gut, alongside a binder to assist in elimination and minimize die-off symptoms
- To address H. Pylori, added in Pylori-plex by Douglas Labs, which contains mastic gum as well as a blend of licorice, marshmallow, and slippery elm.
- Repairvite powder, 1 scoop for 30 days, which is rich in zinc carnosine to aid in healing the stomach and gut mucosa.
- Started an omega-3 supplement, 2 grams twice daily.
- Started taking DIM, 200mg/day, to support phase 1 estrogen metabolism and to push more towards the 2-OH pathways rather than the 16-OH pathway and FemGuard + Balance by Designs for Health to help reduce overall estrogen
Nutrition Interventions:
- Amber started to follow an anti-inflammatory, Mediterranean-type diet with plenty of vegetables, fruits, root vegetables, healthy fats, whole grains like gluten-free oats and quinoa, and quality protein sources. We reduced her intake of white bread, processed carbohydrates, processed foods, and wine. Emphasis was on protein sources rich in minerals like zinc to help address micronutrient deficiencies, including grass-fed beef, shellfish, and whole eggs.
- We found a local meal prep service to help prep healthy meals to cut down on the overwhelm that can sometimes come with making big dietary shifts, and Amber appreciated that it saved her a lot of prep time
- Foods high in glucuronic acid, like apples, Brussel sprouts, cooked cruciferous vegetables, and oranges were included to help reduce the high levels of beta-glucuronidase.
- Brought her caffeine intake down to just one cup daily with her first meal.
- Prebiotic and probiotic foods were emphasized to help support the growth of beneficial commensal microbes in the gut.
- We also focused on eating hygiene: chewing food well, slowing down and stepping away from work while eating, and taking a few slow breaths before starting a meal.
- To help nutritionally support the reduction of H. Pylori, we also had Amber:
Lifestyle Recommendations:
- Amber started walking consistently every day and began working with a personal trainer 2x a week to get into more of a routine with exercise.
- Additionally, we focused on bringing more “breaks” into Amber’s day, which involved short walks, getting outside, or doing something fun to break up her demanding work schedule.
- We had Amber incorporate stress reduction and nervous system regulation strategies, including breathwork and meditation, to help address her high stress levels.
- Amber started using castor oil packs over the abdomen 2-3x per week, which can help with constipation, liver support, and pain reduction.
- Last, we did a clean-up of Amber’s personal care products, swapping out her most commonly used beauty and cleaning products for fragrance-free, low or non-tox products to help reduce exposure to xenoestrogens.
Within 6 weeks, Amber’s constipation had improved dramatically, and she was having a daily bowel movement. She had lost about 10 pounds and had told us she was feeling better than she had in years. Within 4 months, Amber reported she had minimal pain around her periods and had had two consecutive 29-day cycles instead of the varying length cycles she had been experiencing previously. We stopped the FemGuard + Balance at that point and continued to emphasize the nutritional recommendations and estrogen-metabolizing foods.
Follow-Up Labs 6 Months Later
Micronutrient Testing Follow-Up Results:
All were within normal range.
GI-MAP Follow-up Results:
- H. pylori not detected
- Commensal/keystone bacteria all within normal limits
- Low beta-glucuronidase
- Normal pancreatic elastase
- No “high” levels of opportunistic bacteria
DUTCH Adrenal Results (To Retest 4-point Cortisol):
All measurements were back within normal range, though morning cortisol looked a bit at the high end of the range.
Follow-Up Interpretations and Continued Interventions
Over the course of 6 months, Amber implemented all of the recommendations with regular check-ins and guidance. Amber found she really enjoyed working with her personal trainer and had increased her sessions to 3x per week, as she felt it kept her stress in check.
