Abstract
I read with great interest the systematic review written by Dr Gloviczki et al. 1 on the possibilities of using venoactive drugs (VADs) in the treatment of venous origin chronic pelvic pain (VO-CPP). Despite the small number of studies on this topic and the predominance of studies with the micronized purified flavonoid fraction (MPFF), the authors managed to present readers with a very concentrated, well-structured and objective review. Indeed, such an analysis is extremely necessary, and there are several reasons for this.
First, there is clearly a bias in the studies, as hundreds of them are aimed at evaluating VADs in chronic venous diseases (CVD) 2 but only a dozen of them investigate VADs in the treatment of pelvic venous disorders (PeVDs). However, CVD and PeVDs share a common pathophysiological basis, namely the venous reflux, so the use of VADs in the treatment of PeVDs is completely rational and justified.
Second, the available literature data on the use of hormonal agents in the treatment of patients with VO-CPP create an impression that this is an acceptable method for treating PeVDs and relieving VO-CCP.3,4 But this is not at all the case. Hormonal therapy for VO-CPP may adversely impact fertility in younger patients and is accompanied by serious side events that are far from urticaria or gastralgia occasionally occuring in the treatment with VADs. And here it is appropriate to mention a study of Whiteley and Imran, pointing out to a low involvement of gynecologists in the diagnosis of PeVDs and the detection of VO-CPP, and poor communication between vascular surgeons and gynecologists. 5
Indeed, a woman with CPP primarily seeks a gynecologist’s care, so it is of utmost importance that gynecologists are aware of PeVDs as a common cause of CPP, perform an adequate diagnostic evaluation (or intentionally refer patients to a vascular surgeon or venous specialist) and do not rush to prescribe unnecessary hormonal agents. Prescribing VAD to a patient with verified VO-CPP has long been considered a routine recommendation. However, this requires regulatory documents in place and the inclusion of PeVDs in the list of diseases for which VADs can be considered for use. And this is the third point that confirm importance of and necessity for the review of Dr Gloviczki M.L. et al.
The authors analysed a total of 11 studies, of which only 3 were randomized. Nevertheless, their results showed that, despite the heterogeneity of patient groups and outcome assessment methods, VADs appear to be effective and safe in eliminating or reducing VO-CPP. The low quality of the studies raised doubts among the authors about the credibility of the clinical data obtained, although some of them were confirmed by reference methods (including single photon emission computerized tomography [SPECT], which is the most objective and operator-independent method).
It is still unknown how VADs effect on VO-CPP and what are the mechanisms underlying their analgesic effect. These studies are still limited6,7 and leave the questions unanswered. Furthermore, what is the optimal treatment regimen for VADs in a patient with VO-CPP? Considering the severity of the clinical manifestations of PeVDs, it can be assumed that the standard dose and duration of VAD use may be insufficient in some cases. 8 All of the above predetermines the need for continued research aimed at studying the neurobiological processes that provide the analgesic effect of VADs, an objective assessment of the impact of VADs on VO-CPP and pelvic venous hemodynamics. Here, the authors of the review present a number of constructive suggestions that can provide a solution to these issues.
The authors’ proposal to differentiate studies in patients with pelvic venous reflux and with the renal or iliac vein obstructions is quite logical. However, a number of circumstances should be taken into account. Venous obstruction can be post-thrombotic and non-thrombotic, and this should be born in mind as in patients with postthrombotic obstruction the CVD symptoms come to the fore, but VO-CPP is most often absent. Venous obstructions may be hemodynamically significant or insignificant, i.e. it is necessary to evaluate their role in the development of pelvic venous incompetence (PVI) and pelvic venous pain. If compression of the left common iliac vein (LCIV) did not result in the development of secondary pelvic varicose veins and reflux in them, then this is a hemodynamically insignificant compression, since there is no VO-CPP without pelvic venous reflux. Therefore, it is not appropriate to evaluate the effect of VADs on VO-CPP in a patient with the LCIV stenosis and without pelvic venous reflux. Moreover, the LCIV or the left renal vein (LRV) stenosis does not hurt, so VO-CPP is associated specifically with PVI and reflux in the pelvic veins, even if it is secondary. 8 Thus, when evaluating the effect of VADs on VO-CPP in a patient with venous obstruction, we still evaluate its effect on pelvic varicose veins and reflux in them, rather than on the obstruction itself. For example, in our recent study, there were patients with hemodynamically insignificant LCIV or LRV compression, but this did not affect the efficacy of treatment with diosmin-containing VADs. 9
The authors of the review highlighted the need for careful selection of patients for randomized trials, and this is an extremely important point. It is necessary to accurately determine the venous cause of CPP, exclude the organ and psychological factors of CPP, and here the help from gynecologists, urologists, and neurologists is also needed. Evaluating the VADs efficacy in a female with endometriosis or interstitial cystitis and pelvic varicose veins is a futile task.
In conclusion, I would like to once again support the authors in choosing directions for further research and congratulate them on their interesting and important work. We do need new and convincing evidence of the efficacy and safety of VADs in the treatment of patients with VO-CPP. We need to get the show on the road.
