Many women, and even some doctors, are basing fears of estrogen therapy (ET) on outdated research and are underutilizing estrogen when it’s safely indicated to ease menopausal symptoms in women in their 40s, 50s and possibly 60s, says Bruce Carr, MD, director of the Reproductive Endocrinology and Infertility Fellowship Program at UT Southwestern Medical Center in Dallas, speaking at the 26th Annual Meeting of American Association of Clinical Endocrinologists on May 3, 2017, in Austin, Texas. There is a mistaken belief that ET for these age groups causes an increase in breast cancer risk and heart disease, though that has been disproven. “I believe estrogen is grossly underused in healthy women who have the indications for it,” Dr. Carr says. When it comes to vasomotor symptoms (night sweats, hot flushes) urogenital symptoms (such as burning, itching and painful intercourse), and the prevention of osteoporosis, there’s no other drug as potent as estrogen, says Dr. Carr.
Other experts in the field agree. “Women are suffering unnecessarily from the negative impact of hot-flushes on their day-to-day lives when many of them could safely and effectively be treated with hormone therapy,” Kristen A. Matteson, MD, Associate Professor of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, and a spokesperson for the American Congress of Obstetricians and Gynecologists (ACOG). (ET is also referred to as hormone therapy, aka HT, when progestin is added to lower a woman’s risk of uterine cancer.)
Why aren’t more women with menopausal symptoms offered ET or willing to consider it when it’s suggested by their doctor? Because of an older study that has been found flawed, but which is still embedded in the thinking: In 2002, the Women’s Health Initiative (WHI)1 found a slight increase in breast cancer risk, as well as an increased risk of heart disease, blood clots, and stroke for women on ET. Upon its publication, millions of women and their doctors concluded that ET for menopausal symptoms was not worth the risk. “Studies have suggested that systemic hormone therapy has decreased by about 80% over the past 15 years since the results of the Women’s Health Initiative were first published,” Dr. Matteson tells EndocrineWeb.com.
In the years since the WHI was first published, however, the vast majority of doctors view the results as skewed because it included an older set of women (the average age was 63), patients who were more than a decade past the average age of menopause and when there is rarely an indication for using ET to ease menopausal symptoms. (ET in women older than 70 does slightly increase the risk of breast cancer.) [In addition, the WHI wasn’t really designed to look at breast cancer. “The WHI was designed to determine the benefits and risks of hormone therapy when used by post-menopausal women for the prevention of chronic disease, focusing on cardiovascular outcomes,” says Dr. Matteson.]
More recent research, including results from the Nurses Health Study, have found that there is no increased risk of breast cancer in women under age 70 taking estrogen alone and only a slight increase in risk (1.24) for women on combination estrogen-progestin therapy under age 70, says Dr. Carr. “The increased risk of BC for women under 70 is equal to the risk incurred from being overweight or having started your period before age 12,” he says.
Starting ET in a woman’s 40s or 50s can actually improve her health and mortality as she ages. “There’s a window of opportunity to lower heart disease risk if you start women on estrogen therapy in her 50s,” says Carr.
Indeed, a 2013 analysis in the British Medical Journal 2 showed that “estrogen avoidance” of women in their 50s who’d undergone a hysterectomy contributed to an increased risk in death, attributable in part to the cardiovascular disease that progresses in younger women when estrogen is absent. “We know from a number of animal studies and some human studies that before a woman develops atherosclerosis, estrogen can help prevent the development of atherosclerotic plaque,” says David Archer, MD, director of the clinical research center, department of obstetrics and gynecology at Eastern Virginia Medical School, adding that once the plaque process has started, however, estrogen could hasten the process (which may account for the increased risk of heart disease in women in their 60s and 70s in the WHI trial).
In addition, research has also found that HT may be linked to decrease in the risk of Alzheimer’s and colorectal cancer in women using hormone therapy (HT), says Dr. Carr. However, at this time, experts do not recommend putting women on ET or HT simply as primary prevention for chronic disease such as cardiac disease, osteoporosis or Alzheimer’s in the absence of menopausal symptoms.
While the data is clear that ET is safe and effective for healthy women in their 40s and 50s, women in their 60s should take an individualized approach. The North American Menopause Society recommends that at age 60, patients discuss all their risks with their doctor, acknowledging that around 42% of women continue to have symptoms that impair sleep and health between ages 60 and 65 3 The American College of Obstetrics and Gynecologists (ACOG) does not include age-based recommendations for or against ET or HT in their practice guidelines, stating that “systemic hormone therapy, with estrogen alone or in combination with progestin, is the most effective therapy for vasomotor symptoms related to menopause.” They recommend that the lowest dose of HT be used for the shortest amount of time to reduce symptoms, and that regardless of age, HT be individualized. Dr. Archer says doctors should also consider the beneficial role of estrogen on bone density when considering whether to place a woman on ET for menopausal symptoms.
Women who should not take ET for menopausal symptoms at any age, says Dr. Matteson, include those with porphyria cutane tarda (a rare enzyme deficiency that affects iron production) and should generally not be used by women with current, past or suspected breast cancer; undiagnosed genital bleeding; untreated pre-cancer changed of the uterus; previous or current venous thromboembolism; active or recent arterial thromboembolic disease (angina, myocardial infarction); untreated high blood pressures; or active liver disease.
As for breast cancer risk, Dr. Archer says, “If women are truly concerned about their risk for breast cancer and heart disease, the best thing they can do is to lose weight, exercise, reduce alcohol intake to less than two drinks/day,” regardless of hormone therapy status.
Financial disclosures: Dr. Archer is a consultant for Agile Therapeuts, AbbVei, TherapeuticsMD, Exceltis, Allergan.