August 9, 2021

Increasing Incidence of Carcinoma Endometrium

Endometrial cancer (cancer of uterus) is the sixth most common cancer in women worldwide. It is mainly a disease of high-income countries, where the highest incidence of endometrial cancer is in North America, and Central and Eastern Europe; and the lowest incidence in Middle and Western Africa.

Cancer of the endometrium is the second most common genital cancer in Indian women, second only to carcinoma of the cervix.

The incidence of ca Endometrium is very low in India but highest being observed in Bangalore and Delhi. There are few factors contributing to increased incidence of carcinoma endometrium in urban areas of our country.

When the balance of progesterone and estrogen shifts at the time of menopause, with a decrease in progesterone production, even small amounts of circulating estrogens may not be adequately counterbalanced, and can lead to the thickening of the endometrium and potential subsequent endometrial cancer. Several studies have demonstrated that unopposed estrogen therapy increased the risk for endometrial hyperplasia and cancer, whereas the addition of a progestogen prevents such risk.

In addition to the use of menopausal hormone therapy (HT), a number of factors may influence a woman's risk of developing endometrial cancer, including certain medications, obesity, diabetes, hypertension, reproductive factors, and diet and exercise.

Endometrial cancer incidence (SEER data of NCI, USA)

Data showed that endometrial cancer rates declined between 1975 and 1992, and then remained relatively constant up to 2002 in women 50 years of age or older. Extracting data further, it’s calculated that the age-adjusted incidence rate per 100,000 people increased 2.5% annually with a 10% increase from 2006 to 2012.

Reasons for this increasing incidence are reviewed here specially in terms of risk factor.

Menopausal HT

Decrease in FDA-approved estrogen and progesterone therapies

Increased risk for endometrial cancer was unequivocally shown in earlier studies of unopposed oral estrogen. Early data also showed that addition of a progestogen prevented the increased risk of endometrial cancer with unopposed estrogens. Currently, women with a uterus taking systemic estrogens (oral/transdermal) are to be prescribed a progestogen to prevent endometrial hyperplasia, and the potential for subsequent endometrial cancer.

Increase in FDA-approved vaginal estrogens

Local vaginal estrogen use has not been associated with increased risk of endometrial cancer and does not result in endometrial hyperplasia rates as reported for systemic unopposed estrogens.

Obesity

Obesity may account for up to 40% of the observed endometrial cancer incidence, with obese women having a twofold to fivefold increased risk of developing endometrial cancer compared with normal weight women. In general, obesity is associated with higher levels of circulating estrogens in postmenopausal women, likely accounting for their increased risk of endometrial cancer. Increasing incidence of obesity is also a factor contributing to increasing incidence of carcinoma endomentrium.

Diabetes

Diabetes has also been associated with a significant increased risk of endometrial cancer. Data suggest that the increase in diabetes observed may have contributed to the increase in endometrial cancer incidence.

Reproductive factors

Certain reproductive factors may also influence the incidence of endometrial cancer by affecting the relative estrogen/progesterone balance. Women with an increased lifetime exposure to estrogens, including women with an early age at menarche, later age at menopause, lower parity, and no history of oral contraceptive use, have been linked to a higher incidence of endometrial cancer

Cancer and cancer-related treatments

Cancer-related treatments, such as the selective estrogen receptor modulator tamoxifen, may also affect endometrial cancer risk. Although effective in reducing breast cancer incidence by acting as an antiestrogen in breast tissue, evidence suggests that tamoxifen acts as an estrogen in the uterus and increases endometrial cancers.

Exercise

Epidemiological evidence has shown that physical activity can lower the risk of endometrial cancer by 20%–40% compared with physical inactivity. In conclusion, an increase in endometrial cancer incidence may be associated with a number of risk factors like obesity, and diabetes, lack of physical activity, as well as decreased use of approved estrogen–progestogen HT.

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