Pathophysiological Basis of Endometriosis-Linked Stress Associated with Pain and Infertility: A Conceptual Review
Abstract
:1. Introduction
2. Methods
3. A Brief Overview on How Endometriosis Affects Women’s Health and Beyond
4. Different Facets of Endometriosis-Associated Stress
5. Pathophysiological Impact of Inflammatory Stress in Endometriosis
5.1. Endometriosis-Associated Pain
5.2. Endometriosis-Associated Infertility
6. Physiological Basis of Management of Endometriosis-Associated Medical Problems
7. Potential Impact of Patient Centric Multidisciplinary Healthcare in Endometriosis
8. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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Factor | Reference [Reference No.] |
---|---|
• Disturbed folliculogenesis | Nakahara et al., 1998 [143] |
• Luteinized unruptured follicle | Kaya and Oral, 1999 [144] |
• Oocyte quality | Sanchez et al., 2016 [145] |
• Adhesions | De Venecia, Ascher, 2015 [140] |
• Dysfunctional uterotubal motility | Kissler et al., 2005 [138] |
• Detrimental effects on spermatozoa | Reeve et al., 2005 [139] |
• Peritoneal inflammation | Malvezzi et al., 2019 [85]; Anupa et al. 2020 [86] |
• Progesterone resistance plus estrogen dominance | Sengupta et al., 2017 [5]; Anupa et al., 2019 [146]; Bulun, 2019 [147] |
• Endometrial hostility | Sengupta and Ghosh, 2014 [148]; Lessey and Kim, 2017 [149]; Miravet-Valenciano et al., 2017 [150]; Lessey, Young, 2019 [151] |
• Immune dysfunctions | Schatz et al., 2016 [152]; Jørgensen et al., 2017 [96]; Lin et al., 2018 [124] |
Therapy | Major Observations [Reference No.] |
---|---|
Danazol | Danazol is a weak androgen and anabolic steroid, a weak progestogen, a weak antigonadotropin, a weak steroidogenesis inhibitor and a functional antiestrogen [174]. A large number of patients do not report any significant relief of pain. Moreover, 1 out of 3 patients reported of recurrence of pain at the end of treatment [175,176,177]. According to some reports the treatment may reduce endometriosis related pain but has androgenic effects and causes cysts and infertility [178]. |
Gestrinone | Gestrinone is a mixed progestogen and antiprogestogen, a weak androgen and anabolic steroid, a weak antigonadotropin, a weak steroidogenesis inhibitor, and a functional antiestrogen [174]. 1 out of 4 patients did not report any significant relieve of pain. Also, 1 out of 4 patients reported of recurrence of pain at the end of treatment or pain remaining at the end of treatment [179,180]. The main side effects are similar but less intense than those caused by danazol [181]. |
GnRH agonist | 14% of patients did not experience any change in pain, while 40% patients experienced non-pain status remaining at end of treatment and 34% experienced recurrence at the end of treatment [43]. GnRHa alone has adverse side effects of estrogen deficiency and reduction in bone mineral density and sexual functioning [182,183]. |
GnRH antagonist | Reported studies conducted in industry setup. With Elagolix, 19% of patients did not experience any change in pain [184,185]. Effective in improving dysmenorrhea and non-menstrual pelvic pain with significant lessening of fatigue, however, with associated hypoestrogenic adverse effects [186,187]. |
GnRH agonist (Leuprolide) + progestin (NETA) | 61% pain reduction during treatment and 52% continued pain reduction after stopping treatment. 80% had at least one long term side effect more than 6 months after the completion of treatment [188]. |
Synthetic progestogen | With dienogest, pooled analyses from clinical studies showed its tolerability with good safety profile and progressive improvement in pain scores in Caucasian [189] and Chinese population [190]. Comparable results were reported with norethindrone acetate [191]. Reductions in serum high density lipoproteins with use of norethindrone acetate and minor loss of bone density with dienogest are issues of concern [191]. |
CHCs, COCs, POCs | CHCs and POCs are effective for the relief of endometriosis-related dysmenorrhoea, pelvic pain and dyspareunia and for improving the quality of life. A few COCs (ethinylestradiol/norethisterone acetate, ethinylestradiol/desogestrel and ethinylestradiol/gestodene) decreased risk of recurrence. Additional well-designed, blind, comparative trials required for effective management of endometriosis-related pain. For details, see Grandi et al. [192]. |
Letrozole | Letrozole is an orally active, nonsteroidal, selective aromatase inhibitor used in the treatment of hormonally responsive breast cancer after surgery [193]. It may be administered in combination with oral contraceptive pills, progestogens or GnRH analogues for treating endometriosis associated pain to the patients with pain from rectovaginal endometriosis, and also to the patients who are refractory to other medical or surgical treatments it can be considered prescribing aromatase inhibitors [194,195]. Major side effects are hot flushes, myalgia and arthralgia [196]. It is as yet not globally approved. |
NSAIDs | NSAIDs are the most commonly used over the counter drugs for the management of endometriosis related pain and dysmenorrhea; the evidence to indicate whether NSAIDs such as naproxen sodium are indeed effective for the management of pain caused by endometriosis is as yet inconclusive. There are insufficient studies to prove either way, as well as to prove the efficacy and safety of NSAIDs in the management of pain in endometriosis [197]. |
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Ghosh, D.; Filaretova, L.; Bharti, J.; Roy, K.K.; Sharma, J.B.; Sengupta, J. Pathophysiological Basis of Endometriosis-Linked Stress Associated with Pain and Infertility: A Conceptual Review. Reprod. Med. 2020, 1, 32-61. https://doi.org/10.3390/reprodmed1010004
Ghosh D, Filaretova L, Bharti J, Roy KK, Sharma JB, Sengupta J. Pathophysiological Basis of Endometriosis-Linked Stress Associated with Pain and Infertility: A Conceptual Review. Reproductive Medicine. 2020; 1(1):32-61. https://doi.org/10.3390/reprodmed1010004
Chicago/Turabian StyleGhosh, Debabrata, Ludmila Filaretova, Juhi Bharti, Kallol K. Roy, Jai B. Sharma, and Jayasree Sengupta. 2020. "Pathophysiological Basis of Endometriosis-Linked Stress Associated with Pain and Infertility: A Conceptual Review" Reproductive Medicine 1, no. 1: 32-61. https://doi.org/10.3390/reprodmed1010004