DESOGESTREL IN THE PREOPERATIVE TREATMENT OF ENDOMETRIOTIC CYSTS

Rev. Med. Chir. Soc. Med. Nat., Iaşi 2015 vol. 119, no. 3 SURGERY ORIGINAL PAPERS DESOGESTREL IN THE PREOPERATIVE TREATMENT OF ENDOMETRIOTIC CYSTS Daniela-Roxana Albu (Matasariu) 1, Maria Iacob 1, Irina Dumitrascu 1*, M. Onofriescu 1, Carmen Vulpoi 2 University of Medicine and Pharmacy Grigore T. Popa -Iasi Faculty of Medicine 1. Department of Mother and Child Medicine 2. Department of Medical Specialties (II) *Corresponding author. E-mail: irina10021968@yahoo.com DESOGESTREL IN THE PREOPERATIVE TREATMENT OF ENDOMETRIOTIC CYSTS (Abstract): Endometriosis is an estrogen dependent disease characterized by the presence of endometrial tissue outside the uterus. It affects women of reproductive age and is associated with infertility and pelvic pain, with impact on their mental, physical and social well-being. Aim: To evaluate the effects of continuous desogestrel treatment on cyst size and the risk of intraoperatively bleeding. Material and methods: Our study included two hundred fifty-five patients with infertility and endometriotic cysts operated at the Iasi Cuza Voda University Hospital in the interval 2006-2014. One hundred fifty-five patients received 6-month preoperative treatment with 75 micrograms of desogestrel daily. The patients were monitored every three months by vaginal ultrasound associated with Doppler for assessing the cysts size,homogeneity, shape, vascularization, position relative to the uterus and the contralateral ovary, presence of sludge and horizontal levels. Results:There was asignificant decrease in cyst diameter and vascularization in most cases with sludge and low echogenicity. Intraoperatively we noticed less bleeding during cyst dissection and a better cleavage plan between the cyst capsule and the normal ovarian tissue. Conclusions: Treatment with desogestrel for at least 6 months preoperatively has a shrinking effect on the endometriotic cyst, reduces i n- traoperative bleeding and improves the dissection and operative conditions. Keywords: ENDOMETRIOSIS, INFERTILITY, DESOGESTREL, PELVIC PAIN. Endometriosis is an estrogen-dependent inflammatory disease defined by the growth of endometrial stroma and glands outside of the uterus, especially on the ovaries and in the peritoneum. Affected women often present with chronic pelvic pain, dysmenorrhea, dyspareunia and infertility (1, 2). The prevalence of endometriosis increases dramatically to as high as 25% to 50% in women with infertility, and 30% to 50% of women with endometriosis are infertile (3). It is often cited that retrograde menstruation is the cause of this condition; however retrograde menstruation occurs in nearly all women, yet not all women are afflicted with this condition. Therefore, it has been suggested that women with endometriosis are likely to have underlying molecular abnormalities that allow the continued growth of this endometrial tissue outside the uterus 710

Desogestrel in the preoperative treatment of endometriotic cysts and that ectopic implantation is possible as a consequence of altered immunity or preexisting peritoneal lesions (4,5). Ovarian endometriotic cysts are usually detected ultrasonographically but peritoneal lesions and small ovarian cysts are more difficult to detect, so laparoscopy and histopathological diagnosis remain the gold standard. Endometriomas are particularly difficult to excise as the cyst wall is very adherent and well vascularized, thus surgery may reduce the ovarian reserve. The surgical treatment of endometriosis is effective in the short-term, but if the patient does not get pregnant very soon after surgery, it is most probably because endometriosis has relapsed. Recurrence rates after surgical intervention can be decreased with the use of menstrual suppression, such as hormonal contraceptives (6). Hormone therapy is frequently effective in reducing or even eliminating endometriosis-related pain. The success of various hormonal therapies depends on the location and type of the endometriotic lesions. Superficial peritoneal and ovarian implants seem to respond better to hormone therapy than deep ovarian, peritoneal or lesions within organs. Moreover, hormone treatment has no effect on adhesion of endometriotic cells and cannot improve fertility. Nonetheless, a number of hormonal agents remain the mainstay of endometriosis therapy (7,8). Progesterone is a potent antagonist of estrogen-induced proliferation in the endometrium and may play a pivotal role in the pathogenesis of endometriosis (9). Desogestrel is a progestogenic 19- nortestoterone derivative, which is widely used for oral contraception both combined with ethinyl estradiol and alone in progestin-only pills (10). Our primary goal was to assess the results of treatment with desogestrel regarding improvement of clinical symptoms, ultrasonographic findings and intraoperative bleeding, adhesions and ease of cyst dissection. MATERIAL AND METHODS Our study included two hundred fiftyfive patients with infertility and endometriotic cysts (diameter less than 20 mm) operated laparoscopically at the Iasi Cuza Voda University Hospital Iasi between the years 2006-2014. One hundred fifty-five patients (60.78%) - group A, received a 6- month preoperative treatment with 75 micrograms of desogestrel per day and one hundred patients (39.22%) group B, received preoperative placebo treatment. Women with body mass index > 30, neoplasias, autoimmune diseases, diabetes mellitus, infectious diseases, pregnant, under anti-inflammatory or hormonal treatment were excluded from the study. A written informed consent was obtained from all patients enrolled in the study. The consent form was approved by the Medical Ethics Committee of the Iasi Grigore T. Popa University of Medicine and Pharmacy. The patients were monitored monthly both clinically and ultrasonographically by evaluating the cyst size, homogeneity, shape, vascularization, position relative to the uterus and contralateral ovary, presence of sludge and horizontal levels. All patients were examined by vaginal ultrasound associated with Doppler at the moment of diagnosis and then every 3 months. In all cases the diagnosis was confirmed postoperatively by histological examination, which demonstrated the presence of histopathologic features similar to endometrium, namely endometrial stroma, endo- 711

