Valerie A. Flores, MD

What is the value of considering noninvasive methods for the diagnosis of endometriosis?

Dr. Flores: There is great value in noninvasive diagnostics for endometriosis. This is because while surgical diagnosis is the “gold standard,” surgery is invasive, and waiting until a surgical diagnosis can be made further contributes to delays in diagnosis. However, more recently there has been a shift toward utilizing noninvasive approaches to the diagnosis of endometriosis, with the primary one focusing on clinically diagnosing endometriosis. 

One of the first things to remember is the importance of gathering a patient history and conducting a physical exam. We've all learned this in medical school, and it comes into play even more so with a condition such as endometriosis. Endometriosis is defined as a benign gynecologic disease characterized by endometrial-like tissue outside of the uterus, but this definition does not reflect the true scope and manifestations of endometriosis. Research over the years has demonstrated that endometriosis has systemic effects—affecting regions of the brain associated with anxiety/depression, altering pain sensitization, and having inflammatory effects that can not only affect the reproductive organs but also other organ systems. As such, our questions when evaluating patients for endometriosis need to focus on these various aspects of the disease. 

Endometriosis usually leads to cyclic pain. This is because just as the lining of the uterus (the endometrium) grows and sheds every month in response to hormones, endometriotic lesions—which are endometrial-like tissue outside of the uterus—also grow and shed each month. However, there is no outflow for this shed tissue and, as a result, there is an inflammatory response as well as pain. Depending on where those lesions implant, symptoms can include not only cyclic pelvic pain but also cyclic bowel/bladder pain. I’ve also had patients complain of cyclic sharp/shooting leg pain. 

Many times, patients present to us after having seen several different types of providers and having been diagnosed with conditions such as irritable bowel syndrome or painful bladder syndrome. However, if you talk to patients and ask them to tell you a little bit more about this bowel or bladder pain, they will frequently endorse that their symptoms are cyclic/most severe during their menses. With respect to pelvic pain, endometriosis-related pelvic pain is usually progressive—becoming progressively more painful over the years. These symptoms are strong indicators that endometriosis is the cause. A pelvic exam is also helpful as findings of nodularity or a fixed uterus may lend further support for endometriosis; a normal exam, however, does not rule out endometriosis. 

What are the primary imaging techniques used to diagnose endometriosis?

Dr. Flores: While history and physical exam are the primary components of the clinical diagnosis, imaging can also be helpful. The 2 techniques most often used are pelvic ultrasound and magnetic resonance imaging (MRI). 

While transvaginal ultrasound is sensitive and specific for diagnosing endometriomas (ovarian cysts of endometriotic tissue) and may also be able to accurately identify deep-infiltrating endometriosis, it is limited in its ability to visualize peritoneal disease. MRI can improve diagnosis of endometriosis and better estimate the depth of invasion of deep-infiltrating disease, as well as confirm diagnosis of an endometrioma. While MRI is an option for peritoneal endometriosis, superficial disease is usually not detected. Lastly, computed tomography imaging of the chest can be used when thoracic endometriosis is suspected but is otherwise not routinely recommended. Imaging is also helpful in ruling in/out other potential etiologies of pelvic pain such as fibroids and adenomyosis. It is important to recognize, however, that the absence of any findings of endometriosis on imaging does not rule out the disease. 

What other best practices do you implement in your day-to-day to aid in diagnosis?

Dr. Flores: Take the time to listen to your patient. Often, they’ve seen several providers before ultimately seeing a provider who can diagnosis their endometriosis without the need for surgical evaluation. We have to ask questions related to their pain and when the pain occurs, and we can’t forget to also ask about pain during intercourse, as well as non-menstrual pelvic pain. Additionally, it is important to recognize that, for patients who may have been suffering from endometriosis for several years before reaching a diagnosis, they may present with chronic pelvic pain. In this case, it is important to ask what their menstrual cycles were like before the pelvic pain became chronic, and usually patients note cyclic pelvic pain that became progressive. We also know that patients who have a first-degree relative with endometriosis are 7 times more likely to be affected by the disease, so asking about a family history of endometriosis is important. 

