Estrogen – Frantic Shanti

Melatonin As Cancer Fighter? Maaaaybe…

The last time I was researching the link between cancer and sleep, noting the myriad benefits gained from solid nighttime rest, I was surprised to see mention of melatonin’s role in decreasing the risk of cancer.

For anyone who might not be familiar with it, melatonin (a tryptophan derivative) is a naturally-occuring hormone secreted by the pineal gland that signals when it’s time to sleep and wake. It’s mediated by light levels, with the amount of melatonin in your body increasing as the sun goes down. You’ve probably seen melatonin on the vitamin shelves at your local store, as in recent years it’s been popularized as a non-addictive sleep aid. What I hadn’t realized was that its effect on cancer cells has become an active area of study.

I dug into the PubMed database to find there was quite a bit on this topic. However, note that not all the journals in which these results were published were familiar to me, so I cannot vouch for the rigor of the peer review, however, there was a general consensus that melatonin showed promise.

Melatonin shows a lot of promise as a cancer fighting hormone.

It’s well-established that women who work night shifts experience disruption of their circadian cycle and have an increased risk of breast cancer risk, purported to result from extra circulating estrogen (Cohen et al., 1978, Lancet). Researchers are now linking that disruption with a decrease in melatonin production.

Amin et al. (2019, J Cell Biochem) describe the action of melatonin as it relates to cancer: “Melatonin via its receptors and various second messenger pathways decrease[s] cell duplication and increase[s] cell differentiation.” Since cancer tumors are composed of a proliferation of poorly differentiated cells, this means that the action of melatonin works against the process by which cancer develops and progresses.

Amin et al. continue by noting that melatonin “regulates estrogen-dependent pathways (by nonreceptor-dependent means) and reduces the production of oxidants; as a result, melatonin inhibits cell toxicity and mutations….Melatonin interrupts estrogen-dependent cell signaling and also causes reduced estrogen-stimulated cells in breast cancer. [It] is a mammary tumor inhibitor…[as relates to the] development, progression, and metastasis of breast cancer via a number of molecular mechanisms.”

A randomized, double-blind, placebo-controlled research study showed that melatonin has a neuroprotective effect that can counteract the effects of chemotherapy on “cognitive function, sleep quality and depressive symptoms” (Palmer et al., 2020, PLOS One). These are significant side effects that have a profound impact on the patient’s quality of life, and anything that may relieve these will improve the entire treatment experience.

Griffin & Marignol (2018, Int J Radiat Biol) noted that melatonin administered to subjects before they were exposed to ionizing radiation resulted in the breast cancer cells being more sensitized to the radiation therapy, rendering it more effective. And melatonin seemed to reduce the radiation-induced side effects exhibited by both human and rodent subjects.

No matter how many drug treatments are available for cancer, they do no good if the cancer cells develop a resistance to them. In a study published this year, Sang et al. (2021, Cancer Lett) found that melatonin increased the effectivess of drug lapatinib in HER2 receptor-positive breast cancer cells that were originally resistant to the drug, suggesting that melatonin could be a promising adjuvant therapy for treating advanced HER2+ tumors.

So, melatonin may reduce breast cancer risk, make existing treatments more effective and help protect patients against negative effects of these therapies. Does that mean you should run out and gobble melatonin every night?

Many studies are first run on animal subjects, but to truly determine whether a treatment will be effective for cancer patients, it must be tested on humans.

No! As tempting as it sounds, that’s not an advisable course of action. Many more studies still have to be run to evaluate the exact mechanisms by which melatonin acts on physiological processes. Some of the results in the cited studies were based on small sample sizes; good for proof of concept, but following up with larger scale studies is critical. Some studies were run on animal models which are not the best human analogues. In addition, there’s little direction regarding proper therapeutic dosages. Establishing those will take additional research.

Keep in mind: a naturally-occurring hormone like melatonin likely has a “sweet spot” in terms of dosing, and determining the ideal amount may be tricky. Just because you can buy melatonin gummies in 10mg doses does not mean you should be taking that much.