Daniela-Roxana Albu (Matasariu) et al. metrial epithelium, glands that respond to hormonal stimuli and hemosiderin deposits. Age of the patients ranged from 20 to 49 years (mean age 32 years), all of them still menstruating. The parameters followed intraoperatively were the ease of dissection, amount of bleeding, possibility of conservative treatment, extension of adhesions, and disease staging. Postoperatively the patients were reevaluated three months later by clinical examination and vaginal ultrasound. RESULTS AND DISCUSSION In group A patients (on desogestrel treatment) we found a significant decrease in cyst diameter and vascularization associated with sludge and decrease in echogenicity (tab. I). TABLE I Preoperative ultrasonographic changes Group A Group B Cyst diameter /- Vascularization /- Sludge and hyperechogenicity /- During the follow-up we noticed in the patients treated desorgestrel (group A) an improvement in clinical symptoms with impact on their mental, physical and social well-being. In the same group A patients we noticed intraoperatively less bleeding during cyst dissection and a better cleavage plan between the cyst capsule and the normal ovarian tissue (tab. II). Desorgestrel was well tolerated and no patient had to stop the administration because of side effects. Eighty women became amenorrheic, 58 had irregular vaginal bleeding and 17 women had regular periods. The bleeding amount was described as much lower than a normal period. Fifty-one patients complained of weight gain, the maximum being 5 kg. Twenty-eight patients complained of vaginal dryness and sexual discomfort. Fifty-five patients had decreased libido (fig.1). TABLE II Surgical parameters Group A Group B Easy dissection and capsule cleavage +++ +/- Heavy bleeding +/- +++ Thick adhesions + +++ Operative time + ++ Fig.1. Side effects of Desogestrel treatment 712

Desogestrel in the preoperative treatment of endometriotic cysts Endometriosis is a major public health problem, due to the number of cases that continues to increase and the risk of consecutive ovarian and endometrial tumors (10% of endometrioid carcinomas of the ovary being associated with uterine endometrioid carcinomas), fact that motivates many researches focused on the mechanisms of endometriosis development and progression (3). Although endometriosis is considered a chronic benign condition, it can present invasive characters, inducing severe symptoms (13). The study of endometriosis is not fortuitous since this gynecologic disease has an increased incidence, accounting for 2% of the general population, and is the third cause of gynecological checkup for infertility, chronic pelvic pain, dyspareunia and dysmenorrhea. Endometriosis affects 7-15% of women of childbearing age, accounting for 25-30% of cases of sterility, with important social impact (3). In endometriosis research there are numerous scientific data, with big names in the scientific world who say the same things about its incidence, mechanism of production and social repercussions. Laparoscopic intervention is the gold standard approach in the treatment of endometriosis, and the results may be enhanced with an appropriate technique and reasonable adjuvant therapies (14). Of the adjuvant therapies for endometriosis, desogestrel may be one of them. This study showed that treatment with desogestrel improves the operative conditions mainly by decreasing the bleeding and increasing the laxity of the connective tissue between the cyst capsule and the normal ovarian tissue. However its side effects, such as amenorrhea, irregular bleeding, weight gain and decreased libido as well as its contraceptive action might reduce patient compliance to this treatment. CONCLUSIONS In our study, progestative treatment improved the operative conditions and decreased the recurrence risks of ovarian endometriotic cysts. Treatment with desogestrel for at least 6 months preoperatively has a shrinking effect on the endometriotic cyst, decreases intraoperative bleeding and makes dissection and surgery easier. In progress researches will demonstrate the action of preoperative treatment with desogestrel on the factors involved in the progression of endometriotic lesions. ACKNOWLEDGEMENS This paper was published under the frame of European Social Found, Human Resources Development Operational Programme 2007-2013, project no. POSDRU/ 159/1.5/S/136893. REFERENCES 1. Bulun SE. Endometriosis. N. Engl. J. Med. 2009; 360: 268-279. 2. Giudice LC. Clinical practice. Endometriosis. N. Engl. J.Med. 2010; 362: 2389-2398. 3. Verkauf BS. Incidence,symptoms and signs of endometriosis in fertile and infertile women. J Fla Med Assoc. 1987; 74(9): 671-675. 4. Lucidi RS, Witz CA, Chrisco M, Binkley PA, Shain SA, Schenken RS. A novel in vitromodel of the early endometriotic lesion demonstrated that attachment of endometrial cells to mesothelial cells is dependent on the source of endometrial cells. FertilSteril. 2005; 84:16-21. 713

