Is hormone replacement therapy (HRT) appropriate after endometrial carcinoma?

From the Guidelines

Hormone replacement therapy (HRT) can be a reasonable option for patients with endometrial carcinoma who are at low risk for tumor recurrence, but the decision to initiate HRT should be individualized and discussed in detail with the patient. When considering HRT, it is essential to weigh the benefits of relieving menopausal symptoms and protecting against osteoporosis against the potential risks, particularly in women with a history of estrogen-linked malignancies 1.

Key Considerations

• The type and stage of endometrial cancer: HRT may be more suitable for early-stage, low-grade endometrial cancers, such as Type 1 endometrioid adenocarcinomas.
• Time since treatment: A waiting period of 6-12 months after completing therapy is recommended before initiating HRT 1.
• Individual patient factors: Smoking history, history of breast cancer, and history of multiple strokes may make non-hormonal therapy a more suitable option 1.

HRT Regimens

• Estrogen-only therapy may be considered for women who have had a hysterectomy, with regimens such as oral estradiol 0.5-1mg daily or transdermal estradiol 0.025-0.05mg patches.
• Combined estrogen-progestin therapy may be suitable for women with an intact uterus, but this should be approached with caution due to the potential increased risk of breast cancer and cardiovascular disease 1.

Safety Rationale

• The risk of estrogen stimulating recurrence is significantly reduced after complete surgical removal of the uterus and any cancer tissue 1.
• However, HRT is generally not recommended for high-risk endometrial cancers, advanced-stage disease, or cases with specific high-risk features.

Decision-Making

• Any decision about HRT should be made in consultation with both an oncologist and gynecologist, weighing individual symptom severity against potential risks 1.
• Participation in clinical trials is strongly encouraged to further understand the safety and efficacy of HRT in women with a history of endometrial cancer 1.

From the FDA Drug Label

The use of unopposed estrogens in women with intact uteri has been associated with an increased risk of endometrial cancer The reported endometrial cancer risk among unopposed estrogen users is about 2- to 12- fold greater than in non-users, and appears dependent on duration of treatment and on estrogen dose.

The FDA drug label does not provide information to support the use of Hormone Replacement Therapy (HRT) after endometrial carcinoma. In fact, it highlights the increased risk of endometrial cancer associated with unopposed estrogen use. Therefore, HRT is not appropriate after endometrial carcinoma, as it may increase the risk of recurrence or worsening of the disease 2.

From the Research

Hormone Replacement Therapy after Endometrial Carcinoma

• The use of hormone replacement therapy (HRT) after endometrial carcinoma is a topic of ongoing debate, with some studies suggesting that it may be considered in certain cases 3, 4.
• According to current opinion, HRT after stage I or II endometrial cancer is still considered an option, and continuous combined oestrogen/progestogen replacement therapy (CCEPT) would be recommended 3, 4.
• However, the currently discussed possible progestogen effects regarding an increased risk of breast cancer have to be taken into account 3, 4.
• Alternatives such as phytopreparations, tibolone, or particular psychotherapeutic drugs, such as venlafaxine, should be considered for the relief of climacteric complaints 3, 4.
• Progestogen-only therapy (PT) particularly has been considered, but the wider discussion about the gestagen effects regarding the risk of breast cancer is to be considered 3, 4.

Considerations for HRT Use

• The decision to use HRT after endometrial cancer treatment should be individualized, taking into account the woman's symptoms and preferences, and the uncertainty of evidence for and against HRT use 5.
• The available evidence does not suggest significant harm if HRT is used after surgical treatment for early-stage endometrial cancer, but there is no information available regarding use of HRT in higher-stage endometrial cancer (FIGO stage II and above) 5.
• Low-dose oestrogen therapy (patches or gels) instead of CCEPT is recommended for patients after endometrial cancer, especially for those with cardiovascular risk factors 3, 4.
• Each form of HRT should only be exceptionally recommended, and the patients must be informed about the risks that exist and the use of alternatives 3, 4.

Recent Studies and Reviews

• A 2022 literature review suggests that hormonal therapy can be considered in endometrial cancer treatment in both the early-stage upfront setting for patients who are not surgical candidates and in advanced and recurrent endometrial cancer 6.
• A 2018 systematic review found that there is insufficient high-quality evidence to inform women considering HRT after treatment for endometrial cancer, and the use of HRT after endometrial cancer treatment should be individualized 5.
• A 2006 review of the biological and clinical evidence in favour and against HRT use after gynaecological cancers found that, with the exception of breast and endometrial cancer, there is no biological evidence that HRT may increase the recurrence risk 7.