Furthermore, melatonin may elicit negative side effects in some people, including headaches, nightmares and nausea. Side effects tend to be short-lived with short-term usage but there’s still not enough information available about long-term safety, so taking it for longer periods of time is strongly discouraged.

Note also, the articles I’ve mentioned above were selected because they describe recent research, although some of these are review articles that espouse the authors’ opinion, backed up by research selected for the purpose. If you’d like to read the above studies yourself and the links I’ve posted do not provide you full access, please consult your local university library for copies (copyright laws prohibit me from providing access to pay-only articles, regrettably).

Finally, it may be that some of melatonin’s benefits might be its undoing. Reiter et al. (2017, Int J Mol Sci) note that melatonin is inexpensive and readily available, and therefore there might not be the same level of interest in researching and developing it for cancer use as there might be with a novel drug with the potential to be more lucrative.

Where does this leave us?

I would urge you to:
1) Ask your oncologist about what they would recommend, given the research that’s coming out. They are still your best source for information. FranticShanti.com is only a blog and can be used as food-for-thought but definitely not for determining your course of treatment.
2) Learn how to read scientific studies. There are free courses on educational site such as Coursera.com that explain research design and interpretation in layperson terms. They can offer instruction on reading research with a critical eye.
3) Keep an eye on emerging research. Databases such as PubMed are excellent sources for health research. Even if you’re not well-versed in research design, you can look up articles to bring to your next visit with a health provider.
4) Do not take megadoses of melatonin! There is still so much we have to learn about this hormone as it relates to cancer, and self-medicating with melatonin in the hopes that “maybe it’ll help” is dangerous. Again, your oncologist remains your best source of information.

I do encourage you to respect your circadian rhythm by establishing good sleep hygiene practices to improve the conditions for your body to create and release its own melatonin. Proper and adequate sleep will always benefit you!

And so we get back to the idea that launched this post: sleep remains the ultimate good.

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It bears repeating: ALWAYS ask your cancer team about starting any new medication or supplement, regardless of how well-supported it is by research.

Soy and Breast Cancer: What Does the Science Say?

IMPORTANT: Please discuss the information below with your oncological and nutritional team prior to making changes to your diet! They will be able to provide you with the proper guidelines for your situation.

One common area of contention within the context of hormone-positive breast cancer is the effect of soy consumption on cancer risk. There has been some back-and-forth on this topic, and “to soy or not to soy?” is a frequently-heard question coming from newly-diagnosed cancer patients.

It was a concern for me. I became vegetarian at age 18 and consumed a soy-heavy diet until my mid-40s, at which point, partly spooked by warnings about soy, I backed off. As recent research shows, I needn’t have.

For a little background, the main concern for breast cancer patients is the presence of phytoestrogens in soy, known as isoflavones, and how they function in the human body. They have a mild estrogenic effect, which is why many women use them in supplement form to ameliorate the uncomfortable effects of menopause. In that sense, they are acting like estrogen, although it’s important to stress that they are not estrogen.

Soy (here, both tofu and edamame) is a staple in Asian and vegetarian cuisines, and is the only plant-based protein that is a complete protein.

But given this similarity to estrogen, does soy increase the risk of breast cancer and breast cancer recurrence? In short, studies show that if you grew up eating soy and eat it daily, as is the case in many Asian countries where soy products are dietary staples, soy has a significant protective effective against breast cancer. Results of these studies have been inconclusive in Western populations, however this seems to be due to differences in diet: not only do Westerners eat considerably less soy compared to Asians, they also don’t eat it throughout all stages of their lives.

Is there a difference in how these diverse cultures handle isoflavones? It appears that a major isoflavone-derived metabolite, equol, has well-documented antioxidant and estrogen-like actions and seems to be associated with numerous positive outcomes, but only about 30-50% of the human population has the gut microbiota to derive it from the diet. There is a need for more research on how this conversion takes place and under what conditions.

But most importantly, as stated by the American Institute for Cancer Research, “Population studies don’t link soy consumption with an increased risk of any cancer.” While the childhood and adolescent consumption of soy is what seems to offer the most long-term benefits, for those who increased their intake at a later age or don’t eat it regularly, the current view is that even if eating soy doesn’t significantly reduce your risk of cancer, there is no definitive evidence that it will make your risk worse.

