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Endometriosis may cause pain. Classically, the pain of endometriosis is most intense during the menstrual flow (dysmenorrhea) and it 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 an 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
Endometriosis and Pain: treatment
Management of the pain associated with endometriosis using medications is reported to be frequently (in up to 85% of women) 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 immediately effective treatment. 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 and 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 (facial, 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 sorts 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.
(4) Surgery
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 occasionally 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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