Hormones in the body do not function in isolation; they operate as an interconnected system. In particular, oestrogen, progesterone and melatonin play key roles in sleep, mood and the body’s circadian rhythm.
From the reproductive years through to the perimenopausal period, fluctuations in sex hormones often have a clear impact on sleep quality. Many people experience difficulty falling asleep, waking during the night, or early morning waking. These issues are largely linked to the interaction between these hormones.
Oestrogen and progesterone are not only responsible for regulating the menstrual cycle; they are also directly connected to the circadian rhythm and melatonin.
The role of oestrogen
Oestrogen is a key female hormone that helps regulate sleep balance. Its effects extend beyond the reproductive system to the brain and various neurotransmitters. Oestrogen helps to:
- Increase serotonin, which is a precursor to melatonin
- The main pathway is: tryptophan → serotonin → melatonin
- Regulate the circadian rhythm (via the hypothalamus)
- Control body temperature
- Reduce hot flushes
- Support stable sleep cycles
When oestrogen levels are optimal, the body can produce melatonin more effectively, making it easier to fall asleep and stay asleep. When oestrogen declines, such as during menopause, serotonin production and signalling to melatonin may decrease, leading to sleep disturbances.
The role of progesterone
Progesterone is often referred to as the “calming” or “sleep-supporting” hormone. It promotes relaxation and deep sleep.
Progesterone and its metabolites, such as allopregnanolone, stimulate GABA-A receptors in the brain—the same system responsible for calming neural activity.
GABA is a neurotransmitter that:
- Reduces brain excitability
- Lowers anxiety
- Helps with falling asleep
- Improves deep sleep quality
This explains why, when progesterone levels fall, many people experience:
- A racing mind at bedtime
- Repetitive thoughts
- Light, easily disturbed sleep
- Reduced deep sleep
Even if melatonin signals that it is time to sleep, if the GABA system is not calm, falling asleep can still be difficult.
The role of melatonin
Melatonin is the body’s “timing hormone”. It is produced by the pineal gland in the brain and is released in response to darkness.
Its key functions include:
- Regulating the 24-hour circadian rhythm
- Signalling to the brain that it is time to sleep
- Helping to control night-time body temperature
Melatonin does not directly induce sleep like a sedative; rather, it acts as a time signal.
How the three hormones work together
In simple terms:
- Melatonin = signals that it is time to sleep
- Progesterone = calms the brain and promotes deep sleep
- Oestrogen = stabilises sleep and reduces disturbances
An analogy:
- Melatonin = turns the lights off
- Progesterone = quietens the brain
- Oestrogen = creates a comfortable sleep environment
When all three are balanced, sleep quality is at its best.
Why is sleep more difficult during menopause?
During perimenopause and menopause, oestrogen and progesterone levels decline and fluctuate significantly. This leads to:
- Reduced melatonin with age
- Night-time hot flushes
- Night sweats
- Increased brain alertness
- Frequent waking between 2–4 a.m.
This is why many people feel “tired but unable to sleep” or find it difficult to return to sleep after waking.
When hormones are imbalanced
Even if the body still produces melatonin, it may not function effectively if oestrogen and progesterone are out of balance. For example:
- The brain may remain alert
- Cortisol may be elevated at night
- GABA activity may be reduced
- Circadian rhythm may become disrupted
This leads to the common experience of feeling sleepy but unable to fall asleep.
Summary of the relationship
- Oestrogen: enhances melatonin production and responsiveness
- Progesterone: calms the brain and supports sleep initiated by melatonin
- Melatonin: sets the timing of sleep
Together, oestrogen and progesterone support melatonin to improve sleep quality.
Longevity insight
Oestrogen, progesterone and melatonin form a key triad for repair, recovery and healthy ageing.
- Oestrogen enhances circadian signalling and increases serotonin
- Progesterone promotes calmness and deep sleep
- Melatonin acts as an antioxidant and supports mitochondrial repair
When balanced, they contribute to:
- Deep, restorative sleep
- Reduced chronic inflammation (inflammaging)
- Enhanced cellular repair and longevity signalling
When all three hormones are imbalanced
A decline or imbalance in sex hormones reduces melatonin efficiency:
- Low oestrogen (e.g. perimenopause/menopause) → reduced melatonin, insomnia, night waking
- Low progesterone
- Reduced GABA → increased anxiety and fragmented sleep
- Elevated cortisol → suppresses melatonin and may accelerate ageing
Overall effects:
- Sleep disruption
- Increased inflammation
- Increased oxidative stress and accelerated ageing
Laboratory biomarkers
To assess these interactions:
- Hormones: oestradiol (E2), progesterone
- Sleep axis: melatonin (or indirectly via sleep quality)
- Stress: cortisol (morning/evening)
- Inflammation: hs-CRP
- Oxidative stress markers
References
- Chuffa, L. G. A., et al. (2019). Melatonin promotes uterine and placental health: Interactions with oestrogen and progesterone. International Journal of Molecular Sciences, 21(1), 300.
- Fang, L., et al. (2019). Melatonin stimulates progesterone production in human granulosa-lutein cells via MT1/MT2 receptors. Journal of Pineal Research, 66(3), e12534.
- Greendale, G. A., et al. (2020). Melatonin patterns and levels during the human menstrual cycle. Journal of the Endocrine Society, 4(11), bvaa115.
- Sadeghpour, S., et al. (2025). Effects of melatonin on follicular oxidative stress and reproductive hormones. Reproductive Biology and Endocrinology.
- Taketani, T., et al. (2011). Protective role of melatonin in progesterone production by human granulosa cells. Journal of Pineal Research, 51(2), 207–213.
- Webley, G. E., & Leidenberger, F. (1986). The circadian pattern of melatonin and its positive relationship with progesterone during the menstrual cycle. Journal of Clinical Endocrinology & Metabolism, 63(2), 323–328.