For me, that means that I will continue using soy as an important protein source in my diet.

Take note:

As with other foods, unprocessed and minimally-processed soy is still the healthiest option.

Overdoing anything is not good, so don’t overload on overly processed soy supplements in the hopes of preventing cancer development and/or recurrence — particularly if you’re postmenopausal and not a life-long soy eater. Having said that, there is ample room for minimally-processed soy foods (tofu, edamame, tempeh, miso) in a healthy plant-based diet, and that will definitely benefit you.

No single thing will prevent cancer 100%, so you’d be well-served to consider your lifestyle as a whole. As a matter of fact, Zhang et al. (2017, Cancer) noted that “[w]omen who consumed high levels of dietary isoflavone were more likely to be Asian Americans, young, premenopausal, physically active, more educated, not overweight or obese, never smokers, and drank either no alcohol or <7 drinks per week.” [Emphasis mine.] That means protection came not only from soy; the women were also engaging in other behaviors associated with a lower risk of breast cancer. Bottom line, lifestyle matters!

Finally, this is only a brief summary of what I found. Soy is a topic that I’ll be keeping my eye on and will report back as newer studies are published.

In the meantime, here are three excellent reader-friendly websites for more information:

1. American Institute for Cancer Research website, “Soy: Intake Does Not Increase Risk for Breast Cancer Survivors – https://www.aicr.org/cancer-prevention/food-facts/soy/

2. Harvard School of Public Health website, “Straight Talk About Soy” – https://www.hsph.harvard.edu/nutritionsource/soy/

3. Oncology Nutrition website, “Soy and Breast Cancer” – https://www.oncologynutrition.org/erfc/healthy-nutrition-now/foods/soy-and-breast-cancer

References for this post (all articles are available online free of charge):

Baglia ML, Zheng W, Li H, Yang G, Gao J, Gao Y-T, Shu X-O (2016) The association of soy food consumption with the risk of subtype of breast cancers defined by hormone receptor and HER2 status. Int J Cancer. 139: 742–748. https://doi.org/10.1002/ijc.30117

Kucuk O (2017) Soy foods, isoflavones, and breast cancer. Cancer. 123: 1901-1903. https://doi.org/10.1002/cncr.30614

Lee SA, Shu XO, Li H, Yang G, Cai H, Wen W, Ji BT, Gao J, Gao YT, Zheng W (2009) Adolescent and adult soy food intake and breast cancer risk: results from the Shanghai Women’s Health Study. Am J Clin Nutr. 89: 1920-1926. https://doi.org/10.3945/ajcn.2008.27361

Mayo B, Vázquez L, Flórez AB (2019) Equol: A bacterial metabolite from the daidzein isoflavone and its presumed beneficial health effects. Nutrients. 11: 2231. https://doi.org/10.3390/nu11092231

Messina M, Rogero MM, Fisberg M, Waitzberg D (2017) Health impact of childhood and adolescent soy consumption. Nutr Rev. 75: 500–515. https://doi.org/10.1093/nutrit/nux016

Nagata C (2010) Factors to consider in the association between soy isoflavone intake and breast cancer risk. J Epidemiol. 20: 83-89. https://doi.org/10.2188/jea.je20090181

Patisaul HB, Jefferson W (2010) The pros and cons of phytoestrogens. Front Neuroendocrinol. 31: 400–419. https://doi.org/10.1016/j.yfrne.2010.03.003

WuAH, Yu MC, Tseng C-C, Pike MC (2008) Epidemiology of soy exposures and breast cancer risk. Br J Cancer. 98: 9-14. https://doi.org/10.1038/sj.bjc.6604145

Zhang FF, Haslam DE, Terry MB, Knight JA, Andrulis IL, Daly MB, Buys SS, John EM (2017) Dietary isoflavone intake and all‐cause mortality in breast cancer survivors: The Breast Cancer Family Registry. Cancer. 123: 2070-2079. https://doi.org/10.1002/cncr.30615

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When I asked my oncologist about soy, he shrugged and said, “Yes, it’s true that soy foods contain plant estrogens…but you’re not a plant.”

