This study describing the gynaecologic and obstetric symptoms in a large cohort of women with hEDS suggests that most women experience significant gynaecologic symptoms and that few severe complications occur during pregnancy. In addition, this is the first study to describe the impact of reproductive life on hEDS clinical outcomes.
Abnormal bleeding, dysmenorrhea and dyspareunia were the most common gynecologic complaints in our hEDS population. Dysmenorrhea was not correlated with age and did not improve after deliveries contrary to what is observed with idiopathic dysmenorrhea [
19]. A recent comprehensive literature review reported that severe dysmenorrhea affected between 2 and 29 % of women and that dysmenorrhea was negatively associated with women’s age and parity [
20]. Easy bruising and bleeding are frequently described in EDS, a result of weakness in the capillaries and perivascular connective tissue rather than from hemostatic dysfunction [
11]. The sexual life of these women is also adversely affected by a high incidence of dyspareunia. Previous studies have also found an increase in abnormal bleeding, dyspareunia and dysmenorrhea in patients with EDS [
9,
10,
13,
14]. The two last publications have selectively reported on the gynaecologic and obstetric outcomes in patients with hEDS/JHS. The first involved 82 women in Italy with 93 pregnancies [
10] and the second study included about 770 women with both hypermobility type and other EDS types as well based on an email questionnaire with no clinical validation [
9]. Both studies reported similar prevalence of dysmenorrhea and dyspareunia in women with hEDS/JHS than in our population. The combination of these symptoms is highly suggestive of endometriosis. The rate of endometriosis we found was the same as that for the general population (3–6 %) and much less than in women with chronic pain [
21]. While it is possible that we underestimated the frequency of endometriosis because we did not perform systematic laparoscopy, we suggest that endometriosis may be over-diagnosed in hEDS patients because of reports of chronic pain and bleeding. A systematic study would nevertheless be interesting to evaluate the prevalence of adenomyosis at a young age in women with EDS as it may play a role in the high risk of spontaneous abortion. A previous study, which also used a questionnaire, found a 15 % prevalence of reported endometriosis [
9]. A 22 % prevalence of endometriosis among women with suspected infertility was reported by women with EDS from an emailed questionnaire which did not allow to validate the diagnosis of endometriosis. In our patient population, the conception rate was close to that for women in France in general (fertility rate: 1.8–2.03 between 1980 and 2013 [
22]). This finding further argues against the hypothesis of an abnormally high prevalence of endometriosis in this population. However, while the rate of conception in our population was similar to the normal range, the rate of spontaneous abortions was higher than in the general population (28 % versus about 20 %, respectively). Furthermore, the rate of multiple abortions was much higher in our population than in the French population as a whole (13 % versus about 1 %, respectively) [
23]. The cause of the miscarriages is unclear. An increased contractility of the uterus or a fragile cervix, related to the connective tissue defect and dysautonomic syndrome could be a cause [
24]. Another possible explanation could be implantation defects.
One novel aspect of our study is the relationship between hEDS symptoms and reproductive life. It is significant that estradiol receptors are present in many of the body structures and organs including joints, skin, and cartilage. Puberty does appear to significantly exacerbate symptoms. This may result either from the rapid growth that is characteristic of this time in life — and that significantly affects skin, joints and muscles—and/or to the rapid increase in estrogen secretion. In the subset of patients who deteriorate during the perimenstrual period, CHC was also correlated with an increase in symptoms. Our analysis of contraception suggests that, in some women at least, the hEDS symptoms responsible for increased disability might improve with the use of POP. Our findings suggest that, when menstrual disorders are treated and alleviated either by CHC or by POP, EDS symptoms improve and women report less fatigue. In the literature, there is conflicting data as to the effects of hormones on connective tissue, joint laxity and tendons. It has been demonstrated that estradiol decreases the formation of collagen in tendons following exercise [
25]. Joint laxity increases during pregnancy in some women. Another smaller study found increased knee laxity during ovulation compared with the luteal phase, but no significant changes during the phases of the menstrual cycle [
26]. A prospective trial would be useful to determine the precise nature of the role of estrogens and progestins on various symptoms of hEDS.
This study also reveals that the prevalence of obstetric complications is not substantially greater compared to the healthy population and lower [
27] in comparison with the previously mentioned large, recently-published study [
14]. This discrepancy may result from the different methodologies used in the two studies, or from a difference in the protocols for management of pregnancies from one country to another. Indeed, the Italian study fitted more with our results with 10.7 % preterm deliveries; we agree with these authors than caesarean section is not indicated systematically in women with hEDs and was performed only in 14 % of our patients.