Surgical Medical The “Pragmatic Approach” to treatment of … · 2019. 1. 29. · Prof. Thomas Römer, M.D. Department OB/GYN Academic Hospital University of Cologne / Germany

05/01/2017

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Prof. Thomas Römer, M.D.

Department OB/GYNAcademic HospitalUniversity of Cologne / Germany

14th ESC Congress, May 4-7, Basel, Switzerland

Contraception and the treatmentof medical disorders -Endometriosis

Immune function and inflammation

Cell proliferation and differentiation

Ectopic endometrial cell

Pathogenesis of endometriosis

Apoptosis

Ectopic implant

Chronic inflammation

ER βα

PR AB

Invasion and neoangiogenesis

ER βα

PR A B

ProgesteroneEstrogens

GnRH analogs / antagonistsaromatase inhibitors

-Estroprogestins

ProgestinsSPRM

+

-Angiogenes is

inhibitors

Statins

Botanicalextracts

- NSAIDs

Antioxidants-Thiazolidinediones

ProgestinsSPRM+SERM

Treatment for endometriosis in 2016

MedicalSurgical

To destroy the lesion

To prevent the lesion

Removal of the lesions

Adhesiolysis

Chapron C. Ann NY Acad Sci 2004; Nez hat C. Fertil Steril 2010.

The Patient Experience Matters

The “Pragmatic Approach” to treatment of endometriosis

Treat the Patient NOT THE LESIONS

• Verc e l l in i P. e t a l . Endometrios is : c urrent and future medic a l therapies . Bes t Prac t Res Cl in Obs tet Gy naec ol 2008

Treatment Options

Surgical managementMedical management

• COCs* • Progestin only (oral, IM, SC) • GnRH agonist + addback • LNG-IUS* • Danazol • Aromatase inhibitors* • NSAIDs, other analgesics

• Excision vs ablation• Conservative vs Definitive

But – expertise & resources are not always available &

recurrence is common

*No approved indication for treatment of endometriosis/symptoms of endometriosisCOCs, combined oral contraceptive; GnRH, gonadotropinreleasing hormone; IM, intramuscular; LNG-IUS, levonorgestrel-releasing intrauterine system; NSAIDs, nonsteroidal anti-inflammatory drugs; SC, subcutaneous

When is medical treatment required?

*Practice Committee of the American Society for Reproductive Medicine. Fertil Steril. 2008.

First-line treatment

After surgery to reduce recurrence

When surgery is not possible or refused

“Endometriosis should be viewed as a chronic disease that requires a life-long management plan with the goal of maximizing the use of

medical treatment and avoiding repeated surgical procedures”*

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Estrogen in COCs may stimulate disease progression

“COCs may be a ‘rescue factor’ for regurgitated endometrial glands that would otherwise undergo necrosis and resorption during the physiologically hypoestrogenic menstrual milieu”

-Vercellini P, et al. Hum Reprod Update 2011


• # 410 patients with histologically proven endometriosis –

ü RR in current OC users [1.22 (0.60-2.52)] for all rAFS classifications [NS]

ü RR in past OC users [2.79 (1.74-5.12)] for all rAFS classifications

ü RR in past OC users [5.60 (3.20-9.80)] for severe primary dysmenorrhea

ü RR in past OC users [16.2 (7.80-35.3)] for severe primary dysmenorrhea (DIE)

• Parameters best predict the later finding of DIE

ü OC user for severe dysmenorrhe a ≥18 years of age (8%) vs <18 (21%) [RR 4.2 (1.8-10.0)]

ü OC use longer 8.4 vs 5.1 years ; at a younger age 16.5 vs 18.1 years [RR 4.5 (1.9-10.4)

(Chapron C et a l ., 2011)

Rationale for the Use of Progestins in the Treatment of Endometriosis

Laz z eri L , e t a l . J Endometrios is 2010;2:169–181;Kappou D, e t a l . Minerv a Ginecol 2010;62:415–432;Cros ignanI P, e t a l . Hum Reprod Update 2006;12:179–189

