The researchers from Porto Alegre have completed the phase II clinical trial entitled “Efficacy of melatonin in the treatment of endometriosis” (1). It provides evidence concerning the analgesic effects of melatonin on endometriosis-associated chronic pelvic pain (EACPP). Taking this popular OTC drug for jet lag resulted in an almost 40% reduction of daily endometriosis-related pain scores in comparison to placebo(1). The report is a fruit of research conducted by members of the International Association for the Study of Pain.

Melatonin is a customary name for a chemical compound N-acetyl-5-methoxytryptamine. It occurs naturally in animals, plants and microbes. In humans this hormone is produced by the pineal gland. Its release is inhibited by light signal detected by the retina and permitted by darkness. Melatonin serves mainly as a synchronizer of a biological clock. The hormone is available as a FDA-approved dietary supplement. Melatonin is commonly linked with therapy of sleep disorders. However, a 2006 review reported that there is no evidence that melatonin is effective in treating sleeping disturbances (2).

Let us take a look at why scientist came up with an idea of treating endometriosis with melatonin. This gynecologic condition is chronic, estrogen-dependent and inflammatory. Apart from infertility, it is connected with a great deal of pelvic pain. This results probably partly from a compression of endometriotic lesions on adjacent nerves (3). C-fiber nociceptors are irritated also by the increased oxidative stress. In response they release various factors to the environment causing additional vascular permeability. This chain of reactions can be referred to as “neurogenic inflammation”(1). If melatonin should work, it would need to influence some of the pathophysiologic mechanisms that lead to the further growth of endometriotic lesions or fuelling the pain response.

Mounting evidence shows that melatonin is, in fact, a powerful antioxidant (4). Studies prove that it presents actual antiinflammatory and analgesic properties (5). Melatonin is also thought to influence other hormonal pathways. It was found that exogenous N-acetyl-5-methoxytryptamine reduces the plasma levels of luteinizing hormone and 17-beta-estradiol in rats (6). Research conducted on animal model of endometriosis shows that melatonin causes regression and atrophy to the lesions (7). Activities of antioxidant enzymes superoxide dismutase and catalase significantly increased in the rat peritoneal fluid after melatonin treatment when compared with a control group. The findings have been confirmed in later studies (8). Brazilian authors claim that new therapy for endometriosis is needed as the current treatment has a limited impact on the course of the disease and causes poorly-tolerated side-effects. Many agree and search for alternative treatment (9, 10).

Researchers from Porto Alegre designed their study to assess a number of female patients with diagnosed chronic pelvic pain. In all of them endometriosis had been confirmed laparoscopically by the same clinician. According to the randomized double-blind placebo-controlled protocol, subjects were randomly allocated to two groups. The first was taking 10 mg of melatonin at bedtime for 8 weeks, the second a placebo pill instead. Women were asked to complete a survey systematically in which they marked their EACCP symptoms intensity using the Visual Analogue Scale. Levels of pain connected with common implications of endometriosis: dysmenorrhea, dyspareunia, dysuria and dyschezia were also investigated. Participants were encouraged to take analgesics if necessary and record them in their diary, but no other treatment for endometriosis could be used. In addition sleep quality was assessed daily.

36 subjects finished the trial. The melatonin group had significantly lower EACCP scores than the placebo group, also during menstruation, intercourse, urination and defecation. In time the differences in pain scores of both groups grew even bigger. Analgesic use during the treatment occurred in around 40% of women in the placebo group and about 20% of those assigned for taking melatonin. Researchers calculated that the placebo-treated group was 80% more likely to use analgesics at least 3 times a week than the melatonin group. In addition, when compared with the control group, melatonin caused a mean 42% improvement in how patients felt when they awoke. It has been speculated that the melatonin-induced amelioration of sleep quality could alleviate the chronic pain alone. However, researchers are sure that melatonin’s analgesic properties are independent of its main functionv (11).

The above findings suggest that melatonin has a direct influence on pain pathways or chemical signals regulating pain. To the authors’ knowledge, this study is the first to provide evidence on the impact of melatonin on EACCP. Brazilian scientists emphasize that the magnitude of the reported pain reduction exceeded 30%, which is thought to be the outcome reached by placebo treatment (12). Therefore, they suggest, melatonin has a potential for use in clinical setting. The reported scarcity of melatonin’s side-effects is a just another ace up her sleeve.

Written: Natalia Neumann

Source:

1.Schwertner A, Conceicao Dos Santos CC, Costa GD et al.Efficacy of melatonin in the treatment of endometriosis: a phase II, randomized, double-blind, placebo-controlled trial. Pain. 2013 Jun;154(6):874-81. doi: 10.1016/j.pain.2013.02.025. Epub 2013 Mar 5.

2.Buscemi N, Vandermeer B, Hooton N et al. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. BMJ 332 (7538): 385–93. doi:10.1136/bmj.38731.532766.F6

3.Stratton P, Berkley KJ. Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications. Hum Reprod Update2011;17:327–46.

4.Hardeland R. Antioxidative protection by melatonin: multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine. 2005 Jul;27(2):119-30.

5.] El-Shenawy SM, Abdel-Salam OM, Baiuomy AR et al. Studies on the anti-inflammatory and anti-nociceptive effects of melatonin in the rat. Pharmacol Res 2002;46:235–43.

6.Chuffa LG, Seiva FR, Favaro WJ et al. Melatonin reduces LH, 17 beta-estradiol and induces differential regulation of sex steroid receptors in reproductive tissues during rat ovulation. Reprod Biol Endocrinol 2011;9:108.

7.Guney M, Oral B, Karahan N et al. Regression of endometrial explants in a rat model of endometriosis treated with melatonin. Fertil Steril 2008;89:934–42.

8.Yildirim G, Attar R, Ozkan F et al. The effects of letrozole and melatonin on surgically induced endometriosis in a rat model: a preliminary study. Fertil Steril 2010;93:1787–92.

9.Neumann Natalia (2012) Resveratrol przezwycięża endometriozę – kobiety mogą potwierdzić. MEDtube Tribune [online ]. https://medtube.pl/tribune-pl/2012/12/resveratrol-przezwycieza-endometrioze-kobiety-moga-potwierdzic/ [dostęp 29 grudnia 2012]

10.Neumann Natalia (2011) Endometrioza – nowe możliwości terapii, czyli wyleczyć nieuleczalne. MEDtube Tribune [online]. https://medtube.pl/tribune-pl/2011/09/endometrioza-%E2%80%93-nowe-mozliwosci-terapii-czyli-wyleczyc-nieuleczalne/ [dostęp 26 września 2011 ]

11.Vidor LP, Torres IL, de Souza IC et al. Analgesic and sedative effects of melatonin in temporomandibular disorders: a double-blind,randomized, parallel-group, placebo-controlled study. J Pain Symptom Manage 2012. http://dx.doi.org/10.1016/j.jpainsymman.2012.08.019.

12.Koninckx PR, Craessaerts M, Timmerman D et al. Anti-TNFalpha treatment for deep endometriosis-associated pain: a randomized placebo-controlled trial. Hum Reprod 2008;23:2017–23.

Would You like to know more? Watch on MEDtube.net: Laparoscopic Ureteral Dissection On Pelvic Endometriosis