What is the relationship between hormone replacement therapy (HRT) and the risk of cervical cancer?

Hormone Replacement Therapy and Cervical Cancer Risk

Hormone replacement therapy (HRT) is not contraindicated in cervical cancer patients and appears to be safe for managing menopausal symptoms in cervical cancer survivors, with no evidence of increased risk of recurrence or negative impact on survival. 1, 2

Safety of HRT in Cervical Cancer Patients

Evidence on Safety

• HRT has been shown to be safe in cervical cancer patients, with no significant influence on disease-free and overall survival, despite the expression of estrogen and progesterone receptors in some cervical adenocarcinomas (39% and 33% respectively) 1
• The British Journal of Cancer guidelines specifically state that "hormone replacement therapy is not contra-indicated" in cervical cancer patients, though caution is advised with adenocarcinomas 1
• A 2021 systematic review found no evidence of harmful effects of HRT on cervical cancer oncological outcomes, while noting several benefits in terms of reduced metabolic risk and improved quality of life 2

Specific Considerations for Adenocarcinomas

• While caution is traditionally advised with adenocarcinomas due to their hormone receptor expression, recent research suggests HRT may not be detrimental to survival even in this subtype 3
• A small study of women with cervical adenocarcinomas showed a trend toward improved survival with HRT use, with 5-year disease-specific survival of 95% in HRT users compared to 73% in non-users (though not statistically significant) 3

Benefits of HRT for Cervical Cancer Survivors

• HRT effectively treats genitourinary menopause syndrome and is useful in managing post-radiotherapy menopausal symptoms 1
• Systemic or local estrogen therapy is a valid option for acute radiotherapy-related changes and can prevent later vaginal complications through epithelial regeneration and anti-inflammatory properties 1
• Vaginal estrogens specifically reduce superficial dyspareunia and relieve urogenital symptoms related to vaginal atrophy with minimal systemic absorption 1

Current Utilization Patterns

• Despite the safety evidence, HRT is underutilized in cervical cancer survivors
• Low compliance rates with HRT in post-treatment menopausal cervical cancer patients have been reported due to:
  • Lack of awareness of benefits by patients and physicians
  • Clinician hesitancy to prescribe due to unfounded fears about second malignancies 1
  • Only 46% of women who experience therapy-induced early menopause from cervical cancer treatment receive ≥75% of the recommended HRT dose 4

Recommendations for HRT Use

1. For women with intact uterus:

   • Combined estrogen-progestogen therapy is mandatory to prevent endometrial hyperplasia and cancer 5
   • Estrogen-only HRT is not advised due to the risk of secondary endometrial cancer, as residual endometrial function may persist after high-dose radiotherapy 1

2. For hysterectomized women:

   • Estrogen-only HRT is sufficient 5

3. Duration considerations:

   • For women with premature menopause due to cancer treatment, HRT appears safe to use until the age of natural menopause 1

Key Caveats and Monitoring

• Regular follow-up is essential: initially at 3 months, then annually to monitor symptoms, bleeding patterns, and potential complications 5
• Combined HRT (estrogen plus progestogen) should be used in women with an intact uterus to prevent endometrial hyperplasia 5
• Transdermal estrogen routes may be preferable for women with hypertension 5

HRT represents an important intervention to improve quality of life in cervical cancer survivors experiencing treatment-induced menopause, with current evidence supporting its safety in this population.