Reduction of serumestrogen levels

Immunomodulatoryeffect

Anti-inflammatoryeffect

Decidualisation + atrophyof endometrial tissue

Inhibition of matrixmetalloproteinases

Anti-angiogenic effect

Progestins

Possibilities of hormonal long termtreatment (>1 year)

1. Combined hormonal contraceptions (oral/vaginal)

2. Progestins • systemic (oral, Injektions, Implants)• local (LNG-IUS)

3. GnRH-analogues• continuous (with add back)• intermittent

4. Aromatase inhibitors5. SPRM (?)

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Studies of long-term hormone therapyafter surgery to treat endometriosis

Study and source Studydesign

Hormone therapy

No. of women(treated/control)

Follow-up, months

Primary result: rate ofrecurrence, %

p value

Outc ome: Rec urrenc e of pelv ic pain

Dysmenorrhea

Verc el l in i e t a l 2003

Serac c hio l i e t a l 2010

Tammahas amut et a l 2012

RCT

RCT

RCT

LNG-IUD/EM

Cy c l ic OC/ c ontinuous OC/EM

LNG-IUD/EM

20/20

92/95/87

28/26

12

24

12

10/45

31/4/40

7/39

.01

<.01

.01

Somigliana et al (2014)

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Studies of long-term hormone therapy after surgery to treat endometriosis


Hormone therapy


Follow-up, months


p value


Dyspareunia




RCT

RCT

RCT

LNG-IUD/EM


LNG-IUD/EM

9/8

92/95/87

12/7

12

24

12

Median VAS s c ore reduc tion31/15

27/29/35


NS

NS

NS


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Hormone therapy


Follow-up, months


p value


Nonmenstrual pain




RCT

RCT

RCT

LNG-IUD/EM


LNG-IUD/EM

5/7

92/95/87

17/19

12

24

12


29/27/40


NS

NS

.04


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Efficacy of postoperative use of COC for more than 6 months on pain recurrence

Koga et al (2015)

Author Year Dysmenorrhea Chronic pelvicpain

Dyspareunia

Seracchioli et al. 2010 ++ n.s. n.s.

Vlahos et al. 2013 ++ + n.s.

The use of COCs in continuous mode reduces only frequency of return dysmenorrhea Application COC in the postoperative period does not affect the return of chronic pelvic pain and dyspareunia

OC after surgery: efficacy in prophylactic recurrence

Дисменоррея

Диспареуния

Хроническая тазовая боль

• Randomize research, 311 pts• Placebo - 104, Cyclic OC– 103, w/o break -

104• Duration of observation 24 moths• Evaluate pain reccurence

Renato Seracchioli, Fertility and Sterility , Volume 94, Issue 2, 2010, 464–471 i16

Efficacy of postoperative use of LNG-IUS for more than 6 months on pain recurrence

Koga et al (2015)

Author Year Dysmenorrhea Chronic pelvicpain

Dyspareunia

Vercellini et al. 2003 + n.s. n.s.

Tammahasamu tet al.

2012 +++ + n.s.

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Hormone therapy


Follow-up, Months


p value

Outc ome: Anatomic a l re laps e

Endometrioma


Tak amura et a l 2009


Lee et a l 2010

Cuc c ine l la et a l 2013

Cohort

Cohort

RCT

Cohort

Cohort

Cy c l ic OC/EM

Cy c l ic OC/EM


Cy c l ic OC/EM

Cy c l ic OC/EM

102/46

34/39

75/73/69

175/187

126/38

28

24

24

35

24

9/56

3/44

15/8/29

7/29

8/39

<.001

.001

.003

.001

.001


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Efficacy of postoperative medication formore than 6 months on endometrioma recurrence (RCT)

Author Year Interventions No. of patients Follow-upperiod, (months)

Results(recurrencerate)

P value

Seracchioliet al.

