Endometriosis, Leiomyomata and related disorders

1
Endometriosis, Leiomyomata and related
disorders

• Sanjay K. Agarwal, MD
• Associate Professor of Reproductive Medicine,
  UCSD
• San Diego, CA

2
EndometriosisDefinition

• Presence of endometrial tissue outside
• the uterine cavity

3
Common appearance of endometriosis
4
Etiology Theories

• Sampson Retrograde Menstruation
• Hematologic Spread
• Lymphatic Spread
• Coelomic Metaplasia
• Genetic Factors
• Immune Factors
• Combination of the Above
• No Single Theory Explains All Cases of
  Endometriosis

5
Age at Diagnosis
gt 45
lt 19
3
36 45
6
15
19 25
24
26 35
52
6
Prevalence
7
Common endometriosis related problems

• Dysmenorrhea, Chronic Pelvic Pain
• Infertility
• Deep Dyspareunia
• Pelvic Mass (Endometrioma)
• Other Tenesmus, Hematuria, Hemoptysis

8
In the USA, endometriosis is the leading
indication for hysterectomies in women aged 30-34
years.CDC data for 1980 - 1993
9
Diagnosis

• Laparoscopy
• Laparotomy
• Inconclusive CA-125, Pelvic Exam, History,
  Imaging Studies, empiric medical therapy
• Biopsy Preferable Over Visual Inspection

10
Classification / Staging

• Several Proposed Schemes
• Revised AFS System Most Often Used
• Ranges from Stage I (Minimal) to Stage IV
  (Severe)
• Staging Involves Location and Depth of Disease,
  Extent of Adhesions

11
(No Transcript)
12
Endometriosis can have a variety of appearances

• Brown
• Black
• Clear
• Red
• Chocolate cyst on ovary

13
Common appearance of endometriosis
14
76 Painful
Demco L. J Am Assoc Gynecol Laparosc.
19985241-245.
15
Non-human primates suffer from endometriosis too!
16
(No Transcript)
17
(No Transcript)
18
(No Transcript)
19
Medical therapy estrogen suppression for the
control of pain

• NSAIDs
• OCPs (Continuous)
• Progestins
• Danazol
• GnRH-a
• GnRH-a Add-Back Therapy
• Misc Opoids, TCAs, SSRIs

20
Inflammation in Endometriosis
ENDOMETRIOSIS
COX-2
PGH2
PGE2
Arachadonic Acid
PGG2


17b-HSD 2
Aromatase
Estradiol
Androgens
Estrone
17b-HSD 1
Estradiol
Estrone
21
Oral Contraceptives in the Treatment of
Endometriosis

• Commonly used
• Usually tried after analgesics including NSAIDs
• Produce a state of pseudopregnancy, resulting in
  decidualization and atrophy of endometrial
  tissues
• Continuous versus cyclic?
• Are ones with androgenic progestins better than
  those without?

22
Common Side Effects of OCs

• Common side effects include
• Breakthrough bleeding
• Weight gain
• Breast tenderness
• Bloating
• Nausea
• Side effects can limit use

Canavan TP, Radosh L. Postgrad Med
2000107213216, 222224.
23
Danazol
Danazol is an isoxazole derivative of the
synthetic steroid 17alpha-ethinyl testosterone
24
Danazol in the Treatment of Endometriosis

• Creates an environment that is
• Anovulatory
• Hyperandrogenic
• Hypoestrogenic

25
Adverse Reactions to Danazol
26
GnRH-a

• Initially Stimulate FSH / LH Release
• Down-Regulates GnRH Receptors leading to
  Pseudomenopause
• Expensive
• Use Limited by Hypoestrogenic Effects on bone

27
GnRH Agonist TherapyCommon Side Effects

• Reversible bone mineral density loss
• Vasomotor symptoms
• Vaginal dryness
• Mood alteration
• Diminished libido

28
Strategies to overcomeGnRHa induced side effects

• Add-Back
• Rationale GnRHa over suppress HPO axis.
  Replacement of sex steroids can maintain efficacy
  whilst reducing side effects.
• Low Dose GnRHa
• Rationale GnRHa vary in their suppression of the
  HPO. Use of agents/protocols that produce optimal
  suppression of HPO allow for maintenance of
  efficacy whilst reducing side effects.

