Department of Obstetrics and Gynecology, the Chaim Sheba Medical Center, (affiliated to the Sackler Faculty of Medicine, Tel-Aviv University), Tel-Hashomer, Israel
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key words: contraception/Doppler flow/endometrium/LNG-IUS/ultrasonography
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Menorrhagia in IUD users can be caused by decreased vascular resistance in the uterine artery with concomitant increased blood flow to the uterus, changes which can be detected using colour Doppler flow (Kurjak et al., 1989; Momatz et al., 1994). However, only a few studies describe the haemodynamic changes in LNG-IUS users (Pakarinen et al., 1995
; Jarvela et al., 1998
).
Our aim was to evaluate the uterine blood flow in copper IUD and LNG-IUS users, and to try to determine the cause for the different bleeding pattern in both groups, especially the cause of amenorrhoea in the LNG-IUS users.
![]() |
Materials and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Two main parameters were examined. First, blood flow velocity waveforms were evaluated in the uterine artery on either side at the level of the inner cervical os, as well as in the spiral artery at the region of the endometrial cavity. Second, endometrial width was measured in both groups. It was measured as the thickest part in the sagittal section. In order not to include the device itself (copper as well as LNG-IUS) in the measurement and to avoid the acoustic shadowing created by the LNG-IUS, endometrial measuring was done at the side of the vertical arm.
Exclusion criteria in this study included use of any contraceptive pills during the previous 3 months, ingestion of any other medications, pregnancy, previous pelvic inflammatory disease, genital tumour or thromboembolic phenomena.
All patients enrolled gave their informed consent to participate in the study. Clinical parameters of degree of menstrual flow, intermenstrual bleeding, and cessation of menstrual bleeding were obtained using a simple questionnaire filled 12 months and 46 months after insertion. Menstrual flow was graded using a modified pictorial questionnaire including questions on the number and look of pads/tampons per menstruation (spotted, half-full and full) as well as occurrence of intermenstrual bleeding.
Ultrasonography was done using 48 MHz transvaginal transducer (Ultramark HDI 3000; ATL, Bothwell, WA, USA). All women were examined in the midlate follicular phase (up to day 10 from the beginning of the menstrual cycle).
Blood flow velocity waveforms were evaluated in the uterine artery on either side at the level of the inner cervical os, as well as in the spiral artery at the region of the endometrial cavity. Blood flow patterns were displayed within a 90° sector. The spatial peak temporal average intensity was <100 mW/cm2. The high-pass filter was set at the lowest available setting (to eliminate low-frequency signals originating from vessel wall movements) with sample volume size of 24 mm. When good colour signals were obtained, blood flow velocity waveforms were recorded. Uterine artery blood flow was evaluated according to the Pourcelot index. The resistance index (RI), defined as the difference between peak systolic and end diastolic flow divided by the peak systolic flow, was calculated. The mean value of three consecutive waveforms was obtained.
Results are given as mean ± SEM. All the variables were analysed for the normality of their distribution by the one-sample KolmogorovSmirnov test procedure. A significant difference was defined using the two-sided non-paired t-test, or the non-parametric MannWhitney test, as appropriate. Fishers exact test was used to compare the rate of outcome measures in different subgroups. All statistics were performed using SPSS for windows version 8.0 (SPSS Inc., Chicago, IL). P < 0.05 was considered statistically significant.
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
When the existence of blood flow in the spiral artery was examined (at the subendometrial area), no blood flow was found in 35 (75%) women examined in group A while blood flow was found in all patients in group B.
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Abnormal uterine bleeding, such as menorrhagia and intermenstrual bleeding, is one of the most undesirable side-effects of the use of IUD. Hence, the advantage of the introduction of the new IUD, LNG-IUS, which, in addition to the better contraceptive effect, is characterized by reduction of menstrual blood loss, as well as the number of days of bleeding per cycle (Luukkainen and Toivonen, 1995).
The oligomenorrhoea or amenorrhoea in LNG-IUS users is hypothesized to be mediated by suppression of endometrial proliferation (Barbosa et al., 1995) as well as endometrial vascular changes that include thickening of the arterial walls, suppression of spiral arterioles and capillary thrombosis (Zhu et al., 1989
).
