Conference Coverage

Early postmenopausal risk management leads to ‘optimum health’ for women


 

EXPERT ANALYSIS FROM ASRM 2019

– Postmenopausal women are at risk of numerous medical conditions after the onset of menopause, but many ob.gyns feel uncomfortable treating those patients, according to a keynote speaker at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

Dr. Rogerio A. Lobo

The population of women entering menopause continues to rise, and they are at risk for developing chronic diseases about a decade after the onset of menopause, said Rogerio A. Lobo, MD, professor of obstetrics and gynecology at Columbia University, New York.

“For me, from a primary care perspective, there’s a major opportunity for all of us providers at the onset of menopause to identify risks and initiate preventive strategies,” he said.

These newly menopausal women are at risk for diseases across multiple specialty areas, which include obesity, metabolic syndrome, diabetes, cardiovascular disease, osteoporosis, chronic arthritis, dementia, cognitive decline, depression, and cancer. “My focus along these lines is really longevity, reduction in mortality as well as quality of life,” said Dr. Lobo.

Understanding of the benefits of estrogen therapy for postmenopausal women began with work in two studies in the 1990s. One paper by Meir J. Stampfer, MD, and associates on 15 studies examining the effects of hormone therapy on coronary heart disease (CHD) found that the relative risk of estrogen therapy on the disease was 0.50 (95% confidence interval, 0.43-0.56) after adjusting for only prospective and angiographic studies (Prev Med. 1991;20[1]:47-63).

A second paper by Deborah Grady, MD, MPH, and associates found that hormone therapy with estrogen plus progestin decreased the risk of CHD and hip fracture in women but increased the risk of endometrial and breast cancer, and carried a recommendation for using estrogen plus progestin for women who have received a hysterectomy or who are at high risk for CHD (Ann Intern Med. 1992 Dec 15;117[12]:1016-37).

In the early 2000s, data from the Women’s Health Initiative (WHI) began to show a different story: Therapy with estrogen plus progestin was shown to carry risks of early harm in postmenopausal women, and one study by JoAnn E. Manson, MD, DrPH, and associates had a hazard ratio of 1.24 (nominal 95% confidence interval, 1.00-1.54) for CHD in postmenopausal women aged 50-79 years receiving the combined therapy (N Engl J Med. 2003;349:523-34).

The confidence intervals were later adjusted so the association was not significant, but the results led to conclusions that hormone therapy was harmful to women and increased risk of breast cancer, declining cognition, and dementia, as well as cardiovascular diseases such as coronary disease, stroke and thrombosis.

“That was the dogma for many people to this day, but it was clearly a rush to judgment,” said Dr. Lobo. “More harm than good was done for the field.”

The contradictory findings from the WHI and other studies may be explained by the timing of hormone therapy, Dr. Lobo explained. In the ELITE trial, 643 postmenopausal women, stratified into early-postmenopausal (less than 6 years) and late-postmenopausal (equal to or greater than 10 years) groups, received 1 mg of daily oral 17-beta-estradiol with 45 mg of progesterone vaginal gel or placebo. Researchers found that it was beneficial for preventing the progression of subclinical atherosclerosis when therapy was initiated in early but not in late menopause (N Eng J Med. 2016; 374:1221-31).

Estrogen also has benefits for the brain, and might help improve rates of cognitive decline and Alzheimer’s disease in postmenopausal women, Dr. Lobo said. Of the 1,768 women in the Cache County Study who described their use of hormone therapy after menopause, 176 women developed Alzheimer’s; however, use of hormone therapy within 5 years of menopause was associated with a 30% reduced risk of Alzheimer’s (95% confidence interval, 0.49-0.99) and had better benefits for long-term use up to 10 years. But this effect was not present in women who started hormone therapy 5 years or more after onset of menopause (Neurology. 2012 Oct 30. doi: 10.1212/WNL.0b013e318271f823).

Clinicians also should look at the risk of hormone therapy in terms of absolute real risk rather than relative risk. “In WHI, even though many of these events were not statistically significant, even if they assumed they were, the absolute numbers were 7-8 events per 10,000 women per year,” he said. “Those, according to WHI, are rare events if they’re even true.”

“For breast cancer, which is a big concern a lot of women have, endogenous risk factors are much higher than what hormones do,” he added.

Yet clinicians continue to act on data from the WHI, Dr. Lobo noted. In fact, many ob.gyns. report that they are uncomfortable treating women with symptoms associated with menopause.

“Post WHI, we have lost at least a generation of providers who do not deal with menopause,” he added. “Three out of four women who seek help for symptoms don’t receive it. The practice of menopause has largely disappeared from for many, many practices.”

The American Society for Reproductive Medicine used to have a “menopause day,” but the society no longer offers a track for menopause, Dr. Lobo said. One solution aimed at addressing the absence of training might be a menopause curriculum for ob.gyn. residents to help them initiate prevention strategies for postmenopausal women and have the confidence to manage this patient population. Dr. Lobo cited one study from Johns Hopkins where ob.gyn. residents underwent a 2-year menopause medicine curriculum and scored significantly higher on posttest scores after completing the program (78.7% vs. 57.3%; P less than .05). After the curriculum, 85.7% also reported they were more comfortable treating patients with menopause (Menopause. 2016 Mar. 23[3]:275-9).

Work also needs to be done on the front of understanding which hormone therapies are most effective for postmenopausal women. While there is currently no one hormone therapy to specifically recommend, in the future, pharmacogenetics and genetic or molecular risk analyses will play a role in knowing which products to prescribe. “It can be done, to be able to have a clear path for longevity and improved quality of life,” Dr. Lobo said.

Dr. Lobo reported serving as a consultant to Amgen, Mithra, Sojournix, and TherapeuticsMD. In addition, his institution is receiving support from Bayer and the National Institutes of Health for a clinical trial.

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