All of Amber’s lab marks returned to normal ranges by the 6-month mark, and she had had 4 consecutive 27-8 day cycles with minimal pain. She was having 1-2 bowel movements daily, had lost 18 pounds overall, and had started working to hire more help in her business so she could continue to strike a better balance. Amber had decided to continue with the nutritional style we had put in place for her, though she felt confident she could now sometimes have a “night off” when out with friends without worrying it would derail her progress. Amber planned to continue the following supplements: omega-3, magnesium and Cortisol Manager, digestive bitters as needed, and vitamin D at 2000IU/day.
[signup]
Summary
This case highlights the inflammatory nature of endometriosis as well as the importance of deeply investigating not only estrogen levels but estrogen metabolism as well. For Amber to experience relief, we had to support her gut microbiome, stress levels, and detoxification pathways to help ensure she could metabolize and eliminate excess estrogen while also evaluating her nutritional and environmental factors that could impact estrogen levels. Amber had to make a lot of changes in her lifestyle to get the results she wanted, and with consistency, she was able to address her overall health and strike a sustainable balance to support her body and minimize symptoms.
Lab Tests in This Article
References
16alpha Hydroxyestrone - an overview | ScienceDirect Topics. (n.d.). Www.sciencedirect.com. https://www.sciencedirect.com/topics/medicine-and-dentistry/16alpha-hydroxyestrone
Amanda’s 6 Month Journey to Healing Her IBS and Endometriosis Pain: A Case Study. (2023, May 17). Rupa Health. https://www.rupahealth.com/post/endometriosis-case-study
Appleyard, C. B., Flores, I., & Torres-Reverón, A. (2020). The Link Between Stress and Endometriosis: from Animal Models to the Clinical Scenario. Reproductive Sciences, 27(9), 1675–1686. https://doi.org/10.1007/s43032-020-00205-7
Biscione, A., Bernardi, M., Barrasso, G., Verrone, A., Amoruso, N., Starace, A., Bellone, E., Darino, I., Centini, G., & Luisi, S. (n.d.). Role of DHEA and DHEA-S in the pathogenesis and progression of endometriosis * Introduction * Results. Retrieved October 27, 2023, from https://seud.org/wp-content/uploads/2018/06/193-Biscione.pdf
Claus, S. P., Guillou, H., & Ellero-Simatos, S. (2016). The gut microbiota: a major player in the toxicity of environmental pollutants? Npj Biofilms and Microbiomes, 2(1). https://doi.org/10.1038/npjbiofilms.2016.3
Endometriosis | Office on Women’s Health. (n.d.). Www.womenshealth.gov. https://www.womenshealth.gov/a-z-topics/endometriosis#:~:text=How%20common%20is%20endometriosis%3F
Ervin, S. M., Li, H., Lim, L., Roberts, L. R., Liang, X., Mani, S., & Redinbo, M. R. (2019). Gut microbial β-glucuronidases reactivate estrogens as components of the estrobolome that reactivate estrogens. The Journal of Biological Chemistry, 294(49), 18586–18599. https://doi.org/10.1074/jbc.RA119.010950
Halpern, G., Schor, E., & Kopelman, A. (2015). Nutritional aspects related to endometriosis. Revista Da Associação Médica Brasileira, 61, 519–523. https://www.scielo.br/j/ramb/a/FCFF8JMHW7YqL9RN6w38xPp
He, S., Li, H., Yu, Z., Zhang, F., Liang, S., Liu, H., Chen, H., & Lü, M. (2021). The Gut Microbiome and Sex Hormone-Related Diseases. Frontiers in Microbiology, 12. https://doi.org/10.3389/fmicb.2021.711137