Daniela-Roxana Albu (Matasariu) et al. 5. Vercellini P, Crosignani CG, Somigliana G,Vigano P, Frattaruolo M, Fedele L. Waiting for Godot : a commonsense approach to the medical treatment of endometriosis. HumReprod. 2011; 26(1): 3-13. 6. Johnson NP, Hummelshoj L; World. Endometriosis Society Montpellier Consortium. Consensus on current management of endometriosis. Hum Reprod. 2013; 28(6): 1552-1568. 7. Aznaurova YB, Zhumataev MB, Roberts TK, Aliper AM, Zhavoronkov AA. Molecular aspects of development and regulation of endometriosis.reprodbiolendocrinol. 2014; 12: 50-74. 8. Streuli I, de Ziegler D, Santulli P, et al An update on the pharmacological management of endometriosis. Expert OpinPharmacother. 2013; 14: 291-305. 9. Matasariu DR, Tirnovanu MC, Gonta Olga, Holicov M, Dumitrascu I. Comparison of various progestins in the preoperative treatment of endometriosic cysts CIC. 2012; 34(1): 244-245. 10. MatasariuDR, Tirnovanu MC, Gonta O,Grigore M, Dumitrascu I. Desorgestrel prevention of recurrences after surgical treatment of ovarian endometriosic cysts.giornaleitaliano di Ostetrica e Ginecologia 2012; 34(1): 246-247. 11. Socolov R, Butureanu S, Sindilar A,Luchian A, Marcus S, Cozma L. Clinical and paraclinical diagnosis of pelvic endometriosis. Clinical study. Rev Med ChirSoc Med Nat Iasi. 2009; 113(3): 799-802. 12. HolicovLutuc M, Nemescu D, Onofriescu A,Tirnovanu M, Moscalu M, Onofriescu M. Pregnancy and recurrence rates in infertile patients operated for ovarian endometriosis. Rev Med ChirSoc Med Nat Iasi. 2015; 119(1): 127-134. 13. Ilea C, Lupascu I, Socolov D, Carauleanu A. Pelvic endometriosis and uretero-hydronephrosis: clinical, imagistic and surgical implications case report. Rev Med ChirSoc Med Nat Iasi. 2015; 119(1): 170-174. 14. Garry R. The effectiveness of laparoscopic excision of endometriosis. CurrOpinObstet Gynecol. 2004; 16 (4): 299-303. NOUTĂȚI NEWS TEA DRINKING AND TUBERCULOSIS Numerous studies showed that tea drinking helps to prevent obesity, cardiovascular diseases, autoimmune diseases, neurodegenerative diseases and tumors. Chinese researchers discovered the negative association between tea drinking and tuberculosis (TB). Tea leaves contain epigallocatechin-3-gallate, a flavonoid which inhibit the bacterial growth and the bacillus survival in macrophages. The increasing tea consumption is associated with a decreased risk of TB. Subjects who consumed 151-300 g tea / month had a lower risk to develop TB than those with a lower intake of tea. The green tea led to the most evident protection against TB, compared to oolong and black tea. Future studies are needed to determine whether drinking tea can be used in the prevention and control of TB (Mengshi Chen; Jing Deng; Wufei Li; Dan Lin; Congxu Su; Mian Wang; Xun Li; Benjamin Kwaku Abuaku; Hongzhuan Tan; Shi Wu Wen. Impact of tea drinking upon tuberculosis: a neglected issue. BMC Public Health 2015;15(515)). Cătălina Luncă 714