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Category Archives: Treatment

3 years ago Treatment

Pain Management

Pain Management Options

Besides medication and surgery, there are many other methods to help you treat your pain. Pain often comes from more than one source, so it is important to look at several different possibilities that could be contributing to your pain. (see “Related Conditions“) Often a pain management specialist can help you navigate the variety of options to help you feel better.

Links:

Studies:

“Nerve Blocks: Neurolytic blocks of ganglion can be used effectively in some cases. The ganglion impar, or ganglion of Walther, is found on the ventral surface of the coccyx where it forms the caudal origin of the bilateral sympathetic chain. It has sympathetic innervation to the perineal and anal regions and a block of this innervation can disrupt afferent sympathetic and nociceptive signals from that area.13 Superior hypogastric plexus blocks (SHPB) with fluoroscopy or computed tomography (CT) guidance have also been used in malignant and non-oncological chronic pelvic pain.14 The superior hypogastric plexus is a retroperitoneal structure extending below the aortic bifurcation in association with the common and internal iliac vessels. It innervates much of the pelvic viscera including the bladder, urethra, uterus, vagina, vulva, perineum, prostate, penis, testes, rectum, and descending colon.

“Pelvic Floor Trigger Point Injections: Trigger point injections have been described in myofascial pain, including CPP.15 These injections can be beneficial when a patient presents with pelvic pain and is found to have one or more myofascial trigger points in the pelvic floor muscles. Trigger point injections are generally not used as a first-line treatment or monotherapy but are generally more beneficial when used alongside physical therapy, medication management, and behavioral therapy.15

“Pelvic Floor Botulinum Toxin Injections: For patients with refractory pelvic floor muscle spasm, botulinum toxin has been utilized to decrease spasm, therefore reducing pelvic pain. Botulinum toxin type A blocks the cholinergic transmission at the neuromuscular junction. Abbott et al.16 performed a double-blinded randomized, placebo-controlled trial in patients with CPP and demonstrated a significant decrease in dyspareunia and non-menstrual pain in the botulinum toxin group. In addition, they reported a significant reduction in pelvic floor pressure in the botulinum toxin group when compared to the pre-injection values. It is important to note that there were no statistically significant differences demonstrated between the groups in any of the previously mentioned parameters.

“Neuromodulation: Neuromodulation has also been used as a treatment for CPP. Neuromodulation is a nondestructive, neuromodulatory technique that delivers electrical stimulation to the spinal cord or peripheral nerves for the treatment of chronic pain. Patients with CPP may benefit from spinal cord stimulation, sacral stimulation, or peripheral nerve stimulation. In particular, tibial nerve stimulation, which is an in-office weekly procedure, has shown some promise in the treatment of pelvic pain, fecal incontinence, and overactive bladder.”

“Pain management should be individualized. The goal of medical therapy is to reduce pain by decreasing inflammation as well as ovarian and local hormone production (Table 1). Complete estrogen suppression may not be necessary to relieve endometriosis-associated pain.11 Medical treatment is usually not curative but suppressive, and symptoms will often recur after therapy discontinuation. The recurrence rate of endometriosis is highly variable, ranging from 4–74%.2,3 Initial treatment is typically use of combined oral contraceptive pills, which are effective in decreasing pain as well as in preventing postoperative recurrence.12 For those who cannot tolerate or have contraindications to estrogen, progestins such as medroxyprogesterone acetate, norethindrone acetate, or levonorgestrel are indicated. However, there are patients who have decreased receptor sensitivity as a result of aberrant gene expression in the eutopic endometrium that leads to progesterone resistance.13 For those unable to tolerate oral medications, the levonorgestrel-releasing intrauterine system can reduce pain and recurrence.4,14 However, the levonorgestrel-releasing intrauterine system does not inhibit ovulation and the recurrence of endometriomas. For those patients for whom the previous options have failed, we recommend using a gonadotropin-releasing hormone (GnRH) agonist with add-back therapy to prevent bone loss and to ease side effects. Patients taking GnRH agonists for endometriosis may develop resistance because endometrial-like tissue expresses aromatase and produces its estradiol.

“Our experience is mixed with GnRH antagonists, aromatase inhibitors, and bazedoxifene along with conjugated estrogens. Some patients obtain pain relief from these medications, but others discontinue them prematurely owing to high expectations of fast mitigation of symptoms.

“Since use was legalized in California, tetrahydrocannabinol and cannabidiol, either separately or in combination, present an alternative option. Patients frequently prefer these compounds over opioids, and their use is associated with less nausea and constipation. The use of tetrahydrocannabinol or cannabidiol is especially beneficial for managing postoperative pain, and their use does not have the addictive concerns associated with opioid use. We use an enhanced recovery after surgery protocol and highly discourage opioid use.

“Acupuncture is another potentially useful adjunct in treating the pain. It has been proposed to work by activating descending inhibitory pain pathways while centrally deactivating pain signals. Acupuncture also increases the pain threshold and leads to production of neurohumoral factors such as dopamine, nitric oxide, noradrenaline, acetylcholine, and others.15 In addition, it increases natural killer cells, thereby modifying immune function and decreasing estrogen production.15

“Pelvic physical therapy has been shown in a retrospective study to improve endometrial pain in 63% of patients after at least six sessions.4 Deep pressure massage, stretching pelvic floor muscles, joint mobilization, foam rollers with breathing, and relaxation techniques are the integral elements.

“Surgery remains the mainstay in definitive diagnosis. High-definition video laparoscopy with or without robotic assistance is the standard initial approach. In our extensive experience, laparotomy is seldom necessary. Excellent illumination with enhanced video magnification enables better recognition of subtle lesions as well as the depth of infiltrative lesions. Depending on the patient’s desire, the location of the lesion, the availability of proper instrumentation, as well as the experience and skill of the surgeon, eradication of endometriosis can be achieved with surgical management techniques that include excision, vaporization, and ablation. The non-surgical options discussed above can be used to supplement surgical treatment for long-term results.4 

“Laparoscopic uterosacral nerve ablation to disrupt efferent nerve fibers has been tested. However, multiple large randomized controlled trials did not find it to be beneficial in reducing endometriosis-associated pain. Complications of subsequent uterine prolapse and intraoperative ureteral transection have been reported with this procedure.16 In contrast, laparoscopic presacral neurectomy was 87% efficacious in reducing severe midline pelvic pain.2,4–6 We find this procedure especially effective in patients with mild or no endometriosis.17 The adverse effects associated with presacral neurectomy are constipation and bladder and urinary symptoms.17 We perform presacral neurectomy in only about 1% of our patients.

“A prospective, multicenter cohort study of 981 women with varying degrees of disease showed significant postsurgical symptom improvement over 36 months in patients who underwent laparoscopic excision of endometriosis. The most notable improvement was seen in dysmenorrhea, with a 57% reduction in symptoms; chronic pelvic pain and dyspareunia were reduced by 30%. Owing to recurrent pain, a second-look surgery was performed in 9% of patients and histologically confirmed endometriosis recurrence was documented in 5%. Of these patients, 7% benefited from medical therapy.18 Abbott et al demonstrated significant pain relief (80%) after surgery compared with a placebo group (32%). They report progression of disease with second-look laparoscopy in 45%, no change in 33%, and improvement in 22% of patients. Twenty percent of cases were not responsive to surgery.18”

3 years ago Treatment

Alternative and Complementary Therapies

People often turn to alternative and complementary therapies (ACT) to seek symptom relief and to support health in general. Several studies indicate that therapies such as yoga, acupuncture, and other ACTs can help ameliorate symptoms such as pelvic pain and provide overall support for health and well-being. Due caution is important when a product claims to be a “cure”. Before use, any therapy should be discussed with your provider. Here are a few things that have been studied:

Yoga

  • Goncalves, A. V., Barros, N. F., & Bahamondes, L. (2017). The practice of hatha yoga for the treatment of pain associated with endometriosis. The journal of alternative and complementary medicine, 23(1), 45-52. Retrieved from https://www.liebertpub.com/doi/abs/10.1089/acm.2015.0343 

“Results: The degree of daily pain was significantly lower among the women who practiced yoga compared with the non-yoga group (p = 0.0007). There was an improvement in QoL in both groups between the baseline and the end of the study evaluation. In relation to EHP-30 domains, pain (p = 0.0046), impotence (p = 0.0006), well-being (p = 0.0009), and image (p = 0.0087) from the central questionnaire, and work (p = 0.0027) and treatment (p = 0.0245) from the modular questionnaire were significantly different between the study groups over time. There was no significant difference between the two groups regarding the diary of menstrual patterns (p = 0.96). Conclusions: Yoga practice was associated with a reduction in levels of chronic pelvic pain and an improvement in QoL in women with endometriosis.”

*QoL – Quality of Life, EHP-30 – Endometriosis Health Profile

  • Gonçalves, A. V., Makuch, M. Y., Setubal, M. S., Barros, N. F., & Bahamondes, L. (2016). A qualitative study on the practice of yoga for women with pain-associated endometriosis. The journal of alternative and complementary medicine, 22(12), 977-982. Retrieved from https://www.liebertpub.com/doi/abs/10.1089/acm.2016.0021   

“Results: All participants reported that yoga was beneficial to control pelvic pain. They related that they were aware of the integration of body and psyche during yoga practice and that this helped in the management of pain. Women said they had identified a relationship between pain management and breathing techniques (pranayama) learned in yoga and that breathing increased their ability to be introspective, which relieved pain. The participants have developed greater self-knowledge, autonomy, and self-care and have reduced the use of pain and psychiatric medications. They created ties among themselves, suggesting that the yoga group allowed psychosocial support. Conclusions: Bodily and psychosocial mechanisms to control pain were identified in women with endometriosis. To reach such control, it is crucial that mind and body integrative techniques are learned.”

“Interventions included yoga, mindfulness, relaxation training, cognitive behavioral therapy combined with physical therapy, Chinese medicine combined with psychotherapy, and biofeedback. Results indicate that no studies have yet used gold-standard methodology and, thus, definitive conclusions cannot be offered about PMB efficacy. However, the results of these pilot studies suggest that PMB interventions show promise in alleviating pain, anxiety, depression, stress, and fatigue in women with endometriosis, and future well-designed RCTs including active control groups are warranted.”

  • Saxena, R., Gupta, M., Shankar, N., Jain, S., & Saxena, A. (2017). Effects of yogic intervention on pain scores and quality of life in females with chronic pelvic pain. International Journal of Yoga, 10(1), 9. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225749/

“Results: After 8 weeks of yogic intervention, Group II patients showed a significant decrease in the intensity of pain seen by a decrease in VAS score (P < 0.001) and improvement in the quality of life with a significant increase (P < 0.001) in physical, psychological, social, and environmental domain scores of WHOQOL-BREF. Conclusions: The practice of yoga causes a reduction in pain intensity and improves the quality of life in patients with chronic pelvic pain.”

*WHOQOL-BREF – World Health Organization Quality of Life

“Conclusion: The results support the use of yoga to improve pain and QOL in women with CPP. Future studies should aim to determine the minimal dosage needed for a successful yoga intervention and use a randomized controlled design with assessor blinding to increase the quality of evidence.”

*QOL- quality of life, CPP – chronic pelvic pain

Acupuncture:

  • Kong, S., Zhang, Y. H., Liu, C. F., Tsui, I., Guo, Y., Ai, B. B., & Han, F. J. (2014). The complementary and alternative medicine for endometriosis: a review of utilization and mechanism. Evidence-Based Complementary and Alternative Medicine, 2014. Retrieved from https://www.hindawi.com/journals/ecam/2014/146383/  

“Acupuncture therapy includes needling, auricular point, and moxa-moxibustion. It has the function of dredging meridian, regulating the balance of Yin and Yang (Chinese medicine believes that the balance of Yin and Yang determines people’s health), enhancing “Qi-Blood” circulation, thereby strengthening body’s resistance to disease and eliminating pathogenic factors. In clinic, acupuncture therapy for EM is confirmed to improve efficacy with fewer side effects, especially in EM-associated dysmenorrhoea. Acupuncture analgesia is usually used to treat pelvic pain and dysmenorrhoea related to EM by mediating the central nervous system (CNS) and releasing some specific neurotransmitters.”

