HYPOTHALAMIC-PITUITARY-OVARIAN AXIS

Endometriosis
Endometriosis is a common benign
gynecologic disorder defined as the presence
of endometrial glands and stroma outside of
the normal location.

Endometriosis is a hormonally dependent disease

Endometrial tissue located within the myometrium is

termed adenomyosis.
 Pathogenesis (several theories)

1- “The implantation theory”

Proposes that endometrial tissue desquamated during
menstruation passes through the fallopian tubes, where it
gains access to and implants on pelvic structures.
Retrograde Menstruation
The development of endometriosis depends:
The quantity of endometrial tissue reaching the peritoneal
cavity.
The capacity of a woman's innate immune system to remove
the refluxed menstrual debris.
Anatomic alternations of the pelvis that increase tubal reflux of menstrual
endometrium increase a woman's chance of developing endometriosis

“tract obstruction”
Pathogenesis (several theories)

2- “The direct transplantation theory”

Endometriosis that develops in episiotomy, cesarean section,
and other scars following surgery.

3- “Lymphatic or Vascular Spread”

Endometriosis in locations outside the pelvis likely develops
from dissemination of endometrial cells or tissue through
lymphatic channels or blood vessels
Pathogenesis (several theories)

4- The coelomic metaplasia theory: proposes that the

coelomic (peritoneal) cavity contains undifferentiated cells or
cells capable of differentiating into endometrial tissue.

This theory is based on embryologic studies demonstrating

that all pelvic organs, including the endometrium, are derived
from the cells lining the coelomic cavity.
Pathogenesis (several theories)

5.”Induction Theory”
The induction theory proposes that some hormonal or biologic
factor(s) may induce the differentiation of undifferentiated
cells into endometrial tissue.
 Epidemiology
The true prevalence of endometriosis in the general population
is unknown
approximately 1% of women undergoing major surgery for all
gynecologic indications
•6% to 43% of women undergoing sterilization
•12% to 32% when laparoscopy is performed to determine the
cause of pelvic pain in reproductive-age women
•21% to 48% of women undergoing laparoscopy for infertility

•Endometriosis is found in 50% of teenagers undergoing

laparoscopy for evaluation of chronic pelvic pain or
dysmenorrhea.
 Epidemiology
The age at time of diagnosis is commonly 25 to 35 years,
and endometriosis rarely is diagnosed in postmenopausal
women

•Many believe that endometriosis is more common in women

of upper economic classes because they delay pregnancy

•Evidence indicates that blacks have a prevalence of

endometriosis similar to that in whites when controlled for
socioeconomic status
 Anatomic Sites of Endometriosis
Endometriosis may develop anywhere within the pelvis and on other
extrapelvic peritoneal surfaces.

Pelvis: (Most commonly) Less commonly

Vagina
The ovary. Cervix
Anterior and posterior cul-de-sac Rectovaginal septum
Posterior broad ligaments
Uterosacral ligaments. Uncommon locations.(rarely)
Inguinal canal
Uterus (adenomiosis)
Abdominal or perineal scar
Fallopian tubes
Pleura
Sigmoid colon
Ureters.
Round ligament.
Urinary bladder.
Pelvic peritoneum.
Kidney
Lung
Liver
Diaphragm
 Anatomic Sites of Endometriosis
Rare sites of endometriosis may present with atypical
cyclic symptom.For example:
 Women with urinary tract endometriosis may describe cyclic
irritative voiding symptoms and hematuria.

 Those with rectosigmoid involvement may note cyclic rectal

bleeding.

Those with pleural lesions have been associated with

menstrual pneumothorax or hemoptysis
 Endometrial tissue Fallopian tube
Ovary
Uterus

Adhesions

Bladder

Rectum
Vagina

Principal Anatomic Sites of endometriosis found on the pelvic

 Clinical presentation
Symptoms: (common signs and symptoms of endometriosis)
Women with endometriosis may be asymptomatic, subfertile, or
suffer varying degrees of pelvic pain
Pelvic Pain
Dysmenorrhea
Dyspareunia
Dysuria
Infertility
Abnormal uterine Bleeding
Defecatory Pain
The type and severity of symptoms are dependent on the
extent of disease, the location, and the organs involved.
Clinical presentation

Clinical Signs
Localized tenderness in the cul-de-sac or uterosacral
ligament.

Palpable tender nodules in the cull-de-sac,

uterosacral ligament, or rectovaginal septum

Pain with uterine movement

Tender, enlarged adnexal masses.