29
Add-Back Therapies

• Estrogens progestins
• Progestins
• Progestins bisphosphonate
• Tibolone
• Others

30
The use of variable suppression of the HPO to
maintain efficacy with reduced side effects

• Agarwal SK, et al. Efficacy and safety of
  intranasal nafarelin compared with intramuscular
  leuprolide depot for the treatment of
  endometriosis. Changes in bone mineral density
  and vasomotor symptoms. J Reprod Med, 1997 42
  413-423
• Barbieri, RL. Hormone treatment of endometriosis
  The estrogen threshold hypothesis. Am J Obstet
  Gynecol 1992 166740-5

31
(No Transcript)
32
Treatment of endometriosis with a decreased dose
of GnRH agonist- Pain symptoms -
8
7
Symptom score/12
P 0.05
Week
Tahara M, et al. Fertil Steril 4/00
33
Treatment of endometriosis with a decreased dose
of GnRH agonist- Hot flashes -
6
6
5
women with hot flashes
3
2
2
0
0


P0.05
Week
Tahara M, et al. Fertil Steril 4/00
34
Treatment of endometriosis with a decreased dose
of GnRH agonist- Bone loss -
8
Change in BMD after 24 weeks treatment
7
P 0.05
Tahara M, et al. Fertil Steril 4/00
35
(No Transcript)
36
(No Transcript)
37
Surgical Treatment of endometriosis related
pelvic pain and infertility

• PAIN
• Excision / Fulguration
• Lysis of Adhesions, Cul-de-sac Reconstruction
• Resection of Endometrioma
• Uterosacral Nerve Ablation?
• Appendectomy
• Hysterectomy /- BSO
• INFERTILITY
• Conservative surgery improves fertility in those
  with severe endometriosis and may improve
  fertility of those with minimal endometriosis.

38
Endometriosis Summary

• Endometriosis is a common, chronic disease
• Typical symptoms include pain and/or infertility
• Conservative surgery is cytoreductive not
  curative
• Better medical therapies are needed
• GnRH antagonists, ERb ligands, Vaginal ring
  releasing danazol, aromatase inhibitors, COX -2
  inhibitors, SPRMs,..

39
ADENOMYOSIS
40
Endometrial tissue within myometrium- often
leads to an enlarged, tender uterus
41
(No Transcript)
42
Associated problems

• Dysmenorrhea and infertility.

Management

• Analgesics, oral contraceptives, GnRH-a,
  hysterectomy (often leading to diagnosis)

43
LeiomyomataMyomasFibroids

• - Benign, smooth muscle tumors of the uterus -

44
LeiomyomataEpidemiology Etiology

• lt0.5 become malignant leiomyosarcomas
• Run in families
• More common in African American
• Initiation probably related to rapid and
  uncontrolled division of myometrial cell

45
Nomenclature
46
(No Transcript)
47
(No Transcript)
48
(No Transcript)
49
Histology
50
Consequences

• Majority are asymptomatic
• Menorrhagia - anemia
• Infertility miscarriage
• Pregnancy complications
• Pain
• Degeneration of fibroids
• Parasitic fibroids

51
Treatment of Leiomyomata

• No treatment
• Symptomatic Analgesics, oral contraceptives
• Medical shrinkage - GnRHa
• Radiological Uterine artery embolization
• Conservative surgery - Myomectomy
• Radical Surgery - Hysterectomy

52
Similarities betweenendometriosis, adenomyosis
and leiomyomata

• Endometriosis, adenomyosis and leiomyomata are
  estrogen dependant disorders related to the
  uterus.
• Gonadal suppression with GnRH agonists is
  temporarily helpful in each of these. Disorder
  regresses once therapy is stopped.
• They tend to improve after menopause