Reader’s Choice : Letrozole & Endometriosis

Bottle of Letrozole
Photo courtesy of JLD

One of my local EndoSisters has started a new medication to help with her Endometriosis pain and symptoms, based upon the recommendation of her new physician.  It’s Letrozole, which I had never heard of.  And she asked me if I had any info on it…so…now I’m inspired to do some research!

What is Letrozole?

Letrozole is the generic name for Femara, a drug classified as an aromatase inhibitor.  What is aromatase?  It’s an enzyme that is crucial in the creation of estrogen. Aromatase inhibitors have been FDA approved for treating breast cancer in post-menopausal women.  However, it has piqued the interest of the medical community in controlling Endometriosis symptoms.  It is not yet FDA approved for this treatment, but is used as an off-label, accepted treatment among the medical community. As of today’s research, there are no indications that drug manufacturers are going to seek FDA approval for aromatase inhibitors to treat Endometriosis.

Doodle of aromatase inhibitors Courtesy of: Michiko Maruyama, michiko.maruyama@gmail.com, www.artoflearning.ca
Used with permission: Michiko Maruyama, michiko.maruyama@gmail.com, http://www.artoflearning.ca

Endometriosis has been theorized to be a largely estrogen-driven disease.  Aromatase has been found in increased amounts in the endometrial tissue of women with Endometriosis, as opposed to women without.  Some physicians are now prescribing aromatase inhibitors when no other traditional treatments have helped with a woman’s Endometriosis symptoms.  The hope is that by inhibiting (blocking) aromatase production, it will ease Endometriosis symptoms and progression.  Aromatase inhibition may give rise to ovarian stimulation (widely used to increase fertility) and ovarian cysts; and therefore are often used in combination with other drugs, such as Norethindrone (progestin), Zoladex (GnRH agonist), or birth control pills to help women with Endo to avoid further production of painful ovarian cysts, etc.

Side Effects:

Specifically, Letrozole has been known to cause fatigue,drowsiness, and dizziness, especially when combined with alcohol or when the person is exposed to heat.  A woman who is newly taking Letrozole must be cautious when driving until she truly knows how her body responds to the medication.

The FDA has released an entire list of side effects women complained of while treating with Letrozole for their breast cancer: angina (chest pain), arthritis, bone fractures, cerebrovascular/TIA (similar to a stroke), constipation, diarrhea, endometrial cancer, endometrial proliferation disorders, fractures, dizziness, edema (swelling), fatigue, headaches, hot flashes/flushes, light-headedness, myalgia (muscle pain), myocardial infarction (heart attack), nausea, night sweats, osteoporosis, other cardiovascular issues, other endometrial disorders, thromboembolic event (strokes), vaginal bleeding, vaginal irritation, vomiting, and weight increase.  Some women have also complained of a decrease in their libido.

When used in combination with a progestin or birth control pill, aromatase inhibitors do not cause osteoporosis; however, if used with a GnRH agonist, osteoporosis may develop.  Your physician may recommend frequent bone scans to ensure bone loss is not occurring while treating.  They may also recommend you take Calcium and Vitamin D during your treatments.

RXList.com has an ongoing list of testimonials and reviews of women who take Femara (Letrozole) and what their experiences and side effects have been.  I know that my EndoSister’s going through a lot of joint pain at the moment.  Almost everyone complained of bone and joint pain; stating:

“Then–suddenly I was having bone pain in legs (felt like someone took a 2×4 and whacked me across the leg bones)–joint pain in shoulders, knees, ankles, feet, and fingers.”

“I started having joint pain in the knees, feet, and fingers. Also fatigue and muscle weakness. Feel like I have aged 10 years.”

“I have experienced severe bone and muscle pain to the point that I find it difficult to walk up and down stairs.”

“I hurt so badly I could barely get out of bed or walk down the halls at work”

Many women stopped taking the drug because of the intensity of the side effects and posted their reviews on RxList.

