Transcript Treatment of Endometriosis

Dr seyed Mehdi Ahmadi
OB & Gynecologist
Isfahan Fertility & Infertility Centre
( IFIC )
Iran 17th Oct 2012
Vulvovaginal Candidiasis
Classification of Vulvovaginal Candidiasis
• Uncomplicated
• Complicated
 Sporadic or infrequent
in occurrence
 Recurrent symptoms
 Mild to moderate
symptoms
 Severe symptoms
 Likely to be Candida
albicans
 Immunocompetent
women
 Non-albicans Candida
 Immunocompromised,
e.g., diabetic women
Treatment
The treatment of VVC is summarized as follows:
1. Topically applied azole drugs are the most commonly
available treatment for VVC and are more effective than
nystatin. Treatment with azoles results in relief of symptoms
and negative cultures in 80% to 90% of patients who have
completed therapy. Symptoms usually resolve in 2 to 3 days.
Short-course regimens up to 3 days are recommended.
Although the shorter period of therapy implies a shortened
duration of treatment, the short -course formulations have
higher concentrations of the antifungal agent, causing an
inhibitory concentration in the vagina that persists for several
days.
2. The oral antifungal agent, fluconazole, used in a
single 150-mg dose, is recommended for the
treatment of VVC. It appears to have equal efficacy
when compared with topical azoles in the treatment
of mild to moderate VVC. Patients should be
advised that their symptoms will persist for 2 to 3
days so they will not expect additional treatment.
3. Women with complicated VVC . benefit from an
additional 150-mg dose fluconazole given 72 hours
after the first dose. Patients with complications can
be treated with a more prolonged topical regimen
lasting 10 to 14 days. Adjunctive.
Vulvovaginal CandidiasisTopical Treatment Regimens
Butoconazole
2% cream, 5 g intravaginally for 3 days a.b
Clotrimazole
1% cream, 5 g intravaginally for 7-14 days a.b
2% cream 5 g intravaginally for 3 days
Miconazole
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2% cream, 5 g intravaginally for 7 days a.b
200-mg vaginal suppository for 3 days a
100-mg vaginal suppository for 7 days a.b
4% cream 5 g intravaginally for 3 days
1,200 mg vaginal suppository, one suppository
for one day
Nystatin
100,000-Uvaginal tablet, one tablet for 14
days
Tioconazole
6.5% ointment, 5 g intravaginally, single
dosea
Terconazole
0.4% cream, 5 g intravaginally for 7 daysa
0,8% cream, 5 g intravaginally for 3 daysa
80-mg suppository for 3 daysa
a : Oil-based, may weaken latex condoms.
b : Available as over-the-counter preparation.
Treatment with a weak topical steroid, such as 1%
hydrocortisone cream, may be helpful in relieving some of
the external irrigative symptoms.
Recurrent Vulvovaginal
Candidiasis
The treatment of patients with RVVC consists of
inducing a remission of chronic symptoms
with fluconazole (150 mg every 3 days for three doses).
Patients should be maintained on a suppressive dose of
this agent (fluconazole, 150 mg weekly) for 6 months.
On this regimen, 90% of women with RVVC will remain
in remission. After suppressive therapy, approximately
half will remain asymptomatic. Recurrence will occur in
the other half and should prompt reinstitution of
suppressive therapy.
Bacterial Vaginosis
Treatment:
Ideally, treatment of BV should inhibit anaerobes but not
vaginal lactobacilli. The following treatments are effective:
1. Metronidazole, an antibiotic with excellent activity against
anaerobes but poor activity against lactobacilli, is the drug of
choice for the treatment of BV.A dose of 500 mg administered
orally twice a day for 7 days should be used. Patients should be
advised to avoid using alcohol during treatment with oral
metronidazole and for 24 hours thereafter.
2. Metronidazole gel, 0.75%, one applicator (5 g)
intravaginally once daily for 5 days, may also be prescribed.
