Treatment Choice in Primary Dysmenorrhea
Treatment Choice in Primary Dysmenorrhea
Our aim is to evaluate and compare the pain relief of estradiol valerate/dienogest and
 ethinylestradiol/ drospirenone by using doppler indices.

 100 nullipara patients with symptoms of severe primary dysmenorrhea (PD) requesting
 contraception aged from 18 to 35 were included to the study. Visual analog scale (VAS), the
 uterine artery doppler indices including systole/diastole rates ( S/D), pulsatility index
 (PI) and resistance index (RI) values were evaluated and recorded in both uterine vessels
 before treatment. The 66 PD patients who met the inclusion criteria were divided into 2
 groups and 33 healthy controls created Group 1. Group 2 were administered estradiol
 valerate/dienogest while Group 3 were administered 0.03 mg ethinylestradiol and 3 mg
 drospirenone. Both VAS scores and doppler indices were repeated after 3 months treatment. The
 changes in values were recorded.
This prospective, randomized, controlled clinical trial was conducted in Kayseri Education
 and Research Hospital, in Turkey between 2015 and 2016. Nullipara patients with symptoms of
 severe primary dysmenorrhea (PD) requesting contraception aged from 18 to 35 were included to
 the study. Afterwards, based on computer generated random numbers the patients were allocated
 to one of the two study arms; Group2 (Qlarista group) and Group3 (yasmin group), equally.

 The PD was diagnosed clinically. The characteristic of pain was periodic (at least following
 3 menstrual cycles), midline, lower abdominal cramps or pelvic colic like pain that starts up
 to one day before menses, lasts for the 3 days of bleeding, gradually diminishes over 12 to
 72 hours and ends after period. The pain starts generally in 2 to 3 years after menarche with
 regular menses (25-31 day). Also absence of pelvic pathology was important in these patients
 for diagnosis.

 Patients with history of pelvic inflammatory diseases, endometriosis, ovarian cysts, chronic
 abdominal pain, fibroids, obstructive endometrial polyps, cervical stenosis, inflammatory
 bowel syndrome, irritable bowel syndrome, major abdominal or pelvic surgery, intrauterine
 device and congenital obstructive müllerian malformations were excluded. Smoking,
 overweighted (body mass index (BMI) ≥ 30) patients that oral contraceptive pills (OCP)
 treatment was contraindicated were also excluded. Additionally, patients enrolled
 simultaneously into other studies that require drug intake or otherwise prevent compliance
 with protocol were out of the study.

 Visual analog scale (VAS) from 0 (no pain) to 10 (maximum pain, 'worst pain I have ever
 felt') was applied to patients on the first day of menstrual cycle. Patients with VAS score
 of between 7 to10 and PD accompanied with vomiting, nausea, dizziness, headache, nervousness,
 diarrhea and fatigue were classified as severe PD. The ages (years), BMI (kg/m2), length of
 menstrual cycle (days) and length of bleeding (days) and demographic data of patients were
 recorded.

 Before treatment during menstruation period all ultrasound examinations were carried out
 trans abdominally with Toshiba Xario machine ( Shimoishigami, Otawara-shi, Tochigi 324-8550,
 Japan) equipped with a 2.8-7 megahertz (MHz) transducer by a single radiologist (Ş.T.) The
 uterine artery blood flows were measured at the lateral level of uterine artery neighbour to
 cervicocorporeal junction in both sides (right and left). Doppler indices including
 systole/diastole rates ( S/D), pulsatility index (PI) and resistance index (RI) values were
 evaluated and recorded in both uterine vessels. Both VAS scores and doppler indices were
 repeated after 3 months treatment. The changes in values were recorded.

 According to previously published studies and after power analyses, when α error and β error
 were considered, respectively, as 0.05 and 0.20, with 80% power number of patients for each
 group were determined as minimum 30. Power Analysis and Sample Size Software (PASS) 11
 software (NCSS, Kaysville, USA) was used to perform these analyses. Regarding dropout rates
 (40 % -50 %) in similar studies over the treatment period we planned to include 100 patients
 with PD and 40 healthy controls. The PD patients who met the inclusion criteria were divided
 into 2 groups. Patients in Group 2 were administered estradiol valerate/dienogest (Qlarista;
 Bayer HealthCare Berlin, Germany). Qlarista consists of 28 tablets (including 2 tablets of
 3mg estradiol valerate, 5 tablets of 2mg estradiol valerate plus 2mg dienogest, 17 tablets of
 2mg estradiol valerate plus 3mg dienogest, 2 tablets of 1mg estradiol valerate and 2 non
 hormonal tablets as placebo, respectively). Patients in Group 3 were administered 0.03 mg
 ethinylestradiol and 3 mg drospirenone (21 tablets) (Yasmin; Bayer HealthCare Berlin,
 Germany). Patients were randomly administered to the 2 treatments in a 1:1 ratio. Instead of
 relieving, patients were not allowed to use rescue medication (NSAI drugs) to prevent
 menstruation related pelvic pain.

 All procedures performed in studies involving human participants were in accordance with the
 ethical standards of the institutional and/or national research committee and with the 1964
 Helsinki declaration and its later amendments or comparable ethical standards. Ethics
 approval for the study was obtained from Erciyes University Hospital (protocol
 number:2014/290). Informed consent was obtained from all patients who included in our study.

 All analyses were performed using the SPSS for Windows 21.0 (SPSS Inc. USA) software package.
 The normality of distribution for variables was assessed using the Shapiro Wilk test. Data
 was presented as means ± standart deviation (SD) for continuous variables. To assess the
 differences in variables between groups, the independent t test was used. As the results did
 not have a normal distribution, Kruskal-Wallis, Mann-Whitney U-test and Bonferroni correction
 was used in the comparisons between the groups. For comparison, the Wilcoxon test was applied
 to the results (VAS scores, Doppler flow parameters) before and after receiving therapy. For
 all comparisons, the P < 0.05 value was determined as statistically significant.
Inclusion Criteria:

 -  must be nullipara patients with symptoms of severe primary dysmenorrhea.

 -  The characteristic of pain must be periodic (at least following 3 menstrual cycles),

 -  midline,

 -  lower abdominal cramps or pelvic colic like pain that starts up to one day before
 menses,

 -  lasts for the 3 days of bleeding,

 -  gradually diminishes over 12 to 72 hours,

 -  ends after period.

 -  The pain must start generally in 2 to 3 years after menarche with regular menses
 (25-31 day).

 Exclusion Criteria:

 -  Patients with history of pelvic inflammatory diseases,

 -  endometriosis,

 -  ovarian cysts,

 -  chronic abdominal pain,

 -  fibroids,

 -  obstructive endometrial polyps,

 -  cervical stenosis,

 -  inflammatory bowel syndrome,

 -  irritable bowel syndrome,

 -  major abdominal or pelvic surgery,

 -  intrauterine device,

 -  congenital obstructive müllerian malformations.

 -  patients that OCP treatment was contraindicated

 -  patients enrolled simultaneously into other studies that require drug intake or
 otherwise prevent compliance with protocol.