2010 Cyclic OC/continuousOC/EM

75/73/69 24 Cyclic OC (14,7%)/continuous OC (8,2%)/EM (29%)

<.005

Wong et al. 2010 LNG-IUS/MPA depot

15/15 36 No recurrencewere detectedin both groups

NS

Cucinellaet al.

2013 OC withdesogestrel/OC withgestodene/OCwithdienogest/EM

43/44/43/38 24 Desogestrel(26,5%)/

Gestodene(31,8%)/

Dienogest(20,5%)/

EM (74,7%)

<.005 (allOC vs. EM)

Koga et al. (2015)

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LNG-IUS vs. Depot MPA as a long term maintenance therapy for patients with moderate and severe endometriosis

• randomized controlled trial• 30 patients after conservative surgery• 15 LNG-IUS / 15 Depot MPA (3 years)• improvement of symptoms in both groups• compliance: LNG-IUS (13/15) better vs. Depot MPA (7/15)• BMD (after 3 years) (hip and lumbar regiones)

LNG-IUS: +0,023 / + 0,071 g/cm2

Depot-MPA: - 0,030 / – 0.017 g/cm2

• Conclusions: LNG-IUS better compliance and no bone loss

Wong et al. (2010)

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Efficacy of postoperative medication for more than 6 months on endometrioma recurrence (Cohort Studies)



P value

Takamuraet al.

2009 OC for 24 months/EM

34/39 24 OC (2,9%)/EM (43,5%)

<.001

Lee et al. 2010 GnRHa 3 or 6 months+OC/GnRHa 3 or 6 monthsalone

175/187 35(12-114)

GnRHa+OC(7,4%)/ GnRHaalone (28,9%)

<.001

Vlahos et al. 2013 Cyclic OC/ continuous OC atleast 6 months

167/85 21/23 Cyclic OC (16,6%)/ continuous OC

<.05

Koga et al. (2015)

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Efficacy of postoperative medication for more than 6 months on endometrioma recurrence (Cohort Studies)



P value

Cho et al. 2014 GnRHa 3 monthsfollowed by LNG-IUS/followed by OC

42/57 17 LNG-IUS (4,8%)/OC(10,5)

NS

Ouchi et al. 2014 OC (always)/OC (ever)/ Dienogest/ GnRHa 6 months/EM

25/9/7/16/110 38.3 OC (always)(0%)/OC (ever) (56%)/Dienogest(0%)/GnRHa (25%)/EM (23%)

<.05 (OC always vsOC ever)

Ota et al. 2015 Dienogest/EM 151/417 60 Dienogest(4%)/EM (69%)

<.0001

Koga et al. (2015)

Visanne long therm experience during 5 year for endometrioma prevention after surgery

ü 568 women (32,8 ±5,7 лет):ü 151 Visanneü 417 Placeboü Duration of observation- 5 yearü Visanne usage - 60 monthes

Endometrioma frequency recurrence: Placebo-69%, Visanne 4%Long-term administration of dienogest reduces recurrence after excision of endometr ioma. Yoshiaki Ota. Journal of Endometr iosis and Pelvic Pain Disorders 2015; 7(2): 63-67

диеногест

плацебо

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DNG in women with persistent endometriosis related pelvic pain duringNETA treatment

• 25 women with symptomatic rectovaginal endometriosis with

persistance of pain after 6 months NETA

• change treatment to 2 mg DNG treatment

• after 6 months: improvement of VAS (pelvic pain, dyspareunia),

increase of Qol-score

• no significant change of endometriotic nodules

• „NETA-resistant“ patients with rectovaginal endometriosis

symptoms have benefits from a DNG-treatmentMorotti et al. (2014)

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POP (DSG) vs. Vaginal ring in treatment of rectovaginal endometriosis infiltration the rectum

• 143 patients with rectovaginal endometriosis infiltrating the rectum• 12 months POP vs. ring• rate of satisfied patients higher in POP treated group

