We’ve looked at some studies that showed significant effects of melatonin on cancer and quality of life, but how does melatonin  achieve this? There are several different mechanisms, but today we will focus on just one: melatonin’s anti-estrogenic effects. This might be important for breast cancer (BC) and other hormonal imbalances. 

Melatonin’s different anti-cancer mechanisms of action

This year, a fascinating paper was published that summarizes the different ways that melatonin produces its anti-cancer effects [1]. These are known as its ‘mechanism of action.’ Looking at how something works is as important as seeing that it does work. We need to understand the ‘how’ so that we can know when it is appropriate to use a particular treatment.

The diagram at the beginning of this blog post comes from that paper. From the research, it identifies ten potential mechanisms through which melatonin exerts its anti-cancer effects. These are:

  • anti-proliferative effects
  • induction of apoptosis
  • modulation of the immune system
  • metabolic effects
  • anti-angiogenic activity
  • anti-metastatic effects
  • anti-estrogenic effects
  • inhibition of telomerase activity
  • anti-oxidant activity
  • regulation of genomic stability

Today we’ll look in a little more depth at melatonin’s anti-estrogenic effects. 

Melatonin effects on estrogen

The anti-cancer effects of melatonin have been studied extensively in hormone-dependent breast cancer, in particular regarding estrogen. Melatonin is seen to interfere with

i) the activation of the estrogen receptor.  It is thus considered to be a selective estrogen receptor modulator (SERM), that decreases both the expression of estrogen receptors alpha (ERα), and the ability of ERα to bind to DNA

ii) the invasiveness of breast cancer cells,  thus reducing the risk of metastasis

iii) in the production and metabolism of estrogen. Melatonin inhibits the enzymes involved in the synthesis of estrogen, thus leads to lower levels of estrogens. It is thus considered to be a selective estrogen enzyme modulator. 

iv) Melatonin is also seen to be involved in the metabolism of estrogen, transforming estradiol into its inactive estrogen sulphate/sulfate form. This is another example of SEEM activity.

Melatonin is, as far as is known, the only molecule that has both SERM and SEEM properties. This double mechanism of anti-estrogenic effects, plus its invasiveness effects yields melatonin’s unique advantages for the treatment of hormone positive breast cancer.

These anti-estrogen effects may also important beyond BC, for example in estrogen dominance and other conditions associated with estrogen imbalances. 

Melatonin levels and risk of developing breast cancer

Many observational studies have looked at whether low melatonin levels are associated with increased risk of breast cancer. In a study on 3,699 post-menopausal women [2], the results show that those with the highest levels of melatonin (from urine assessment)  have a 44% reduced risk of invasive BC compared to those with lowest levels. This association was even stronger (62%) in those who had never smoked or were past smokers. Two other large studies showed similar results. [3,4].

Women working night shifts are also shown to have higher rates of breast cancer. Studies have shown that these women have lower (approx 50%) melatonin levels. The reduction in peak melatonin levels was even shown to correlate directly with the size of tumors in these women. 

Conclusion

Concerning BC, studies show that:

  • low levels of melatonin are a risk factor for BC
  • there is an inverse relationship between melatonin levels and tumor size (i.e., the lower the peak level, the larger the tumor)
  • concurrent supplemental melatonin can improve chemotherapy outcomes and reduce side effects in BC
  • melatonin has effects on both estrogen receptors and estrogen production

Considering melatonin has other anti-cancer mechanisms, such as anti-oxidant, immune-modulating, anti-inflammatory, etc., in addition to its anti-estrogen effects suggests that supplemental melatonin may be of use for BC patients. This seems to be indicated for both prevention and for combined treatment with chemotherapy and radiotherapy. While further definitive trials are needed, melatonin has been demonstrated to be nontoxic, and its benefits on sleep are also important for cancer patients. 

Remember, as always, that we are all individual. What works for one person, might not work for you. And results from clinical trials come up with statistics, and you aren’t a statistic. If you decide you want to add melatonin to your regimen, try working with a health care provider; if you have cancer, make sure you tell your oncologist. 

References

[1] Cardinali et al., 2016. Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance. J. Integr. Oncol., S1: 006.

[2] Schernhammer ES, Berrino F, Krogh V, et al. 2008. Urinary 6-sulfatoxymelatonin levels and risk of breast cancer in postmenopausal women. J Natl Cancer Inst. 100(12):898-905.

[3] Schernhammer ES, Hankinson SE. 2005. Urinary melatonin levels and breast cancer risk. J Natl Cancer Inst. 97(14):1084-1087.

[4] Schernhammer ES, Hankinson SE. 2009. Urinary melatonin levels and postmenopausal breast cancer risk in the Nurses’ Health Study cohort. Cancer Epidemiol Biomarkers Prev. 18(1):74-79.

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