Dr. Keith Roach
DEAR DR ROACH: I was first diagnosed with breast cancer in 1987 at the age of 39. I was treated with a lumpectomy, radiation and 5-FU chemotherapy (seven treatments). Nine years ago, in the same breast, I had a small tumor and elected to have a bilateral mastectomy followed by a prescription of tamoxifen for seven years.
I have been plagued with urine infections, and my oncologist is now suggesting estetrol hormone therapy, which will be approved soon by the U.S. Food and Drug Administration. This should help my infections and my overall well-being. My urologist thinks it’s a great idea, but my internist is concerned with the 10% potential risk of uterine cancer. I would appreciate your thoughts before I make a decision on whether to start it. — S.L.G.
ANSWER: Estrogens stimulate growth in the lining of the vulva and vagina. In women with low levels of estrogen, such as postmenopausal women or those who have undergone oophorectomy (removal of the ovaries), the lining may become atrophic, causing symptoms like frequent urine infections. Estrogens can be very helpful in preventing urine infections by promoting a healthy lining and keeping bacteria out of the bladder. These can be given systemically or topically.
Estetrol is one of four human estrogens. It is sometimes called E4, to signify the fourth human estrogen. Unlike medicines such as Premarin that derive from horses, the medicine estetrol is the exact human hormone made only by the fetal liver.
Natural and synthetic estrogens, as well as estrogen-like drugs, have variable results in regards to the risk of side effects, especially breast cancer and endometrial cancer. For approved doses of estetrol in particular, there does not appear to be a risk for breast cancer; however, since this is a very new drug, it’s impossible to be certain of this. I am very conservative and would defer you to your oncologist, given your history of estrogen-sensitive breast cancer despite this minimal theoretical risk. Estetrol does, however, stimulate the cells in the lining of the uterus, but less so than other estrogen-like drugs, such as estradiol (E2) or tamoxifen.
When given alone, estrogens increase the risk of endometrial cancer, but I was unable to confirm the 10% risk you quote. In studies using other estrogens, the risk of endometrial cancer for women taking estrogens alone is much lower, about 1%. It will be many years before the risk of endometrial cancer from estetrol takes effect.
However, we typically do not give estrogens alone to a woman with a uterus. Combining estrogen with a progesterone nearly abolishes the increased risk of uterine cancer. Although it’s never good to get any kind of cancer, endometrial cancer in women taking estrogens tends to be more easily treated.
Based on the limited data I found about estetrol, I don’t recommend it in a woman with a uterus, except when used in combination with a progesterone. However, I do recommend you discuss the use of topical estrogens to help reduce your risk of urine infections with your team of doctors (especially your oncologist). This should help solve your urine infection problem.
The risk of endometrial or breast cancer from topical estrogens seems to be minimal, but I still insist that all my patients discuss the risks with their oncologist.
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Dr. Roach regrets that he is unable to answer individual letters, but will incorporate them in the column whenever possible. Readers may email questions to ToYourGoodHealth@med.cornell.edu or send mail to 628 Virginia Dr., Orlando, FL 32803.
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