Effect of Ubiquinol on Serum Reproductive Hormones of Amenorrhic Patients.

In neuroendocrine system the increase in oxidative status is produced by a glucocorticoid—dependent and transcriptional increase in pro-oxidative drive, with concurrent inhibition of the antioxidant defense system, ultimately leading to increased neuronal cell death. Functional hypothalamic disturbances and neuroendocirne aberrations have both short and long term consequences for reproductive health. Understandably, an impaired or diminished hypothalamic–pituitary–ovarian axis leads to anovulation and hypoestrogenism. Anovulation is directly linked to the neurohormonal and hormonal background of Functional Hypothalamic Amenorrhea. Impairment of pulsatile Gonadotropin Releasing Hormone secretion causes the impairment of pulsatile Lutenizing Hormone (LH) and Follicle Stimulating Hormone (FSH) secretion. The importance of oxidative stress in various pituitary disorders suggesting a possible clinical usefulness of antioxidant molecules like the lipophilic antioxidant Ubiquinol. Coenzyme Q10 or Ubiquinol is an essential part of the cell energy-producing system of mitochondria. However, it is also a powerful lipophilic antioxidant, protecting lipoproteins and cell membranes from autooxidation. Due to these unique actions Ubiquinol is used in clinical practice as an antioxidants for neurodegenerative diseases. So to identify the role of Ubiquinol on reproductive hormones FSH and LH, we have included 50 infertile patients of age group of 20–40, which are mostly amenorrhic. Out of 50 only 30 patients were in continuous follow up after supplementing them with 150 mg of Ubiquinol every day for 4 months. The hormonal levels were estimated by Enzyme Linked Immuno Sorbent Assay technique at follicular phase. The result suggests that FSH concentration is increased up to three times (from 3.10 ± 2.70 to 10.09 ± 6.93) but remains within the normal limit (P < 0.05). LH values were found doubled (P 0.05). The supplementation of 150 mg of Ubiquinol may reduce the oxidative stress in neuroendocrine system which further improves the function of diminished HPA axis. Hence increased level of FSH and LH may be due to reduced oxidative stress by Ubiquinol. Similar content being viewed by others

Agarwal A, Allamaneni SSR (2004) Oxidants and antioxidants in human fertility. In: Free radicals in human fertility, vol 9. Middle East Fertil Soc J. 2004;9(3):187. Meczekalski B, Katulski K, Czyzyk A, Podfiguina-Stopa A, Maciejewska-Jeske M. Functional hypothalamic amenorrhea and its influence on women’s health. J Endocrinol Invest. 2014;37:1049–56. O’Connor TM, O’Halloran DJ, Shanahan F. The stress response and the hypothalamic–pituitary–adrenal axis: from molecule to melancholia. Q J Med. 2000;93:323–33. Mancini A, Festa R, Di Donna V, Leone E, Littarru GP, Silvestrini A, Meucci E, Pontecorvi A. Hormones and antioxidant systems: role of pituitary and pituitary-dependent axes. J Endocrinol Invest. 2010;33(6):422–33. Spiers JG, Chen H-JC, Sernia C, Lavidis NA. Activation of the hypothalamic–pituitary–adrenal stress axis induces cellular oxidative stress. Front Neurosci. www.frontiersin.org. 2015 January; vol 8: article 456. [Mini Review Article, Published: 19 January 2015. doi:10.3389/fnins.2014.00456]. Sugino N, Karube-Harada A, Taketani T, Sakata A, Nakamura Y. Withdrawal of ovarian steriods stimulates prostaglandin F2alpha production through nuclear factor-kappaB activation via oxygen radicals in human endometrial stromal cells: potential relevance to menstruation. J Reprod Dev. 2004;50:215–25. Agarwal A, Saleh RA, Bedaiwy MA. Role of reactive oxygen species in the pathophysiology of human reproduction. Fertil Steril. 2003;79:829–43. Paszkowski T, Traub AI, Robinson SY, McMaster D. Selenium dependent glutathione peroxidase activity in human follicular fluid. Clin Chim Acta. 1995;236:173–80. Bedaiwy MA, Falcone T, Sharma RK, Goldberg JM, Attarn M, Nelson DR, et al. Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial. Hum Reprod. 2002;17:426–31. Fenkci V, Fenkci S, Yilmazer M, Serteser M. Decreased total antioxidant status and increased oxidative stress in women with polycystic ovary syndrome may contribute to the risk of cardiovascular disease. Fertil Steril. 2003;80:123–7. Dincer Y, Akcay T, Erdem T, Ilker Saygili E, Gundogdu S. DNA damage, DNA susceptibility to oxidation and glutathione level in women with polycystic ovary syndrome. Scand J Clin Lab Invest. 2005;65:721–8. Palacio JR, Iborra A, Ulcova-Gallova Z, Badia R, Martinez P. The presence of antibodies to oxidative modified proteins in serum from polycystic ovary syndrome patients. Clin Exp Immuno. 2006;144:217–22. Wang Y, Sharma RK, Falcone T, Goldberg J, Agarwal A. Importance of reactive oxygen species in the peritoneal fluid of women with endometriosis or idiopathic infertility. Fertil Steril. 