The impact of progesterone on weight and sleep

In Friday morning's session - 'Hormone therapy in menopause: Beyond hot flushes', sponsored by EMAS - Petra Stute presented data exploring the impact of progesterone on weight and sleep.

For women aged 55-65 years, weight gain is one of their major health concerns. Worldwide, the prevalence of obesity has more than doubled since 1980. It is not surprising then, that obesity is a major risk factor for chronic non-communicable diseases. Unsurprisingly, this has been one of the over-arching themes at the conference this year.

A key questioned posed by Peta was: Is weight gain at midlife a consequence of menopause or ageing?

Existing literature tends to support the theory that weight gain in mid-life is primarily a result of ageing and lifestyle changes. However, as visceral fat deposits increase in women, combined with a decrease of lean body weight and an increase in weight circumference, Petra argued that it is unlikely that ageing alone can explain this.

What might explain weight gain in the menopause?

Normal physiological sleep is characterised by non-REM and REM sleep stages - the former of which can be classified further into 4 sub-stages. The most crucial stage of sleep (in regards to quality) is non-REM 3 (NREM3).

In NREM3 sleep glucose tolerance is minimal, growth hormone peaks and inhibition of the hypothalamus-pituitary-adrenal axis is high, reducing cortisol levels. This results in low stress levels and reduced glucose uptake.

The metabolic consequences of decreased sleep quality lead to decreased insulin sensitivity, extra energy expenditure, increased hunger and reduced physical activity. Consequently, energy intake exceeds increased energy expenditure - resulting in an increase in body weight. As such, poor sleep increases risk of obesity, diabetes and CVD.

During the ageing process, circadian hormonal secretion changes - cortisol levels increase and growth hormone and melatonin decrease. In menopause, oestrogens and progesterone decrease.

How does progesterone affect sleep?

Progesterone is metabolised to allopregnanolone, promoting a sedative effect via modulation of GABA receptors. It significantly positively correlates with NREM3 duration and treatment with progesterone significantly increases total sleep time and decreases sleep onset latency and awakenings. Importantly, progesterone increases growth hormones peaks at night, triggering NREM3 sleep.

To investigate this further, Petra performed a systematic literature search. Of the 10 results, 3 found a significant impact on body weight. The studies, using oestrogens combined with micronized progesterone, did not demonstrate a change or reduction in body weight in normal weighted post-menopausal women.

Petra argued that further investigation, using progesterone alone is required for more robust results. Perhaps a larger, more focussed trial will yield more valuable insight into this under-explored area of research.