Paul Thompson, MD: Estrogen-Like Effects of Tamoxifen on Triglycerides

Paul Thompson, MD

I recently had a repeat visit with a 49-year-old woman whom I first saw for hyperlipidemia in May 2018. Her lipid levels at that time showed a total cholesterol of 228, an HDL of 40, triglycerides (TGs) of 258, and an LDL of 145 mg/dL on no medications.

She subsequently underwent bilateral mastectomies in September 2019 for breast cancer and was started on tamoxifen 20 mg daily for suppressive therapy. She was referred to me in July 2020 because her lipid levels had increased. Specifically, her total cholesterol had increased to 355, her HDL was 43, TGs were 651, and her LDL was 155 mg/dL again on no medication. She was unable to see me until August 2020 because of COVID. In August her fasting TGs were 1,344.

We started her immediately on prescription fish oil 2 gms twice daily and fenofibrate 145 mg daily because fasting TGs over 1,000mg/dl can cause life-threatening, hemorrhagic pancreatitis.

I explained to her that the increase in TGs was probably due to her tamoxifen and that we would have to decide with her oncologist whether or not it should be continued. Her oncologist did not think tamoxifen was contributing to the TG elevation because tamoxifen, in contrast to estrogen, could not increase TGs because it was an estrogen blocker.

Tamoxifen does block estrogen’s binding to the estrogen receptor in breast tissue, but tamoxifen activates the estrogen receptor in the liver. We reported the 4th case of marked hyperTGS (TGs=4,4420 mg/dl) linked to tamoxifen in 1997^1, and one of the previously 3 reported patients had died from pancreatitis. The increase in TGs with tamoxifen is usually around 20%^2, but some patients experience greater increases in TGs that may be due to genetic variants in the estrogen receptor. ^3​

So, take home messages: Estrogen increases TGs.

Tamoxifen also increases TGs despite its estrogen-blocking properties in breast tissue. Fasting TGs over 1,000 mg/dl can cause hemorrhagic pancreatitis so such patients should be seen and treated immediately. In fact, I often start prescription fish oil and fenofibrate over the phone, if I cannot see them that day.