Akdeniz University, School of Medicine, Antalya, Turkey E-mail: omurtaskin{at}hotmail.com
Dear Sir,
We read the article by Soysal et al. which was focusing on pelvic congestion (PC)/chronic pain (CPP) dynamics with interest (Soysal et al., 2001). While reading the article, we were confused by the presentation of the methods, results and the final conclusion. We do agree with the concept and follow-up of the study. If the purpose was to identify PC by venography and all the patients had laparoscopy, what was the sensitivity/specificity of venography among their 148 CPP patients? Furthermore, why were asymptomatic patients used as controls, since they have their internal controls among symptomatic patients (without PC)? Was that group used to test the diagnostic efficacy of venography? Besides, dealing with vein stability and the possible effect of ovarian steroidogenesis on the aetiology of PC, the control group should have been age, body mass index and hormonally matched to avoid selection bias (Taskin et al., 1996
; Ciardullo et al., 2000
). Thus, endogenous hormonal status of the studied patients had to be compared.
Although the therapy arm was randomized, a placebo group or a cross-over design would be better in outlining the associated social/psychological variables/biases, despite extensive testing performed, which were indeed subjective. What was the power of the study? The limited study group impairs the validity of their conclusion. What was the power for such a statistically significant conclusion given in Table IV?
How were the hypoestrogenic side-effects of the GnRH agonist prevented? What were the effects of vasomotor reaction, mood changes and coital problems due to GnRH agonist on the tests, or how have the authors dealt with these confounding factors that may ameliorate their initial evaluation following therapy?
Most confusing is the continuing effect of GnRH agonist beyond 12 months, which needs to be explained. If estrogens were a possible cause affecting venous distensibility, congestion, and mediatory factors, (such as vascular endothelial growth factor and prostaglandins), causing pain in PC, how did the beneficial clinical effects of GnRH agonist persist despite normal estrogen status (Wang, 1993; Bausero et al., 2000
; Ceballos et al., 2000
; Ciardullo et al., 2000
)? Was an unknown variable, confounding factor or placebo effect missed, or a was psychosocial effect overlooked?
Moreover, as reported by Gangar et al. GnRH agonist/hormone replacement therapy (HRT) given for 4 months was not effective despite hypoestrogenism (Gangar et al., 1993). In the present study, GnRH agonist given for 6 months without HRT revealed a prolonged effect for 12 months, despite the return of ovarian function. How can this 2 months difference end up with such a significant improvement? If the HRT makes the difference, then how did not much more elevated estradiol levels following GnRH agonist compared with HRT alter the efficacy?
Overall, the authors appear to believe that the estrogen status and/or sensitivity of pelvic veins is the underlying problem in PC (Foong et al., 1992). However, neither their results or their discussion support how GnRH agonist-induced effects are maintained clinically, despite the normalized ovarian function. Moreover, how GnRH agonist therapy may be offered cost-effectively in the long-term remains elusive. What is the take home point from the study? Do they recommend adnexectomy and/or hysterectomy to the patients who did improve following GnRH agonist or intermittent GnRH agonist-only therapy (since HRT given to prevent GnRH agonist side-effects, impaired the clinical efficacy despite hypoestrogenism)?
References
Bausero, P., Ben-Mahdi, M., Mazucatelli, J., Bloy, C. and Perrot-Applanat, M. (2000) Vascular endothelial growth factor is modulated in vascular muscle cells by estradiol, tamoxifen, and hypoxia. Am. J. Physiol. Heart Circ. Physiol., 279, H2033H2042.
Ceballos, C., Ribes, C., Amado, J.A., Perez, J., Garcia, M.T. and de Berrazuta, J.R. (2000) Venous endothelial function in postmenopausal women who are receiving long-term estrogen and progestagen therapy. Fertil. Steril., 74, 268273.[ISI][Medline]
Ciardullo, A.V., Panico, S., Bellati, C., Rubba, P., Rinaldi, S., Ianuzzi, A., Cioffi, V., Iannuzzo, G. and Berrino, F. (2000) High endogenous estradiol is associated with increased venous distensibility and clinical evidence of varicose veins in menopausal women. J. Vasc. Surg., 32, 544549.[ISI][Medline]
Foong, L.C., Gamble, J., Sutherland, I.A. and Beard, R.W. (2000) Altered peripheral vascular response of women with and without pelvic pain due to congestion. Br. J. Obstet. Gynecol., 107, 157164.[ISI]
Gangar, K.F., Stones, R.W., Saunders, D., Rogers, V., Rae, T., Cooper, S. and Beard, R.W. (1993). An alternative to hysterectomy? GnRH-a combined with HRT. Br. J. Obstet. Gynecol., 100, 360364.[ISI][Medline]
Soysal, M.E., Soysal, S., Vicdan, K. and Ozer, S. (2001) A randomized controlled trial of goserelin and medroxy-progesterone acetate in the treatment of pelvic congestion. Hum. Reprod., 16, 931947.
Taskin, O., Uryan, I., Buhur, A., Burak, F., Erden, F., Atmaca, R. and Wheeler, J.M. (1996) The effects of daflon on pelvic pain in women with Taylor Syndrome. J. Am. Assoc. Gynecol. Laparosc., 3 (4, Suppl.), S49.
Wang, Z.H. (1993) Correlation between serotonin and prostaglandins in peritoneal fluid collected from patients with pelvic congestion. Zhonghua. Fu. Chan. Ke. Za Zhi., 28, 3379, 380.[Medline]