THE EFFECT OF 1,25 DIHYDROXY D3 AND DIENOGEST FOR THE TREATMENT
OF ENDOMETRIOSIS
Endometriosis, affecting approximately 10% of women, is an inflammatory disease characterized by excessive growth of endometrial tissue outside of the uterine lining resulting from a hormone imbalance of estrogen dominance and progesterone resistance. In endometriosis, there is an overexpression of estrogen receptors (ER). Specifically, the overexpression of ERβ, one type of
ER, inhibits the expression of progesterone receptors. The signaling of progesterone receptors is necessary to maintain proper endometrial function and thickness. The upregulation of ERs
increases inflammation in the uterus. The most common treatment is hormonal therapy which may have detrimental side effects including osteoporosis, menopausal symptoms, and is
inconsistently effective. Dienogest is a synthetic form of progesterone approved for use in Europe and Japan, but not within the U.S. Dienogest acts as an agonist to the progesterone receptor by mimicking the effects of naturally occurring progesterone molecules, restoring progesterone levels in the endometrium. Vitamin D is a naturally occurring steroid with receptors present on
endometriotic lesions. It is known to have anti-inflammatory properties and to induce the progesterone receptor. Vitamin D has also been shown to downregulate the production of CD44,
a key biomarker of endometriosis. This research investigated the efficacy of combinatorial Dienogest and Vitamin D therapy on the upregulation of the progesterone receptor and the downregulation of CD44. Combined Dienogest and Vitamin D therapy demonstrated no effect on progesterone receptor signaling but did show significant downregulation of CD44. Future research will investigate combination therapy using a primary endometriotic cell line and the
resulting inflammatory response.
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