{"paper_id":"157055cc-0bba-4746-9ecf-2b08d93096bf","body_text":"Endometriosis is a benign gynecologic disease ( 1 ) defined\nas the presence of uterine endometrial stroma and glands\nsomewhere other than their natural location (i.e. uterine endometrial\ncavity). The most frequent places in the pelvic cavity\ninclude ovaries, uterosacral ligaments, and the recto-uterine\npouch ( 2 ). Symptoms of endometriosis are dysmenorrhea,\ndyspareunia, chronic pelvic pain, irregular menstruation, and/\nor infertility ( 3 ). Although endometriosis is considered to be\na disease of the 21st century, the first references and related\nsymptoms were discovered in ancient Egypt in 1500 BC ( 4 ).\nThe prevalence of endometriosis in the general population is\nestimated at 7-10% ( 1 ). Endometriosis is one of the causes of\nprimary and secondary infertility in 30% of women ( 2 ).\nEndometriosis has a complex and multifactorial etiology\n( 5 ). The factors involved in the development of endometriosis\ninclude hormonal changes ( 6 ), genetic changes ( 7 ), and\nchanges in the immune system ( 8 ). It has been well documented\nthat endometriosis may be present for a long time before\nit is diagnosed ( 9 ). This is especially observed in European\ncountries, as the overall delay in diagnosing the disease\nis ten years in Austria and Germany, eight years in Spain and\nUK, seven years in Norway, seven to ten years in Italy and\nfour to five years in Ireland and Belgium (10-1\nAlthough no theory can cover all the manifestations of\nthis disease, the retrograde menstruation is widely accepted\nto describe the dissemination of endometrial tissue to\nthe peritoneal cavity through open fallopian tubes during\nmenstruation ( 3 ,  5 ). Previous studies report that in 90% of\nhealthy women with open fallopian tubes menstrual blood\nis present in the peritoneal cavity, as shown by laparoscopy\n( 13 ). However, it is assumed that the level and volume of\nretrograde menstruation and the backward movement of\nendometrial cells have significant effects on the emergence\nand improvement of endometriosis ( 14 ). Studies on uterine \npressure during menstruation have shown that myometrium \nand fallopian tube contraction significantly increase \nduring menstruation and ovulation, respectively, supporting \nthe theory of retrograde menstruation ( 15 ). Since this \nevent is regarded as the major etiology for the improvement \nof endometriosis ( 9 ), it is essential to identify factors, \nwhich block menstrual blow flow and facilitate the retrograde \nmovement of menstrual blood ( 16 ).\nIt is hypothesized that sexual activity leading to orgasm during \nmenstruation may increase retrograde menstruation, seeding \nendometrial tissue in other locations, and thus increasing \nthe risk of endometriosis. So far, few studies have examined \nthe relationship between sexual activity during menstruation \nand endometriosis ( 16 - 18 ). Based on a case-control study in \nthe Yale University School of Medicine, on the relationship between \nprevalence of endometriosis and sexual behaviors leading \nto orgasm during menstruation, the tendency to perform \nsuch activities during menstruation was lower in women with \nendometriosis compared to women without endometriosis \n( 17 ). The results of another study at the University of Pennsylvania, \nPhiladelphia, on the relationship among sexual activity \nduring menstruation, endometriosis and pelvic inflammatory \ndisease showed that endometriosis was higher in women who \nhad sexual intercourse during menstruation compared to those \nwho stated they did not ( 16 ). Based on the noted contradictory \nresults and the need for further research, the aim of the present \nstudy is to answer the question of whether sexual activity \nleading to orgasm during menstruation can be a risk factor for \noccurrence of endometriosis.\n\nThis case-control study, which was done in 2017, recruited \nwomen at reproductive age (20-50 years), with or without \nendometriosis. The participants in the case group were \nselected from women with endometriosis visiting Alzahra \nHospital over the past two years, who had undergone laparoscopy \nand open surgery with a histological diagnosis of \nendometriosis. Participants in the control group were selected \nfrom the same age group of women visiting the same \nhospital for other reasons including vaginitis and an annual \ncheckup. The absence of endometriosis in the control group \nwas confirmed by a gynecologist colleague based on their \nsigns and symptoms. The final selections were done based \non our inclusion and exclusion criteria. The study inclusion \ncriteria were: i. Age of 20-50 years, ii. Diagnosis of endometriosis \nby open surgery or laparoscopy and histologic diagnosis \nof endometriosis or the presence of endometrioma \n(case group), iii. Being married, iv. Being Iranian, v. Willingness \nto participate, vi. Absence of endometriosis (control \ngroup), vii. No history of tubectomy (control group), \nand viii. No history of infertility (control group).