The overall cure rates range from 75% to 84% with the
aforementioned regimens. Clindamycin in the following
regimens is effective in treating BV:
1. Clindamycin ovules, 100 mg, intravaginally once at
bedtime for 3 days
2. Clindamycin bioadhesive cream, 2%, 100 mg
intravaginally in a single dose
3. Clindamycin cream, 2%, one applicator full (5 g)
intravaginally at bedtime for 7 days
4. Clindamycin, 300 mg, orally twice daily for 7 days
Many clinicians prefer intravaginal treatment to
avoid systemic side effects such as mild to moderate
gastrointestinal upset and unpleasant taste.
Treatment of the male sexual partner does not
improve therapeutic response and therefore is not
recommended.
Trichomonas Vaginitis
Treatment
The treatment of trichomonal vaginitis can be
summarized as follows:
1. Metronidazole is the drug of choice for treatment
of vaginal trichomoniasis. Both a single-dose (2 g
orally) and a multidose (500 mg twice daily for 7
days) regimen are highly effective and have cure
rates of about 95%.
2. The sexual partner should be treated.
3. Metronidazole gel, although effective for the treatment of
BV, should not be used for the treatment of vaginal
trichomoniasis.
4. Women who do not respond to initial therapy should be
treated again with metronidazole, 500 mg, twice daily for 7
days. If repeated treatment is not effective, the patient should
be treated with a single 2-g dose of metronidazole once daily for
5 days or tinidazole, 2 g, in a single dose for 5 days.
5. Patients who do not respond to repeated treatment with
metronidazole or tinidazole and for whom the possibility of
reinfection is excluded should be referred for expert
consultation.
In these uncommon refractory cases, an important part of
management is to obtain cultures of the parasite to determine
its susceptibility to metronidazole and tinidazole.
Inflammatory Vaginitis
• Initial therapy is the use of 2% clindamycin
cream, one applicator full (5 g)
intravaginally once daily for 7 days.
Relapse occurs in about 30% of patients.
who should be retreated with intravaginal
2% clindamycin cream for 2 weeks. When
relapse occurs in postmenopausal patients.
supplementary hormonal therapy
should be considered
Cervicitis
Treatment:
Treatment of cervicitis consists of an antibiotic regimen
recommended for the treatment of uncomplicated lower genital
tract infection with both chlamydia and gonorrhea.
Fluoroquinolone resistance is common in Neisseria
gonorrhoeae isolates, and, therefore, these agents are no longer
recommended for the treatment of women with gonococcal
cervicitis.
It is imperative that all sexual partners be treated with a
similar antibiotic regimen. Cervicitis is commonly associated
with BV, which, if not treated concurrently, leads to significant
persistence of the symptoms and signs of cervicitis.
Treatment Regimens for
Gonococcal and Chlamydial
Infections
Neisseria gonorrhoeae endocervicitis
Ceftriaxone, 250 mg 1Min a single dose, or, if not an option
Cefexime, 400 mg in a single dose
Chlamydia trachomatis endocervicitis
Azithromycin, 1 g orally (single dose), or
Doxycycline, 100 mg orally twice daily for 7 days
Pelvic Inflammatory
Disease
Clinical Criteria for the Diagnosis of Pelvic
Inflammatory Disease:
Symptoms:
None necessary
Signs:
Pelvic organ tenderness
leukorrhea and/or mucopurulent endocervicitis
Additional criteria to increase the specificity or the
diagnosis:
 Endometrial biopsy showing endometritis
 Elevated C-reactive protein or erythrocyte
sedimentation rate
 Temperature higher than 38°C (1OOAOF)
 leukocytosis
 Positive test for gonorrhea or chlamydia
Elaborate criteria:
Ultrasound documenting tubo-ovarian abscess
laparoscopy visually confirming salpingitis
Guidelines for Treatment of
Pelvic Inflammatory Disease
Outpatient Treatment
Cefoxitin, 2 g intramuscularly, plus probenecid, 1 g orally concurrently, or
Ceftriaxone, 250 mg intramuscularly, or Equivalent cephalosporin
Plus:
Doxycycline, 100 mg orally 2 times daily for 14 days, or
Azithromycin, 500 mg initially and then 250 mg daily for a total of 7 days
Inpatient Treatment:
Regimen A:
Cefoxitin, 2 g intravenously every 6 hours, or
Cefotetan, 2 g intravenously every 12 hours
Plus:
Doxycycline, 100 mg orally or intravenously every 12 hours
Regimen B:
Clindamycin, 900 mg intravenously every 8 hours
Plus:
Ceftriaxone, 1-2 g intravenously every 12 hours, or
Gentamicin, loading dose intravenously or intramuscularly (2 mg/kg of
body weight)
followed by a maintenance dose (1.5 mg/kg) every 8 hours
Genital Ulcer Disease
Treatment:
Chancroid:
Recommended regimens for the treatment of chancroid
include azithromycin, 1 g orally in a single dose; ceftriaxone,
250 mg intramuscularly in a single dose; ciprofloxacin, 500
mg orally twice a day for 3 days; or erythromycin base, 500
mg orally four times daily for 7 days. Patients should be
reexamined 3 to 7 days after initiation of therapy to ensure
the gradual resolution of the genital ulcer, which can be
expected to heal within 2 weeks unless it is unusually large.
