14-05-2025
Hormone Therapy Safe After Early Salpingo-Oophorectomy
Younger women carrying BRCA 1/2 mutations and intact breasts but with no personal history of breast cancer who undergo bilateral salpingo-oophorectomy (BSO) before age 45 years can safely start systemic menopausal hormone therapy (MHT) and continue it at least up to the average age of menopause (about 52 years).
Andrew M. Kaunitz, MD, FACOG, MSCP
This was the recommendation of a narrative review in Obstetrics & Gynecology led by Andrew M. Kaunitz, MD, FACOG, MSCP, associate chair of the Department of Obstetrics and Gynecology at the College of Medicine — Jacksonville, University of Florida, Jacksonville, Florida. In addition to reducing menopausal symptoms and enhancing quality of life, MHT appears to help prevent coronary events and improve bone health and quality of life. Moreover, estrogen-only MHT appears to substantially reduce breast cancer risk.
In patients older than 45 years at surgery, however, MHT has been associated with a threefold higher risk for breast cancer, underscoring the importance of factoring in age during risk assessment.
To reduce future risk for ovarian, tubal, and peritoneal cancer, the National Comprehensive Cancer Network guidance recommends BSO for BRCA1 or BRCA2 carriers between age 35 years and 40 years and between age 40 years and 45 years, respectively.
Many BRCA mutation carriers, however, are reluctant to undergo lifesaving BSO, recognizing that hot flashes and other menopausal symptoms will likely result and having concerns about the safety of MHT. 'Keep in mind that many of these women have relatives who were diagnosed with and sometimes died from breast cancer,' Kaunitz told Medscape Medical News. ' Given that the general population of women — and clinicians — feel that MHT is dangerous, it's understandable that high-risk women would have even greater concerns regarding its safety.'
Although most appropriately counseled mutation carriers proceed with risk-reducing surgery — about 67% according to Kauntiz — 'a substantial minority do not, with one prominent reason being concerns regarding the safety of MHT.'
Molly J. Pederson, MD
Nevertheless, 'it's critical to raise clinician awareness and confidence in prescribing MHT to this group,' commented Molly J. Pederson, MD, a professor of medicine at the Cleveland Clinic Lerner College of Medicine and the clinic's director of medical breast services in Cleveland, who was not involved in the review.
As observational data suggest MHT is safe and long-term prospective studies have not raised concerns, 'depriving a young surgically menopausal woman without contraindications to MHT can be devastating both in terms of quality of life and in preservation of bone and cardiovascular health,' she said.
Compared with natural menopause, surgical menopause
involves a more rapid decline in serum estrogen levels and more severe vasomotor symptoms, as well as higher rates of sleep disturbances, mood disorders, arthralgias, sexual dysfunction, and impaired quality of life.
On the therapeutic front, the comprehensive review covered a range of systemic and topical treatments, both hormonal and nonhormonal, for multiple problems including vasomotor and genitourinary symptoms and sexual dysfunction. Treatments comprised testosterone therapy, antidepressants, fezolinetant, and elinzanetant, which are now under review by the US Food and Drug Administration.
Lingering Impact of the Women's Health Initiative (WHI)
Some of the MHT safety concerns stem from the WHI clinical trials, which assessed oral conjugated equine estrogens (CEEs) and the synthetic progestational agent medroxyprogesterone acetate (MPA) — primarily for cardiovascular outcomes. 'These were the MHT formulations most in use in the 1990s, when WHI was conceived,' Kaunitz said. 'Statistically, the most important adverse impact of MHT was a more than doubling of the risk of venous thromboembolism. Moving beyond WHI, we now recognize that in contrast with oral estrogens, transdermal estradiol does not elevate risk of venous thromboembolism, including pulmonary embolism.'
In the WHI, women with an intact uterus were randomized to CEE/MPA vs placebo. 'Good-quality observational data suggest that in contrast with CEE/MPA, which modestly elevates risk of invasive breast cancer, estrogen plus micronized progesterone appears to have little if any impact on risk,' he said. 'In my practice, most of my patients with an intact uterus who are using MHT are using transdermal estradiol plus micronized progesterone.'
According to Pederson, MHT use plummeted following the WHI's erroneous announcement in 2002 that 'hormones increased the risk of developing breast cancer by 26%.' 'The publicity around this statistic regarding relative riskhas had dangerous consequences for both patients and providers, creating a bias against MHT that clearly persists.'
Reflecting this bias, she added, only about 5% of US women now use MHT, a decline from about 27% in 1999, despite widespread menopause-related quality of life issues.
Fortunately, said Kaunitz, attitudes are changing. 'My sense is that my colleagues are receptive to learning about newer data pointing the way toward safer approaches to MHT.' But there remains a significant unmet need for educating clinicians to provide appropriate care for individuals at highest risk for breast cancer, including underserved minority populations underrepresented in clinical trials and observational studies.