*Dysmenorrhoea- pain with menstruation

“Recent advances in neuroendocrinology and immunology have provided an entry to understanding acupuncture….estrogen promotes the endometriosis progression through on-site inflammation. Current treatments for endometriosis involve hormonal therapy and surgical procedures, however, they both may induce several side effects. Several studies have shown that the administration of exogenous dopamine agonists can significantly suppress endometriosis progression. Acupuncture is multivalent in that it can simultaneously stimulate the secretion of endogenous dopamine to modulate the GnRH neuroendocrine pathway in CNS and the COX-2 inflammatory pathway in PNS. Hence, acupuncture can smoothly manage endometriosis without the side effects of exogenous dopamine. The endometriosis management by acupuncture provides us with an example of how to incorporate acupuncture into current biomedical systems. Acupuncture may provide a convenient, physiological method to regulate the neuroendocrine system in an integrative, systematic means.”

“To test the efficacy of acupuncture, we selected 42 women who were on the waiting list to undergo a video laparoscopy at the University Hospital of Florianópolis, Santa Catarina, Brazil. These women were divided into two sample groups. The first received the experimental treatment of acupuncture, and the other received placebo therapy, for which the needles were inserted 3 cm apart from the points of energy. Each group underwent five treatment sessions lasting an average of 40 min. Randomization was carried out using Clinical Trial Management System software, and the allocation sequence was performed by a laboratory assistant and hidden from the team conducting the project, which was responsible for collecting the information. To monitor the effects of this intervention, we used the visual analog scale (VAS) and the quality-of-life questionnaire for Endometriosis Health Profile 30 (EHP-30) endometriosis. Variables were measured at three-time points: pre-therapy, post-therapy, and 2 months after therapy. Results: The results were analyzed with SAS software version 9.1.3 using analysis of variance. A decrease in VAS scores for chronic pelvic pain and dyspareunia was observed in both groups analyzed. However, 2 months after therapy, the results were maintained only in the experimental group. Regarding quality of life, we observed an improvement in all variables analyzed, although these were statistically significant only in the experimental group. In contrast, the variable for infertility did not reach significance in either group. Conclusions: We concluded that acupuncture confers beneficial and long-lasting effects, even 2 months after therapy, as demonstrated by the variables studies.”

“Twenty‐four studies were identified that involved acupuncture for endometriosis; however only one trial, enrolling 67 participants, met all the inclusion criteria. The single included trial defined pain scores and cure rates according to the Guideline for Clinical Research on New Chinese Medicine. Dysmenorrhoea scores were lower in the acupuncture group (mean difference ‐4.81 points, 95% confidence interval ‐6.25 to ‐3.37, P < 0.00001) using the 15‐point Guideline for Clinical Research on New Chinese Medicine for Treatment of Pelvic Endometriosis scale. The total effective rate (‘cured’, ‘significantly effective’ or ‘effective’) for auricular acupuncture and Chinese herbal medicine was 91.9% and 60%, respectively (risk ratio 3.04, 95% confidence interval 1.65 to 5.62, P = 0.0004). The improvement rate did not differ significantly between auricular acupuncture and Chinese herbal medicine for cases of mild to moderate dysmenorrhoea, whereas auricular acupuncture did significantly reduce pain in cases of severe dysmenorrhoea.”

“Results: Three studies were found including 99 women, 13–40 years old, with diagnosed endometriosis. The studies were different in research design, needle stimulation techniques, and evaluation instruments. Methodological similarities were seven to 12 needle insertions per subject/session and 15–25 minutes of needle retention time. The needles were placed in the lower back/pelvic-abdominal area, in the shank, feet, and hands. Treatment numbers varied from nine to 16 and patients received one to two treatments per week. Similarity in reported treatment effects in the quoted studies, irrespective of research design or treatment technique, was reported decrease of rated pain intensity. Conclusion: Endometriosis is often painful, although with various origins, where standard treatments may be insufficient or involve side effects. Based on the reported studies, acupuncture could be tried as a complement as it is an overall safe treatment. In the future, studies designed for evaluating effectiveness between treatment strategies rather than efficacy design would be preferred as the analyses of treatment effects in the individual patients.”

Links:

3 years ago Treatment

The Importance of Mental Health Support in Endometriosis

by Deanna Denman, PhD, Licensed Psychologist, Clinical Health Psychologist

Endometriosis is intimately linked to mental health. While depression and anxiety together impact 10-20% of the general population, metanalyses (studies looking at the results of other studies to find trends) show higher rates of depression and anxiety in people with endometriosis (Delanerolle et al., 2021; Estes et al., 2021). Unfortunately, people with endometriosis also have a higher rate of self-directed violence (suicide and other forms of self-harm) than women without (Estes et al., 2021). In our efforts to spread awareness of endometriosis and effective treatments, it’s important we discuss the impact of living with endometriosis on mental health as well and normalize finding support.

Several factors related to endometriosis have demonstrated impact on mental health and several others are currently being researched. Pre-surgical and persistent post-surgical pain, hormone treatments, inflammation, and significant medical trauma may all contribute to depression, anxiety, and potentially PTSD in people living with endometriosis.

Pain & Mental Health

Chronic pain is the most recognized symptom of endometriosis. Painful periods, painful sex, and non-cyclical pelvic pain are associated with depression, anxiety, and self-harm. We have evidence more broadly that living with chronic pain causes depression and anxiety. Mood disturbance and anxiety are also associated with prolonged stress, disturbed sleep, disability, and isolation (from being unable to participate in social activities)—common concerns related to endometriosis.

In addition, depression makes the experience of pain worse. This is not simply a statement of “your attitude affects your pain.” The pathways to the brain that receive information about pain, also connect to the areas of the brain that process emotion (Sheng et al., 2017). We see decreases in neurotransmitters in the central nervous system that impact mood (i.e., dopamine, serotonin, and norepinephrine; IsHak et al., 2018; Sheng et al., 2017). There is also evidence of changes in the nerve factors and genes that affect re-wiring in the brain (Mamillapalli, et al., 2018; Sheng et al., 2017).

You may have read, or heard your doctor talking, about “central sensitization.” The International Association for the Study of Pain (IASP) has renamed this “nociplastic pain (Raja et al., 2020).” Research has shown that prolonged experience of pain can cause changes in the brain and spinal cord that magnify pain signals (Raja et al., 2020). The chronic pelvic pain among those suffering from endometriosis places people at high risk for developing nociplastic pain and other pain conditions (Li et al., 2018; Tokushige et al., 2007). On a positive note, there is evidence that our nervous systems can re-wire to turn the pain signals back down after the original pain source is resolved and this re-wiring can be supported with the help of a pain psychologist (Salomons et al., 2014).

Hormone Treatments and Mental Health

The hormone treatments commonly recommended for endometriosis can impact mood. Depression and anxiety are commonly recognized, but underappreciated, side effects of treatment with GnRHa’s (Warnock et al., 1998). One study showed prior use of GrHa’s and OCPs was associated with increased rates of depression (Estes et al., 2021). The larger literature shows mixed effects of combined hormonal contraceptives on mental health. There is, however, evidence to suggest there are potential negative effects of hormonal oral contraceptives among women who are already vulnerable to depression/anxiety (Siddall & Emmott, 2021).

Medical Trauma & Mental Health

The medical field is increasingly becoming aware of the trauma associated with life-altering and life-threatening medical diagnoses. Most often when thinking about a “trauma,” we consider some external threat (e.g.., car accident, war, sexual assault). Medical traumas, however, account for diagnoses, treatments, and medical events that may result in development of trauma symptoms (ISTSS, 2020). As a chronic, life-altering condition, endometriosis may result in medical trauma. The prolonged stress of living with pain, various medical treatments, and the impact of the condition on overall quality of life (e.g., work, social life, finances) can all contribute to medical trauma.

Nancy recently wrote an article on the rampant gaslighting in the medical community around endometriosis (https://www.linkedin.com/pulse/endometriosis-gaslighting-gold-standard-nancy-petersen/). The frustrations of repeatedly asking for help from your medical team and being denied, shamed, and sometimes blamed for pain can lead to depression, self-doubt, and shame. The delays in diagnosis of endometriosis often result in people suffering without explanation of their pain, but worse with messaging that their pain is “in their head,” or that endometriosis doesn’t cause the symptoms they are experiencing. On average, it still takes more than 7 years to receive a diagnosis of endometriosis. This does not include the time it takes obtain a consult with an expert and receive treatment (i.e., surgery).

Mental Healthcare & Endometriosis

All of these factors, of course, highlight the need for expert surgical excision and pelvic floor rehabilitation to treat endometriosis, rather than simple medication management. It is, however, also evident that ensuring patients have access to psychological care in the management of endometriosis is key to their overall wellbeing.

This is important. You do not need psychological care instead of medical care. I am advocating for mental health care in ADDITION to, and as part of, medical care. Mental health care is integrated in care of patients with other health conditions— we have long understood the psychological sequelae of cancer diagnoses and involved psychologists from the point of diagnosis through survivorship.

A good mental health provider can help with processing your experiences and frustrations around your endometriosis. Psychotherapy can also help patients work through medical trauma or trauma histories that make access to adequate medical care difficult (i.e., history of sexual trauma or abuse). Finally, some providers specialize in working with patients with chronic conditions and are trained to help manage chronic post-surgical pain, teach you relaxation techniques, and provide communication strategies to assist in advocating for your care and your needs within your relationships.

See tips on Choosing a Mental Health Therapist

References

Delanerolle, G., Ramakrishnan, R., Hapangama, D., Zeng, Y., Shetty, A., Elneil, S., … & Raymont, V. (2021). A systematic review and meta-analysis of the Endometriosis and Mental-Health Sequelae; The ELEMI Project. Women’s Health, 17, 17455065211019717.

Estes, S. J., Huisingh, C. E., Chiuve, S. E., Petruski-Ivleva, N., & Missmer, S. A. (2021). Depression, anxiety, and self-directed violence in women with endometriosis: A retrospective matched-cohort study. American Journal of Epidemiology, 190(5), 843-852.

International Society for Traumatic Stress Studies. (2020). Medical trauma clinician fact sheet. Retrieved from https://istss.org/ISTSS_Main/media/Documents/Medical-Trauma-Clinician-Fact-Sheet-2.pdf

IsHak, W. W., Wen, R. Y., Naghdechi, L., Vanle, B., Dang, J., Knosp, M., Dascal, J., Marcia, L., Gohar, Y., Eskander, L., Yadegar, J., Hanna, S., Sadek, A., Aguilar-Hernandez, L., Danovitch, I., & Louy, C. (2018). Pain and depression: A systematic review. Harvard Review of Psychiatry, 26(6), 352–363. https://doi.org/10.1097/HRP.0000000000000198

Li, T., Mamillapalli, R., Ding, S., Chang, H., Liu, Z. W., Gao, X. B., & Taylor, H. S. (2018). Endometriosis alters brain electrophysiology, gene expression and increases pain sensitization, anxiety, and depression in female mice. Biology of Reproduction, 99(2), 349-359.

Salomons, T. V., Moayedi, M., Erpelding, N. and Davis, K. D. (2014) A brief cognitive-behavioural intervention for pain reduces secondary hyperalgesia. Pain, 155 (8). pp. 1446- 1452. ISSN 0304-3959 doi: https://doi.org/10.1016/j.pain.2014.02.012

Sheng, J., Liu, S., Wang, Y., Cui, R., & Zhang, X. (2017). The link between depression and chronic pain: Neural mechanisms in the brain. Neural Plasticity, 2017, 1-10. https://doi.org/10.1155/2017/9724371

Siddall, J. R., & Emmott, E. H. (2021). Hormonal Oral Contraceptive Use and Depression and Anxiety in England.

Warnock, J. K., Bundren, J. C., & Morris, D. W. (1998). Depressive symptoms associated with gonadotropin‐releasing hormone agonists. Depression and anxiety, 7(4), 171-177.

3 years ago Treatment

Physical Therapy Resources

Endometriosis can cause problems with the surrounding muscles and soft tissues. Pelvic floor spasms, tight muscles, other myofascial changes, and more will often contribute to symptoms (such as pain with defecation or pain with sex). These muscular and soft tissue changes can benefit from pelvic physical therapy. However, appropriate therapy for endometriosis-associated problems requires a specific skill set by your physical therapist (Amundsen & Kawasaki, 2011). Here are some resources to help you know what to expect and what to look for with physical therapy:

Links:

Studies:

  • dos Bispo, A. P. S., Ploger, C., Loureiro, A. F., Sato, H., Kolpeman, A., Girão, M. J. B. C., & Schor, E. (2016). Assessment of pelvic floor muscles in women with deep endometriosis. Archives of gynecology and obstetrics, 294(3), 519-523. Retrieved from https://link.springer.com/article/10.1007/s00404-016-4025-x

“Women with deep endometriosis have increased prevalence of pelvic floor muscle spasms when compared to the control group.”