• gastrointestinal symptoms: improvement: 50 % (POP) 31 % (Ring)

Maggiore et al. (2014)

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Postoperative use of Depot MPA vs. continuous COC in the treatment of endometriosisassociated pain

• 48 patient after conservative surgery→ DMPA (150 mg) every 12 weeks or COC (EE 0,03 mg/Gestoden

0,075 mg) for 24 weeks

• satisfaction rate after: 12 weeks: 93 vs. 90 %

• pain score improvement in both groups• dysmenorrhoea score higher in COC group• no differences in side effects

• both treatments are effectiveCheewadhavenaraks et al. (2012)

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POP vs. COC in treatment of endometriosis –pain in patient with migraine without aura

• 6 months treatment in women with symptomatic rectovaginal endometriosis and migraine without aura

• satisfied with treatment: POP: 61,2 % (38/62) COC: 37,8 % (31/82)

• significant reduction of pelvic pain and dyspareunia in both groups• number of migraine attacks was lower than at baseline in POP group

• no reduction in COC group• also the intensity of migraine attacks was reduced in POP group• Conclusion: POP should be peferred in patients with migraine

Morotti et al. (2014)

Treatment of endometriosis : COC vs. POP

COC Progestin (POP, DeptoMPA, Implanon)

Efficacy - Contraception

Thrombembolic Risk

Bleeding disorders

Efficacy - Endometriosis

higher

higher

lower

lower

lower

lower

higher

higher

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Implanon vs. MPA: effects on pain scores in patients with symptomatic endometriosis

• randomized trial: 41 patients with histological proven endometriosis and pain or/and dyspareunia

• 1 year treatment implanon (n=21) or Depot MPA (n=20)• improvement of pain in both groups• reduction of VAS-Score: Implanon: 68 %, DMPA: 53 %• no difference in satisfaction and side effect profiles

Walch et al. (2008)

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ESHRE Endometriosis Guidelines 2013Treatment of PainClinicians are recommended to use progestagens[medroxyprogesterone acetate (oral or depot),dienogest, cyproterone acetate, norethisteroneacetate or danazol] or anti-progestagens(gestrinone) as one of the options, to reduceendometriosis-associated pain (Brown, et al., 2012).

A

The GDG recommends that clinicians take thedifferent side effect profiles of progestagens andanti-progestagens into account when prescribingthese drugs, especially irreversible side effects (e.g.thrombosis, androgenic side effects).

GPP

Clinicians can consider prescribing alevonorgestrel-releasing intrauterine system as oneof the options to reduce endometriosis-associatedpain (Ferreira, et al., 2010, Gomes, et al., 2007, Petta, et al., 2005).

B

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ESHRE Endometriosis Guidelines 2013Treatment of Pain

In women operat ed on for endomet riosis,clinicians are recommended to prescribepostoperative use of a levonorgest rel-releasingintrauterine syst em (LNG-I US) or a combinedhormonal cont racepti ve for at least 18-24months, as one of the options for thesecondary p revention of endometrio sis-associated dysmenorrhea, but not for non-men stru al pelvic pain or dyspareunia (Abou-Setta,et al., 2006,Seracchioli, et al., 2009).

A

Intrauterine System (IUS)Concept invented by Pr T. Luukkainen

Releases the progesteronelevonorgestrel at 20µg/day

Provides 5 years reliable contraception

Has other non-contraceptivehealth benefits

What is Mirena®

• Decidualization and subsequent atrophy of endometrium

• Direct action of the hormone on the foci of adenomyosisDown regulation of ER in glandular and stromal tissue

shrinkage of adenomyosis foci

• Reduction of PG production within the endometriumRelieve of dysmenorrheapelvic pain

Possible mechanisms for the treatment of Adenomyosis

Cho et al. Am J Obstet Gynecol 2008

Sheng et al. Contraception 2009

Mirena® and Adenomyosis

• 29 patients MRI-diagnosed adenomyosis suffering from metrorrhagia and dysmenorrhoea (age: 24-46 years)

