SAN DIEGO – Endometrial cancer (EC) rates increased after 2002, coinciding with the release of results from the Women’s Health Initiative and including a 10% spike between 2006 and 2014, according to a large analysis of national data.
“Be aware of an increase of endometrial cancer and, whenever possible, look to minimize possible inciting causes,”, lead study author, said in an interview prior to the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Be certain that the hormonal products that patients are taking are delivering adequate progesterone to the endometrium in those patients at an increased risk of endometrial cancer, such as those with unopposed estrogen.”
“We sought to look at possible causes for the increase of the known risk factors for EC,” she said. “What has changed in the years leading up to 2006?” To find out, she and her associates obtained EC incidence from the Surveillance, Epidemiology, and End Result Program database from 1975 through 2014. They evaluated the incidence of risk factors thought to be associated with EC, including age, obesity, race, number of menstrual cycles, gravidity and parity, metabolic syndromes, diet and exercise, and medications, including various types of hormone therapy, tamoxifen, and hormonal contraceptives.
Shelli Graham, PhD, vice president of medical affairs for Boca Raton, Florida–based TherapeuticsMD, presented the study findings on behalf of Dr. Constantine, who was unable to attend the meeting. The rates of EC were relatively constant from 1992 to 2002 (at about 76/100,000 cases per year) but have increased 2.5% annually, with a 10% increase from 2006 to 2014, especially in women aged 55-64 years.
Use of estrogen and progestin combinations have decreased while risk factors remained constant or decreased during the same time period. However, the researchers observed a “huge increase (of 1-2.5 million U.S. women) using non-FDA approved compounded estrogen and estrogen and progesterone, which may not provide adequate endometrial protection from estrogen, a known cause of EC,” Dr. Constantine said. “Additionally, there is less progestin use subsequent to the [Women’s Health Initiative] and it is known that progestin is protective on the endometrium.”
The researchers also examined the incidence of obesity – another known risk factor for EC – and found that, although obesity has continued to increase in incidence, “it does not appear to be increasing at the same rate as EC, so [it] does not appear to be enough to explain the increase in EC from 2006,” Dr. Constantine said. “I was surprised at the rate of increase of EC from 2006 to 2014 and have also been surprised by the amount of non-FDA compounded hormone use.”
Dr. Graham characterized the increase in EC incidence as “a public health concern that is most likely multifactorial in etiology.” Contributors, she said, include the combination of an increase in obesity with an inherent increase in endogenous estrogen, decreasing progesterone use from a decrease in the use of FDA-approved hormone therapy products, and an increase in compounded hormone therapy that may not deliver adequate endometrial protection.
Dr. Constantine acknowledged certain limitations of the study, including the fact that it is “an ecological analysis, not a randomized clinical trial. It is hypothesis-generating.”
Dr. Constantine reported that she is a consultant/advisory member for TherapeuticsMD and other pharmaceutical companies. She owns stock in TherapeuticsMD. Coauthor Steven R. Goldstein, MD, reported having numerous financial relationships with pharmaceutical companies including TherapeuticsMD. Dr. Graham is an employee of TherapeuticsMD.