Blog #12: New Drugs – Dr Albee’s Recommendations for Doctors & Patients Evaluating a New Drug Therapy


It is prudent to have a good idea of the risk/benefit ratio of virtually everything we put into our bodies. Think of foods, supplements, skin treatments, tattoos, and the like (for example, I do not use artificial sweeteners because I believe that the long-term risks are too high).

Drug therapies are no different and should be evaluated on the basis of a thorough evaluation of this ratio. Don’t forget that this ‘ratio’ should be personalized for each patient based on other coincident illnesses, medications in use, activity levels, compliance capabilities, tolerance for side effects, etc.


As a patient looks to establish a risk/benefit ratio, it is also important to consider the source and quality of the information being used. In general, the greater the number of confirming sources the better. The more independent the source of information is from those who stand to profit from widespread use of the drug, the better also.


First I would like to remind the reader of the general classifications of potential benefits from drug therapy for patients with endometriosis:

  • Symptom Control: As we know, the symptoms of patients with endo are many and varied. Symptoms are those things that make us aware of the underlying disease. Things like anti-inflammatory drugs, muscle relaxants, pain relievers, etc. are all used to reduce symptoms. It is not expected that they will make endo regress or go away.
  • ‘Disease’ Control: The ‘disease’ is the presence of endometrial glands and stroma in locations outside of the uterine lining. Certain drugs may have value in some patients because there is no evidence that the endo is advancing while the patient is on the drug and symptoms are not worsening. In my previous blogs on treatments, you will find some of these drugs listed in the category referred to as ‘suppressive medication.’
  • ‘Disease’ Regression: If a drug causes the ‘disease’ to be reduced in volume, I label the benefit as ‘disease regression’. Certain drugs have been able to show reduction in endometrioma size during treatment (again, I refer you to my ‘treatment blogs’)
  • ‘Disease’ Eradication: If a drug makes endometriosis actually go away, it would be in this class. I am not aware of any convincing data that documents endometriosis disappearing due to the effects of a drug. To my knowledge, this claim can only be made by surgical techniques.

The first step in evaluation a new drug is to be sure you know which of the above benefits you should expect.


  • Potentially Serious:
    • Drug Reactions: Any individual may have a unique reaction to a drug. These reactions may be mild or serious (i.e. life-threatening). The FDA makes an effort to note (in the package insert) any potentially serious drug reactions that have been experienced. The problem is that package inserts are not updated as often as I think they should be when events occur that have not previously been observed.
    • Drug Interactions: Each time a new drug is marketed for general use, there begins a growing list of drug interactions. Drug interactions are untoward and often unexpected effects of the drugs when taken together. These drug interactions may negate the effectiveness of one or both drugs, and they may cause a variety of new health issues for the patient. In some cases it may take months or even years for these interactions to be recognized.
  • Side Effects:
    • When a drug is ingested for a specific benefit, it is common to experience other things that are not beneficial. For example, taking a strong iron supplement often leads to an upset stomach. Side effects can be minor irritations or significant impacts on quality of life.
  • Ineffectiveness:
    • Drug treatments are considered successful even when there is a significant failure rate. It is wise to know the failure rate when considering the risk/benefit ratio.

As an exercise, let’s pick a new drug chosen by the FDA to ‘fast track’ called ‘Elagolix’ (currently in ‘phase 3’ clinical trials) and come up with a risk/benefit ratio.

Elagolix is a GnRH antagonist. Drugs in this group work at the level of the pituitary gland in the brain to reduce or stop the natural process of ovarian stimulation (gonadotropins are normally involved in signaling the ovary to begin to mature an ova [egg] for ovulation and to signal the time of ovulation). This down-regulation of ovarian activity normally reduces estrogen production. In theory, the reduced estrogen secretion reduces stimulation to all estrogen sensitive cells including but not limited to endo.

