Low melatonin and dyspepsia during menopause

Relation

Chojnacki C, Mędrek-Socha M, Konrad P, Chojnacki J, Błońska. The value of melatonin supplementation in postmenopausal womenHelicobacter pylori-associated dyspepsia.BMC Women's Health. 2020;20(1):262.

Study objective

This study aims to assess the cause of chronic dyspepsia in patients with low melatonin levels (ie, postmenopausal women) and its associationHelicobacter pyloriInfection.

Draft

Randomized, placebo-controlled trial

Participant

All 152 participants were postmenopausal women between the ages of 49 and 64. Exclusion criteria included those who were receiving hormone replacement therapy or had a history of inflammatory, metabolic, allergic, or mental illness.

The participants were divided into 3 groups:

• Gruppe 1: Nein Helicobacter-pylori oder Dyspepsiesymptome (n=30)
• Gruppe 2: Asymptomatisch Helicobacter-pylori Infektion (n=60)
• Gruppe 3: Symptomatisch Helicobacter-pylori Infektion (n=64)
  • Gruppe 3a war die Placebogruppe
  • Gruppe 3b war die Melatonin-Behandlungsgruppe

intervention

Only group 3 received the intervention. Group 3b received 1 mg melatonin in the morning and 3 mg melatonin at bedtime, while group 3a received a matching placebo taken at the same times of the day.

Study parameters assessed

Researchers initially performed a urea breath test, upper gastrointestinal (GI) endoscopy, and histological examination to confirm thisHelicobacter pyloriInfection. They repeated the urea breath test again after 3 and 6 months.

They rated dyspepsia symptoms using the visual analogue scale.

Researchers assessed other parameters at baseline and again at 1-, 3-, and 6-month follow-ups. These included a complete blood count (CBC), C-reactive protein, glycosylated hemoglobin, bilirubin, liver enzymes, pancreatic enzymes, urea, creatinine, lipid assay, 17-beta-estradiol, follicle-stimulating hormone, serum melatonin, and urinary 6-sulfatoxymelatonin.

Therapeutic approach

All participants in the symptomaticHelicobacter pyloriInfection group (group 3) received an antibiotic protocol: pantoprazole (2 x 40 mg), amoxicillin (2 x 1,000 mg) and levofloxacin (2 x 500 mg) daily for 14 days.

Group 3 was then divided into 2 equal groups: Group 3a received placebo, 2 tablets per day; Group 3b received melatonin, 1 mg every morning and 3 mg at bedtime for 6 months.

Researchers instructed all participants to stick to 1,600 calories a day for the 6-month study period.

Key insights

Initial observations showed that women in group 3 (symptomaticHelicobacter pyloriinfection) had lower serum melatonin levels (5.72 ± 1.42 pg/ml;P<0.001) compared to Group 1 (12.5 ± 2.72 pg/ml) and Group 2 (10.5 ± 3.73 pg/ml) arms.

At baseline, 24-hour urine 6-sulfatoxymelatonin levels were lower in women with asymptomatic (P<0.001) and symptomatic (P<0.001)Helicobacter pyloriinfection compared to the control group.

There was no statistically significant difference between the 3 groups for 17-beta-estradiol (P>0.05), follicle stimulating hormone (P>0.05) or other laboratory parameters.

Per protocol, both groups received 3a (placebo) and 3b (melatonin).Helicobacter pyloriEradication treatments for 2 weeks. Extermination ofHelicobacter pyloritended to be higher in group 3b (84.3%) than in group 3a (75%) (P>0.5).

After 6 months, symptoms of dyspepsia disappeared in 84.3% of patients in group 3b versus 43.7% of patients in group 3a (P<0.001).

Practice implications

Melatonin is synthesized from L-tryptophan in the pineal gland in a 4-step process that includes serotonin as a mediator. Melatonin is most commonly used to treat insomnia due to circadian rhythm abnormalities or jet lag. Also found to be an endogenous antioxidant,¹Melatonin supports almost every system in the body, including immune,²Eye,³and gastrointestinal functions.^4.5As previously reported, after adulthood, melatonin production naturally decreases with age.⁶In the current study, Chojnacki et al show that lower melatonin levels are also associated with symptoms of dyspepsia.

Hormonal changes are part of the natural menopause process, but this study implies that low melatonin levels may be the difference between symptomatic and asymptomaticHelicobacter pyloriInfection.

This is not the first study on melatonin and dyspepsia. Various studies have already been carried out on the effects of melatonin on the gastrointestinal tract.^7-9This study adds to the evidence of the connection between gut health and melatonin levels. Chojnacki et al. suggest that dyspepsia symptoms may be caused by reduced production of melatonin locally in the gastric mucosa. This is done through a publication inJournal of Pineal Researchwho found an association between gastric luminal melatonin levels and bicarbonate secretion in the gastrointestinal tract.¹⁰Other hypotheses regarding mechanisms of melatonin-induced symptom relief include effects on the parasympathetic nervous system¹¹and stimulation of the Migrating Motor Complex (MMP)¹²Systems closely involved in digestion.

This study adds to the evidence on the connection between gut health and melatonin levels.

Melatonin administered orally is well tolerated. For insomnia, melatonin is typically taken 1 to 3 hours before bedtime in doses between 0.1 and 6 mg. Serum melatonin levels peak after approximately 40 minutes with an elimination half-life of 54 minutes when taken orally.¹³Therefore, in this study, researchers used a more frequent dosage to treat dyspepsia. The dosage in this study was 1 mg in the morning and 3 mg at bedtime, and only 4 of 32 women reported fatigue. However, taking it has been shown to cause daytime sleepiness,¹⁴Therefore, caution should be exercised when dosing outside of bedtime.