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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, and
- 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.
Surgical considerations in treating the pain associated with endometriosis
should encorporate what is known about the nerve supply to the
affected pelvic structures. The primary goal is generally to
remove (ablate) all visible endometriosis. Wide margins in the
areas of known pain can be considered (for treatment of microscopic
foci of endometriosis) when using a tool like the ultrapulse laser
since it has little lateral thermal damage and postoperative adhesion
formation appears to be minimal.
Sensory nerves help to carry the signal of pain to the brain.
If there are no sensory nerves functioning in an area of the
body then this area is incapable of feeling pain. For example,
if the sensory nerves to a person's hand have been destroyed then
that person will not be able to "feel" with the hand.
If the hand is accidentally hurt (pinched, burned, cut) the affected
person may not notice the damage until the damage is sensed via
vision.
The sensory nerve supply to the pelvis can differ in amount between
different women. This is most commonly believed to be the reason
why some women have incapacitating pain with minimal endometriosis
(lots of nerve endings in the areas of endometriosis) while other
women have no pain at all despite massive endometriosis (few nerve
endings in the areas of endometriosis).
Pelvic organs receive their sensory nerve supply from the autonomic
(sympathetic and parasympathetic) nervous system. The sensory
innervation of the fallopian tubes, uterus and upper vagina is
predominantly via sympathetic fibers at the spinal cord level
of T-10 to L-1 (area of the lower back).
To reach the spinal cord, nerves from the uterus generally travel
through ligaments behind the cervix (the uterosacral ligaments)
to a "uterine plexus." Other uterine nerves join other
sensory nerves from the pelvis and follow the uterine arteries
to an "inferior hypogastric plexus = pelvic plexus"
which is at the level of the vagina and rectum. Sensory nerves
from the upper vagina, cervix and lower uterus may also travel
through parasympathetic nerves to the sacral spine (at S-2 to
S-4) via the paracervical "Frankenhauser's plexus."
Ovarian sensory nerves travel independently with the ovarian
arteries to an "ovarian plexus." Importantly, converging
nerve fibers from these networks (that supply the pelvic structures
most commonly associated with endometriosis) pass through a common
"superior hypogastric plexus = presacral nerve."
Surgical transection or removal of the nerves that carry pain
sensation from the pelvic structures most commonly associated
with endometriosis has been performed for some time. For midline
pain, the uterosacral ligament transection (also called "LUNA"
= laparoscopic uterine nerve ablation) is occassionally beneficial.
For recurring severe pain throughout the pelvis, a presacral
nerve ablation (neurectomy) can be considered.
I have generally had good results with the aggressive removal
of all visible foci of endometriosis. For women with little relief
or recurrent endometriosis, the uterosacral ligament transection
and presacral nerve ablation can be considered. The serious potential
complications with the presacral nerve ablation (neurectomy) have
limited the use of this treatment.
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