Endometriosis is a gynecological disease. It is characterized by the presence of endometrial tissue outside the uterine cavity, for example on the ovaries or other pelvic and abdominal structures. It is a debilitating disease that affects up to 10% of women of reproductive age. About 30% -50% of women complain of severe pain and infertility. Today, more than 176 million women worldwide suffer from endometriosis symptoms. These symptoms greatly affect their physical, mental and social well-being.

Estrogens stimulate the proliferation of endometrial and endometriotic tissue; however, in endometriosis, progesterone fails to effectively counteract these estrogenic effects and therefore endometriosis is also considered a disease of the dysregulated action of progesterone or resistance to progesterone.

Progesterone acts by activating the nuclear receptors of progesterone A and B (PR-A, PR-B), which are encoded by the PGR gene.

In PR knock-out (PRKO) mice that are therefore devoid of both receptors, ectopic uterine tissue was found to be resistant to progesterone and exhibited a greater predisposition to estrogen-dependent proliferation.

Resistance to progesterone is often explained by the altered levels of PR-A and PR-B and the PR-C junction variant. Altered levels of PR-A and PR-B may result from PRB hypermethylation or postranscriptional regulation by microRNA.

Current data on PR-A and PR-B mRNA levels in ectopic tissue suggest a mutated PR-A / PR-B ratio in favor of PR-A among different endometriosis subtypes.

A lack of response to progesterone can also be explained by alterations in progesterone metabolism at the pre-receptor level.

The Authors Huhtinen et al. observed higher median levels of progesterone in ovarian (24.7-fold) and extra-ovarian (4.3-fold) ectopic tissue compared to eutopic tissue of patients in the proliferative phase.

In the secretory phase, on the other hand, there were median levels of progesterone in the serum of the patients (2 times) compared to the serum of healthy women and thus also in the eutopic endometrium of the patients (1.9 times) and ectopic endometrium (ovarian endometriosis, 1.9 times; and extra ovarian endometriosis, 4.5 times) compared to the eutopic endometrium obtained from healthy women.

These data imply that progesterone biosynthesis and / or metabolism is dysregulated in patients with endometriosis. It is therefore hypothesized that there is a greater synthesis of progesterone or a decrease in its metabolism during the proliferative phase of the endometrium, while in the secretory phase the biosynthesis of progesterone in the corpora lutei is probably reduced while the local metabolism of progesterone is improved.