Definition: Unopposed estrogen means estrogen taken without a progestin by a woman who still has a uterus. Estrogen labels call it estrogen-alone therapy. They warn that it raises the risk of endometrial cancer, and that adding a progestin lowers the risk of endometrial hyperplasia, a possible precursor.
The boxed warning on Climara, Vivelle-Dot, Minivelle and Premarin begins with estrogen-alone therapy. It says unexplained, persistent or recurring bleeding after menopause is checked, including with endometrial sampling when needed.
The Climara label puts the endometrial cancer risk with estrogen alone at about 2 to 12 times that of non-users, rising to 15 to 24 times with 5 to 10 years or more of use, and lasting 8 to 15 years after stopping. In Premarin's 1-year trial of women with a uterus, endometrial hyperplasia was 5% on 0.625 mg against 0% on placebo.
Combined products pair the estrogen with a progestin: Prempro adds medroxyprogesterone acetate, Climara Pro adds levonorgestrel and CombiPatch adds norethindrone acetate. Some labels say progestogen and others progestin; both refer to the progesterone-like part.
Adding a progestin changes other risks. In the Women's Health Initiative, estrogen plus progestin raised invasive breast cancer (41 vs 33 per 10,000 women-years), while estrogen alone did not.
If estrogen and a progestin come as separate products, logging both shows whether the progestin days were kept. Logging any bleeding with the date gives the prescriber what the label asks them to check.
Read more on Dose Track: Menopause · Premarin side effects · Prempro side effects · Climara Pro side effects