DNA damage, greatly impacting oocyte quality
Therefore, targeting oxidative stress may be a valid line of treatment for endometriosis (7).
Melatonin is a hormone secreted by the pineal gland that controls the wake/sleep cycles, circadian rhythms and reproduction (8).
Melatonin is by nature an agent able to pass through any cellular membranes. It is a potent anti-oxidant that prevents oxidative stress induced by reactive oxygen species. While melatonin has a direct effect on oxidative stress by scavenging ROS and RNS (9), its metabolites (product of its degradation) are also active and act indirectly by inducing the production of anti-oxidative enzymes and lowering the synthesis of pro-oxidative molecules (10) leading to an overall reduction of oxidative stress thus inducing a significant decrease in inflammation.
Further, melatonin has immunostimulatory properties through its action on T helper (Th) lymphocytes and can also inhibit the secretion of the pro-inflammatory cytokine tumor necrosis factor α (TNFα) by monocytes (11).
Many animal studies have shown the dramatic and positive effect of melatonin on Endometriosis as reported in the recent review.
In a rat model for endometriosis where endometriotic implants were introduced by surgery (12), melatonin injection for 4 weeks causes a significant regression of lesions by decreasing angiogenesis, increasing tissue levels of antioxidants and reducing matrix metalloproteinases activity (enzyme enabling lesions invasiveness and adhesion).
These results were confirmed in many independent studies (13-14) and further showed the melatonin dose-response effect (15) as well as its ability to decrease the endometriotic lesions recurrence rate (16).
In a same way, in a rat model for endometriosis, a pinealectomy (ablation of the pineal gland) was associated with significant growth of endometrial explants and decreased antioxidant activity while melatonin supplementation reverses the progression of endometriosis implants (17).
The effects of melatonin may directly impact the apoptosis process leading to the cell death in these growing lesions (18) and preventing peritoneal adhesion (19) in a rat model. Lastly, the only study in human (double-blind, placebo-controlled trial) showed that melatonin at a dose of 10mg/day is a proven medication in the treatment of pain associated with endometriosis and dysmenorrhea (20).
Melatonin use is safe and did not show any teratogenic effects in both human and animal (21-22) as well as no toxicity (23) even at very high dose (5-20mg/day). Given the potential clinical benefits of melatonin and its safety, it is a target of choice to counteract oxidative stress, reduce inflammation and limit endometriotic lesions progression and recurrence.
As world leader in the field of Reproductive Immunology, we have, at Braverman Reproductive Immunology, developed a dietary supplement “The Endo-Optimize” containing many ingredients including melatonin, with beneficial actions on reducing ROS and free-radicals’ production, reducing endometriotic lesions and their recurrence and enhancing oocyte maturation and quality. In addition, this “all in one” pill contains many other ingredients enhancing mitochondrial activity (a key component in oocyte development) and reducing inflammation thus allowing optimal microenvironment for the oocyte to develop and mature into a fertilizable egg (for more information read our blog “ENDO-optimize: an "all in one" dietary supplement with beneficial effects on egg quality, endometriosis and PCOS”).
Our diet supplements are available for purchase.
For more information about our supplements range, please consult our website.
Questions? Call 516.584.8710 We would be happy to help you take control of your fertility journey and answer any questions you may have.
References
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2- Giudice, L.C., Kao, L.C., 2004. Endometriosis. Lancet 364, 1789–1799.
3- Buck Louis, G.M., Hediger, M.L., Peterson, C.M., Croughan, M., Sundaram, R., Stanford, J., Chen, Z., Fujimoto, V.Y., Varner, M.W., Trumble, A., Giudice, L.C., 2011. Incidence of endometriosis by study population and diagnostic method: the ENDO study. Fertil. Steril. 96, 360–365.
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