• Mirena® -insertion• MRI-monitoring after 6 months

Bragheto et al (2007)

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Mirena® and Adenomyosis

Results:

• significant reduction of junctional zone thickness (MRI)= 24 %

• no significant reduction of uterus volumen (142 → 136 ml)• significant reduction of VAS (pelvic pain) (6 patients without improvement)

• reduction of metrorrhagia (33 % spottings after 6 months)

Bragheto et al (2007)

Contraception and the treatment ofmedical disorders - Endometriosis• COC and LNG-IUS after surgery

- significant reduction of recurrence rate for dysmenorrhea

- no significant effects for improvement of dyspareunia and nonmenstrual pain

• COC after surgery of endometriomas

- significant reduction of recurrence rate (anatomical relapses)- continuous use of COC is more effective than cyclic use of COC

- in selected studies COC containing dienogest are more effective than COC containing other progestins

• LNG-IUS is effective in reduction of recurrence of rectovaginal endometriosisand in treatment of adenomyosis

• Depot MPA is also effective the treatment of endometriosis

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Back up

Different localizations of endometriosis

Brain

Lung

Liver

Pelvis

Urinary tract

Bowel

Typical endometriosis localizations

Atypicalendometriosis localizations

Genital tract

Umbilicus Abdominal muscle

Kumakiri J , et a l. J Minim Invasive Gynecol 2010; Vilos GA, et a l. J Minim Invasive Gynecol 2011.

Clinical symptoms and Localization of endometriosis

Clinical symptoms Localisation

dysmenorrhoea peritoneal endometriosisdyspareunia rectovaginal endometriosisrecurrent cystitis peritoneal bladder endometriosiscyclic scar pain scar endometriosiscyclic upper abdominal pain diaphragma endometriosiscyclic haematuria bladder endometriosisbladder paincyclic bowel bleeding bowel endometriosisbowel pain (often constipation)

Römer (2011)Römer (2014)

ENDOMETRIOSIS – Medical Treatment Options

Drug Comments

NSAIDS In primary dysmenorrhea:NSAIDs have been shown to be effective compared to placeboLimited data is available for pain related to endometriosis

COCs Widely used off-label for endometriosisEffective in primary dysmenorrheaLack of RCT evidence in endometriosis

GnRHAnalogue

Considered ‘standard’ treatment for endometriosis due to high efficacyLimited to short-term use (6 months) due to adverse effects.

Synthetic Androgens

Not widely used anymore due to poor tolerability with many androgenic s ide effects (weight gain, acne, oily skin, hirsutism, deepening of voice).

Progestins Most were not developed for treatment of endometriosis

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Medical therapy – COCs• Widely used off-label for endometriosis• Effective in primary dysmenorrhea1• Lack of RCT evidence in endometriosis2

Only 1 study included in Cochrane review1

• Not all types of pain respond equally to COCs use (e.g. dyspareunia, chronic pelv ic pain)3

• May cause estrogenic AEs (nausea, weight gain, water retention, increased thromboembolic risk)2

Relevant factor:Progestins in COC

1. Wong Cl et a l . Coc hrane Database Sy st Rev 20092. Dav is LJ et a l . Coc hrane Database Sy st Rev 20073. Chapron C et a l . Hum Reprod 2011

Non-specific therapies –not approved in endometriosis

Including non-steroidalanti-inflammatory drugs and combined oral contraceptives

• lowest effective dose of OCs given

ü the dose in each tablet is a poor indicator of the systemic exposure

ü E2 levels vary widely among ♀ on the same COC

ü between ♀ differences > than dosages between current & older OCs

ü different Ps in combination with EE2 also contribute to pharmacokinetics

ü adverse events increase with greater systemic exposure(Wes thoff CL et a l ., 2010, 2015)

• Some ovarian activity (follicular growth beyond 10 mm)