Herpes:
A first episode of genital herpes should be treated with
acyclovir, 400 mg orally three times a day; or famciclovir,
250 mg orally three times a day; or valacyclovir, 1.0
orally twice a day for 7 to 10 days or until clinical
resolution is attained. Although these agents provide
partial control of the symptoms and signs of clinical
herpes, it neither eradicates latent virus nor affects
subsequent risk, frequency, or severity of recurrences
after the drug is discontinued. Daily suppressive therapy
(acyclovir, 400 mg orally twice daily; or famciclovir, 250
mg twice daily; or valacyclovir, 1.0g orally once a day)
reduces the frequency of HSV recurrences by at least
75% among patients with six or more recurrences of
HSV per year. Suppressive treatment partially, but not
totally, decreases symptomatic and asymptomatic viral
shedding and the potential for transmission.
Syphilis
Parenteral administration of penicillin G is the
preferred treatment of all stages of syphilis.
Benzathine penicillin G, 2.4 million units
intramuscularly in a single dose, is the
recommended treatment for adults with primary,
secondary, or early latent syphilis. The JarischHerxheimer reaction-an acute febrile response
accompanied by headache, myalgia, and other
symptoms may occur within the first 24 hours after
any therapy for syphilis; patients should be
advised of this possible adverse reaction.
Genital Warts
Papillomavirus Treatment
• Primary goal for treatment of visible warts is
the removal of symptomatic warts
• Therapy may reduce but probably does not
eradicate infectivity
• Difficult to determine if treatment reduces
transmission
–No laboratory marker of infectivity
–Variable results utilizing viral DNA
HPV Treatment Options
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Chemical agents
Cryotherapy
Electrosurgery
Surgical excision
Laser surgery
Imiquimod (Aldara)
Defer treatment
Natural therapies
Papillomavirus
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Surgical removal
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Patient-applied
Podofilox (Condylox) 0.5% solution or gel
Apply 2x/day for 3 days, followed by 4 days of no therapy.
Repeat as needed, up to 4x
or
Imiquimod (Aldara) 5% cream
Apply 1x/day @ bedtime 3x/week for up to 16 weeks
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Provider-administered
Cryotherapy (liquid nitrogen) *repeat every 1-2 weeks
or
Podophyllin resin 10-25% *thoroughly wash off in 1-4 hrs
or
Trichloroacetic or
Bichloroacetic acid 80-90%
*can be repeated weekly
Papillomavirus
Vaginal warts
Cryotherapy or TCA/BCA 80-90%
Urethral meatal warts
Cryotherapy or podophyllin 10-25%
Anal warts
Cryotherapy or TCA/BCA 80-90%
Papillomavirus
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Therapy choice needs to be guided by
preference of patient, experience of
provider, and patient resources (time
and/or money)
No evidence exists to indicate that any one
regimen is superior
An acceptable alternative may be to do
nothing but watch and wait; possible
regression/uncertain transmission
Human
Immunodeficiency Virus
• Decisions regarding the initiation of antiretroviral
therapy should be guided by monitoring the
laboratory parameters of HIV RNA (viral load)
and CD4+ T-cell count, and the clinical condition
of the patient. The primary goals of antiretroviral
therapy are maximal and durable suppression of
viral load, restoration or preservation of
immunologic function, improvement of quality of
life, reduction of mV-related morbidity and
mortality, and prevention of mv transmission.
