1. Brigitte Frey Tirri, Switzerland
The Emergency contraception Ulipristal acetat and the interaction with hormonal contraception
Brigitte Frey Tirri, Switzerland
ESC Masterclass
Antalya, Turkey
18. May 2017
EllaOne_Interaction with hormonal contraception – Brigitte Frey

2. Conflict of interest ellaOne® Advisory board of HRA-Pharma
Speaker for Gedeon Richter Budapest about emergency contraception
(LNG-EC)
EllaOne_Interaction with hormonal contraception – Brigitte Frey

3. Overview of available emergency contraceptives (EC)
Inhaltsverzeichnis
Overview of available emergency contraceptives (EC)
mecanism of action of Ulipristalacetat (UPA) EllaOne®
Interaction of UPA with hormonal contraceptives
EllaOne_Interaction with hormonal contraception – Brigitte Frey

4. Overview of available emergency contraceptives (EC)
Mechanical :
Cupper- IUD (Cu-IUD)
Hormonal EC:
Levonorgestrel 1.5mg
Combined EC (estrogen and progestin, Yuzpe-regimen)
Antiprogestins : Ulipristalacetat 30mg (EllaOne®) and mifepriston
EllaOne_Interaction with hormonal contraception – Brigitte Frey

5. Mechanism of action of UPA
Second generation progesteron receptor modulator
Antiprogestin
It mainly delays ovulation by suppressing LH (luteinizing hormone)
This effect occurs also after the LH surge and even in some
cases after the LH peak+, but not after ovulation*
+ BracheV et al, Hum Reprod- 2010;25:
* LiHWR et all, Hum Reprod. 2016;31:
EllaOne_Interaction with hormonal contraception – Brigitte Frey

6. Mechanism of action of EC
Gemzell K., Meng Ch., Int.JWH2010

7. Mechanism of action of UPA
Delay of ovulation of 5 days, time sperms survive in the body
Caveat: unprotected sexual intercourse (UPSI) after the intake of a
hormonal EC, can lead to an unwanted pregnancy, if the woman doesn’t take
another EC.
EllaOne_Interaction with hormonal contraception – Brigitte Frey

8. Efficacy of UPA Comparison of UPA, LNG and Yuzpe regimen
Numbers of cycles without ovulation in 5 days time after taking the EC at the time the leading follicule has a diameter of 18 mm.
Gemzell K., Meng Ch., Int.JWH2010
EllaOne_Interaction with hormonal contraception – Brigitte Frey

9. Efficacy of UPA after Quickstart with Desogestrel (DSG)
study design:
pharmacodynamic, randomised, single-blind, incomplete crossover study
49 patients included, y, BMI < 30 kg/m2
Contraception with condoms, or sexualy inactive during study, or after tubal sterilisation
Regular ultrasound, leading follicle ≥ 14 mm < 16 mm, then randomization occured:
3 arms:
30 mg UPA, DSG 75 mcg, the day after UPA for 20 days
30 mg UPA , followed by DSG- placebo the day after UPA for 20 days
30 mg UPA-placebo, followed by DSG the day after UPA for 20 days
aim: - influence on efficacy of UPA, (ovarian quiescence and cervical mucus)
EllaOne_Interaction with hormonal contraception – Brigitte Frey

10. Efficacy of UPA after quickstarting DSG
n= 29 cycles
n= 29 cycles
n= 29 cycles
EllaOne_Interaction with hormonal contraception – Brigitte Frey

11. Results
DSG seams to reactivate the progesterone signaling that leads to follicule rupture, thereby impacting the effectiveness of UPA as EC.
UPA on the other hand has almost no influence on the contraceptive efficacy of DSG.
No sifgnificant differences were found in time to ovarian quiescence or cervical mucus penetrability
EllaOne_Interaction with hormonal contraception – Brigitte Frey

12. Efficacy of UPA after quickstarting DSG
Questions arising out of this study
Can these data be transferred on UPA and COC?
Can these data be transferred on UPA and other hormonal methods of contraception?
Can these data be transferred to other methods of EC?
Do we have to wait 5 days after UPA or 5 days after UPSI?
What is more dangerous, risking a pregnancy while waiting until starting with a hormonal contraception, or reduced efficacy of UPA?
30% of all women have SI in the same cycle
Can these data from a pharmacodynamic study be transferred in clinical practice?, meaning will we have more pregnancies after quickstarting a HC?
Is the pill intake before taking UPA influencing the efficacy of UPA?
EllaOne_Interaction with hormonal contraception – Brigitte Frey

13. EllaOne_Interaction with hormonal contraception – Brigitte Frey 18. 05

14. Why using a chemical contraceptive for 14 days after UPA
Cameron S.T. et al, hum.reprod. 2015
UPA is not influencing the capability of the COC, to achieve ovarian
quiescence
- The effect occured in most women after 7 days in all after 14 days
- This study design doesn’t allow to say, if the effect of UPA is reduced.
EllaOne_Interaction with hormonal contraception – Brigitte Frey

15. Recommendations in different countries
EMA (european Medicines Agency), Swissmedic
Continuation / or quickstarting of hormonal contraception after UPA intake
Additional use of condoms for 14 days or until next menstruation
advantage:
Higher Compliance of the patient
disadvantage:
Risk of reducing the efficacy of UPA  higher pregnancy risk
FDA / ICEC/ AJCOG/FSRH/Frankreich /working group of EC
5 (7) days of pause with hormonal contraception or quickstarting
Additional use of condoms for (7) 14 days or until next menstruation
advantage:
No reduced efficacy of UPA
disadvantage:
Risk to forget to start with the pill
EllaOne_Interaction with hormonal contraception – Brigitte Frey

16. Take home messages
meta-analysis of data from two large RCTs suggests that UPA is significantly more effective y than LNG at preventing prenancy when taken from h after UPSI. (EL 1+)
wait 5 days after UPA before quickstarting a hormonal contraception
wait 5 days after UPA before continuing a ongoing hormonal contraception, no direct clinical data for this but theoretical possible
use in both above mentioned situations condoms until next menstruation or at least 14 days.
1 FSRH Guideline emergency contraception dec.2016
EllaOne_Interaction with hormonal contraception – Brigitte Frey

17. Thank you for your attention
EllaOne_Interaction with hormonal contraception – Brigitte Frey

19. EllaOne_Interaction with hormonal contraception – Brigitte Frey 18. 05