What is the recommended estrogen replacement therapy (Estrogen Replacement Therapy, ERT) for post-menopausal patients who have undergone a total hysterectomy (surgical removal of the uterus)?

From the Guidelines

For post-menopausal patients who have undergone a complete hysterectomy, estrogen-only therapy is the recommended treatment, with options including oral estradiol, transdermal estradiol patches, or estradiol vaginal rings, as it has been shown to reduce the incidence of fractures and have a small reduction in the risk for developing or dying of invasive breast cancer, as stated in the USPSTF recommendation statement 1. When considering estrogen treatment for these patients, it's essential to weigh the benefits and harms. The USPSTF found that estrogen alone results in a small reduction in the risk for developing or dying of invasive breast cancer, and it is of moderate benefit in reducing the incidence of fractures 1. However, it's also associated with moderate harms, including the risk for stroke, gallbladder disease, and urinary incontinence, as well as a small increase in the risk for DVT. Some key points to consider when prescribing estrogen therapy for post-menopausal patients with a complete hysterectomy include:

• Starting with the lowest effective dose and adjusting based on symptom response
• Considering the patient's individual risk factors and characteristics that may affect the likelihood of having a specific therapy-associated adverse event
• Evaluating the patient's quality of life and symptom severity to determine the best course of treatment
• Regularly reassessing the risk-benefit profile of hormone therapy, ideally on an annual basis
• Being aware of contraindications, such as history of estrogen-sensitive cancers, active liver disease, history of blood clots, or undiagnosed vaginal bleeding, as mentioned in the example answer. It's crucial to note that the USPSTF concludes with moderate certainty that the chronic disease prevention benefits of estrogen are unlikely to outweigh the harms in most postmenopausal women who have had a hysterectomy 1. Therefore, treatment decisions should be made on a case-by-case basis, taking into account the individual patient's needs and risk profile.

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 For treatment of moderate to severe vasomotor symptoms, vulval and vaginal atrophy associated with the menopause, the lowest dose and regimen that will control symptoms should be chosen and medication should be discontinued as promptly as possible. The usual initial dosage range is 1 to 2 mg daily of estradiol adjusted as necessary to control presenting symptoms.

The recommended estrogen treatment for a post-menopausal patient who has had a complete hysterectomy is estradiol at a dose of 1 to 2 mg daily, adjusted as necessary to control symptoms, without the need for progestin 2.

• The treatment should be started at the lowest dose for the indication.
• The minimal effective dose for maintenance therapy should be determined by titration.
• Administration should be cyclic (e.g., 3 weeks on and 1 week off).

From the Research

Estrogen Treatment for Post-Menopausal Women with Hysterectomy

• Estrogen treatment is the recommended hormone therapy for post-menopausal women who have had a complete hysterectomy, as it is all that is needed to alleviate hot flashes and/or genital atrophic symptoms associated with surgical or natural menopause 3.
• The addition of a progestogen to an estrogen-only therapy regimen is not necessary for women without a uterus, as the risk of endometrial neoplasia is eliminated 3, 4.
• Multiple lines of evidence suggest that regimens containing both estrogen and progestogen are associated with a greater relative risk of breast cancer, without additional improvement in relief of hot flashes or vaginal symptoms 3.
• The decision to use or not use menopausal hormone therapy in women without a uterus should involve an individualized risk/benefit analysis, taking into account the patient's age, time since menopause, and comorbidity status 3, 5.

Considerations for Estrogen Therapy

• Estrogen therapy alone is associated with a more favorable benefit/risk balance, particularly for breast cancer risk and cardiovascular protection, compared to combined estrogen and progestogen therapy 4, 6.
• The timing of estrogen therapy initiation is crucial, with younger women (close proximity to menopause) experiencing more favorable effects on coronary heart disease and all-cause mortality 5, 6.
• The type and route of administration of estrogen therapy should also be considered, with some evidence suggesting that estradiol may have a better safety profile compared to other estrogens 7.

Patient-Specific Considerations

• Women with a prior hysterectomy and bilateral oophorectomy may experience more severe menopausal symptoms and require earlier initiation of hormone therapy 3, 6.
• The effects of estrogen therapy may vary by age, with older women (≥70 years) experiencing adverse effects during the treatment period, while younger women (<60 years) may derive mortality benefits over the long term 6.