Combining estrogen with progesterone in HRT for women with a uterus became standard in the 1970s to oppose estrogen's effects on the endometrium.

“but where were we in the early 90s clearly that had been figured out what were the formulations that were most common well that's a very important question Peter and the most common formulations were conjugated estrogen with and without medroxy progesterone acetate and so women who had a hysterectomy could use estrogen alone but women with an intact uterus needed to take take a what we call a progestogen which counteracts the effect of estrogen on increasing the thickness of the uterine lining the endometrium and so if women who have an intact uterus take estrogen alone they have a very high risk of developing endometrial cancer and early on they will just have proliferation of the lining of the uterus and increased vaginal bleeding related to taking estrogen without the progestogen”

“They initially were just replacing estrogen. Um figured out pretty quickly, i.e. within a few years that if you only gave a woman estrogen, you were going to run the risk of endometrial cancer going up because the endometrial lining just continued to get bigger and bigger and bigger and you eventually developed hyperplasia which presumably became metiplasia and ultimately cancer.”