\nThe study exclusion criteria were: i. Being menopausal \n(amenorrhea for over a year), ii. Being suspected of \nendometriosis or endometrioma (control group), iii. Having \nendometriosis in the surgical site or involvement of \nremote organs, e.g. lungs or brain, iv. Having breast, ovarian, \nor endometrial cancer, v. Having polycystic ovarian \nsyndrome (PCOS), vi. Having any other life-threatening \ndisease, and vii. Suffering from chronic pelvic pain.\nIn this study, the sample size was determined according \nto the results of a pilot study on 150 participants and \nconsidering an odds ratio (odds of having sexual activity \nin the menstruation in the case group compared with the \ncontrol group) to be about 1.8, was determined as n1=185 \n(case group), n2=370 (control group), and n=555 (total) \n(with the case-to-control ratio of 1:2).\nThe present study was confirmed by the Ethics Council \nof Tabriz University of Medical Sciences (ethics code: 5/\nD1003687). Afterward, data collection was started in Alzahra \nHospital, Tabriz, which is a referral Gynecology and Midwifery \nHospital in Northwest of Iran. We reviewed pathological \nresults in the medical files that were available at Alzahra \nHospital and registered women patients with endometriosis, \nas confirmed by histological diagnosis through laparoscopy or \nopen surgery, for our study. The addresses and phone numbers \nof all considering patients, who had been identified over the \npast two years, were extracted from their records. They were \ncontacted by telephone, the research objectives and methods \nwere briefly explained to them, the study inclusion and exclusion \ncriteria were checked, and finally they were invited to \nparticipate in the study. For those who were willing to take \npart, questionnaires were filled in through the interview. For \nthe patients’ comfort, the interviewer and the patients were of \nthe same gender. After sampling was done in the case group, \nthe members of the control group were selected through purposive \nsampling from those visiting the gynecology clinic of \nthe same center for other issues, such as vaginitis or an annual \nvisit, and did not have endometriosis, as diagnosed based on \nsymptoms by a gynecologist colleague. Research objectives \nand methods were first explained to them. For those who were \nwilling to participate, inclusion and exclusion criteria were \nchecked, and in case they met the criteria, they were recruited \nand questionnaires were completed by the researcher through \ninterviews. Informed consent forms were obtained from all \nparticipants, and those in both case and control groups were \nmatched for age ± 2 years.\nData were collected by the researchers through interviews \nand using researcher-made questionnaires based \non previous studies, highlighting sociodemographic and \nsexual activity characteristics. The sociodemographic \ncharacteristics questionnaire included questions on age; \nthe level of education, employment, the level of income, \nsmoking, alcohol use, the history of any diseases, allergies, \nand endometriosis in first-degree relatives (mother, sisters, \nand aunts). The sexual activity and reproductive and \nmenstruation characteristics questionnaire included questions \non vaginal or non-coital sexual activity (by touching \nother body parts by the person or her spouse to achieve \nsexual pleasure) and anal intercourse, leading to orgasm \nduring menstruation, cycle length, cycle intervals, number \nof pregnancies, menarche age, age at first pregnancy, oral \ncontraceptive pill (OCP) user, intrauterine device (IUD) \nuser, dysmenorrhea, dyspareunia, and recurrent vaginitis. \nContent and face validity were used to confirm the validity \nof the questionnaires, they were given to 10 faculty members \nand corrections were applied based on their opinions.