Fixation of adnexa or uterus in retroverted position

 Endometriosis and Infertility
Proposed Mediators and Mechanisms of Infertility
Anatomic distortion and tubal obstruction.
Anovulation, luteal phase defects, and hormonal
abnormalities.
Galactorrhea or hyperprolactinemia.
Autoimmunity.
Peritoneal leukocytes and the peritoneal inflammatory
response.
Peritoneal fluid prostaglandins.
Peritoneal fluid cytokines.
Embryo implantations defect and spontaneous abortions
 Diagnosis
CA-125 concentration may provide corroborative evidence of
disease, the sensitivity of the test is too low to make it an effective
screening tool
Transvaginal ultrasonography and MRI are both highly sensitive
and specific for detection of ovarian endometriomas but cannot
reliably image peritoneal implants of disease

Therapeutic Trial: A clinical response to empiric medical

treatment does not establish the diagnosis of endometriosis

Laparoscopy: is the primary method of diagnosis, with

or without biopsy for histology diagnosis.
The optimal way to diagnose endometriosis is by direct
visualization of the site of suspected involvement
 Expectant Medical
Management therapy

Treatment

Surgical Combination
therapy therapy
 Expectant Management
Avoiding specific therapy is considered when patients:
- have minimal or no symptoms
- have suspected minimal or mild endometriosis

 NSAIDs/Analgesics: Minor pain may be controlled

Cyclic or continuous oral contraceptives: retard

progression of the disease and protect against unwanted pregnancy.

Infertile women having suspected limited disease may

be observed without treatment

Perimenopausal women may be managed expectantly

even when the disease is advanced, because
endometriotic implants usually regress in the absence of
ovarian hormone production after menopause.
 Medical therapy
Endometriotic implant growth is highly dependent on ovarian
steroids.
 Medical therapy attempts to induced pseudopregnancy or
menopause

Drugs:
Progestins
Continuous oral contraceptives
Danazol
GnRH analogues
 Medical therapy
Progestins:
 inhibit endometriotic tissue growth
Mecanism.
 inhibit pituitary gonadotropin secretion and ovarian hormone
production.

Treatment:
Medroxyprogesterone acetate (10 mg three times a day)
Or
Norethindrone acetate (5 mg daily for 2 weeks), increased by 2.5
mg per day every 2 weeks until a daily dose of 15.0 mg is
reached.

Depot medroxyprogesterone:150 mg im/3 months.

Treatment usually is continued for at least 6 months

 Medical therapy
Danazol
Mechanisms of action:
(a)inhibition of pituitary gonadotropin secretion
(b)direct inhibition of endometriotic implant growth.
(c)direct inhibition of steroidogenic enzymes.
Doses:
- orally in divided doses from: 400 to 800 mg
daily/for 6 months.

Endometriomas and adhesions do not respond well

to danazol treatment

Most women taking danazol have side effects.

 Medical therapy
Side effects of Danasol:
weight gain
 muscle cramps
 decreased breast size
 acne
 hirsutism
 oily skin
 decreased high-density lipoprotein levels
increased liver enzyme levels
 hot flashes
 mood changes
depression.
 Medical therapy
The GnRH analogues:

Mechanism: profoundly suppress ovarian estrogen

production by inhibiting pituitary gonadotropin secretion.

Doses: (nasal spray or depot injections).

 400.00 to 800.00 mg daily for nasal nafarelin

 3.60 mg for monthly subcutaneous goserelin

3.75 mg for monthly intramuscular leuprolide.

 Medical therapy
Side effects of GnRH analogues:

Side effects of the hypoestrogenemia are common:

 hot flashes
 vaginal dryness
 decreased libido
 insomnia
 breast tenderness
 depression
 headaches
transient menstruation.

In addition, GnRH analogue treatment for the recommended 6-

month period decreases bone density and total body calcium, but
most of the bone loss is reversible.
 Surgical therapy
Laparoscopy or Laparotomy
Conservative: retains uterus and ovarian tissue

Definitive: removal of uterus and possibly ovaries

Indications for Surgery:
when the symptoms are severe
incapacitating
when the disease is advanced.
anatomic distortion of the pelvic organs
endometriotic cysts
obstruction of the bowel or urinary tract.

Women who are older than 35 years, infertile, or symptomatic

following expectant or medical management should be
treated surgically.
 Surgical therapy
Laparoscopy: is the preferred to perform conservative surgery

Conservative surgery involves:

excision
fulguration
laser ablation of endometriotic implants
removal of associated adhesions

Definitive surgery is indicated when:

significant disease is present and pregnancy is not desired
when incapacitating symptoms persist following medical therapy
or conservative surgery
and when coexisting pelvic pathology requires hysterectomy

The ovaries may be conserved in younger women to avoid

the need for estrogen replacement therapy.
 Combination therapy
Combination Medical and Surgical Therapy

Medical therapy is used before surgery:

-to decrease the size of endometriotic implants.
-reduce the extent of surgery.

Postoperative medical therapy:

When complete removal of implants is not possible or advisable
is used to treat residual disease.

Progestin, danazol, or GnRH analogues may be used in conjunction

with conservative or definitive surgery.

Preoperative medical therapy may decrease the amount

of surgical dissection required to remove implants.
 Summary Points
The pathogenesis of endometriosis is poorly understood, but
emerging evidence supports the role of retrograde menstruation
and implantation of endometrial tissue.

Endometriosis is common in women with pelvic pain and/or

infertility.

Laparoscopy is the optimal technique to diagnose pelvic

endometriosis.

In most cases, surgical therapy at the time of initial diagnosis

effectively relieves pain and may enhance fertility.
Alternatively, medical therapy with progestins, progestin-
releasing intrauterine devices, danazol, or GnRH analogues will
ameliorate pelvic pain, but they do not enhance fertility.
Endometriosis is a recurrent disease, and definitive treatment
with removal of pelvic organs may be necessary.