What is the relevant medical history for patients taking vaginal estradiol (estrogen) for postmenopausal hormone therapy?

From the Guidelines

When evaluating patients taking vaginal estradiol for postmenopausal hormone therapy, clinicians should prioritize obtaining a comprehensive medical history, including a detailed personal history of breast cancer, endometrial cancer, venous thromboembolism, stroke, coronary artery disease, and liver disease, as these conditions may represent contraindications to estrogen therapy, as suggested by the NCCN guidelines 1.

Key Components of Medical History

The medical history should include:

• Duration and severity of menopausal symptoms, particularly vaginal dryness, dyspareunia, and urinary symptoms
• Personal history of hormone-sensitive cancers, such as breast and endometrial cancer
• Family history of hormone-sensitive cancers
• Current medication use, including anticoagulants, anticonvulsants, and certain antibiotics, which may interact with estrogen therapy
• Previous hormone therapy use and response, as well as any adverse effects experienced
• Vaginal bleeding patterns, as unexpected bleeding may warrant further investigation to rule out endometrial pathology
• Smoking status, as it increases thrombotic risk

Rationale for Comprehensive History

A comprehensive medical history is essential to maximize the benefits of vaginal estradiol therapy while minimizing potential complications, as the treatment carries some risks related to estrogen exposure, particularly with long-term use or higher doses 1. The NCCN guidelines emphasize the importance of careful patient selection and monitoring to ensure safe and effective use of vaginal estrogen therapy.

Considerations for Safe Use

The safety of vaginal hormones, including vaginal estradiol, has not been firmly established in survivors of estrogen-dependent cancers, and therefore, should be used with caution in these patients 1. Additionally, the use of vaginal androgens, such as DHEA, should also be approached with caution in survivors receiving aromatase inhibitor therapy, as they may impact AI activity 1.

From the FDA Drug Label

ESTROGENS INCREASE THE RISK OF ENDOMETRIAL CANCER Close clinical surveillance of all women taking estrogens is important. The Women’s Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5 years of treatment with oral conjugated estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2. 5 mg) relative to placebo. One large meta-analysis of prospective cohort studies reported increased risks that were dependent upon duration of use and could last up to >10 years after discontinuation of estrogen plus progestin therapy and estrogen-alone therapy. The use of estrogen plus progestin has been reported to result in an increase in abnormal mammograms requiring further evaluation. A 2- to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported. Estrogen administration may lead to severe hypercalcemia in patients with breast cancer and bone metastases. Retinal vascular thrombosis has been reported in patients receiving estrogens

The relevant medical history for patients taking vaginal estradiol (estrogen) for postmenopausal hormone therapy includes:

• Endometrial cancer: history of or risk factors for endometrial cancer
• Cardiovascular disease: history of or risk factors for myocardial infarction, stroke, pulmonary emboli, and deep vein thrombosis
• Breast cancer: history of or risk factors for breast cancer
• Ovarian cancer: history of or risk factors for ovarian cancer
• Dementia: history of or risk factors for dementia
• Gallbladder disease: history of or risk factors for gallbladder disease
• Hypercalcemia: history of breast cancer and bone metastases
• Visual abnormalities: history of retinal vascular thrombosis or other visual abnormalities 2 2

From the Research

Relevant Medical History

The relevant medical history for patients taking vaginal estradiol (estrogen) for postmenopausal hormone therapy includes:

• History of breast cancer, as estrogen therapy may increase the risk of breast cancer recurrence 3, 4
• History of cardiovascular disease, as estrogen therapy may affect cardiovascular risk 5, 6
• History of osteoporosis, as estrogen therapy may help maintain bone density 5, 6
• History of vasomotor symptoms, such as hot flashes, as estrogen therapy may help alleviate these symptoms 5, 6
• History of vaginal atrophy, as estrogen therapy may help improve vaginal health 5, 6
• History of hypertriglyceridemia, as non-oral estrogen administration may be preferred in these patients 5, 6
• History of diabetes, as non-oral estrogen administration may be preferred in these patients 6

Estrogen-Receptor Status

The estrogen-receptor status of any previous breast cancer is also important, as this may affect the decision to use estrogen therapy 4.

• Estrogen receptor-negative women may be able to use continuous combined hormone replacement therapy (HRT) without increased risk of breast cancer recurrence
• Estrogen receptor-positive women may need to use a non-aromatizable progestin, such as medrogestone or medroxyprogesterone acetate (MPA), to relieve postmenopausal symptoms

Other Considerations

Other considerations in the medical history of patients taking vaginal estradiol include:

• History of endometrial hyperplasia or cancer, as unopposed estrogen therapy may increase the risk of endometrial cancer 6
• History of venous thromboembolism, as estrogen therapy may increase the risk of venous thromboembolism 6
• Use of other medications, such as tamoxifen or aromatase inhibitors, which may interact with estrogen therapy 3, 4