“The Gun Show”: Assessing Biceps Muscle Loss Due To Endocrine Therapy [PHOTOS]

In my last post, I whined about the repercussions of taking aromatase inhibitors (in my case, letrozole) as a way to diminish the amount of estrogen in my body, for the purpose of reducing the risk of breast cancer recurrence.

While I also mentioned letrozole’s effects on my exercise habits, in this post I wanted to drill down on one aspect in particular: muscle loss.

Before I go further, I need to add a disclaimer. Since the time the first photo was taken (the morning before my first chemo infusion), three and a half years passed and I went through menopause. Notably, the menopause was pharmaceutically-driven, starting with tamoxifen and then, after my hormone levels were low enough, continuing with letrozole. However, my body now is dealing with the same aging effects as someone who had transitioned naturally.

Except that my transition came before its time.

The below photo is from April 27, 2017, before I headed to the infusion center for my first dose of chemo. I had been training as normally as I could, under the conditions of lumpectomy and port placement that I wrote about here, and finding work-arounds for exercises that I’d been told not to do.

This is my 51-year-old biceps muscle, before I started the pharmaceutical portion of my breast cancer treatment.

While I lost some size and strength throughout my chemo infusions (here are all the photos), I was able to bounce back and had a particularly strong 2018 (sorry, don’t have good photos of that). But as the endocrine therapy with tamoxifen continued in 2019, to be replaced by letrozole in 2020, I could feel the effects of low estrogen.

On December 11, 2020, I struck the same pose again for sake of comparison.

Is something missing? This is my 54-year-old biceps muscle, struggling to keep up. Note: I am still working out as hard as I can!

As far as muscle appearance is concerned, I have experienced a slow downhill slide. My shoulder is not as peak-y, the biceps itself has decreased in size and I even find it more difficult to hold this muscular contraction. In addition, there’s more looseness in my skin, particularly at the back of my arm, which in part may be due to loss of collagen, also affected by estrogen levels (nice dermatological review by Shah & Maibach, 2001, Am J Clin Dermatol).

I’m busting my butt trying to increase the amount that I’m lifting, but I’m not making progress. Not surprisingly, the decrease in estrogen plays a role in this. As stated by Chidi-Ogbolu & Baar (2019, Front Physiol), “estrogen improves muscle mass and strength, and increases the collagen content of connective tissues”.

It makes sense then that lack of estrogen is going to be detrimental to maintaining muscle. To that point, Kitajima & Ono (2016, J Endocrinol), working with animal models, have found that “estrogen insufficiency leads to muscle atrophy and decreased muscle strength of female mice.”

Not just mice, obviously.

This information comes as no surprise to any woman who’s gone through menopause, I’m sure. But the experience of being slammed through menopause instead of having the opportunity to transition more gradually is yet another frustrating way that having cancer pulls the rug out from under you and reminds you that you are not in control of your life.

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Slowly, yoga is becoming more important in my life and my view of fitness is changing. Good thing too, since I can’t keep beating myself up like this.

(Almost) Six Months on Letrozole

WARNING: IF YOU ARE STARTING ON AN AROMATASE INHIBITOR, I highly recommend that you not read this and instead give yourself the chance to gauge the medication’s effects without being influenced by someone else’s experiences. Note that I started letrozole just out of menopause, so my side effects from this drug have been more dramatic than they might be for a women who’s been postmenopausal for longer.

First a bit about aromatase inhibitors: according to breastcancer.org, “Aromatase inhibitors work by blocking the enzyme aromatase, which turns the hormone androgen into small amounts of estrogen in the body. This means that less estrogen is available to stimulate the growth of hormone-receptor-positive breast cancer cells.” Think of this as starving a hormone-positive cancer of its food.