  • Aredo, J. V., Heyrana, K. J., Karp, B. I., Shah, J. P., & Stratton, P. (2017, January). Relating chronic pelvic pain and endometriosis to signs of sensitization and myofascial pain and dysfunction. In Seminars in Reproductive Medicine (Vol. 35, No. 1, p. 88). NIH Public Access. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585080/

“Treatment for pelvic pain associated with endometriosis warrants identification and therapy directed to the pathological findings that generate and sustain pain symptoms. Since a myofascial source may contribute to endometriosis-associated CPP even after hormonal and surgical treatment has been undertaken, a growing number of practitioners are exploring pain management methods that directly address myofascial pain.”

“Levator myalgia, myofascial pelvic pain syndrome, and pelvic floor spasm are all terms that describe a condition that may affect as many as 78% of women who are given a diagnosis of chronic pelvic pain.1 This syndrome may be represented by an array of symptoms, including pelvic pressure, dyspareunia, rectal discomfort, and irritative urinary symptoms such as spasms, frequency, and urgency. It is characterized by the presence of tight, band-like pelvic muscles that reproduce the patient’s pain when palpated…Physical therapy of the pelvic floor—otherwise known as pelvic myofascial therapy—requires a therapist who is highly trained and specialized in this technique. It is more invasive than other forms of rehabilitative therapy because of the need to perform transvaginal maneuvers.”

3 years ago Treatment

Effects of Long-Term Low Estrogen States

An often used treatment for endometriosis is to lower the estrogen in a woman’s body via hormonal suppression. Birth control can mimic a pregnancy state, while other treatments, such as gonadotrophin-releasing hormone agonists (GnRHa), can mimic a menopausal state. So what does estrogen do in the body and why do they want to lower it? 

Estrogen not only affects the reproductive organs, but it also affects the heart and blood vessels, bones, breasts, skin, hair, mucous membranes, pelvic muscles, the urinary tract, and the brain (University of Rochester Medical Center Rochester, n.d.). All these different tissues have estrogen receptors (ER) on them that, when activated by estrogen, tell the cell how to behave. Endometriosis also has estrogen receptors. Estrogen, via these receptors, cause an increase in endometriotic “lesion size, fluid volume, increased epithelial cell height, and epithelial cell proliferation” (Burns et al., 2012). The thought is that by decreasing estrogen, the endometriotic lesions can be “tamed”, so to speak. However, estrogen still has receptors in all those other tissues and has an important role in the functioning of those other areas.

According to Medical New Today (De Pietro, 2018), low estrogenic states can have the following effects:

  • “Weak bones: Estrogen helps keep the bones healthful and strong. As estrogen levels decrease, bone loss may occur. For example, women who are post-menopausal are at an increased risk of developing osteoporosis and bone fractures.
  • Painful intercourse: Estrogen can affect vaginal lubrication. If levels become too low, vaginal dryness can occur, which often leads to painful sex.
  • Hot flashes: Hot flashes often happen during menopause due to low estrogen levels.
  • Depression: Estrogen is thought to increase serotonin, which is a chemical in the brain that boosts mood. Estrogen deficiency may cause a decline in serotonin that contributes to mood swings or depression.
  • Increase in urinary tract infections: Increased urinary tract infections may occur due to the thinning of the tissue in the urethra, which can develop with decreased estrogen.”

The low estrogenic states induced by the medications can cause side-effects similar to menopause: “hot flashes/sweats, headache/migraine, decreased libido (interest in sex), depression/emotional lability (changes in mood), dizziness, nausea/vomiting, pain, vaginitis, and weight gain” (LupronDepot, n.d.). When estrogen is lowered to a chemically induced menopausal state for a long time, it can cause serious effects. “Regardless of the cause,…women who experience premature menopause (before age 40 years) or early menopause (between ages 40 and 45 years) experience an increased risk of overall mortality, cardiovascular diseases, neurological diseases, psychiatric diseases, osteoporosis, and other sequelae” (Shuster et al., 2010). The effect on bone health is why GnRHa medications are recommended as treatment for no longer than 12 months total therapy (two 6-month treatments)- “due to concerns about adverse impact on bone thinning” (LupronDepot, n.d.). This thinning of the bones “may not be completely reversible in some patients” (LupronDepot, n.d.). This should be considered and discussed with your provider when looking at long term options. 

When looking at effectiveness of treatment with hormonal medications:

“Combined oral contraceptive pills (COCP), GnRHa and progestogens are equally effective in relieving endometriosis associated pelvic pain. COCP and progestogens are relatively cheap and more suitable for long-term use as compared to GnRHa. Long-term RCT of medicated contraceptive devices like Mirena and Implanon are required to evaluate their long-term effects on relieving the endometriosis associated pelvic pain.” (Wong & Lim, 2011)

References

Burns, K. A., Rodriguez, K. F., Hewitt, S. C., Janardhan, K. S., Young, S. L., & Korach, K. S. (2012). Role of estrogen receptor signaling required for endometriosis-like lesion establishment in a mouse model. Endocrinology, 153(8), 3960-3971. doi: 10.1210/en.2012-1294

De Pietro, M. (2018). What happens when estrogen levels are low?. Retrieved from https://www.medicalnewstoday.com/articles/321064.php#diagnosis

LupronDepot. (n.d.). Lupron Depot for endometriosis. Retrieved from https://www.luprongyn.com/lupron-for-endometriosis

Shuster, L. T., Rhodes, D. J., Gostout, B. S., Grossardt, B. R., & Rocca, W. A. (2010). Premature menopause or early menopause: long-term health consequences. Maturitas, 65(2), 161-166. doi: 10.1016/j.maturitas.2009.08.003

University of Rochester Medical Center Rochester. (n.d.). Estrogen’s effects on the female body. Retrieved from https://www.urmc.rochester.edu/encyclopedia/content.aspx?ContentTypeID=85&ContentID=P00559

Wong, W. S. F., & Lim, C. E. D. (2011). Hormonal treatment for endometriosis associated pelvic pain. Iranian journal of reproductive medicine, 9(3), 163. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575749/

3 years ago Treatment

Medication to Prevent Recurrence

Understanding Medications That Help Prevent Recurrence

“Should I take medication to prevent recurrence of my endo?” There is no definitive answer to this question- it is an individual choice that should be discussed with your provider. However, evidence points to it not being needed if ALL endometriosis is removed with surgery. A few things to consider:

Is it truly a “recurrence” or just missed disease?

A significant factor to consider is if all endometriotic lesions were removed in the first place:

  • “…findings all support that residual lesions seems to be the primary reason for the recurrence of the disease” (Selçuk & Bozdağ, 2013).
  • “Lack of complete surgical excision was another independent risk factor for recurrence of disease” (Ianieri, Mautone, & Ceccaroni, 2018).
  • Deep infiltrating disease has a much lower recurrence rate with complete excision versus incomplete (3.9% versus 35.3%!) (Cao et al., 2015).
  • “The experience of the surgeon is also a factor that implies the risk of recurrence” (Selçuk & Bozdağ, 2013).
  • Interestingly, prior medical treatment before excision can increase the risk for recurrence (Koga et al., 2013).

Does it involve a type of endometriosis that has higher recurrence risk, such as ovarian, peritoneal, or deep infiltrating disease (stage 3 or 4)? Are you at a young age (under 21 years)?

  • There is a higher recurrence risk with ovarian, peritoneal, or deep infiltrating disease (stage 3 or 4) (Selçuk & Bozdağ, 2013). Ovarian endometriomas have a recurrence rate of 11-32% (higher risk in younger patients and those with advanced disease) (Koga et al., 2013).
  • Those at a younger age (under 21 years) have a higher recurrence rate (Tandoi et al., 2011).
  • However, these factors depend again on the ability to remove the disease. The skill of the surgeon and having an interdisciplinary team can increase the odds of removing more advanced disease and decrease the risk of recurrence- this holds true even for younger patients (Fischer et al., 2013; Yeung et al., 2011). (See Why Excision)

Are there other conditions that can be causing continued symptoms that are similar to endometriosis symptoms (adenomyosis, interstitial cystitis, etc.)?

  • Most of us with endometriosis have more than one condition that can mimic the symptoms of endometriosis. Those conditions need treatment and might benefit from medical management, depending on your situation and your goals.  (See Related Conditions)

Remember, medications overall are “suppressive rather than curative” (Falcone & Flyckt, 2018). In addition, hormonal medication may not stop the progression of disease- this is particularly important where the ureters and/or bowel are involved (Barra et al., 2018; Ferrero et al., 2011; Millochau et al., 2016).

There are many studies and arguments for both sides. Here are a few:

Against it:

  • “There is currently no evidence to support any treatment being recommended to prevent the recurrence of endometriosis following conservative surgery.” (Sanghera et al., 2016)
  • “Many studies have investigated factors determining the recurrence of endometrioma and pain after surgery [16, 19, 20]…. Regardless of the mechanism, the present and previous studies suggest that postoperative medical treatment is known to delay but not completely prevent recurrence…. In our study, we also failed to observe a benefit for postoperative medication in preventing endometrioma and/or endometriosis-related pain recurrence.” (Li et al., 2019)
  • “Complete laparoscopic excision of endometriosis in teenagers–including areas of typical and atypical endometriosis–has the potential to eradicate disease. These results do not depend on postoperative hormonal suppression.” (Yeung et al., 2011)
  • “A systematic review found that post-surgical hormonal treatment of endometriosis compared with surgery alone has no benefit for the outcomes of pain or pregnancy rates…it found that there is insufficient evidence to conclude that hormonal suppression in association with surgery for endometriosis is associated with a significant benefit with regard to any of the outcomes identified….Moreover, even if post-operation medication proves to be effective in reducing recurrence risk, it is questionable that ‘all’ patients would require such medication in order to reduce the risk of recurrence. It has been reported that about 9% of women with endometriosis simply do not respond to progestin treatment….Therefore, the use of post-operation medication indiscriminately may cause unnecessary side effects (and an increase in health care costs) in some patients who may intrinsically have a much lower risk than others and in others who may be simply resistant to the therapy. The identification of high-risk patients who may benefit the most from drug intervention would remain a challenge.” (Guo, 2009)
  • “GnRHa administration is followed by a temporary improvement of pain in patients with incomplete surgical treatment. It seems that it has no role on post-surgical pain when the surgeon is able to completely excise DIE implants.” (Angioni et al., 2015)

For it:

  • “Post-operative hormonal suppression following conservative endometriosis surgery decreases the odds of disease recurrence and results in greater reductions in pelvic pain/dysmenorrhea compared to expectant management.” (Zakhari et al., 2019)
  • “Laparoscopic excision is considered as the ‘gold standard’ treatment of ovarian endometrioma. However, a frustrating aspect is that disease can recur….Regarding post-operative medical management for preventing recurrence, GnRH analogue and danazol have not been proved to be effective mainly because most trials used these drugs over short periods. In contrast, long term administration of OC is safe and tolerable and recommended for those who do not want to conceive immediately after the surgery.” (Koga et al., 2013)

References

Angioni, S., Pontis, A., Dessole, M., Surico, D., Nardone, C. D. C., & Melis, I. (2015). Pain control and quality of life after laparoscopic en-block resection of deep infiltrating endometriosis (DIE) vs. incomplete surgical treatment with or without GnRHa administration after surgery. Archives of gynecology and obstetrics, 291(2), 363-370.  Retrieved from https://link.springer.com/article/10.1007/s00404-014-3411-5

Barra, F., Scala, C., Biscaldi, E., Vellone, V. G., Ceccaroni, M., Terrone, C., & Ferrero, S. (2018). Ureteral endometriosis: a systematic review of epidemiology, pathogenesis, diagnosis, treatment, risk of malignant transformation and fertility. Human reproduction update, 24(6), 710-730. https://academic.oup.com/humupd/article/24/6/710/5085039?login=true

