Although treatment with dienogest, duphaston, or Esmya (ulipristal acetate) all decreased lesion size in a mouse model of endometriosis, dienogest was found to be the most effective of the three, a study suggests.
The study, “Efficacy, safety and recurrence of new progestins and selective progesterone receptor modulator for the treatment of endometriosis: a comparison study in mice,” appeared in the journal Reproductive Biology and Endocrinology.
Current endometriosis treatments with surgery and hormonal medicines are problematic for women who want to preserve their fertility without experiencing side effects or disease recurrence.
Esmya has been used to treat uterine fibroids, but its effectiveness as an endometriosis therapy is unknown. Duphaston, which contains the progestin dydrogesterone, has the ability to reduce pain in endometriosis and avoid pregnancy interruption, but more research is required regarding its use for the disease. Dienogest (marketed under the brand name Visanne), also a progestin, can inhibit growth and implantation of endometriotic lesions, but its exact mechanism is unclear.
Researchers have also never evaluated the recurrence of endometriosis after stopping treatment with Esmya, duphaston or dienogest.
To study these issues, scientists in Hong Kong compared the anti-endometriotic effects, adverse events on reproduction, therapeutic mechanism, and disease recurrence of Esmya, duphaston, and dienogest in a mouse model of endometriosis. The treatments were given orally for a maximum of four weeks.
They evaluated lesion size, weight and markers, body, uterus and ovaries’ weights, follicle count, and endometrial glands and thickness. Scientists also monitored lesion growth before and after therapy to analyze disease recurrence.
Results showed that all three medications reduced lesion size and weight. Levels of proliferating cell nuclear antigens (Pcna), a protein associated with cell proliferation, were lower with all three, but only duphaston decreased the number of proliferating cells. Duphaston also increased levels of cell death markers.
“Compared with Esmya and Duphaston, Dienogest has the strongest anti-endometriosis efficacy in terms of the reduced lesion size up to 61%,” the investigators wrote.
Mice treated with dienogest had an increase in the number of endometrial glands in the uterus. According to the authors, this is an indicator of glandular hyperplasia, a thickening of the uterus lining that can increase the risk of endometrial cancer. Treatment with duphaston decreased endometrium thickness, a sign of endometrial atrophy, while mice treated with Esmya had suppressed ovulation. These effects with duphaston and Esmya may be relevant for women considering pregnancy, the authors cautioned.
“Because of the anti-proliferation effect on endometrium and suppressive effect on endometriotic lesions, Duphaston could be a better option for endometriosis patient during perimenopause [before menopause], while Esmya is suitable for endometriosis patient who cannot tolerate progesterone effect due to the heavy irregular uterine bleeding,” the authors said.
None of the medications caused changes in body weight nor mouse behavior, which supports their safety, they observed.
All three groups showed disease recurrence upon stopping treatment, but lesion regrowth was slower in mice that had received Esmya.
“All Esmya, Duphaston and Dienogest can suppress endometriotic growth on mouse model and Dienogest has the best suppressive effect,” the researchers concluded.