Should a 60-year-old postmenopausal woman, experiencing a brown discharge after three months of unopposed estradiol (estrogen) patch therapy, undergo endometrial evaluation if the discharge resolves with the addition of progesterone?

From the Guidelines

An endometrial evaluation is still necessary for this 60-year-old woman, despite the resolution of vaginal discharge after adding progesterone to her estradiol patch therapy. The brown vaginal discharge that occurred after three months of unopposed estrogen therapy (estradiol patch without progesterone) is concerning for possible endometrial hyperplasia or malignancy, as unopposed estrogen therapy increases the risk of endometrial cancer, with a relative risk of 2.3 (95% CI, 2.1 to 2.5) compared to nonusers 1. Key points to consider include:

• The risk of endometrial cancer increases with the duration of unopposed estrogen use, with a relative risk of 9.5 for 10 years of use 1
• The risk for endometrial cancer remains elevated 5 or more years after discontinuation of unopposed estrogen therapy 1
• Combined estrogen-progestin regimens have been shown to decrease the risk for endometrial cancer (RR, 0.4; 95% CI, 0.2 to 0.6) compared to nonusers, in cohort studies 1
• The addition of progesterone to estrogen therapy does not necessarily rule out underlying endometrial pathology, and an endometrial biopsy or transvaginal ultrasound should be performed to assess endometrial thickness
• Moving forward, she should continue on a combined hormone therapy regimen, such as estradiol patch plus oral medroxyprogesterone acetate 5-10mg daily for 12-14 days per month, or continuous combined therapy with daily progesterone if she wishes to avoid monthly bleeding.

From the Research

Endometrial Hyperplasia and Cancer Risk

• The use of unopposed estrogen, such as estradiol patch without progesterone, increases the risk of endometrial hyperplasia and cancer 2, 3.
• Endometrial hyperplasia is a precursor to endometrial cancer, and the risk of progression to cancer is higher in women with atypical hyperplasia 2, 4.
• Abnormal uterine bleeding, such as a slight brown tinge discharge, is a common presenting symptom of endometrial hyperplasia 2, 5.

Diagnostic Options

• Endometrial biopsy is a safe and cost-effective option for diagnosing endometrial hyperplasia and cancer, with a sensitivity of 90% for endometrial cancer and 82% for atypical hyperplasia 5.
• Hysteroscopy and fractional dilatation and curettage (D&C) are also diagnostic options, but the accuracy of these methods is still debated 6.
• Immunohistochemical biomarkers and genomic analysis may also be used to diagnose and stratify women at risk of endometrial cancer 4.

Treatment and Management

• Progestins, such as medroxyprogesterone acetate (MPA) and megestrol acetate, are commonly used to treat endometrial hyperplasia without atypia 2, 6.
• Hysteroscopic focal resections and hormonal therapies, such as levonorgestrel intrauterine systems (LNG-IUS), may be used to treat atypical hyperplasia and preserve fertility 6.
• Hysterectomy may be recommended for women with atypical hyperplasia or endometrial cancer, unless other factors preclude surgery 2, 6.