Journal of Endometriosis and Pelvic Pain Disorders:

Adenomyosis is a common gynecological disease in premenopausal women and late reproductive age. The most common symptoms are progressive dysmenorrhea, chronic pelvic pain, dyspareunia, heavy menstrual bleeding, and abnormal uterine bleeding.

The severity and frequency of symptoms often correlate with the size and depth of the inclusion of the endometrium in the myometrium, which corresponds to the pathology of endometriosis and disease progression.

A randomized control study was conducted from 2016 to 2019 on the basis of the gynecology clinic of Saint Petersburg emergency institute. This randomized controlled trial compared the number and severity of endometrioid glands in the myometrium in women with adenomyosis after 6–12 months of treatment with dienogest and in women before treatment.

The results showed that dienogest-containing preparations statistically significantly reduced the number and activity of the glandular structures of the ectopic endometrium. This suggests that progestin has a direct effect on the endometrioid glands in addition to its systemic effect, and thus may contribute to their atrophy.

Abstract

Introduction: The aim of this study was to analyze the effect of dienogest on the endometrioid glands in myometrium, a morphological assessment of the effect of the drug, considering its safety, as well as an assessment of changes in the quality of life of women associated with a decrease in the severity of symptoms of adenomyosis.

Materials and methods: The study included women aged 20–50 years, with histologically confirmed adenomyosis, which was manifested in them by the presence of pelvic pain, abnormal uterine bleeding, painful, and/or heavy menstruation, as well as the presence of anemia. Patients were divided into three groups depending on the name of the drug that they used: 24 patients of Group I received the drug “Dienogest” at 2 mg/day for 6 months. In the second group, 24 patients received the combined oral contraceptive drug. The third group included 24 patients who received the Jeanine preparation continuously (21–21–21) for 6 months and then received it for an additional 6 months according to the scheme (7 + 21), containing ethinyl estradiol and dienogest.

Results: After the appointment of drugs for 6–12 months, bloody discharge from the genital tract in Group I completely stopped in all 10 women; in Group II, the discharge decreased in four women and completely stopped in eight women; and in group III, the discharge decreased in three women and completely stopped in seven women, pain in Group I completely stopped in six women out of eight (75%) and decreased in two women out of eight (25%); in the second group, the pain stopped completely in 7 women out of 12 (58.3 %) and decreased in 5 women out of 12 (41.6%); in the third group, pain completely recovered in 6 women out of 10 (60%) and decreased in 4 women out of 10 (40%).

According to the morphological assessment (Figures 1 and 2) of the myometrium section with endometrioid glands before treatment, Group I had 12.2 ± 3.8* glands before treatment and from 1.4 ± 0.8* endometrioid glands after treatment. In the second group, the number of glands before treatment was 10.8 ± 1.4* and after treatment from 3.8 ± 0.7 glands, and in the third group before treatment, 6.7 ± 2.1 endometrioid glands were determined and aftertreatment 2.7 ± 1.4 glands in the field of view.

Figure 1. Endometrial tissue site with endometrioid glands before treatment with dienogest-containing drugs. Increase 40. Hematoxylin-eosin stain. Ectopic endometrium in the myometrium of women with adenomyosis in the untreated group.

Figure 2. Site of endometrial tissue with atrophied endometrioid glands after treatment with dienogest-containing drugs. Increase 40. Hematoxylin–eosin stain. Atrophied ectopic endometrium in the myometrium of women with adenomyosis in the group receiving dienogest-containing drugs.

Conclusion: Dienogest is effective in the treatment of endometriosis and reduces both the clinical manifestations of adenomyosis (abnormal uterine bleeding and chronic pelvic pain) and laboratory blood counts, increasing hemoglobin levels, together with a decrease in the activity of the endometrioid glands in myometrium.

Dienogest is a highly selective progestogen against progesterone receptors and has anti-proliferative activity in isolated human endometrial cells. Given the indicators of the 36-Item Short Form Survey questionnaire, the quality of life in all the studied groups improved in all parameters, which indicates the effectiveness of the dienogest-containing drugs used.