Cao, Q., Lu, F., Feng, W. W., Ding, J. X., & Hua, K. Q. (2015). Comparison of complete and incomplete excision of deep infiltrating endometriosis. International journal of clinical and experimental medicine, 8(11), 21497. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4723943/

Falcone, T., & Flyckt, R. (2018). Clinical management of endometriosis. Obstetrics & Gynecology, 131(3), 557-571. Retrieved from https://journals.lww.com/greenjournal/Abstract/2018/03000/Clinical_Management_of_Endometriosis.23.aspx?context=FeaturedArticles&collectionId=4

Ferrero, S., Camerini, G., Venturini, P. L., Biscaldi, E., & Remorgida, V. (2011). Progression of bowel endometriosis during treatment with the oral contraceptive pill. Gynecological Surgery, 8(3), 311-313. Retrieved from https://link.springer.com/article/10.1007/s10397-010-0610-3

Fischer, J., Giudice, L. C., Milad, M., Mosbrucker, C., & Sinervo, K. R. (2013). Diagnosis & management of endometriosis: pathophysiology to practice. APGO Educational Series on Women’s Health Issues. Retrieved from https://www.ed.ac.uk/files/atoms/files/diagnosis_and_management_of_endometriosis_booklet.pdf

Guo, S. W. (2009). Recurrence of endometriosis and its control. Human reproduction update, 15(4), 441-461. Retrieved from http://humupd.oxfordjournals.org/content/15/4/441.full

Ianieri, M. M., Mautone, D., & Ceccaroni, M. (2018). Recurrence in deep infiltrating endometriosis: a systematic review of the literature. Journal of minimally invasive gynecology, 25(5), 786-793. Retrieved from https://www.sciencedirect.com/science/article/pii/S1553465018300372

Koga, K., Osuga, Y., Takemura, Y., Takamura, M., & Taketani, Y. (2013). Recurrence of endometrioma after laparoscopic excision and its prevention by medical management. Front Biosci (Elite Ed), 5, 676-683.  Retrieved from https://pdfs.semanticscholar.org/2da7/5702eac08b0a32fb31bd5478be9e5d43a8b7.pdf

Li, X. Y., Chao, X. P., Leng, J. H., Zhang, W., Zhang, J. J., Dai, Y., … & Wu, Y. S. (2019). Risk factors for postoperative recurrence of ovarian endometriosis: long-term follow-up of 358 women. Journal of Ovarian Research, 12(1), 79. Retrieved from https://ovarianresearch.biomedcentral.com/articles/10.1186/s13048-019-0552-y

Millochau, J. C., Abo, C., Darwish, B., Huet, E., Dietrich, G., & Roman, H. (2016). Continuous amenorrhea may be insufficient to stop the progression of colorectal endometriosis. Journal of minimally invasive gynecology, 23(5), 839-842. Retrieved from https://www.jmig.org/article/S1553-4650(16)30047-4/abstract?fbclid=IwAR2Q7o1kJtfNNgMd0Q4_5K0BDe9_DjH1QOUTxTLK2HpgiFVgws5NT9xVdwo

Sanghera, S., Barton, P., Bhattacharya, S., Horne, A. W., & Roberts, T. E. (2016). Pharmaceutical treatments to prevent recurrence of endometriosis following surgery: a model-based economic evaluation. BMJ open, 6(4), e010580. Retrieved from http://bmjopen.bmj.com/content/6/4/e010580.long

Selçuk, İ., & Bozdağ, G. (2013). Recurrence of endometriosis; risk factors, mechanisms and biomarkers; review of the literature. Journal of the Turkish German Gynecological Association, 14(2), 98. Retrieved from https://journals.sagepub.com/doi/full/10.2217/whe.15.56

Tandoi, I., Somigliana, E., Riparini, J., Ronzoni, S., & Candiani, M. (2011). High rate of endometriosis recurrence in young women. Journal of pediatric and adolescent gynecology, 24(6), 376-379. Retrieved from https://doi.org/10.1016/j.jpag.2011.06.012

Yeung Jr, P., Sinervo, K., Winer, W., & Albee Jr, R. B. (2011). Complete laparoscopic excision of endometriosis in teenagers: is postoperative hormonal suppression necessary?. Fertility and sterility, 95(6), 1909-1912.  Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21420081

Zakhari, A., Delpero, E., McKeown, S., Murji, A., & Bougie, O. (2019). Long Term Outcomes of Post-Operative Hormonal Suppression in Patients with Endometriosis: A Systematic Review and Meta-Analysis. Journal of Minimally Invasive Gynecology, 26(7), S90.  Retrieved from https://www.sciencedirect.com/science/article/pii/S1553465019311641

3 years ago Treatment

A Quick Guide to Pain Control

By Elaine Bird
This is meant to be a quick guide to help members understand the reasoning behind their doctors choice of pain relief. It is not meant to replace medical advice.The WHO’s pain relief ladder is a guide to controlling pain:

STEP 1: Non-opioid agent, including NSAIDs and acetaminophen Adjucant analgesia, including corticosteroids and antidepressants

pain resisting or increasing

STEP 2: Opioid for mild to moderate pain Non-opioid agent
Adjuvant analgesia

pain resisting or increasing

STEP 3: Opioid for moderate to severe pain Non-opioid agent
Adjuvant analgesia

Paracetamol or acetaminophen as it is also known is a very safe and effective painkiller when taken in regular intervals. It has been used to reduce the levels of narcotics that patients have to use to control their pain. I would always recommend that a patient suffering chronic pain should be on regular paracetamol.

NSAIDs (non steroidal anti-inflammatory drugs) such as aspirin, ibuprofen, naproxen and mefenamic acid to name a few can be very beneficial BUT can be harsh on the stomach and kidneys. Anyone taking long term NSAIDs should be on tablets known as PPIs such as omeprazole or lansoprazole to protect the stomach from damage. NSAIDs should always be taken on a full stomach, a glass of milk and a biscuit is not sufficient, with a large glass of water. It is very important not to become dehydrated while taking NSAIDs as this can cause kidney damage.

Antidepressants also have a valuable role to play in treating chronic pain. This does not mean your doctor thinks it’s all in your head or you’re just depressed. Science does not completely understand how we perceive pain yet. However there is evidence that the increase in certain brain chemicals such as serotonin and noradrenaline that antidepressants cause help with pain relief. Also there is a link between chronic pain and depression so the use of antidepressants to treat chronic pain is two-fold. The most common antidepressant to treat chronic pain is amitriptyline, which is used at doses of 150mg to 200mg to treat depression but used at 10mg to 50mg to treat pain. Amitriptyline has the added bonus of causing drowsiness and so can help with the insomnia that often accompanies chronic pain. Of course it is not for everyone and if this dosen’t work or the side effects are too much there are alternatives available. This can be discussed further with your doctor.

As for opiates, yes they are addictive and cause drowsiness and are not the most effective pain killers for all kinds of pain such as nerve pain but they still have a role to play in treating pain. If you find you need to start on opiates adding a weak opiate such as codeine 15-30mg to your regular paracetamol dose is the best way to do it to keep your dose as low as possible for as long as possible. When or if this stops being as effective then a controlled release formula is the next best option so that your pain relief levels stay the same all the time rather than dipping and rising as you take your dose every four to six hours or as prescribed.

I would not be too worried about addiction when taking opiates for pain. Addiction is rare when taking them for pain relief, although not unheard of, however if you were to become addicted then detox is a lot easier to deal when you don’t have all the psychosocial problems that illegal users have. There is already a great article in the files regarding the difference between dependence and addiction so I’m not going to go into detail here but getting your pain under control is much more important in the short term.

If your pain is not chronic but only occurs when you have your period or when you are ovulating it might be better to start your pain relief regime before you actually experience any pain, say a day or two before your due your period or at the first sign of bleeding at the latest. Waiting until you are in pain means you’ve got to wait for the pain killers to kick in and may mean you have to take a stronger dose initially to get the same pain relief.

For more information on pain relief the British Pain Society www.britishpainsociety.org has some excellent resources.

Just to add that although the ladder here lists corticosteroids such as prednisolone as a treatment for pain they are not appropriate for endometriosis. They can cause a huge range of side effects and can be very effective in reducing the damage done by inflammation in diseases like arthritis but since the inflammation endometriosis causes doesn’t cause any real long term damage then the risk of side effects outweighs any potential benefits.

3 years ago Treatment

Pain Medications

Medications are used to help alleviate the symptoms of endometriosis. They do not get rid of the disease itself. Often, once medications are stopped, the symptoms return. Taking any medication for an extended amount of time can have significant effects on your body. It is important that you educate yourself about what medications you decide to take and understand both the short-term and long-term effects on your body. Also, medications alone for most will be insufficient to help with symptoms from endometriosis and other related conditions. A multidisciplinary approach, such as pelvic physical therapy, is necessary to enhance relief of chronic pelvic pain for the long term. 

It is also important to discuss a long term plan with your provider. As long as endometriosis lesions are present, irritation to muscles and nerves that can cause pain will continue. Addressing the underlying problem is important for long term goals. It is also important to address other pain generators, such as pelvic floor dysfunction or interstitial cystitis/bladder pain syndrome. 

Different medications can be used to help alleviate chronic pelvic pain and other related conditions. Alleviate does not necessarily mean eliminate. It is important to discuss with your provider the risks and benefits to your body, because everyone will respond differently and have other issues to consider when choosing a medication. Hormonal treatments are also meant to address pain (see “Hormonal Medications“).

Medication to treat pain might include:

  • Nonsteroidal anti-inflammatory drugs (NSAID’s): These work by decreasing the inflammatory response of your body to endometriosis. (see “Fatigue” and “Inflammation“)

“Nonsteroidal anti-inflammatory drugs are readily available without prescription for pain relief. They work by preventing or slowing down the production of prostaglandins, which helps to relieve the painful cramps associated with endometriosis. However, a Cochrane review on the use of NSAIDs for painful periods found greater risk of stomach upset (e.g. nausea, diarrhoea) or other side effects (e.g. headache, drowsiness, dizziness, dryness of the mouth).”

  • Brown, J., Crawford, T. J., Allen, C., Hopewell, S., & Prentice, A. (2017). Nonsteroidal anti‐inflammatory drugs for pain in women with endometriosis. Cochrane Database of Systematic Reviews, (1). Retrieved from https://doi.org/10.1002/14651858.CD004753.pub4

Many times, the use of nonsteroidal anti-inflammatories (NSAIDs), such naproxen, are suggested to help with pelvic pain. A meta-analysis done by Brown et al. (2017), however, couldn’t find much evidence to prove “the effectiveness of NSAIDs (specifically naproxen) for management of pain caused by endometriosis”. But the authors also point out that “nonsteroidal anti‐inflammatory drugs are readily available without prescription for pain relief. They work by preventing or slowing down the production of prostaglandins, which helps to relieve the painful cramps associated with endometriosis”. But they do caution about the side effects to the gastrointestinal system.

“NSAIDs are a type of pain medicine that can help to relieve the pain caused by endometriosis. The medicine works by stopping the release of prostaglandins, one of the main chemicals responsible for pain in general as well as painful menstrual periods. Starting these medications one to two days before your period works best to prevent prostaglandin production and therefore reduce pain. It may take some time, and several doses, for the NSAIDs to block the prostaglandin production and reduce pain. NSAIDs do not shrink or prevent the growth of endometriosis. Most NSAIDs are available without a prescription, including: Ibuprofen (sold as Advil, Motrin, and store brands) or Naproxen sodium (sold as Aleve, Anaprox, Naprosyn, and store brands). If over-the-counter NSAIDs are not effective, prescription doses and formulations may be helpful. The disadvantage of NSAIDs is that they do not always relieve endometriosis-related pain. NSAIDs probably work better when combined with another treatment, like hormonal birth control. Serious side effects from NSAIDs, although uncommon, include stomach upset, kidney problems, and worsened high blood pressure.”

“First-line medical treatment for pain due to endometriosis is often a nonsteroidal anti-inflammatory drug, either by prescription or over-the-counter. Although these antiprostaglandin agents have been shown to be effective for the treatment of primary dysmenorrhea (58), a Cochrane analysis found insufficient data to show that they significantly reduce endometriosis pain (59).”