Aromatase inhibitors have been shown to be more effective than tamoxifen, with fewer serious side effects, although they are certainly not risk-free as they can cause “more heart problems, more bone loss (osteoporosis), and more broken bones than tamoxifen.” (breastcancer.org)

When it was time to start letrozole, I took a different tack than when I began tamoxifen. For the latter drug, I did all the research I could, researching relevant studies, digging into possible side effects and visiting lots of forums to learn about what other women were experiencing.

I wish I hadn’t. I think all the negatives affected my perception and made me anxious about taking the medication.

The letrozole pill looks so teeny and cute – how bad could the side effects be?

So after two years of tamoxifen, when my hormone levels suggested that I was postmenopausal and it was time to switch to an aromatase inhibitor, I stayed away from clinical literature about letrozole. I decided to give it a chance, since my oncologist felt that I had confused the effects of anxiety about taking tamoxifen with the actual effects of tamoxifen.

Okay, then. As I was leaving my oncologist’s office, letrozole prescription in hand, he added that some women complain of “joint pain”. I think he felt it was his duty to warn me.

My experience? I’m finding it harder to recover from workouts. I train with free weights and am a rower (currently, indoor) and the change in my resilience and stamina is striking. In 2018, a year after finishing up chemo, I was able to power through tough workouts and felt like I’d gotten most of my pre-cancer strength back.

Fast-forward to now, just two years later, I feel old. My joints are creakier and I’m having increased muscle pain and overall stiffness. I’m experiencing bone pain in the leg that I broke skateboarding when I was 12. Yeah, I push through workouts, but they’re taking their toll on me.

I’m fortunate to have a full complement of gym equipment at home, so the COVID-19 lockdown didn’t hinder my workouts. To get some fresh air, I incorporated more hiking into my routine, in addition to my regular workouts.

It was too much and left me with hip pain that made it difficult to fall asleep. So I took a rare break from vigorous workouts and for two weeks incorporated more gentle movements and focused on yoga, which I had been doing intermittently.

When I started ramping back up, I didn’t feel rested, I felt weak! Weights that had been easy to lift a couple of weeks before felt challenging. I had to restart the process of building my strength. You could pass it off as simply “age”, but I’m only 54, and the drop in strength and energy has felt precipitous, even demoralizing. While it’s true that I went through menopause during the last two years, it was a medication-induced menopause and I was literally shoved through the change.

Letrozole has been shown to be very effective in preventing cancer recurrence, presumably because it works to keep estrogen levels low. However, most women on letrozole are in their 60s and have been postmenopausal for a number of years. For a woman in her 50s, the aging effect of estrogen suppression has felt dramatic.

My libido dipped even lower than I’d experienced with tamoxifen, something I was warned about by my GP and gynocologist (both females). My male oncologist didn’t talk about it. I believe this is a seriously underreported side effect of aromatase inhibitors and one that many women suffer from in silence, because they don’t feel comfortable bringing it up.

Likewise, I feel my appearance changed. Now, this may simply be my perception of myself, as my post-chemo hair transitioned from super-cool and spikey to thin and limp (and, now, untrimmed!), and my eyebrows never recovered. But it’s not just in my head: A bus driver recently tried to offer me a senior citizen discount, whereas four years ago someone had told me they thought I was in my late 30s! That’s a big difference. The fact that the lack of estrogen is making me look like I’m older than I really am has become distressing:

And that difference is felt in my relationship with my family. There have been times that I’ve looked at my husband (four years my junior) and my high school-aged kids, and I feel like don’t belong with them. I feel like a stranger, an old lady that’s just hanging around. That hurts a lot.

And on my worst days, I feel dark clouds rolling in, bringing with them frustration and hopelessness. Is it letrozole or menopause? Does it even matter? Take a woman, throw her in a bag, tie it to a tree branch and then beat it with a stick. That is how I feel when I have to take a pill that does these things to me. No control, no future, lots of pain. The longer that I continue with medications like this, the more I feel that they are pointless, since I’m starting to not care whether or not the cancer comes back. And that’s the worst side effect of all.

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So, this blog is about being honest about the cancer experience. But it’s also about mindfulness. I have to open the door and let the negative feelings into the room so that I can offer them compassion and a kind ear. I sit with them for a while, and eventually, I feel better.