Several Doppler flow studies evaluated the haemodynamic changes in LNG-IUS users. Pakarinen et al., who examined the impedance to uterine blood flow before and after the insertion of LNG-IUD in 10 women of fertile age, did not find any change in the uterine PI (Pakarinen et al., 1995). Jarvela et al. demonstrated an increase in the main uterine artery PI in the mid-luteal phase, but not on the first day of menustration, and that the extent of increase in the PI correlated with serum levonorgestrel concentration (Jarvela et al., 1998
).
IUD-related menorrhagia might be caused by decreased vascular resistance in the uterine artery with increased blood flow to the uterus (Momtaz et al., 1994). Frajndlich et al. have examined the Doppler sonographic changes in women carrying copper IUD with and without abnormal bleeding. They found an increase in the uterine artery blood flow in women with abnormal uterine bleeding carrying IUD when compared with the control groups (Frajndlich et al., 2000
).
We have conducted this study in view of the differing results regarding blood flow in LNG-IUS users, as well as in normal-bleeding and abnormal-bleeding women carrying copper IUD. Its main aim was to evaluate the Doppler flow patterns in the main uterine artery and the spiral artery, along with the sonographic appearance of the endometrium, in LNG-IUS versus copper IUD users.
According to the present results, Doppler flow did not reveal any significant change in the uterine artery (cervical branch) between the groups, whereas there was a marked reduction in the subendometrial blood flow only in the LNG-IUS users. Furthermore, this observation was reinforced by the significant reduction in endometrial thickness in LNG-IUS users (from a mean of 7.3 mm to 4.1 mm, P < 0.0001).
We think, according to these study results, that the main effect of the LNG-IUS is due to its local progestational effect (i.e. no change in uterine blood flow along with marked reduction in spiral artery blood flow and endometrial width). These haemodynamic changes correlate well with the morphological changes in the endometrial spiral arterioles and capillaries (Zhu et al., 1989; Jones and Critchley, 2000
). These authors have demonstrated a remarkable transformation of the endometrium, mediated by the local levonorgestrel delivery and manifested by extensively decidualized and atrophic morphology, significant reduction in steroid receptor content, resulting in the alteration of many progesterone-regulated locally acting mediators (Jones and Critchley, 2000
). They have also stated that this phenomenon is independent of ovarian function and circulating sex steroid concentrations. In addition it should be acknowledged that levonorgestrel has androgenic and anti-estrogenic activities on the endometrium that result mainly from down-regulation of estrogenic receptors (Jones and Critchley, 2000
).
We agree with French et al., who stated that the amenorrhoea in LNG-IUS users is benign, end-organ suppression of bleeding, and associated with normal estrogen levels (French et al., 2000). Since the amenorrhoea was the main reason for discontinuation of the LNG-IUS in their study, and in view of our results, every effort should be made in the pre-contraceptive counselling to inform the patient of the possible amenorrhoea and to assure her that the main effect is benign and local. This may add to the data on the recovery of fertility after LNG-IUS discontinuation, which were reported to be very similar to copper IUD (Belhadj et al., 1986
; Andersson et al., 1992
). All these data can reassure the patients carrying LNG-IUS of the merely local effect of the device and thus may serve to provide reassurance at consultation and thereby decrease the rate of discontinuation.
![]() |
Notes |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Andersson, K., Batar, I. and Rybo, G. (1992) Return to fertility after removal of a levonorgestrel-releasing intrauterine device and Nova-T. Contraception, 46, 575584.[ISI][Medline]
Barbosa, I., Olsson, S.E., Odlind, V., Goncalves, T. and Coutinho, E. (1995) Ovarian function after seven years use of a levonorgestrel IUD. Adv. Contracept., 11, 8595.[ISI][Medline]
Belhadj, H., Sivin, I., Diaz, S,. Pavez, M., Tejada, A.S., Brache, V., Alvarez, F., Shoupe, D., Breaux, H., Mishell, D.R. Jr et al. (1986) Recovery of fertility after use of the levonorgestrel 20 mcg/d or Copper T 380 Ag intrauterine device. Contraception, 34, 261267.[ISI][Medline]
Frajndlich, R., von Eye Corleta, H. and Frantz, N. (2000) Color Doppler sonographic study of the uterine artery in patients using intrauterine contraceptive devices. J. Ultrasound Med., 19, 577579.
