Melatonin and infertility

Melatonin, also known as the “Dracula Hormone” because it is only released at night, is more commonly associated with helping us sleep. However, since researchers discovered that melatonin receptors are also found on tissues and organs throughout the body, the race was on to find out if it did more than help us sleep.

Melatonin levels in infertile men

One of the places where melatonin receptors were found was on the testicular cells, and it was found that in animal studies, melatonin affects testicular development.1 Studies also found that the levels of melatonin in both the serum and seminal fluid in the testes were lower in infertile men.2 

Causes of male infertility

Infertility levels in men are increasing with environmental endocrine disruptors such as estrogen analogues. In addition, the cells in the testes are susceptible to reactive oxygen species (ROS). Infertility, which is defined as the inability to conceive after at least 12 months of regular, unprotected sexual activity, is estimated to affect between 8 and 12 per cent of reproductive-aged couples.3 In this situation, male factor infertility (MFI) is identifiable in approximately 50% of cases.4 

Oxidative stress, recognized for its role in various diseases, can significantly affect sperm function. Therefore, lifestyle factors like smoking, alcohol consumption, obesity, varicocele, infections, and psychological stress, which are linked to infertility and diminished sperm quality, may exert their influence through oxidative stress pathways.5 It’s estimated that this process affects between 30% and 80% of cases involving subfertility. As a result, the term MOSI (male oxidative stress infertility) was coined to describe this category.6 

Reactive oxidative species in semen and infertility

So, infertile men often have an imbalance in their blood’s oxidation status. The level of reactive oxygen species (ROS) in their seminal fluid has been linked to sperm motility, shape, and count in males with certain types of sperm abnormalities like asthenospermia (poor sperm motility)  and oligoasthenoteratospermia (low numbers of mobile sperm).7

The antioxidant effect of melatonin

This is where melatonin makes its grand entrance. Melatonin, a hormone produced by the pineal gland in the brain, is primarily regulated by darkness and plays a crucial role in controlling our internal body clocks. Moreover, melatonin and its byproducts serve as scavengers, helping to remove harmful free radicals from cells. This antioxidant effect is important in safeguarding cells from oxidative stress linked to infertility.8

Since melatonin is considered a highly efficient free radical scavenger and an efficient antioxidant that can cross all physiological barriers and enter every cell and subcellular compartment, many researchers study whether infertile men have lower melatonin levels.

Do infertile men have lower melatonin levels?

Awad and colleagues examined a potential link between melatonin levels and fertility status in both fertile and infertile men, distinguishing the latter based on semen analysis abnormalities. 

Their study included 120 male participants divided into six equal groups: fertile normozoospermic men, men with oligoasthenozoospermia (OA), OA with leucocytospermia (white blood cells in semen) OA with varicocele, non-obstructive azoospermia (NOA) with high serum follicle-stimulating hormone (FSH), and NOA with normal FSH. Various analyses were conducted, including semen analysis and estimation of melatonin, FSH, testosterone (T), and prolactin (PRL) hormone levels.

They found that men with non-obstructive azoospermia, impaired sperm motility, and leucocytospermia had lower melatonin levels, particularly those with leucocytospermia.9

Similarly, in 2016, Kratz et al. investigated melatonin levels in seminal plasma and oxidative stress markers in fertile men with normal sperm and infertile men with abnormal sperm morphology or azoospermia. They discovered higher melatonin levels in fertile men, while infertile subjects had elevated levels of oxidation products, particularly in azoospermic patients.10 These findings again suggest a potential association between melatonin and oxidative stress in infertile males.

Summary

In summary, the current study and previous research suggest a potential link between melatonin levels and male fertility. Fertile men with normal sperm exhibited higher levels of melatonin in both semen and blood compared to infertile men with various sperm abnormalities. However, the precise relationship between melatonin levels and sperm health indicators remains unclear and requires further investigation.

References: 

1. Kasahara, T.; Abe, K.; Mekada, K.; Yoshiki, A.; Kato, T. Genetic variation of melatonin productivity in laboratory mice under domestication. Proc. Natl. Acad. Sci. USA 2010, 107, 6412–6417.
2. Frungieri, M.B.; Calandra, R.S.; Rossi, S.P. Local actions of melatonin in somatic cells of the testis. Int. J. Mol. Sci. 2017, 18, 6.
3. Vander, M.; Borght, E.C. Wyns, Fertility and infertility: Definition and epidemiology. Clin. Biochem. 2018, 62, 2–10.
4. Zegers-Hochschild, F.; Adamson, G.D.; Dyer, S.; Racowsky, C.; De Mouzon, J.; Sokol, R.; Rienzi, L.; Sunde, A.; Schmidt, L.; Cooke, I.D.; et al. The International Glossary on Infertility and Fertility Care, 2017. Fertil. Steril. 2017, 108, 393–406.
5. Lopes, F.; Pinto-Pinho, P.; Gaivão, I.; Martins-Bessa, A.; Gomes, Z.; Moutinho, O.; Oliveira, M.M.; Peixoto, F.; Pinto-Leite, R. Sperm DNA damage and seminal antioxidant activity in subfertile men. Andrologia 2021, 53, e14027.
6. Showell, M.G.; Mackenzie-Proctor, R.; Brown, J.; Yazdani, A.; Stankiewicz, M.T.; Hart, R.J. Antioxidants for male subfertility. Cochrane Database Syst. Rev. 2014, 12, CD007411.
7. Colagar, A.H.; Karimi, F.; Jorsaraei, S.G.A. Correlation of sperm parameters with semen lipid peroxidation and total antioxidants levels in astheno- and oligoasheno- teratospermic men. Iran. Red Crescent Med. J. 2013, 15, 780–785.
8. Hu, K.L.; Ye, X.; Wang, S.; Zhang, D. Melatonin Application in Assisted Reproductive Technology: A Systematic Review and Meta-Analysis of Randomized Trials. Front. Endocrinol. 2020, 11, 160
9. Awad, H., Halawa, F., Mostafa, T. and Atta, H., 2006. Melatonin hormone profile in infertile males. international journal of andrology, 29(3), pp.409-413.
10. Kratz, E.M.; Piwowar, A.; Zeman, M.; Stebelová, K.; Thalhammer, T. Decreased melatonin levels and increased levels of advanced oxidation protein products in the seminal plasma are related to male infertility. Reprod. Fertil. Dev. 2016, 28, 507–515.