  • Acetaminophen/Paracetamol (Tylenol): Acetaminophen, like NSAIDs, can inhibit prostaglandins that contribute to pain sensation. Some people may tolerate acetaminophen better than NSAIDs.  Because it is combined with many other over-the-counter as well as prescription medications, it is important that you examine the contents of medications you take carefully to avoid taking too much. 

“The exact mechanism of action of paracetamol is unknown, however, it is also believed to work by inhibiting central prostaglandin synthesis, and works well as a drug potentiator, increasing the effectiveness of other analgesic medications. Dose-related hepatotxicity is a major known risk of acetaminophen [27]. Few studies have identified it as an effective pain reliever alone [24]; however, when combined with NSAIDs or caffeine, paracetamol has been shown to achieve moderate levels of pain relief with menstrual pelvic pain [28,29].”

  • Muscle Relaxants: These might be used to help with cramping and muscular pain. The uterus as well as the bladder are muscular organs. Irritation to the surrounding pelvic floor muscles can also cause pain. Muscle relaxants include baclofen, tizanidine (Zanaflex), cyclobenzaprine (Flexeril) hyoscyamine, oxybutynin, or diazepam. Muscle relaxants are available to take by mouth but may be prescribed to use in a topical lotion or cream, or used intravaginally (inside of the vagina). It is important you follow the directions on the prescription from your provider.

“Muscle relaxants are also commonly used for symptom relief when pelvic floor muscle spasm is contributing to the patient’s pain. Oral muscle relaxants may help reduce overall muscle tone that is perceived to be painful but are not specific for the pelvic floor. Cyclobenzaprine, when taken daily, has an effect similar to the tricyclic antidepressants. It may be best prescribed at night given its sedative side effects. Of note, patients should be monitored for urinary retention when on cyclobenzaprine. Certain muscle relaxants, such as diazepam and baclofen can be made into a suppository or compounded cream and used intravaginally. Vaginal diazepam is generally well tolerated, with the major side effect being drowsiness. In a retrospective review by Carrico and Peters, 67% of women reported no adverse effects from the vaginal diazepam, while 33% of women reported some drowsiness.11 Topical lidocaine can also been used in the treatment of severe penetrative dyspareunia. This medication is especially useful when used prior to intercourse. Lidocaine gel can also be used internally prior to physical therapy for patients that have trouble tolerating internal myofascial release of the pelvic floor muscles.”

  • Antidepressant medications: If your provider mentions antidepressant medications, they are not suggesting it’s “all in your head”. Serotonin and norepinephrine (chemicals in the brain), which antidepressant medications affect, are implicated in pain as well as mood. (see “Pain with Endometriosis“) 

“In the brain stem, the neurotransmitters serotonin and norepinephrine modulate pain transmission through ascending and descending neural pathways. Both serotonin and norepinephrine are also key neurotransmitters involved with the pathophysiology of depression. Tricyclic antidepressants are effective treatments for pain and depression; selective serotonin reuptake inhibitors provide less benefit. Duloxetine and venlafaxine, which are serotonin and norepinephrine reuptake inhibitors, were shown in clinical trials to alleviate pain and depressive symptoms. Diabetic neuropathy and other chronic pain syndromes were also shown to benefit from duloxetine and venlafaxine. Antidepressants remain fundamental therapeutic agents for depression and anxiety disorders. Their extended use into chronic pain, depression with physical pain, physical pain with or without depression, and other potential medical conditions should be recognized.”

“Tricyclic antidepressants (TCAs) are a first-line treatment of many neuropathic chronic pain conditions, increasing the amount of available norepinephrine, thus reducing pain [32]. Unfortunately, data pertaining to CPP in women are minimal. One study randomized 56 women with CPP to amitriptyline, gabapentin to amitriptyline/gabapentin combined for 24 months. While each drug and drug combination resulted in a significantly reduced pain response, fewer side effects were noted in gabapentin alone when compared with the addition of amitriptyline [33]. Unfortunately, poor compliance and early discontinuation is common due to the anticholinergic side effects [34]. Nortriptyline and imipramine have also been studied limited in small groups of women with CPP with some improvement of pain symptoms [35,36]. The majority of the studies evaluating TCAs effect on pelvic pain is restricted to urologic pain disorders, not necessarily generalizable to women with CPP without urologic symptoms [37–40]…. Increasing the availability of serotonin may affect pain disorders. The selective serotonin reuptake inhibitors sertraline, has been studied in a single, small, placebo controlled randomized controlled trial in women with CPP, in which 23 women were randomized to sertraline or placebo. Despite 6 weeks of use, there was no notable difference in pelvic pain scores between the groups [41]. Like serotonin, norepinephrine also inhibits pain by inhibiting the descending pain pathways. Selective neurotransmitter reuptake inhibitors result in the increased availability of serotonin and norepinephrine, and have been highly successful in the treatment of many pain disorders. The significant analgesic effect may be predominately from the increase in norepinephrine centrally. While no studies have been performed in women with CPP exclusively, duloxetine has been identified as an effective pain modulator in urologic pelvic pain disorders in men and women [42,43] and is widely used in the treatment of diabetic peripheral neuropathy, fibromyalgia and chronic musculoskeletal pain [44]. Other antidepressants have shown modest improvement in chronic pain include bupropion (noradrenergic and dopaminergic pump inhibitor) and trazodone (serotonin-2 antagonist/reuptake inhibitor), though again there remains a lack of literature pertaining specifically to women with CPP.”

  • Anti-convulsant Medications: Medications such as gabapentin (Neurontin), pregabalin (Lyrica), topiramate (Topamax) are often recommended for neuropathic pain. 

“In Gabapentin group, pain was significantly reduced at 12 and 24 weeks (mean = 5.12 ± 0.67 and 3.72 ± 0.69, respectively) than in placebo group (mean = 5.9 ± 0.92 and 5.5 ± 1.13, respectively); this difference was significant. At 24 weeks, there was significantly higher proportion of patients reporting 30% or more reduction in pain scores; 19 out of 20 patients (95%) in Gabapentin group compared to 8 out of 14 patients (57.1%) in placebo group. The relative risk for pain after gabapentin treatment was 0.5 with 95% confidence interval = 0.34 to 0.75 and number needed to treat = 3 (p = 0.007). Regarding adverse effects there was significantly higher incidence of dizziness with Gabapentin (26.1%) compared to placebo (3.3%).”

  •  
  • Opioids: Opioids are effective for pain management. They are generally used for short term acute pain (such as after surgery), break through pain, or as a last resort for chronic pain. Your provider may send you to a pain management specialist if they are considering using opioids for chronic pain management. A pain management specialist can be helpful in finding the right combination of therapies for your body. Opioids come with significant risks that should be discussed carefully with your provider. It is important to follow your provider’s direction for usage and to discuss side effects, such as nausea and constipation. Over time, your body can become tolerant to the medicine and it may not work as effectively. There is also a phenomenon called opioid-induced hyperalgesia (increased sensitivity to pain caused by opioids) that your provider will consider if medication is not effective. 

“Opioids are highly effective for acute pain and chronic malignant pain; however, their role in chronic nonmalignant pelvic pain remains controversial. In fact, there is extremely limited data on the role of opioid therapy and pelvic pain [30], opioid receptors are G-protein receptors with three known subtypes μ, δ and κ and these receptors are primarily located in the brain (cortex, thalamus and periaqueductal gray) and spinal cord. Traditionally, analgesics have directed therapy to the μ receptor or the δ receptor (though activation of the latter is responsible for the significant side effect profile that can accompany these medications despite analgesic effect) [31]. Opioid receptors are found in both the CNS and PNS and the gastrointestinal system. While excellent analgesics, the short and long-term side effect profiles remain high, and the risks of long-term opioid use should be seriously measured in reproductive aged women with CPP.”

“The adequate treatment of pain remains one of the major medical challenges. Morphine and other opioid drugs are most commonly used to counteract moderate to severe pain, but they are also increasingly accessed by patients with chronic non-malignant pain. To achieve long-term analgesia, opioid therapy still represents the standard treatment for chronic pain alleviation…. To provide sustained analgesia in chronic pain patients, regular administration of drugs is required to ensure that the next dose of an analgesic is given before the effects of the previous dose have dissipated. Unfortunately, despite advances in understanding its etiology and pathophysiology, chronic pain remains inadequately treated to date. In general, the appropriate management of chronic pain [3] aims to improve quality of life and daily function by alleviating not only pain symptoms, but also comorbid conditions…. Opioid use for treating chronic pain may be justified only in patients who have not responded to any other therapy, as long term effects of clinical and excessive use of opioid drugs can affect nearly every organ system of the body…. Overall, pain management guidelines advise the use of extended-release (ER) formulations, rather than immediate-release (IR) formulation because they provide sustained analgesia [26], [27]. For patients suffering from moderate to severe chronic pain, ER formulations represent a viable option for around-the-clock analgesia, allowing a simpler dosing schedule (‘less clock-watching’), but also a more consistent and durable pain relief.”

  • Mao, J. (2016). Practical Management of Opioid-Induced Hyperalgesia in the Primary Care Setting. In Opioid-Induced Hyperalgesia (pp. 105-112). CRC Press. 

“Beside the many known side effects of opioids such as sedation and constipation, chronic opioid exposure is associated with the development of tolerance to opioid analgesics. This process is largely due to the adaptive change of opioid analgesic system that leads to the desensitization of opioid receptors and associated cellular cascade. Another consequence of chronic opioid exposure is the development of opioid dependence. A notable feature of opioid dependence is that hyperalgesia (exacerbated painful response to noxious stimulation) occurs during a precipitated opioid withdrawal.”

“Naltrexone hydrochloride is a competitive opioid antagonist, traditionally used as a treatment for opioid addiction 6,7,8. More recently, naltrexone has been evaluated as a novel treatment for chronic pain and autoimmune disorders. When used for this indication, a significantly lower dosage of 3-4.5 mg is employed. This decreased, off-label daily dosing is typically referred to as “low-dose naltrexone” (LDN). Using lower doses exploits naltrexone’s ability to act (directly on microglia cells of the) on the central nervous system, in addition to its more widely known action at opioid receptors6 . Prior studies suggest that LDN may be beneficial in patients with fibromyalgia, Crohn’s disease, multiple sclerosis, and complex regional pain syndrome. Evidence shows that LDN can function as an anti-inflammatory agent, acting on non-opioid receptors of central nervous system microglia cells (Liu). The non-opioid pathway decreases activation of microglia, blocking TNF alpha synthesis, among multiple other inflammatory factors. Reduced plasma levels of pro-inflammatory cytokines have been seen with use of LDN7,8. Given that endometriosis is characterized by increased peritoneal inflammation, patients may benefit from the nontraditional anti-inflammatory properties of LDN. Additionally, LDN has been shown to intermittently block all 3 subtypes (µ,κ,δ) of opioid receptors. The transient blockade results in an upregulation of endogenous opioids and opioid receptors. This rebound elevation of endogenous opioid levels may improve endogenous analgesia and further enhance QOL in patients with chronic pain 6.”

Links:

3 years ago Treatment

Hormonal Medications

Just as discussed with pain medications, hormonal medications may help alleviate the symptoms of endometriosis. They work for some and not others. Your provider should tailor your treatment to fit your needs and desires. Here are some points to consider:

  • Hormonal treatments, while they can relieve symptoms, do not get rid of the disease itself. They are “suppressive rather than curative” (Falcone & Flyckt, 2018). Symptoms often return rapidly once medications are stopped. Taking any medication for an extended amount of time can have significant effects on your body. It is important that you educate yourself about what medications you decide to take and understand both the short-term and long-term effects on your body when discussing with your provider.
  • In addition, hormonal medication may not stop the progression of disease- this is particularly important where the ureters and/or bowel are involved (Barra et al., 2018; Ferrero et al., 2011; Millochau et al., 2016).
  • Endometriosis lesions are different from normal endometrium (the lining of the uterus), therefore endometriosis responds differently to hormones than the endometrium. Some people’s endometriosis does not respond to progestin therapy (Guo, 2009). Many hormonal treatments aim at decreasing estrogen, as estrogen signals endometriosis lesions to increase in size, volume, height, and proliferation (see “In-depth on Endo“). However, long-term low estrogenic state can cause substantial side effects that you should discuss with your provider (see “Effects of long term low estrogen”.

