"Ask Dr. Cook" is a series of questions and answers regarding endometriosis. The current subject and answer can be found on Current Ask Dr. Cook web page. The questions may represent a summary of questions I have been asked by several different patients. I hope you find this information helpful. If you have a question you would like answered, please Submit A Question.

Aromatase Inhibitors for Treatment of Endometriosis

Question:
A recent study has shown that aromatase inhibitors may be effective in treating endometriosis. What do you think about this study and aromatase inhibitors as a possible treatment of endometriosis?

Answer:
Dr Bulun published an article in the April issue of Fertility and Sterility describing the successful treatment of one postmenopausal endometriosis patient with an aromatase inhibitor. This may be the first chink in the seemly impenetrable armor of endometriosis. However, it is not time to pop the cork on the champagne bottle quite yet. It is too early to know if this will prove to be an effective treatment with an acceptable level of side effects. It may prove to be an effective treatment but it is just too early to tell.

First, I would like to congratulate Dr. Bulun and his colleagues on their excellent work. Aromatase converts estrogen precursors into estrogens. Thus aromatase is required in the last step of estrogen production. At first glance this would provide an alternative treatment approach to GnRH agonists in reducing the circulating estrogen levels. In other words, aromatase inhibitors provide another way to get the same results as Lupron treatment. However aromatase inhibitors prevent estrogen production by two other mechanisms. Aromatase inhibitors have the advantage of preventing peripheral production (body fat) of estrogen. Peripheral estrogen production is usually very small unless the individual has a large amount of body fat. Finally, Dr. Bulun's work indicates that the endometriotic lesion produces its own estrogen. At least in the patient in this article, aromatase inhibitors also stop the local estrogen production within the endometriotic lesion itself. Thus estrogen can be produced by three different pathways; (1) the hypothalamic-pituitary-ovarian pathway, (2) peripheral conversion, and (3) locally within the endometriosis itself. Lupron stops only the first pathway. Aromatase inhibitors apparently stop estrogen production by all three pathways.

Let's take a look at the study and what we can derive from the information presented. First, this is a case report of one patient. This is one of the primary reasons for using caution in concluding that aromatase inhibitors may offer an effective treatment for endometriosis. The purpose of a study group is to provide a sample that is representative of the overall population in question (e.g. women with endometriosis). The woman in this study is postmenopausal, 5' 7", weighs 219 lbs. and has a level of estrogen production (after a hysterectomy and both ovaries have been removed) that is still in the range of a woman with functioning ovaries. This is a big woman who is producing a fair amount of estrogen through "peripheral conversion". Peripheral conversion is a process whereby a person's body fat converts the estrogen precursors into estrogen. Most women do not have the necessary build to produce this much estrogen or we would not have to worry about estrogen replacement postmenopausally. This may or may not make a difference in the effectiveness of aromatase inhibitors in the treatment of endometriosis. A larger study group will help to answer this question.

The most concerning side effect reported in this case is the large amount of bone loss. The woman in this study experienced a 6% loss of bone from her spine over a nine month period while taking Fosamax (an anti-osteoporosis drug). Normally, the maximum rate of bone loss in postmenopausal women (not taking hormone replacement) is no more than 3% over a 12-month period. Thus the rate of bone loss in this study patient was very high. Bone loss can be a serious complication. More women die of osteoporosis related medical problems that breast and uterine cancer combined. The patient is this study had an acceptable post-treatment bone density because she had a higher than average bone density prior to treatment with the aromatase inhibitor. However, an increased rate of bone turnover is a secondary risk factor of bone fracture, independent of bone density. The risk of bone loss and the associated morbidity and mortality may out weigh the benefits for some women, at least for an extended treatment period.

As a surgeon well versed in both the operative laparoscopic and microsurgical treatment of endometriosis, I am forever skeptical of the thoroughness of the surgical treatment provided to patients. This patient was treated for an extended time medically. I wonder if an approach of combined surgical and short medical treatment would not offer the same results with fewer side effects. This would be similar to the approach used in the treatment of many cancers. All visible disease is eradicated surgically with post-operative medical treatment to eliminate any microscopic disease. The medical treatment could also be used as "booster treatments" to knock down any early recurrent endometriosis.

This study suggests that endometrial implants may have there own cycle of estrogen production independent of the hypothalamic-pituitary-ovarian estrogen cycle that can be shut off with GnRH agonists (Lupron, Synarel etc.). If most endometrial implants do produce their own estrogen, this could help explain why endometriosis patients can still experience severe symptoms even though the GnRH agonists have bottomed out their circulating blood estrogen levels with all of the associated side effects.

In conclusion, this article presents new possibilities for the treatment of endometriosis. One must be careful, however, not to get caught up in unbridled enthusiasm. I believe it is important to keep an optimistic, but realistic outlook on all aspects of endometriosis, including new developments. But, it will be interesting to see how this develops!

Updatede October 29, 2005