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Unravelling the Mysteries of Hormones

Hormones are very tiny, very sensitive chemical messengers that were evolved to manage our reproductive, stress and metabolic responses. In an ideal world, out hormones would ebb and flow in their natural rhythmic cycles with no symptoms, pain or drama, just a smooth flow from puberty to post menopause. Unfortunately, the environment in which we evolved, changed dramatically after the industrial revolution and even more so after World War II.

Hormones are affected by many internal factors, such as the gut microbiome, liver health, genetic variants; but they are also affected by external factors such as food, chemicals found in food, air and water, toxins from mould, inflammation, stress, lack of sleep, just to name a few. These external factors are called endocrine disruptors. Xenoestrogens (oestrogen like compounds not made in the body) from the environment can even affect how genes express themselves and early exposure to them likely contributes to increased risk of oestrogen-related disease in adults.[1]

In the following case study, I will demonstrate a case of oestrogen dominance and adrenal fatigue that weren’t what they seemed on paper. The symptoms were not caused by the ovaries and adrenals, but rather they are caused by a direct effect of a specific mycotoxin.

According to the World Health organisation, mycotoxins are naturally occurring toxins produced by certain moulds (fungi) and can be found in food or water damaged buildings. The moulds that produce these toxins grow on a variety of different crops and foodstuffs including cereals, nuts, spices, dried fruits, apples and coffee beans, often under warm and humid conditions. Mycotoxins can cause a variety of adverse health effects and pose a serious health threat to humans the adverse health effects of mycotoxins range from acute poisoning to long-term effects such as immune deficiency and cancer[2]

Zearalenone – Courtesy Wikipedia

Zearalenone (ZEA) is specific oestrogenic mycotoxin. It is a non-esteroidal estrogenic mycotoxin produced as a secondary metabolite by numerous species of Fusarium, including F. culmorum, F. roseum, F.graminearum, and others.[3,4,5]

Natural exposure to ZEA in contaminated food has been implicated as a cause of female reproductive changes as a result of its powerful oestrogenic activity: its hormonal action exceeds that of most other naturally occurring non-steroidal oestrogens, including soy and clover isoflavones.[6]

Bearing all of this information in mind, let’s go over the case study that I presented at the General Council and Register of Naturopaths (GCRN) AGM in 2019:

A 42-year-old female presented with symptoms resembling oestrogen dominance. She had gained weight, most noticeably in her breasts and hips. She noted that her menstruation was heavier than normal. She had no previous history of PMS. She had a history of insomnia and this had also worsened. These are all fairly typical symptoms of perimenopause; but she was also very thirsty and needed to urinate frequently. She was also experiencing muscle pains that were making exercise more difficult.

In her history it was also noted that she had moved into a water damaged building around the same time her symptoms had become noticeably worse. Mycotoxins can inhibit anti diuretic hormone being released from the pituitary, hence the need to urinate more frequently.[7]

She agreed to do a dried urine metabolites test that comprehensively assesses adrenal and gonadal hormones along with a few organic acids, as well as a separate mycotoxin test.

The mycotoxin urine test was positive for mycotoxins but most relevant was Zearalenone.

I chose the dried urine test to assess the hormones, not only because her symptoms suggested oestrogen dominance, but because the test also includes some useful organic acids and also assesses melatonin and a very important marker 8-Oxo-2'-deoxyguanosine, a marker or oxidative damage to the DNA. This test was also relevant as her weight gain was one of her concerns. Studies suggest that current BMI and oestrogen related disease risk are associated with oestrogen metabolism profiles in premenopausal women.[8]

The results came back with very high Estradiol (E2 – the more active oestrogen), very low free cortisol but high metabolized cortisol, indicating that the adrenals were making enough cortisol even though the free cortisol make it seem she has adrenal fatigue. If there is underlying infection or inflammation cortisol is metabolized at a far greater rate than normal, which is what we saw in her results. She was also favouring the less active cortisone production, thus compounding the effect of low free cortisol.

She was also high in the toxic intermediary of oestrogen metabolism 4-OH estradiol. This is problematic as it can create quinones which in turn cause adducts to form on DNA, thus exposing it to reactive oxidative species and damaging the DNA.[9]

Along with these findings, her melatonin was low. This is not surprising as melatonin is used by the body to protect against the mycotoxins oxidative damage to the mitochondria, our body’s batteries.[10]

Another important antioxidant used by the body to combat myotoxicity is glutathione. The glutathione antioxidant and detoxification systems play a major role in the antioxidant function of cells. Exposure to mycotoxins in humans requires the production of glutathione on an “as needed” basis. Research suggests that mycotoxins can decrease the formation of glutathione due to decreased gene expression of the enzymes needed to form glutathione. Mycotoxin-related compromise of glutathione production can result in an excess of oxidative stress that leads to tissue damage and systemic illness.[11] Not surprisingly, her need for glutathione was high.