We have to think about endometriosis as a systemic disease. Previously, endometriosis was incorrectly thought of as solely a pelvic disease, but we've been learning more and more through research that it truly is a chronic, systemic disease with multifactorial effects throughout the body. For example, we have found that endometriosis affects regions of the brain associated with anxiety and depression, as well as causing changes in metabolism. For example, a common misconception is that women with a low body mass index (BMI) were at risk for endometriosis, when in fact it's just the opposite—it is the endometriosis that is causing changes in metabolism that lead to a decreased BMI. Patients with endometriosis also frequently struggle with mood disorders; therefore, we cannot dismiss this aspect of the disease process. It is imperative that we help patients feel heard and let them know that some of the mood symptoms they are experiencing may be related to their endometriosis. Expanding our view of endometriosis as a disease that extends beyond the pelvis and thinking about the systemic effects of endometriosis is key.

We have also identified small molecules (microRNAs) that are predictive of endometriosis. They are continuing to be investigated as a noninvasive biomarker of endometriosis.  

Can you talk a little more about these biomarkers?

Dr. Flores: In terms of biomarkers, this is actually some exciting work I was fortunate to be involved in with Dr. Hugh Taylor at Yale. We studied circulating molecules known as microRNAs—these are small, noncoding RNAs that can modify gene expression. In endometriosis, we've identified several that, when combined, have a high sensitivity and specificity for diagnosing endometriosis. These specific microRNAs are undergoing continued studies to ensure that they are reliable in predicting endometriosis. Hopefully they will be available soon for clinical use, as this would be of great value to help shorten the time to diagnosis of endometriosis and ultimately avoid delays in endometriosis treatment.

What is the value of considering noninvasive methods for the diagnosis of endometriosis?

Dr. Flores: There is great value in noninvasive diagnostics for endometriosis. This is because while surgical diagnosis is the “gold standard,” surgery is invasive, and waiting until a surgical diagnosis can be made further contributes to delays in diagnosis. However, more recently there has been a shift toward utilizing noninvasive approaches to the diagnosis of endometriosis, with the primary one focusing on clinically diagnosing endometriosis. 

One of the first things to remember is the importance of gathering a patient history and conducting a physical exam. We've all learned this in medical school, and it comes into play even more so with a condition such as endometriosis. Endometriosis is defined as a benign gynecologic disease characterized by endometrial-like tissue outside of the uterus, but this definition does not reflect the true scope and manifestations of endometriosis. Research over the years has demonstrated that endometriosis has systemic effects—affecting regions of the brain associated with anxiety/depression, altering pain sensitization, and having inflammatory effects that can not only affect the reproductive organs but also other organ systems. As such, our questions when evaluating patients for endometriosis need to focus on these various aspects of the disease. 

Endometriosis usually leads to cyclic pain. This is because just as the lining of the uterus (the endometrium) grows and sheds every month in response to hormones, endometriotic lesions—which are endometrial-like tissue outside of the uterus—also grow and shed each month. However, there is no outflow for this shed tissue and, as a result, there is an inflammatory response as well as pain. Depending on where those lesions implant, symptoms can include not only cyclic pelvic pain but also cyclic bowel/bladder pain. I’ve also had patients complain of cyclic sharp/shooting leg pain. 

Many times, patients present to us after having seen several different types of providers and having been diagnosed with conditions such as irritable bowel syndrome or painful bladder syndrome. However, if you talk to patients and ask them to tell you a little bit more about this bowel or bladder pain, they will frequently endorse that their symptoms are cyclic/most severe during their menses. With respect to pelvic pain, endometriosis-related pelvic pain is usually progressive—becoming progressively more painful over the years. These symptoms are strong indicators that endometriosis is the cause. A pelvic exam is also helpful as findings of nodularity or a fixed uterus may lend further support for endometriosis; a normal exam, however, does not rule out endometriosis. 

What are the primary imaging techniques used to diagnose endometriosis?

Dr. Flores: While history and physical exam are the primary components of the clinical diagnosis, imaging can also be helpful. The 2 techniques most often used are pelvic ultrasound and magnetic resonance imaging (MRI). 

