Collaborative Care: Improving Patient Satisfaction

and Outcomes in Endometriosis

While traditionally characterized by its pelvic manifestation, it is important to recognize that

endometriosis is much more than a pelvic disease; it is a systemic disease, with multifactorial
effects throughout the body.[1,2] Overall, an estimated 4 million reproductive-age women are
diagnosed with endometriosis in the US annually and about 6 of 10 endometriosis cases
remain undiagnosed.[1] It affects up to 80% of women with pelvic pain, up to 50% of women with
infertility, with an economic burden that exceeds $22 billion annually in the US.[2]

CHRONIC SYSTEMIC DISEASE AFFECTING MULTIPLE ORGANS[2]

• The lesions seen in the pelvis are just a small component of the disease
• The systemic nature of the disease may explain the extensive symptoms often associated with endometriosis
• Stem cells, microRNAs, and inflammation are some of the mechanisms that mediate these long-range effects[3]
• Psychosocial effects:[1,2]
o Decreases quality of life
o Negatively impacts daily activities and relationships
o Anxiety/depression
• Low body mass index (BMI) and altered metabolism[4,5]
o Induction of hepatic (anorexigenic) gene expression
o MicroRNA-mediated changes in adipocyte (metabolic) gene expression
• Systemic inflammation[6]
o Estradiol-mediated increased prostaglandin E2
o Aberrant microRNA expression and immune cell dysfunction
o Increased production of inflammatory cytokines
• Mood disorders (eg, depression and anxiety)[7,8]
o Altered gene expression in regions of the brain associated with anxiety and depression
o Decreased volume brain regions associated with emotional/sensory nerve processing

CHALLENGES IN MAKING A DIAGNOSIS[9-11]

• 6 to 11 year delay from symptom onset to diagnosis and treatment
• Many primary care physicians (PCPs) are unaware of the disease
• Symptoms are nonspecific or associated with other disorders
• Pain is subjective
• A non-invasive diagnostic test is not yet available
DIAGNOSING ENDOMETRIOSIS[2]
• While the current "gold standard" is surgically-based, it is important to recognize that with an increased understanding of the
systemic nature of the disease, a shift towards a clinical diagnosis can and should be made

o Current "gold standard" is surgery/direct visualization o Clinical diagnosis -- a diagnosis can and should be made
• Can remove lesions/be an additional treatment option, based on presenting (usually cyclic) symptoms, ultimately
and can at time allow for a pathologic diagnosis allowing treatment to be initiated much sooner
o Cons of surgery: o Symptoms vary but typically reflect area of involvement and
• Invasive procedure may include:
• Has its own risk of morbidity and rarely, mortality • Secondary dysmenorrhea
• Costly • Cyclic bowel/bladder pain
• Still difficult to detect microscopic and/or • Dyspareunia
subperitoneal lesions • Infertility
o Other methods of diagnosis include:
• Serum biomarkers
• Imaging and gynecological exam (serve to also help
rule out other diagnoses)

TREATMENT
• While surgical therapy treats local disease, medical therapy remains first line (and an important component of post-operative
management) as the risk of recurrence is up to 50% at 2 to 5 years following surgery[2]
First Line [2] Prediction of Response to Progestin-Based Second Line [2]
Therapy [12]
• Progestin-based therapy (including • Progesterone receptor (PR) expression Gonadotropin releasing hormone (GnRH)
combined oral contraceptives) in lesions predicted response to progestin- analogues
• At least 1/3 of women fail first based therapy • GnRH agonists
line therapy • High PR expression has a 100% response • GnRH antagonists
rate; low PR expression had only a 6% • Androgen derivatives
response rate • Aromatase inhibitors

CLINICAL IMPLICATIONS FOR PATIENT CARE

• Efforts to diagnose endometriosis must include recognition of the systemic manifestations
• While surgical therapy treats local disease, medical therapy may be needed to treat systemic manifestations
• Precision medicine may lead to better treatment with conventional medical therapies
• Future therapies will include agents that specifically target disseminated disease (eg, blocking stem cell recruitment or
microRNA signaling)
• Improved HCP and patient education regarding symptomatology and patient-centered communication by the healthcare team can
facilitate earlier diagnosis and timely individualized treatment of endometriosis
• The interprofessional healthcare team (including nurses) plays a role in counseling patients on endometriosis, fostering patient
engagement in care, and allowing for individualized management that is guided by each patient’s own priorities and preferences

References
1. Agarwal SK, et al. Clinical diagnosis of endometriosis: a call to action. Am J Obstet Gynecol. 2019;220:354.e1-354.e12.
2. Taylor HS, et al. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. Lancet. 2021;397:839-852.
3. Bjorkman S, et al. MicroRNAs in endometriosis: biological function and emerging biomarker candidates†. Biol Reprod. 2019;100:1135-1146. Erratum in: Biol
Reprod. 2019 Dec 24;101(6):1179.
4. Goetz TG, et al. Low body mass index in endometriosis is promoted by hepatic metabolic gene dysregulation in mice. Biol Reprod. 2016;95:115
5. Zolbin MM, et al. Adipocyte alterations in endometriosis: reduced numbers of stem cells and microRNA induced alterations in adipocyte metabolic gene
expression. Reprod Biol Endocrinol. 2019;17:36.
6. Nematian SE, et al. Systemic inflammation induced by microRNAs: endometriosis-derived alterations in circulating microRNA 125b-5p and let-7b-5p regulate
macrophage cytokine production. J Clin Endocrinol Metab. 2018;103:64-74.
7. Li T, et al. Endometriosis alters brain electrophysiology, gene expression and increases pain sensitization, anxiety, and depression in female mice. Biol Reprod.
2018;99:349-359.
8. As-Sanie S, et al. Changes in regional gray matter volume in women with chronic pelvic pain: a voxel-based morphometry study. Pain. 2012;153:1006-1014.
9. Ballard K, et al. What's the delay? A qualitative study of women's experiences of reaching a diagnosis of endometriosis. Fertil Steril. 2006;86:1296-1301.
10. Nnoaham KE, et al. Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril. 2011;96:366-373.e8.
11. Rogers PA, et al. Defining future directions for endometriosis research: workshop report from the 2011 World Congress of Endometriosis In Montpellier, France.
Reprod Sci. 2013;20:483-499.
12. Flores VA, et al. Progesterone receptor status predicts response to progestin therapy in endometriosis. J Clin Endocrinol Metab. 2018;103:4561-4568.

Independently developed by Medscape LLC and funded by AbbVie.

This information is provided for educational and informational purposes only and is not intended to recommend a particular product or therapy or to substitute for the clinical
judgment of a qualified healthcare professional.