Does Letrozole Cause Weight Gain?

Weight gain is one of the many potential side effects of Letrozole, an Aromatase Inhibitor. In fact, “will Letrozole make me gain weight?” is one of the most common questions we hear in our support groups. Not every person taking Letrozole gains weight. Everyone responds differently to these endocrine therapies. However, in today’s post, we are going to look at the most common factors associated with weight changes and provide some recommendations for how to combat some of the unwanted cushioning we develop as a result of this estrogen depletion.




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A large percentage of people report weight gain after a breast cancer diagnosis and treatment [1]. Explanations for the change in weight can be attributed to lifestyle changes that normally come with a breast cancer diagnosis. For example, you may feel more fatigued and therefore reduce your level of physical activity. If you are on steroids, you may notice the feeling of being hungry more often. Increasing calories can also be associated with coping as you deal with the stresses of a breast cancer diagnosis. Weight changes can also occur in younger women who are premenopausal during chemotherapy [2].


The Women’s Healthy Eating and Living (WHEL) study indicates that 65% of people treated with chemotherapy were more likely to put on few extra pounds [3]. On average, women report gaining 2-5kg (approximately 4-11 lbs). However, that is not the time to worry about weight gain or to start a new diet plan. Remember, you are going through cancer treatment and it is a time to be kind to yourself!


Chances are, if your cancer is hormone receptor positive, meaning that the cells have either estrogen or progesterone receptors, you will most likely be advised to take endocrine therapy as part of your longer-term treatment plan. Endocrine therapy, also known as hormonal therapy, reduces estrogen levels or blocks the estrogen receptor. In some cases, your oncologist will advise you to take Tamoxifen, or one of the Aromatase Inhibitors (Anastrozole, Exemestane, Letrozole).


The goal of hormonal therapy is to reduce the chances of the breast cancer returning or progressing. That is the great advantage of the drug! However, as we look into the quality of life and survivorship/thrivership, we must also be cognizant of the impact estrogen depletion has on overall health. We know that these aromatase inhibitors can cause osteoporosis, increase cardiovascular events and diabetes [4]. But does it also cause weight gain?


It's easy to associate weight gain with being less active, one’s metabolism slowing down with age, or making poor dietary choices. But whatever the reasons, there seems to be a consensus that those diagnosed with breast cancer who are on endocrine therapies are gaining weight, even if they are exercising and making healthy conscious and nutritional choices.


One factor that is seldom discussed (and more research is certainly warranted) is the role that Letrozole has on lipid metabolism. While there have been some trials and research investigating the impact aromatase inhibitors have on the lipid profile, results have been elusive [5]. What we do understand is that these AI’s can have an adverse effect on blood levels. For example, increasing total cholesterol, LDL (the “bad” cholesterol) and HDL (the “good” cholesterol) levels can lead to increased risk of cardiovascular disease [6]. Additionally, we know that the enzyme lipoprotein lipase (LPL), which is controlled by insulin, pulls fat out of the bloodstream and into the cell. If this enzyme is on a muscle cell, it will turn the fat into energy. If the enzyme is sitting on a fat cell, it will pull fat into the cell and make it fatter [7]. Estrogen suppresses LDL and with lower levels of estrogen in the body, this could be a reason some women gain weight during menopause or as part of breast cancer treatment.


As noted, there are several factors at play for why people may gain weight when undergoing chemotherapy or hormonal therapies. Some of these biological side effects are out of one’s control. However, there are actions you can take to maintain a healthy weight. Examples include what foods we decide to consume and our activity level. Here are some of our favorite recommendations! This list is not comprehensive and you can feel free to choose. It is important to start with realistic and achievable goals. We are in this for the long haul!


· Choose foods that are unprocessed and nutrient dense

· Eat a diet low in added sugar

· Limit (or avoid) alcohol

· Increase fruits, vegetables and whole grains

· Find an enjoyable activity that enables you to move your body daily (walking, light weights, swimming, etc.)


Fruits and vegetables are known to contain phytochemicals packed with antioxidants and are nutrient dense, meaning they are rich in vitamins and minerals relative to their caloric content.


Whole grains are unprocessed foods that are high in complex carbohydrates, fiber, and nutrients, such as wheat, rye, oats, rice, bulgur and barley.


Green leafy vegetables include: spinach, swiss chard, beat greens, lettuce and romaine

Cruciferous vegetables include: broccoli, turnips, brussel sprouts, cauliflower, bok choy, kale, mustard greens


Umbelliferous vegetables include celery, parsley, fennel, carrots, parsnip


Solanaceous vegetables are the nightshades like eggplant and tomatoes

Cucurbitaceous vegetables are your gourd family like squash, pumpkin, cucumbers, watermelon


Understanding how you body responds to cancer treatment is complex. You have been through a lot! What works for your body pre-cancer, may no longer do the trick. We are human and we evolve. If you are struggling with weight gain because of breast cancer treatment or hormonal therapies, speak to your oncologist about your concerns. Ask for a referral to a nutritionist. Get confirmation on what an ideal exercise plan should look like for you!


I know it is easier said than done, and I am right there with you! Cancer takes a toll on us but continue to love yourself and your body; nurture it with compassion, movement, and wholesome food and it will love you back in spades.




References

[1] Raghavendra, A., Sinha, A. K., Valle-Goffin, J., Shen, Y., Tripathy, D., & Barcenas, C. H. (2018). Determinants of Weight Gain During Adjuvant Endocrine Therapy and Association of Such Weight Gain With Recurrence in Long-term Breast Cancer Survivors. Clinical breast cancer, 18(1), e7–e13. https://doi.org/10.1016/j.clbc.2017.11.006 [2] Gu, K., Chen, X., Zheng, Y., Chen, Z., Zheng, W., Lu, W., & Shu, X. O. (2010). Weight change patterns among breast cancer survivors: results from the Shanghai breast cancer survival study. Cancer causes & control : CCC, 21(4), 621–629. https://doi.org/10.1007/s10552-009-9491-z [3] Lauby-Secretan, B., Scoccianti, C., Loomis, D., Grosse, Y., Bianchini, F., Straif, K., & International Agency for Research on Cancer Handbook Working Group (2016). Body Fatness and Cancer--Viewpoint of the IARC Working Group. The New England journal of medicine, 375(8), 794–798. https://doi.org/10.1056/NEJMsr1606602 [4] Buch, K., Gunmalm, V., Andersson, M., Schwarz, P., & Brøns, C. (2019). Effect of chemotherapy and aromatase inhibitors in the adjuvant treatment of breast cancer on glucose and insulin metabolism-A systematic review. Cancer medicine, 8(1), 238–245. https://doi.org/10.1002/cam4.1911 [5] Boutas, I., Pergialiotis, V., Salakos, N., Agrogiannis, G., Konstantopoulos, P., Korou, L. M., Kalampokas, T., Gregoriou, O., Creatsas, G., & Perrea, D. (2015). The impact of Anastrazole and Letrozole on the metabolic profile in an experimental animal model. Scientific reports, 5, 17493. https://doi.org/10.1038/srep17493 [6] Zidan, J., Chetver, L., Hussein, O., & Zucker, M. (2010). Effect of letrozole on plasma lipids, triglycerides, and estradiol in postmenopausal women with metastatic breast cancer. The oncologist, 15(11), 1159–1163. https://doi.org/10.1634/theoncologist.2009-0222 [7] Breastcancer.org, Eating to lose weight after treatment, https://www.breastcancer.org/tips/nutrition/after_treat/lose_weight

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