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Medical Management of Fibroid
1
2
Dr Sujoy Dasgupta
MBBS (Gold Medalist, Hons)
MS (OBGY- Gold Medalist) DNB (OBGY)
MRCOG (London) FIAOG
Fellow- Reproducti...
• Fibroids occur when a single
uterine smooth muscle connective
tissue cell replicates until a cluster
of cells form a mas...
• The management of symptomatic fibroids has been traditionally surgical
• No medical therapy can completely eliminate fib...
Symptomatic Uterine Fibroids
Medical Therapy Surgical Therapy Other modalities
Non Hormonal
Hormonal
Open /Laparoscopic
My...
Advantages
Uterus Preserved
Able to become
pregnant
Symptoms Usually Improve
Myomectomy
New Fibroid Growth
Symptoms May Not go
away
Need for future surgery
C section to
Deliver Babies
Major Surgery
Potential
Di...
9
Advantages
No More Periods
Patient Satisfaction:
Very High
No Need For Contraception
Fibroids Can Not
Grow Back
No Chang...
Potential Disadvantages
Hysterectom
y
Unable to become pregnant
i.e.
Complete loss of fertility
Loss of Uterus
Need For Fu...
Gn Rh Agonists
MEDICAL TREATMENT
NSAIDs
Oral Contraceptive pills
Progesterone Releasing
IUD
Progesterone
Pills
No Medical ...
OCPs
 Often used to treat menorrhagia & dysmenorrhea
 Breakthrough bleeding
 Drawback: increase the size of myoma
LNG I...
13
Progesterone
plays a vital role in promoting uterine fibroid growth
1. Human Reproduction Vol.21, No.9 pp. 2408–2416, 2...
Has stimulated interest in modulating the progesterone pathway
Thus, SPRMs* are innovative therapy in uterine
fibroid mana...
• Selective Progesterone Receptor Modulators (SPRMs) are new
class of Progesterone receptor (PR) ligands displaying tissue...
16
Ulipristal Acetate
(CDB 2914)
The only SPRM approved for the treatment
of Uterine Fibroids
Ulipristal Acetate Approval
17
16th
Dec 2011 24th
June 2013 2014
• A first-in-class, effective, well-tolerated
SPRM specifically designed for uterine
fibroids
• Reversible blockage of pro...
• Management of symptomatic uterine fibroids
• Pre-operatively to reduce the size & symptoms of fibroids
• Dosage : One ta...
20
Potent antiprogesterone action
Fibroids HPO axis Endometrium
Decreasing Bcl-2 expression & TIMP2
&
Increases TNF expres...
Reprod Sci. 2014 Sep 16.
Pharmacokinetics
Premya Study
Objective: Treatment with UPA in a Pre-operative setting
22
Multicentre, Prospective, non interventional Stud...
23
CGI-I scale at 3 months:
61% patients “Much
improved” & “Very
improved”
• Out of total only 39% patients underwent surg...
Ulipristal acetate does not disturb the surgical
planes in patients who had to undergo
myomectomy for removal of Uterine F...
Clinical benefits of Ulipristal introduced before
scheduled surgery
25
Prz Menopauzalny 2014; 13(1): 18-21
Correction of
p...
26
VENUS II study
Quality of life with Ulipristal acetate (UPA) treatment of symptomatic uterine
fibroids (UF)
CONCLUSIONS...
27
Ulipristal acetate (UPA) treatment of symptomatic uterine fibroids (UF):
VENUS II subgroup analyses by race and BMI
CON...
28
Absolute & Relative Contraindications
29
Special Warnings and Precautions
System Organ Very common Common Uncommon
Reproductive &
Breast
Amenorrhea
Endometrial
thickness
Pelvic pain, Hot
flushes, ...
Patients with
symptomatic
uterine fibroids
eligible for surgery
Age: 18 to 50 years
Fibroid related anemia
At least one fi...
33N Engl J Med. 2012 Feb 2;366(5):409-20
• 91% patients with control of uterine bleeding
• Fibroid volume reduction of ≥25...
Premenopausal
women with
symptomatic
uterine fibroids
eligible for surgery
Age: 18 to 50 years
HMB
At least one fibroid ≥3...
• Excessive bleeding was controlled significantly more rapidly in UPA than
leuprolide (p<0.001)
• Amenorrhea was induced m...
