Is menopause hormone therapy (MHT) with estrogen (oestrogen) and progesterone safe for a postmenopausal woman with stage one estrogen receptor (ER) positive endometrial cancer?

Hormone Therapy for Stage I ER-Positive Endometrial Cancer

For postmenopausal women with stage I ER-positive endometrial cancer who have undergone hysterectomy, estrogen-only therapy (without progesterone) is reasonable and safe, with no evidence of increased recurrence risk, and should be initiated 6-12 months after completing adjuvant treatment. 1, 2

Recommended Hormonal Regimen

Estrogen-Only Therapy (No Progesterone Required)

• Transdermal 17β-estradiol 50-100 mcg daily is the preferred formulation because it avoids hepatic first-pass metabolism, provides superior safety regarding thrombotic risk, and has more favorable effects on lipids and blood pressure compared to oral preparations 2

• Progesterone should NOT be added after total hysterectomy, as it introduces avoidable harms including increased breast cancer risk without providing additional benefit for menopausal symptoms or endometrial protection when the uterus has been removed 2

• Oral alternatives (1-2 mg daily of 17β-estradiol or 0.625-1.25 mg conjugated equine estrogens) may be used if transdermal route is not feasible 2

Timing and Eligibility Criteria

When to Initiate Therapy

• Wait 6-12 months after completion of adjuvant treatment before starting hormone therapy to allow for surveillance of early recurrence 1, 2

• This waiting period applies regardless of whether the patient received radiation or other adjuvant therapies 2

Patient Selection Requirements

• Stage I-II, low-grade endometrioid adenocarcinoma with ER-positive status represents the appropriate population for hormone therapy consideration 1, 2

• ER-positive status is NOT a contraindication for hormone replacement therapy in early-stage disease 2

• The favorable risk/benefit profile applies specifically to early-stage endometrial cancer patients who have undergone complete surgical staging 1

Absolute Contraindications to Screen

Do not prescribe hormone therapy if any of the following are present:

• History of breast cancer 1, 2
• Active or recent thromboembolic events (stroke, myocardial infarction, pulmonary embolism, deep venous thrombosis) 1, 2
• Current smoking status 1, 2
• Rapidly progressive or visceral metastatic disease 2

Evidence Supporting Safety

Recurrence Risk Data

• Randomized trials demonstrate no increased recurrence rates or cancer-related deaths in women with early-stage endometrial cancer who use hormone replacement therapy 2

• The evidence is strongest for stage I-II, low-grade, ER-positive disease, which directly matches this clinical scenario 2

• A meta-analysis investigating hormone replacement therapy in endometrial cancer survivors showed variable results, but the 2022 GCIG consensus guideline confirms that the risk/benefit profile remains favorable for early-stage patients 1

Important Nuance on Race

• One meta-analysis reported significantly increased recurrence risk in Black American women using hormone therapy after endometrial cancer, though this finding requires cautious interpretation due to study limitations including lack of molecular subtype data and inclusion of only early-stage disease 1

Monitoring Strategy

• Educate patients on symptoms of recurrence including vaginal bleeding, pelvic pain, or new pelvic masses while on hormone replacement therapy 2

• Regular surveillance follows standard endometrial cancer follow-up protocols, not modified specifically for hormone therapy use 2

• No routine endometrial biopsies are required in women who have undergone total hysterectomy for endometrial cancer 2

Common Pitfalls to Avoid

• Do not deny estrogen therapy to all women with prior endometrial cancer - this represents outdated practice, as current evidence demonstrates safety in low-risk cases 2

• Do not add progesterone after total hysterectomy - this is a critical error that increases breast cancer risk without providing endometrial protection when no uterus remains 2

• Do not use oral estrogen when transdermal is available - transdermal formulations have a superior safety profile regarding thrombosis 2

• Do not prescribe hormone therapy for advanced endometrioid adenocarcinoma - hormone treatment is contraindicated in advanced-stage disease 1

Alternative Considerations

• For women with contraindications to estrogen therapy, selective serotonin reuptake inhibitors or norepinephrine reuptake inhibitors can manage vasomotor symptoms, though they do not address vaginal atrophy 1

• Non-pharmacological approaches including cognitive behavioral therapy, yoga, and acupuncture may be used in conjunction with or instead of hormone therapy 1

• Selective estrogen receptor modulators (SERMs) may be considered as alternatives for women with contraindications, though they do not relieve vasomotor symptoms 2