Antiprogestins
Gestrinone is a 19-nortestosterone (androgen) derivative with antiprogestagenic properties. It is a long-acting drug that also possesses antiestrogenic and antigonadotropic properties.[62]Brown J, Kives S, Akhtar M. Progestagens and anti-progestagens for pain associated with endometriosis. Cochrane Database Syst Rev. 2012 Mar 14;(3):CD002122.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002122.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/22419284?tool=bestpractice.com
[117]Bromham DR, Booker MW, Rose GL, et al. Updating the clinical experience in endometriosis - the European perspective. Br J Obstet Gynaecol. 1995 Oct;102(suppl 12):12-6.
http://www.ncbi.nlm.nih.gov/pubmed/7577849?tool=bestpractice.com
Side effects are primarily androgen-excess-related (oily skin, irreversible voice changes, acne). It is not currently available in the US. Mifepristone may improve symptoms of dysmenorrhea and dyspareunia, although further research is required to determine safety profiles and optimal dosage.[118]Fu J, Song H, Zhou M, et al. Progesterone receptor modulators for endometriosis. Cochrane Database Syst Rev. 2017 Jul 25;(7):CD009881.
http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD009881.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/28742263?tool=bestpractice.com
Selective progesterone receptor modulators (SPRMs)
In early clinical trials, SPRMs effectively treated endometriosis-associated pain when compared with controls.[73]Strowitzki T, Marr J, Gerlinger C, et al. Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial. Hum Reprod. 2010 Mar;25(3):633-41.
http://humrep.oxfordjournals.org/content/25/3/633.long
http://www.ncbi.nlm.nih.gov/pubmed/20089522?tool=bestpractice.com
[119]Chwalisz K, Perez MC, Demanno D, et al. Selective progesterone receptor modulator development and use in the treatment of leiomyomata and endometriosis. Endocr Rev. 2005 May;26(3):423-38.
https://academic.oup.com/edrv/article/26/3/423/2355256
http://www.ncbi.nlm.nih.gov/pubmed/15857972?tool=bestpractice.com
[120]Kohler G, Faustmann TA, Gerlinger C, et al. A dose-ranging study to determine the efficacy and safety of 1, 2, and 4mg of dienogest daily for endometriosis. Int J Gynaecol Obstet. 2010 Jan;108(1):21-5.
http://www.ncbi.nlm.nih.gov/pubmed/19819448?tool=bestpractice.com
The mechanism of action is thought to be the antiproliferative actions on the endometrium without suppressing estrogen production (avoiding vasomotor symptoms and loss in bone mineral density). Progesterone blockade may result in endometrial hyperplasia.
Anti-tumor necrosis factor alpha
Currently, there is insufficient evidence to recommend the use of anti-tumor necrosis factor alpha agents for the relief of pelvic pain in women with endometriosis.[121]Lu D, Song H, Shi G. Anti-TNF-α treatment for pelvic pain associated with endometriosis. Cochrane Database Syst Rev. 2013 Mar 28;(3):CD008088.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008088.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/23543560?tool=bestpractice.com
Adjunctive surgical procedures
Adjunctive surgeries that interrupt nerve pathways have been extensively studied in the gynecological literature. These include laparoscopic uterosacral nerve ablation or LUNA (interrupt bundles that attach to the cervix/uterus) and presacral neurectomy or PSN (interrupt larger, general pathways to the pelvis). Despite the potential benefit seen in small groups of specific cohorts, LUNA and PSN remain investigational procedures.[122]Proctor ML, Latthe PM, Farquhar CM, et al. Surgical interruption of pelvic nerve pathways for primary and secondary dysmenorrhoea. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD001896.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001896.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/16235288?tool=bestpractice.com
[123]National Institute for Health and Care Excellence (UK). Laparoscopic uterine nerve ablation (LUNA) for chronic pelvic pain. Oct 2007 [internet publication].
https://www.nice.org.uk/guidance/ipg234
There are, however, more recent data that support the use of PSN for central pelvic pain.[124]Yeung PP Jr, Shwayder J, Pasic RP. Laparoscopic management of endometriosis: comprehensive review of best evidence. J Minim Invasive Gynecol. 2009 May-Jun;16(3):269-81.
http://www.ncbi.nlm.nih.gov/pubmed/19423059?tool=bestpractice.com
Complementary medicines
Side-effect profiles and lack of efficacy of various medications used to treat endometriosis have motivated women to seek complementary and alternative medicines. One 2016 Cochrane review found limited evidence for the use of vitamin B1 and fish oil, among other supplements, in treating primary dysmenorrhea, but these findings are limited by a lack of studies, small sample sizes, low-quality evidence, and no standardized dosing regimen. Given the studies available for review, there is insufficient evidence to recommend these supplements.[125]Pattanittum P, Kunyanone N, Brown J, et al. Dietary supplements for dysmenorrhoea. Cochrane Database Syst Rev. 2016 Mar 22;(3):CD002124.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002124.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/27000311?tool=bestpractice.com
Another Cochrane review found that Chinese herbal medication was beneficial in alleviating endometriosis-related pain post-laparoscopy when compared with hormonal therapy. However, further research into the role of complementary medicines is required before they may be considered for use as standard therapy.[125]Pattanittum P, Kunyanone N, Brown J, et al. Dietary supplements for dysmenorrhoea. Cochrane Database Syst Rev. 2016 Mar 22;(3):CD002124.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD002124.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/27000311?tool=bestpractice.com
[126]Flower A, Liu JP, Lewith G, et al. Chinese herbal medicine for endometriosis. Cochrane Database Syst Rev. 2012 May 16;(5):CD006568.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006568.pub3/pdf
http://www.ncbi.nlm.nih.gov/pubmed/22592712?tool=bestpractice.com