3 months 3 months
Ulipristal
10 mg
3 months 3 months
PEARL III
N=203
PEARL III extension
N=132
Ulipristal
10 mg
Ulipristal...
37
• Effectively controls bleeding & pain:78.5% Amenorrhea with first course &
90% with repeated course
• Reduces fibroid ...
•Limitations of SPRMs
•Endometrial changes unique to progesterone receptor modulators (PRM) are described and
referred to ...
39
Total volume of 3 largest fibroids
(cm3
)
Ulipristal 5
mg
Ulipristal 10
mg
Baseline 42.6 43.6
After
treatment
Course 1
...
40
56 patients
aged 29-47
yrs with
symptomatic
uterine
fibroids,
qualified for
surgical
treatment
Treatment
with
uliprista...
• Mean Hb prior to therapy was 10.1 g/dL rising to 12.6 g/dL after 12 weeks of
ulipristal treatment
• 46.4% patients opted...
Retrospective analysis of a series of 52 patients included
Among 52 patients, 21 wished to conceive upon completion of tre...
43
Fertil Steril 2014;102:1404–9
Endometrium of sufficient quality for blastocyst implantation
Median time to achieve preg...
44
NICE Recommendations (2016)
<3 cm
1. LNG-IUS
2. Tranexaemic acid/
Mefenamic Acid/ COC
3. Norethisterone Day5-25
≥3 cm
• Hb...
NICE Recommendations (2016)
<3 cm
1. LNG-IUS
2. Tranexaemic acid/
Mefenamic Acid/ COC
3. Norethisterone Day5-25
Not resolv...
Before Myomectomy
• Both GnRH or LA can be used
47
Before UAE
• GnRH agonist MUST be stopped
• UPA is safe
48
•Mifepristone
•Mifepristone has been associated with development of endometrial
changes in some reportsand its use in trea...
Fibroids?
50
Experience with UPA
51
54
55
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Medical Management of Fibroids

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Dr Dasgupta was invited to deliver a lecture on this topic in a CME

Publicada em: Saúde e medicina
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Medical Management of Fibroids

  1. 1. Medical Management of Fibroid 1
  2. 2. 2 Dr Sujoy Dasgupta MBBS (Gold Medalist, Hons) MS (OBGY- Gold Medalist) DNB (OBGY) MRCOG (London) FIAOG Fellow- Reproductive Endocrinology & Infertility (ACOG) Visiting Consultant, •Bavishi Pratiksha Fertility Institute •RSV Hospital •Iris Hospital •Behala balananda Brahmachary Hospital •AMRI Hospitals Secretary, Website Committee, Bengal Obstetric and Gynaecological Society (BOGS)- 2017-18 Managing Committee Member, BOGS- 2017-18 Member, Quiz Committee, FOGSI East Zone 2017-19 Executive Committee Member, Medical College Ex-Student’s Association •Peer-Reviewer, BMJ Case Reports, UK •15 Publications- National & International Journals •Lecture delivered- at 40 International, National, Regional Conferences •Faculty, MRCOG Course, AICC RCOG East Zone
  3. 3. • Fibroids occur when a single uterine smooth muscle connective tissue cell replicates until a cluster of cells form a mass that is distinct from the normal muscular tissues. • genetic factors (fibroids tend to run in families) • hormonal causes (fibroid tissue has more estrogen and progesterone receptors than normal uterine tissue and therefore are more sensitive to alteration of these two hormones during the menstrual cycle). 4 Causes of Fibroids
  4. 4. • The management of symptomatic fibroids has been traditionally surgical • No medical therapy can completely eliminate fibroids • However alternative pharmacological treatments have been proposed to control symptoms • Choice of appropriate therapeutic modality depends on several factors including : 1. Age & Parity 2. Child bearing expectations 3. Extent & Severity of Symptoms 4. Size, number & location of myomas 5. Proximity of menopause 6. Risk of Malignancy Current Therapies for uterine fibroids: Are they Satisfactory?
