Melatonin Treatment May Be Able to Restore Menstrual Cyclicity in Women With PCOS: A Pilot Study

Tagliaferri, Valeria; Romualdi, Daniela; Scarinci, Elisa; Cicco, Simona De; Florio, Christian Di; Immediata, Valentina; Tropea, Anna; Santarsiero, Carla Mariaflavia; Lanzone, Antonio; Apa, Rosanna

doi:10.1177/1933719117711262

Cited by 61 publications

(27 citation statements)

References 47 publications

(61 reference statements)

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“…Women with PCOS have significantly elevated melatonin concentrations and hyperandrogenemia along with an elevated number of atretic follicles (19). After 6 months of supplementation, melatonin significantly improved menstrual irregularities and biochemical hyperandrogenism in women with PCOS through a direct, insulin-independent effect on the ovary (42). In another study, melatonin administration to a PCOS mouse model potentially induced oocyte nuclear maturation and guaranteed fertilization potential (43).…”

Section: Discussionmentioning

confidence: 99%

Effects of Melatonin Supplementation on Hormonal, Inflammatory, Genetic, and Oxidative Stress Parameters in Women With Polycystic Ovary Syndrome

et al. 2019

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Purpose: The aim of the current study was to evaluate the effect of melatonin administration on clinical, hormonal, inflammatory, and genetic parameters in women with polycystic ovarian syndrome (PCOS). Methods: The present randomized, double-blinded, placebo-controlled clinical trial was conducted among 56 patients with PCOS, aged 18–40 years old. Subjects were randomly allocated to take either 5 mg melatonin supplements ( n = 28) or placebo ( n = 28) twice a day for 12 weeks. Results: Melatonin administration significantly reduced hirsutism (β −0.47; 95% CI, −0.86, −0.09; P = 0.01), serum total testosterone (β −0.11 ng/mL; 95% CI, −0.21, −0.02; P = 0.01), high-sensitivity C-reactive protein (hs-CRP) (β −0.61 mg/L; 95% CI, −0.95, −0.26; P = 0.001), and plasma malondialdehyde (MDA) levels (β −0.25 μmol/L; 95% CI, −0.38, −0.11; P < 0.001), and significantly increased plasma total antioxidant capacity (TAC) levels (β 106.07 mmol/L; 95% CI, 62.87, 149.28; P < 0.001) and total glutathione (GSH) (β 81.05 μmol/L; 95% CI, 36.08, 126.03; P = 0.001) compared with the placebo. Moreover, melatonin supplementation downregulated gene expression of interleukin-1 (IL-1) ( P = 0.03) and tumor necrosis factor alpha (TNF-α) ( P = 0.01) compared with the placebo. Conclusions: Overall, melatonin administration for 12 weeks to women with PCOS significantly reduced hirsutism, total testosterone, hs-CRP, and MDA, while increasing TAC and GSH levels. In addition, melatonin administration reduced gene expression of IL-1 and TNF-α. Clinical Trial Registration: www.irct.ir , identifier IRCT2017082733941N9, Available online at: https://www.irct.ir/trial/26051

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Section: Discussionmentioning

confidence: 99%

Effects of Melatonin Supplementation on Hormonal, Inflammatory, Genetic, and Oxidative Stress Parameters in Women With Polycystic Ovary Syndrome

et al. 2019

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“… 114 This suggests that elevated melatonin levels described in women with PCOS may be a result of androgen excess. Conversely, chronic administration of melatonin to women with PCOS (2 mg per day for six months) significantly decreased testosterone levels and reduced menstrual irregularities, 115 suggesting that supraphysiological levels of melatonin can reduce androgen levels.…”

Section: How Pathophysiology Of Pcos Is Linked To Sleep Disturbancesmentioning

confidence: 98%

Sleep disturbances in women with polycystic ovary syndrome: prevalence, pathophysiology, impact and management strategies

Fernandez

Moore

Ryswyk

et al. 2018

NSS

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Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting the reproductive, metabolic and psychological health of women. Clinic-based studies indicate that sleep disturbances and disorders including obstructive sleep apnea and excessive daytime sleepiness occur more frequently among women with PCOS compared to comparison groups without the syndrome. Evidence from the few available population-based studies is supportive. Women with PCOS tend to be overweight/obese, but this only partly accounts for their sleep problems as associations are generally upheld after adjustment for body mass index; sleep problems also occur in women with PCOS of normal weight. There are several, possibly bidirectional, pathways through which PCOS is associated with sleep disturbances. The pathophysiology of PCOS involves hyperandrogenemia, a form of insulin resistance unique to affected women, and possible changes in cortisol and melatonin secretion, arguably reflecting altered hypothalamic–pituitary–adrenal function. Psychological and behavioral pathways are also likely to play a role, as anxiety and depression, smoking, alcohol use and lack of physical activity are also common among women with PCOS, partly in response to the distressing symptoms they experience. The specific impact of sleep disturbances on the health of women with PCOS is not yet clear; however, both PCOS and sleep disturbances are associated with deterioration in cardiometabolic health in the longer term and increased risk of type 2 diabetes. Both immediate quality of life and longer-term health of women with PCOS are likely to benefit from diagnosis and management of sleep disorders as part of interdisciplinary health care.

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“…Luboshitzky et al (115) documented increased excretion of the major melatonin metabolite (6-sulfatoxymelatonin) in women with PCOS, although whether this was a consequence of increased or decreased plasma melatonin levels was not apparent. More recently, in a pilot study Tagliaferri et al (116) administered pharmacological doses of oral melatonin for 6 months to 40 women with PCOS and reported significant improvements in menstrual cyclicity and normalization of androgen balance.…”

Section: Summary and Future Perspectivesmentioning

confidence: 99%

Melatonin and Female Reproduction: An Expanding Universe

Olcese

2020

Front. Endocrinol.

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For more than a half century the hormone melatonin has been associated with vertebrate reproduction, particularly in the context of seasonal breeding. This association is due in large measure to the fact that melatonin secretion from the pineal gland into the peripheral circulation is a nocturnal event whose duration is reflective of night length, which of course becomes progressively longer during winter months and correspondingly shorter during the summer months. The nocturnal plasma melatonin signal is conserved in essentially all vertebrates and is accessed not just for reproductive rhythms, but for seasonal cycles of metabolic activities, immune functions, and behavioral expression. A vast literature on melatonin and vertebrate biology has accrued over the past 60 years since melatonin's discovery, including the broad topic of animal reproduction, which is far beyond the scope of this human-focused review. Although modern humans in the industrialized world appear in general to have little remaining reproductive seasonality, the relationships between melatonin and human reproduction continue to attract widespread scientific attention. The purpose of this chapter is to draw attention to some newer developments in the field, especially those with relevance to human fertility and reproductive medicine. As the vast majority of studies have focused on the female reproductive system, a discussion of the potential impact of melatonin on human male fertility will be left for others.

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Melatonin Treatment May Be Able to Restore Menstrual Cyclicity in Women With PCOS: A Pilot Study

Cited by 61 publications

References 47 publications

Effects of Melatonin Supplementation on Hormonal, Inflammatory, Genetic, and Oxidative Stress Parameters in Women With Polycystic Ovary Syndrome

Effects of Melatonin Supplementation on Hormonal, Inflammatory, Genetic, and Oxidative Stress Parameters in Women With Polycystic Ovary Syndrome

Sleep disturbances in women with polycystic ovary syndrome: prevalence, pathophysiology, impact and management strategies

Melatonin and Female Reproduction: An Expanding Universe

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