• Antiretroviral therapy should be initiated in all
women with a history of an AIDS-defining
illness or with a CD4 count less than 350 cells
per mm3.
• Antiretroviral treatment should be started
regardless of CD4 count in women with the
following conditions: pregnancy, HIVassociated nephropathy, and hepatitis B
coinfection when treatment of hepatitis B is
indicated. Patients must be willing to accept
therapy to avoid the emergence of resistance
caused by poor compliance.
• Dual nucleoside regimens used in addition to
a protease inhibitor or non nucleoside reverse
transcriptase inhibitor provide a better
durable clinical benefit than monotherapy.
• Patients with less than 200 CD4+ T cells per
µ,L should receive prophylaxis against
opportunistic infections, such as
trimethoprim/sulfamethoxazole or aerosol
pentamidine for the prevention of PCP
pneumonia. Those with less than 50 CD4+ T
cells per uL should receive azithromycin
prophylaxis for mycobacterial infections.
Aberrations of Pubertal
Development
I.
Delayed or interrupted puberty
A. Anatomic abnormalities of the genital outflow tract
1. Mullerian dysgenesis (Rokitansky-Kuster-Hauser syndrome)
2. Distal genital tract obstruction
a. Imperforate hymen
b. Transverse vaginal septum
B. Hypergonadotropic (follicle-stimulating hormone >30 mlUlmL)
hypogonadism
(gonadal "failure")
1. Gonadal dysgenesis with stigmata of Turner syndrome
2. Pure gonadal dysgenesis
a. 46,XX
b. 46,XY
3. Early gonadal "failure" with apparent normal ovarian development
C. Hypogonadotropic (luteinizing hormone and follicle
stimulating hormone < 10 mlU/mL) hypogonadism
1. Constitutional delay
2. Isolated gonadotropin deficiency
a. Associated with midline defects (Kallmann syndrome)
b. Independent of associated disorders
c. Prader-Labhart-Willi syndrome
d. Laurence-Moon-Bardet-Biedl syndrome
e. Many other rare syndromes
3. Associated with multiple hormone deficiencies
4. Neoplasms of the hypothalamic-pituitary area
a. Craniopharyngiomas
b. Pituitary adenomas
c. Other
5. Infiltrative processes (Langerhans cell-typehistiocytosis)
6. After irradiation of the central nervous system
7. Severe chronic illnesses with malnutrition
8. Anorexia nervosa and related disorders
9. Severe hypothalamic amenorrhea (rare)
10. Antidopaminergic and gonadotropin-releasing
hormone-inhibiting drugs (especially psychotropic agents,
opiates)
11. Primary hypothyroidism
12. Cushing syndrome
13. Use of chemotherapeutic (especially alkylating) agents
II. Asynchronous pubertal development
A. Complete androgen insensitivity syndrome (testicular
feminization)
B. Incomplete androgen insensitivity syndrome
III. Precocious puberty
A. Central (true) precocious puberty
1. Constitutional (idiopathic) precocious puberty
2. Hypothalamic neoplasms (most commonly hamartomas)
3. Congenital malformations
4. Infiltrative processes (Langerhans cell-type histiocytosis)
5. After irradiation
6. Trauma
7. Infection
B. Precocious puberty of peripheral origin (precocious
pseudopuberty)
1. Autonomous gonadal hypersecretion
a. Cysts
b. McCune-Albright syndrome
2. Congenital adrenal hyperplasia
a. 21-Hydroxylase (P450c21) deficiency
b. 11,ß-Hydroxylase (P450cll) deficiency
c. 3ß-Hydroxysteroid dehydrogenase deficiency
3. Iatrogenic ingestion/absorption of estrogens or
androgens
4. Hypothyroidism
5. Gonadotropin-secreting neoplasms
a. Human chorionic gonadotropin secreting
i. Ectopic germinomas (pinealomas)
ii. Choriocarcinomas
iii. Teratomas
iv. Hepatoblastomas
b. Luteinizing hormone-secreting (pituitary adenomas)
6. Gonadal neoplasms
a. Estrogen-secreting
i. Granulosa-theca cell tumors
