HRT for Gynecologic Cancer Survivors – Part 1: Endometrial Cancer

Menopause can be challenging for any woman, but for those who have undergone treatment for gynecologic cancers, it is often more severe and abrupt. Many treatments, including surgery, chemotherapy, and radiation, can induce menopause suddenly, leaving patients with intense symptoms that significantly impact quality of life.

For endometrial cancer survivors, the use of hormone replacement therapy (HRT) is a nuanced topic. While many women are told that HRT is not an option, the reality is more complex. I want to partner with these patients and their oncologists to help them make informed decisions about managing menopausal symptoms.

Endometrial cancer and HRT

HRT and Uterine Cancer: What the Research Says

The safety of HRT depends largely on the stage and type of endometrial cancer:

• Stage I and II grade I and II endometrial cancer: HRT is generally considered safe. Studies suggest that in early-stage endometrial cancer, HRT may even be associated with longer progression-free survival and decreased recurrence rates. Fortunately, this makes up the vast majority of uterine cancers.

• Stage III and IV endometrial cancer and uterine sarcomas: HRT is not recommended due to lack of safety evidence and the fact that sarcomas tend to be very estrogen-sensitive.

• Young women diagnosed with endometrial cancer (<40-50 years old): Genetic testing is highly recommended to assess for hereditary cancer syndromes like Lynch syndrome, which can impact treatment and surveillance strategies.

Key Studies on HRT After Endometrial Cancer

2006 Study on Estrogen Replacement in Endometrial Cancer Survivirs

This study included patients with Stage I-II endometrial cancer (including various subtypes such as endometrioid, villoglandular, mucinous, adenosquamous, papillary serous, and clear cell carcinomas but not sarcomas).

Findings:

• There was no increased risk of recurrence in patients who took HRT compared to those on placebo.

• Unfortunately, the study did not have enough data on patients with stage II grade 3 tumors (which tend to be more aggressive), so conclusions about this subgroup remain unclear.

• The study was stopped early due to fears surrounding the Women’s Health Initiative (WHI) study, limiting its ability to provide more definitive long-term data.

2014 Meta-Analysis on HRT and Endometrial Cancer:

This review examined multiple studies assessing the impact of HRT on endometrial cancer survivors.

Findings:

• Many more patients with stage I and II disease who did not use HRT experienced cancer recurrence compared to those who used HRT.

• HRT did not increase the risk of recurrence.

• The authors concluded: “Although the results do not completely exclude the possibility of HRT increasing the risk of recurrence, they suggest that the magnitude of such a risk is not large. The positive effect of HRT on the quality of life seems to outweigh the unfounded suspicion about an increased risk of recurrence.”

HRT Considerations for Younger Patients

Interestingly, for younger women with grade I or II early-stage cancers, some oncologists may feel comfortable leaving the ovaries in place during hysterectomy. This allows the patient to retain her natural estrogen and progesterone, reducing menopausal symptoms naturally. When the ovaries are removed, available evidence suggests that treating these women with HRT may improve overall and cancer-specific survival.

Allowing a woman to keep her ovaries means that she is allowed to keep her estrogen and progesterone which further supports the approach to allowing patients with these low-grade cancers to use HRT for (peri)menopausal symptoms if desired.

What About Vaginal Estrogen?

There is very little data on vaginal estrogen use after endometrial cancer. However, the British Gynecological Cancer Society guidelines support the use of vaginal estrogen for most endometrial cancer survivors.

• We should be cautious in patients with Stage III or IV endometrial cancer and estrogen-sensitive uterine cancers, as these types tend to recur in the vagina.

• If vaginal estrogen is used in these patients, it is recommended to choose low-dose options.

• Vaginal estrogen is not recommended for patients with uterine sarcoma, as this cancer is highly estrogen-sensitive and more likely to recur in the vagina.

Summary: Who is a Candidate for HRT?

Safe to prescribe HRT:

• Stage I and II endometrial cancer (confined to the uterus, no extrauterine spread)

• Grade I and II tumors (lower-risk, well to moderately differentiated)

  
  

HRT is NOT considered safe due to lack of safety data:

• Stage III and IV endometrial carcinoma (cancer that has spread beyond the uterus)

  
  

HRT is NOT considered safe due to lack of safety data and high estrogen-sensitivity:

• Uterine sarcomas (very estrogen-sensitive and high risk)

  
  

Gray areas:

• Stage I/II grade 3 tumors: Due to a lack of conclusive data, decisions should be individualized.

• Higher-grade/stage cancers where patients understand the risks but still wish to pursue HRT: This should involve a thorough discussion of risks and benefits.

  
  

Patient Autonomy and Shared Decision-Making

If you are a uterine cancer survivor considering HRT, my goal is to ensure you are well-informed and empowered to make the best decision for your health. You are the boss of you. If the data is uncertain, but you feel that the benefits of HRT outweigh the risks, we can have a discussion to determine the best course of action for your unique case. Non-hormonal alternatives may be the right option for you.

Before Your Appointment

If you would like to discuss HRT for menopause symptom management after uterine cancer, please bring the following information to your appointment:

• Cancer histology (the type of cancer)

• Tumor grade (how aggressive the cancer cells appear)

• Cancer stage (extent of spread at the time of diagnosis)

  
  

Together with your oncologist we can create a plan that prioritizes both safety and quality of life, ensuring you feel your best while making informed choices about your menopause care.

For more information about this subject, check out Rachel Frankenthal, PA-C in Instagram and the Menopause and Cancer podcast with Dr. Dani Binnington