Endometriosis may cause pain. Classically, the pain of endometriosis
is most intense during the menstrual flow (dysmenorrhea) and may
involve a wide range of pelvic and abdominal regions. The pain
may also be associated with intercourse (dyspareunia) that lasts
for several hours after the conclusion of relations (since vaginal
penetration commonly results in the movement of pelvic structures
most often affected by endometriosis). The cyclic nature of the
pain is based on the extraordinary responsiveness of endometrial
tissue (wherever located) to the sex steroids, estrogen and progesterone.
During the menstrual cycle, the ovary produces a tremendous amount
of estrogen and progesterone in a sequence that promotes the orderly
growth of endometrium. If a pregnancy does not occur, then the
uterine lining sheds predominantly through the uterine cervix
and out the vagina as menstrual flow. If the patient has endometriosis,
the endometrial cells that are "shed" in the pelvis
have no escape from the body and often cause a dramatic local
inflammatory reaction. This inflammation is the most widely accepted
cause for the pelvic pain associated with endometriosis.
The pain of endometriosis can range widely from a dull ache to
a severe piercing sharp pain. Typically the pain lasts for days
starting 1-2 days prior to the onset of the menstrual flow. The
pain may be greater in certain locations, but often involves the
- * midline pelvis (around and behind the uterus)
- * adnexal region (around the ovaries and tubes immediately
lateral to the uterus)
- * lower back deep in the pelvis (around the rectosigmoid
colon or uterosacral ligaments behind the uterus) where it is
often thought to be gastrointestinal
- * pelvis with radiation down one or both legs or into
the groin
Management of the pain associated with endometriosis with medications
is reported to be frequently effective. Medical management often
takes 3-4 months to become effective and many of these medications
can only be given safely for up to 6 months. Therefore, the woman
suffering from the endometriosis will often request more aggressive
care. Surgery is clearly an alternative with a typically rewarding
outcome. I have generally recommended consideration of surgical
intervention (operative laparoscopy) at the point when the woman's
pelvic pain interferes with her daily activities to such an extent
that she would rather have a surgical procedure to try to remove
the source of the pain than continue with the pain.
All the medical management options for treating endometriosis
include medications that temporarily prevent pregnancy by disrupting
ovulation. To be perfectly safe, one should consider contracepting
after initiating these medications until a state of anovulation
is achieved. Clinical reports comparing the various medications
in terms of effectiveness in pain management suggest that they
are generally comparable to one another. Many of these medications
have significant side effects that the patient may find disagreeable.
The medications in use today include
* (1) GnRH agonists:
GnRH agonists essentially turn off the ovary in terms of egg maturation.
The dramatic decrease in circulating estrogen is thought to be
the primary mechanism of action for GnRH agonists in the treatment
of endometriosis.
One should be certain that the patient is not pregnant or able
to become pregnant before the ovary is suppressed with a GnRH
agonist. The effect of agonist treatment on pregnancy is not known.
There is a report in the literature describing an uneventful pregnancy
and delivery of a normal baby despite GnRH agonist therapy effectively
for the first 3 months of pregnancy (injections at 4 and 8 weeks).
The effectiveness of the GnRH agonists is comparable to Provera
and Danazol with respect to treatment of the pain associated with
endometriosis. Excellent large studies (prospective, randomized,
controlled clinical trials) have demonstrated that GnRH agonists
and Danazol have comparable effects on endometriosis in terms
of pain and reduction of visible disease (determined by comparing
pre and post treatment findings at laparoscopy).
There have been no reports demonstrating a benefit in the treatment
of stage I or II endometriosis with GnRH agonists in terms of
fertility.
* (2) Progestagens:
Progesterone counteracts the effect of estrogen on the endometrium.
The mechanism for this includes a progesterone stimulated reduction
in estrogen receptor number (so estrogen in the circulation has
fewer cellular receptors to bind resulting in less effect), an
accelerated metabolism of estrogen to less active or inactive
forms that are rapidly excreted, and an inhibition of some of
the molecules formed as a result of estrogen that help in creating
the "estrogen effect."
The effectiveness of Provera in providing relief for the pain
associated with endometriosis is reported to be comparable to
that of Danazol and the GnRH agonists.
There is no apparent benefit of Provera or other medical management
in the treatment of stage I or II endometriosis with respect to
fertility. In a solid research study (prospective, randomized,
placebo controlled clinical trial) there was no significant difference
in the pregnancy rates following Provera treatment (100 mg per
day) of stage I or II endometriosis compared to placebo (inert
tablets without medication).
* (3) Danazol:
Danazol was widely used when introduced into clinical practice
in 1972 because it was the only medication available. It is consistently
effective in treating pain associated with endometriosis. At this
time, Danazol is not used much since equally effective medications
are available and the side effects of Danazol can be undesirable.
Side effects of Danazol include weight gain and fluid retention,
decreased breast size, acne and oily skin, excessive male pattern
hair growth (fascial, chest, back), mood swings, muscle cramps,
fatigue, irreversible deepening of the voice, hot flashes, and
atrophic vaginitis (with decreased elasticity of the wall of the
vagina). Side effects occur in about 80% of women but only 10%
of those who take the medication actually discontinue the medication
because of the side effects. Most young reproductive age women
find these sort of side effects to be highly unattractive and
prefer to use one of the other available medications if medical
management is chosen for treatment.
Danazol is effective in relief of pain due to endometriosis about
90% of the time, has similar efficacy to GnRH agonists and Progestagens,
and the pain will reportedly return in about a third of patients
within a year.
There is no known benefit for the treatment of infertility associated
with stage I or II endometriosis.
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