ii. Sex-cord tumors
b. Androgen-secreting
i. Sertoli-Leydig cell tumors (arrhenoblastomas)
ii. Teratomas
7. Adrenal neoplasms
a. Adenomas
b. Carcinomas
IV. Heterosexual puberty
A. Polycystic ovarian syndrome
B. Nonclassic forms of congenital adrenal
hyperplasia
C. Idiopathic hirsutism
D. Mixed gonadal dysgenesis
E. Rare forms of male pseudohermaphroditism
(Reifenstein syndrome, Sa-reductase
deficiency)
F. Cushing syndrome (rare)
G. Androgen-secreting neoplasms (rare)
Differential Diagnosis of Acute
Pelvic Pain
Acute Pain
1. Complication of pregnancy
a. Ectopic pregnancy
b. Abortion, threatened or incomplete
2. Acute infection
a. Endometritis
b. Pelvic inflammatory disease (acute PID) or
salpingo-oophoritis
c. Tubo-ovarian abscess
3. Adnexal disorders
a. Hemorrhagic functional ovarian cyst
b. Torsion of adnexa
C. Rupture of functional, neoplastic, or inflammatory
ovarian cyst
Recurrent Pelvic Pain
1. Mittelschmerz (midcycle pain)
2. Primary dysmenorrhea
3. Secondary dysmenorrhea
Gastrointestinal
1. Gastroenteritis
2. Appendicitis
3. Bowel obstruction
4. Diverticulitis
5. Inflammatory bowel disease
6. Irritable bowel syndrome
Genitourinary
1. Cystitis
2. Pyelonephritis
3. Ureteral lithiasis
Musculoskeletal
1. Abdominal wall hematoma
2. Hernia
Other
1. Acute porphyria
2. Pelvic thrombophlebitis
3. Aortic aneurysm
4. Abdominal angina
Leaking or Rupture of an
Ovarian Cyst
Management:
Orthostatic, significant anemia, hematocrit of the
culdocentesis fluid of greater than 16%, or a large amount
of free peritoneal fluid on ultrasound suggests significant
hemoperitoneum
and
usually
requires
surgical
management by laparoscopy or laparotomy. Patients who
are not orthostatic or febrile, who are not pregnant or
anemic, and who have only a small amount of fluid in the
cul-de-sac can often be observed in the hospital, without
surgical intervention, or even discharged home from the
emergency room after observation.
Adnexal Torsion
Adnexal torsion must be treated surgically.
The adnexa may be untwisted and a
cystectomy Performed if appropriate. Even if
it appears that necrosis occurred, there is
evidence that it remains functional and
sparing the adnexa can preserve its hormonal
and reproductive function. Treatment can be
accomplished by laparoscopy or laparotomy,
depending on the size of the mass.
Tubo-Ovarian Abscess
Tubo-ovarian abscesses should always be
treated as an inpatient, and conservative
medical therapy with broad spectrum
antibiotics can be attempted . In one study,
this yielded a treatment success rate of
75% . If the patient is persistently febrile or
not improving clinically, CT or ultrasoundguided drainage of the abscesses should be
undertaken.
CT-guided percutaneous drainage can be
achieved trans abdominally or Trans
vaginally.
Drainage
along
with
intravenous antibiotics is considered firstline therapy. If fertility is not desired,
bilateral
salpingo-oophorectomy
and
hysterectomy will provide definitive
therapy.
A ruptured tubo-ovarian abscess rapidly
leads to diffuse peritonitis, evidenced by
tachycardia and rebound tenderness in all
four quadrants of the abdomen. With
endotoxic shock, hypotension and oliguria
ensue, and the result can be fatal.
Exploratory laparotomy with resection of
infected tissue is mandatory
Uterine Leiomyomas
Diagnosis and Management:
With degeneration there is usually leukocytosis.
Ultrasound can distinguish adnexal from uterine
etiology of an eccentric mass. If diagnosis is still
uncertain, a pelvic MRI is more accurate. The
fibroid can be excised laparoscopically; however,
surgery is not mandatory.