Hormonal medications treat symptoms of other conditions such as menorrhagia (heavy menstrual periods), dysmenorrhea (painful menstrual periods), and adenomyosis. When discussing treatment plans with your provider, it is important to understand what other conditions you have that may benefit from hormonal medications. It is also important that your provider respect your priorities and preferences. Everyone will respond differently to hormonal treatments. Some may tolerate it well while others cannot. Some may find relief and others may find it worsens their symptoms or find the side effects may be intolerable. One size does not fit all!

1. Combined hormonal contraceptives: This is often where many providers will start when a patient complains of endometriosis symptoms. Combined hormonal contraceptives contain estrogen and progestin. They include birth control pills, patches or vaginal rings. Sometimes, providers recommend taking these medications continuously so that you do not have a period at all. This might help eliminate painful periods. 

“Nine randomized controlled trials and nine observational studies met the inclusion criteria. The quality of data was low: only two of the nine randomized trials were placebo controlled, and most trials were not blinded. The CHC agents were reported to significantly reduce dysmenorrhea, pelvic pain, and dyspareunia from baseline in most studies; continuous administration seemed to be more useful than cyclic administration. The effectiveness of CHC agents for pain reduction was similar to or less than that of oral progestins and GnRH agonists. Conclusions: The available literature suggests that CHC treatment is effective for relief of endometriosis-related dysmenorrhea, pelvic pain, and dyspareunia; however, the supportive data are of low quality. Furthermore, insufficient data exist to reach conclusions about the overall superiority of any given CHC therapy, and the relative benefit in comparison to other approaches. Additional high-quality studies are needed to clarify the role of CHC agents and other treatments in women with endometriosis-related pain.”

  • Grandi, G., Barra, F., Ferrero, S., Sileo, F. G., Bertucci, E., Napolitano, A., & Facchinetti, F. (2019). Hormonal contraception in women with endometriosis: a systematic review. The European Journal of Contraception & Reproductive Health Care, 24(1), 61-70.  Retrieved from https://www.tandfonline.com/doi/abs/10.1080/13625187.2018.1550576   

“A search of the Medline/PubMed and Embase databases was performed to identify all published English language studies on hormonal contraceptive therapies (combined hormonal contraceptives [CHCs], combined oral contraceptives [COCs], progestin-only pills [POPs] and progestin-only contraceptives [POCs]) in women with a validated endometriosis diagnosis, in comparison with placebo, comparator therapies or other hormonal therapies. Main outcome measures were endometriosis-related pain (dysmenorrhoea, pelvic pain and dyspareunia), quality of life (QoL) and postoperative rate of disease recurrence during treatment. Results: CHC and POC treatments were associated with clinically significant reductions in dysmenorrhoea, often accompanied by reductions in non-cyclical pelvic pain and dyspareunia and an improvement in QoL. Only two COC preparations (ethinylestradiol [EE]/norethisterone acetate [NETA] and a flexible EE/drospirenone regimen) demonstrated significantly increased efficacy compared with placebo. Only three studies found that the postoperative use of COCs (EE/NETA, EE/desogestrel and EE/gestodene) reduced the risk of disease recurrence. There was no evidence that POCs reduced the risk of disease recurrence. Conclusions: CHCs and POCs are effective for the relief of endometriosis-related dysmenorrhoea, pelvic pain and dyspareunia, and improve QoL. Some COCs decreased the risk of disease recurrence after conservative surgery, but POCs did not. There is insufficient evidence, however, to reach definitive conclusions about the overall superiority of any particular hormonal contraceptive.”

“For decades, combined estrogen-progestin oral contraceptive pills (OCPs) have been the first-line treatment for menstrual and pelvic pain associated with endometriosis without any clinical evidence of efficacy. Initial relief provided by OCPs is likely a result of improvement in primary dysmenorrhea. Biologic data and limited clinical evidence support a potential adverse effect of long-term use of OCPs on the progression of endometriosis.” 

2. Progestins (including progestin-only contraception): Progestins come in a variety of forms, including pills , injections, implants, or as an intrauterine device (IUD), such as levonorgestrel IUD (Mirena®Skyla®,), contraceptive implant (Nexplanon® ), contraceptive injection (Depo-Provera®) or progestin pill (Camila®). Progestins taken continuously, like combined hormonal contraception, may temporarily stop menstrual periods. This can be useful for other related conditions such as adenomyosis. However, studies have indicated that endometriosis lesions may not respond to progestins due to altered progesterone receptors.

“Progestins, synthetic progestational agents, have been used in the management of symptomatic endometriosis both as primary therapy and as an adjunct to surgical time. A variety of oral agents have been employed in this regard and investigators have demonstrated differing degrees of benefit. The lack of a standardized instrument to evaluate painful symptoms makes comparative analysis more difficult. Concern about efficacy and side effect has pushed the research on the development of new well-tolerated drugs and to develop new administration routes to minimize general side effects.”

  • Flores, V. A., Vanhie, A., Dang, T., & Taylor, H. S. (2018). Progesterone receptor status predicts response to progestin therapy in endometriosis. The Journal of Clinical Endocrinology & Metabolism, 103(12), 4561-4568. Retrieved from https://academic.oup.com/jcem/article/103/12/4561/5139742 

“Although serum levels of progesterone in women with endometriosis are similar to those of women without the disease, endometriotic lesions (ectopic endometrium) do not respond appropriately to progesterone (10, 11). The inappropriate response to progesterone (i.e., progesterone resistance) in endometriotic lesions explains the impaired efficacy of progestin-based therapies for endometriosis management (8, 12). Endometriotic lesions have altered expression of the progesterone receptor (PR) (12, 13). Specifically, it has been postulated that progesterone resistance is mediated by lower levels of PR (8, 14). Low PR may explain why progestin-containing agents [including combined oral contraceptives (OCs)] are associated with treatment failure in some patients (8, 14).”

“Progestogens most commonly used for the treatment of endometriosis include medroxyprogesterone acetate (MPA) and 19-nortestosterone derivatives (e.g., levonorgestrel, norethindrone acetate, and dienogest). As with OCs, their proposed mechanism of action involves decidualization and subsequent atrophy of endometrial tissue. Another more recently proposed mechanism involves progestogen-induced suppression of matrix metalloproteinases, a class of enzymes important in the growth and implantation of ectopic endometrium (60). Inhibition of angiogenesis has also been proposed as a mechanism to explain the effectiveness of progestins in the treatment of endometriosis (64). In observational studies involving treatment with MPA, dydrogesterone, or norethindrone acetate, pain has been reduced by 70%–100% (65). A meta-analysis of four randomized, controlled trials comparing MPA to danazol alone, danazol and combined OCs, or a GnRH-a (goserelin acetate) concluded that MPA was as effective as the other treatments (odds ratio [OR] 1.1; 95% CI 0.4–3.1) (65). Randomized studies concluded that dienogest was significantly better than placebo and as effective as the GnRH-a buserelin, LA, or triptorelin in reducing pain symptoms with diminished side effects of hot flushes and bone mineral density loss (66). The levonorgestrel-releasing intrauterine system (LNG-IUS) represents another approach to the medical treatment of endometriosis. A randomized, controlled trial comparing the LNG-IUS to expectant management after laparoscopic surgical treatment for symptomatic endometriosis found that the LNG-IUS was more effective than no treatment in reducing symptoms of dysmenorrhea (67). Other studies have demonstrated improved symptoms associated with rectovaginal endometriosis (68) and a significant decrease in the extent of disease observed at second-look laparoscopy after 6 months of treatment with the LNG-IUS (69). Relief of endometriosis pain with the LNG-IUS is similar to GnRH-a (52, 70).”

3. Gonadotropin-releasing hormone (Gn-RH) agonists and antagonists: These medications significantly lower estrogen levels and can halt menstruation, creating a medically induced menopause. The medications block the production of ovarian-stimulating hormones. This often causes side effects similar to menopause, such as hot flashes, vaginal dryness and bone loss. This bone loss may not be reversible. Due to this, recommended use is limited to a 6 month course of treatment, with no more 12 months total use (such as 2 six-month courses of treatment). Medications are available by injection, pill, or nasal spray and include Orilissa®, Lupron®, Synarel®, Zoladex®.

  • American College of Obstetricians and Gynecologists. (2010). Practice bulletin no. 114: management of endometriosis. Obstet Gynecol, 116(1), 223-236. doi: 10.1097/AOG.0b013e3181e8b073

“However, a Cochrane review found little to no difference between GnRH agonist and other medical treatments for endometriosis, suggesting again that this regimen is not recommended as a primary treatment approach.”

“Gonadotropin-releasing hormone agonist treatment for endometriosis has been studied more extensively than other medical treatment regimens. Gonadotropin-releasing hormone agonists are modified forms of GnRH that bind to receptors in the pituitary but have a longer half-life than native GnRH and thereby result in down-regulation of the pituitary-ovarian axis and hypoestrogenism. The likely mechanism of action for relief of endometriosis pain involves the induction of amenorrhea and progressive endometrial atrophy (60). Gonadotropin-releasing hormone agonists can be administered by a calibrated nasal spray twice daily (nafarelin acetate), by injection of either a short-acting formulation daily, or by injection of a depot formulation (LA, goserelin acetate) every 1–3 months. Side effects relate primarily to the induced hypoestrogenic state and include hot flushes, vaginal dryness, decreased libido, mood swings, headache, and bone mineral depletion (75). A Cochrane analysis found that GnRH-a were more effective than placebo for endometriosis pain relief but were similar to the LNG-IUS and danazol (52). A long-term follow-up study of patients treated with a GnRH-a alone for 6 months revealed a 53% recurrence of disease/symptoms 2 years after treatment (28). To reduce negative effects of E deprivation (e.g., bone loss, hot flushes) and allow for longer treatment periods, ‘‘add-back’’ therapy with norethindrone acetate or a combination of E and progestogen has been advocated. This treatment regimen decreases bone loss seen with GnRH-a alone and also reduces the severity of hypoestrogenic side effects associated with GnRH-a treatment. The underlying theory of add-back treatment is the ‘‘E threshold hypothesis,’’ which holds that the amount of E and/or progestogen necessary to prevent hot flushes, bone loss, and other hypoestrogenic symptoms and side effects is less than that which would stimulate endometriosis (76). Although norethindrone acetate is the only hormone approved by the US Food and Drug Administration for add-back therapy, other combinations of low-dose E and progestogens also have been shown to be effective in decreasing hypoestrogenic side effects and maintaining bone density, and not adversely affecting the extent of pain relief achieved with GnRH-a treatment (52, 77). The add-back therapy should be started at the same time as the agonist rather than delaying until a period of hypoestrogenism has occurred. This approach has been shown to decrease bone loss and improve vasomotor symptoms and compliance (78).”

“GnRH-a is commonly used for symptomatic treatment and prevention of endometriosis with good clinical efficacy. However, the side effects of GnRH-a (such as hot flashes, night sweats, dizziness, fatigue, vaginal dryness, loss of libido, mood changes and bone pain) limit its long-term use [7,8]. According to the report by Sagsveen et al. [9], the bone mineral density (BMD) of lumbar vertebra decreased by 3.2% after a 6-month usage of GnRH-a and by 6.3% after a 12-month usage. The treatment course of GnRH-a is limited to 6 months because of the side effect of bone loss [10].”

“From a national healthcare perspective, laparoscopic conservative surgery for endometriosis is more cost-effective than Elagolix for the primary treatment of moderate to severe pain from endometriosis that has been refractory to standard medical care.”

