Control

of endometriosis-associated pain
with etonogestrel-releasing contraceptive
implant
and 52-mg levonorgestrel-releasing
intrauterine system: randomized clinical
trial
Chanasorn Plodkratoke
Jetsadaporn Phansamrong
 By Who?

qNelsilene Carvalho M.D., Ph.D.

qDeborah Margatho M.D.
qKleber Cursino M.D., Ph.D.
qCristina L. Benetti-Pinto M.D., Ph.D.
qLuis Bahamondes M.D., Ph.D.

Oversight Where ?

qDepartment of Obstetrics and Gynecology,

University of Campinas Faculty of Medical
Sciences, Campinas, São Paolo, Brazil

When ?

qPublished on November 2018

IMPACT FACTOR =3.481
Profile • Nelsilene Carvalho, M.D., Ph.D.
• University of Campinas, Faculty of Medical Sciences department
• Top journals :
• International Journal of Gynecology & Obstetrics
• Journal of Obstetrics and Gynaecology Research
• Publication & Presentation
• A randomized controlled pilot study of ulipristal acetate for
abnormal bleeding among women using the 52-mg
levonorgestrel intrauterine system (Nov 2019)
• Relationship between user satisfaction with the
levonorgestrel-releasing intrauterine system and bleeding
patterns: Satisfaction, bleeding, and LNG-IUS (Aug 2017)
Background

• Pelvic pain is a major concern of women affected by endometriosis

because it can be severe and exert a negative impact on health-
related quality of life.
• To assess the efficacy of an etonogestrel (ENG)-releasing
contraceptive implant or the 52-mg levonorgestrel-releasing
intrauterine system (LNG-IUS) in the control of endometriosis-
associated pelvic pain.
 Participants
Inclusion criteria
•Clinically healthy
•Not pregnant
•Aged ≥ 18 and ≤ 45 years
•Able to keep a menstrual diary
•Willing to return to the clinic for follow-up visits
•Willing to be randomized to the use of an ENG implant or an LNG-IUS
 Participants
Exclusion criteria
•Undergone surgical or hormonal treatments for endometriosis
within 2 months
•None of the women wished to conceive within the next 12
months
•Exclusion criteria for use of the ENG implant and for the LNG-IUS
were those established by WHO
Method

Study Design :
Noninferiority randomized clinical trial
Population :
One hundred three women, with endometriosis-
associated chronic pelvic pain, dysmenorrhea, or both for
more than 6 months.
Methods

• Interventions :
• The ENG implant or the LNG-IUS were inserted within the first
5 days of the menstrual cycle.
• Outcome
• Daily scores of noncyclic pelvic pain and dysmenorrhea
• Health-related quality of life
• Bleeding patterns
Methods

• Women were randomized (1:1) to receive :

• ENG-releasing contraceptive implant OR the 52-mg 20-ug/d
LNG-IUS.
• Randomization :
• Computerized Randomization
Methods

• Outcomes
• Primary Outcome
• Pain score diary based on the visual analogue scale (VAS)
• Secondary Outcome
• Changing in HRQoL using the Endometriosis Health Profile-30 (EHP-30)
questionnaire
• Bleeding Pattern were assessed from a menstrual calendar
Statistical analysis
ØDescriptive statistics
•Continuous variable
§Mean±SD
•Categorical variable
§Frequency
§Percentage
Statistical analysis
ØInterferential statistics
•Parameter estimation
§95% Confidence Interval
•Hypothesis testing
§P-value
§SAS/STAT software program, version 9.4 (SAS Institute)
Result

• Both contraceptives improved significantly the mean visual

analogue scale endometriosis-associated pelvic pain and
dysmenorrhea
• no significant differences between ENG implant and LNG-
IUS users.
• Noncyclic pain (p= 0.241)
• Dysmenorrhea (p=0.431)
 • Secondary Outcome
• Health-related quality of life improved significantly in
Result all domains.
• no difference between both treatment groups
Result

• Secondary Outcome
• Bleeding patterns at 180
days of follow-up :
• ENG Implant
• amenorrhea and
infrequent bleeding
• LNG-IUS
• infrequent bleeding
and spotting
 Result

VAS noncyclic pelvic pain scores

baseline 180 treatment days
ENG implant 7.6 +/- 1.7 (95% CI 7.1, 8.0) 2.0 +/- 2.4 (95% CI 1.2, 2.7)
LNG-IUS 7.4 +/-1.7 (95% CI 6.9, 7.9) 1.9 +/- 1.7 (95% CI 1.3, 2.4)

P<.0001 for both groups

VAS dysmenorrhea scores
baseline
ENG implant 7.5 +/- 1.7 (95% CI 6.9, 8.1)
LNG-IUS 7.3 +/-1.7 (95% CI 6.9, 7.9)
P<.0001 for both groups.
180 treatment days
2.2 +/-3.2 (95% CI 1.1, 3.2),
1.9 +/- 2.2 (95% CI 1.2, 2.7)
Results
• At 180 days, VAS treatment noncyclic pain and dysmenorrhea
profiles
• did not significantly differ (P=.241 and .431) comparing ENG implant and
LNG-IUS users
• Noncyclic pelvic pain scores decreased significantly
• P<.0001 for both groups
• Dysmenorrhea scores decreased significantly
• P<.0001 for both groups
 Results

•The HRQoL evaluation showed significant improvement

both treatment groups
§no significant differences both groups
 Results
• ENG implant
• reductions of noncyclic pelvic pain at 30 days after device placement
• reductions of VAS score for dysmenorrhea at 30 days after device placement
• bleeding patterns
At 90 days
§ Infrequent bleeding (30.0%)
§ Spotting (22.1%)
At 180 days
§ Amenorrhea (28.8%)
§ Infrequent bleeding (24.4%)
 Results
• LNG-IUS
• reductions of noncyclic pelvic pain at 60 days after device placement
• reductions of VAS score for dysmenorrhea at 60 days after device placement
• Bleeding patterns
At 90 days
§ spotting (36.1%)
§ prolonged bleeding (21.6%)
At 180 days
§ infrequent bleeding (30.0%)
§ spotting (22.1%)
 Results
•After 60 days after placement of both devices VAS noncyclic
pelvic pain and dysmenorrhea scores changes did not differ
significantly
Discussion

• Previous Literature
• A Study has evaluated the long-term effectiveness of the LNG-IUS
in patients with endometriosis-associated pelvic pain.
• LNG-IUS for up to 30 months after insertion following surgical
excision of endometriotic lesions.
• *Significant decrease of the recurrence rate of dysmenorrhea (P=0.019)
• *Significant reduction in the mean dysmenorrhea
*When compared to non-users ü
Discussion

• Our findings indicated that the ENG implant is not inferior to

the 52-mg LNG-IUS
• Both devices equally effective treatments for the control of :
ü noncyclic pelvic pain
üdysmenorrhea
ü improvement of HRQoL during the first 6 months.
Discussion

• ENG implant potentially represents a safe, new, effective,

and convenient alternative treatment for :
üLNG-IUS fails owing to cervical stenosis.
üwho refuse to use any intrauterine device.
Discussion

• Main Strengths
• RCT design
• Limitation
• 10% loss to follow-up
• short duration of follow-up
• lack of blinding
• the lack of a control
 Conclusion
•In this noninferiority study both contraceptives improved
significantly pelvic pain, dysmenorrhea, and health-related
quality of life in endometriosis.