What are the effects of estrogen therapy in a patient without a uterus (womb)?

From the Guidelines

Estrogen therapy can be safely administered to postmenopausal women without a uterus, but its benefits for chronic disease prevention are unlikely to outweigh the harms in most cases, as evidenced by the USPSTF recommendation statement 1. The effects of estrogen therapy in a patient without a uterus (womb) are multifaceted, involving both benefits and harms.

• Benefits include the management of menopausal symptoms such as hot flashes and vaginal dryness, as well as the potential reduction in the risk of fractures.
• Harms associated with estrogen therapy, as outlined in the USPSTF recommendation statement 1, include an increased risk for stroke, gallbladder disease, urinary incontinence, and deep vein thrombosis (DVT). Given the absence of a uterus, estrogen-only therapy is appropriate, eliminating the need for progesterone, which is primarily used to protect the uterine lining from excessive growth that could lead to endometrial cancer.
• Estrogen-only therapy regimens may include oral estradiol (0.5-1mg daily), estradiol patches (0.025-0.1mg/day changed twice weekly), or estradiol gel (0.5-1.5mg daily), with the goal of using the lowest effective dose for the shortest duration necessary to manage symptoms while minimizing risks. Regular monitoring and follow-up with a healthcare provider are crucial to assess the effectiveness of the therapy and to promptly identify and manage any adverse effects that may arise, as suggested by the clinical considerations in the USPSTF recommendation 1.

From the FDA Drug Label

When estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should also be initiated to reduce the risk of endometrial cancer. A woman without a uterus does not need progestin Use of estrogen, alone or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman.

The effects of estrogen therapy in a patient without a uterus (womb) are not directly stated in terms of benefits, but it is mentioned that a woman without a uterus does not need progestin. This implies that the risk of endometrial cancer, which is a concern for women with a uterus taking estrogen, is not applicable.

• The lowest effective dose should be used for the shortest duration.
• The treatment goals and risks for the individual woman should be considered.
• Patients should be reevaluated periodically (e.g., 3-month to 6-month intervals) to determine if treatment is still necessary 2.
• Common side effects of estrogens include headache, breast pain, irregular vaginal bleeding or spotting, stomach/abdominal cramps, bloating, nausea and vomiting, and hair loss 2.
• Less common but serious side effects include breast cancer, cancer of the uterus, stroke, heart attack, blood clots, and dementia 2.

From the Research

Effects of Estrogen Therapy in Patients Without a Uterus

• Estrogen therapy is effective for the prevention and treatment of postmenopausal osteoporosis and can alleviate menopausal symptoms such as hot flushes and genitourinary symptoms 3.
• In women without a uterus, estrogen therapy can be used without the need for progestogen, which is typically added to reduce the risk of endometrial cancer in women with a uterus 4, 3.
• Estrogen therapy is the most effective treatment for hot flashes, and short-term therapy (not more than 4-5 years) is considered a reasonable option for recently menopausal women with moderate to severe symptoms who are in good cardiovascular health 5.
• Low-dose vaginal estrogens are highly effective for genitourinary atrophy symptoms, with minimal systemic absorption and endometrial effects, and can be used in women without a uterus 5.
• The decision to use hormone therapy depends on clinical presentation, a thorough evaluation of the risks and benefits, and an informed discussion with the patient 4, 5.

Benefits and Risks of Estrogen Therapy

• Benefits of estrogen therapy include reduction of osteoporotic fractures, alleviation of menopausal symptoms, and potential favorable effects on lipoprotein profiles 3, 6.
• Risks of estrogen therapy include breast tenderness, hypertension, vascular headaches, and the potential for increased risk of breast cancer with long-term use 3, 5.
• The risk of breast cancer increases with longer duration of hormone therapy, and short-term therapy is recommended to minimize this risk 4, 5.

Alternative Therapies

• Nonhormonal alternatives such as low-dose paroxetine, venlafaxine, and gabapentin are effective alternatives for treating hot flashes 4.
• Selective estrogen receptor modulators (SERMs) have been developed as an alternative to estrogen therapy, with the goal of providing therapeutic benefits without adverse effects on the breast and uterus 6, 7.
• Tissue selective estrogen complexes, which pair a SERM with estrogens, may provide a new approach to menopausal therapy with improved tolerability and safety 7.