  • Vercellini, P., Viganò, P., Barbara, G., Buggio, L., & Somigliana, E. (2019). Elagolix for endometriosis: all that glitters is not gold. Human Reproduction, 34(2), 193-199. Retrieved from https://academic.oup.com/humrep/article/34/2/193/5245999

“Elagolix, an orally active non-peptidic GnRH antagonist, has been approved by the Food and Drug Administration for the management of moderate to severe pain associated with endometriosis. As the degree of ovarian suppression obtained with elagolix is dose-dependent, pain relief may be achieved by modulating the level of hypo-oestrogenism while limiting side effects. Elagolix may thus be considered a novelty in terms of its endocrine and pharmacological properties but not for its impact on the pathogenic mechanisms of endometriosis, as the target of this new drug is, yet again, alteration of the hormonal milieu. Given the oestrogen-dependent nature of endometriosis, a reduction of side effects may imply a proportionate decrease in pain relief. Furthermore, if low elagolix doses are used, ovulation is not consistently inhibited, and patients should use non-hormonal contraceptive systems and perform serial urine pregnancy tests to rule out unplanned conception during periods of treatment-induced amenorrhoea. If high elagolix doses are used to control severe pain for long periods of time, add-back therapies should be added, similar to that prescribed when using GnRH agonists. To date, the efficacy of elagolix has only been demonstrated in placebo-controlled explanatory trials. Pragmatic trials comparing elagolix with low-dose hormonal contraceptives and progestogens should be planned to verify the magnitude of the incremental benefit, if any, of this GnRH antagonist over currently used standard treatments. The price of elagolix may impact on patient adherence and, hence, on clinical effectiveness. In the USA, the manufacturer AbbVie Inc. priced elagolix (OrilissaTM) at around $10 000 a year, i.e. $845 per month. When faced with unaffordable treatments, some patients may choose to forego care. If national healthcare systems are funded by the tax payer, the approval and the use of a new costly drug to treat a chronic condition, such as endometriosis, means that some finite financial resources will be diverted from other areas, or that similar patients will not receive the same level of care. Thus, defining the overall ‘value’ of a new drug for endometriosis also has ethical implications, and trade-offs between health outcomes and costs should be carefully weighed up.”

  • Leyland, N., Estes, S. J., Lessey, B. A., Advincula, A. P., & Taylor, H. S. (2020). A Clinician’s Guide to the Treatment of Endometriosis with Elagolix. Journal of Women’s Health. Retrieved from https://www.liebertpub.com/doi/full/10.1089/jwh.2019.8096

“Elagolix is the first orally administered FDA-approved treatment option for endometriosis-associated pain in more than 10 years. Unlike GnRH agonists, which induce a hypoestrogenic state through complete suppression of the hypothalamic-pituitary-ovarian axis, GnRH antagonists such as elagolix partially suppress estradiol, thereby lessening hypoestrogenic side effects (e.g., hot flush, vaginal dryness, reduced BMD, and lipid changes), while maintaining therapeutic efficacy….In clinical trials, elagolix has been shown to reduce pelvic pain (including dysmenorrhea, NMPP, and dyspareunia), improve quality of life, and decrease the need for rescue analgesics in women with endometriosis-associated pain.22–26 These improvements were maintained during 12 months of treatment….Given the mechanism of action for elagolix, the study did not include women with a history of nonresponse to GnRH agonists or antagonists, depot medroxyprogesterone acetate, or aromatase inhibitors.26 Patients with a history of osteoporosis or other metabolic bone disease were also excluded. Screening dual-energy X-ray absorption scans for BMD of the lumbar spine, femoral neck, or total hip could not be 1.5 or more standard deviations below normal (i.e., Z score ≤ −1.5)….The pivotal elagolix clinical trials were predominantly white (88%), which limits the ability to draw conclusions for other racial groups due to the small sample size…. Elagolix is not recommended for patients with a history of nonresponse to GnRH agonists or antagonists, and is contraindicated in women who are pregnant, have known osteoporosis, or have severe hepatic impairment. Elagolix should not be used concomitantly with strong organic anion-transporting polypeptide 1B1 inhibitors (e.g., cyclosporine and gemfibrozil)….Consistent with the mechanism of action, hypoestrogenic effects are among the most common adverse events reported during elagolix clinical trials. As this was an anticipated effect, special attention was given to the occurrence of vasomotor symptoms and to changes in BMD, lipids, and endometrial thickness….Dose- and duration-dependent decreases in BMD have been observed in elagolix clinical trials. The magnitude of decrease was generally modest.23–27 After 6 months of treatment in phase 3 studies, mean percentage changes in lumbar spine BMD were −0.3% to −0.7% with elagolix 150 mg once daily and −2.5% to −2.6% with elagolix 200 mg twice daily.27 Follow-up assessments in a long-term extension study revealed partial recovery of BMD at 6 and 12 months post-treatment,27 although the influence of these BMD changes on bone health and fracture risk over time is currently not known….Other common mild adverse events that occurred during elagolix clinical trials included headache, insomnia, mood swings, night sweats, and arthralgia.26 Patients should be made aware that elagolix may decrease menstrual bleeding or cause amenorrhea, thereby obscuring early recognition of pregnancy. Depression and mood changes, particularly if these include suicidal ideation, warrant further investigation, with assessment of the benefits and risks of continuing treatment and referral to a mental health professional, as appropriate.”

4. Aromatase inhibitors: These medications also decrease the amount of estrogen in your body. Bone loss is a significant side effect of this class of medications as well and should be discussed with your provider.

“In several studies involving small numbers of patients, aromatase inhibitors have been shown to be effective for the treatment of endometriosis and pelvic pain in premenopausal and postmenopausal women (79, 80)….Endometriotic tissue, unlike disease-free endometrium, exhibits a high level of aromatase activity that may result in increased local concentrations of E that may favor growth of endometriosis (20, 79). This observation may help to explain the presence of endometriosis in postmenopausal women and the persistence of disease symptoms in some patients receiving GnRH-a treatment. A randomized trial of women on goserelin treated with anastrozole or placebo reported no difference in symptom scores during treatment, but the anastrozole group had a lower recurrence rate as well as a longer time to symptom recurrence (81). However, anastrozole increased bone loss compared with goserelin alone (81). In premenopausal women aromatase inhibitors lead to an increase in FSH levels and subsequent follicular development and therefore must be used in combination with additional agents (progestogens, combined OCs, or GnRH-a) to down-regulate the ovaries. The combination of an aromatase inhibitor with a combined OC may improve endometriosis pain while suppressing follicle development and preserving bone mineral density (79).”

“Unlike oral contraceptives, gestagens, aGnRHs, and danazol, which suppress ovarian oestrogen synthesis, aromatase inhibitors inhibit mainly extra-ovarian synthesis of oestrogens. Therefore, the use of aromatase inhibitors seems to be particularly relevant in older patients, as most of the body’s oestrogen is produced outside the ovaries after menopause…. Aromatase activity is absent in normal human endometrium and is increased in endometriosis [9]. It was demonstrated that extrauterine endometrial tissue is a source of oestrogens. Moreover, oestrogens stimulate synthesis of PGE2, which is a potent inducer of aromatase activity in endometrium….Long-term use of aromatase inhibitors is associated with increased risk of osteoporosis and bone fractures [18, 30]. The incidence of fractures was 2-11% in women receiving aromatase inhibitors as adjuvant therapy for breast cancer [34, 35]. The incidence of bone fractures was 11% (n = 3092) in the anastrozole group and 7.7% (n = 3094) in the tamoxifen group after five years of treatment. The incidence of bone fractures was 9.3% among patients receiving letrozole and 6.5% in those treated with tamoxifen after five years of treatment. After six months of treatment with exemestane, BMD decreased by 2.6% (n = 78) at the lumbar spine. The ASCO (American Society of Clinical Oncologists) guidelines recommend BMD testing once a year to all patients receiving aromatase inhibitors as adjuvant therapy for breast cancer, and treatment with bisphosphonates for those with BMD T-scores ≤ –2.5 [36]. After six months, combination treatment with anastrozole and goserelin was associated with a greater decrease in BMD than was goserelin alone. This effect was maintained after discontinuation of treatment.” 

5. Danazol: Although not used much anymore, danazol has been used in endometriosis. Its main side effects stem from its hyperandrogenic effects, such as acne, weight gain, and deepening of the voice. 

“Danazol is an oral androgenic agent that induces amenorrhoea through suppression of the hypothalamic-pituitary-ovarian (HPO) axis, accompanied by increased serum androgen concentrations and low serum estrogen levels (Rotondi et al., 2002; Valle et al., 2003). Multiple studies have demonstrated the efficacy of danazol in reducing endometriosis-associated pain symptoms (Telimaa et al., 1987a,b; Fraser et al., 1991; Crosignani et al., 1992; Cirkel et al., 1995; Chang and Ng, 1996; The Australian/New Zealand ZOLADEX Study Group, 1996)….However, danazol was poorly tolerated, and 18.5% of patients treated with this agent withdrew during the study due to adverse events compared with 5.5% of patients receiving a GnRH analogue (P < 0.05) (Rotondi et al., 2002). In fact, poor tolerability represents the major drawback of danazol as a treatment for endometriosis: this agent has both androgenic and anabolic properties, leading to side effects, such as weight gain, edema, myalgia, acne, oily skin and hirsutism (Biberoglu and Behrman, 1981; Rotondi et al., 2002). These concerns limit treatment duration to 6 months, and the use of this agent has been in decline in recent years (Valle et al., 2003). Danazol should not be used in women with liver disease or hyperlipidemia, and women receiving danazol therapy also must use effective contraception during the entire course of treatment (Valle et al., 2003).”

References

Barra, F., Scala, C., Biscaldi, E., Vellone, V. G., Ceccaroni, M., Terrone, C., & Ferrero, S. (2018). Ureteral endometriosis: a systematic review of epidemiology, pathogenesis, diagnosis, treatment, risk of malignant transformation and fertility. Human reproduction update, 24(6), 710-730. https://academic.oup.com/humupd/article/24/6/710/5085039?login=true

Falcone, T., & Flyckt, R. (2018). Clinical management of endometriosis. Obstetrics & Gynecology, 131(3), 557-571. Retrieved from https://journals.lww.com/greenjournal/Abstract/2018/03000/Clinical_Management_of_Endometriosis.23.aspx?context=FeaturedArticles&collectionId=4

Ferrero, S., Camerini, G., Venturini, P. L., Biscaldi, E., & Remorgida, V. (2011). Progression of bowel endometriosis during treatment with the oral contraceptive pill. Gynecological Surgery, 8(3), 311-313. Retrieved from https://link.springer.com/article/10.1007/s10397-010-0610-3

Guo, S. W. (2009). Recurrence of endometriosis and its control. Human reproduction update, 15(4), 441-461. Retrieved from http://humupd.oxfordjournals.org/content/15/4/441.full

Millochau, J. C., Abo, C., Darwish, B., Huet, E., Dietrich, G., & Roman, H. (2016). Continuous amenorrhea may be insufficient to stop the progression of colorectal endometriosis. Journal of minimally invasive gynecology, 23(5), 839-842. Retrieved from https://www.jmig.org/article/S1553-4650(16)30047-4/abstract?fbclid=IwAR2Q7o1kJtfNNgMd0Q4_5K0BDe9_DjH1QOUTxTLK2HpgiFVgws5NT9xVdwo

3 years ago Treatment

Adhesion prevention

Adhesions are bands of scar-like, fibrous tissue that can form when there is any kind of tissue injury. According to Van Den Beukel et al. (2017), adhesions can cause pelvic pain. They also reports that “reformation of adhesions has been linked to relapse of pain after adhesiolysis” (Van Den Beukal et al., 2017). Hermann and Wilde (2016) note that adhesion formation is “highly prevalent in patients with a history of operations or inflammatory peritoneal processes”. (Endometriosis is an inflammatory disorder.) Careful technique at surgery can help minimize postoperative adhesions.

(More about adhesions can be found at: Adhesions)

Adhesion prevention 

  • Koninckx, P. R., Gomel, V., Ussia, A., & Adamyan, L. (2016). Role of the peritoneal cavity in the prevention of postoperative adhesions, pain, and fatigue. Fertility and sterility, 106(5), 998-1010. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/27523299

“Prevention of adhesion formation therefore consists of the prevention of acute inflammation in the peritoneal cavity by means of gentle tissue handling, the addition of more than 5% N2O to the CO2 pneumoperitoneum, cooling the abdomen to 30°C, prevention of desiccation, a short duration of surgery, and, at the end of surgery, meticulous hemostasis, thorough lavage, application of a barrier to injury sites, and administration of dexamethasone. With this combined therapy, nearly adhesion-free surgery can be performed today. Conditioning alone results in some 85% adhesion prevention, barriers alone in 40%-50%.”