  5. 5. Symptomatic Uterine Fibroids Medical Therapy Surgical Therapy Other modalities Non Hormonal Hormonal Open /Laparoscopic Myomectomy & Hysterectomy Endometrial Ablation & Hysteroscopic Myomectomy U A E (Polyvinyl Particles) Magnetic Resonance- guided focused Ultrasound Surgery (MRgFUS) & & &
  6. 6. Advantages Uterus Preserved Able to become pregnant Symptoms Usually Improve Myomectomy
  7. 7. New Fibroid Growth Symptoms May Not go away Need for future surgery C section to Deliver Babies Major Surgery Potential Disadvantages Myomectomy
  8. 8. 9 Advantages No More Periods Patient Satisfaction: Very High No Need For Contraception Fibroids Can Not Grow Back No Change In Hormones Symptoms Go Away Hysterectomy
  9. 9. Potential Disadvantages Hysterectom y Unable to become pregnant i.e. Complete loss of fertility Loss of Uterus Need For Future Surgery For ovary and other complications Risk for Surgical Complications e.g. Adhesions & Pelvic organs injury and relaxations
  10. 10. Gn Rh Agonists MEDICAL TREATMENT NSAIDs Oral Contraceptive pills Progesterone Releasing IUD Progesterone Pills No Medical treatment completely eliminates Fibroids
  11. 11. OCPs  Often used to treat menorrhagia & dysmenorrhea  Breakthrough bleeding  Drawback: increase the size of myoma LNG IUD  Leads to more irregular bleeding  System expulsion GnRH agonists:  Monthly IM injections for 3-6 months  Effects are transient & the myoma usually return to the pre-therapy size within a few months of discontinuation*  Suppresses estradiol  Cause hypoestrinism#  67% patients report Hot flushes  Reduced BMD *Drug Des Devel Ther. 2014 Feb 20;8:285-92. #. Int J Endocrinol. 2012;2012:436174 Drawbacks of available medical therapies
  12. 12. 13 Progesterone plays a vital role in promoting uterine fibroid growth 1. Human Reproduction Vol.21, No.9 pp. 2408–2416, 2006 2. Curr Opin Obstet Gynecol 2009;21:318-24 3. Eur J Obstet Gynecol Reprod Biol 2012 Aug 14 4. n engl j med 366;5 Newer pathology as authenticated by
  13. 13. Has stimulated interest in modulating the progesterone pathway Thus, SPRMs* are innovative therapy in uterine fibroid management * Selective Progesterone Receptor Modulators N Engl J Med. 2012 Feb 2;366(5):409-20 14 Role of progesterone in promoting the growth of fibroids
  14. 14. • Selective Progesterone Receptor Modulators (SPRMs) are new class of Progesterone receptor (PR) ligands displaying tissue- selective agonist/antagonist/mixed activity on target cells 15 About SPRMs
  15. 15. 16 Ulipristal Acetate (CDB 2914) The only SPRM approved for the treatment of Uterine Fibroids
  16. 16. Ulipristal Acetate Approval 17 16th Dec 2011 24th June 2013 2014
  17. 17. • A first-in-class, effective, well-tolerated SPRM specifically designed for uterine fibroids • Reversible blockage of progesterone receptors# • It binds progesterone receptors, but not estrogen receptors • No affinity on mineralocorticoid receptors* • Action only on fibroid cells & not in normal myometrial cells *http://link.springer.com/article/10.1007/BF03262118#page-1 About Ulipristal acetate
  18. 18. • Management of symptomatic uterine fibroids • Pre-operatively to reduce the size & symptoms of fibroids • Dosage : One tablet of 5 mg OD to be started during first week of menstruation continuously for 3 months 19 Indications & Dosage
  19. 19. 20 Potent antiprogesterone action Fibroids HPO axis Endometrium Decreasing Bcl-2 expression & TIMP2 & Increases TNF expression Decreasing Bcl-2 expression & TIMP2 & Increases TNF expression Decreases fibroid size and volume1,2 Inhibits ovulation2 Shows Proapoptotic/antiproliferative action1 Shows Proapoptotic/antiproliferative action1 Induces amenorrhea3 Decreases LH & FSH levels Decreases LH & FSH levels Shows antiproliferative action3 Shows antiproliferative action3 1. Fertil Steril. 2014 Jun;101(6):1565-73.e1-18. 2. Drug Des Devel Ther. 2014 Feb 20;8:285-92 3. N Engl J Med 2012; 366:421-432 *HPO: Hypothalamic-pituitary-ovarian axis * Bcl2: B-Cell Lymphoma 2 * TIMP: Tissue Inhibitor of Metalloproteinase Ulipristal : MOA
  20. 20. Reprod Sci. 2014 Sep 16. Pharmacokinetics
  21. 21. Premya Study Objective: Treatment with UPA in a Pre-operative setting 22 Multicentre, Prospective, non interventional Study 75 Centres in 10 EU countries 1473 patients with Symptomatic Fibroids Premenopausal women & those who have been recommended surgery 5mg UPA OD for 3 months Follow up was done at 3,6,9,12 and 15M post treatment Mean age :42 yrs 25 % patients were between 30-40 yrs,12 % patients were >=50 yrs 14% patients had undergone myomectomy before Premya Study Cont..