\nData were analyzed in SPSS 21 software. Sociodemographic \nand sexual activity characteristics during menstruation were \ndescribed using descriptive statistics including frequency (percentage). \nSociodemographic characteristics were compared \nbetween the two groups using chi-squared test, chi-squared \ntest for trend, independent samples t test, and Fisher’s exact \ntest. To determine the relationship between sexual activity \nduring menstruation and endometriosis, chi-squared test was \nperformed in the bivariate analysis. Conditional logistic regression \nwas employed in the multivariate analysis to control \nconfounding variables (level of education, level of income, \noccupation, cycle length, cycle interval, number of pregnancies, \nmenarche age, age at first pregnancy, OCP user, IUD \nuser, dysmenorrhea, dyspareunia and recurrent vaginitis). Because \nno woman in the control group reported a history of this \ndisease in her first-degree relatives, the family history was not \nincluded in the multivariate regression as a confounding factor. \nIn this analysis, the odds ratio and confidence interval was \nset at 95%, and P<0.05 was considered significant.\n\nIn this study, 185 women with endometriosis and 370 \nwomen without endometriosis were analyzed. The participants’ \nmean age was 35.21 years (SD: 7.09) in the case \ngroup and 35.28 years (SD: 7.03) in the control group. The \ntwo groups significantly were differed regarding the level \nof education; the percentage of participants with academic \ndegrees in the case group was twice as high as those in the \ncontrol group (P<0.001). Moreover, 32 (17.3%) women of \nthe case group and 10 (2.7%) women of the control group \nwere employed, again indicating a significant difference between \nthe two groups (P<0.001). However, the two groups \nwere similar regarding the sufficiency of monthly income \n(P=0.698). The two groups were compared in a history of \ndiseases such as diabetes, hypothyroidism, hypertension, \ncardiovascular diseases, cerebrovascular diseases, seizures \nand asthma, and did not show any significant differences \n(P=0.860). The two groups were also similar regarding an \nautoimmune disease history, e.g. rheumatoid arthritis, multiple \nsclerosis, and lupus erythematosus (P=0.669). There \nwere 38 (20.5%) women in the case group and 47 (12.7%) \nwomen in the control group with a history of allergies, indicating \na significant difference between the two groups \n(P=0.016). Nevertheless, both groups were similar regarding \nthe type of allergies (seasonal, food, drug, or skin) \n(P=0.946). In the case group 13 (7%) women reported a \nhistory of endometriosis in their mothers and sisters, and 7 \n(3.8%) women reported this in their aunts, while no woman \nin the control group reported a history of this disease in \nher first-degree relatives, demonstrating a significant difference \nbetween the groups (P<0.001). Only one woman in \nthe control group had a history of smoking, and no one in \neither group had a history of alcohol use ( Table 1 ).\nComparison of sociodemographic characteristics in case and control groups\nData are presented n (%). *; Chi-squared test, ‡; Chi-squared test for trend, †; Fisher’s \nexact test, §; Mean ±SD, and **; Independent samples t test. Only one woman in the control \ngroup had a history of smoking, and no one in either group had a history of alcohol use.\nRegarding vaginal intercourse during menstruation, the \ntwo groups were compared using multivariate logistic regression, \nwhile controlling the effects of possible confounding \nvariables, such as the level of education, income, occupation, \ncycle length, cycle interval, number of pregnancies, \nmenarche age, age at first pregnancy, OCP user, IUD user, \ndysmenorrhea, dyspareunia and recurrent vaginitis. The results \nshowed that the risk of endometriosis approximately \nwas five times higher in those women who stated they had \nvaginal intercourse during menstruation compared to those \nwho stated they did not [(P<0.001), odds ratio (OR) (95% \nconfidence interval (CI)=5.23 (2.16 to 12.66)]. Furthermore, \n6 (20%) participants in the case group and 1 (3.6%) \nparticipant in the control group reported that they always \nhad vaginal intercourse during menstruation, demonstrating \na significant difference between the groups (P<0.001). \nBoth groups were similar with regard to the days of vaginal \nintercourse (first three days, second 3 days, all days of menstruation) \n(P=0.111). Moreover, the risk of endometriosis \nwas approximately three times higher in those women who \nstated they had non-coital sexual activity during menstruation \ncompared to those who stated they did not [(P=0.010), \nOR (95% CI)=2.90 (1.28 to 6.55)]. In addition, 9 (23.7%) \nparticipants in the case group and 6 (14.6%) participants in \nthe control group reported that they always had non-coital \nsexual activity during menstruation, indicating no significant \ndifference between the two groups based on a chi-\nsquared test (P=0.141). Moreover, 2 (1.1%) participants \nin the case group and 15 (4.1%) participants in the control \ngroup stated that they have anal intercourse during menstruation, \nbut there was no significant difference between \nthe two groups [(P=0.130), OR (95% CI) = 0.08 (0.03 to \n2.09)] (Tables 2 ,  3 ).