Menopause
The relationship between melatonin and sex steroid hormones (i.e., estrogen, testosterone, progesterone) was first identified in 1999, though the exact effects were unclear (1). It has since been established that there is a bidirectional relationship between melatonin and sex hormones, as well as differences in melatonin profiles between males and females (1). In the younger population, women have higher serum melatonin levels (2) and 50% more bioavailability than men (3). On the contrary, older women (mean 72 years) have significantly lower melatonin levels as measured by urinary-6-sulfaoxymelatonin (4).
Using melatonin in animal studies has demonstrated varying results based on age, including significant reductions in luteinizing hormone (LH) and follicle-stimulating hormone (FSH), without any changes to estradiol or progesterone levels in elderly rats (5), whereas middle-aged rats had an increase or decrease in LH and an increase in FSH and estradiol levels (5–7).
In peri- and postmenopausal women, a reduction in melatonin and estrogen levels contributes to disrupted circadian rhythms and climacteric symptoms (vasomotor symptoms, sleep, and mood) (8–10).
One early study (11) found that administering intravenous melatonin decreased luteinizing hormone (LH) in postmenopausal women, which was further supported by additional studies that also reported a decrease in follicle-stimulating hormone (FSH) in early peri-menopausal women (12). Another study of postmenopausal women who received 3 mg of melatonin in the morning* and 5 mg of melatonin at bedtime for 12 months did not result in changes in estradiol or FSH levels, though it did produce a significant decrease (47%) in menopausal symptoms as measured by Kupperman’s Menopausal Index (KMI) and a decrease in body mass index (BMI) (9).
A systematic review that included 24 studies with a total of 1,173 peri- and postmenopausal women found benefits to include reduction in blood pressure, LH, hot flashes and other symptoms of menopause, fat mass, sleep disturbances (improved sleep latency, efficiency, REM sleep), and depression with an increase of daytime cortisol, HDL, bone density, lean body mass, and sexual function. The doses used ranged from 1-100 mg, with the most common dose of 3 mg studied (13). Another systematic review and meta-analysis also reported significant improvements in mood (depression and anxiety) in postmenopausal women after melatonin therapy (14). A clinical study, including 100 perimenopausal women who took 3 mg of melatonin for 12 weeks, experienced decreased LH and FSH levels and significant improvements in menopausal symptoms and mood (Images 1 and 2) (15).
Image 1: Kupperman and MENQOL score in the two groups before and after treatment.
Image credit: Zhang J, Jiang B. Influence of Melatonin Treatment on Emotion, Sleep, and Life Quality in Perimenopausal Women: A Clinical Study. J Healthc Eng. 2023;2023:2198804. Published 2023 Oct 10. doi:10.1155/2023/2198804. CC-BY. (Note: Baseline is spelled incorrectly.)
Image 1: LH, FSH, E2, and melatonin levels before and after treatment in the two groups.
Image credit: Zhang J, Jiang B. Influence of Melatonin Treatment on Emotion, Sleep, and Life Quality in Perimenopausal Women: A Clinical Study. J Healthc Eng. 2023;2023:2198804. Published 2023 Oct 10. doi:10.1155/2023/2198804. CC-BY. (Note: Baseline is spelled incorrectly.)
Further, based on the current evidence, melatonin therapy in doses up to 5 mg daily may be beneficial for other health concerns that arise in menopausal women, such as dyslipidemia, bone density (13,16), and weight gain (9,17).
*The researchers of this study (9) indicated that since melatonin is produced in peripheral organs, they designed the study to include daytime and bedtime dosing. There may be some flaws in this design. It is speculated that about 5% of total melatonin is produced in the pineal gland, which is circulated through the body through serum and cerebrospinal fluid and can be taken up by the mitochondria as needed. Conversely, melatonin that is produced elsewhere in the body, including the mitochondria, is used by cells and referred to as a “non-releasable pool of melatonin.” Two exceptions include the gastrointestinal tract and skin, which may release melatonin produced based on the conditional needs of the body (18).
Author: Kim Ross, DCN
Reviewer: Deanna Minich, PhD
November 13, 2023
References
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