Clinical Trials:

In 2004, a pilot study was published in the Fertility and Sterility journal on the effectiveness of managing Endometriosis symptoms using Letrozole.  The study involved 10 women who did not respond to surgical or medical treatment of their Endometriosis.  They were given 2.5mg of Letrozole, 2.5mg of Norethindrone, as well as Calicum Citrate and Vitamin D supplements for six months.  The study concluded that there was a “marked reduction of laparoscopically visible and histologically confirmed endometriosis in all 10 patients and significant pain relief in nine out of 10 patients who had not responded previously to currently available treatments,” and they strongly urge the use of this regimen in treating Endometriosis symptoms.

Another study in 2004, again published in the Fertility and Sterility journal, followed the treatment of two women.  They were given Anastrozole (a different aromatase inhibitor), as well as a progesterone pill, calcitriol, and rofecoxib for three months.  Both of the women had a rapid reduction in their pain and symptoms, and remained so even 24 months after receiving the treatment.  One underwent a diagnostic laparoscopy 15 months after treatment and was confirmed free and clear of any Endometriosis implants.  Both women were able to conceive within 24 months of treatment.

The Middle East Fertility Society Journal published an article in 2014 which reviewed several different types of drugs emerging in Endometriosis treatment, including aromatase inhibitors.  It also summarizes several past studies regarding Endometriosis and aromatase inhibitors. 

In 2015, a study was published in BioMed Research International of a clinical trial of Letrozole and its effectiveness in decreasing the size of endometrioma (blood-filled cysts).  The lead author of this study is also the doctor whom prescribed Letrozole to my EndoSister who inspired today’s blog.  It was a three-month study of eight women, each of whom agreed to the “off-label and unproven therapy,” in the hopes it would reduce their Endometriomas and Endometriosis pain.  They were given daily 5mg doses of Letrozole, as well as daily 5mg doses of Norethindrone (the FDA-approved “add back” therapy used with Lupron Depot).  A typical daily dose of Letrozole is 2.5mg, but since this study was only three months long, they upped the dosage.  And Norethindrone was used “…to minimize the negative effects of induced hypoestrogenemia and thus make the letrozole therapy more tolerable.”  Hypoestrogenemia is a deficiency of estrogen in the blood. Over the three-month period, they found the Endometriomas decreased by 50%, and the women had significant reductions of pelvic pain and painful sex.  More studies are needed, including double-blind tests with placebo, as well as longer studies, and smaller doses. It is their hope that these studies will lead to a lesser need for surgical intervention in suppressing the pain and manifestations of Endometriosis.

I encourage you to look online for a plethora of additional studies regarding aromatase inhibitors and Endometriosis. 

Conclusion

Although the treatment of Endometriosis with aromatase inhibitors is not approved by the FDA, and there’s no indication that such approval will be sought, the studies and trials do appear to support the notion that they help reduce and control the pain and progression of this disease.  If you are able to swallow the idea of an experimental drug, you may want to talk to your physician about this treatment regimen.

(Updated March 27, 2019)

Resources:

Advanced Fertility Center of Chicago

Endometriosis.org

Fertility and Sterility (2004; Article) : Treatment of Endometriosis and Chronic Pelvic Pain with Letrozole and Norethindrone Acetate : A Pilot Study

Fertility and Sterility (2004; Article) : Successful Treatment of Severe Endometriosis in Two Premenopausal Women with an Aromatase Inhibitor

Hindawi Publishing Corporation (2015; Article) : Reduction of Endometrioma Size with Three Months of Aromatase Inhibition and Progestin Add-Back

Merriam-Webster

Northwestern University Feinberg School of Medicine

RXList

Science Direct (2014: Article) : Emerging Treatment of Endometriosis

U.S. Food and Drug Administration : Femara (Letrozole tablets) drug information page

~Again, I am a layman.  I do not hold any college degrees, nor mastery of knowledge.  Please take what I say with a grain of salt.  If curious, do your own research 😉 Validate my writings.  Or challenge them.  And ALWAYS feel free to consult with your physician (or in this case, attorneys). Always.  Yours ~ Lisa