From the Guidelines
Taking estrogen without progesterone when you still have a uterus can lead to endometrial hyperplasia, which significantly increases your risk of developing endometrial cancer, as evidenced by a relative risk of 2.3 (95% CI, 2.1 to 2.5) for users of unopposed estrogen compared with nonusers 1. When estrogen stimulates the endometrium to grow without the balancing effect of progesterone, the cells can proliferate excessively and potentially become cancerous over time. This is why healthcare providers typically prescribe combination hormone therapy (estrogen plus progesterone or a progestin) for women who have not had a hysterectomy. The progesterone component helps shed the endometrial lining regularly, preventing dangerous buildup. Common progestins used include medroxyprogesterone acetate (Provera) at doses of 5-10mg daily for 10-14 days each month, or continuous low-dose regimens like 2.5mg daily when combined with estrogen. Other symptoms of unopposed estrogen can include:
- Irregular or heavy bleeding
- Fluid retention
- Breast tenderness If you're considering hormone therapy and still have your uterus, always discuss with your healthcare provider to ensure you receive the appropriate combination therapy to protect your endometrial health, as unopposed estrogen, but not combined estrogen–progestin therapy, increases risk for endometrial cancer 1.
From the FDA Drug Label
An increased risk of endometrial cancer has been reported with the use of unopposed estrogen therapy in a woman with a uterus. The reported endometrial cancer risk among unopposed estrogen users is about 2 to 12 times greater than in non-users, and appears dependent on duration of treatment and on estrogen dose Adding a progestin to postmenopausal estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. When estrogen therapy is prescribed for a postmenopausal woman with a uterus, progestin should also be initiated to reduce the risk of endometrial cancer.
Key Risks:
- Increased risk of endometrial cancer
- Increased risk of endometrial hyperplasia, a potential precursor to endometrial cancer
If you take estrogen without progesterone and still have a uterus, you may be at an increased risk of developing endometrial cancer and endometrial hyperplasia. To minimize this risk, it is recommended to add a progestin to your estrogen therapy 2, 2.
From the Research
Risks of Taking Estrogen Without Progesterone
If you still have a uterus and take estrogen without progesterone, several risks can occur, including:
- Endometrial hyperplasia: a condition where the lining of the uterus grows too thick, which can lead to cancer 3, 4, 5, 6, 7
- Endometrial cancer: a type of cancer that affects the lining of the uterus, which can be caused by unopposed estrogen therapy 3, 5
- Atypical hyperplasia: a precancerous condition that can develop into endometrial cancer if left untreated 6
Protection Against Endometrial Hyperplasia and Cancer
Progesterone or progestin can protect the endometrium against the proliferative effects of estrogens in women with a uterus 3, 4, 6, 7. Studies have shown that:
- Combining estrogen with progesterone or progestin can prevent or treat endometrial hyperplasia and reduce the risk of endometrial cancer 3, 4, 5, 6, 7
- Lower doses of conjugated equine estrogens and medroxyprogesterone acetate can provide endometrial protection comparable to that seen with commonly prescribed doses 7
- Micronized progesterone may be less efficient than synthetic progestin in protecting the endometrium, but it can still prevent hyperplasia 3, 6