While transvaginal ultrasound is sensitive and specific for diagnosing endometriomas (ovarian cysts of endometriotic tissue) and may also be able to accurately identify deep-infiltrating endometriosis, it is limited in its ability to visualize peritoneal disease. MRI can improve diagnosis of endometriosis and better estimate the depth of invasion of deep-infiltrating disease, as well as confirm diagnosis of an endometrioma. While MRI is an option for peritoneal endometriosis, superficial disease is usually not detected. Lastly, computed tomography imaging of the chest can be used when thoracic endometriosis is suspected but is otherwise not routinely recommended. Imaging is also helpful in ruling in/out other potential etiologies of pelvic pain such as fibroids and adenomyosis. It is important to recognize, however, that the absence of any findings of endometriosis on imaging does not rule out the disease. 

What other best practices do you implement in your day-to-day to aid in diagnosis?

Dr. Flores: Take the time to listen to your patient. Often, they’ve seen several providers before ultimately seeing a provider who can diagnosis their endometriosis without the need for surgical evaluation. We have to ask questions related to their pain and when the pain occurs, and we can’t forget to also ask about pain during intercourse, as well as non-menstrual pelvic pain. Additionally, it is important to recognize that, for patients who may have been suffering from endometriosis for several years before reaching a diagnosis, they may present with chronic pelvic pain. In this case, it is important to ask what their menstrual cycles were like before the pelvic pain became chronic, and usually patients note cyclic pelvic pain that became progressive. We also know that patients who have a first-degree relative with endometriosis are 7 times more likely to be affected by the disease, so asking about a family history of endometriosis is important. 

We have to think about endometriosis as a systemic disease. Previously, endometriosis was incorrectly thought of as solely a pelvic disease, but we've been learning more and more through research that it truly is a chronic, systemic disease with multifactorial effects throughout the body. For example, we have found that endometriosis affects regions of the brain associated with anxiety and depression, as well as causing changes in metabolism. For example, a common misconception is that women with a low body mass index (BMI) were at risk for endometriosis, when in fact it's just the opposite—it is the endometriosis that is causing changes in metabolism that lead to a decreased BMI. Patients with endometriosis also frequently struggle with mood disorders; therefore, we cannot dismiss this aspect of the disease process. It is imperative that we help patients feel heard and let them know that some of the mood symptoms they are experiencing may be related to their endometriosis. Expanding our view of endometriosis as a disease that extends beyond the pelvis and thinking about the systemic effects of endometriosis is key.

We have also identified small molecules (microRNAs) that are predictive of endometriosis. They are continuing to be investigated as a noninvasive biomarker of endometriosis.  

Can you talk a little more about these biomarkers?

Dr. Flores: In terms of biomarkers, this is actually some exciting work I was fortunate to be involved in with Dr. Hugh Taylor at Yale. We studied circulating molecules known as microRNAs—these are small, noncoding RNAs that can modify gene expression. In endometriosis, we've identified several that, when combined, have a high sensitivity and specificity for diagnosing endometriosis. These specific microRNAs are undergoing continued studies to ensure that they are reliable in predicting endometriosis. Hopefully they will be available soon for clinical use, as this would be of great value to help shorten the time to diagnosis of endometriosis and ultimately avoid delays in endometriosis treatment.

What is the value of considering noninvasive methods for the diagnosis of endometriosis?

Dr. Flores: There is great value in noninvasive diagnostics for endometriosis. This is because while surgical diagnosis is the “gold standard,” surgery is invasive, and waiting until a surgical diagnosis can be made further contributes to delays in diagnosis. However, more recently there has been a shift toward utilizing noninvasive approaches to the diagnosis of endometriosis, with the primary one focusing on clinically diagnosing endometriosis. 

One of the first things to remember is the importance of gathering a patient history and conducting a physical exam. We've all learned this in medical school, and it comes into play even more so with a condition such as endometriosis. Endometriosis is defined as a benign gynecologic disease characterized by endometrial-like tissue outside of the uterus, but this definition does not reflect the true scope and manifestations of endometriosis. Research over the years has demonstrated that endometriosis has systemic effects—affecting regions of the brain associated with anxiety/depression, altering pain sensitization, and having inflammatory effects that can not only affect the reproductive organs but also other organ systems. As such, our questions when evaluating patients for endometriosis need to focus on these various aspects of the disease. 

Endometriosis usually leads to cyclic pain. This is because just as the lining of the uterus (the endometrium) grows and sheds every month in response to hormones, endometriotic lesions—which are endometrial-like tissue outside of the uterus—also grow and shed each month. However, there is no outflow for this shed tissue and, as a result, there is an inflammatory response as well as pain. Depending on where those lesions implant, symptoms can include not only cyclic pelvic pain but also cyclic bowel/bladder pain. I’ve also had patients complain of cyclic sharp/shooting leg pain. 

