Melatonin Effects on Cardiovascular Disease Mechanisms in the Menopause Transition: A Randomized Clinical Trial

Inclusion Criteria

• Age 40-55 years old

• Female individuals with intact uterus and at least one ovary

• Currently in the menopause transition

o Defined as self-reported bleeding patterns encompassing the early and late perimenopause phases, in accordance with the Stages of Reproductive Aging Workshop (STRAW) Criteria:6 a difference of ≥7 days in the length of consecutive menstrual cycles which recurs within 10 cycles from the first occurrence (early menopause), or 2 to 12 months of amenorrhea (late perimenopause)

• Hypertension

o Defined as a prior diagnosis of hypertension, use of antihypertensive agents, or office SBP/DBP ≥130/80 mmHg

• On stable medical regimen (≥ 2 months) if taking other medications

Exclusion Criteria

• Prescription sleeping medications or melatonin supplementation

• Pregnant or lactating

• Night shift work

• Current or recent (within the past 2 months) use of hormonal contraceptives

• Current or recent (within the past 2 months) use of hormone replacement therapy

• On prescription aspirin

• Severe lactose intolerance

• History of substance use disorder

• History of suicidal ideation

• History of clinically diagnosed anemia or low hemoglobin levels (<11.6 g/dL) within the past 12 months

• Active cancer

• Severe daytime sleepiness (score >15 at the Epworth Sleepiness Scale)

• Current or recent (within the past 2 months) participation in other research studies at the discretion of study investigators

• Inability to provide written consent and/or to speak and read English

• Any other medical, geographic, or social factor making study participation impractical