1997;68:826–30. Polak G, Koziol-Monetewka M, Gogacz M, Blaszkowska I, Kotarski J. Total antioxidant status of peritoneal fluid in infertile women. Eur J Obstet Gynecol Reprod Biol. 2001;94:261–3. Yeh J, Bowman MJ, Browne RW, Chen N. Reproductive aging results in a reconfigured ovarian antioxidant defense profile in rats. Fertil Steril. 2005;84(Suppl 2):1109–13. Ebisch IM, Peters WH, Thomas CM, Wetzels A. Peer thiols affect fertility parameters in the (sub)fertile couple. Hum Reprod. 2006;21:1725–33. Takahashi T, Takahashi E, Igarashi H, Tezuka N, Kurachi H. Impact of oxidative stress in aged mouse oocytes on calcium oscillation at fertilization. Mol Reprod Dev. 2003;66:143–52. Kodaman PH, Behrman HR. Endocrine-regulated and protein kinase C-dependent generation of superoxide by rat preovulatory follicles. Endocrinology. 2001;142:687–93. Carbone MC, Tatone C, Delle Monache S, Marci R, Caserta D, Colonna R, Amicarelli F. Antioxidant enzymatic defences in human follicular fluid: characterization and age-dependent changes. Mol Hum Reprod. 2003;9:639–43. Basini G, Grasselli F, Bianco F, Tirelli M, Tamanini C. Effect of reduced oxygen tension on reactive oxygen species production and activity of antioxidant enzymes in swine granulose cells. BioFactors. 2004;20:61–9. Takami M, Preston SL, Toyloy VA, Behrman HR. Antioxidants reversibly inhibit the spontaneous resumption of meiosis. Am J Physiol. 1999;276:E684–8. Duleba AJ, Foyouzi N, Karaca M, Pehlivan T, Kwintkiewicz J, Behrman HR. Proligeration of ovarian theca-interstitial cells is modulated by antioxidants and oxidative stress. Hum Reprod. 2004;19:1519–24. Mancini A, Resta R, Raimondo S, Pontecorvi A, Littarru GP. Hormonal influence on coenzyme Q10 levels in blood plasma. Int J Mol Sci. 2011;12:9216–25. Tietz NW. Text book of clinical guide to laboratory tests. 3rd ed. Philadelphia: W.B. Saunders Company; 1995. p. 578–80. Das P, Chowdhury M. Vitamin E-deficiency induced changes in ovary and uterus. Mol Cell Biochem. 1999;198:151–6. Oyawoye O, Abdel Gadir A, Garner A, Constantinovici N, Perrett C, Hardiman P. Antioxidants and reactive oxygen species in follicular fluid of women undergoing IVF: relationship to outcome. Hum Reprod. 2003;18:2270–4. Liu H, Zhang C, Zeng W. Estrogenic and antioxidant effects of a phytoestrogen daidzein on ovarian germ cells in embryonic chickens. Domest Anim Endocrinol. 2006;31:258–68. Ikeda S, Kitagawa M, Imai H, Yamada M. The roles of vitamin A for cytoplasmic maturation of bovine oocytes. J Reprod Dev. 2005;51:23–35. Do Amaral VF, Bydlowski SP, Peranovich TC, Navarro PA, Subbiah MT, Rerriani RA. Lipid peroxidation in the peritoneal fluid of infertile women with peritoneal endometriosis. Eur J Obstet Gynecol Reprod Biol. 2005;119:72–5. Luck MR, Zhao Y. Identification and measurement of collagen in the bovine corpus luteum and its relationship with ascorbic acid and tissue development. J Reprod Fertil. 1993;99:647–52. Behl R, Pandey RS. FSH induced stimulation of catalase activity in goat granulose cells in vitro. Anim Reprod Sci. 2002;70:215–21. Zuelke KA, Jones DP, Perreault SD. Glutathione oxidation is associated with altered microtubule function and disrupted fertilization in mature hamster oocytes. Biol Reprod. 1997;57:1413–9. Tarin JJ, Perez-Albala S, Cano A. Oral antioxidants counteract the negative effects of female aging on oocyte quantity and quality in the mouse. Mol Reprod Dev. 2002;61:385–97. Guerin P, El Mouatassim S, Menezo. Y. Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Hum Reprod Update. 2001;7:175–89. Kobayashi N, Machida T, Takahashi T, Takatsu H, Shinkai T, Abe K, Urano S. Elevation by oxidative stress and aging of hypothalamic–pituitary–adrenal activity in rats and its prevention by vitamin E. J Clin Biochem Nutr. 2009;45:207–13. Acknowledgments The study was actively supported by Kaneka Corporation, Japan. Funding This study was not funded by any agency. But the Q10 samples were provided by Kaneka Corporation, Japan. Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of interest A. S. Thakur, G. P. Littaru, I. Funahashi, U. S. Painkara, N. S. Dange, P. Chauhan declares that have no conflict of interest. Ethical approval All procedures performed in this study were in accordance with ethical standards of the institution and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study has been conducted on approval by the college ethical committee. Informed consent Informed consent was obtained from all the individual participants included in the study. Rights and permissions About this article Cite this article Thakur, A.S., Littaru, G.P., Funahashi, I. et al. Effect of Ubiquinol on Serum Reproductive Hormones of Amenorrhic Patients. Ind J Clin Biochem 31, 342–348 (2016). https://doi.org/10.1007/s12291-015-0542-9 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s12291-015-0542-9