Expected benefits:

  • Daily non-menstrual pelvic pain and daily dysmenorrhea (menstrual cramps) are the two most commonly evaluated symptoms. In a New England Journal of Medicine study (conducted by authors I know and respect), a dose related improvement in these two types of pain was documented at intervals up to 6 months. At the higher dose of Elagolix roughly 75% of patients reported a clinically significant reduction in menstrual cramps and roughly 50% reported a significant reduction in non-menstrual pelvic pain. If the lower dose was used, improvement in both categories was less.
  • A possibly unique benefit (that is unproven) is the ability to use Elagolix to gain symptom relief at doses that do not result in bone loss. Bone loss is an expected consequence of both GnRH agonists and antagonists.
  • Serious drug reactions were not reported in 872 women.


  • We do not know if the disease progresses in some despite the improvement in symptoms.
  • Studies of other GnRH antagonists give no evidence that the disease is eradicated.
  • Side effects were reported in roughly 70% of patients. Most of these are those expected from estrogen deficiency and include: hot flashes, headache, sleep problems, mood swings, and joint pain.
  • 5-10% of study participants discontinued the drug before the end of 6 months due to an ‘adverse event’.
  • No data on long-term use is available. My personal experience is that soon after drugs in this class are discontinued, symptoms return.
  • If the diagnosis of endometriosis has not already been established by a surgical observation, it is possible that the wrong disease is being treated. The incorrect presumption that endo is present then leads to mistreatment and the consequences.

To sum up the risk benefit ratio of Elagolix based on available data, I would say that Elagolix is an as yet mostly unknown drug that has a moderately good chance of reducing an endo patient’s non-menstrual pelvic pain and dysmenorrhea. Its benefits are in the ‘symptom control’ group. Side effects should be expected and can be significant. The treatment is temporary, and is not expected to eradicate the underlying disease. Long-term follow-up of patients who have used Elagolix is not available. Drug interactions and effects on fertility are not known for this specific GnRH antagonist.

OK! Get busy before you put anything into your body and figure out your personal risk/benefit ratio.

Disclaimer: any and all material(s) presented herein are offered for informational purposes only. Such material is not intended to offer or replace medical advice offered by your personal physicians or healthcare professionals. No information herein should be considered as party to any doctor/patient relationship. All contents herein are © copyright by Robert B. Albee, Jr., MD except where otherwise explicitly noted. All rights reserved. This material may not be reproduced or utilized in any form, including electronic or mechanical, photocopying, recording, or by any information storage and retrieval system except for personal or teaching use with prior permission. Thank you.


This article addresses hysterectomy in common benign (not cancerous) disorders, with emphasis on the role of the procedure in endometriosis.

uterus_xs_27232026Technically speaking, the surgical treatment of  endometriosis rarely requires removal of the uterus (see prior article on ‘the Gold Standard‘). Lesions of ‘endo’ are less common on the uterus, and superficial (serosal) uterine endometriosis can be excised without removing the uterus itself. The primary objective of surgical treatment should be the complete excision of each and every endometriosis lesion. The secondary objectives are the removal of adhesions and restoration of normal anatomy if at all possible (predicated on the degree of irreversible destructive change already present).


The majority of patients are even more interested in pain relief and quality of life than the technicalities of the surgical procedure. Each patient has a unique clinical expression of her disease. This clinical picture is made up of how she feels, where she hurts and when, and her doctor’s observations and examination results. Special tests (like ultrasound, CT and MRI scans, etc.) may add to this picture.

If the ‘gold standard’ surgical treatment of Laparoscopic Excision (LAPEX) is performed and all endo is removed, but the clinical expression of her surgically treated disease remains a problem (despite the successful removal of all endometriosis), the treatment is a failure in the mind of the patient.

In my experience, the overall success of LAPEX in reversing the clinical picture of a patient’s endo is about 80%. This figure is based on our patient follow-up efforts regarding quality of life, any ongoing pain issues, and the frequency and outcomes of any subsequent surgical procedures for persistent pain.


