HRT side effects

HRT's most consistent side effect is a small, real rise in breast cancer risk, and it depends almost entirely on whether you take estrogen alone or with a progestin.

The two are not the same drug. Estrogen plus progestin raises breast cancer incidence and deaths from it [1][2]. Estrogen alone, in women who have had a hysterectomy, was associated with lower breast cancer incidence and mortality in the same trial [1]. That split is the single most important thing to know before deciding.

The combined regimen's numbers are modest but not zero. In a Norwegian cohort of 160,881 women, current estrogen-progestin users had about a 44% higher rate of breast cancer than never-users, and risk climbed roughly 4% per year of use [2]. Breast cancer deaths were also higher [2]. A 2002 review noted the same pattern but concluded the added risk was "not proved" [3]; the later randomized and cohort data settled that question against it [1][2].

The endometrial cancer tradeoff runs the other way: unopposed estrogen raises it, and adding a progestin offsets that [1]. So the progestin that protects the uterus is the piece that raises the breast signal. That is the real tradeoff, and it is not a small one.

My call: if you have a uterus and need a progestin, the breast risk is real and rises with years of use, so the shortest effective course is the honest default. If you have had a hysterectomy, estrogen alone looks materially safer on the breast. Confidence: moderate on the direction of both signals, low on how much dose, route, and formulation shift the numbers, because the records here do not settle that.