References

Herrmann, A., & De Wilde, R. L. (2016). Adhesions are the major cause of complications in operative gynecology. Best Practice & Research Clinical Obstetrics & Gynaecology, 35, 71-83. Retrieved from https://www.sciencedirect.com/science/article/abs/pii/S1521693415001935

Van Den Beukel, B. A., de Ree, R., van Leuven, S., Bakkum, E. A., Strik, C., van Goor, H., & ten Broek, R. P. (2017). Surgical treatment of adhesion-related chronic abdominal and pelvic pain after gynaecological and general surgery: a systematic review and meta-analysis. Human Reproduction Update, 23(3), 276-288. Retrieved from https://academic.oup.com/humupd/article/23/3/276/3058801

3 years ago Treatment

Pelvic Adhesions

by Nick Kongoasa MD 

I am often asked about adhesions and thought it might be helpful to explain my approach to them. 

Adhesions are formed as a protection your body provides. When you fall and skin your knee, a scab forms to protect the raw area until the skin heals. Internally, adhesions perform much the same way. They are created in response to a raw area (that can be caused by endo, or surgery, or infection or trauma. You can’t look at an adhesion and know what caused it). 

If the adhesion just covered the raw area until it healed, all would be well. However, it doesn’t work that way because all the organs in the pelvis are right next to one another. This causes the tendency for things to get adhered to or ‘’stuck’’ to the raw area. When they first form, it’s not a problem, because they are flimsy like wet tissue paper, and they are flexible. You’d not even be aware they are there. 

But over time, the adhesions can become shorter, and tighter, and harder. The flexibility disappears and they can become like concrete. Worse still, they can trap organs that should be movable and make them yank and pull. And then pain can increase, and may become constant, as organs that should be able to move freely (like an ovary or the bowel) are stuck and can’t. What to do? 

Although medical science hasn’t discovered the magic fix for adhesions, we have learned many techniques to lessen the chances that they will form. Here are the steps I take: 

  1. Patient health is important both before and after surgery. You’re having surgery because of endo, but you can take measures to help your recovery. Take recommended vitamins (especially vitamin C) and probiotics. Get adequate and restful sleep. Exercise if you can. Try to reduce stress. Eat well. Don’t smoke. You want to prepare your body as best you can to face the challenges of surgical excision and recovery. After your surgery, focus on healing while increasing your activity a little each day. Start taking your vitamins, supplements and probiotics as soon as possible. Drink plenty and rest plenty. This part of the procedure is in your own hands, so take full advantage of what you can do to help yourself. 
  2. We know that bleeding in the pelvis encourages adhesion formation (your body trying to help you, right?), so I take great pains to stop every bit of bleeding during surgery. This can slow the procedure, but the time spent to seal tiny bleeders is well worth it, in my opinion, if it reduces the chances of adhesion formation. I use a small instrument that looks a little bit like a staple remover (only smaller) to grasp the bleeding vessel, and then use a pulse of energy to seal it and stop the bleeding or oozing. Copious irrigation clears the field and lets me double check that all bleeding has stopped. Only then do we continue the procedure. 
  3. Adhesions like to form where the tissue has become dried, so we use warmed carbon dioxide gas during the surgery, to keep the tissues moist. We also constantly use Lactated Ringers (LR) irrigation to keep the area moist. This, combined with controlling bleeding with high precision will reduce devitalized (dead) tissue and further reduce adhesions. 
  4. Complete excision is paramount. We need to remove every bit of endometriosis. Even a little bit left behind can continue to cause inflammation and irritate the tissue it’s on and cause adhesions to form. All endo must be completely removed. 
  5. I use PRP in surgery. PRP stands for Platelet Rich Plasma, and it is effective in helping prevent adhesion formation. Before surgery we do a blood draw from you, and spin down the blood to separate the plasma. This is then used to promote healing. It’s your own blood product, so there is no chance of rejection as we are not introducing a foreign substance. This process has been used widely in joint procedures by orthopedic surgeons. The joint is the last place where you want adhesions to form. It seemed a logical step to use it to prevent pelvic adhesions, too. 
  6. I use a reconstituted amniotic membrane product in select patients. The reasoning is this. As a baby develops in the womb, she/he is a completely distinct individual from the mother. And yet, we don’t see adhesions form within the uterus after pregnancy. Reconstituted amniotic membranes also have other healing and anti-inflammatory properties. Many surgeons adapted this concept and use it to help prevent adhesions in surgical patients. 

Although there is currently no way to guarantee that no adhesions will form postop, I do feel we have a number of techniques to minimize the chances of adhesion formation. The ultimate goal is to remove all the endo and restore functionality to the pelvic organs. In my opinion, it is always worthwhile to excise all endo while taking all appropriate steps to reduce or eliminate adhesion formation. 

3 years ago Treatment

Robotic Surgery

From Dr John F. Dulemba

ROBOTIC SURGERY: 

I think it is time to explain the Davinci robot from the viewpoint of someone that actually uses the device. There are many people that may disagree with some of the things I will mention, or describe, but this is based on my published data, my experience, and my opinion. This explanation is related to endometriosis, adhesions, and pelvic pain. Before starting robot laparoscopy, I had completed over 3,500 standard laparoscopic cases for endometriosis, and was considered by many as an expert standard laparoscopic surgeon. I started using the Davinci robot in early 2007, but have been doing some form of robotics since 1997 (in 2001, a gallbladder was removed in Strasbourg, France, but the surgeon was in New York City). I now have over 1,400 endometriosis cases using the robot, and I think that may be the most endometriosis robotic cases by any single surgeon in the world. I only perform Davinci robotic laparoscopy, so, I think that enables me to compare both approaches to laparoscopy better than surgeons that have never used the robot, only have a few robotic cases, or still divide their cases between standard laparoscopy and robotic laparoscopy.

Robotic surgery is still just laparoscopy. That is the first hurdle that needs to be understood. There is nothing magical about the robot, but there are many benefits to robotic surgery in comparison to standard laparoscopy. Patients have stated that they did not want robotic surgery, because they wanted the surgeons hands “doing” the surgery. Even in laparoscopy, the surgeon does not touch the tissue with his hands. The surgeon uses instruments, and often the same type of instruments as standard laparoscopy, to perform the surgery.

A major difference is the comfort of the surgeon. With standard laparoscopy, the surgeon is standing next to the patient, and often has to reach across the patient to manipulate the instruments, and can be in uncomfortable positions for hours. I sit in a comfortable chair at a console with my arms resting on padded armrests. Why is resting the arms during surgery important besides fatigue factors? Try threading a needle with thread and have your arms extended. It makes the threading more difficult, because tiny movements may occur. The console adjusts to many positions for added comfort (ergonomics). In a long case, or cases, fatigue is less likely to occur from standing or reaching during that time. Physical fatigue may not seem like a big deal, but it can affect decision making and surgical skills. This is extremely important when dealing with hard and difficult endometriosis cases, such as dissecting around important organs and structures.

The movements of the instruments are “wristed”. This means that the instruments have actions of movements similar to the human wrist (520 degrees of rotation), and 7 degrees of freedom. What does that mean? That means there are areas of the robotic instrument arm that are similar to the human arm, such as the elbow. That way the instrument can move in different directions, bend, turn twist in ways that standard laparoscopic straight instruments cannot move. Standard laparoscopy instruments can still reach tissue, but more torque and pulling is needed to reach the desired positions. Try to imagine your arm in a cast, and trying to perform certain tasks. You can do it, but more difficult than if your arm does not have restricted movements. Then the instruments have “intuitive” movements. Again, what is that? With standard laparoscopy, if you move your hand to the right, your instrument will go to the left (counter-intuitive). To the left, the instrument goes to the right. With Davinci robotic surgery, when I move my hand to the right the instrument goes to the right. To the left, the instrument goes to the left. Another benefit is when I move the robotic instrument an inch, it moves an inch, or I can scale the movement so that if I move an inch the instrument will move 1/5th of an inch. The advantage in that is any tremors in the hand are minimized, and (in my opinion again) more accuracy when making movements, cuts, or dissection. I normally use scissors in my right hand, but a few times it was difficult to reach an area behind my scissors. I then switched the scissors to my left hand. I “swapped” control of the left hand so now the left hand scissors were controlled by the right hand. That way I was using the same hand I normally would cut with, but now n the left. That may be a little confusing, but a huge benefit to me. When I lift my head from the console viewer, my instruments lock into place. The benefit from this is that I can use an instrument to hold things out of the way, and that instrument will not move until I make it move. That is very important when retracting tissue away from the surgical field. If need be, I can add an extra arm/instrument. This would require an additional tiny incision but with a tap of my foot, I can toggle between two different types of instruments on one side, and one of the instruments can then be a retractor.

Visualizing endometriosis is so important when dealing with endometriosis. Why? It is a common thought that ANY amount of endometriosis may cause pain. If that is true, then all endometriosis needs to be seen, and then should be removed. Experts have the surgical skills to remove endometriosis, and they are aware of the different appearances of endometriosis. Most gynecologists are trained to look for the “powder burn” blue/black lesions. In my opinion, the greatest difference between standard laparoscopy and Davinci robotic surgery is the visualization. Davinci robot is 3D versus 2D for Standard laparoscopy, but both have HD visualization. For those that do not think there is a difference between 3D and 2D, then drive your automobile with one eye closed. If you drive like that all the time, then your one eye will adapt, but you can see better with two eyes. The surgical field is magnified 10 times, so all of the tissue and organs appear to be bigger, and “tissue planes” are more visible. This helps with dissection, excising endometriosis, and separating organs and adhesions. My published data, unpublished data, and other data from physicians have shown that more endometriosis can be visualized with the 3D and magnification. An appearance of endometriosis not visualized with 2D is “terrain changes”. Unless the surgeon actually uses 3D visualization, the changes in the surface of the tissue cannot be seen. Some doctors drip the patient’s blood across the surface of the tissue, or use a dye, to try and check for changes. Many doctors say you don’t need 3D, but if there is a chance they are not visualizing all of the endometriosis, then why are they dripping liquids to look for areas not seen with the 2D? There are some 3D cameras for standard laparoscopy, but the small movements of the hand held camera make the 3D difficult to use. It has been shown that when evaluating skills with new laparoscopic surgeons, there are significantly less errors when using 3D versus 2D, and the surprising outcome was that with expert laparoscopists, they also had significantly less errors when using 3D versus 2D. The camera with the robot is perfectly still, and only moves when I move it. This aspect is important when working around important structures, because you don’t want movement of the surgical field as you operate. I now find it difficult to watch surgery when someone is doing standard laparoscopy, because the small imperceptible movements now seem like huge movements to me after the stable robot camera. I almost get motion sickness watching the screen. Firefly is a function of the camera that changes the light filter so that abnormal blood vessels can be visualized using a special dye and green light. I have found that in early disease, the firefly enables me to see blood vessel changes consistent with endometriosis that is not seen in the normal spectrum of light. If any blood is present, then firefly is not useful.

There are negatives to the Davinci robot. A complaint is that there is a loss of tactile sense (touch and feel). Over time, the brain adapts, and the surgeon seems to develop a visual tactile sense. I can detect soft and hard tissue. The visual tactile sense allows me to be as gentle as normal hands and laparoscopic hands. Some surgeons say that you cannot put your hands in the vagina to feel for masses, well, all the surgeon has to do is stand up from the console, put on a pair of gloves, and do the exam. To use that one issue as a reason to not use robotic surgery does not make sense. There are often one to two more incisions than standard laparoscopy when using the robot, and the incisions need to be higher to get the full range of motion from the instruments. If cosmetic appearance of tiny incisions is more important than all of the listed benefits, then maybe standard laparoscopy is better for you. The cost of the hospital robotic surgery may be more expensive by $800-1,000 more than standard laparoscopy, but again, the benefits may make that cost worthwhile. Surgeons that go back and forth between standard laparoscopy and robot laparoscopy are not allowing their skills to develop completely for each approach. As robotic skills increase, there will be a decrease in standard laparoscopic skills. Movements that were second nature with standard laparoscopy are not the same movements with robotic laparoscopy, and so more thinking is needed to perform routine movements. To reach the highest level of skills in any area, repetition is needed, and not the confusion of opposite activities.

I have seen people saying the robot is just a tool, and I agree, but disagree. Using standard laparoscopy does not mean a surgeon is an expert in endometriosis, and on the same thought, a surgeon using the Davinci robot laparoscopy does not make them experts. I have heard patients state that “my doctor uses the robot”. That may increase their surgical skill level, but there are more aspects of treating endometriosis than just surgical skills. All of these positives and negatives of robotic surgery do not mean better outcomes, but the Davinci robot laparoscopic surgery is more accurate and precise than standard laparoscopy.

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