ü is present w/o ovulation during pill use (Cros ignaniPG et a l ., 1996)

Exposure to ethinyl estradiol

OC user group(n=34) Controlgroup(n=36)

Variable Mean ± S D Ran g e Mean ± SD Ran g e p

FSH (IU/L) 4.73±3.86 0.44-15.39 6.59±0.93 4.99-8.33 0.015

LH (IU/L) 3.46±3.17 0.38-10.39 5.76±2.52 1.43-11.29 0.005

E2 (pg/ml) 27.54 ±16.36 0.57- 62.53 43.10±2.38 24.20-104.03 0.001

(Deb et a l., 2012) Mean E2 over 24 hour withoral E2V/DNG (Zeun S et a l., 2009)

Mean E2 over 24 hr with oral EE20µg//LNG 100µg

(Endrtkat J et a l., 2002)

The E treshold hypothesis - E2 >50 pg/mLneeded to support the growth of endometr iosis lesions (Barbieri R., 1992)

Exposure to ethinyl estradiol

EE2 levels vary widely among ♀ on the same COC

Medical therapy – Progestins

• Synthetic hormones with progesterone-l ike activity1,2

• Most were not developed for treatment of endometriosis

• Adverse events include: irregular bleeding and (especially with older agents) weight gain, headaches, acne and adverse lipid changes3,4

• Newer types selectively bind progesterone receptors specifically1

Minimize androgenic, estrogenic or glucocorticoid side-effects

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1. Si truk -Ware R. Hum Reprod Update 2006;2. Sc hind ler AE et a l . Maturi tas 2003;3. Wink el CA & Sc ia l l i AR. J Womens Heal th Gend Based Med 2002;4. Verc e l l in i P et a l . Hum ReprodUpdate 2003.

Specific therapies –approved in endometriosis

e.g. gonadotropin-releasinghormone agonists, danazol and some progestins

Summary of Activities for Various Progestogens

Progestogenic Androgenic Antiandrogenic Antimineralocorticoid Glucocorticoid

Progesterone + – (+) + –

Drospirenone + – + + –

Levonorgestrel + (+) – – –

Gestodene + (+) – (+) –

Norgestimatea + (+) – – –

Desogestelb + (+) – – –

Dienogest + – + – –

Cyproterone acetate + – + – (+)

Krattenmac her R. Contrac eption 2000;62:29–38

aMain metabolite levonorgestrel; bActive metabolite 3-ketodesogestrel; + indicates activity; (+) indicates negligible activity at therapeutic dosages; – indicates no activity

Conclusions Progestins

• progestins effective in treatment of endometriosis, but a lack of evidence in the most of progestins

• evidence available for DNG, limit evidence for DSG, NETA and MPA

• evidence for LNG-IUS and treatment of adenomyosis• important for clinical use: selection of progestins (different

efficacy and side effects)

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Comparison of different progestinsDSG MPA NETA DNG

approval for endometriosis

- - - +++

studies for treatment endometriosis

+ + ++ +++

antiandrogeniceffect

- - - ++

endometrium effect

+ + ++ ++

approval for contraception

++ ++ - -

long term treatment possible

++ + ++ ++

negative effect to bone

- + - -

effect to weight - + - -

Guidelines for Progestins

• ESHRE guideline:– Progestins ‘…can be considered as a first choice for the treatment of endometriosis

because they are as effective in reducing [laparoscopy] scores and pain as danazol or GnRH agonists, and have a lower cost and a lower incidence of adverse effects ’1

• Other expert comment:– ‘Given their good tolerability , minor metabolic effects and low cost, progestogens

must therefore be considered the drugs of choice’2

• Recent Canadian clinical practice guidelines include dienogest as an effective long-term treatment option3