A submucous leiomyoma with pain and
hemorrhage should be excised transcervically with
hysteroscopic guidance.
Differential Diagnosis of
Chronic Pelvic Pain
Gynecologic
Noncyclic
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Adhesions
Endometriosis
Salpingo-oophoritis
Ovarian remnant or retained ovary syndrome
Pelvic congestion
Ovarian neoplasm benign or malignant
Pelvic relaxation
Cyclic:
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Primary dysmenorrhea
Mittelschmerz
Secondary dysmenorrhea
Endometriosis
Uterine or vaginal anomalies with obstruction of
menstrual outflow
Intrauterine synechiae (Asherman syndrome)
Endometrial polyps intrauterine device(IUD)
Uterine leiomyomata
Adenomyosis
Pelvic congestion syndrome
Atypical cyclic:
 Endometriosis
 Adenomyosis
 Ovarian remnant syndrome
 Chronic functional cyst formation
Gastrointestinal
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Irritable bowel syndrome
Ulcerative colitis
Granulomatous colitis (Crohn's disease)
Carcinoma
Infection
Recurrent partial bowel obstruction
Diverticulitis
Hernia
Abdominal angina
Recurrent appendiceal colic
Genitourinary
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Recurrent or relapsing cystourethritis
Urethral syndrome
Interstitial cystitis/bladder pain syndrome
Ureteral diverticuli or polyps
Carcinoma of the bladder
Ureteral obstruction
Pelvic kidney
Neurologic
 Nerve entrapment syndrome, neuroma, or other
neuropathies
 Trigger points
Musculoskeletal
 Myofascial pain and trigger points
Low-back pain syndrome
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Congenital anomalies
Scoliosis and kyphosis
Spondylolysis
Spondylolisthesis
Spinal injuries
Inflammation
Tumors
Osteoporosis
Degenerative changes
Coccydynia
Myofascial syndrome
Systemic
• Fibromyalgia
• Acute intermittent porphyria
• Abdominal migraine
• Connective tissue disease including systemic
lupus erythematosus
• Lymphoma
• Neurofibromatosis
Secondary Dysmenorrhea
Adenomyosis
Management
The management of adenomyosis depends on the
patient's age and desire for future fertility. Relief of
secondary dysmenorrhea caused by adenomyosis
can be ensured after hysterectomy, but less invasive
approaches can be tried initially. NSAIDs, hormonal
contraceptives, and menstrual suppression using
oral, intrauterine, or injected progestins or
gonadotropin-releasing hormone agonists are all
useful. Treatment follows the same protocol as
treatment for endometriosis. Uterine artery
embolization can be effective.
Endometriosis
Management of Secondary
Dysmenorrhea Due to
Endometriosis:
Pharmacologic
Medications can be used to reduce the cyclic hormonal
stimulation of these lesions and eventually decidualize or
atrophy the lesions. No studies directly compared medical versus
surgical management of endometriosis. However, given the
excellent response rate, relatively low cost, and fair tolerability
with hormonal therapy, an expert consensus panel
recommended that women with suspected endometriosis who
are not actively trying to conceive and who do not have an
adnexal mass start with first-line medical management before
laparoscopy.
. First-line treatment consists of a trial of NSAIDs with or
without combined estrogen-progestin formulations.
Both cyclic and continuous combined oral contraceptives
(OCs) can be used with equal efficacy.
Most studies used OCs containing low-dose estrogen and
more androgenic progestins; however, newer generation
progestins are also effective. For women who continue to
have dysmenorrhea after using hormonal contraceptives in
a cyclical fashion, continuous OCs regimen can be tried,
without a hormonal break or with menstruation every 3
months.
Second-line medical therapy involves high-dose progestins
or gonadotropin-releasing hormone (GnRH) analogues.
This can be initiated for refractory symptoms or for
patients with contraindication to estrogen. Progestins alone
are associated with few metabolic concerns and are safe and
inexpensive alternatives to surgical intervention. Progestins
or progestins plus estrogen effectively manage pain
symptoms in approximately three-quarters of the women
with endometriosis. High-dose medroxyprogesterone
acetate and norethindrone acetate are equally effective to
the GnRH analogues. Progestins should be given at a dose
to achieve amenorrhea, then the dose can be tapered to
control symptoms.