Helmreich, D. L., Parfitt, D. B., Lu, X.-Y. ., Akil, H., & Watson, S. J. (2005). Relation between the Hypothalamic-Pituitary-Thyroid (HPT) Axis and the Hypothalamic-Pituitary-Adrenal (HPA) Axis during Repeated Stress. Neuroendocrinology, 81(3), 183–192. https://doi.org/10.1159/000087001
Howell, A. B. (2020). Clinical evidence supporting cranberry as a complementary approach to Helicobacter pylori management. Food Frontiers, 1(3), 329–331. https://doi.org/10.1002/fft2.47
Kahlon, B. K., Simon-Collins, M., Nylander, E., Segars, J., & Singh, B. (2023). A systematic review of vitamin D and endometriosis: role in pathophysiology, diagnosis, treatment, and prevention. F&S Reviews, 4(1), 1–14. https://doi.org/10.1016/j.xfnr.2022.11.005
Maholy, Dr. N. (2023b, March 16). Integrative Medicine Approach to Estrogen Excess: Testing, Diagnosis, & Treatment. Rupa Health. https://www.rupahealth.com/post/integrative-medicine-approach-to-estrogen-excess-testing-diagnoses-treatment
Mayo Clinic. (2018, July 24). Endometriosis - Symptoms and Causes. Mayo Clinic; Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/endometriosis/symptoms-causes/syc-20354656
Messalli, E. M., Schettino, M. T., Mainini, G., Ercolano, S., Fuschillo, G., Falcone, F., Esposito, E., Di Donna, M. C., De Franciscis, P., & Torella, M. (2014). The possible role of zinc in the etiopathogenesis of endometriosis. Clinical and Experimental Obstetrics & Gynecology, 41(5), 541–546. https://pubmed.ncbi.nlm.nih.gov/25864256/
Murali, M. R., Naveen, S. V., Son, C. G., & Raghavendran, H. R. B. (2014). Current knowledge on alleviating Helicobacter pylori infections through the use of some commonly known natural products: bench to bedside. Integrative Medicine Research, 3(3), 111–118. https://doi.org/10.1016/j.imr.2014.04.001
Othman, E. R., Markeb, A. A., Khashbah, M. Y., Abdelaal, I. I., ElMelegy, T. T., Fetih, A. N., Van der Houwen, L. E., Lambalk, C. B., & Mijatovic, V. (2020). Markers of Local and Systemic Estrogen Metabolism in Endometriosis. Reproductive Sciences, 28(4), 1001–1011. https://doi.org/10.1007/s43032-020-00383-4
Roshanzadeh, G., Jahanian Sadatmahalleh, S., Moini, A., Mottaghi, A., & Rostami, F. (2023). The relationship between dietary micronutrients and endometriosis: A case-control study. International Journal of Reproductive Biomedicine, 21(4), 333–342. https://doi.org/10.18502/ijrm.v21i4.13272
Stoicov, C., Saffari, R., & Houghton, J. (2009). Green tea inhibits Helicobacter growth in vivo and in vitro. International Journal of Antimicrobial Agents, 33(5), 473–478. https://doi.org/10.1016/j.ijantimicag.2008.10.032
Sweetnich, J. (2023, February 15). How to Support Optimal Liver Estrogen Detoxification. Rupa Health. https://www.rupahealth.com/post/how-the-liver-affects-female-hormones
Weinberg, Dr. J. (2022b, November 16). 4 Science Backed Health Benefits of The Mediterranean Diet. Rupa Health. https://www.rupahealth.com/post/4-science-backed-health-benefits-of-the-mediterranean-diet
Weinberg, Dr. J. (2023b, May 9). What are Xenoestrogens and How To Test for Exposure. Rupa Health. https://www.rupahealth.com/post/what-are-xenoestrogens-and-how-you-can-avoid-them
Wieczorek, K., Szczęsna, D., & Jurewicz, J. (2022). Environmental Exposure to Non-Persistent Endocrine Disrupting Chemicals and Endometriosis: A Systematic Review. International Journal of Environmental Research and Public Health, 19(9), 5608. https://doi.org/10.3390/ijerph19095608
Zizolfi, B., Foreste, V., Gallo, A., Martone, S., Giampaolino, P., & Di Spiezio Sardo, A. (2023). Endometriosis and dysbiosis: State of art. Frontiers in Endocrinology, 14(14). https://doi.org/10.3389/fendo.2023.1140774