Selective progesterone receptor modulators (SPRMs) Stimulates growth : Up regulating epidermal growth factor (EGF) Down regulating tumour necrosis factor-alpha expression Inhibits growth : Downregulating insulin-like growth factor-1 (IGF-1) expression NO EFFECT ON ESTRADIOL LEVELS Mifepristone : 5 or 10 mg per day for 1 year Ulipristal acetate: 5-10mg/day for 13 weeks Pro apoptotic and anti-proliferative effects on fibroid cells

1. Ulipristal Acetate in
Treatment of Fibroids
By Indraneel Jadhav
Secondary DNB Resident

2. Medical management
 Pharmaceutical treatment should be considered in
 Fibroids less than 3 cm in diameter
 Causing no distortion of the uterine cavity
NICE Guideline January 2007

3. NICE Survellience for Uterine Fibroids
30 March 2015
 Hysterectomy vs levonorgestrel inter-uterine device
 Hysterectomy was the most cost-effective treatment
 Progesterone receptor modulators for the treatment
of uterine fibroids
 Progesterone receptor modulators (ulipristal acetate or
mifepristone) were also identified as a potential new
treatment by members of the Guideline Development
group (GDG)
 Pre-surgical medical treatment of uterine fibroids
(progesterone receptor modulaters and
gonadotrophin releasing hormone analogues)
 The new evidence may favour ulipristal acetate over
gonadotrophin releasing hormone analogue for some, but
not all outcomes as a pre-treatment for uterine fibroids
before myomectomy

4. SOGC CLINICAL PRACTICE
GUIDELINE
No. 318, February 2015 (Replaces, No. 128, May 2003)
Acute uterine bleeding associated with uterine
fibroids: conservative management with
Estrogens
Selective progesterone receptor modulators
Antifibrinolytics
Foley catheter tamponade
Operative hysteroscopic intervention
Intervention by uterine artery embolization

5. Selective progesterone receptor
modulators (SPRMs)
 Stimulates growth :
 Up regulating epidermal growth factor (EGF)
 Down regulating tumour necrosis factor-alpha
expression
 Inhibits growth :
 Downregulating insulin-like growth factor-1 (IGF-1)
expression
 NO EFFECT ON ESTRADIOL LEVELS
 Mifepristone : 5 or 10 mg per day for 1 year
 Ulipristal acetate: 5-10mg/day for 13 weeks
 Pro apoptotic and anti-proliferative effects on fibroid cells

6. Selective progesterone receptor
modulators (SPRMs)

7. Ulipristal accetate - Efficacy
Menstrual Bleeding:
Median times of amenorrhea - < 6 days
Resumed after course - < 28 days
PBAC – reduced by < 200 single course
Fibroid volume :
After course 1-38 %
After course 1-58 %
Pain and Quality of life:
Median visual analogue scale – decrease from 43 to 6
Off treatment period – marked improvement

8. Ulipristal accetate - Efficacy
Surgical pre treatment:
Lower diameter and volume of largest myoma
Higher Hb and Hct levels
Shorter duration of surgery with less intra-op
blood loss
Management of fibroid related Acute AUB:
Well tolerated, effective with minimal side
effects
No risk of thromboembolism

9. Ulipristal accetate – safety and side effect
Minor effects (< 10 %) :
Headache ,breast tenderness and hot flushes
Laboratory Parameters:
Increase LDL and HDL
Rarely increase ALT and GGT
Endometrial Safety:
Longer than 3 months:PRM-associated endometrial
changes (PAEC) :Cystic glandular dilation
Hysteroscopic pattern:
Hypotrophic/Secretory Endometrium
Isolated cysts
Chicken wire appearance

10. Ulipristal accetate – PEARL Studies
 Ulipristal acetate may be a proven alternative option to
surgery in patients with associated fibroids and menorrhagia
 Higher dose of 10mg/day is not significantly superior to
licensed dose of 5mg/day
Efficacy of ulipristal in women with fibroids
Trial Total
number
of
patients
Duration of treatment Proportion of patients with amenorrhea
after treatment
5 mg 10 mg Placebo GnRH
PEARL I 242 13 weeks 73% 82% 6% –
PEARL II 307 13 weeks 75% 89% – 80%
PEARL III 209 Four 12–week courses – 90% – –
PEARL IV 451 Four 12–week courses 63% 73% – –

11. Ulipristal Acetate V/S Levonorgestrel-
releasing intrauterine system (LNG-IUS)
Advantages of ulipristal acetate:
No breakthrough Bleeding
Expulsion of LNG-IUD are present
Effect on fibroid volume is certain
Could be used in sub mucosal fibroids
Can be used even if Cavity is distorted

12. Ulipristal Acetate V/S Gonadotrophin-
releasing hormone analogues
Advantages of ulipristal:
No hypo estrogenic state seen, hence
incidence of hot flushes, loss of bone mineral
density very minimal
No requirement of ‘Add-back' therapy
No Rapid rebound growth on cessation
No loss of surgical planes if used pre-
operatively

13. Ulipristal Acetate V/S Selective estrogen
receptor modulators (SERMs)
 Hypothesis: Any molecule that blocks estrogen activity
has potential therapeautic effect on fibroid
 Raloxifene : Shrinkage of uterine fibroids in
postmenopausal women
 Daily 60 mg doses of raloxifene over a 2-year
period exhibited no change in leiomyoma size
(Fertil Steril. 2007 Dec;88(6):1637-44)

14. THANK
THANK
YOU
YOU