A randomized controlled trial comparing levonorgestrel
intrauterine system (LNG-IUS) with depot GnRH for the
treatment of endometriosis-related chronic pain found that
both were effective treatments. Androgenic hormones such
as danazol are thought to inhibit the luteinizing hormone
surge and steroidogenesis and may have anti-inflammatory
effects. These medications increase free testosterone,
resulting in possible side effects such as deepening of voice,
weight gain, acne, and hirsutism. Vaginal danazol in lower
doses may be effective.
GnRH agonist and add-back treatment can be used as
pharmacologic treatments for endometriosis. A randomizedcontrolled trial of GnRH agonist therapy for 6 months in
cases of confirmed endometriosis showed decreased size of
endometriotic lesions and pain symptoms. Side effects are
related to the hypo estrogenic state and include vasomotor
symptoms, mood swings, vaginal dryness, decreased libido,
myalgias, and, eventually, bone loss. These side effects can be
reduced with supplemental calcium and hormonal add-back
therapy with norethindrone acetate 2 to 5 mg daily with or
without low-dose estrogen (0.625 mg of conjugated estrogen or
I mg of 17 ,B-estradiol).
Given the side effects, GnRH agonists usually are not used for
more than 8 to 12 months, but with add-back hormones and/or
bisphosphonate, GnRH therapy can be considered for use for
more than I year. Recurrence of symptoms after
discontinuation of GnRH agonist ranges from 36% to 70% 5
years after completion of treatment.
Aromatase p-450 and prostaglandin E2 (PgE2) pathways arc
thought to be involved in the genesis of endometriotic implants.
Aromatase plays an important role in estrogen biosynthesis by
catalyzing the conversion of androstenedione and testosterone
to estrone and estradiol. Although aromatase activity is not
detectable in normal endometrium, it is found in eutopic
endometrium and endometriotic lesions. Thus, aromatase
inhibitors (AIs) are now being used as adjunctive therapy with
medical therapies in refractory cases.
A 2008 review of eight studies evaluated Als for
management of endometriosis and found that AIs
combined with progestins or OCs or GnRH
analogues decreased mean pain scores and lesion
size and improved quality oflife. In the only
randomized controlled trial (97 women) evaluated
in this meta-analysis, aromatase inhibitor
(anastrozole) in combination with GnRH agonist
significantly improved pain (P <0.0001) compared
with GnRH agonist alone at 6-month follow-up, and
there was no significant reduction in spine or hip
bone density
Management of
Endometriosis: Surgical
Laparoscopy and laparotomy are appropriate and for
some patients, they are the preferred treatment for
the management of secondary dysmenorrheal pain
related to endometriosis that is unresponsive to
hormonal agents. Excellent operative skill is required
to manage endometriosis surgically. Endometriotic
lesions should be ablated or resected. Endometriomas
must be removed with their capsule.
Resection of endometriomas by ovarian cystectomy
improves pain and fertility in women with chronic
pelvic pain and endometriosis when compared to
fenestration, drainage, and coagulation. In a
randomized controlled trial of laser ablation for
minimal to moderate endometriosis, over 90% of
women felt improved at 1-year follow-up, and 87% of
women with stage III to IV endometriosis were
satisfied with the results at I-year follow-up.
Recurrent pain after 24 months is close to 50%
In women who no longer desire fertility with
severe secondary dysmenorrhea, hysterectomy
with bilateral salpingo-oophorectomy (BSO) and
removal of endometriosis lesions is the preferred
treatment. Hysterectomy without BSO results in
a higher rate of disease recurrence and a 30%
reoperation rate. The risk of recurrent
endometriosis with hormone replacement is small
if combined estrogen-progestin preparations are
used and unopposed estrogen is avoided.