• German guidelines stated that dienogest is equally effective as GnRH agonist

ESHRE, European Soc iety of Human Reproduc tion and Embry ology ; GnRH, gonadotropin-re leas ing hormone1ESRHE 2007 guide l ine. h ttp ://gu ide l ines .endometrios is.org/pa in.html ;2Verc e l l in i P, et a l . Hum Reprod Update 2003;9:387–396;3Ley land N, e t a l . J Obs tet Gy naec ol Can 2010;32:S1–S32

Medical therapy – Progestins

• Synthetic hormones with progesterone-l ike activity1,2

• Most were not developed for treatment of endometriosis

• Adverse events include: irregular bleeding and (especially with older agents) weight gain, headaches, acne and adverse lipid changes3,4

• Newer types selectively bind progesterone receptors specifically1

Minimize androgenic, estrogenic or glucocorticoid side-effects

51

1. Si truk -Ware R. Hum Reprod Update 2006;2. Sc hind ler AE et a l . Maturi tas 2003;3. Wink el CA & Sc ia l l i AR. J Womens Heal th Gend Based Med 2002;4. Verc e l l in i P et a l . Hum ReprodUpdate 2003.

Specific therapies –approved in endometriosis

e.g. gonadotropin-releasinghormone agonists, danazol and some progestins

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Gestagen applications

1. systemic - oral- injections- implants

2. local - LNG-IUS (Mirena®)

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Disadvantages of systemic progestins

- different efficacy (no appoval for many progestins)

- side effects- bleeding disorders (depend on the

endometrium effect)- depression in long term use possible- androgenic effect (skin, hair)

NETA in treatment of colorectal endometriosis: a pilot study

• 40 patients with symptomatic colorectal endometriosis• 2,5 mg NETA / 12 months• dosage increased (5 mg NETA) in cases of breakthrough bleedings• significant improvement of symptoms during treatment (pelvic pain,

dyspareunia, dyschezia)• no significant effect to gastrointestinal symptoms (constipation)

(patients with gastrointestinal symptoms related to the menstrual cycle has a greater benefit)

Ferrero et al. (2010)

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Hormonal treatment of endometriosis(state of the art)

OC - treatment of mild endometriosis

Progestins - treatment of severe endometriosis

- treatment of recurrence of endometriosis (long term treatment of endometriosis with high risk of surgery)

GnRH-analogue - severe progestin-resistant endometriosis

- IVF pretreatment in severe endometriosis

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Progestagen for pain associated withendometriosisCochrane Review (2012)

• MPA (10 mg) more effective than placebo (12 months follow up)• significant more side effects (acne, oedeme)• no evidence between dydrogesterone and placebo

• no evidence of a benefit with Depot progestin vs. other treatments (COC, GnRH-a)

• more side effects

Conclusions: Limited evidence for the most progestins

Brown et al. (2012)


• Current use

ü reduced risk

• Past use

ü an increased risk

of diagnosis of endometriosis when compared with never users

ü RR in nulliparous ♀ w / <5 years [1.8 (1.30–2.53)] and >5 years [2.3 (1.59–3.40)] of OCP use

ü RR in multiparous ♀ w / <5 years [0.4 (0.15–0.56)] and >5 years [0.4 (0.16–1.23)] of OCP use

• RR in ♀ noncontrace ptiv e OCP use [2.0 (1.72-2.51)]

(Verc e l l in i P et a l . 2011)

Comparison LNG-IUS and GnRH-analogue for treatment of chronic pelvic pain in women with endometriosis

1) both treatments effective in CPP-associated endometriosis (Petta et al. 2005; Bayoglu Tekin et al. 2011)Clinical problems:- LNG-users: higher bleeding scores (satisfaction rate lower)

- GnRH-analogue: hypoestrogenismus (side effects)2) limit evidence showing that postoperative LNG-IUS use

reduces the recurrence of painful periods in women with endometriosis (Abou-Setta et al. 2013)

Documents

Surgical Medical The “Pragmatic Approach” to treatment of … · 2019. 1. 29. · Prof. Thomas Römer, M.D. Department OB/GYN Academic Hospital University of Cologne / Germany