We addressed dietary interventions that would help. Firstly, we removed some of the more problematic foods. She bought mycotoxin free coffee beans for her coffee but was only allowed 1 cup a day as the caffeine may have a negative impact on the adrenals. I got her to drink some liquorice tea at 10am instead as this slows the conversion of the active cortisol to cortisone as frees up some cortisol for the body to use. She also went on a grain free diet, as the main food sources of ZEA are maize, although it can also be found also in other crops such as wheat, barley, sorghum and rye.[12]

She added broccoli sprouts for the sulforaphane to assist the transition from phase 1 to phase 2 detoxification as well as help with inflammation. She added cruciferous vegetables such as broccoli, brussels sprouts or cabbage to each meal, which she ate while drinking an apple cider vinegar and lemon juice mix. Indole-3-carbinole from the cruciferous vegetables needs good stomach acid to convert to Diindolylmethane which would then help the liver to change its preference of the 4-OH estradiol to the better 2-OH estradiol pathway.[13] Ground flaxseeds,[14] grated lemon rind[15] and rosemary (the herb)16were also included in her day to day diet as they all assist with oestrogen detoxification.

To improve her sleep, she added tart cherry juice as a bedtime drink. Tart cherry juice has been found to significantly increases time in bed, total sleep time and sleep efficiency.[17]

She also invested in both a water filter and an air purifier. To decrease her total toxic burden, she cooked all her food fresh from scratch and only as much as she needed for 1 meal, leftovers exposed to mould spores can also be a problem. She stored any foods she needed to in glass, so as not to be exposed to Bisphenol A or other plastic xenoestrogenic compounds.

This patient was lucky enough to have access to an infrared sauna. Heat therapy is effective at removing many toxic compounds from the body and sauna therapy is a passive form of heat therapy.[18] She was also instructed to follow guided meditations while in the sauna and to follow the sauna with an Epsom salts bath to ease her sore muscles. Once she was feeling a little better, we also introduced exercise that she could slowly build up her strength again.

Along with all the lifestyle adjustments made, we also used some supplements to assist her methylation and detoxification of both the mycotoxins and the oestrogen. I won’t go into specifics here as her program was tailormade to her and may not be relevant to you, the reader. Suffice to say that after a few months of hard work, she was feeling more like herself. On follow up results, all the markers had improved and she was well on her journey back to hormonal balance.

So, at this point, you may be wondering how this case unravels the mysteries of hormones. Well simply put, in order for your hormones to function optimally you need clean air, clean water, good sleep, no stress, healthy food, sunshine and exercise. These all involve some effect when it comes to lifestyle, but it is possible, in even our current environment.

References

1. E.M.Jorgensen, M.H Aldermann, H.S Taylor. Preferential epigenetic programming of estrogen response after in uteroxenoestrogen (bisphenol-A) exposure. Published online 2016 Jun 16. 
2. World health organisation - https://www.who.int/news-room/fact-sheets/detail/mycotoxins
3. Caldwell R.W., Tuite J., Stob M., Baldwin R. Zearalenone production by Fusarium species. Appl. Microbiol. 1970; 20:31–34
4. Kuiper-Goodman T., Scott P.M., Watanabe H. Risk assessment of the mycotoxin zearalenone. Regul. Toxicol. Pharmacol. 1987; 7:253–306.
5. Hestbjerg H., Nielsen K.F., Thrane U., Elmholt S. Production of trichothecenes and other secondary metabolites by Fusarium culmorum and Fusarium equiseti on common laboratory media and a soil organic matter agar: An ecological interpretation. J. Agric. Food Chem. 2002;50:7593–7599
6. Bennett J.W., Klich M. Mycotoxins. Clin. Microbiol. Rev. 2003;16:497–516
7. https://carpathiacollaborative.com/moldhormones/
8. J. Xie et.al. Body Size in Relation to Urinary Estrogens and Estrogen Metabolites (EM) among Premenopausal Women during the Luteal Phase. Horm Cancer. 2012 Dec; 3(0): 249–260.
9. S. Miao et.al. 4-Hydroxy estrogen metabolite, causing genomic instability by attenuating the function of spindle-assembly checkpoint, can serve as a biomarker for breast cancer. Published online 2019, Aug 15.
10. YAO Xu et.al. Protective Effects of Melatonin Against Zearalenone Toxicity on Porcine Embryos in vitro. Front. Pharmacol 05 April 2019.
11. F.T Guilford and J Hope. Deficient Glutathione in the Pathophysiology of Mycotoxin-Related Illness. Published online 2014 Feb 10.
12. European food safety authority - https://www.efsa.europa.eu/en/efsajournal/pub/2197.
13. H.L Bradlow and M.A Zeligs. Diindolylmethane (DIM) spontaneously forms from indole-3-carbinol (I3C) during cell culture experiments. In Vivo. 2010 Jul-Aug;24(4):387-91.
14. J.D Boorks et.al. Supplementation with flaxseed alters estrogen metabolism in postmenopausal women to a greater extent than does supplementation with an equal amount of soy. Am j Clin Nutrition 2004 Feb; 318-25
15. J.A. Miller et.al. Human breast tissue disposition and bioactivity of limonene in women with early stage breast cancer. Cancer Prev res (Phila), 2003 June; 577-584
16. J Moore et.al. Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols. Published online 2016 June 17.
17. G Howatson et.al. Effect of tart cherry juice (Prunus cerasus) on melatonin levels and enhanced sleep quality. Epuc 2011 Oct 13.
18. https://www.greatplainslaboratory.com/gpl-blog-source/2016/12/12/how-to-maximize-the-benefits-of-sauna-for-detoxification