progesteronlu rİa : kime ? prof.dr.umur Çolgar the levonorgestrel intrauterine device steroid...
TRANSCRIPT
![Page 1: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/1.jpg)
Progesteronlu RİA : Kime ?
Prof.Dr.Umur Çolgar
![Page 2: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/2.jpg)
THE LEVONORGESTREL INTRAUTERINE DEVICE
Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane
T frame
Removal threads
32 mm
![Page 3: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/3.jpg)
Mirena®: Levonorgestrel release 20 µg/24 hours
THE LEVONORGESTREL INTRAUTERINE SYSTEM
![Page 4: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/4.jpg)
Mirena®
Levonorgestrel Intrauterine System
Multiple modes of action
Main: Prevention of
endometrial proliferation Thickening of utero-
cervical fluidMinor: Occasional prevention of
ovulation Foreign body reaction in
endometrium
![Page 5: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/5.jpg)
Which Patient ?
Desire for contraceptionMenorrhagiaHRT programme for
perimenopausal and menopausal women
![Page 6: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/6.jpg)
![Page 7: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/7.jpg)
Barcelona1 7
Effects of LNG-IUD
Suppression of IGF-1 by abandoned production of IGFBP-1 causes inhibition of the IGF-1-mediated estrogen effects.Inhibition of angiogenesis.Hamptom et al Human Reprod. 20, 2653, 2005
![Page 8: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/8.jpg)
Levonorgestrel concentration in plasma, fat myometrium, endometrial and oviduct tissues
Tissue LNG-IUS Oral**
Plasma(pg/ml) 202 559
Fat tissue * 1.23 4.41
Myometrium * 2.43 1.4
Endometrium* 808 3.5
Oviduct * 1.8 1.7
*ng/g wet weight** Oral administration of levonorgestrel
Clinical Endocrinology ,Nilsson et al 1982
![Page 9: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/9.jpg)
LEVONORGESTREL IUS
Proliferative Secretory Inactive
Courtesy Dr E-M Rutanen, Helsinki
![Page 10: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/10.jpg)
SEVERE PELVIC INFLAMMATION
12.5% risk of tubal infertility with first attack
33% risk with second attack
Weström 1980
![Page 11: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/11.jpg)
![Page 12: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/12.jpg)
Return to Fertility
No delay
Ovulation occurs within 2 weeks
& menstruation within 23 days
Rates of conception post removal
are normal
![Page 13: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/13.jpg)
Definition
Regular heavy bleedingfrom a secretory endometriumexceeding 80 ml per cycle
![Page 14: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/14.jpg)
Patient Selection for Menorrhagia Treatment
Organic factors should be diagnosed
Pathologies of the endometrium should be examined
![Page 15: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/15.jpg)
Causes of menorrhagiaIdiopathic (no obvious cause)Fibroidsendometriosis / adenomyosisgenital infectionsendometrial polypshyperplasiamalignancycoagulation or endocrine
disordersmedications
![Page 16: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/16.jpg)
Efficacy of Mirena® in menorrhagia
Mirena effectively reduces menstrual blood loss (MBL)
0
50
100
150
200
Beforeinsertion
3 6 12
Months of Mirena use
Med
ian
MB
L (m
L)
Andersson and Rybo. Br J Obstet Gynaecol. 1990; 97: 690-4
* * *
* p<0.001
─86%─97%─91%
% Reduction
(80mL MBL = menorrhagia)
![Page 17: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/17.jpg)
Mirena® compared with flurbiprofen, and tranexamic acid
Mirena® is significantly more effective than flurbiprofen or tranexamic acid in reducing menstrual blood loss
-95.8
-20.7
-44.4
-100-90-80-70-60-50-40-30-20-10
0
Mirena Flurbiprofen
(FL)Tranexamicacid (TA)
Per
cent
age
chan
ge fr
om
base
line
in M
BL
Milsom et al. Am J Obstet Gynecol 1991; 164: 879-83
***
**
*
* P<0.05 (FL vs TA)
**P<0.01 (Mirena vs TA)
***P<0.001 (Mirena vs FL)
![Page 18: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/18.jpg)
Mirena® compared with endometrial ablation/resection
Mirena has comparable efficacy with endometrial resection in reducing menstrual blood loss
Crosignani et al. Obstet Gynecol 1997; 90: 257-63
184.8203.2
38.823.5
0
50
100
150
200
250
Mirena Endometrialresection
Mea
n bl
eedi
ng s
core
Baseline
12 months
79% 89
%
![Page 19: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/19.jpg)
LNG-IUS therapeutic effect on Fibroid uterus
The local direct endometrial suppression is the principal mechanism explaining the effect of the LNG-IUS on menstrual blood loss in cases of leiomyoma.
![Page 20: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/20.jpg)
Single intramural fibroid less than 5 cm or multiple intramural fibroids < 3 cm in diameter and < 5 in number.
Submucousal extension less than 30% and not causing major distortion of uterine cavity.