French, R.S., Cowan, F.M., Mansour, D., Higgins, J.P., Robinson, A., Procter, T., Morris, S. and Guillebaud, J. (2000) Levonorgestrel-releasing (20 microgram/day) intrauterine systems (Mirena) compared with other methods of reversible contraceptives. Br. J. Obstet. Gynaecol., 107, 12181225.[ISI]
Guillebaud, J., Bonnar, J., Morehead, J. and Matthews, A. (1976) Menstrual blood-loss with intrauterine devices. Lancet, 1, 387390.[ISI][Medline]
Hurskainen, R., Teperi, J., Rissanen, P., Aalto, A.M., Grenman, S., Kivela, A., Kujansuu, E., Vuorma, S., Yliskoski, M. and Paavonen, J. (2001) Quality of life and cost-effectiveness of levonorgestrel-releasing intrauterine system versus hysterectomy for treatment of menorrhagia: a randomised trial. Lancet, 357, 273277.[ISI][Medline]
Jarvela, I., Tekay, A. and Jouppila, P. (1998) The effect of a levonorgestrel-releasing intrauterine system on uterine artery blood flow, hormone concentrations and ovarian cyst formation in fertile women. Hum. Reprod., 13, 33793383.[Abstract]
Jones, R.L. and Critchley, H.O. (2000) Morphological and functional changes in human endometrium following intrauterine levonorgestrel delivery. Hum. Reprod., 15 (Suppl. 3), 162172.[Medline]
Kurjak, A., Zalud, I., Jurkovic, D., Alfirevic, Z. and Miljan, M. (1989) Transvaginal color Doppler for the assessment of pelvic circulation. Acta Obstet. Gynecol. Scand., 68, 131135.[ISI][Medline]
Lahteenmaki, P., Haukkamaa, M., Puolakka, J., Riikonen, U., Sainio, S., Suvisaari, J. and Nilsson, C.G. (1998) Open randomised study of use of levonorgestrel releasing intrauterine system as alternative to hysterectomy. Br. Med. J., 316, 11221126.
Luukkainen, T. and Toivonen, J. (1995) Levonorgestrel-releasing IUD as a method of contraception with therapeutic properties. Contraception, 52, 269276.[ISI][Medline]
Momtaz, M., Zayed, M., Rashid, K. and Idriss, O. (1994) Doppler study of the uterine artery in patients using intrauterine contraceptive device. Ultrasound Obstet. Gynecol., 4, 231235.[ISI][Medline]
Pakarinen, P., Luukkainen, T., Laine, H. and Lahteenmaki, P. (1995) The effect of local intrauterine levonorgestrel administration on endometrial thickness and uterine blood circulation. Hum. Reprod., 10, 23902394.[Abstract]
Rybo, G., Andersson, K. and Odlind, V. (1993) Hormonal intrauterine devices. Ann. Med., 25, 143147.[ISI][Medline]
Zalel, Y., Kreizer, D., Soriano, D. and Achiron, R. (1999) Sonographic demonstration of a levonorgestrel-releasing IUD (Mirena). Harefuah, 137, 3031.[Medline]
Zhu, P.D., Luo, H.Z., Cheng, J., Xu, R.H., Liu, Y.F., Zheng, W.M., Song, G.Y., Chen, J.H., Zhou, Z.H., Wu, Y.M. et al. (1989) The effect of intrauterine devices (stainless steel ring, copper-T220 and levonorgestrel) on the DNA content in isolated human endometrial cells. Contraception, 40, 591604.[ISI][Medline]
Submitted on April 26, 2002; resubmitted on June 25, 2002; accepted on August 2, 2002.