There are limited data regarding outcomes for
repeated conservative surgical procedures,
including pelvic denervating procedures. The
authors conclude that although re-operation is
often considered the best option, the long-term
outcome appears suboptimal with a cumulative
probability of recurrent pain between 20% and
40% and of a further surgical procedure of at
least 20%. Hysterectomy with BSO decreased the
need for re-operation to treat pelvic pain by
sixfold. Postoperative medical treatment with
OCs can be effective.
Re-operation in a symptomatic patient after
previous conservative surgery should take into
account the psychological state of the patient, desire
for future fertility, and whether the pain responded
to prior surgical therapy with at least I, but
preferably 3 to 5 years of pain relief.
Rectovaginal endometriosis is often deeply
infiltrating, highly innervated, and associated with
severe cyclic pelvic pain and dyspareunia. These
lesions can be surgically challenging for
laparoscopic resection. Hormonal therapy can be
effective. Vercellini et al. reviewed hormonal
therapy in 217 patients: 68 in five observational
studies, 59 in a cohort study, and 90 in a
randomized controlled trial.
The study compared aromatase inhibitor, vaginal
danazol, GnRH agonist, intrauterine progestin, and
two estrogen-progestin combinations, transvaginally
or transdermally and an oral progestin. With the
exception of an aromatase inhibitor used alone, the
pain relief with medical therapies was satisfactory
over the 6- to 12-month course of the treatment,
with 60% to 90% of women reporting substantial
decrease or complete relief from pain symptoms.
Medical Treatment of
Endometriosis-Associated
Pain: Effective Regimens
(Usual Duration: 6 Months)
Progestogens
Administration
Dose
Frequency
Merlroxyprogesterone
acetate
PO
30 mg
Daily
Dienogest
PO
2 mg
Daily
Megestrol acetate
PO
40 mg
Daily
Lynestrenol
PO
10 mg
Daily
Dydrogesterone
PO
20-30 mg
Daily
Antiprogestins
Administration
Dose
Frequency
Gestrillone
PO
1.25 or 2.5 mg
Twice weekly
Danazol
PO
400 mg
Daily
Gonadotropill-Rt'/easing
Hormone
Administration
Dose
Frequency
Leuprolide
SC
500 mg
Daily
IM
3.75 mg
Monthly
Goserelin
SC
3.6 mg
Monthly
Buserelin
IN
300 µg
Daily
SC
200 µg
Daily
Nafarclin
IN
200 µg
Daily
Triptorelin
IM
3.75 mg
Monthly
Treatment of EndometriosisAssociated Subfertility
Surgical Treatment
Abnormal uterine bleeding
Low risk for
Endometrial cancer
medical management
Bleeding
stop
Bleeding continues
Observe
TVS
Endometrial <stripe>
≤ 5𝑚𝑚𝑎
continued bleeding
Obvious pathology
or > 5𝑚𝑚𝑎
moderate or high risk
for endometrial cancer
SISb
Normal
Continued
Bleeding
Hysteroscopy
D&C
Hysteroscopy/mass biopsy b,c
Uniform thickening> 3𝑚𝑚 of a
single layer of the endometriuma
or inconclusive results
EMB
Inadequate
biopsy
Adequate
biopsy
Focal lesion
NSAID
Mefenamic acid
Naproxen
Ibuprofen
Flurbiprofen
Meclofenamate
Medical treatment of
Menorrhagia
500 mg tid for 5 days, beginning with menses
Bonnar,1996
550 mg on first day of menses, then 275 mg daily Hall, 1987
600 mg daily throughout menses
Makarainen, 1986
100 mg bid for 5 days, beginning with menses
Andersch, 1988
100 mg tid for 3 days, beginning with menses
Vargays, 1987
Other classes
COCs
Tranexamic acid
Norethindrone
Danazol
GnRH agonists
LNG-IUS
one orally daily
1 g qid for 5 days, beginning with menses
5 mg tid days 5 through 26 of cycle
(ovulatory DUB).5 mg tid days 15 through
26 of cycle (anovulatory DUB)
100 mg or 200 mg daily throughout cycle
3.75 mg intramuscularly each month
(maximum 6 months of use)
Intrauterine placement
Agarwal, 2001
Bonnar, 1996
Irvine, 1998
Higham, 1993
Chimbira, 1980b
Shamonki,2000
Reid, 2005