  22. 22. 23 CGI-I scale at 3 months: 61% patients “Much improved” & “Very improved” • Out of total only 39% patients underwent surgical procedure during 12 months following treatment • 42% patients were not operated • Using UPA prior to surgery : delays or avoids surgery by lastingly improving symptoms, even after stopping treatment • One can avoid surgery prior to menopause • To avoid or delay surgery prior to pregnancy as there is a possibility of avoiding complications secondary to myomectomy(by limiting the risks of postoperative adhesions and their consequences on fertility) PTB scale at 3 months: 88% patients “greatly” & “somewhat improved” Pain assessment score Prior to treatment: 47 Post treatment: 8-15 (3-15 months period) considering that 20% patients lost to follow up all underwent surgery J Gynecol Obstet Hum Reprod 46 (2017) 249–254
  23. 23. Ulipristal acetate does not disturb the surgical planes in patients who had to undergo myomectomy for removal of Uterine Fibroids Clinical benefits of Ulipristal introduced before scheduled surgery
  24. 24. Clinical benefits of Ulipristal introduced before scheduled surgery 25 Prz Menopauzalny 2014; 13(1): 18-21 Correction of patient’s anemia Reduction of intraoperative blood loss Facilitation of myomectomy instead of hysterectomyReduction of operative time Reduces the need for blood transfusion • Even mild anaemia can lead to increased risk of morbidity & postoperative mortality • Intraoperative transfusion does not modify these risks By reducing fibroid volume & correcting anaemia UPA allows for less invasive surgery J Gynecol Obstet Hum Reprod 46 (2017) 249–254
  25. 25. 26 VENUS II study Quality of life with Ulipristal acetate (UPA) treatment of symptomatic uterine fibroids (UF) CONCLUSIONS: UPA 10 mg and 5 mg significantly improved quality of life . Significant improvement in all UFS-QoL subscales demonstrates that UPA treatment improves a woman’s ability to lead a normal life. VENUS II Study The Second US-Based Phase 3 Study of Ulipristal acetate (UPA) for the treatment of Symptomatic Uterine Fibroids (UF) CONCLUSIONS: Numerically greater responses in efficacy were observed with UPA 10 mg vs 5 mg, though the safety profiles were similar. Both UPA 10 mg and 5 mg were generally well tolerated Latest ASRM 2017 Highlights
  26. 26. 27 Ulipristal acetate (UPA) treatment of symptomatic uterine fibroids (UF): VENUS II subgroup analyses by race and BMI CONCLUSIONS: UPA 10 mg and 5 mg showed higher responses than PBO in the proportion of women achieving amenorrhea, regardless of race and BMI. Both doses of UPA also led to increased QoL, with improvements in physical and social activities compared with placebo in all subgroups evaluated. Numerically greater responses were observed with UPA 10 mg vs 5 mg.