\nComparison of sexual activity during menstruation and reproductive and menstruation characteristics in case and control groups based on bivariate test\n*; Chi-squared test and †; Fisher’s exact test.\nComparison of sexual activity during menstruation in case and control groups based on bivariate and multivariate logistic regression\nConditional logistic regression was employed (P<0.1) in the multivariate analysis to control \nconfounding variables: level of education, level of income, occupation, cycle length, \ncycle interval, pregnancy number, menarche age, age at first pregnancy, OCP user, IUD \nuser, dysmenorrhea, dyspareunia, and recurrent vaginitis. CI; Confidence interval, OR; \nOdds ratio, OCP; Oral contraceptive pill, and IUD; Intrauterine device.\n\nThe present study is the first study in Iran, which examined \nthe association between sexual activity during \nmenstruation and endometriosis. Our results revealed that \nvaginal intercourse and non-coital sexual activity leading \nto orgasm during menstruation increase the risk of endometriosis.\nThe case and control groups were significantly different \nregarding the level of education and occupation. Most recent \nepidemiological studies on risk factors for endometriosis \nhave shown an increased incidence of the disease \namong women of high socioeconomic and occupational \nstatus ( 19 ). Results of the present study are consistent \nwith the noted results. One possible justification for this \nrelationship may be attributed to the diagnostic bias, because \nwomen of high socioeconomic status may have \nmore awareness of their health-related issues ( 19 - 21 ). A \nstrong evidence that shows the importance of a family \nhistory of endometriosis among women with the disease, \nis occurrence of endometriosis in twins ( 22 ,  23 ). In the \npresent study, the participants in the case group reported a \nfamily history of endometriosis in their first-degree relatives, \nwhile no women in the control group reported a history \nof this disease in her first-degree relatives, therefore, \nfamily history was not employed into the model as a confounding \nvariable.\nThere are few studies on the association between sexual \nactivity during menstruation and endometriosis. For \ninstance, Meaddough et al. ( 17 ) in the US explored the \neffect of sexual activity, orgasm, and health-related behaviors \nduring menstruation on endometriosis. Results \ndemonstrated that women with endometriosis were less \nwilling to have repeated or occasional sexual activity during \nmenstruation compared to those without endometriosis, \na difference which turned out to be statistically significant. \nMoreover, in their study the case group reported \nless sexual activity leading to orgasm during menstruation \nthan the control group, showing a significant difference \nbetween the two groups. Based on Meaddough’s inference \na possible explanation for these results could be the \nlimitation of the research instrument or the presence of \nconfounding variables such as dyspareunia, which was \nnot included in the questionnaire. Dyspareunia may lead \nto an unwillingness in women with endometriosis to have \nsex, thereby making them report a lower willingness than \nthe control group. Furthermore, Meaddough concluded \nthat sexual activity or orgasm during menstruation might \nfacilitate the blood flow through the cervix ( 17 ). Other \nstudies have shown that uterine contractions and pressure \nare increased during menstruation ( 16 ). Since sexual activity \nand orgasm during menstruation appear to increase \nuterine contractions as well, this type of activity may in \nfact lead to retrograde menstruation, which is the major \netiology of endometriosis. In Meaddough’s study, the \nnumber of women with and without endometriosis was \ndetermined based on self-report and not based on specialized \ncriteria. Furthermore, questionnaires were sent and \ncompleted by the participants via email. Therefore, this \nstudy recommended further detailed studies on the effect \nof sexual activity during menstruation on the development \nof endometriosis ( 17 ). On the other hand, in the present \nstudy, women with endometriosis were selected based \non histological diagnosis through laparoscopy, and those \nwithout endometriosis were selected based on signs and \nsymptoms, inclusion and exclusion criteria, and confirmation \nof the absence of endometriosis by a gynecologist. \nMoreover, questionnaires were completed by the same interviewer \nfor both groups, and all confounding variables \nwere controlled as much as possible. To this end, the two \ngroups were matched for age, and all possible confounding \nvariables were controlled in statistical analyses.\nAnother study was conducted by Filer and Wu ( 16 ) in \nthe University of Pennsylvania, Philadelphia to investigate \nthe effect of sexual activity on endometriosis and \npelvic inflammatory disease. The definite diagnosis of \nendometriosis and tubal factor infertility was done by \nlaparoscopy or laparotomy. Subjects were asked about \ntheir history of sexual activity during menstruation and \nhistory of the pelvic inflammatory disease. The results \nshowed that the prevalence of endometriosis was higher \nin women who tended to have repeated or occasional sexual \nactivity during menstruation compared to those who \ndid not. The prevalence of endometriosis was (17.5%) \nin women who had repeated or occasional sexual activity, \nand (10.9%) in those who rarely had sexual activity \nduring menstruation, demonstrating a significant difference \nbetween the two groups. However, the groups were \nsimilar regarding pelvic inflammatory disease. Another \nstudy was conducted by Samir et al. ( 18 ) in Doha, Qatar, \nto examine sexual activity during menstruation as a \npredisposing factor for endometriosis. First, participants \nwere asked about sexual activity during menstruation. A \ntotal of 78 participants were divided into two groups: the \nfirst group: 51 participants with a sexual activity history \nduring menstruation and the second group: 27 women \nwithout a history of sexual activity during menstruation. \nThen, abdominal ultrasound, transvaginal ultrasound, or \nboth were performed before laparoscopy or open surgery. \nTheir results revealed that in the first group: 36 (66%) \nwomen tested positive for endometriosis and the second \ngroup: 9 (34%) were negative for endometriosis, showing \na significant difference between the presence and absence \nof sexual activity leading to orgasm during menstruation \nand endometriosis ( 18 ). The results of the present study \nare consistent with the results of Samir’s group. Based on \nour findings, the risk of endometriosis is approximately \nfive times higher in women who stated they had vaginal \nintercourse leading to orgasm during menstruation and \nthree times higher in those with non-coital sexual activity \nleading to orgasm during menstruation, compared to \nthose who stated they did not.\nIn this study, there was no significant difference between \nthe groups in terms of having anal intercourse leading \nto orgasm during menstruation. However, due to the \nlimited number (only two women in the control group), a \ncomplete conclusion is not possible.\nIn this study, an attempt was made to select women with \nand without endometriosis based on precise medical diagnosis. \nFurthermore, the most important and relevant factors \nwith endometriosis were examined while controlling \nconfounding variables.\nIn this study, validity was only confirmed through face \nand content validity qualitatively and the quantitative indices \nsuch as content validity index (CVI) and content validity \nratio (CVR) weren’t calculated. Also, considering \nthe criterion for the definite diagnosis of endometriosis is \nhistologic diagnosis through laparoscopy or laparotomy, \none of the other shortcoming of this study is that the control \ngroup wasn’t selected based on histologic diagnosis. \nThus, future studies should be conducted on selected case \nand control participants from women, in whom the presence \nor absence of endometriosis is confirmed by laparoscopy \nor laparotomy.\n\nBased on the results of the present study, vaginal intercourse \nor non-coital sexual activity leading to orgasm \nduring menstruation increases the risk of endometriosis in \nwomen during reproductive age. This study has raised interesting \nissues and requires further investigation to better \nunderstand the mechanism of occurrence of endometriosis \nin such cases.","source_license":"CC0","license_restricted":false}