In my practice, the patient has always made the decision herself to have the uterus surgically removed, usually after my consultation and often additional  consultations. In these patients, I have advised them to consider hysterectomy, because there is evidence that they have additional uterine disease (e.g. adenomyosis) that is part of their clinical picture. Although we may have removed their endo prior to hysterectomy, we have not removed all of their sources of pain. Here are a few examples:

  • Adhesion Recurrence: in advanced stage patients, the surgical removal of all endo can leave many injured areas that must heal. The ultimate objective is that each treated area heals completely and independently (i.e not joined to any other structure). The greater the number and size of the areas treated, the more likely it is that tissues will be conjoined in the healing process. The recurrence or new formation of adhesions can cause pain very similar to the pain caused by the endo that we have removed. If these adhesions significantly involve the uterus, repeat surgery may be required for pain relief (about 25% of my stage 4 patients), and of this 25%, a few will choose to have the uterus removed so that it can no longer be encumbered by adhesions.
  • Adenomyosis: some patients have secondary problems in addition to endometriosis, such as adenomyosis. From Latin, this term literally means ‘gland in muscle’. If endometrial glands are present in the uterine wall interspersed amongst the smooth muscle fibers normally found in that area, it is called ‘adenomyosis’. If you look at the holes in a common sea sponge, you get a visual idea of what I am referring to.  Adenomyosis can cause severe pelvic pain and uterine cramping. Sometimes the degree of pain is intolerable, and the patient may choose hysterectomy. I will blog more about adenomyosis in greater detail in the future, so stay tuned.
  • Fibroids=Leiomyomata Uteri: fibroid tumors (usually benign growths of encapsulated muscle in the uterine wall) are typically treated conservatively, but recurrence after conservative treatments (hormone suppression, uterine embolization, myomectomy, etc.) or very large fibroids may require a hysterectomy. This of course can be a problem independent of endo, but I have treated endometriosis and performed a hysterectomy coincidentally at my patient’s request on a few occasions.

There are a few other indications for the consideration of hysterectomy for benign disorders, but this gives you the general idea.


It is critically important to point out that hysterectomy does not cure endometriosis. Each lesion of the disease must also be removed. I have operated on literally dozens of patients who have not only had their uterus removed but also one or both ovaries, only to have the untreated areas of endometriosis that were left behind previously continue to cause pain and ultimately require another surgery to remove the remaining disease.

Hysterectomy may be an option for an indivdual, considering the unique nature of her personal case, after careful and informed discussions with her physician. Stay tuned for the next blog!

Disclaimer: any and all material(s) presented herein are offered for informational purposes only. Such material is not intended to offer or replace medical advice offered by your personal physicians or healthcare professionals. No information herein should be considered as party to any doctor/patient relationship. All contents herein are © copyright by Robert B. Albee, Jr., MD except where otherwise explicitly noted. All rights reserved. This material may not be reproduced or utilized in any form, including electronic or mechanical, photocopying, recording, or by any information storage and retrieval system except for personal or teaching use with prior permission. Thank you.

Blog #10: Endometriosis & Pain

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We might think that endometriosis (‘endo’) pain would be something that every sufferer could understand in the same way. Unfortunately, this is not the case. Endo pain is multi-factorial and different for each patient. So, when a person says, ‘I am experiencing pain from my endometriosis’, other sufferers might assume that they know exactly what is being experienced. The truth is that pain from endo is often unique to the individual experiencing it.

One undesirable result of associating one specific group of symptoms with the diagnosis of endo is that this can lead to a delayed diagnosis – or no diagnosis at all, thus prolonging suffering and increasing the likelihood of disease advancement.

The factors influencing the type of pain a patient experiences include:

  • The location of the endometriosis lesion(s)
  • The amount of inflammation around the lesion and the blood supply to it
  • The proximity of the lesion(s) to local nerve supply
  • The organs affected by endo (peritoneum, fallopian tube, ovary, bladder wall, bowel wall, ureteral wall, vaginal wall, etc.
  • The presence of adhesions in the area
  • The presence or absence of prior pain in the same area
  • The concomitant use of medication including but not limited to:
    • Anti-inflammatory agents
    • Narcotic agents
    • Muscle relaxants
    • Seratonin modulating drugs
    • Ovulation suppressing medications
  • Physical activity
  • Application of heat and/or cold
  • Any practical or psychological benefit (whether the patient is aware of it or not) that the patient receives by way of ‘being in pain’
  • Anger and resentment that results in muscle tension

It is a daunting task to try to point out every type and location of pain that endo sufferers might feel and why it occurs in the way that it does, but I would like to try to describe some of them. If your specific situation does not seem to be adequately covered, send me an email and I will try to cover it as I have an opportunity.


