Endometriosis can have a variety of appearances

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Endometriosis can have a variety of appearances

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

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Common appearance of endometriosis
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76 Painful
Demco L. J Am Assoc Gynecol Laparosc.
19985241-245.
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Non-human primates suffer from endometriosis too!
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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

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


17b-HSD 2
Aromatase
Estradiol
Androgens
Estrone
17b-HSD 1
Estradiol
Estrone
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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?

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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.
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Danazol
Danazol is an isoxazole derivative of the
synthetic steroid 17alpha-ethinyl testosterone
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Danazol in the Treatment of Endometriosis

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

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Adverse Reactions to Danazol
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GnRH-a

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

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GnRH Agonist TherapyCommon Side Effects

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

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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.

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Add-Back Therapies

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

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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

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Treatment of endometriosis with a decreased dose
of GnRH agonist- Pain symptoms -
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Symptom score/12
P 0.05
Week
Tahara M, et al. Fertil Steril 4/00
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Treatment of endometriosis with a decreased dose
of GnRH agonist- Hot flashes -
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women with hot flashes
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P0.05
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Tahara M, et al. Fertil Steril 4/00
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Treatment of endometriosis with a decreased dose
of GnRH agonist- Bone loss -
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Change in BMD after 24 weeks treatment
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P 0.05
Tahara M, et al. Fertil Steril 4/00
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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.

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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,..

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Endometrial tissue within myometrium- often
leads to an enlarged, tender uterus
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Associated problems

• Dysmenorrhea and infertility.

Management

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

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LeiomyomataMyomasFibroids

• - Benign, smooth muscle tumors of the uterus -

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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

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Nomenclature
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Histology
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Consequences

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

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Treatment of Leiomyomata

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

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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