Many times, patients present to us after having seen several different types of providers and having been diagnosed with conditions such as irritable bowel syndrome or painful bladder syndrome. However, if you talk to patients and ask them to tell you a little bit more about this bowel or bladder pain, they will frequently endorse that their symptoms are cyclic/most severe during their menses. With respect to pelvic pain, endometriosis-related pelvic pain is usually progressive—becoming progressively more painful over the years. These symptoms are strong indicators that endometriosis is the cause. A pelvic exam is also helpful as findings of nodularity or a fixed uterus may lend further support for endometriosis; a normal exam, however, does not rule out endometriosis. 

What are the primary imaging techniques used to diagnose endometriosis?

Dr. Flores: While history and physical exam are the primary components of the clinical diagnosis, imaging can also be helpful. The 2 techniques most often used are pelvic ultrasound and magnetic resonance imaging (MRI). 

While transvaginal ultrasound is sensitive and specific for diagnosing endometriomas (ovarian cysts of endometriotic tissue) and may also be able to accurately identify deep-infiltrating endometriosis, it is limited in its ability to visualize peritoneal disease. MRI can improve diagnosis of endometriosis and better estimate the depth of invasion of deep-infiltrating disease, as well as confirm diagnosis of an endometrioma. While MRI is an option for peritoneal endometriosis, superficial disease is usually not detected. Lastly, computed tomography imaging of the chest can be used when thoracic endometriosis is suspected but is otherwise not routinely recommended. Imaging is also helpful in ruling in/out other potential etiologies of pelvic pain such as fibroids and adenomyosis. It is important to recognize, however, that the absence of any findings of endometriosis on imaging does not rule out the disease. 

What other best practices do you implement in your day-to-day to aid in diagnosis?

Dr. Flores: Take the time to listen to your patient. Often, they’ve seen several providers before ultimately seeing a provider who can diagnosis their endometriosis without the need for surgical evaluation. We have to ask questions related to their pain and when the pain occurs, and we can’t forget to also ask about pain during intercourse, as well as non-menstrual pelvic pain. Additionally, it is important to recognize that, for patients who may have been suffering from endometriosis for several years before reaching a diagnosis, they may present with chronic pelvic pain. In this case, it is important to ask what their menstrual cycles were like before the pelvic pain became chronic, and usually patients note cyclic pelvic pain that became progressive. We also know that patients who have a first-degree relative with endometriosis are 7 times more likely to be affected by the disease, so asking about a family history of endometriosis is important. 

We have to think about endometriosis as a systemic disease. Previously, endometriosis was incorrectly thought of as solely a pelvic disease, but we've been learning more and more through research that it truly is a chronic, systemic disease with multifactorial effects throughout the body. For example, we have found that endometriosis affects regions of the brain associated with anxiety and depression, as well as causing changes in metabolism. For example, a common misconception is that women with a low body mass index (BMI) were at risk for endometriosis, when in fact it's just the opposite—it is the endometriosis that is causing changes in metabolism that lead to a decreased BMI. Patients with endometriosis also frequently struggle with mood disorders; therefore, we cannot dismiss this aspect of the disease process. It is imperative that we help patients feel heard and let them know that some of the mood symptoms they are experiencing may be related to their endometriosis. Expanding our view of endometriosis as a disease that extends beyond the pelvis and thinking about the systemic effects of endometriosis is key.

We have also identified small molecules (microRNAs) that are predictive of endometriosis. They are continuing to be investigated as a noninvasive biomarker of endometriosis.  

Can you talk a little more about these biomarkers?

Dr. Flores: In terms of biomarkers, this is actually some exciting work I was fortunate to be involved in with Dr. Hugh Taylor at Yale. We studied circulating molecules known as microRNAs—these are small, noncoding RNAs that can modify gene expression. In endometriosis, we've identified several that, when combined, have a high sensitivity and specificity for diagnosing endometriosis. These specific microRNAs are undergoing continued studies to ensure that they are reliable in predicting endometriosis. Hopefully they will be available soon for clinical use, as this would be of great value to help shorten the time to diagnosis of endometriosis and ultimately avoid delays in endometriosis treatment.