Lack of biopsy-controlled studies has led to ambiguous results which are made all the more so by the now well-known concern over accurate identification of endometriosis. Have all clinicians participating in medical studies had the same expertise in the diagnosis of disease?
Lack of long-term follow-up makes it difficult to know where to put medical therapy in the context of treating endometriosis. What happens to these patients later? How many require surgery later? How many have persistent endometriosis? These are important common-sense questions that patients and practicing gynecologists need to have answered.
The assumption has been made in medical therapy studies that the symptoms of pain and infertility are caused by endometriosis, and that resolution of either symptom means that the disease is responding to treatment, perhaps even being physically destroyed by that treatment. In fact, many pain symptoms may not be due to endometriosis, yet may respond during cessation of ovarian function by medical therapy. Dysmenorrhea will always improve with cessation of menses, and inclusion of this symptom in a global score for pain is misleading. Medical therapy for endometriosis is non-specific and will always seem to be better than it really is.
The lack of untreated control groups in studies of infertility patients is disturbing in light of recent concern that patients with Stages I and II endometriosis (most patients who have endometriosis are in these two stages) conceive without treatment at rates equal to or better than the rates of patients undergoing medical therapy. There is increasing recognition that this means endometriosis may not be the potent cause of infertility it was once thought to be. Actually, many studies have found that fertile women predominate in populations of patients with endometriosis.
One of the most important, fundamental errors of the past is the notion that infertility is the most common symptom of the disease. As a result, success in treatment of the disease is still measured primarily in terms of pregnancy rates. Even though pain seems to be a more common symptom of endometriosis than is infertility, the patient with pain has been largely ignored, both by gynecologists in search of patients for study and by the current measure of successful treatment, i.e. pregnancy. These patients have also been slighted by the AFS Classification System of Endometriosis, which exists primarily for comparing infertility patients.
These problems continue to be magnified today. Thus, many endometriosis patients targeted for study are recruited from the ranks of the infertile rather than the ranks of pain sufferers. Many papers on endometriosis are produced from departments of infertility/reproductive endocrinology at metropolitan medical schools rather than from clinicians in general practice. Once this infertile minority is selected out, they are subjected to medical treatments based on scientifically unproven clinical impressions (that menopause or pregnancy makes endometriosis go away or get better). Many modern studies have shown these medical therapies to be ineffective in eradicating endometriosis and to have no apparent beneficial effect on pregnancy rates. Therapy based on these errant findings is then offered to the majority of patients with pain as a primary symptom.
Kempers reported 138 endometriosis patients who were 2 or more years post-menopausal. Only two had been on estrogen. Sixty-one percent had been pregnant and 41 had clinically significant intestinal disease. At St. Charles' Endometriosis Treatment Program, we had a series of 65 patients with biopsy-proven endometriosis after hysterectomy and oophorectomy. Some of these patients were in their 20's and had not had children. They were told that hysterectomy and castration with retention of their disease would cure their endometriosis.
A final difficulty facing medical treatment is the finding that many recent studies have shown that individual endometriosis lesions have widely varying concentrations of estrogen and progesterone receptors, and that these hormones are usually present in amounts lower than the native endometrium. For this reason, endometriosis does not bleed predictably or reliably with the menstrual cycle as generations of gynecologists have been taught. (This is one of the explanations for atypical, subtle or non-hemorrhagic forms of the disease.) For pregnancy, birth control pills, Danazol, GnRH , or menopause to have a beneficial hormonal effect on endometriosis, the lesions would have to respond to the presence of estrogen and progesterone (birth control pills or pregnancy), or lack of estrogen and progesterone, (Danazol, GnRH, menopause). The first problem is that these therapeutic endpoints are diametrically opposed and irreconcilable. You can't have it both ways. Progesterone and estrogen cannot have both a positive and a negative impact on the disease (many would argue that they have no impact at all). In addition, for any of these hormonal states to have a therapeutic effect, the estrogen and/or progesterone would have to have a fairly uniform effect on all populations of endometriosis cells.
The low and varying population of estrogen and progesterone receptors in endometriosis cells in the same patient predicts that any hormonal effect based on our current knowledge would be erratic, inconstant, ineffective, and therefore irrational. If we have been putting most of our eggs in the infertility basket, and we now realize the basket has holes and the eggs have cracks, why do we persist in using obsolete thought processes which run down our legs like yolk? Why do we still try to cram the square peg of endometriosis into the round hole of infertility? Why is this happening? Who is in control?
One argument is often offered in support of medical therapy. One traditional theory of origin proposes that endometriosis is caused by monthly regurgitation of viable endometrial cells in a reverse flow through the fallopian tubes. These cells are thought to fall like seeds on fertile soil, implant and grow. Following this theory, if the monthly regurgitation could be stopped or reduced, it might reduce the likelihood of future implants and perhaps allow resorption of implants already there.
For starters, this theory of reflux menstruation and implantation is just one of at least 10 theories of origin and it has not been proven. The real problem, however, is that physicians continue to prescribe ineffective and experimental medicines in a relative vacuum populated only by words such as "perhaps", "might", and "is thought to". Greater insight is needed into the basics of this disease before rational medical treatment can be offered. Actually, it will be impossible ever to study the effect of medical therapy on endometriosis for a simple reason: you can't biopsy the same cell twice to study it.