Is Hormone Replacement Therapy (HRT) safe in BRCA carriers after Bilateral Salpingo-Oophorectomy (BSO)?

Hormone Replacement Therapy Safety in BRCA Carriers After Bilateral Salpingo-Oophorectomy

Short-term hormone replacement therapy (HRT) is safe for healthy BRCA1/2 mutation carriers following risk-reducing bilateral salpingo-oophorectomy (RRSO) to alleviate menopausal symptoms. 1

Safety of HRT Post-RRSO in BRCA Carriers

Evidence Supporting Safety

• Short-term use of HRT following RRSO is considered safe among healthy BRCA1/2 mutation carriers who have not had breast cancer 1
• HRT does not negate the protective effect of RRSO on subsequent breast cancer risk in BRCA1/2 mutation carriers 2
• For women undergoing RRSO at a young age (before natural menopause), HRT can mitigate some of the adverse effects of surgical menopause 3

Age-Related Considerations

• Recent evidence suggests HRT is safe for women up to age 45, but beyond that age, there may be an increased risk of breast cancer 1
• Longer-term use of HRT for unaffected carriers >45 years who have also previously undergone bilateral risk-reducing mastectomy (BRRM) may be considered on a case-by-case basis 1

Recommendations for HRT Use

Duration and Approach

• HRT should be used for the shortest duration possible to control menopausal symptoms 4
• The lowest effective dose should be used to minimize potential risks 4
• HRT should be offered up to the age of natural menopause for BRCA carriers who undergo RRSO and do not have a personal history of breast cancer 5

Contraindications

• HRT is contraindicated in BRCA mutation carriers who have a personal history of breast cancer 5, 1
• The relationship between hormonal influences and different breast cancer subtypes, including triple-negative breast cancers (common in BRCA1 carriers), has not been fully elucidated 1

Management of Menopausal Symptoms

Systemic vs. Local Therapy

• Systemic HRT can be used for vasomotor symptoms and to prevent bone loss 1
• Local vaginal therapies, including low-dose intravaginal estrogens, may be considered to manage genitourinary symptoms of menopause (vulvovaginal dryness, dyspareunia, urinary symptoms) 1
• Topical estrogens to alleviate vaginal dryness may be used with caution due to variable systemic absorption 1

Non-Hormonal Options

• Vaginal moisturizers and lubricants should be prescribed to all women following risk-reducing surgery 1
• Non-hormonal options should be considered first for managing menopausal symptoms in women with higher risk profiles 4

Long-Term Health Considerations

Bone Health

• Regular assessment of clinical risk factors for accelerated bone loss and measurement of bone mineral density is recommended for women who underwent RRSO while premenopausal 1
• Resistance and weight-bearing exercise, smoking cessation, reduced alcohol intake, vitamin D and calcium supplements are recommended 1
• Antiresorptive therapy should be considered when indicated 1

Cardiovascular and Cognitive Health

• Benefits of HRT on cardiovascular and cognitive health remain controversial 1
• Premature menopause adversely impacts bone health and potentially cardiovascular health 1

Special Considerations

Hysterectomy Considerations

• When hysterectomy is performed at the time of RRSO, progesterone addition is not needed, potentially reducing breast cancer risk concerns 6
• There was no difference in the use of HRT between women who had total abdominal hysterectomy with RRSO versus those with RRSO alone 7

Quality of Life Impact

• BRCA mutation carriers experience significant worsening of menopausal symptoms and decline in sexual functioning after RRSO, particularly among those who underwent surgery prior to natural menopause 3
• HRT mitigates some but not all effects of surgical menopause on quality of life 3

Counseling Recommendations

• Limitations and risks of HRT should be clearly communicated to patients 1
• Appropriate counseling should be available to address psychological distress related to changes in body image and sexuality 1

In conclusion, while data on HRT use in BRCA carriers after RRSO are limited and mostly retrospective, the current evidence supports that short-term HRT is safe for healthy BRCA mutation carriers who undergo RRSO before natural menopause to manage menopausal symptoms and prevent bone loss.