Uterine length less than 10cm
Hysteroscopy, endometrial biopsy
liquid base cytology
Transvaginal ultrasound
Criteria of selection
ESH classification
X
XX
![Page 21: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/21.jpg)
ESH Submucous Myoma Classification
TypeIntramural Extension
0 None
I < 50%
II > 50%
European Society for Hysteroscopy Classification
![Page 22: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/22.jpg)
Changes in Uterine and Leimyoma Volume
Baseline(n=67)
3 months (n=56)
6 months (n=56)
12 months (n=61)
Uterine volume (mL)
138±72 131±68p<0.01
125±58 p<0.01
122±73p<0.01
Total leiomyoma volume (mL)
30±29 27±34p=0.10
19±21 p<0.001
19±21 p<0.001
![Page 23: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/23.jpg)
Barcelona 2 23
![Page 24: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/24.jpg)
![Page 25: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/25.jpg)
![Page 26: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/26.jpg)
Barcelona 2 26
Suvanto-Luukkonen et al Acta Obstet. Gynecol. Scand. 77, 758, 1998
![Page 27: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/27.jpg)
Barcelona 2 27
Anderson et al Obstet. Gynecol. 79, 963, 1992
![Page 28: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/28.jpg)
28
Mirena® combined with 2 mg oral estradiol valerate in postmenopausal women
At 6 and 12 month endometrial histology was nonproliferative.
The thickness of the endometrium was 3.6 mm.Conclusion: Mirena® protects against endometrial
hyperplasia. In most of the women it induces amenorrhea.
Varila et al Fert. Steril. 76,969,2001
![Page 29: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/29.jpg)
Barcelona 2 29
Percutaneous gel (1.5 mgE2 daily) and Mirena®
1. Spotting was frequent during the first 6 month and declined thereafter.
2. At 1 one year 80 % of the women were amenorrheic
3. Endometrium morphology showed epithelial atrophy accompanied by decidual reaction of the stroma.
Suvanto-Luukkonen, Kauppila Fert. Steril. 72, 161, 1999
![Page 30: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/30.jpg)
30
Levonorgestrel-IUD Mirena® with oral conjugated estrogens in perimenopausal women
n=82
Length of treatment
(month)
Nonproliverative endometrium
(%)
Propotion of amenorrhea
(%)
12 98,6 % 54,4
24 98,6 %
36 95,5 %
48 96,8 %
60 95,2 % 92,7
No endometrial hyperplasia was detected throughout the period of 60 month.
Hampton et al Human Reprod. 20, 2653, 2005
![Page 31: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/31.jpg)
LNG-IUD in ERT-users1 Year Follow-Up
Raudaskoski et al. BritJ Obstet Gynaecol 2002;109:136
168 postmenopausal women in 4 Finish Menopause ClinicsAll did get oral 2mg E2-valeriate daily Randomised:
LNG-IUD 10 microgram per dayLNG-IUD 20 microgram per dayCyclic MPA: 5mg/day 14/30
Endometrial protectionAtrophia in both LNG-IUD18/47 had endometrial proliferation in MPA group
Serum lipid profileTotal cholesterol decreased in all 3 groupsHDL increased in MPA and LNG-IUD 10 micrograms per day
InsertionEasy: 70% for smaller versus 46% for larger (Mirena)Difficult: 4% for smaller versus 21% for larger (Mirena)
![Page 32: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/32.jpg)
LNG-IUD – Beyond Contraception
Down regulation of ER/PRIncrease in apoptosis and decreased proliferationEndometrial glandular atrophy in 87%Endometrial stromal decidualisation in 96%Stromal inflammatory cell infiltrate in 79%Insuline-like growth factor 1 (IGF1-BP)Increase in impedance to blood flow to uterine a.Endometrial angiogenic growth factorsMany locally acting mediators of breakthrough
beeding: Interleukin-8, Cyclooxygenase-2
![Page 33: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/33.jpg)
Barcelona1 33
Varma et al Obstet. Gynecol. in press
![Page 34: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/34.jpg)
MIRENA and Endometriosis
StudyStudy size
Duration ResultsLNG IUS vs control
Vercellini et al (2003)
20 LNG IUS
20 surgery
only
12 months
10% vs 45% recurrence of dysmenorrhea
75% vs 50% satisfied with the treatment
![Page 35: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/35.jpg)
Barcelona1 35
Petta et al Human Reprod. 20, 1993-1998, 2004
![Page 36: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/36.jpg)
![Page 37: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/37.jpg)
The nulliparous modern woman
Appropriate method NICE
Possible less PID Investment in fertility
◦ Less menorrhagia◦ Less dysmenorrhea
Switch off/Switch on contraception
Fit and forgetHigher continuation in 80%
compared to 73% for COC Suhonen, Contraception 2004;69:407
![Page 38: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/38.jpg)
38
![Page 39: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/39.jpg)
Meme Kanseri İnsidansı/100.000
Yaş Grupları 30-34 35-39 40-44 45-49 50-54
Mirena 27,2 74,0 120,3 203,6 258,5
Kontrol 25,5 49,2 122,4 232,5 272,6
BackmanT. ObstetGynecol 106:813,2005
![Page 40: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/40.jpg)
40
Varma et al Obstet. Gynecol. in press
![Page 41: Progesteronlu RİA : Kime ? Prof.Dr.Umur Çolgar THE LEVONORGESTREL INTRAUTERINE DEVICE Steroid reservoir: Levonorgestrel 52mg Silicone rate-limiting membrane](https://reader035.vdocument.in/reader035/viewer/2022062322/56649e735503460f94b72594/html5/thumbnails/41.jpg)