  27. 27. 28 Absolute & Relative Contraindications
  28. 28. 29 Special Warnings and Precautions
  29. 29. System Organ Very common Common Uncommon Reproductive & Breast Amenorrhea Endometrial thickness Pelvic pain, Hot flushes, Breast tenderness & ovarian cyst Breast swelling & breast discomfort CNS Headache Dizziness ENT Nasopharyngitis Vertigo GIT Abdominal pain & Nausea Dyspepsia, Dry mouth, Constip Psychiatric Disorder Anxiety, Emotional disorder Skin Acne Alopecia, Dry skin General Disorder Hot flushes Oedema, Fatigue Renal Incontinence Musculoskeletal Pain Back pain Investigations ⇑ Blood Cholesterol ⇑ Trigly and Wt⇑ Adverse Drug Reactions
  30. 30. Patients with symptomatic uterine fibroids eligible for surgery Age: 18 to 50 years Fibroid related anemia At least one fibroid ≥3 cm in diameter & none >10 cm Once daily oral Ulipristal 5 mg + concomitant iron (80 mg) N=96 Once daily oral Ulipristal 10 mg + concomitant iron (80 mg) N=98 Placebo+ concomitant iron (80 mg) N=48 Surgery 3 & 6 month follow- up visits 3 months N Engl J Med. 2012 Feb 2;366(5):409-20 32 (1) Ulipristal Acetate Vs Placebo for Fibroid Before Surgery
  31. 31. 33N Engl J Med. 2012 Feb 2;366(5):409-20 • 91% patients with control of uterine bleeding • Fibroid volume reduction of ≥25% in 37% of pts • Time to persistent amenorrhea :Approximately 50% of patients in the 5 mg ulipristal group became amenorrhea within the first 10 days • Significant reduction in pain CONCLUSION Treatment with Ulipristal acetate effectively controls excessive bleeding due to uterine fibroids & reduces size of the fibroids
  32. 32. Premenopausal women with symptomatic uterine fibroids eligible for surgery Age: 18 to 50 years HMB At least one fibroid ≥3 cm in diameter & none >10 cm Once daily oral Ulipristal 5 mg N=97 Once daily oral Ulipristal 10 mg N=103 3.75 mg leuprolide acetate once monthly N=101 Surgery 3 & 6 month follow- up visits 3 months Treatment started within 4 days after the start of menstrual period & was continued until week 13 after which patients could go for surgery N Engl J Med 2012; 366:421-432 34 (2) Ulipristal Acetate Vs Leuprolide Acetate for Uterine Fibroids
  33. 33. • Excessive bleeding was controlled significantly more rapidly in UPA than leuprolide (p<0.001) • Amenorrhea was induced more rapidly (7 days) in UPA 5 mg than leuprolide (21 days) (p<0.001) • Sustained effect seen up to 6 months after treatment cessation • Median oestradiol levels were maintained in the mid-follicular range About 5% of patients of reproductive age experiencing heavy menstrual bleeding have an endometrial thickness of greater than 16 mm • Oral UPA was not inferior to monthly inj.of leuprolide in women with symptomatic fibroids before planned surgery & had a better side-effect profile N Engl J Med 2012; 366:421-432 35
  34. 34. 3 months 3 months Ulipristal 10 mg 3 months 3 months PEARL III N=203 PEARL III extension N=132 Ulipristal 10 mg Ulipristal 10 mg Norethisterone acetate (NETA) or placebo (10-day) (double-blind) Menses Double-blind NETA or placebo added after each course to explore any effect on histological endometrial changes & on timing & magnitude of next menstruation, off treatment Ulipristal 10 mg Enrolled pre-menopausal women (18-48 years) with at least one fibroid ≥3 cm in diameter & none >10 cm, HMB 103 Placebo & 98 NETA 68 Placebo & 64 NETA Fertil Steril. 2014 Jun;101(6):1565-73.e1-18. 36 (3) Long term treatment of Uterine Fibroids with Ulipristal Acetate
  35. 35. 37 • Effectively controls bleeding & pain:78.5% Amenorrhea with first course & 90% with repeated course • Reduces fibroid volume: 45% reduction in Fibroid volume with first course & 72% with repeated course • Symptomatic improvement & fibroid volume shrinkage can be largely maintained during the off-treatment periods • Restore QoL • Ovarian ultrasound – no significant change • Change in hematology – no significant change • Serum levels of E2 – no significant change • Headache (16.3%) and nasopharyngitis (6.7%) were the most common adverse events associated with UPA, but fewer were experienced after the first course of treatment • Changes in endometrial thickness • Transient increase in endometrial thickness in <10% of pts • No case of endometrial hyperplasia Fertil Steril. 2014 Jun;101(6):1565-73.e1-18. Effect & Outcome due to long term usage
