Melatonin is a hormone that is synthesised by the pineal gland in response to darkness. It is the product of a multi-step conversion of the amino acid trypophan to serotonin and subsequently through acetylation and methylation to melatonin.
Melatonin has important effects on integrating photoperiod and affecting circadian rhythms. As a result of this activity it has been shown to have significant effects on sleep-wake cycles and has been used to manage sleep disorders in people, often marketed as a “natural” sleep aid.
Melatonin has been used to treat dogs with noise-related phobias, such as those that become stressed due to thunderstorms and fireworks. Epileptic dogs that seizure during the night between 11pm and 6am have demonstrated a reduction in seizure activity when treated with melatonin.
Melatonin has also been shown to have effects to improve coat condition leading to its use to treat hair cycle arrest alopecia such as cyclical flank alopecia and pattern baldness.
Its effect to inhibit the secretion of luteinizing hormone and follicle stimulating hormone may be the reason why it has been useful in some of the more unusual “endocrine type” alopecias in dogs such as Alopecia X.
Research into its use in the therapy of melanoma in man has centred on its ability to alter melanocyte stimulating hormone secretion and modulate IL2 activity. It has also been shown to have immune stimulating effects and the author will use it as a non-specific immune stimulant in some cases of demodicosis.
Although it undoubtedly has many potential benefits, it should only be used under veterinary supervision and it should be used with caution in animals with autoimmune disease and in animals that are intended to be used in breeding.
Effect on circadian rhythms and sleep patterns
Melatonin secretion each day is directly proportional to the length of the night and is regulated by the pineal gland by light exposure to the eyes. Melatonin levels therefore increase throughout the autumn, peak at the winter solstice and then decrease as the spring approaches.
On a daily basis, work in man has shown that melatonin levels rise sharply during periods of darkness and are essentially undetectable during the daytime. Very similar patterns are seen in other species. It is because of this circadian rhythm that melatonin levels have been linked to sleep disorders in man.
Although melatonin is not the only regulator of normal sleep patterns, it has been used with phototherapy to treat sleep disorders and is widely used to treat jet lag.
Melatonin levels are reported to reduce with age. There is evidence to suggest that elderly insomniacs have lower levels of melatonin than age-matched controls.
It is for this reason therefore that melatonin has been advocated as a sleep aid in older dogs that are restless at night and wander about the house and also in blind dogs that lose the visual clues that promote changes in melatonin and therefore a perception of day and night.
Melatonin given at night can help to re-establish a normal circadian rhythm and promote sleep.
Effect on hair coat
Melatonin is involved in the neuroendocrine control of photoperiod dependent moulting in many different mammals. Although the role it plays is indisputable, the mechanism by which it produces its effects is poorly understood.
Melatonin may work at a cellular level directly on the hair follicles or centrally by modulation of the secretion of such hormones as melanocyte stimulating hormone or prolactin.
One of the best examples of melatonin’s effect on hair quality is in the mink. Mink exhibit a seasonal fur growth cycle which is regulated by photoperiod. During the winter months, starting in Northern latitudes in about September, as daylight length decreases melatonin levels increase, initiating the growth of a thick winter coat.
In the spring as daylight length increases again, melatonin levels drop and moulting occurs. This effect of melatonin has been used to manipulate the coat growth of mink.
Melatonin implants have been used commercially for many years on mink farms to produce high quality “winter” coats out of season.
Treating hair cycle arrest alopecias
Melatonin has been used to treat a range of different hair cycle arrest alopecias in dogs (Table 1). These are diseases where the normal orderly progression of hair growth through the different phases – anagen, catagen and telogen – is halted leading to hair loss.
Melatonin has also been shown to be beneficial in some of the tardive onset breed specific follicular dysplasias (Table 2). The response of this latter group of conditions to melatonin is probably because they represent a cross-over between true dysplastic diseases where hair is lost due to the formation of abnormal hairs and hair cycle arrest alopecia.