CHRONIC ACHE: See above example. I often think of nerve involvement or internal pressure when I hear this complaint.

COLICKY:  This pain is a slowly building and then residing pain. It is often associated with lesions on/in/or close to the wall of the intestine. As the bowel wall dilates to allow passage of gas/liquid/solid material, the lesion is variably impacted.

MENSTRUAL: Abnormal menstrual bleeding, clotting and cramping, etc. can be associated with several different causes. Endo is one of them. We will discuss other causes for difficult menstrual periods at a future time. Here it is important to know that other diagnoses should be considered as well as endo when trying to understand unusually difficult menses.

BLOATING: Usually means that for one reason or another, the transfer of gas/liquid/solid through the intestine is slowed and the bowel diameter is increasing. The patient is essentially ‘pregnant’ with a dilated intestine.

SHARP/KNIFE-LIKE/TEARING: May occur if blood is released into the abdominal cavity and irritates the peritoneum, or if muscle, containing lesions of endo, is stretched or moved. Sharp pain is also reported when any area of endo receives direct pressure such as the vaginal wall lesions during intercourse.


Pain occurring from above the knee to the mid chest still only covers about 95% of the locations that have been reported.

Pain location is certainly dependent on disease location and the nerves close by, but it is also dependent on the proximity of the lesion(s) to nearby organs and the impact of the lesion(s) on the natural function of the organ involved. For example:

A lesion at the top of the vaginal wall may not cause any pain in a resting situation, but may make sexual intercourse extremely painful, because intercourse puts direct pressure on the site of the lesion. A patient might say, “It only hurts when I have sex.”

Or, a lesion on the bowel wall in the area of the rectum may cause an ache when there is a need to have a bowel movement, and extreme pain (‘I faint every time I have to go to the bathroom’) as someone tries to have a bowel movement. Yet, after defecation, this individual may feel fine.

Or, a lesion on the surface of the ovary (or an endometrioma inside the ovary) may cause extreme pain around the time of ovulation. This person’s pain may gradually increase after menses and actually go away when the next menses finally starts (when the ovary returns to its resting size).

Or, a lesion in the posterior pelvis close to the local nerve supply may cause a chronic low back pain that never seems to go away.

Pain from ureteral involvement may mimic urinary obstruction symptoms, and pain from bowel wall lesions may cause distension of the entire abdomen.

The well-described scenario of painful menstrual cramps and backache is certainly very common and may even be associated with menstrual nausea and vomiting, but it is very important to understand the many other symptoms that may be caused by endo so that the diagnosis gets consideration.


Inflammation is defined as ‘the reaction of tissues to injurious agents’ and ‘may be associated with redness, swelling, pain, tenderness, and heat.’ Inflammation commonly causes pain.

Endo lesions may have surrounding inflammation or they may not. Some lesions seem to be tolerated by the body without any surrounding reaction. We know that this is true because we can see at the time of surgery obvious differences in the surrounding tissue reaction when inflammation is present.

Endo lesions without inflammation may cause no pain at all. For example,  endo may be diagnosed by the surgeon at the time of an unrelated surgery (think appendectomy). When asked post-operatively, some have had no symptoms what-so-ever.


Sensory nerve supply is not uniformly distributed throughout the body and particularly the floor of the pelvis. One side of the body may actually be different than the other. Mesenteric fatty tissues have a different configuration of sensory nerves than the utero-sacral ligaments. As a result, lesions located far from nerve bundles may have little or no effect on pain.


Ovaries, fallopian tubes, intestinal walls, ureters, vaginal walls, and bladder walls are all vital organs that function independently in the lower abdomen and pelvis. When the function of one or more of these organs is impacted by the presence of endometriosis, it may cause pain. See above for examples of the different types of pain that might occur.


Adhesions are created when the body reacts to injury. They may be fine, filamentous webs, hard dense white bands, or glue-like attachments that extend from one structure to the other. Adhesions may form around areas of endo or occur after surgery to remove the disease. Whenever these attachments limit the free mobility of and organ, they are likely to cause pain.