  36. 36. •Limitations of SPRMs •Endometrial changes unique to progesterone receptor modulators (PRM) are described and referred to as PRM-associated endometrial changes (PAEC). It is therefore not always possible to identity patients taking PRM on histology alone and it is therefore important to inform the pathologist when sending a hysterectomy or an endometrial biopsy specimen. •PAEC were evaluated in women taking short courses of SPRMs (asoprisnil, ulipristal acetate and telapristone acetate) and no hyperplasia, premalignant or malignant lesions were identified in these specimens. •Due to the theoretical concerns, however, the use of ulipristal acetate is currently limited to 3 months. •Although nonphysiological changes were seen frequently in the ulipristal group, these changes had resolved 6 months after treatment demonstrating reversibility of these changes and safety in this respect of their short-term use. •At present, there do not appear to be any significant side effects of ulipristal acetate but it is recommended that they be used with caution in those with severe asthma uncontrolled by oral glucocorticoids and in those with hepatic dysfunction, hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. 38
  37. 37. 39 Total volume of 3 largest fibroids (cm3 ) Ulipristal 5 mg Ulipristal 10 mg Baseline 42.6 43.6 After treatment Course 1 -38 -58.1 After treatment Course 1 -54.1 -58.0 Fertil Steril. 2014 Dec 30. Secondary end-points: Surgery performed in only 3 & 5 patients receiving 5 & 10 mg of UPA
  38. 38. 40 56 patients aged 29-47 yrs with symptomatic uterine fibroids, qualified for surgical treatment Treatment with ulipristal at a dose of 1x5 mg starting on the first day of menstruation Duration: 3 months 26 patients did not go for surgery 27 patients went for surgery 46.4% 9 patients Follow-up for 9 months End-point analysis: 1.Volume of the dominant fibroid 2.Cessation of menstrual bleeding 3.Mean Hb%levels 4.Recurrence rate Prz Menopauzalny 2014; 13(1): 18-21 (4) The effect of Ulipristal Acetate treatment on symptomatic uterine multiple fibroids within 12 months follow up
  39. 39. • Mean Hb prior to therapy was 10.1 g/dL rising to 12.6 g/dL after 12 weeks of ulipristal treatment • 46.4% patients opted against scheduled surgery due to the fact that all the clinical symptoms of fibroids had disappeared • No recurrence of fibroid growth • In 1/3rd of followed-up patients, the effect of 3 month ulipristal therapy persisted for the next 9 months 41 Prz Menopauzalny 2014; 13(1): 18-21 Results
  40. 40. Retrospective analysis of a series of 52 patients included Among 52 patients, 21 wished to conceive upon completion of treatment Among the 21 who attempted to get pregnant, 15 succeeded (71%) totaling 18 pregnancies Among the 18 pregnancies, 12 resulted in birth of 13 healthy babies & 6 ended in miscarriage No regrowth of fibroids observed during pregnancy This confirms the long-term effect after ulipristal therapy Fertil Steril 2014;102:1404–942 (5) First series of 18 pregnancies after UPA treatment for uterine fibroids
  41. 41. 43 Fertil Steril 2014;102:1404–9 Endometrium of sufficient quality for blastocyst implantation Median time to achieve pregnancy after the end of treatment was 10 months No maternal complications related to myoma. All babies were healthy No regrowth of fibroids during pregnancy
  42. 42. 44
  43. 43. NICE Recommendations (2016) <3 cm 1. LNG-IUS 2. Tranexaemic acid/ Mefenamic Acid/ COC 3. Norethisterone Day5-25 ≥3 cm • Hb <10.2 g/dl- UPA up to 4 courses (total 20 months) • Hb ≥ 10.2 g/dl- Consider UPA (Total 20 months) 45
  44. 44. NICE Recommendations (2016) <3 cm 1. LNG-IUS 2. Tranexaemic acid/ Mefenamic Acid/ COC 3. Norethisterone Day5-25 Not resolved Endometrial Ablation ≥3 cm • Hb <10.2 g/dl- UPA up to 4 courses (total 20 months) • Hb ≥ 10.2 g/dl- Consider UPA (Total 20 months) Not resolved Myomectomy/ UAE GnRH Ago→ Hysterectomy 46
  45. 45. Before Myomectomy • Both GnRH or LA can be used 47
  46. 46. Before UAE • GnRH agonist MUST be stopped • UPA is safe 48
  47. 47. •Mifepristone •Mifepristone has been associated with development of endometrial changes in some reportsand its use in treatment of fibroids is currently restricted to research settings. •Ulipristal acetate •It induces apoptosis in uterine fibroid cells and inhibits proliferation of cells. • There was no difference in the control of menstrual bleeding between UA and leuprolide. However, UA was tolerated better and controlled bleeding more rapidly than leuprolide. 49
  48. 48. Fibroids? 50
  49. 49. Experience with UPA 51
  50. 50. 54
  51. 51. 55

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