Is the Pineal Gland Involved in the Pathogenesis of Endometrial Carcinoma

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Abstract
The pathogenesis of endometrial carcinoma, which is the most common malignant neoplasm of the female genital tract, is unknown. It is believed that a prolonged period of increased estrogenic exposure unopposed by progesterone may underlie the malignant transformation of the endometrial cells. In the following communication, we propose that deficient melatonin functions may be an additional endocrine factor implicated in the pathogenesis of endometrial carcinoma. This hypothesis is based on the observations that: (a) melatonin has antiestrogenic properties; (b) melatonin stimulates progesterone production which opposes the action of estrogens; (c) an increased rate of endometrial hyperplasia, a premalignant condition, has been noted during the winter, a time of year associated with diminished melatonin secretion; (d) an increased incidence of anovulatory cycles, which is a risk factor for endometrial carcinoma, occurs in the winter; (e) melatonin secretion decreases sharply during the menopause, a period associated with an increased risk of endometrial carcinoma; (f) obesity, which is a major risk factor for endometrial carcinoma, is associated with impaired circadian melatonin secretion; (g) diabetes mellitus, which is an additional risk factor for endometrial carcinoma, is associated with decreased melatonin secretion and an increased rate of pineal calcification; and (h) the prevalence of endometrial carcinoma is lower in the black population compared to the white population. Similarly, the incidence of pineal calcification, which reflects the secretory activity of the gland, is significantly lower in the African and American black populations as compared to the white population. If this hypothesis is correct, then plasma melatonin levels could be used as an indicator for susceptibility to endometrial carcinoma and administration of oral melatonin could be used alone or in conjunction with progesterones (progestin). or antiestrogens (tamoxifen) in the treatment of hyperplasia and carcinoma. Furthermore, melatonin plasma levels could be used as a laboratory marker in monitoring the efficacy of progestins and antiestrogens in the treatment of endometrial carcinoma. Finally, administration of bright light therapy or the application of a low intensity external magnetic field, which has been shown to synchronize the circadian release of melatonin, could be useful in the management of endometrial hyperplasia and carcinoma.