When someone has had severe pain in a specific area in the past, sensitivity in that area may increase. I do not understand the scientific reason for this to occur, but I believe it is real – not imagined.


First of all, I would like to make a plea for personal vigilance in the use of medication and supplements. In my experience, health care professionals and pharmacists do only a fair job of anticipating medication interaction. The best and safest way to add any medication is to first research it for yourself. This can be done online at various sites like

Narcotics, muscle relaxants, anti-inflammatories, and serotonin modulating drugs can all impact the pain a patient experiences at a given point in time. Because their mechanisms of action are different, healthcare professionals may use them independently or sometimes in combination. In each category, prolonged regular use of the drug may encourage a psychological dependence; therefore I advise extreme caution with regular professional re-evaluation when prolonged pain therapies are being used. Additionally, both narcotics and muscle relaxants may induce a physical addiction/dependence requiring medical attention.

Drugs that suppress ovulation may reduce pain by inhibiting the natural increase in ovarian size that occurs during the natural ovarian cycle. The secondary effect of minimizing estrogen/progesterone ups and downs may also reduce pain by reducing menstrual flow (or causing menstruation cessation altogether). We will talk about the mechanism of action of other drug therapies in a different blog.


Heat tends to increase circulation to tissues and can be a great aid to healing; however, it may be associated with localized swelling in the tissues. This can be increase discomfort.

Cold tends to reduce blood supply and reduce swelling. It may also tend to relax tense muscles.

Alternating heat/cold therapies is a well-known method for enhancing healing and controlling pain, and is appropriate for endo patients.

See also my note about avoiding extreme heat on the abdominal wall. I have seen many cases of fat dystrophy from intense heat used because of disabling abdominal pain.


As noted previously, physical activity may or may not increase pain. Movement of tissues containing lesions/cysts surrounded by inflammation often makes exercise uncomfortable. However, there is great individual variation and there are some who are able to exercise without pain.

It is rare that anyone needs to avoid exercise if it causes no pain (perhaps large ovarian cysts require caution), and in general, I think exercise when possible is a strong positive.


Neurogenic pain is defined as pain due to dysfunction of the peripheral or central nervous system, in the absence of nociceptor (nerve terminal) stimulation by trauma or disease.

It is difficult to know how often neurogenic pain occurs in endo patients, but there are times when I suspect that this is the origin of pain. For example, I excise endo from a patient who has suffered for years secondary to misdiagnosis and ineffective treatments. She returns with the same pain that she has reported in the past. Yet, at a second-look Laparoscopy, there is no endo and there are no adhesions to explain the pain.


I should not neglect to mention that psychologists/psychiatrists tell us that pain may be experienced when there is no obvious cause. Sometimes, the cause is present, but we just can’t find it. Sometimes, the presence of pain allows the avoidance of specific “undesirable” activities (work, sex, travel, physical exercise, etc.). In the latter situation, we labor to solve the wrong problem by looking for a pain source when none is going to be found. I advocate a thorough search for pain sources, but I try to also look for secondary benefits from having pain. Often the individual involved has no conscious awareness that the presence of pain is achieving another benefit in her life.


This is probably not something that you would expect an expert on endo to be including in his blog, but I think that it may have value to a few individuals.

Anger (of any type and from any source) causes increased muscle tension and increased gastric motility amongst may other physiologic responses in the body. If there is a place in the body that is injured or inflamed, it will be particularly sensitive to surrounding increases in muscle tension. Those endo patients with GI symptoms may see their symptoms increase around times of significant anger.

Stay tuned for more on endometriosis, coming soon!

Disclaimer: any and all material(s) presented herein are offered for informational purposes only. Such material is not intended to offer or replace medical advice offered by your personal physicians or healthcare professionals. No information herein should be considered as party to any doctor/patient relationship. All contents herein are © copyright by Robert B. Albee, Jr., MD except where otherwise explicitly noted. All rights reserved. This material may not be reproduced or utilized in any form, including electronic or mechanical, photocopying, recording, or by any information storage and retrieval system except for personal or teaching use with prior permission. Thank you.