Prolonged cyclical and continuous regimens of dydrogesterone are effective for reducing chronic pelvic pain in women with endometriosis: results of the ORCHIDEA study.

OBJECTIVE: To compare the effectiveness of two different treatment regimens of dydrogesterone in the management of endometriosis-related chronic pelvic pain. DESIGN: Observational, prospective cohort study over six months. SETTING: Twenty gynecology clinics in the Russian Federation. PATIENT(S): Three hundred fifty women from 18 to 45 years of age with endometriosis and chronic pelvic pain with or without dysmenorrhea. INTERVENTION(S): Dydrogesterone 10 mg 2 or 3 times daily, either between the 5th and 25th days of the menstrual cycle (prolonged cyclical treatment regimen) or continuously (continuous treatment regimen). For all patients, the data cutoff was at six months of treatment. MAIN OUTCOME MEASURE(S): Intensity of chronic pelvic pain on the 11-point numerical rating scale (after 6 months). RESULT(S): A marked reduction in chronic pelvic pain was observed with both the prolonged cyclical and continuous treatment regimens (mean ± standard deviation change from baseline -3.3 ± 2.2 and -3.0 ± 2.2, respectively), with no significant difference between the two groups. With both regimens, patients experienced significant improvements in the intensity of chronic pelvic pain, number of days in which analgesics were required, severity of dysmenorrhea, sexual well-being, and health-related quality-of-life parameters. A favorable safety profile of dydrogesterone was confirmed, and no serious adverse drug reactions were reported during the study. CONCLUSION(S): Prolonged cyclical and continuous treatment regimens of dydrogesterone therapy both demonstrated a pronounced and similar reduction in the severity of chronic pelvic pain and dysmenorrhea and led to marked improvements in all study parameters related to quality of life and sexual well-being. REGISTRATION NUMBER: NCT03690765.

Pelvic organ prolapse patients' attitudes and preferences regarding their uterus: comparing German- and Russian-speaking women.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to compare preferences of patients with pelvic organ prolapse (POP) regarding their uterus between German- and Russian-speaking areas. METHODS: Six urogynecologic tertiary referral centers participated in this prospective study: three centers from German-speaking countries and three from different regions of Russia. To assess the uterus-related preferences as well as the attitude toward hysterectomy versus uterus-sparing prolapse surgery, we developed a structured questionnaire that included 5-point Likert scales related to benefit of uterus (BOU) and benefit of not having uterus (BNU). Each scale consisted of 12 items (range of possible scores: 12-60). Finally, patients were asked if they preferred uterus removal or preservation when undergoing prolapse surgery. RESULTS: One hundred and seventy-eight German-speaking and 206 Russian-speaking patients were included in the study. There was no significant difference in patients' preference before undergoing POP surgery regarding uterus preservation versus hysterectomy between German- and Russian-speaking patients: 40% of German-speaking and 54% of Russian-speaking patients preferred to retain their uterus before undergoing POP surgery. Comparison of BOU mean scores showed a significant difference between groups: 20.6 ± 6.7 for German-speaking compared with 32.5 ± 9.1 for Russian-speaking patients (p < 0.01). The Russian-speaking group had significantly higher mean scores on domains sexuality, body image, and partnership of the BOU scale (2.6 ± 1.0 vs. 1.8 ± 0.9 for sexuality; 2.4 ± 1.1 vs. 1.5 ± 0.7 for body image, and 2.6 ± 0.9 vs. 1.6 ± 0.7 for partnership domains; p < 0.05). CONCLUSIONS: Although a large proportion of German- and Russian-speaking patients prefers uterus preservation when undergoing prolapse surgery, the uterus was more important for sexuality, partnership, and body image in Russian-speaking patients.

Frequency and Spectrum of MED12 Exon 2 Mutations in Multiple Versus Solitary Uterine Leiomyomas From Russian Patients.

Uterine leiomyomas (ULs) are common benign tumors affecting women of different ethnicities. A large proportion of UL has mutations in MED12. Multiple and solitary ULs usually manifest with different severities, suggesting that their origin and growth pattern may be driven by different molecular mechanisms. Here, we compared the frequency and the spectrum of MED12 exon 2 mutations between multiple (n=82) and solitary (n=40) ULs from Russian patients. Overall, we detected MED12 exon 2 mutations in 51.6% (63/122) of ULs. The frequency of MED12 exon 2 mutations was almost two-fold higher in samples from the multiple UL patients than in those from the solitary UL patients - 61% (50/82) versus 32.5% (13/40). The increased MED12 exon 2 mutation frequency in the multiple ULs was not accompanied by significant alterations in the spectrum of mutation categories, which included missense mutations, deletions, splicing defects, and multiple (double/triple) mutations. Each mutation category had a unique mutation set, comprising both frequent and rarely encountered mutations, which did and did not overlap between the studied groups, respectively. We conclude that in contrast to the solitary ULs, the multiple ULs predominantly originate through MED12-associated mechanisms. The nature of these mechanisms seems to be similar in solitary and multiple ULs, as they contain similar mutations. In multiple UL patients, they are likely to be nonsporadic, indicating the existence of specific factors predisposing to multiple UL development. These data suggest that to clearly understand UL pathogenesis, solitary and multiple tumors should probably be analyzed as separate sets.