Βλάχος Νικόλαος, Καθηγητής, Ιατρική Σχολή ΕΚΠΑ.
Δημητρακάκης Κωνταντίνος, Αναπληρωτής Καθηγητής Ιατρικής Σχολής ΕΚΠΑ.
Τριανταφυλλίδου Όλγα, Διδάκτωρ Πανεπιστημίου Αθηνών.
Introduction: Endometriosis is a common gynecological disease which affects about 10% of women of reproductive age. In infertile women the prevalence of endometriosis ranges from 25% to 40%. The organs most commonly involved include the ovaries, the uterosacral ligaments, the fallopian tubes, the cervix, and the cul-de-sac. Endometriosis may be asymptomatic, otherwise the symptoms generally present early in reproductive life and improve after menopause. The adverse effects of endometriosis affect the quality of life, personal relationship and work productivity. Symptoms include painful intercourse (deep dyspareunia) and pain before and/or during menstruation (dysmenorrhoea), bladder and bowel pain, and chronic pelvic pain. Endometriosis is also associated with infertility. According to a large case-control study 58% of women with endometriosis had abdominal and pelvic pain. Half of women with endometriosis are experiencing deep dyspareunia. Compared to women without endometriosis, affected women were 10 times more likely to report dysmenorrhoea and seven times more likely to report symptoms related to sexual intercourse.
The risk of recurrence is a major problem in women who are suffering from endometriosis. Symptomatic recurrence rates of endometriosis have been reported to range from 21,5% at two years to 50% at five years after surgical treatment. The use of oral contraceptives (OCs) has been a time-validated approach for the treatment of endometriosis-related pain in women who do not desire fertility. A few studies have shown the effectiveness of the OCs in the treatment dysmenorrhea, dyspareunia and non-specific pelvic pain associated with endometriosis.
Aim of the cohort study: The aim of this study is to evaluate the efficacy of continuous versus cyclic administration of oral monophasic contraceptives postoperatively on the intensity of dysmenorrhea and dyspareunia in 3,6,9 and 12 months after surgery.
Materials and methods: This prospective cohort study involved 55 symptomatic patients who underwent surgical treatment for endometriosis by laparoscopy in the department of Obstetrics and Gynecology of the «Aretaieion» University Hospital and «Leto» Maternity Hospital of Athens from September 2016 to September 2017. Before surgery, all patients were evaluated by clinical examination and transvaginal sonography to confirm the findings. The patients in both groups were submitted in the same surgical technique, according to the protocol of our clinic, by the same surgeon. All patients were instructed to begin therapy with a low-dose monophasic OC (drosperinone þ+ ethiny-lestradiol [3 þ 0.03 mg]) on the first day of their period after surgery. It’s important to be mentioned that 20 patients, who desired fertility, were instructed to proceed immediately to conception or to use assisted reproduction techniq if needed. Five patients had contraindications in the use of OCs (history of thrombophilia, smokers, etc). The way of OCs administration was patients’ choice. The number of patients in the cyclic group was 17, the number of woman in the continuous group was 11 and 1 woman decided not to participate. All patients were instructed to initiate the treatment with the OCs on the first day of their attendant menstrual cycle for 21 days with 7 days interval without OC, during which time they were expected to have withdrawal bleeding. The women in the continuous group initiated the therapy immediately after the first package without any interruption. The women from both groups were estimated 3 months after surgery and then at three months intervals for one year. At the follow-up period the patients underwent clinical assessment, vaginal and rectal examination and transvaginal ultrasonography. Patients were requested to fulfill self-administered questionnaire (www.endometriosisfoundation.org/WERF-WHSS- Questionnaire-English.pdf). The intensity of dysmenorrhea and dyspareunia was measured in 10-point visual analog scale (VASC). All the patients had to conform with the treatment and to fill in the questionnaires in each visit 3,6,9 and 12 months after surgery.
For the statistical analysis we used IBM SPSS 19 Statistics, which is a software package used for logical batched and non-batched statistical analysis. We used Shapiro-Wilk test as a test of normality in frequentist statistics. T-test was used for a normal distribution and nonparametric Mann-Whitney U test when the criteria for normality were non-compliant. If the value of a scaling term in the test statistic were known, the chi-square test was used for comparisons between proportions was P<.05 was considered statistically significant.
Results: In total, 28 patients fulfilled the questionnaires answering all the questions. Only one woman did not complete the questionnaires for personal reasons.
Looking at the impact of treatment in the mean intensity (MI) of dysmenorrhea and dyspareunia at each specific observational period within each group, the conclusions are remarkable. Patients in the cyclic group entered the study with a MI score of 7.46 for dysmenorrhea and there was a gradual reduction, as expected, with a value of 6.23 at 6 months (p=0.041) and even a greater reduction of the intensity of this symptom at 9 (5.52, p=0.016) and 12 months (4.05, p=0.001). Changes in dysmenorrhea scores were much more pronounced, however, in the continuous group: from a mean intensity of 6.33 at three months to a final elimination of dysmenorrhea at the end of the observational period (MI of 0.91, p=0.04). The rate of reduction of dyspareunia was statistically significant from the beginning of the observational period in both groups, however, significantly more pronounced in the continuous group: from an MI of 7.00 at three months after surgery to 4.16 (p=0.001) and 1.91 (p=0.001) at 9 and 12 months respectively. Whereas in the cyclic group there was a reduction from 7.47 after surgery to 5.47 (p=0.001) at 9 months to 4.88 (p=0.001) at 12 months.
At the primary endpoint, three months after surgery there was no significant difference in dysmenorrhea VAS scores between two groups, (p=0.331). Nevertheless, at the 6-month follow up point, women in the continuous group had a significant reduction in the intensity of dysmenorrhea as compared to the cyclic group (p=0.003). At 9 months postoperatively, there was an even more pronounced reduction on the intensity of dysmenorrhea scores 2.5 (+/-0.313 SE) in the continuous group vs 5.52 (+/-0.53 SE) in the cyclic group (p=0.001). At the end of the observational period (12 months), women treated in the continuous fashion experienced an even further reduction in dysmenorrhea scores (0.91 mean, +/-0.312 SE) whereas in the cyclic group the dysmenorrhea scores reached a plateau (4.05 mean, +/-0.51 SE) (p=0.001).
There were no differences in the mean intensity of dyspareunia between the two groups at 3 months (p=0.679) as well as at 6 months (p=0.303) after surgery. The difference between the cyclic and the continuous group became appreciable at 9 months after surgery. The mean reduction of pain was significantly more pronounced in the continuous group (4.16mean, +/-0.32 SE) as compared to the cyclic group (5.47mean, +/-0.212 SE) (p=0.004). At the end of the 12-months observational period the mean pain VAS score in the continuous group was significantly reduced as compared to the cyclic group (1.91 vs 4.88, p = 0.001).
Conclusion: The risk of recurrence after surgery is a major problem in women who are suffering from endometriosis. There is adequate evidence that continuous treatment with OCs seems to be more effective for women who are suffering from endometriosis associated dysmenorrhea and dyspareunia. Our study elaborated the differential impact of these two therapeutic modalities on the intensity of dysmenorrhea and dyspareunia. These findings should be taken into account when consulting patients on the efficacy of each fashion of OCs use after surgery for endometriosis.