Is menopausal hormone therapy safe when your patient carries a BRCA mutation?
Data suggest that several years of systemic hormone therapy are safe in mutation carriers who have intact breasts and no personal history of breast cancer. If such mutation carriers have undergone risk-reducing bilateral mastectomy, systemic hormone therapy can be used without significantly elevating the risk of breast cancer.
In This Article
- Angelina Jolie describes her surgeries
- Hormone therapy for previvors with intact breasts?
- When a patient refuses hormone therapy
Dr. Simon
Nevertheless, I think it is important to point out that a properly powered study to assess actual risk in this setting is not available in the literature.
When a patient refuses HT
Dr. Pinkerton
Some BRCA mutation carriers may refuse HT despite reassurance that it is safe. Nonhormonal therapies are not as effective at relieving severe menopausal symptoms. Almost all selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) can be offered, although only low-dose paroxetine salt is approved for treatment of postmenopausal hot flashes.10,11 Gabapentin also has shown efficacy in relieving hot flashes.
For genitourinary syndrome of menopause (GSM; formerly known as vulvovaginal atrophy), lubricants and moisturizers may provide some benefit, but they don’t improve the vaginal superficial cells and, therefore, are not as effective as hormonal options. There is now a selective estrogen receptor modulator (SERM) approved to treat GSM—ospemifene. However, in clinical trials, ospemifene has been shown to increase hot flashes, so it would not be a good option for our patient.12
Case: Continued
Christine follows up 3 months after initiating estrogen therapy (oral estradiol 2 mg daily). She reports significant improvement in her hot flashes, with improved sleep and fewer sleep disruptions. In addition, she feels that her “mental sharpness” has returned.
Dr. Pinkerton
What if this patient had an intact uterus? Then she would not be a candidate for estrogen-only therapy because she would need continued endometrial protection. Options then would include low-dose continuous or cyclic progestogen therapy, often starting with micronized progesterone, as the E3N Study suggested it has a less negative effect on the uterus.13 Or she could use a levonorgestrel-releasing intrauterine system off label, as Ms. Jolie Pitt elected to do.
Another option would be combining estrogen with a SERM. The only estrogen/SERM combination currently approved by the US Food and Drug Administration (FDA) is conjugated estrogen/bazedoxefine, which showed no increase in breast tenderness, breast density, or bleeding rates, compared with placebo, in multiple trials up to 5 years in duration.14
Case: Resolved
Christine says she would like to continue HT, although she still experiences dryness and discomfort when sexually active with her husband, despite use of a vaginal lubricant. A pelvic examination is consistent with early changes of GSM.15
You discuss GSM with Christine and suggest that she consider 1 of 2 strategies:
- Switch from daily use of oral estradiol to the 3-month systemic 0.1-mg estradiol ring (Femring), which would address both her vasomotor symptoms and her GSM.
- Continue oral estradiol and add low-dose vaginal estrogen (cream, tablets, or Estring 2 mg).
Christine chooses Option 2. When she returns 6 months later for her well-woman visit, she reports that all of her menopausal symptoms have resolved, and a pelvic examination no longer reveals changes of GSM.
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