Whilst both hair cycle arrest alopecia and the follicular dysplasia are cosmetic diseases, with no concurrent systemic involvement, they are unacceptable clinical manifestations to many owners, especially in the plushcoated breeds such as the Chow chow and Pomeranian.
Although therapy is the preferred option for many owners, it should take into account the benign nature of the disease so that the side-effects of therapy should never be more detrimental than the disease itself.
Many different therapies have been advocated for management of Alopecia X including neutering entire animals, melatonin, methyl testosterone, growth hormone, trilostane, deslorelin acetate or monitoring without specific therapy.
Many of these drugs such as trilostane, growth hormone and methyl testotosterone are not without potential side-effects whereas melatonin appears to be safe and effective in about 40% of cases when used at a dose of 3mg a day given at night for small breeds and 6-12mg for larger dogs. Many of the tardive onset follicular dysplasias also benefit from a similar dose regime with melatonin.
Cyclical flank alopecia (CFA) is, as its name suggests, a disease that waxes and wanes with changing photoperiod. As such it is difficult to assess the benefit of any therapy, as hair will grow back spontaneously in 3-8 months, in most cases.
The best evidence for any drug’s therapeutic benefit is from studies using dogs with a history of CFA for more than three years, where the risk of recurrence in a subsequent year is 80%. Any drug preventing recurrence of the disease can be assumed to be beneficial.
In one study (Paradis, 2000) of nine dogs given melatonin two months prior to the normal onset of their disease, none demonstrated extensive hair loss as they had done in previous years. The dose rates of melatonin for CFA are similar to those used for Alopecia X.
Pattern baldness is another disease that may benefit from melatonin. Although histopathologically dogs have been shown to have miniaturisation of hairs suggesting some sort of follicular abnormality, many dogs show cyclicity of their disease suggesting it may have components of hair cycle arrest alopecia.
Work by Paradis (1996) has shown melatonin is beneficial in some breeds including Dachshunds, Boston terriers and miniature pinschers with pattern baldness.
References/further reading
Cerundolo, R. et al (2000) An analysis of factors underlying hypotrichosis and alopecia in Irish water spaniels in the United Kingdom. Vet Dermatol 11: 107122.
Diaz, S. F., Torres, S. M. F., Dunstan, R. W. et al (2004) An analysis of canine hair regrowth after clipping for a surgical procedure. Vet Dermatol 15: 2530.
Frank, L. A., Hnilica, K. A. and Oliver, J. W. (2004) Adrenal steroid hormone concentrations in dogs with hair cycle arrest alopecia (Alopecia X) before and after treatment with melatonin and mitotane. Vet Dermatol 15: 278284.
Medleau, L. and Hnilica, K. (2006) Hereditary, Congenital and Acquired Alopecia. In: Small Animal Dermatology: A Color Atlas and Therapeutic Guide, 2nd edition. Saunders Elsevier, pp229-273.
Morris, D. O. (2004) Disorders of hair and hair growth. In: Campbell, K. L. Small Animal Dermatology Secrets Hanley and Belfus, pp99-105.
Paradis, M. (1996) Melatonin therapy in canine pattern baldness. Proceedings of the Third World Congress of Veterinary Dermatology. Edinburgh, Scotland, p53.
Paradis, M. (2000) Melatonin therapy in canine alopecia. In: Bonagura, E. D. (ed) In Kirk’s Current Veterinary Therapy XIII Small Animal Practice, W. B. Saunders, Philadelphia, pp546-549.
Perianayagam, M. C. et al (2005) Immune modulating effects of melatonin, N-acetylserotonin and Nacetyldopamine. Ann N Y Acad Sci 1,053: 386-393.
Pohanka, M. (2013) Impact of melatonin on immunity: a review. Central European Journal of Medicine 8 (4): 369-376.
Miller, W. H., Griffin, C. E. and Campbell, K. L. (2012) Chapter 11: Miscellaneous Alopecias. In: Muller and Kirk’s Small Animal Dermatology 7th edition, Elsevier, pp554-571.
