February 2023
Yin W, Zhang J, Guo Y, Wu Z, Diao C, Sun J. Melatonin for premenstrual syndrome: A potential remedy but not ready. Front Endocrinol (Lausanne). 2023;13:1084249. Published 2023 Jan 9. doi:10.3389/fendo.2022.1084249
Overview
The aim of this review was to provide potential pathways in which melatonin can attenuate symptoms commonly experienced by women with premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). Symptoms include sleep disturbances, mood changes, and cognitive impairments. Melatonin can regulate the circadian system, the production of estrogen and progesterone, modulate gamma-aminobutyric acid (GABA) and brain-derived neurotrophic factor (BDNF) and therefore may be a possible therapy in clinical practice for the management of PMS and PMDD.Â
Our clinical takeaway from the article
Based on the data presented in this article, combined with other articles our team has reviewed, we contend that the research on melatonin for PMS and PMDD is an emerging area to monitor. At present, clear clinical guidelines for the dose and timing of melatonin for this specific health concern have not yet been established, however, based on preliminary data, it appears promising and aligns with other research.Â
The research for using melatonin for sleep disturbances, a common symptom of PMS and PMDD, is well-established as a safe and effective therapy and, therefore, can be used clinically to improve sleep, regardless of the underlying reason for the disturbed sleep. Additionally, we have reported on the potential use of melatonin for PCOS,  pregnancy and fertility, and reproductive health, all of which require the proper regulation of estrogen and progesterone. Some of our recent Latest Publication reviews have also included topics like melatonin for anxiety and psychiatric illnesses, in which melatonin has been shown to have a positive influence on mood.Â
Though doses are not mentioned in this article, other research presented supports the lowest effective dose of 0.3 mg per day, for the shortest period of time for sleep, with potentially higher doses used for mood concerns and cognition. Clinically, it is ideal to personalize melatonin use based on the symptoms and health priorities of the patient. Â Â
Article summary
For women with premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD), symptoms such as sleep disturbances, depressed mood, anxiety, and cognitive impairment (i.e., feeling overwhelmed) present in the luteal phase of the menstrual cycle. The connection to melatonin and PMS was first reported 30 years ago by Parry et al., indicating circadian clock dysfunction in those with PMS and PMDD.Â
The literature reviewed by the authors explored the potential impact of melatonin on behavior and molecular aspects. Molecular mechanisms identified in cell, animal, and human models included the following and provide insight into how melatonin-targeted treatment may be impactful for PMS and PMDD (Image 1; original Figure 2):
Circadian genes
Pro-inflammatory cytokines
Enzyme activity
Ovarian estrogen and progesterone
GABA
BDNF
Image 1: Potential molecular actions of melatonin in modulating premenstrual symptoms.
Image Credit: Yin W, Zhang J, Guo Y, Wu Z, Diao C, Sun J. Melatonin for premenstrual syndrome: A potential remedy but not ready. Front Endocrinol (Lausanne). 2023;13:1084249. Published 2023 Jan 9. doi:10.3389/fendo.2022.1084249. https://creativecommons.org/licenses/by/4.0/.
Melatonin has been shown to improve one or more of these molecular actions in cells, animal and human models to improve sleep, mood, and cognition as summarized in Image 2 (original Figure 1).​
Image 2: Mechanisms of melatonin restoration in PMS/PMDD-related symptoms in cells, animals, and humans.
Image Credit: Yin W, Zhang J, Guo Y, Wu Z, Diao C, Sun J. Melatonin for premenstrual syndrome: A potential remedy but not ready. Front Endocrinol (Lausanne). 2023;13:1084249. Published 2023 Jan 9. doi:10.3389/fendo.2022.1084249. https://creativecommons.org/licenses/by/4.0/.
Short summary of melatonin’s functions in managing premenstrual symptoms
Melatonin attenuates PMS-induced sleep disturbances by restoring the altered circadian clock and targeting the circadian system. Melatonin levels are decreased in the luteal phase of the menstrual cycle in those experiencing PMS.
Melatonin improves depressed mood and reduces anxiety by restoring the circadian clock, which is involved in emotional regulation and regulating circadian genes associated with emotional/mood disorders.
Melatonin may alleviate cognitive impairments by aiding in the regulation of ovarian estrogen and progesterone production. Melatonin is produced in the granulosa cells, cumulus oophorus, and oocytes, resulting in higher concentrations of melatonin in follicular cells than in serum.
Melatonin modulates brain GABA and BDNF, resulting in potential improvements in mood and cognition. BDNF is involved in mood regulation, synaptic plasticity (memory), and the etiology of PMS. In PMDD and PMS, higher BDNF levels have been found in the luteal phase compared to control groups.Â
Limitations noted by AuthorsÂ
In order to make clear clinical recommendations, the authors repeatedly stated that more well-conducted and larger clinical trials are needed for each of the areas they reviewed (sleep, mood, and cognitive impairment specific to PMS/PMDD). Further, each of the mechanisms of action should be further explored along with melatonin’s role in the female reproductive system and they provided several suggestions for the future of this research.Â
Other limitations noted in this review
Without reading the articles covered in this review, the dose of melatonin supplementation for sleep, mood, and cognitive improvements in humans was not noted.
PMS and hormonal imbalances are multi-factorial and can require multiple clinical interventions (i.e., diet, nutrients, exercise, etc.) to improve outcomes.Â
Article review completed by Kim Ross, DCN
Content reviewed by Deanna Minich, PhD
February 1, 2023