Early treatment with progesterone, the female sex hormone, can delay endometriosis progression and ease resistance to steroid treatment, according to the results of a study conducted on female mice.
To clarify the effect of progesterone on the development of endometriosis, researchers led by Dr. Quanxi Li, a visiting assistant professor at The Center For Research in Reproduction and Infertility at the University of Illinois, developed a new model of the disease by inducing endometriosis-like lesions in female mice.
Analysis revealed the lesions had an abundant blood supply, and stuck extensively to surrounding tissues. In addition, the lesions had a well-organized endometrial structure, showed extensive proliferation, and fibrotic and inflammatory response similar to that observed in endometriosis patients. They also lost the expression of estrogen and progesterone receptors on their surface, meaning that the lesions would not be able to respond to either of these hormones.
The scientists found that if they treated the animals with progesterone before inducing endometriosis, the expansion of the lesions was suppressed and the expression of estrogen and progesterone receptors on their surface maintained.
They also found that lesions pre-treated with progesterone showed a low expression of proteins associated with cell proliferation, the formation of new blood vessels, and inflammation.
To better understand why progesterone treatment is only beneficial when administered early, and the mechanism by which progesterone resistance develops in the later stages of endometriosis, the researchers suppressed the activity of an enzyme called DNA methyltransferase. This enzyme regulates which genes will be expressed in which tissues, by modifying the DNA.
They found that when the enzyme was suppressed, the lesion expansion was restrained and the expression of estrogen and progesterone receptors in the endometrium of the mice restored.
Together, these findings led the researchers to conclude that progesterone improves the signs of endometriosis by inhibiting cell division, inflammation, and the formation of new blood vessels. Furthermore, changes to the DNA, known as epigenetic regulation, are important factors determining the effectiveness of progesterone, and could be contributing to progesterone resistance in endometriosis.
The research team suggests that progesterone treatment in the early stages of endometriosis could preserve the responsiveness to steroid treatment, and could delay disease progression, while treatment at late disease stages may only have minimal therapeutic effects.
The study, “Progesterone Alleviates Endometriosis via Inhibition of Uterine Cell Proliferation, Inflammation and Angiogenesis in an Immunocompetent Mouse Model,” was published in the journal PLOS One.